Haematology Flashcards

Question

What is the management of beta-thalassemia intermedia?

Answer 1

monitoring and occasional blood transfusions. When they require more transfusions, they may require iron chelation to prevent iron overload.

Answer 2

Patients with beta thalassaemia major are homozygous for the deletion genes. They 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 3

--> Severe microcytic anaemia –> Splenomegaly –> Bone deformities

Answer 4

Management involves regular transfusions, iron chelation, and splenectomy. Bone marrow transplants can potentially be curative.

Answer 5

Iron deficiency is the most common cause of anaemia globally.

Answer 6

Iron is needed to make haemoglobin in red blood cells. A deficiency in iron leads to a reduction in red blood cells/haemoglobin, resulting in anaemia.

Answer 7

--> Excessive blood loss: Chronic gastrointestinal bleeding (e.g., peptic ulcers, colorectal cancer, inflammatory bowel disease) Heavy menstrual bleeding (menorrhagia) Post-surgical blood loss Trauma --> Inadequate dietary intake: Insufficient iron-rich foods (e.g., red meat, leafy greens) Vegetarian or vegan diets without proper iron supplementation --> Poor intestinal absorption: Conditions affecting absorption (e.g., coeliac disease, Crohn’s disease) Post-gastrectomy or bariatric surgery Chronic use of medications that reduce stomach acid (e.g., proton pump inhibitors) --> Increased iron requirements: Pregnancy and breastfeeding Rapid growth during infancy, childhood, and adolescence

Answer 8

Fatigue Shortness of breath on exertion Palpitations Pallor Nail changes: this includes koilonychia (spoon-shaped nails) Hair loss Atrophic glossitis Post-cricoid webs Angular stomatitis

Answer 9

Key history points for investigating iron deficiency anaemia include: Dietary changes (e.g., vegetarian or vegan diet) Medication history (e.g., proton pump inhibitors) Menstrual history (e.g., heavy periods/menorrhagia) Weight loss (unexplained weight loss may suggest malignancy) Changes in bowel habit (e.g., diarrhoea, constipation, blood in stool, which could suggest GI issues)

Answer 10

Hypochromic microcytic anaemia: Red blood cells are smaller than normal and have reduced haemoglobin concentration.

Answer 11

--> Low serum ferritin indicates low iron stores and suggests iron deficiency anaemia. Note: Ferritin is an acute phase reactant, meaning it can be falsely elevated in states of inflammation. A raised ferritin does not rule out iron deficiency if there is concurrent inflammation. Other iron studies may be needed in these cases.

Answer 12

TIBC/transferrin is usually high in iron deficiency anaemia, reflecting low iron stores. Transferrin saturation is low because there is less iron available to bind to transferrin.

Answer 13

Anisopoikilocytosis: Red blood cells of varying sizes and shapes Target cells 'Pencil' poikilocytes

Answer 14

Endoscopy should be considered to rule out malignancy in: Males and post-menopausal females with unexplained iron-deficiency anaemia. Patients with haemoglobin ≤10 in post-menopausal women and ≤11 in men should be referred to a gastroenterologist within 2 weeks.

Answer 15

--> History Taking Dietary changes (e.g., vegetarian or vegan diet) Medication history (e.g., proton pump inhibitors) Menstrual history (e.g., heavy periods/menorrhagia) Weight loss (unexplained weight loss, which may suggest malignancy) Changes in bowel habit (e.g., diarrhoea, constipation, or blood in stool, suggesting gastrointestinal issues) --> Full Blood Count (FBC) Hypochromic microcytic anaemia (small, pale red blood cells due to reduced haemoglobin concentration) --> Serum Ferritin Low ferritin: Indicates low iron stores. Caution: Ferritin may be falsely elevated during inflammation, which could obscure iron deficiency. --> Total Iron-Binding Capacity (TIBC) / Transferrin High TIBC/transferrin: Reflects low iron stores. Low transferrin saturation: Indicates less iron available to bind to transferrin. --> Blood Film Anisopoikilocytosis: Red blood cells of varying sizes and shapes. Target cells Pencil poikilocytes --> Endoscopy Indication: To rule out malignancy, especially in males and post-menopausal females with unexplained iron deficiency anaemia. Referral criteria: Post-menopausal women with haemoglobin ≤10 and men with haemoglobin ≤11 should be referred to a gastroenterologist within 2 weeks.

Answer 16

--> Investigate Further Colonoscopy and OGD to rule out malignancy in adults with new iron deficiency anaemia, unless there is an obvious cause (e.g., heavy menstruation, pregnancy). --> Treatment Options - Oral Iron (e.g., ferrous sulphate, ferrous fumarate): Expected haemoglobin rise of 20 g/L in the first month. Common side effects: constipation, black stools. Prophylactic supplementation for recurrent cases. --> Iron Infusion (e.g., IV CosmoFer): Rapid iron boost, but small risk of allergic reactions and anaphylaxis. Avoid during infections due to risk of bacterial growth. --> Blood Transfusion: For severe anaemia.

