Haematology Flashcards

Question

RBC lifespan?

Answer 1

Megakaryocytes

Answer 2

Their role is to clump together (platelet aggregation) and plug gaps where blood clots need to form

Answer 3

Monocytes then macrophages Neutrophils Eosinophils Mast Cells Basophils

Answer 4

Promyelocytes

Answer 5

Promyelocytes

Answer 6

Lymphoid stem cells

Answer 7

B cells or T cells

Answer 8

Bone marrow

Answer 9

Thymus gland

Answer 10

After maturing in the bone marrow: Plasma Cells Memory B cells

Answer 11

After maturing in the thymus gland CD4 cells (T helper cells) CD8 cells (Cytotoxic T Cells) Natural Killer Cells

Answer 12

A blood film involves a specialist examining the blood using a microscope to manually check for abnormal shapes, sizes and contents of the cells and note abnormal inclusions in the blood

Answer 13

Variation in size of red blood cells Myelodysplastic syndrome, some types of anaemia

Answer 14

RBC that have a central pigmented area, surrounded by a pale area, surrounded by a ring of thicker cytoplasm on the outside. This makes it look like a bull’s eye target. These can be seen in iron deficiency anaemia and post-splenectomy.

Answer 15

Anisocytosis refers to a variation in size of the red blood cells. These can be seen in myelodysplasic syndrome as well as some forms of anaemia

Answer 16

Target cells - have a central pigmented area, surrounded by a pale area, surrounded by a ring of thicker cytoplasm on the outside. This makes it look like a bull’s eye target. These can be seen in iron deficiency anaemia and post-splenectomy.

Answer 17

Howell-Jolly bodies are individual blobs of DNA material seen inside red blood cells. Normally this DNA material is removed by the spleen during circulation of red blood cells. They can be seen in post-splenectomy and in patients with severe anaemia where the body is regenerating red blood cells quickly.

Answer 18

Howell-Jolly bodies are individual blobs of DNA material seen inside red blood cells. Normally this DNA material is removed by the spleen during circulation of red blood cells. They can be seen in post-splenectomy and in patients with severe anaemia where the body is regenerating red blood cells quickly.

Answer 19

Rapid turnover of RBC - rapid turnover of red blood cells, such as haemolytic anaemia. They demonstrate that the bone marrow is active in replacing lost cells.

Answer 20

Schistocytes are fragments of red blood cells. They indicate the red blood cells are being physically damaged by trauma during their journey through the blood vessels.

Answer 21

They may indicate networks of clots in small blood vessels caused by: Haemolytic uraemic syndrome Disseminated intravascular coagulation (DIC) or Thrombotic thrombocytopenia purpura. They can also be present in replacement metallic heart valves and haemolytic anaemia.

Answer 22

Schistocytes are fragments of red blood cells. They indicate the red blood cells are being physically damaged by trauma during their journey through the blood vessels. They may indicate networks of clots in small blood vessels caused by haemolytic uraemic syndrome, disseminated intravascular coagulation (DIC) or thrombotic thrombocytopenia purpura. They can also be present in replacement metallic heart valves and haemolytic anaemia.

Answer 23

Sideroblasts are immature red blood cells that contain blobs of iron. They occur when the bone marrow is unable to incorporate iron into the haemoglobin molecules. They can indicate a myelodysplasic syndrome.

Answer 24

Sideroblasts are immature red blood cells that contain blobs of iron. They occur when the bone marrow is unable to incorporate iron into the haemoglobin molecules. They can indicate a myelodysplasic syndrome.

Answer 25

Smudge cells are ruptured white blood cells that occur during the process of preparing the blood film due to aged or fragile white blood cells. They can indicate chronic lymphocytic leukaemia.

Answer 26

Smudge cells are ruptured white blood cells that occur during the process of preparing the blood film due to aged or fragile white blood cells. They can indicate chronic lymphocytic leukaemia.

Answer 27

Spherocytes are spherical red blood cells without the normal bi-concave disk space. They can indicated autoimmune haemolytic anaemia or hereditary spherocytosis.

Answer 28

Spherocytes are spherical red blood cells without the normal bi-concave disk space. They can indicated autoimmune haemolytic anaemia or hereditary spherocytosis.

Answer 29

T – Thalassaemia A – Anaemia of chronic disease I – Iron deficiency anaemia L – Lead poisoning S – Sideroblastic anaemia

Answer 30

There are 3 As and 2 Hs for normocytic anaemia: A – Acute blood loss A – Anaemia of Chronic Disease A – Aplastic Anaemia H – Haemolytic Anaemia H – Hypothyroidism

Answer 31

Megaloblastic or normoblastic Megaloblastic anaemia is the result of impaired DNA synthesis preventing the cell from dividing normally. Rather than dividing it keeps growing into a larger, abnormal cell. This is caused by a vitamin deficiency. Normblastic is not related to DNA synthesis

Answer 32

B12 deficiency Folate deficiency

Answer 33

Alcohol Reticulocytosis (usually from haemolytic anaemia or blood loss) Hypothyroidism Liver disease Drugs such as azathioprine

Answer 34

Megaloblastic: B12 deficiency Folate deficiency Normoblastic: Alcohol Reticulocytosis (usually from haemolytic anaemia or blood loss) Hypothyroidism Liver disease Drugs such as azathioprine

Answer 35

Tiredness Shortness of breath Headaches Dizziness Palpitations Worsening of other conditions such as angina, heart failure or peripheral vascular disease

Answer 36

Pica describes dietary cravings for abnormal things such as dirt and can signify iron deficiency Hair loss can indicate iron deficiency anaemia

Answer 37

Pale skin Conjunctival pallor Tachycardia Raised respiratory rate

Answer 38

Koilonychia (spoon shaped nails) Angular cheilitis (swollen red patches at corners of the mouth) Atrophic glossitis ( smooth tongue due to atrophy of the papillae) Brittle hair + nails Post-cricoid webs

Answer 39

Oedema, hypertension and excoriations on the skin

Answer 40

Bone deformities

Answer 41

Haemoglobin Mean Cell Volume (MCV) B12 Folate Ferritin Blood film

Answer 42

Oesophago-gastroduodenoscopy (OGD) and colonoscopy to investigate for a gastrointestinal cause of unexplained iron deficiency anaemia. This is done on an urgent cancer referral for suspected gastrointestinal cancer. Bone marrow biopsy may be required if the cause is unclear

Answer 43

Insufficient dietary iron Iron requirements increase (for example in pregnancy) Iron is being lost (for example slow bleeding from a colon cancer) Inadequate iron absorption

Answer 44

Duodenum and jejunum

Answer 45

Acid from the stomach to keep the iron in the soluble ferrous (Fe2+) form. When the acid drops it changes to the insoluble ferric (Fe3+) form. Therefore, medications that reduce the stomach acid such as proton pump inhibitors (lansoprazole and omeprazole) can interfere with iron absorption

Answer 46

Ferrous Fe2+

Answer 47

Ferric - Fe3+

Answer 48

Conditions that result in inflammation of the duodenum or jejunum such as coeliac disease or Crohn’s disease can also cause inadequate iron absorption.

Answer 49

Blood loss is the most common cause in adults (commonly menorrhagia, oesophagitis, gastritis) Dietary Insufficiency is the most common cause in growing children Poor iron absorption (consider Crohn's, coeliac) Increased requirements during pregnancy

Answer 50

GI tract cancer

Answer 51

Ferric ions (insoluble) bound to transferrin (carrier protein)

Answer 52

Total iron binding capacity The total space on the transferrin molecules for the iron to bind. Therefore, total iron binding capacity is directly related to the amount of transferrin in the blood.

Answer 53

Transferrin Saturation = Serum Iron / Total Iron Binding Capacity Expressed as a percentage

Answer 54

LOW - highly suggestive of iron deficiency NORMAL - possible, if there are reasons to have raised ferritin such as infection HIGH - If ferritin is high then this is difficult to interpret and is likely to be related to inflammation rather than iron overload. Ferritin is released from cells in inflammation, such as infection or cancer

Answer 55

Serum iron varies significantly throughout the day with higher levels in the morning and after eating iron containing meals. On its own serum iron is not a very useful measure.

Answer 56

Transferrin saturation gives a good indication of the total iron in the body. In normal adults it is around 30%, however if there is less iron in the body transferrin will be less saturated and if iron levels go up transferrin will be more saturated. It can temporarily increase after eating a meal rich in iron or taking iron supplements so a fasting sample gives the most accurate results.

Answer 57

Total iron binding capacity can be used as a marker for how much transferrin is in the blood. It is an easier test to perform than measuring transferrin. Both TIBC and transferrin levels increase in iron deficiency and decrease in iron overload.

Answer 58

TIBC - which will be low

Answer 59

Supplementation with iron Acute liver damage (lots of iron is stored in the liver) TIBC will be low

Answer 60

New iron deficiency in an adult without a clear underlying cause (for example heavy menstruation or pregnancy) should be investigated with suspicion. This involves doing a oesophago-gastroduodenoscopy (OGD) and a colonoscopy to look for cancer of the gastrointestinal tract. 1. Blood transfusion. 2. Iron infusion e.g. “cosmofer” 3. Oral iron e.g. ferrous sulfate 200mg three times daily When correcting iron deficiency anaemia with iron you can expect the haemoglobin to rise by around 10 grams/litre per week.

Answer 61

Around 10 grams/litre per week.

Answer 62

Blood transfusion. This will immediately correct the anaemia but not the underlying iron deficiency and also carries risks. Iron infusion e.g. “cosmofer”. There is a very small risk of anaphylaxis but it quickly corrects the iron deficiency. It should be avoided during sepsis as iron “feeds” bacteria. Oral iron e.g. ferrous sulfate 200mg three times daily. This slowly corrects the iron deficiency. Oral iron causes constipation and black coloured stools. It is unsuitable where malabsorption is the cause of the anaemia.

Answer 63

Advantages: Immediately corrects the anaemia Disadvantages: Does not correct the underlying iron deficiency Risks and complications of blood transfusion: - Blood borne infections like HIV, hepatitis are possible but rare - Other reactions like graft- versus- host disease, delayed hemolytic reaction and acute immune hemolytic reaction are also seen - Allergic reactions, anaphylactic reaction - Fever

Answer 64

Advantages: Quickly corrects the anaemia iron deficiency Disadvantages: ''Feeds'' bacteria in SEPSIS Small risk of anaphylaxis

Answer 65

Advantages: Quickly corrects the anaemia iron deficiency Disadvantages: ''Feeds'' bacteria in SEPSIS Small risk of anaphylaxis

Answer 66

Advantages: Least invasive Treats underlying iron deficiency (if not due to malabsorption) Disadvantages: Does not work if cause if malabsorption Cn cause constipation and black coloured stools

Answer 67

HIV Epstein-Barr Virus Autoimmune conditions such as rheumatoid arthritis and sarcoidosis Family history

Answer 68

Neck, axilla or inguinal lymph nodes typically affected Non-tender, rubbery May be painful when drinking alcohol

Answer 69

Fatigue Itching Cough Shortness of breath Abdominal pain Recurrent infections

Answer 70

Lymph node biopsy is the key diagnostic test. LDH (often raised in HL but not specific) CT, MRI and PET scans can be used for diagnosing and staging lymphoma and other tumours.

Answer 71

Lactate dehydrogenase (LDH)

Answer 72

REED-STERNBERG CELL They are abnormally large B cells that have multiple nuclei that have nucleoli inside them. This can give them the appearance of the face of an owl with large eyes.

Answer 73

Abnormally large B cell with multiple nuclei with nucleoli inside them - REED STERNBERG CELL The Reed-Sternberg cell is the key finding from lymph node biopsy in patients with Hodgkin’s lymphoma.