Answer 17

Answer: Pernicious anaemia (autoimmune condition affecting intrinsic factor production) Insufficient dietary B12 (especially in a vegan diet, as B12 is mostly found in animal products) Medications that reduce B12 absorption (e.g., proton pump inhibitors and metformin)

Answer 18

--> Autoimmune condition invovling antibodies against the parietal cells or intrinsic factor

Answer 19

--> Pathophysiology: The parietal cells in the stomach produce intrinsic factor, which is essential for vitamin B12 absorption in the distal ileum. In pernicious anaemia, autoantibodies target the parietal cells or intrinsic factor, leading to a lack of intrinsic factor and impaired absorption of vitamin B12. Autoantibodies for Diagnosis: Intrinsic factor antibodies (first-line investigation) Gastric parietal cell antibodies (less helpful)

Answer 20

--> Neurological Symptoms of B12 Deficiency: Peripheral neuropathy (numbness or paraesthesia) Loss of vibration sense Loss of proprioception Visual changes Mood and cognitive changes

Answer 21

--> Initial Treatment with Intramuscular Hydroxocobalamin: - No neurological symptoms: 3 times weekly for 2 weeks. - Neurological symptoms: Alternate days until there is no further improvement. --> Maintenance Treatment: - Pernicious anaemia: Injections every 2-3 months for life. - Diet-related deficiency: Oral cyanocobalamin or injections twice yearly. --> Important Consideration: If both B12 and folate deficiency are present, treat the B12 deficiency first. Treating folate deficiency before correcting B12 can lead to subacute combined degeneration of the spinal cord.

Answer 22

Inherited Causes: Hereditary spherocytosis Hereditary elliptocytosis Thalassaemia Sickle cell anaemia G6PD deficiency Acquired Causes: Autoimmune haemolytic anaemia Alloimmune haemolytic anaemia (e.g., transfusion reactions, haemolytic disease of the newborn) Paroxysmal nocturnal haemoglobinuria Microangiopathic haemolytic anaemia Prosthetic valve-related haemolysis

Answer 23

--> Anaemia --> splenomegaly --> jaundice

Answer 24

--> Full blood count shows a normocytic anaemia --> Blood film shows schistocytes (fragments of red blood cells) --> Direct Coombs test is positive in autoimmune haemolytic anaemia (not in other types)

Answer 25

Hereditary spherocytosis is the most common inherited haemolytic anaemia in northern Europeans. It is an autosomal dominant condition that causes fragile, sphere-shaped red blood cells, which break down easily.

Answer 26

Clinical features include: Anaemia Jaundice Gallstones Splenomegaly Aplastic crisis (especially after parvovirus infection) Positive family history is often noted.

Answer 27

Diagnostic findings include: Raised mean corpuscular haemoglobin concentration (MCHC) on a full blood count. Raised reticulocyte count due to rapid turnover of red blood cells. Spherocytes visible on a blood film.

Answer 28

Management includes: Folate supplementation to support red blood cell production. Blood transfusions as needed. Splenectomy for long-term control. Cholecystectomy if gallstones become problematic

Answer 29

Hereditary elliptocytosis is an autosomal dominant condition where the red blood cells are ellipse-shaped instead of the typical round shape. It is similar to hereditary spherocytosis.

Answer 30

G6PD deficiency is caused by a defect in the gene coding for glucose-6-phosphate dehydrogenase (G6PD), an enzyme that protects cells from oxidative damage. It is an X-linked recessive genetic condition, meaning males are more often affected, and females are typically carriers.

Answer 31

Acute episodes of haemolytic anaemia in G6PD deficiency are triggered by: Infections Certain drugs, such as ciprofloxacin, sulfonylureas (e.g., gliclazide), and sulfasalazine Fava beans (broad beans)

Answer 32

Key features of G6PD deficiency include: Jaundice (often in the neonatal period) Gallstones Anaemia Splenomegaly Heinz bodies on a blood film

Answer 33

G6PD deficiency is diagnosed by performing a G6PD enzyme assay to assess the activity of the enzyme.

Answer 34

Look out for a male patient who becomes jaundiced and anaemic after: Eating fava beans Developing an infection Taking antimalarials These are common triggers of G6PD deficiency.

Answer 35

AIHA occurs when antibodies are created against the patient’s red blood cells, leading to their destruction (haemolysis).

Answer 36

AIHA is classified into two types: warm and cold, based on the temperature at which the auto-antibodies destroy red blood cells.

Answer 37

Warm AIHA is the more common type, where haemolysis occurs at normal or above-normal temperatures and is usually idiopathic.

Answer 38

Cold-reactive AIHA is also called cold agglutinin disease.

Answer 39

Agglutination occurs at lower temperatures, typically below 10ºC.

Answer 40

Cold AIHA can be secondary to conditions like lymphoma, leukaemia, systemic lupus erythematosus, and infections such as mycoplasma, EBV, CMV, and HIV.

Answer 41

Management includes blood transfusions, prednisolone, rituximab (a monoclonal antibody against B cells), and splenectomy.

Answer 42

Alloimmune haemolytic anaemia occurs due to foreign red blood cells or foreign antibodies, typically in transfusion reactions or haemolytic disease of the newborn.

Answer 43

In haemolytic transfusion reactions, the immune system produces antibodies against antigens on transfused foreign red blood cells, leading to their destruction.

Answer 44

Haemolytic disease of the newborn occurs when maternal antibodies cross the placenta and target antigens on the fetus's red blood cells, leading to their destruction.

Answer 45

It typically occurs when the fetus is rhesus D positive and the mother is rhesus D negative.

Answer 46

Sensitization occurs during an event like antepartum hemorrhage, exposing the mother to fetal red blood cells and prompting her to produce anti-D antibodies against the rhesus D antigen.

Answer 47

In subsequent pregnancies, these antibodies can cross the placenta to the baby and cause haemolysis of the fetal red blood cells.

Answer 48

Sensitization can be prevented by using anti-D prophylaxis.

Answer 49

PNH is caused by a specific genetic mutation in haematopoietic stem cells in the bone marrow, resulting in a loss of proteins that inhibit the complement cascade, leading to the destruction of red blood cells.

Answer 50

No, the mutation causing PNH occurs during the patient’s lifetime, not as an inherited genetic condition.

Answer 51

The characteristic symptom is red urine in the morning, which contains haemoglobin and haemosiderin.

Answer 52

Other features include anaemia, thrombosis (e.g., DVT, pulmonary embolism, hepatic vein thrombosis), and smooth muscle dystonia (e.g., oesophageal spasm, erectile dysfunction).

Answer 53

Management includes eculizumab, a monoclonal antibody targeting complement component 5 (C5), or bone marrow transplantation, which can be curative.

Answer 54

MAHA involves the destruction of red blood cells as they travel through the circulation, often due to abnormal activation of the clotting system causing thrombotic microangiopathy.

Answer 55

In thrombotic microangiopathy, blood clots partially obstruct small blood vessels, churning the red blood cells and causing their rupture (haemolysis).

Answer 56

MAHA is usually secondary to conditions such as haemolytic uraemic syndrome (HUS), disseminated intravascular coagulation (DIC), thrombotic thrombocytopenic purpura (TTP), systemic lupus erythematosus (SLE), and cancer.

Answer 57

Schistocytes (fragmented red blood cells) are a key finding on the blood film in patients with microangiopathic haemolytic anaemia.

Answer 58

Prosthetic valve haemolysis is a complication of prosthetic heart valves, leading to haemolytic anaemia caused by turbulence and shearing of red blood cells around the valve.

Answer 59

Yes, haemolytic anaemia can occur in both bioprosthetic and metallic valve replacements, though the severity may vary between types.

Answer 60

The primary mechanism is turbulence flow around the valve, which churns and breaks down red blood cells.

Answer 61

Management includes monitoring, oral iron and folic acid supplementation, blood transfusions if severe, and possible revision surgery in severe cases.

Answer 62

Sickle cell anaemia is a genetic condition that causes sickle (crescent) shaped red blood cells. The abnormal shape makes the red blood cells more fragile and easily destroyed, leading to haemolytic anaemia. Patients with sickle cell anaemia are prone to various sickle cell crises.

Answer 63

--> Hemoglobin Function: Hemoglobin is the protein in red blood cells that transports oxygen. During fetal development (32-36 weeks gestation), fetal hemoglobin (HbF) decreases and adult hemoglobin (HbA) increases. At birth, hemoglobin is ~50% HbF and ~50% HbA; by six months, it consists almost entirely of HbA. --> Sickle-Cell Disease: Caused by a mutation in the beta-globin gene on chromosome 11, it follows an autosomal recessive pattern. One abnormal gene causes sickle-cell trait (asymptomatic carrier); two abnormal genes cause sickle-cell disease. --> Mechanism: In sickle-cell disease, the presence of hemoglobin S (HbS) causes red blood cells to become sickle-shaped under low-oxygen conditions. These rigid cells can obstruct blood flow, leading to pain, increased infection risk, and hemolytic anemia from their premature destruction.

Answer 64

Sickle cell disease is more prevalent in regions traditionally affected by malaria, such as Africa, India, the Middle East, and the Caribbean. Individuals with one copy of the sickle cell gene (sickle cell trait) experience reduced severity of malaria. This trait provides a selective advantage, as those with sickle cell trait are more likely to survive malaria and reproduce, passing on the gene. Consequently, the sickle cell gene is more common in malaria-endemic areas due to this evolutionary advantage.

Answer 65

Newborn Screening: Sickle cell disease is tested during the newborn blood spot screening test, typically conducted around five days of age. Pregnant Women Testing: Pregnant women at high risk of being carriers of the sickle cell gene are offered testing to identify their carrier status.

Answer 66

Anemia Increased risk of infection Chronic kidney disease Sickle cell crises Acute chest syndrome Stroke Avascular necrosis (especially in large joints such as the hip) Pulmonary hypertension Gallstones Priapism (painful and persistent penile erections)

Answer 67

Sickle cell crisis refers to a spectrum of acute exacerbations associated with sickle cell disease. Crises can vary in severity, ranging from mild episodes to life-threatening complications. They can occur spontaneously or be triggered by factors such as: Dehydration Infection Stress Cold weather

Answer 68

Dehydration: Reduced blood volume can increase sickling of red blood cells. Infection: Infections can provoke the crisis through increased metabolic demand and inflammation. Stress: Physical or emotional stress can lead to physiological changes that exacerbate the condition. Cold Weather: Exposure to cold can cause vasoconstriction, reducing blood flow and triggering pain episodes.

Answer 69

--> Supportive Care: There is no specific treatment; management focuses on supportive care. --> Hospital Admission: Maintain a low threshold for admitting patients to the hospital for monitoring and treatment. --> Infection Management: Promptly treat any infections that may have triggered the crisis to prevent further complications. --> Temperature Regulation: Keep the patient warm to prevent vasoconstriction and reduce pain. --> Hydration: Ensure good hydration; intravenous (IV) fluids may be required to maintain adequate hydration levels. --> Analgesia: Provide pain relief. Note that NSAIDs should be avoided in patients with renal impairment due to the risk of further kidney damage

Answer 70

Vaso-occlusive crisis (VOC), also known as a painful crisis, is the most common type of crisis in sickle cell disease. It occurs when sickle-shaped red blood cells clog small blood vessels (capillaries), leading to distal ischemia and subsequent pain.