Answer 74

Stage 1: Confined to one region of lymph nodes. Stage 2: In more than one region but on the same side of the diaphragm (either above or below). Stage 3: Affects lymph nodes both above and below the diaphragm. Stage 4: Widespread involvement including non-lymphatic organs such as the lungs or liver.

Answer 75

The system puts importance on whether the affected nodes are above or below the diaphragm

Answer 76

The key treatments are chemotherapy and radiotherapy. The aim of treatment is to cure the condition. This is usually successful however there is a risk of relapse, other haematological cancers and side effects of medications. Chemotherapy creates a risk of leukaemia and infertility. Radiotherapy creates a risk of cancer, damage to tissues and hypothyroidism.

Answer 77

Burkitt lymphoma MALT lymphoma Diffuse large B cell lymphoma

Answer 78

Epstein-Barr virus Malaria HIV

Answer 79

Affects the mucosa-associated lymphoid tissue, usually around the stomach. It is associated with H. pylori infection.

Answer 80

Diffuse large B cell lymphoma often presents as a rapidly growing painless mass in patients over 65 years.

Answer 81

MALT lymphoma (affects the mucosa-associated lymphoid tissue, usually around the stomach)

Answer 82

HIV Epstein-Barr Virus H. pylori (MALT lymphoma) Hepatitis B or C infection Exposure to pesticides and a specific chemical called trichloroethylene used in several industrial processes Family history

Answer 83

Pesticides Trichloroethylene (used in industrial processes)

Answer 84

The presentation is similar, often they can only be differentiated when the lymph node is biopsied.

Answer 85

Management involves a combination of treatments depending on the type and staging of the lymphoma: Watchful waiting Chemotherapy Monoclonal antibodies such as rituximab Radiotherapy Stem cell transplantation

Answer 86

“ALL CeLLmates have CoMmon AMbitions” to remember the progressive ages of the different leukaemia from 45-75 in steps of 10 years. Remember that ALL (the first in the mnemonic) most commonly affects children under 5 years. Under 5 and over 45 – acute lymphoblastic leukaemia (ALL) Over 55 – chronic lymphocytic leukaemia (CeLLmates) Over 65 – chronic myeloid leukaemia (CoMmon) Over 75 – acute myeloid leukaemia (AMbitions)

Answer 87

Acute Lymphoblastic Leukaemia (ALL)

Answer 88

Under 5s, over 45s

Answer 89

Leukaemia Meningococcal septicaemia Vasculitis Henoch-Schonlein Purpura (HSP) Idiopathic Thrombocytopenia Purpura (ITP) Non-accidental injury

Answer 90

Full blood count is the initial investigation. NICE recommend a full blood count within 48 hours for patients with suspected leukaemia. Children or young adults with ptechiae or hepatosplenomegaly should be referred immediately to the hospital. Blood film can be used to look for abnormal cells and inclusions. Lactate dehydrogenase (LDH) is a blood test that is often raised in leukaemia but is not specific to leukaemia. It can be raised in other cancers and many non-cancerous diseases. Bone marrow biopsy can be used to analyse the cells in the bone marrow. This is the main investigation for establishing a definitive diagnosis of leukaemia. Chest xray may show infection or mediastinal lymphadenopathy. Lymph node biopsy can be used to assess lymph node involvement or investigate for lymphoma. Lumbar puncture may be used if there is central nervous system involvement. CT, MRI and PET scans can be used for staging and assessing for lymphoma and other tumours.

Answer 91

Bone marrow biopsy

Answer 92

Children or young adults with ptechiae or hepatosplenomegaly should be referred immediately to the hospital.

Answer 93

Bone marrow aspiration: involves taking a liquid sample full of cells from within the bone marrow. Bone marrow trephine: involves taking a solid core sample of the bone marrow and provides a better assessment of the cells and structure. Samples from bone marrow aspiration can be examined straight away however a trephine sample requires a few days of preparation. Bone marrow biopsy is usually taken from the iliac crest. It involves a local anaesthetic and a specialist needle.

Answer 94

Acute lymphoblastic leukaemia is where there is malignant change in one of the lymphocyte precursor cells. It causes acute proliferation of a single type of lymphocyte, usually B-lymphocytes. Excessive proliferation of these cells causes them to replace the other cell types being created in the bone marrow, leading to a pancytopenia.

Answer 95

Downs Syndrome Philadelphia chromosome (t(9:22) translocation) - in 30% of adults and 3-5% of children with ALL.

Answer 96

Blast cells - a partially differentiated cell, usually referred to as a unipotent cell that has lost most of its stem cell properties

Answer 97

Chronic lymphocytic leukaemia is where there is chronic proliferation of a single type of well differentiated lymphocyte, usually B-lymphocytes.

Answer 98

Often it is asymptomatic but it can present with infections, anaemia, bleeding and weight loss. It can cause warm autoimmune haemolytic anaemia.

Answer 99

Chronic Lymphocytic Leukaemia - lymphoma - chronic lymphocytic leukaemia

Answer 100

high-grade lymphoma. This is called Richter’s transformation.

Answer 101

Smear or smudge cells

Answer 102

Chronic myeloid leukaemia has three typical phases: the chronic phase, the accelerated phase and the blast phase. The chronic phase can last around 5 years, is often asymptomatic and patients are diagnosed incidentally with a raised white cell count.

Answer 103

Incidentally, with raised WCC

Answer 104

CHRONIC Can last around 5 years, asymptomatic ACCELERATED abnormal clast cell take up a high proportion of the cells in the bone marrow and blood (up to 20%), patients become more symptomatic, develop anaemia and thrombocytopenia and become immunocompromised. BLAST PHASE An even high proportion of blast cells and blood (>30%). This phase has severe symptoms and pancytopenia. It is often fatal.

Answer 105

The Philadelphia chromosome, which is a translocation of genes between chromosome 9 and 22: it is a t(9:22) translocation.

Answer 106

Acute Myeloid Leukaemia It can present at any age but normally presents from middle age onwards.

Answer 107

A blood film will show a high proportion of blast cells. These blast cells can have rods inside their cytoplasm that are named Auer rods.

Answer 108

It can be the result of a transformation from a myeloproliferative disorder such as polycythaemia ruby vera or myelofibrosis.

Answer 109

Acute lymphoblastic leukaemia

Answer 110

Chronic lymphocytic leukaemia

Answer 111

Chronic myeloid leukaemia

Answer 112

Acute myeloid leukaemia

Answer 113

Auer rods, associated with acute myeloid leukaemia

Answer 114

Treatment will be coordinated by an oncology multi-disciplinary team. Leukaemia is primarily treated with chemotherapy and steroids. Other therapies include: Radiotherapy Bone marrow transplant Surgery

Answer 115

Failure Stunted growth and development in children Infections due to immunodeficiency Neurotoxicity Infertility Secondary malignancy Cardiotoxicity Tumour lysis syndrome

Answer 116

Uric acid Potassium, phosphate (can lead to hypocalcemia)

Answer 117

Allopurinol or rasburicase

Answer 118

Myeloma is a cancer of the plasma cells. These are a type of B lymphocyte that produce antibodies. Cancer in a specific type of plasma cell results in large quantities of a single type of antibody being produced. Myeloma accounts for around 1% of all cancers.

Answer 119

These are a type of B lymphocyte that produce antibodies. Cancer in a specific type of plasma cell results in large quantities of a single type of antibody being produced.

Answer 120

Monoclonal gammopathy Smouldering myeloma

Answer 121

Multiple myeloma is where the myeloma (multiple myeloma is where the myeloma affects multiple areas of the body) affects multiple areas of the body.

Answer 122

Where there is an excess of a single type of antibody or antibody components without other features of myeloma or cancer. This is often an incidental finding in an otherwise healthy person and as the name suggests the significance is unclear. It may progress to myeloma and patients are often followed up routinely to monitor for progression.

Answer 123

Smouldering myeloma is where there is progression of MGUS with higher levels of antibodies or antibody components. It is premalignant and more likely to progress to myeloma than MGUS. Waldenstrom’s macroglobulinemia is a type of smouldering myeloma where there is excessive IgM specifically.

Answer 124

Waldenstrom’s macroglobulinemia

Answer 125

Genetic mutation of plasma cells (B lymphocytes that have become activated to produce a certain antibody) causing it to rapidly and uncontrollably multiply. These plasma cells produce one type of antibody (also called immunoglobulins. They are complex molecules made up of two heavy chains and two light chains arranged in a Y shape. They help the immune system recognise and fight infections by targeting specific proteins on the pathogen. They come in 5 main types: A, G, M, D and E) This single type of antibody that is produced by all the identical cancerous plasma cells can be called a monoclonal paraprotein. This means a single type of abnormal protein. The “Bence Jones protein” that can be found in the urine of many patients with myeloma is actually a part (subunit) of the antibody called the light chains.

Answer 126

A G M D and E

Answer 127

When you measure the immunoglobulins in a patient with myeloma, one of those types will be significantly abundant. More than 50% of the time this is immunoglobulin type G (IgG). This single type of antibody that is produced by all the identical cancerous plasma cells can be called a monoclonal paraprotein. This means a single type of abnormal protein.

Answer 128

“Bence Jones protein”

Answer 129

A part (subunit) of the antibody called the light chains

Answer 130

The cancerous plasma cells invade the bone marrow. This is described as bone marrow infiltration. This causes suppression of the development of other blood cell lines leading to anaemia (low red cells), neutropenia (low neutrophils) and thrombocytopenia (low platelets).

Answer 131

Myeloma bone disease is a result of increased osteoclast activity and suppressed osteoblast activity. Osteoclasts absorb bone and osteoblasts deposit bone. This results in the metabolism of bone becoming imbalanced as more bone is being reabsorbed than constructed. This is caused by cytokines released from the plasma cells and the stromal cells (other bone cells) when they are in contact with the plasma cells.

Answer 132

Skull Spine Long bones Ribs

Answer 133

The abnormal bone metabolism is patchy, meaning that in some areas the bone becomes very thin whereas others remain relatively normal. These patches of thin bone can be described as osteolytic lesions.

Answer 134

Myeloma bone disease is a result of increased osteoclast activity and suppressed osteoblast activity. This results in the metabolism of bone becoming imbalanced as more bone is being reabsorbed than constructed The abnormal bone metabolism is patchy, meaning that in some areas the bone becomes very thin (osteolytic lesions) whereas others remain relatively normal. These weak points in bone lead to pathological fractures. For example, a vertebral body in the spine may collapse (vertebral fracture) or a long bone such as the femur may break under minimal force.

Answer 135

Increase in osteoclast activity caused by cytokines released from the plasma cells and the stromal cells (other bone cells) when they are in contact with the plasma cells. Calcium is reabsorbed from the bone into the blood. This results in hypercalcaemia (high blood calcium).

Answer 136

People with myeloma can also develop plasmacytomas. These are individual tumours made up of the cancerous plasma cells. They can occur in the bones, replacing normal bone tissue or can occur outside bones in the soft tissue of the body.

Answer 137

High levels of immunoglobulins (antibodies) can block the flow through the tubules Hypercalcaemia impairs renal function (increase osteoclast activity) Dehydration Medications used to treat the conditions such as bisphosphonates can be harmful to the kidneys

Answer 138

Easy bruising Easy bleeding Reduced or loss of sight due to vascular disease in the eye Purple discolouration to the extremities (purplish palmar erythema) Heart failure

Answer 139

Plasma viscosity increases when there are more proteins in the blood. These are proteins like immunoglobulins and fibrinogen, both of which increase with inflammation. In myeloma there are large amounts of immunoglobulins in the blood causing the plasma viscosity to be significantly higher.