Answer 71

Pain: Often severe, it usually presents in the hands or feet but can also affect: Chest Back Other body areas Swelling: Edema in the affected areas due to ischemia. Fever: May accompany the pain and swelling, indicating possible infection or inflammation.

Answer 72

Priapism: A painful, prolonged erection caused by blood being trapped in the penis due to vascular occlusion. Emergency Treatment: Priapism is considered a urological emergency and may require: Aspiration of blood from the penis to relieve pressure and restore normal blood flow. Other interventions may be necessary if priapism persists.

Answer 73

Splenic sequestration crisis occurs when red blood cells block blood flow within the spleen. This blockage leads to an acutely enlarged and painful spleen due to pooling of blood.

Answer 74

Symptoms: Acute splenomegaly (enlarged spleen) Abdominal pain, particularly in the left upper quadrant Severe anemia due to blood pooling Signs of hypovolemic shock (e.g., low blood pressure, rapid heart rate) Complications: Splenic Infarction: Lack of blood flow can cause tissue death in the spleen. Hyposplenism: Reduced function of the spleen leading to decreased immune response. Increased Susceptibility to Infections: Particularly with encapsulated bacteria such as: Streptococcus pneumoniae Haemophilus influenzae

Answer 75

Supportive Management: Blood transfusions to treat severe anemia. Fluid resuscitation to address hypovolemic shock. Preventive Measures: Splenectomy: Surgical removal of the spleen may be considered in recurrent cases to prevent future sequestration crises.

Answer 76

Aplastic crisis is characterized by a temporary absence of new red blood cell production. It is commonly triggered by infection with parvovirus B19.

Answer 77

The infection (often parvovirus B19) leads to a decrease in erythropoiesis (red blood cell production) in the bone marrow. This results in significant anemia (aplastic anemia) due to insufficient red blood cells to meet the body's oxygen demands.

Answer 78

Symptoms of anemia, which may include: Fatigue Weakness Pallor (pale skin) Dizziness or lightheadedness Shortness of breath

Answer 79

Supportive Management: Blood transfusions may be administered if anemia is severe and symptomatic. Spontaneous Resolution: The condition typically resolves on its own within about a week.

Answer 80

Acute chest syndrome occurs when the blood vessels supplying the lungs become obstructed by sickle-shaped red blood cells. It can be triggered by vaso-occlusive crises, fat embolism, or infections.

Answer 81

Fever Shortness of breath Chest pain Cough Hypoxia (low oxygen levels)

Answer 82

A chest X-ray is performed, which typically shows pulmonary infiltrates, indicating fluid or cells in the lung tissue.

Answer 83

--> Analgesia: Pain relief is crucial for comfort. --> Good Hydration: Intravenous fluids may be needed to maintain hydration. --> Antibiotics or Antivirals: These are administered if an infection is suspected. --> Blood Transfusions: Given for anemia to increase red blood cell levels and oxygen-carrying capacity. --> Incentive Spirometry: Encourages deep breathing to improve lung expansion and function. --> Respiratory Support: Oxygen therapy, non-invasive ventilation, or mechanical ventilation may be required for severe hypoxia.

Answer 84

Acute chest syndrome has a high mortality rate, making prompt recognition and treatment essential to improve patient outcomes.

Answer 85

Avoid Triggers: Prevent crises by avoiding dehydration and other known triggers. Up-to-Date Vaccinations: Ensure vaccinations are current to protect against infections. Antibiotic Prophylaxis: Use penicillin V (phenoxymethylpenicillin) to reduce the risk of infections. Hydroxycarbamide: Stimulates the production of fetal hemoglobin (HbF). Crizanlizumab: A monoclonal antibody that targets P-selectin. Blood Transfusions: Administered for severe anemia. Bone Marrow Transplant: Considered a curative treatment option.

Answer 86

Hydroxycarbamide stimulates the production of fetal hemoglobin (HbF), which does not lead to sickling of red blood cells. It reduces the frequency of vaso-occlusive crises, improves anemia, and may extend lifespan.

Answer 87

Crizanlizumab is a monoclonal antibody that targets P-selectin, an adhesion molecule on endothelial cells and platelets. It prevents red blood cells from sticking to blood vessel walls, thereby reducing the frequency of vaso-occlusive crises.

Answer 88

Individuals with sickle cell disease are at increased risk for infections due to spleen dysfunction. Vaccinations protect against common infections, and antibiotic prophylaxis with penicillin V helps to prevent serious bacterial infections.