Answer 140

C – Calcium (elevated) R – Renal failure A – Anaemia (normocytic, normochromic) from replacement of bone marrow. B – Bone lesions/pain

Answer 141

Normocytic, normochromic - from replacement of bone marrow

Answer 142

Older age Male Black African ethnicity Family history Obesity

Answer 143

Over 60s with persistent bone pain (particularly back pain) or unexplained fractures

Answer 144

FBC (low white blood cell count in myeloma) Calcium (raised in myeloma) ESR (raised in myeloma) Plasma viscosity (raised in myeloma) If any of these are positive or myeloma is still suspected: B – Bence–Jones protein (request urine electrophoresis) L – Serum‑free Light‑chain assay I – Serum Immunoglobulins P – Serum Protein electrophoresis

Answer 145

Anaemia (normocytic + normochromic) Low white blood cell count

Answer 146

Bone marrow biopsy

Answer 147

Imaging is required to assess for bone lesions. The order of preference to establish this is: 1. Whole body MRI 2. Whole body CT 3. Skeletal survey (xray images of the full skeleton) Patients only require one investigation but may not tolerate or be suitable for MRI or CT.

Answer 148

Punched out lesions Lytic lesions “Raindrop skull” caused by many punched out (lytic) lesions throughout the skull that give the appearance of raindrops splashing on a surface

Answer 149

The aim of treatment is to control disease. It usually takes a relapsing-remitting course and treatment aims to improve quality and quantity of life. Management will be undertaken by the haematology and oncology specialist multidisciplinary team.

Answer 150

First line treatment usually involves a combination of chemotherapy with: Bortezomid Thalidomide Dexamethasone

Answer 151

Chemotherapy is first line: bortezomid, thalidomide, dexamethasone Stem cell transplantation (as part of a clinical trial, where patients are suitable) VTE with aspirin or LMWH whilst on certain chemotherapy regimes (e.g. thialidomide) as there is a higher risk of developing a thrombus Myeloma bone disease can be improved using bisphosphonates. Radiotherapy to bone lesions can improve bone pain Orthopaedic surgery can stabilise bones or treat fractures. Cement augmentation can improve spine stability and pain

Answer 152

Myeloma bone disease can be improved using bisphosphonates. These suppress osteoclast activity. Radiotherapy to bone lesions can improve bone pain. Orthopaedic surgery can stabilise bones (e.g. by inserting a prophylactic intramedullary rod) or treat fractures. Cement augmentation involves injecting cement into vertebral fractures or lesions and can improve spine stability and pain

Answer 153

Infection Pain Renal failure Anaemia Hypercalcaemia Peripheral neuropathy Spinal cord compression Hyperviscocity

Answer 154

Primary myelofibrosis Polycythaemia vera Essential thrombocythemia

Answer 155

Conditions occurring due to uncontrolled proliferation of a single type of stem cells consider a type of bone marrow cancer

Answer 156

Hematopoietic stem cells

Answer 157

The erythroid cell line

Answer 158

The megakaryocytic cell line

Answer 159

Essential thrombocythaemia

Answer 160

Polycythaemia vera

Answer 161

Primary myelofibrosis

Answer 162

JAK2 MPL CALR

Answer 163

acute myeloid leukaemia

Answer 164

ruxolitinib JAK2 inhibitor

Answer 165

Myeloproliferative disorders: primary myelofibrosis, polycythaemia vera or essential thrombocythemia

Answer 166

Myelofibrosis is where the proliferation of the cell line leads to fibrosis of the bone marrow. The bone marrow is replaced by scar tissue in response to cytokines that are released from the proliferating cells. One particular cytokine is fibroblast growth factor. This fibrosis affects the production of blood cells and can lead to anaemia and low white blood cells (leukopenia). When the bone marrow is replaced with scar tissue the production of blood cells (haematopoiesis) starts to happen in other areas such as the liver and spleen. This is known as extramedullary haematopoiesis and can lead to hepatomegaly and splenomegaly. This can lead to portal hypertension. If it occurs around the spine it can lead to spinal cord compression.

Answer 167

Initially, myeloproliferative disorders can be asymptomatic. They can present systemic symptoms: Fatigue Weight loss Night sweats Fever There may be signs and symptoms of underlying complications: Anaemia (except in polycythaemia) Splenomegaly (abdominal pain) Portal hypertension (ascites, varices and abdominal pain) Low platelets (bleeding and petechiae) Thrombosis is common in polycythaemia and thrombocythaemia Raised red blood cells (thrombosis and red face) Low white blood cells (infections)

Answer 168

Conjunctival plethora (excessive redness to the conjunctiva in the eyes) A “ruddy” complexion Splenomegaly

Answer 169

Polycythaemia Vera: Raised haemoglobin (more than 185g/l in men or 165g/l in women) Primary Thrombocythaemia: Raised platelet count (more than 600 x 109/l) Myelofibrosis (due to primary MF or secondary to PV or ET) can give variable findings: - Anaemia - Leukocytosis or leukopenia (high or low white cell counts) - Thrombocytosis or thrombocytopenia (high or low platelet counts)

Answer 170

Teardrop-shaped RBCs, Varying sizes of red blood cells (poikilocytosis) Immature red and white cells (blasts).

Answer 171

Bone marrow biopsy is the test of choice to establish a diagnosis. Bone marrow aspiration is usually “dry” as the bone marrow has turned to scar tissue. Testing for the JAK2, MPL and CALR genes can help guide management.

Answer 172

Patients with mild disease with minimal symptoms might be monitored and not actively treated. Allogeneic stem cell transplantation is potentially curative but carries risks. Chemotherapy can help control the disease, improve symptoms and slow progression but is not curative on its own. Supportive management of the anaemia, splenomegaly and portal hypertension.

Answer 173

Venesection can be used to keep the haemoglobin in the normal range. This is the first line treatment. Aspirin can be used to reduce the risk of developing blood clots (thrombus formation). Chemotherapy can be used to control the disease.

Answer 174

Aspirin can be used to reduce the risk of developing blood clots (thrombus formation). Chemotherapy can be used to control the disease.

Answer 175

Myelodysplastic syndrome is caused by the myeloid bone marrow cells not maturing properly and therefore not producing healthy blood cells. There are a number of specific types of myelodysplastic syndrome.

Answer 176

Anaemia Neutropenia (low neutrophil count) Thrombocytopenia (low platelets)

Answer 177

It is more common in patients above 60 years of age and in patients that have previously had treatment with chemotherapy or radiotherapy.

Answer 178

There is an increased risk of transforming into acute myeloid leukaemia.

Answer 179

Patients may be asymptomatic and incidentally diagnosed based on a full blood count. They may present with symptoms of anaemia (fatigue, pallor or shortness of breath), neutropenia (frequent or severe infections) or thrombocytopenia (purpura or bleeding).

Answer 180

Full blood count will be abnormal. There may be blasts on the blood film. The diagnosis is confirmed by bone marrow aspiration and biopsy.

Answer 181

Depending on the symptoms, risk of progression and overall prognosis the treatment options are: Watchful waiting Supportive treatment with blood transfusions if severely anaemic Chemotherapy Stem cell transplantation

Answer 182

immunological: acute haemolytic, non-haemolytic febrile, allergic/anaphylaxis infective transfusion-related acute lung injury (TRALI) transfusion-associated circulatory overload (TACO) other: hyperkalaemia, iron overload, clotting

Answer 183

Thought to be caused by antibodies reacting with white cell fragments in the blood product and cytokines that have leaked from the blood cell during storage due to white blood cell HLA antibodies often the result of sensitization by previous pregnancies or transfusions

Answer 184

Fever, chills Red cell transfusion (1-2%) Platelet transfusion (10-30%)

Answer 185

Slow or stop the transfusion Paracetamol Monitor

Answer 186

Causes by foreign plasma proteins

Answer 187

Can be caused by patients with IgA deficiency who have anti-IgA antibodies

Answer 188

Temporarily stop the transfusion Antihistamine Monitor

Answer 189

Stop the transfusion IM adrenaline ABC support oxygen fluids

Answer 190

Hypotension, dyspnoea, wheezing, angioedema.

Answer 191

Pruritus, urticaria

Answer 192

ABO-incompatible blood e.g. secondary to human error

Answer 193

Fever, abdominal pain, hypotension

Answer 194

Stop transfusion Confirm diagnosis check the identity of patient/name on blood product send blood for direct Coombs test, repeat typing and cross-matching Supportive care fluid resuscitation

Answer 195

Excessive rate of transfusion, pre-exisiting heart failure

Answer 196

Pulmonary oedema, hypertension

Answer 197

Slow or stop transfusion Consider intravenous loop diuretic (e.g. furosemide) and oxygen

Answer 198

Non-cardiogenic pulmonary oedema thought to be secondary to increased vascular permeability caused by host neutrophils that become activated by substances in donated blood

Answer 199

Hypoxia, pulmonary infiltrates on chest x-ray, fever, hypotension, acute respiratory sidress syndrome

Answer 200

Stop the transfusion Oxygen and supportive care

Answer 201

Acute haemolytic transfusion reaction results from a mismatch of blood group (ABO) which causes massive intravascular haemolysis. This is usually the result of red blood cell destruction by IgM-type antibodies.

Answer 202

Symptoms begin minutes after the transfusion is started and include a fever, abdominal and chest pain, agitation and hypotension.

Answer 203

Disseminated intravascular coagulation, and renal failure

Answer 204

Symptoms typically arise within minutes of starting the transfusion and severity can range from urticaria to anaphylaxis with hypotension, dyspnoea, wheezing, and stridor, or angioedema.

Answer 205

Simple urticaria should be treated by discontinuing the transfusion and with an antihistamine. Once the symptoms resolve, the transfusion may be continued with no need for further workup.

Answer 206

within 6 hours of transfusion

Answer 207

TRALI - HYPOTENSION TACO - HYPERTENSION

Answer 208

although the absolute risk is very small, vCJD may be transmitted via blood transfusion a number of steps have been taken to minimise this risk, including: from late 1999 onward, all donations have undergone removal of white cells (leucodepletion) in order to reduce any vCJD infectivity present from 1999, plasma derivatives have been fractionated from imported plasma rather than being sourced from UK donors. Fresh Frozen Plasma (FFP) used for children and certain groups of adults needing frequent transfusions is also imported from 2004 onward, recipients of blood components have been excluded from donating blood

Answer 209

Packed red cells Platelet rich plasma Platelet concentrate Fresh frozen plasma Cryoprecipitate SAG-MAnnitol Blood

Answer 210

Removal of all plasma from a blood unit and substitution with: Sodium chloride Adenine Anhydrous glucose Mannitol Up to 4 units of SAG M Blood may be administered. Thereafter whole blood is preferred. After 8 units, clotting factors and platelets should be considered.

Answer 211

Formed from supernatant of FFP. Rich source of Factor VIII and fibrinogen. Allows large concentration of factor VIII to be administered in small volume.

Answer 212

Single units of blood

Answer 213

Prepared from single units of blood. Contains clotting factors, albumin and immunoglobulin. Unit is usually 200 to 250ml. Usually used in correcting clotting deficiencies in patients with hepatic synthetic failure who are due to undergo surgery. Usual dose is 12-15ml/Kg-1. It should not be used as first line therapy for hypovolaemia.

Answer 214

Prepared by high speed centrifugation and administered to patients with thrombocytopaenia.

Answer 215

Usually administered to patients who are thrombocytopaenic and are bleeding or require surgery.

Answer 216

It is obtained by low speed centrifugation.