Answer 89

--> Definition: DIC is a serious condition characterized by the dysregulation of coagulation and fibrinolysis, leading to widespread clotting and bleeding. --> Homeostasis Overview: Under normal conditions, coagulation and fibrinolysis are coupled. Coagulation activates the cascade resulting in thrombin production, which converts fibrinogen to fibrin, forming stable clots. The fibrinolytic system generates plasmin, which breaks down fibrin clots, producing fibrin degradation products. Role of Plasmin: Plasmin is critical for maintaining balance, as it is essential for both coagulation and fibrinolysis. --> Pathophysiology of DIC: In DIC, coagulation and fibrinolysis become dysregulated, leading to excessive clot formation and subsequent bleeding, regardless of the triggering event. --> Key Mediator: Tissue Factor (TF), a transmembrane glycoprotein, is a critical initiator of DIC. It is released following vascular damage and interacts with coagulation factors, initiating the coagulation cascade. --> Triggers of TF Release: TF is released in response to cytokines (like interleukin-1), tumor necrosis factor, and endotoxin, particularly in septic conditions. --> Coagulation Pathways: Once activated, TF binds with coagulation factors, triggering the extrinsic pathway (via Factor VII) and subsequently the intrinsic pathway (XII to XI to IX), leading to extensive clot formation.

Answer 90

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

Answer 91

ypical Blood Picture in DIC: Platelets: ↓ (thrombocytopenia) Fibrinogen: ↓ Prothrombin Time (PT): ↑ (prolonged) Activated Partial Thromboplastin Time (APTT): ↑ (prolonged) Fibrinogen Degradation Products: ↑ Schistocytes: Present due to microangiopathic haemolytic anaemia

Answer 92

Warfarin Administration: PT prolonged, APTT normal, Bleeding time normal, Platelet count normal. Aspirin Administration: PT normal, APTT normal, Bleeding time prolonged, Platelet count normal. Heparin: PT often normal (may be prolonged), APTT prolonged, Bleeding time normal, Platelet count normal. DIC: PT prolonged, APTT prolonged, Bleeding time prolonged, Platelet count low.

Answer 93

Nosebleeds are also known as epistaxis. Bleeding usually originates from Kiesselbach’s plexus, located in Little’s area, which is in the anterior nasal cavity and contains a rich network of blood vessels.

Answer 94

The bleeding occurs when the nasal mucosa is disrupted, exposing the blood vessels in this area, making them prone to bleeding.

Answer 95

Nosebleeds are common in young children and older adults. Triggers include: Nose picking Colds Sinusitis Vigorous nose-blowing Trauma Changes in the weather Coagulation disorders (e.g., thrombocytopenia, Von Willebrand disease) Anticoagulant medication (e.g., aspirin, DOACs, warfarin) Snorting cocaine Tumours (e.g., squamous cell carcinoma)

Answer 96

The patient may present with vomiting blood.

Answer 97

Bleeding is usually unilateral. Bilateral bleeding may indicate posterior bleeding, which presents a higher risk of aspiration of blood.

Answer 98

Most nosebleeds resolve without medical assistance. Recurrent or significant nosebleeds may require further investigation to identify underlying causes, such as thrombocytopenia or clotting disorders.

Answer 99

Sit up and tilt the head forwards (tilting backwards is not advised as it can direct blood toward the airway). Squeeze the soft part of the nostrils together for 10–15 minutes. Spit out any blood in the mouth instead of swallowing.

Answer 100

Admission may be necessary if: Bleeding does not stop after 10–15 minutes. The nosebleed is severe. Bleeding is from both nostrils. The patient is haemodynamically unstable. Treatment options include: Nasal packing (using nasal tampons or inflatable packs). Nasal cautery (using silver nitrate sticks).

Answer 101

Consider prescribing Naseptin nasal cream (chlorhexidine and neomycin) to reduce crusting, inflammation, and infection. Contraindication: Do not use in patients with peanut or soya allergies.

Answer 102

Thrombocytopenia describes a low platelet count. The normal platelet count is 150–450 x 10^9/L.

Answer 103

Viral infections (e.g., Epstein-Barr virus, cytomegalovirus, HIV). B12 deficiency. Folic acid deficiency. Liver failure (due to reduced thrombopoietin production). Leukaemia. Myelodysplastic syndrome. Chemotherapy.

Answer 104

Medications (e.g., sodium valproate, methotrexate). Alcohol. Immune thrombocytopenic purpura (ITP). Thrombotic thrombocytopenic purpura (TTP). Heparin-induced thrombocytopenia (HIT). Haemolytic uraemic syndrome (HUS).

Answer 105

Asymptomatic in mild cases, often found incidentally on a full blood count.

Answer 106

Easy bruising. Prolonged bleeding times. Nosebleeds. Bleeding gums. Heavy periods (menorrhagia). Haematuria (blood in urine). Rectal bleeding.

Answer 107

High risk of spontaneous bleeding, including: Intracranial haemorrhage. Gastrointestinal bleeding.

Answer 108

--> Thrombocytopenia (low platelet count). --> Von Willebrand disease (deficiency of von Willebrand factor). --> Haemophilia A (factor VIII deficiency) and --> Haemophilia B (factor IX deficiency). --> Disseminated intravascular coagulation (usually secondary to sepsis).

Answer 109

Autoimmune thrombocytopenic purpura Idiopathic thrombocytopenic purpura Primary thrombocytopenic purpura

Answer 110

ITP is a condition where antibodies are created against platelets, leading to an immune response that destroys platelets, resulting in thrombocytopenia (low platelet count).

Answer 111

presents with purpura, which are non-blanching lesions caused by bleeding under the skin.

Answer 112

Care involves monitoring the platelet count, controlling blood pressure, and suppressing menstrual periods.

Answer 113

--> The 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 --> rituximab may be used to target B cells

Answer 114

--> Full blood count: Shows isolated thrombocytopenia. --> Blood film: Assesses blood cell appearance and rules out other causes.

Answer 115

TTP is caused by a deficiency of the ADAMTS13 protein, which normally regulates von Willebrand factor (vWF) activity. Without ADAMTS13, vWF remains active, leading to excessive platelet adhesion and the formation of tiny thrombi throughout small blood vessels. This causes: Thrombocytopenia: Due to platelet consumption Purpura: Resulting from low platelet counts Tissue ischaemia: Thrombi block small vessels, leading to reduced blood supply and end-organ damage

Answer 116

Inherited (Hereditary): A genetic mutation causes a deficiency in ADAMTS13 production. Acquired (Autoimmune): Antibodies target ADAMTS13, reducing its activity.

Answer 117

--> Rare: Typically occurs in adult females --> Fever --> Fluctuating neurological signs: Due to microemboli in small vessels --> Microangiopathic haemolytic anaemia: ----> Destruction of red blood cells as they pass through the small vessel thrombi --> Thrombocytopenia: Low platelet count due to platelet consumption in clot formation --> Renal failure: From ischaemia caused by blocked small vessels

Answer 118

Post-infection: e.g., urinary tract infections, gastrointestinal infections Pregnancy Drugs: Ciclosporin Oral contraceptive pill Penicillin Clopidogrel Aciclovir Tumours Systemic Lupus Erythematosus (SLE) HIV

Answer 119

Treatment is guided by a haematologist and may include: Plasma exchange Steroids Rituximab (a monoclonal antibody targeting B cells)

Answer 120

HIT involves the development of antibodies against platelets in response to heparin (typically unfractionated, but can occur with low-molecular-weight heparin). Mechanism: Antibodies target a protein on platelets called platelet factor 4 (PF4). HIT antibodies bind to platelets, activating the clotting system. This leads to a hypercoagulable state, causing thrombosis (e.g., deep vein thrombosis). Simultaneously, the antibodies lead to platelet destruction, resulting in thrombocytopenia.

Answer 121

HIT usually presents 5-10 days after starting heparin treatment.

Answer 122

Thrombocytopenia: Low platelet count. Thrombosis: Increased risk of abnormal blood clots (e.g., deep vein thrombosis).

Answer 123

Thrombocytopenia: Low platelet count. Thrombosis: Increased risk of abnormal blood clots (e.g., deep vein thrombosis). Less common presentations include: --> Adrenal haemorrhagic necrosis: Secondary to adrenal vein thrombosis. --> Necrotizing skin lesions: At heparin injection sites. --> Cerebral venous thrombosis. --> Acute systemic reaction: Occurring 30 minutes after intravenous bolus of unfractionated heparin or subcutaneous low-molecular-weight heparin (e.g., fever, chills, tachycardia, hypertension, dyspnoea, cardiopulmonary arrest). --> Rarely, patients with HIT-provoked deep vein thrombosis may present with venous limb gangrene due to inappropriate treatment with a vitamin K antagonist.

Answer 124

Diagnosis is made by testing for HIT antibodies on a blood sample.

Answer 125

Immediate management: Stop heparin. Alternative anticoagulants: Use medications guided by a specialist, such as fondaparinux or argatroban.

Answer 126

Definition: Leukemia is a type of cancer that originates in a specific line of stem cells in the bone marrow. Pathophysiology: It leads to the unregulated production of a particular type of blood cell, which can disrupt normal blood cell function and lead to various complications.

Answer 127

Leukemias are classified based on two main criteria: Rate of Progression: Acute: Rapidly progressing Chronic: Slowly progressing Cell Line Affected: Myeloid Lymphoid This results in four main types of leukemia: --> Acute Myeloid Leukemia (AML) Rapidly progressing cancer of the myeloid cell line. --> Acute Lymphoblastic Leukemia (ALL) Rapidly progressing cancer of the lymphoid cell line. Key Fact: Most common leukemia in children; associated with Down syndrome. Chronic Myeloid Leukemia (CML) Slowly progressing cancer of the myeloid cell line. Key Fact: Has three phases (chronic, accelerated, and blast phase) and is associated with the Philadelphia chromosome. Chronic Lymphocytic Leukemia (CLL) Slowly progressing cancer of the lymphoid cell line. Key Fact: Associated with warm autoimmune hemolytic anemia, Richter's transformation, and the presence of smudge cells.

Answer 128

Most types of leukemia occur in patients aged 60-70 years. Exception: ALL most commonly affects children under five years old.

Answer 129

A genetic mutation in one of the precursor cells in the bone marrow leads to excessive production of a single type of abnormal white blood cell.

Answer 130

Leukemia is a cancer of specific stem cells in the bone marrow, characterized by a genetic mutation in a precursor cell that leads to excessive production of a single type of abnormal white blood cell. This overproduction suppresses other blood cell lines, resulting in the underproduction of red blood cells (causing anemia), white blood cells (leading to leukopenia), and platelets (causing thrombocytopenia). Consequently, patients may present with pancytopenia, which is a combination of low counts of all three cell types.

Answer 131

The presentation of leukemia is relatively non-specific and may include: Fatigue Fever Pallor due to anemia Petechiae or bruising due to thrombocytopenia Abnormal bleeding Lymphadenopathy Hepatosplenomegaly Failure to thrive (in children)

Answer 132

A key presenting feature of leukaemia is bleeding under the skin due to thrombocytopenia, resulting in non-blanching lesions categorized by size: Petechiae: Less than 3 mm, caused by burst capillaries. Purpura: Between 3 mm and 10 mm. Ecchymosis: Larger than 1 cm.