Answer 217

Used for transfusion in chronic anaemia and cases where infusion of large volumes of fluid may result in cardiovascular compromise.

Answer 218

Product obtained by centrifugation of whole blood.

Answer 219

Packed red cells Fresh frozen plasma Cryoprecipitate Whole blood

Answer 220

These collect patients own blood lost during surgery and then re-infuse it. There are two main types: Those which wash the blood cells prior to re-infusion. These are more expensive to purchase and more complicated to operate. However, they reduce the risk of re-infusing contaminated blood back into the patient. Those which do not wash the blood prior to re-infusion.

Answer 221

Their main advantage is that they avoid the use of infusion of blood from donors into patients and this may reduce risk of blood borne infection. It may be acceptable to Jehovah's witnesses.

Answer 222

It is contraindicated in malignant disease for risk of facilitating disease dissemination.

Answer 223

1. Stop warfarin 2. Vitamin K (reversal within 4-24 hours) IV takes 4-6h to work (at least 5mg) Oral can take 24 hours to be clinically effective 3. Fresh frozen plasma Used less commonly now as 1st line warfarin reversal 30ml/kg-1 Need to give at least 1L fluid in 70kg person (therefore not appropriate in fluid overload) Need blood group Only use if human prothrombin complex is not available 4. Human Prothrombin Complex (reversal within 1 hour) Bereplex 50 u/kg Rapid action but factor 6 short half life, therefore give with vitamin K

Answer 224

insufficient dietary intake of vitamin B12 or pernicious anaemia.

Answer 225

Pernicious anaemia is a cause of B12 deficiency anaemia. B12 deficiency can be caused by Autoimmune condition - antibodies form against the parietal cells or intrinsic factor A lack of intrinsic factor prevents the absorption of vitamin B12 and the patient becomes vitamin B12 deficient.

Answer 226

Parietal cells of the stomach produce a protein called INTRINSIC FACTOR - essential for the absorption of vitamin B12 in the ileum

Answer 227

PERIPHERAL NEUROPATHY WITH NUMBNESS OR PARAESTHESIA (PINS AND NEEDLES) Loss of vibration sense or proprioception Visual changes Mood or cognitive changes

Answer 228

Autoantibodies - INTRINSIC FACTOR ANTIBODY - first line investigation Gastric parietal cell antibody can also be tested but is less helpful

Answer 229

DIETARY DEFICIENCY (if not severe): oral replacement with cyanocobalamin PERNICIOUS ANEMIA - IM hydroxocobalamin They can be treated with 1mg of intramuscular hydroxocobalamin 3 times weekly for 2 weeks, then every 3 months. (Oral replacement is inadequate because the problem is with absorption rather than intake) More intense regimens are used where there are neurological symptoms (e.g. 1mg every other day until the symptoms improve).

Answer 230

If there is also folate deficiency it is important to check and treat B12 deficiency first before correcting the folate deficiency. Treating patients with folic acid when they have a B12 deficiency can lead to subacute combined degeneration of the cord.

Answer 231

Treating patients with folic acid when they have a B12 deficiency can lead to subacute combined degeneration of the cord. Must correct B12 deficiency quickly

Answer 232

Haemolytic anaemia is where there is destruction of red blood cells (haemolysis) leading to anaemia. There are a number of inherited conditions that cause the red blood cells to be more fragile and break down faster than normal leading to chronic haemolytic anaemia. There are also a number of acquired conditions that lead to increased breakdown of red blood cells and haemolytic anaemia.

Answer 233

Hereditary Spherocytosis Hereditary Elliptocytosis Thalassaemia Sickle Cell Anaemia G6PD Deficiency

Answer 234

Autoimmune haemolytic anaemia Alloimmune haemolytic anaemia (transfusions reactions and haemolytic disease of newborn) Paroxysmal nocturnal haemoglobinuria Microangiopathic haemolytic anaemia Prosthetic valve related haemolysis

Answer 235

(prehepatic) jaundice (unconjugated bilirubin released in breakdown of RBC) Anaemia (reduction in circulating RBC) Splenomegaly (spleen becomes filled with destroyed red blood cells)

Answer 236

FULL BLOOD COUNT Full blood count shows a normocytic anaemia BLOOD FILM Blood film shows schistocytes (fragments of red blood cells) DIRECT COOMBS TEST Direct Coombs test is positive in autoimmune haemolytic anaemia

Answer 237

Hereditary spherocytosis

Answer 238

It is an autosomal dominant condition. It causes sphere shaped red blood cells that are fragile and easily break down when passing through the spleen. - most common hereditary haemolytic anaemia in people of northern European descent - autosomal dominant defect of red blood cell cytoskeleton - the normal biconcave disc shape is replaced by a sphere-shaped red blood cell - red blood cell survival reduced as destroyed by the spleen

Answer 239

Spherocytosis (fragments of RBC) seen in haemolytic anaemia

Answer 240

It presents with jaundice, gallstones, splenomegaly, failure to thrive, MCHC elevated, and notably aplastic crisis in the presence of the parvovirus.

Answer 241

It is diagnosed by family history and clinical features with spherocytes on the blood film. The mean corpuscular haemoglobin concentration (MCHC) is raised on a full blood count. Reticulocytes will be raised due to rapid turnover of red blood cells. the British Journal of Haematology (BJH) guidelines state that 'patients with a family history of HS, typical clinical features and laboratory investigations (spherocytes, raised mean corpuscular haemoglobin concentration [MCHC], increase in reticulocytes) do not require any additional tests if the diagnosis is equivocal the BJH recommend the EMA binding test and the cryohaemolysis test for atypical presentations electrophoresis analysis of erythrocyte membranes is the method of choice

Answer 242

Spherocytes on the blood film. The mean corpuscular haemoglobin concentration (MCHC) is raised on a full blood count. Reticulocytes will be raised due to rapid turnover of red blood cells.

Answer 243

Hereditary elliptocytosis is very similar to hereditary spherocytosis except that the red blood cells are ellipse shaped. It is also autosomal dominant. Presentation and management are the same: - It presents with jaundice, gallstones, splenomegaly and notably aplastic crisis in the presence of the parvovirus. elliptocytosis on the blood film. - The mean corpuscular haemoglobin concentration (MCHC) is raised on a full blood count. Reticulocytes will be raised due to rapid turnover of red blood cells. - Treatment is with folate supplementation and splenectomy. Removal of the gallbladder (cholecystectomy) may be required if gallstones are a problem.

Answer 244

G6PD deficiency is a condition where there is a defect in the red blood cell enzyme G6PD. It is more common in Mediterranean and African patients and is X LINKED RECESSIVE It causes crises that are triggered by infections, medications or fava beans (broad beans).

Answer 245

It presents with jaundice (usually in the neonatal period), gallstones, anaemia, splenomegaly and Heinz bodies on blood film. May also see bite and blister cells.

Answer 246

G6PD enzyme assay levels should be checked around 3 months after an acute episode of hemolysis, RBCs with the most severely reduced G6PD activity will have hemolysed → reduced G6PD activity → not be measured in the assay → false negative results

Answer 247

Infections Fava beans (broad beans) Medications Medications that trigger haemolysis include: - Primaquine (an antimalarial) - Ciprofloxacin - Sulfonylureas - Sulfasalazine and other sulphonamide drugs.

Answer 248

Autoimmune haemolytic anaemia occurs when antibodies are created against the patient’s red blood cells. These antibodies lead to destruction of the red blood cells. There are two types based on the temperature at which the auto-antibodies function to cause the destruction of red blood cells: - Warm Type Autoimmune Haemolytic Anaemia - Cold Type Autoimmune Haemolytic Anaemia

Answer 249

Autoimmune haemolytic anaemia occurs when antibodies are created against the patient’s red blood cells. These antibodies lead to destruction of the red blood cells. Haemolysis occurs at normal or above normal temperatures. In warm AIHA the antibody (usually IgG) causes haemolysis best at body temperature and haemolysis tends to occur in extravascular sites, for example the spleen. It is usually idiopathic, meaning that it arises without a clear cause. Other causes: autoimmune disease: e.g. systemic lupus erythematosus* neoplasia lymphoma chronic lymphocytic leukaemia drugs: e.g. methyldopa

Answer 250

Also known as cold autoimmune haemolytic anemia. At lower temperatures (e.g. less than 10ºC) the antibodies against red blood cells attach themselves to the red blood cells and cause them to clump together. This is called agglutination. This agglutination results in the destruction of the red blood cells as the immune system is activated against them and they get filtered and destroyed in the spleen. The antibody in cold AIHA is usually IgM and causes haemolysis best at 4 deg C. Haemolysis is mediated by complement and is more commonly intravascular. Features may include symptoms of Raynaud's and acrocynaosis. Patients respond less well to steroids

Answer 251

Conditions such as: - Lymphoma - Leukaemia - Systemic lupus erythematosus Infections such as: -Mycoplasma - EBV - CMV - HIV

Answer 252

Blood transfusions Prednisolone (steroids) Rituximab (a monoclonal antibody against B cells) Splenectomy

Answer 253

Alloimmune haemolytic anaemia occurs where an there is either foreign red blood cells circulating in the patients blood causing an immune reaction that destroys those red blood cells or there is a foreign antibody circulating in their blood that acts against their own red blood cells and causes haemolysis. The two scenarios where this occurs are transfusion reactions and haemolytic disease of the newborn. In hemolytic transfusion reactions red blood cells are transfused into the patient. The immune system produces antibodies against antigens on those foreign red blood cells. This creates an immune response that leads to the destruction of those red blood cells. In haemolytic disease of the newborn there are antibodies that cross the placenta from the mother to the fetus. These maternal antibodies target antigens on the red blood cells of the fetus. This causes destruction of the red blood cells in the fetus and neonate.

Answer 254

Paroxysmal nocturnal haemoglobinuria is a rare condition that occurs when a specific genetic mutation in the haematopoietic stem cells in the bone marrow occurs during the patients lifetime. The specific mutation results in a loss of the proteins on the surface of red blood cells that inhibit the complement cascade. The loss of protection against the complement system results in activation of the complement cascade on the surface of red blood cells and destruction of the red blood cells.

Answer 255

The characteristic presentation is red urine in the morning containing haemoglobin and haemosiderin. The patient becomes anaemic due to the haemolysis. They are also predisposed to thrombosis (e.g. DVT, PE and hepatic vein thrombosis) and smooth muscle dystonia (e.g. oesophageal spasm and erectile dysfunction).

Answer 256

Management is with ECULIZUMAB or BONE MARROW TRANSPLANTATION Eculizumab is a monoclonal antibody that targets complement component 5 (C5) causing suppression of the complement system. Bone marrow transplantation can be curative.

Answer 257

Microangiopathic haemolytic anaemia (MAHA) is where the small blood vessels have structural abnormalities that cause haemolysis of the blood cells travelling through them.

Answer 258

This is usually secondary to an underlying condition: - Haemolytic Uraemic Syndrome (HUS) - Disseminated Intravascular Coagulation (DIC) - Thrombotic Thrombocytopenia Purpura (TTP) - Systemic Lupus Erythematosus (SLE) - Cancer

Answer 259

Haemolytic anaemia is a key complication of prosthetic heart valves. It occurs in both bioprosthetic and metallic valve replacement. It is caused by turbulence around the valve and collision of red blood cells with the implanted valve (the valve churns up the cells and they break down)

Answer 260

Monitoring Oral iron Blood transfusion if severe Revision surgery may be required in severe cases

Answer 261

Thalassaemia is related to a genetic defect in the protein chains that make up haemoglobin. Normal haemoglobin consists of 2 alpha and 2 beta-globin chains. Defects in alpha-globin chains leads to alpha thalassaemia. Defects in the beta-globin chains leads to beta thalassaemia. Both conditions are autosomal recessive. The overall effect is varying degrees of anaemia depends on the type and mutation. In thalassaemia, the red blood cells are more fragile and break down more easily. The spleen acts as a sieve to filter the blood and remove older blood cells. The bone marrow expands to produce extra red blood cells to compensate for the chronic anaemia.