Answer 133

The top differentials include: Leukaemia Meningococcal septicaemia Vasculitis Henoch-Schönlein purpura (HSP) Immune thrombocytopenic purpura (ITP) Thrombotic thrombocytopenic purpura (TTP) Traumatic or mechanical causes (e.g., severe vomiting) Non-accidental injury

Answer 134

The diagnostic investigations for suspected leukaemia include: --> Full Blood Count: Recommended within 48 hours for suspected leukaemia. --> Immediate assessment for children or young people with petechiae or hepatosplenomegaly. --> Blood Film: Used to identify abnormal cells and inclusions. --> Lactate Dehydrogenase (LDH): A non-specific marker of tissue damage; often raised in leukaemia but not useful for screening. May be used for assessment and monitoring. -->Bone Marrow Biopsy: Essential for establishing a definitive diagnosis by analyzing bone marrow cells. --> CT and PET Scans: Utilized for staging the condition. --> Lymph Node Biopsy: Assesses abnormal lymph nodes. --> Genetic Tests: Examines chromosomes and DNA changes to guide treatment and prognosis. --> Immunophenotyping: Identifies specific proteins on the surface of the cells to aid in diagnosis and treatment planning.

Answer 135

--> Acute Lymphoblastic Leukaemia (ALL) is a type of leukaemia characterized by: Affected Cell Line: It primarily affects lymphocyte precursor cells, leading to acute proliferation of B-lymphocytes. Pathophysiology: The excessive accumulation of B-lymphocytes replaces other cell types in the bone marrow, resulting in pancytopenia (low levels of red blood cells, white blood cells, and platelets). Demographics: Most commonly affects children under the age of five. Can also occur in older adults. More prevalent in individuals with Down’s syndrome. Associated Conditions: Occasionally associated with the Philadelphia chromosome, though this is more typically linked to chronic myeloid leukaemia (CML).

Answer 136

CLL is a slow proliferation of a single type of well-differentiated lymphocyte, usually B-lymphocytes, affecting mainly adults over 60 years old.

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CLL is often asymptomatic but can present with infections, anaemia, bleeding, and weight loss.

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CLL can cause warm autoimmune haemolytic anaemia.

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Richter’s transformation refers to the rare progression of CLL into high-grade B-cell lymphoma.

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Smear or smudge cells are ruptured white blood cells seen in blood films, particularly associated with CLL due to the fragility of the cells.

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The three phases are: Chronic phase Accelerated phase Blast phase

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The chronic phase is often asymptomatic and diagnosed incidentally due to a raised white cell count. It can last several years before progressing.

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In the accelerated phase, 10-20% of blood and bone marrow cells are abnormal blast cells, leading to symptoms such as anaemia, thrombocytopenia, and immunodeficiency

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In the blast phase, over 20% of the blood and bone marrow cells are blast cells. This phase is associated with severe symptoms, pancytopenia, and is often fatal.

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CML is associated with the Philadelphia chromosome, a translocation between chromosome 9 and 22, creating the BCR-ABL1 gene, which codes for an abnormal tyrosine kinase that drives abnormal cell proliferation.

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AML has many subtypes with different cytogenetics and presentations. It usually presents from middle age onwards.

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AML can result from a transformation of myeloproliferative disorders such as polycythaemia rubra vera or myelofibrosis.

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A high proportion of blast cells is seen, and Auer rods in the cytoplasm of blast cells are a characteristic finding in AML.

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Treatment for leukaemia is coordinated by an oncology and haematology multi-disciplinary team. The main treatment involves chemotherapy and targeted therapies, which depend on the specific type and individual features of the leukaemia. Targeted therapies, especially in CLL, include: Tyrosine kinase inhibitors (e.g., ibrutinib) Monoclonal antibodies (e.g., rituximab, which targets B-cells) Additional treatment options may include: Radiotherapy Bone marrow transplant Surgery

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Complications of chemotherapy include: Failure to treat cancer Stunted growth and development in children Infections due to immunosuppression Neurotoxicity Infertility Secondary malignancy Cardiotoxicity (heart damage) Tumour lysis syndrome

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Tumour lysis syndrome occurs due to the rapid destruction of cancer cells by chemotherapy, leading to the following biochemical changes: High uric acid High potassium (hyperkalaemia) High phosphate Low calcium (secondary to high phosphate)

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Acute kidney injury (due to uric acid crystal formation) Cardiac arrhythmias (due to hyperkalaemia) Systemic inflammation (due to cytokine release)

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Ensure very good hydration and urine output before chemotherapy Use allopurinol or rasburicase to suppress uric acid levels

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Anaemia: lethargy, pallor Neutropaenia: frequent/severe infections Thrombocytopenia: easy bruising, petechiae

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Bone pain (due to Bone pain (due to bone marrow infiltration) Splenomegaly Hepatomegaly Fever in up to 50% of cases (due to infection or constitutional symptom) Testicular swellingbone marrow infiltration) Splenomegaly Hepatomegaly Fever in up to 50% of cases (due to infection or constitutional symptom) Testicular swelling

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Common ALL (75%) with CD10 present, pre-B phenotype T-cell ALL (20%) B-cell ALL (5%)

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Age < 2 years or > 10 years WBC > 20 x 10^9/L at diagnosis T or B cell surface markers Non-Caucasian Male sex

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CLL is caused by a monoclonal proliferation of well-differentiated lymphocytes, almost always B-cells (99%). It is the most common form of leukaemia seen in adults.