Answer 262

Microcytic anaemia (low mean corpuscular volume) Fatigue Pallor Jaundice Gallstones Splenomegaly Poor growth and development Pronounced forehead and malar eminences

Answer 263

Susceptibility to fractures and prominent features such as a pronounced forehead and malar eminences (cheekbones) due to bone marrow expansion (to compensate for the chronic anaemia) Splenomegaly - in thalassaemia the spleen collects all the destroyed red blood cells and swells, resulting in Pallor Jaundice

Answer 264

Full blood count shows a microcytic anaemia. Haemoglobin electrophoresis is used to diagnose globin abnormalities. DNA testing can be used to look for the genetic abnormality Pregnant women in the UK are offered a screening test for thalasseamia at booking.

Answer 265

Iron overload occurs in thalassaemia as a result of faulty creation of red blood cells, recurrent transfusions and increased absorption of iron in response to the anaemia. Patients with thalassaemia have serum ferritin levels monitored to check for iron overload. Management involves limiting transfusions and iron chelation.

Answer 266

Fatigue Liver cirrhosis Infertility and impotence Heart failure Arthritis Diabetes Osteoporosis and joint pain

Answer 267

Alpha-thalassaemia is caused by defects in alpha-globin chains. The gene coding for this protein is on chromosome 16.

Answer 268

Monitoring the full blood count Monitoring for complications Blood transfusions Splenectomy may be performed Bone marrow transplant can be curative

Answer 269

Beta-thalassaemia is caused by defects in beta-globin chains. The gene coding for this protein is on chromosome 11.

Answer 270

1. Thalassaemia minor - carriers of an abnormally functioning beta globin gene, they have one abnormal and one normal gene, mild microcytic anaemia 2. Thalassaemia intermedia - two abnormal copies of the beta-globin gene (x2 defective genes or x1 defective gene + x1 deletion gene), causes a more significant microcytic anaemia 3. Thalassaemia major - patients are homozygous for the deletion genes & have no functioning beta-globin genes at all. This is the most severe form and usually presents with severe anaemia and failure to thrive in early childhood.

Answer 271

1. Thalassaemia minor - usually patients only require monitoring and no active treatment 2. Thalassaemia intermedia - patients require monitoring and occasional blood transfusions. If they need more transfusions they may require iron chelation to prevent iron overload. 3. Thalassaemia major regular transfusions, iron chelation and splenectomy. Bone marrow transplant can potentially be curative.

Answer 272

1. Severe microcytic anaemia 2. Splenomegaly 3. Bone deformities Likely to present with failure to thrive in childhood

Answer 273

Sickle cell anaemia is a genetic condition that causes sickle (crescent) shaped red blood cells. This makes the red blood cells fragile and more easily destroyed leading to an haemolytic anaemia. Patients with sickle cell anaemia are prone to various types of sickle cell crises. Patients with sickle-cell disease have an abnormal variant called haemoglobin S (HbS). HbS causes red blood cells to be an abnormal “sickle” shape. Sickle cell anaemia is an autosomal recessive condition where there is an abnormal gene for beta-globin on chromosome 11. One copy of the gene results in sickle-cell trait. Patients with sickle-cell trait are usually asymptomatic. Two abnormal copies are required for sickle-cell disease.

Answer 274

Having one copy of the gene (sickle-cell trait) reduces the severity of malaria. As a result, patients with sickle-cell trait are more likely to survive malaria and pass on their genes. Therefore, there is a selective advantage to having the sickle cell gene in areas of malaria. This leads to a high proportion of the population in these areas having the gene.

Answer 275

Pregnant women at risk of being carriers of the sickle cell gene are offered testing during pregnancy. Sickle cell disease is also tested for on the on the newborn screening heel prick test at 5 days of age.

Answer 276

Anaemia Increased risk of infection Stroke Avascular necrosis in large joints such as the hip Pulmonary hypertension Painful and persistent penile erection (priapism) Chronic kidney disease Sickle cell crises Acute chest syndrome

Answer 277

Avoid dehydration and other triggers of crises Ensure vaccines are up to date Antibiotic prophylaxis to protect against infection with penicillin V (phenoxymethypenicillin) Hydroxycarbamide can be used to stimulate production of fetal haemoglobin (HbF). Fetal haemoglobin does not lead to sickling of red blood cells. This has a protective effect against sickle cell crises and acute chest syndrome. Blood transfusion for severe anaemia Bone marrow transplant can be curative

Answer 278

Sickle cell crisis is an umbrella term for a spectrum of acute crises related to the condition. These range from mild to life threatening. They can occur spontaneously or be triggered by stresses such as infection, dehydration, cold or significant life events.

Answer 279

There is no specific treatment for sickle cell crises and they are managed supportively: Have a low threshold for admission to hospital Treat any infection Keep warm Keep well hydrated (IV fluids may be required) Simple analgesia such as paracetamol and ibuprofen Penile aspiration in priapism NSAIDs such as ibuprofen should be avoided where there is renal impairment.

Answer 280

Vaso-occlusive Crisis (AKA painful crisis) Splenic sequestration crisis Aplastic crisis Acute chest syndrome

Answer 281

Vaso-occlusive crisis is caused by the sickle shaped blood cells clogging capillaries causing distal ischaemia. It is associated with dehydration and raised haematocrit.

Answer 282

Symptoms are typically pain, fever and those of the triggering infection. It can cause priapism in men by trapping blood in the penis causing a painful and persistent erection. This is a urological emergency and is treated with aspiration of blood from the penis. Supportive management: Have a low threshold for admission to hospital Treat any infection Keep warm Keep well hydrated (IV fluids may be required)

Answer 283

Splenic sequestration crisis is caused by red blood cells blocking blood flow within the spleen. This causes an acutely enlarged and painful spleen. The pooling of blood in the spleen can lead to a severe anaemia and circulatory collapse (hypovolaemic shock). Recurrent crises can lead to splenic infarction and therefore susceptibility to infections.

Answer 284

Splenic sequestration crisis is considered an emergency. Management is supportive with blood transfusions and fluid resuscitation to treat anaemia and shock. Splenectomy prevents sequestration crisis and is often used in cases of recurrent crises.

Answer 285

It leads to significant anaemia. Management is supportive with blood transfusions if necessary. It usually resolves spontaneously within a week.

Answer 286

Aplastic crisis describes a situation where there is a temporary loss of the creation of new blood cells. This is most commonly triggered by infection with parvovirus B19.

Answer 287

Is a medical emergency with a high mortality and requires prompt supportive management and treatment of the underlying cause: Antibiotics or antivirals for infections Blood transfusions for anaemia Incentive spirometry using a machine that encourages effective and deep breathing Artificial ventilation with NIV or intubation may be required

Answer 288

Infection (e.g. pneumonia or bronchiolitis) Non-infective causes (e.g. pulmonary vaso-occlusion or fat emboli).

Answer 289

Fever or respiratory symptoms with New infiltrates seen on a chest xray

Answer 290

Thrombocytopenia describes a low platelet count. The normal platelet count is between 150 to 450 x 109/L. Problems with production or destruction.

Answer 291

Sepsis B12 or folic acid deficiency Liver failure causing reduced thrombopoietin production in the liver Leukaemia Myelodysplastic syndrome

Answer 292

Medications (sodium valproate, methotrexate, isotretinoin, antihistamines, proton pump inhibitors) Alcohol Immune thrombocytopenic purpura Thrombotic thrombocytopenic purpura Heparin-induced thrombocytopenia Haemolytic-uraemic syndrome

Answer 293

Sodium valproate Methotrexate Isotretinoin Antihistamines Proton pump inhibitors Heparin-induced thrombocytopenia

Answer 294

Mild thrombocytopenia - may be asymptomatic and found incidentally on a full blood count. Platelet counts below 50 x 109/L will result in easy or spontaneous bruising and prolonged bleeding times: - Nosebleeds - Bleeding gums - Heavy periods - Easy bruising or blood in the urine or stools. Platelet counts below 10 x 109/L are high risk for spontaneous bleeding: - Spontaneous intracranial haemorrhage - GI bleeds are particularly concerning

Answer 295

50 x 109/L

Answer 296

10 x 109/L

Answer 297

Thrombocytopenia (low platelets) Haemophilia A and haemophilia B Von Willebrand Disease Disseminated intravascular coagulation (usually secondary to sepsis)

Answer 298

autoimmune thrombocytopenic purpura idiopathic thrombocytopenic purpura primary thrombocytopenic purpura ITP is a condition where antibodies are created against platelets. This causes an immune response against platelets, resulting in the destruction of platelets and a low platelet count.

Answer 299

Management options include: Prednisolone (steroids) IV immunoglobulins Rituximab (a monoclonal antibody against B cells) Splenectomy The platelet count needs to be monitored and the patient needs education about concerning signs of bleeding such as persistent headaches and melaena and when to seek help. Additional measures such as carefully controlling blood pressure and suppressing menstrual periods are also important.

Answer 300

This is a condition where tiny blood clots develop throughout the small vessels of the body using up platelets and causing thrombocytopenia, bleeding under the skin and other systemic issues. It affect the small vessels so it is described as a microangiopathy.

Answer 301

Tiny blood clots develop throughout the small vessels clots develop due to a problem with a specific protein called ADAMTS13 This protein normally inactivates von Willebrand factor and reduces platelet adhesion to vessel walls and clot formation. A shortage in this protein leads to von Willebrand factor overactivity and the formation of blood clots in small vessels This causes platelets to be used up leading to thrombocytopenia. The blood clots in the small vessels break up red blood cells, leading to haemolytic anaemia. Deficiency in the ADAMTS13 protein can be due to an inherited genetic mutation or due to autoimmune disease where antibodies are created against the protein.

Answer 302

Treatment is guided by a haematologist and may involve plasma exchange, steroids and rituximab (a monoclonal antibody against B cells).

Answer 303

Heparin induced thrombocytopenia (HIT) involves the development of antibodies against platelets in response to exposure to heparin. These heparin induced antibodies specifically target a protein on the platelets called platelet factor 4 (PF4). These are anti-PF4/heparin antibodies. The HIT antibodies bind to platelets and activate clotting mechanisms. This causes a hypercoagulable state and leads to thrombosis. They also break down platelets and cause thrombocytopenia. Therefore there is an unintuitive situation where a patient on heparin with low platelets forms unexpected blood clots.

Answer 304

Diagnosis is by testing for the HIT antibodies in the patients blood.

Answer 305

Management is by stopping heparin and using an alternative anticoagulant guided by a specialist.

Answer 306

This protein normally inactivates von Willebrand factor and reduces platelet adhesion to vessel walls and clot formation (shortage in this protein leads to von Willebrand factor overactivity and the formation of blood clots in small vessels) Deficiency in the ADAMTS13 protein can be due to an inherited genetic mutation or due to autoimmune disease where antibodies are created against the protein.

Answer 307

Von Willebrand disease

Answer 308

Most causes are autosomal dominant. The causes involve: - a deficiency - absence - malfunctioning of a glycoprotein called von Willebrand factor (VWF). There are three types based on the underlying cause and ranging from type 1 to type 3. Type 3 is the most severe.

Answer 309

Patients present with a history of unusually easy, prolonged or heavy bleeding: Bleeding gums with brushing Nose bleeds (epistaxis) Heavy menstrual bleeding (menorrhagia) Heavy bleeding during surgical operations Family history of heavy bleeding or von Willebrand disease is very relevant.

Answer 310

History of abnormal bleeding, family history Bleeding assessment tools and laboratory investigations Due to all the underlying causes there is no easy von Willebrand disease test. This can make diagnosis challenging

Answer 311

Von Willebrand disease does not require day to day treatment. Management is required either in response to major bleeding or trauma (to stop bleeding) or in preparation for operations (to prevent bleeding): - Desmopressin can be used to stimulates the release of VWF - VWF can be infused - Factor VIII is often infused along with plasma-derived VWF Women with VWD that suffer from heavy periods can be managed by a combination of: Tranexamic acid Mefanamic acid Norethisterone Combined oral contraceptive pill Mirena coil Hysterectomy may be required in severe cases.

Answer 312

Haemophilia A is caused by a deficiency in factor VIII.

Answer 313

Haemophilia B (also known as Christmas disease) is caused by a deficiency in factor IX.

Answer 314

Both haemophilia A and B are X linked recessive. This means in order to have the condition all of the X chromosomes need to have the abnormal gene. Men only require one abnormal copy as they only have one X chromosome. Women require abnormal copies on both their X chromosomes, and if only one copy is affected they are a carrier of the condition. Therefore haemophilia A and B almost exclusively affect males. For a female to be affected they would require an affected father and a mother that is either a carrier or also affected.

Answer 315

Both haemophilia A and B are severe bleeding disorders. Patients can bleed excessively in response to minor trauma and are also at risk of spontaneous haemorrhage without any trauma. Most cases present in neonates or early childhood. It can present with intracranial haemorrhage, haematomas and cord bleeding in neonates. Spontaneous bleeding into joints (haemoathrosis) and muscles are a classic feature of severe haemophilia. If untreated this can lead to joint damage and deformity. Abnormal bleeding can occur in other areas: Gums Gastrointestinal tract Urinary tract causing haematuria Retroperitoneal space Intracranial Following procedures

Answer 316

Management should be coordinated by a specialist. The affected clotting factors (VIII or IX) can be replaced by intravenous infusions. This can be either prophylactically or in response to bleeding. A complication of this treatment is formation of antibodies against the clotting factor resulting in the treatment becoming ineffective. Acute episodes of bleeding or prevention of excessive bleeding during surgical procedures involve: Infusions of the affected factor (VIII or IX) Desmopressin to stimulate the release of von Willebrand Factor Antifibrinolytics such as tranexamic acid

Answer 317

Bleeding scores Coagulation factor assays Genetic testing

Answer 318

- Infusions of the affected factor (VIII or IX) - Desmopressin to stimulate the release of von Willebrand Factor - Antifibrinolytics such as tranexamic acid

Answer 319

haemophilia b

Answer 320

haemophilia A

Answer 321

Venous thromboembolism (VTE) is a common and potentially fatal condition. It involves blood clots (thrombi) developing in the circulation. This usually occurs secondary to stagnation of blood and hyper-coagulable states. When a thrombus develops in the venous circulation, it is called a deep vein thrombosis (DVT). Once a thrombus has developed, it can travel (embolise) from the deep veins, through the right side of the heart and into the lungs, where it becomes lodged in the pulmonary arteries. This blocks blood flow to areas of the lungs and is called a pulmonary embolism (PE). If the patient has a hole in their heart (for example, an atrial septal defect), the blood clot can pass through to the left side of the heart and into the systemic circulation. If it travels to the brain, it can cause a large stroke.

Answer 322

Immobility Recent surgery Long haul travel Pregnancy Hormone therapy with oestrogen (combined oral contraceptive pill and hormone replacement therapy) Malignancy Polycythaemia Systemic lupus erythematosus Thrombophilia

Answer 323

Antiphospholipid syndrome Factor V Leiden Antithrombin deficiency Protein C or S deficiency Hyperhomocysteinaemia Prothombin gene variant Activated protein C resistance

Answer 324

Antiphospholipid syndrome, diagnosed by testing for antiphospholipid antibodies

Answer 325

Every patient admitted to hospital should be assessed for their risk of venous thromboembolism (VTE). If they are at increased risk of VTE, they should receive prophylaxis unless contraindicated. Prophylaxis is usually with low molecular weight heparin, such as enoxaparin. Contraindications include active bleeding or existing anticoagulation with warfarin or a DOAC. Anti-embolic compression stockings are also used, unless contraindicated. The main contraindication for compression stockings is significant peripheral arterial disease.

Answer 326

DVTs are almost always unilateral. Bilateral DVT is rare and bilateral symptoms are more likely due to an alternative diagnosis such as chronic venous insufficiency or heart failure. DVTs can present with: Calf or leg swelling Dilated superficial veins Tenderness to the calf (particularly over the site of the deep veins) Oedema Colour changes to the leg

Answer 327

Wells Score The Wells score predicts the risk of a patient presenting with symptoms having a DVT or PE. It includes risk factors such as recent surgery and clinical findings such as unilateral calf swelling 3cm greater than the other leg. Diagnosis D-dimer is a sensitive (95%), but not specific, blood test for VTE. This makes it helpful in excluding VTE where there is a low suspicion. It is almost always raised if there is a DVT; however other conditions can also cause a raised d-dimer: Pneumonia Malignancy Heart failure Surgery Pregnancy Doppler ultrasound of the leg is required to diagnose deep vein thrombosis. NICE recommends repeating negative ultrasound scans after 6-8 days if a positive D-dimer and the Wells score suggest a DVT is likely. Pulmonary embolism can be diagnosed with a CT pulmonary angiogram (CTPA) or ventilation-perfusion (VQ) scan. CTPA is usually preferred, unless the patient has significant kidney impairment or a contrast allergy.

Answer 328

To examine for leg swelling, measure the circumference of the calf 10cm below the tibial tuberosity. More than 3cm difference between calves is significant.

Answer 329

The initial management for a suspected or confirmed DVT or PE is with anticoagulation. In most patients, NICE (2020) recommend treatment dose apixaban or rivaroxaban. It should be started immediately in patients where DVT or PE is suspected, and there is a delay in getting the scan. The NICE guidelines (2020) recommend considering catheter-directed thrombolysis in patients with a symptomatic iliofemoral DVT and symptoms lasting less than 14 days. This involves inserting a catheter under x-ray guidance through the venous system to apply thrombolysis directly into the clot.

Answer 330

The options for long term anticoagulation in VTE are a DOAC, warfarin, or LMWH. DOACs are oral anticoagulants that do not require monitoring. They were called “novel oral anticoagulants” (NOACs), but this has been changed to “direct-acting oral anticoagulants” (DOACs). Options are apixaban, rivaroxaban, edoxaban and dabigatran. They are suitable for most patients, including patients with cancer. Warfarin is a vitamin K antagonist. The target INR for warfarin is between 2 and 3 when treating DVTs and PEs. It is the first-line in patients with antiphospholipid syndrome (who also require initial concurrent treatment with LMWH). Low molecular weight heparin (LMWH) is the first-line anticoagulant in pregnancy.

Answer 331

3 months if there is a reversible cause (then review) Beyond 3 months if the cause is unclear, there is recurrent VTE, or there is an irreversible underlying cause such as thrombophilia (often 6 months in practice) 3-6 months in active cancer (then review)

Answer 332

Inferior vena cava filters are devices inserted into the inferior vena cava, designed to filter the blood and catch any blood clots travelling from the venous system, towards the heart and lungs. They act as a sieve, allowing blood to flow through whilst stopping larger blood clots. They are used in unusual cases of patients with recurrent PEs or those that are unsuitable for anticoagulation.

Answer 333

When patients have their first VTE without a clear cause, the NICE guidelines from 2020 recommend reviewing the medical history, baseline blood results and physical examination for evidence of cancer. In patients with an unprovoked DVT or PE that are not going to continue anticoagulation (they have finished 3-6 months of treatment and are due to stop), NICE recommends considering testing for: - Antiphospholipid syndrome (check antiphospholipid antibodies) - Hereditary thrombophilias (only if they have a first-degree relative also affected by a DVT or PE)

Answer 334

Budd-Chiari syndrome is where a blood clot (thrombosis) develops in the hepatic vein, blocking the outflow of blood. It is associated with hyper-coagulable states. It causes acute hepatitis.

Answer 335

Abdominal pain Hepatomegaly Ascites

Answer 336

Management involves anticoagulation (heparin or warfarin), investigating for the underlying cause of hyper-coagulation and treating hepatitis.

Answer 337

Granulocyte transfusions Intra-uterine transfusions Neonates up to 28 days posts expected date of delivery Pregnancy: elective transfusion during pregnancy (not labour or delivery)

Answer 338

Granulocyte transfusion Intra-uterine transfusions Neonates up to 28 days post expected date of delivery Bone marrow/stem cell transplants Immunocompromised Patients with/previous Hodgkin lymphoma

Answer 339

most suited for 'clinically significant' but without 'major haemorrhage' in patients with a prothrombin time (PT) ratio or activated partial thromboplastin time (APTT) ratio > 1.5 typically 150-220 mL can be used prophylactically in patients undergoing invasive surgery where there is a risk of significant bleeding In contrast to red cells, the universal donor of FFP is AB blood because it lacks any anti-A or anti-B antibodies

Answer 340

contains concentrated Factor VIII:C, von Willebrand factor, fibrinogen, Factor XIII and fibronectin, produced by further processing of Fresh Frozen Plasma (FFP). much smaller volume than FFP, typically 15-20mL

Answer 341

Clinically it is most commonly used to replace fibrinogen most suited for patients for 'clinically significant' but without 'major haemorrhage' who have a fibrinogen concentration < 1.5 g/L example use cases include disseminated intravascular coagulation, liver failure and hypofibrinogenaemia secondary to massive transfusion. It may also be used in an emergency situation for haemophiliacs (when specific factors not available) and in von Willebrand disease can be used prophylactically in patients undergoing invasive surgery where there is a risk of significant bleeding where the fibrinogen concentration < 1.0 g/L

Answer 342

used for the emergency reversal of anticoagulation in patients with either severe bleeding or a head injury with suspected intracerebral haemorrhage can be used prophylactically in patients undergoing emergency surgery depending on the particular circumstance

Answer 343

Patients without ACS - 70 g/L Patients with ACS - 80 g/L

Answer 344

Patients without ACS - 70-90 g/L Patients with ACS - 80-100 g/L ie. up to 20 above the transfusion threshold

Answer 345

red blood cells should be stored at 4°C

Answer 346

90-120 minutes

Answer 347

Graft versus host disease (GVHD) is a multi-system complication of allogeneic bone marrow transplantation. Less frequently, it may also occur following solid organ transplantation or transfusion in immunocompromised patients. The disease occurs when T cells in the donor tissue (the graft) mount an immune response toward recipient (host) cells. It is not to be confused with transplant rejection (in which recipient immune cells activate an immune response toward the donor tissue). Prognosis is generally poor.

Answer 348

Three conditions required for diagnosis of GVHD, known as the Billingham criteria 1: The transplanted tissue contains immunologically functioning cells The recipient and donor are immunologically different The recipient is immunocompromised

Answer 349

Poorly matched donor and recipient (particularly HLA) Type of conditioning used prior to transplantation Gender disparity between donor and recipient Graft source (bone marrow or peripheral blood source associated with higher risk than umbilical cord blood)

Answer 350

Classically 100 days following transplantation May occur following acute disease, or can arise de novo

Answer 351

Has a more varied clinical picture: often lung and eye involvement in addition to skin and GI, although any organ system may be involved Skin: Many manifestations including poikiloderma, scleroderma, vitiligo, lichen planus Eye: Often keratoconjunctivitis sicca, also corneal ulcers, scleritis GI: Dysphagia, odynophagia, oral ulceration, ileus. Oral lichenous changes are a characteristic early sign (2) Lung: my present as obstructive or restrictive pattern lung disease

Answer 352

Usually affects the skin (>80%), liver (50%), and gastrointestinal tract (50%) Multi-organ involvement carries a worse prognosis** Painful maculopapular rash (often neck, palms and soles), which may progress to erythroderma or a toxic epidermal necrolysis-like syndrome Jaundice Watery or bloody diarrhoea Persistent nausea and vomiting Can also present as a culture-negative fever

Answer 353

Investigations (largely dependent on which organs are involved): LFTs may demonstrate cholestatic jaundice. Hepatitis screen/ultrasound may be useful to exclude other causes Abdominal imaging may reveal air-fluid levels and small bowel thickening ('ribbon sign') Lung function testing Biopsy of affected tissue may aid in diagnosis if there is uncertainty

Answer 354

Management consists of immunosuppression and supportive measures. Intravenous steroids are the mainstay of immunosuppressive treatment in severe cases of acute GVHD. Extended courses of steroid therapy are often needed in chronic GVHD and dose tapering is vital. Second-line therapies include anti-TNF, mTOR inhibitors and extracorporeal photopheresis. Excessive immunosuppression may predispose patients to infection, and also limit the beneficial graft-versus-tumour effect of the transplant. Topical steroid therapy may be sufficient in mild disease with limited cutaneous involvement.

Answer 355

Characterised by pancytopenia and a hypoplastic bone marrow Peak incidence of acquired = 30 years old Features: normochromic, normocytic anaemia leukopenia, with lymphocytes relatively spared thrombocytopenia may be the presenting feature acute lymphoblastic or myeloid leukaemia a minority of patients later develop paroxysmal nocturnal haemoglobinuria or myelodysplasia

Answer 356

hyperkalaemia, hyperphosphataemia, hyperuricaemia and hypocalcaemia.

Answer 357

Fortnightly blood transfusions

Answer 358

Piperacillin with tazobactam is recommended as the first-line antibiotic by NICE,

Answer 359

Hydroxycarbamide (previously known as hydroxyurea) is a ribonucleotide reductase inhibitor that increases the levels of foetal haemoglobin (Hb F) in the blood, which has been shown to reduce the frequency of sickle cell crises, reduce hospitalisation and decrease mortality.

Answer 360

Prevents activation factors 2,9,10,11

Answer 361

Affects synthesis of factors 2,7,9,10

Answer 362

Factors 1,2,5,8,11

Answer 363

Factors 1,2,5,7,9,10,11

Answer 364

VITAMIN K DEF

Answer 365

Haemophilia

Answer 366

von Willebrand's disease

Answer 367

Acute intermittent porphyria (AIP) is a rare autosomal dominant condition caused by a defect in porphobilinogen deaminase, an enzyme involved in the biosynthesis of haem. The results in the toxic accumulation of delta aminolaevulinic acid and porphobilinogen. It characteristically presents with abdominal and neuropsychiatric symptoms in 20-40-year-olds. AIP is more common in females (5:1)

Answer 368

abdominal: abdominal pain, vomiting neurological: motor neuropathy psychiatric: e.g. depression hypertension and tachycardia common

Answer 369

Diagnosis classically urine turns deep red on standing raised urinary porphobilinogen (elevated between attacks and to a greater extent during acute attacks) assay of red cells for porphobilinogen deaminase raised serum levels of delta aminolaevulinic acid and porphobilinogen Management avoiding triggers acute attacks IV haematin/haem arginate IV glucose should be used if haematin/haem arginate is not immediately available

Answer 370

Features are largely related to bone marrow failure: anaemia: pallor, lethargy, weakness neutropenia: whilst white cell counts may be very high, functioning neutrophil levels may be low leading to frequent infections etc thrombocytopenia: bleeding splenomegaly bone pain

Answer 371

> 60 years > 20% blasts after first course of chemo cytogenetics: deletions of chromosome 5 or 7

Answer 372

associated with t(15;17) fusion of PML and RAR-alpha genes presents younger than other types of AML (average = 25 years old) Auer rods (seen with myeloperoxidase stain) DIC or thrombocytopenia often at presentation good prognosis The importance of identifying APML lies in both the presentation (classically disseminated intravascular coagulation) and management

Answer 373

Classification - French-American-British (FAB) MO - undifferentiated M1 - without maturation M2 - with granulocytic maturation M3 - acute promyelocytic M4 - granulocytic and monocytic maturation M5 - monocytic M6 - erythroleukaemia M7 - megakaryoblastic

Answer 374

recurrent miscarriage IUGR pre-eclampsia placental abruption pre-term delivery venous thromboembolism

Answer 375

low-dose aspirin should be commenced once the pregnancy is confirmed on urine testing low molecular weight heparin once a fetal heart is seen on ultrasound. This is usually discontinued at 34 weeks gestation these interventions increase the live birth rate seven-fold

Answer 376

idiopathic congenital: Fanconi anaemia, dyskeratosis congenita drugs: cytotoxics, chloramphenicol, sulphonamides, phenytoin, gold toxins: benzene infections: parvovirus, hepatitis radiation

Answer 377

Characterised by pancytopenia and a hypoplastic bone marrow Peak incidence of acquired = 30 years old Features - normochromic, normocytic anaemia - leukopenia, with lymphocytes relatively spared thrombocytopenia may be the presenting feature acute lymphoblastic or myeloid leukaemia a minority of patients later develop paroxysmal nocturnal haemoglobinuria or myelodysplasia

Answer 378

treatment of any underlying disorder steroids (+/- rituximab) are generally used first-line

Answer 379

general features of haemolytic anaemia anaemia reticulocytosis low haptoglobin raised lactate dehydrogenase (LDH) and indirect bilirubin blood film: spherocytes and reticulocytes specific features of autoimmune haemolytic anaemia positive direct antiglobulin test (Coombs' test).

Answer 380

presents in the first year of life with failure to thrive and hepatosplenomegaly microcytic anaemia HbA2 & HbF raised HbA absent

Answer 381

repeated transfusion this leads to iron overload → organ failure iron chelation therapy is therefore important (e.g. desferrioxamine)

Answer 382

mild hypochromic, microcytic anaemia - microcytosis is characteristically disproportionate to the anaemia HbA2 raised (> 3.5%)

Answer 383

TARGET CELLS Sickle-cell/thalassaemia Iron-deficiency anaemia Hyposplenism Liver disease

Answer 384

POIKILOCYTES 'Tear-drop' Myelofibrosis

Answer 385

SPHEROCYTES Hereditary spherocytosis Autoimmune hemolytic anaemia

Answer 386

BASOPHILLIC STRIPPING Lead poisoning Thalassaemia Sideroblastic anaemia Myelodysplasia

Answer 387

Howell Jolly bodies Hyposplenism

Answer 388

HEINZ BODIES G6PD deficiency Alpha-thalassaemia

Answer 389

Schistocytes ('helmet cells') Intravascular haemolysis Mechanical heart valve Disseminated intravascular coagulation

Answer 390

'Pencil' poikilocytes Iron deficency anaemia

Answer 391

Burr cells (echinocytes) Uraemia Pyruvate kinase deficiency

Answer 392

Acanthocytes Abetalipoproteinemia

Answer 393

megaloblastic anaemia

Answer 394

target cells Howell-Jolly bodies Pappenheimer bodies siderotic granules acanthocytes

Answer 395

target cells 'pencil' poikilocytes if combined with B12/folate deficiency a 'dimorphic' film occurs with mixed microcytic and macrocytic cells

Answer 396

high-grade B-cell neoplasm

Answer 397

endemic (African) form: typically involves maxilla or mandible sporadic form: abdominal (e.g. ileo-caecal) tumours are the most common form. More common in patients with HIV

Answer 398

Burkitt's lymphoma is associated with the c-myc gene translocation, usually t(8:14). The Epstein-Barr virus (EBV) is strongly implicated in the development of the African form of Burkitt's lymphoma and to a lesser extent the sporadic form

Answer 399

'starry sky' appearance: lymphocyte sheets interspersed with macrophages containing dead apoptotic tumour cells

Answer 400

Management is with chemotherapy. This tends to produce a rapid response which may cause 'tumour lysis syndrome'. Rasburicase (a recombinant version of urate oxidase, an enzyme which catalyses the conversion of uric acid to allantoin*) is often given before the chemotherapy to reduce the risk of this occurring. Complications of tumour lysis syndrome include: hyperkalaemia hyperphosphataemia hypocalcaemia hyperuricaemia acute renal failure *allantoin is 5-10 times more soluble than uric acid, so renal excretion is more effective

Answer 401

anaemia hypogammaglobulinaemia leading to recurrent infections warm autoimmune haemolytic anaemia in 10-15% of patients transformation to high-grade lymphoma (Richter's transformation)

Answer 402

Ritcher's transformation occurs when leukaemia cells enter the lymph node and change into a high-grade, fast-growing non-Hodgkin's lymphoma. Patients often become unwell very suddenly. Ritcher's transformation is indicated by one of the following symptoms: lymph node swelling fever without infection weight loss night sweats nausea abdominal pain

Answer 403

often none: may be picked up by an incidental finding of lymphocytosis constitutional: anorexia, weight loss bleeding, infections lymphadenopathy more marked than chronic myeloid leukaemia

Answer 404

monoclonal proliferation of well-differentiated lymphocytes which are almost always B-cells (99%)

Answer 405

full blood count: - lymphocytosis - anaemia: may occur either due to bone marrow replacement on autoimmune hemolytic anaemia (AIHA) - thrombocytopenia: may occur either due to bone marrow replacement on immune thrombocytopenia (AIHA) blood film: smudge cells (also known as smear cells) immunophenotyping is the key investigation: most cases can be identified using a panel of antibodies specific for CD5, CD19, CD20 and CD23

Answer 406

The Philadelphia chromosome is present in more than 95% of patients with chronic myeloid leukaemia (CML). It is due to a translocation between the long arm of chromosome 9 and 22 - t(9:22)(q34; q11). This results in part of the ABL proto-oncogene from chromosome 9 being fused with the BCR gene from chromosome 22. The resulting BCR-ABL gene codes for a fusion protein that has tyrosine kinase activity in excess of normal.

Answer 407

Presentation (60-70 years) anaemia: lethargy weight loss and sweating are common splenomegaly may be marked → abdo discomfort an increase in granulocytes at different stages of maturation +/- thrombocytosis decreased leukocyte alkaline phosphatase may undergo blast transformation (AML in 80%, ALL in 20%)

Answer 408

imatinib is now considered first-line treatment inhibitor of the tyrosine kinase associated with the BCR-ABL defect very high response rate in chronic phase CML hydroxyurea interferon-alpha allogenic bone marrow transplant

Answer 409

Immunoglobulins which undergo reversible precipitation at 4 deg C, dissolve when warmed to 37 deg C. One-third of cases are idiopathic Three types - type I (25%): monoclonal - IgG or IgM associations: multiple myeloma, Waldenstrom macroglobulinaemia type II (25%) mixed monoclonal and polyclonal: usually with rheumatoid factor associations: hepatitis C, rheumatoid arthritis, Sjogren's, lymphoma type III (50%) polyclonal: usually with rheumatoid factor associations: rheumatoid arthritis, Sjogren's

Answer 410

- Raynaud's only seen in type I - cutaneous vascular purpura distal ulceration ulceration arthralgia renal involvement - diffuse glomerulonephritis

Answer 411

Investigations low complement (esp. C4) high ESR Management treatment of underlying condition e.g. hepatitis C immunosuppression plasmapheresis

Answer 412

Direct thrombin inhibitor Majority Renal Idarucizumab

Answer 413

Direct factor Xa inhibtor Majority liver Andexanet alfa

Answer 414

Direct factor Xa inhibitor Majority feacal Andexanet alfa*

Answer 415

Direct factor Xa inhibitor Majority feacal Andexanet alfa*

Answer 416

Direct factor Xa inhibitor Majority feacal None

Answer 417

Warfarin administration

Answer 418

Aspirin administration?-

Answer 419

↓ platelets ↓ fibrinogen ↑ PT & APTT ↑ fibrinogen degradation products schistocytes due to microangiopathic haemolytic anaemia

Answer 420

sepsis trauma obstetric complications e.g. aminiotic fluid embolism or hemolysis, elevated liver function tests, and low platelets (HELLP syndrome) malignancy

Answer 421

Under homeostatic conditions: - Coagulation and fibrinolysis are coupled. - The activation of the coagulation cascade yields thrombin that converts fibrinogen to fibrin; the stable fibrin clot being the final product of hemostasis. - The fibrinolytic system breaks down fibrinogen and fibrin. Activation of the fibrinolytic system generates plasmin (in the presence of thrombin), which is responsible for the lysis of fibrin clots. - The breakdown of fibrinogen and fibrin results in - polypeptides (fibrin degradation products). - In a state of homeostasis, the presence of plasmin is critical, as it is the central proteolytic enzyme of coagulation and is also necessary for fibrinolysis. In DIC: - processes of coagulation and fibrinolysis are dysregulated, and the result is widespread clotting with resultant bleeding. - Regardless of the triggering event of DIC, once initiated, the pathophysiology of DIC is similar in all conditions. - One critical mediator of DIC is the release of a transmembrane glycoprotein (tissue factor =TF). - TF is present on the surface of many cell types (including endothelial cells, macrophages, and monocytes) and is not normally in contact with the general circulation, but is exposed to the circulation after vascular damage. For example, TF is released in response to exposure to cytokines (particularly interleukin 1), tumour necrosis factor, and endotoxin. - This plays a major role in the development of DIC in septic conditions. - TF is also abundant in tissues of the lungs, brain, and placenta. This helps to explain why DIC readily develops in patients with extensive trauma. - Upon activation, TF binds with coagulation factors that then triggers the extrinsic pathway (via Factor VII) which subsequently triggers the intrinsic pathway (XII to XI to IX) of coagulation.

Answer 422

Factor V Leiden (activated protein C resistance) is the most common inherited thrombophilia, being present in around 5% of the UK population.

Answer 423

It is due to a gain of function mutation in the Factor V Leiden protein. The result of the mis-sense mutation is that activated factor V (a clotting factor) is inactivated 10 times more slowly by activated protein C than normal. Factor V Leiden heterozygous is more common than homozygous, whereas homzygous carries a bigger risk of VTE

Answer 424

Antithrombin III deficiency

Answer 425

Autosomal recessive inherited anemia. Features haematological: aplastic anaemia increased risk of acute myeloid leukaemia neurological skeletal abnormalities: short stature thumb/radius abnormalities cafe au lait spots

Answer 426

G6PD is the first step in the pentose phosphate pathway, which converts glucose-6-phosphate→ 6-phosphogluconolactone this reaction also results in nicotinamide adenine dinucleotide phosphate (NADP) → NADPH i.e. glucose-6-phosphate + NADP → 6-phosphogluconolactone + NADPH NADPH is important for converting oxidizied glutathine back to it's reduced form reduced glutathine protects red blood cells from oxidative damage by oxidants such as superoxide anion (O2-) and hydrogen peroxide ↓ G6PD → ↓ reduced NADPH → ↓ reduced glutathione → increased red cell susceptibility to oxidative stress

Answer 427

Recombinant human granulocyte-colony stimulating factors are used to increase neutrophil counts in patients who are neutropenic secondary to chemotherapy or other factors. Examples include: filgrastim perfilgrastim

Answer 428

t(9;22) - Philadelphia chromosome t(15;17) t(8;14) t(11;14) t(14;18)

Answer 429

present in > 95% of patients with CML this results in part of the Abelson proto-oncogene being moved to the BCR gene on chromosome 22 the resulting BCR-ABL gene codes for a fusion protein which has tyrosine kinase activity in excess of normal poor prognostic indicator in ALL

Answer 430

seen in acute promyelocytic leukaemia (M3) fusion of PML and RAR-alpha genes

Answer 431

seen in Burkitt's lymphoma MYC oncogene is translocated to an immunoglobulin gene

Answer 432

Mantle cell lymphoma deregulation of the cyclin D1 (BCL-1) gene

Answer 433

follicular lymphoma increased BCL-2 transcription

Answer 434

Viruses EBV: Hodgkin's and Burkitt's lymphoma, nasopharyngeal carcinoma HTLV-1: Adult T-cell leukaemia/lymphoma HIV-1: High-grade B-cell lymphoma Bacteria Helicobacter pylori: gastric lymphoma (MALT) Protozoa malaria: Burkitt's lymphoma

Answer 435

In intravascular haemolysis, free haemoglobin is released which then binds to haptoglobin. As haptoglobin becomes saturated haemoglobin binds to albumin forming methaemalbumin (detected by Schumm's test). Free haemoglobin is excreted in the urine as haemoglobinuria, haemosiderinuria

Answer 436

mismatched blood transfusion G6PD deficiency* red cell fragmentation: heart valves, TTP, DIC, HUS paroxysmal nocturnal haemoglobinuria cold autoimmune haemolytic anaemia

Answer 437

haemoglobinopathies: sickle cell, thalassaemia hereditary spherocytosis haemolytic disease of newborn warm autoimmune haemolytic anaemia

Answer 438

Hereditary angioedema (HAE) is an autosomal dominant condition associated with low plasma levels of the C1 inhibitor (C1-INH, C1 esterase inhibitor) protein. C1-INH is a multifunctional serine protease inhibitor - the probable mechanism behind attacks is uncontrolled release of bradykinin resulting in oedema of tissues.

Answer 439

Investigation C1-INH level is low during an attack low C2 and C4 levels are seen, even between attacks. Serum C4 is the most reliable and widely used screening tool Symptoms attacks may be proceeded by painful macular rash painless, non-pruritic swelling of subcutaneous/submucosal tissues may affect upper airways, skin or abdominal organs (can occasionally present as abdominal pain due to visceral oedema) urticaria is not usually a feature

Answer 440

acute HAE does not respond to adrenaline, antihistamines, or glucocorticoids IV C1-inhibitor concentrate, fresh frozen plasma (FFP) if this is not available prophylaxis: anabolic steroid Danazol may help

Answer 441

acute haemolytic crisis: treatment is generally supportive transfusion if necessary longer term treatment: folate replacement splenectomy

Answer 442

Nodular sclerosing Mixed cellularity Lymphocyte predominant Lymphocyte depleted

Answer 443

Nodular sclerosing

Answer 444

Lymphocyte predominant

Answer 445

Lymphocyte depleted

Answer 446

Nodular sclerosing

Answer 447

Lymphocyte depleted subtype 'B' symptoms also imply a poor prognosis weight loss > 10% in last 6 months fever > 38ºC night sweats age > 45 years stage IV disease haemoglobin < 10.5 g/dl lymphocyte count < 600/µl or < 8% male albumin < 40 g/l white blood count > 15,000/µl

Answer 448

most commonly in the neck (cervical/supraclavicular) > axillary > inguinal

Answer 449

alcohol-induced lymph node pain is characteristic of Hodgkin's lymphoma but is seen in less than 10% of patients

Answer 450

normocytic anaemia - may be multifactorial e.g. hypersplenism, bone marrow replacement by HL, Coombs-positive haemolytic anaemia etc eosinophilia - caused by the production of cytokines e.g. IL-5 LDH raised lymph node biopsy: Reed-Sternberg cells are diagnostic: these are large cells that are either multinucleated or have a bilobed nucleus with prominent eosinophilic inclusion-like nucleoli (thus giving an 'owl's eye' appearance)

Answer 451

A = no systemic symptoms other than pruritus B = weight loss > 10% in last 6 months, fever > 38c, night sweats (poor prognosis)

Answer 452

chemotherapy is the mainstay of treatment. Two combinations may be used: 1. ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine): considered the standard regime 2. BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone): alternative regime with better remission rates but higher toxicity radiotherapy combined modality therapy (CMT) chemotherapy followed by radiotherapy hematopoietic cell transplantation - may be used for relapsed or refractory classic Hodgkin lymphoma

Answer 453

most patients now achieve long-term survival free of Hodgkin's lymphoma with modern therapy complications of treatment are therefore more of an issue for these patients: - secondary malignancies are a risk, in particular - solid tumours: breast and lung

Answer 454

Causes splenectomy sickle-cell coeliac disease, dermatitis herpetiformis Graves' disease systemic lupus erythematosus amyloid Features Howell-Jolly bodies siderocytes

Answer 455

Immune (or idiopathic) thrombocytopenic purpura (ITP) is an immune-mediated reduction in the platelet count. Antibodies are directed against the glycoprotein IIb/IIIa or Ib-V-IX complex. Children with ITP usually have an acute thrombocytopenia that may follow infection or vaccination. In contrast, adults tend to have a more chronic condition.

Answer 456

Presentation may be detected incidentally following routine bloods symptomatic patients may present with petechiae, purpura bleeding (e.g. epistaxis) catastrophic bleeding (e.g. intracranial) is not a common presentation Investigations full blood count: isolated thrombocytopenia blood film a bone marrow examination is no longer used routinely, shows megakaryocytes in the marrow. This should be carried out prior to the commencement of steroids in order to rule out leukaemia antiplatelet antibody testing has poor sensitivity and doesn't affect clinical management so is not commonly done, but will usually show IgG antibodies

Answer 457

ITP in association with autoimmune haemolytic anaemia (AIHA)

Answer 458

first-line treatment for ITP is oral prednisolone pooled normal human immunoglobulin (IVIG) may also be used - it raises the platelet count quicker than steroids, therefore may be used if active bleeding or an urgent invasive procedure is required splenectomy is now less commonly used, indicated when if platelets < 30 after 3 months of steroid therapy immunosuppressive drugs e.g. cyclophosphamide

Answer 459

hypochromic microcytic anaemia

Answer 460

Blood film anisopoikilocytosis (red blood cells of different sizes and shapes) , target cells, 'pencil' poikilocytes

Answer 461

Serum ferritin this will likely be low, as serum ferritin correlates with iron stores. However, it is important to recognise that ferritin can be raised during states of inflammation; so a raised ferritin does not necessarily rule out iron deficiency anaemia if the is co-occurring inflammation. For patients with co-occurring inflammatory disease, other iron studies can be performed. Total iron-binding capacity (TIBC)/transferrin this will be high. A high TIBC reflects low iron stores. . Note that the transferrin saturation will however be low

Answer 462

Post-menopausal women with a haemoglobin level ≤10 and men with a haemoglobin level ≤11 should be referred to a gastroenterologist within 2 weeks.

Answer 463

LDH (initial + monitoring) Bilirubin (intiial +monitoring) Reticulocytes (initial +monitoring) Blood film (not req. for monitoring) Haptoglobin (not req. for monitoring) Direct antiglobulin test (direct coombes) (not req. for monitoring)

Answer 464

Platelet infusion

Answer 465

Vit K + prothrombin complex concentrate

Answer 466

Cryoprecipitate