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Often asymptomatic; may be discovered incidentally due to lymphocytosis Constitutional symptoms: anorexia, weight loss Bleeding and infections Lymphadenopathy, more marked than in chronic myeloid leukaemia

Answer 160

Full blood count: Lymphocytosis Anaemia (may be due to bone marrow replacement or autoimmune hemolytic anaemia (AIHA)) Thrombocytopenia (may be due to bone marrow replacement or immune thrombocytopenia (ITP)) Blood film: Presence of smudge cells (or smear cells) Immunophenotyping: Key investigation; most cases can be identified using a panel of antibodies specific for CD5, CD19, CD20, and CD23.

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Symptoms of Richter's transformation may include: Lymph node swelling Fever without infection Weight loss Night sweats Nausea Abdominal pain

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Anaemia Hypogammaglobulinaemia leading to recurrent infections Warm autoimmune haemolytic anaemia in 10-15% of patients Transformation to high-grade lymphoma (Richter's transformation)

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Richter's transformation occurs when leukaemia cells enter the lymph node and transform into a high-grade, fast-growing non-Hodgkin's lymphoma. Patients often become unwell very suddenly.

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Acute myeloid leukaemia is the more common form of acute leukaemia in adults. It may occur as a primary disease or following a secondary transformation of a myeloproliferative disorder. Features are largely related to bone marrow failure, including: Anaemia: pallor, lethargy, weakness Neutropenia: high white cell counts with low functioning neutrophils leading to frequent infections Thrombocytopenia: bleeding Splenomegaly Bone pain

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Poor prognostic features include: Age > 60 years 20% blasts after the first course of chemotherapy Cytogenetics: deletions of chromosome 5 or 7

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Acute promyelocytic leukaemia (APL) is classified as M3 and is associated with the t(15;17) translocation, resulting in the fusion of PML and RAR-alpha genes. Key characteristics include: Presents at a younger age (average = 25 years) Auer rods seen with myeloperoxidase stain Disseminated intravascular coagulation (DIC) or thrombocytopenia often at presentation Good prognosis

Answer 167

Answer: The Philadelphia chromosome is present in more than 95% of patients with chronic myeloid leukaemia (CML). It results from a translocation between the long arm of chromosome 9 and the long arm of chromosome 22, denoted as t(9:22)(q34; q11). This translocation causes the ABL proto-oncogene from chromosome 9 to fuse with the BCR gene from chromosome 22, resulting in the BCR-ABL gene, which codes for a fusion protein with excess tyrosine kinase activity.

Answer 168

Common presentations of CML (typically in patients aged 60-70 years) include: Anaemia: lethargy Weight loss and sweating Marked splenomegaly, which may cause abdominal discomfort An increase in granulocytes at different stages of maturation, possibly with thrombocytosis Decreased leukocyte alkaline phosphatase Potential for blast transformation (80% progress to acute myeloid leukaemia [AML], 20% to acute lymphoblastic leukaemia [ALL])

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The first-line treatment for chronic myeloid leukaemia (CML) is imatinib, a tyrosine kinase inhibitor targeting the BCR-ABL defect. It has a very high response rate in the chronic phase of CML. Other management options include: Hydroxyurea Interferon-alpha Allogenic bone marrow transplant

Answer 170

Lymphoma is a type of cancer that affects lymphocytes within the lymphatic system. In lymphoma, cancerous cells proliferate inside the lymph nodes, leading to abnormal enlargement of the lymph nodes, a condition known as lymphadenopathy.

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The two main categories of lymphoma are: Hodgkin’s lymphoma (a specific disease) Non-Hodgkin’s lymphoma (which includes all other types of lymphoma)

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Hodgkin’s lymphoma is the most common specific type of lymphoma. It has a bimodal age distribution, with peaks in incidence around ages 20-25 and 80 years.

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Risk factors for Hodgkin’s lymphoma include: HIV infection Epstein-Barr virus infection Autoimmune conditions (e.g., rheumatoid arthritis and sarcoidosis) Family history of Hodgkin’s lymphoma

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A few notable types of Non-Hodgkin lymphoma include: Diffuse large B cell lymphoma: Typically presents as a rapidly growing painless mass in older patients. Burkitt lymphoma: Particularly associated with Epstein-Barr virus and HIV. MALT lymphoma: Affects the mucosa-associated lymphoid tissue, usually around the stomach.

Answer 175

Risk factors for Non-Hodgkin lymphoma include: HIV infection Epstein-Barr virus infection Helicobacter pylori (H. pylori) infection (associated with MALT lymphoma) Hepatitis B or C infection Exposure to pesticides Exposure to trichloroethylene (an industrial chemical) Family history of lymphoma

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The key presenting symptom of lymphoma is lymphadenopathy. Enlarged lymph nodes may be found in the neck, axilla, or inguinal region. These lymph nodes are typically non-tender and feel firm or rubbery.

Answer 177

Key Presenting Symptom: Lymphadenopathy is the primary symptom, characterised by enlarged lymph nodes that may be located in the neck, axilla, or inguinal region. These nodes are typically non-tender and feel firm or rubbery. Hodgkin’s Lymphoma Specific Symptom: Patients may experience lymph node pain after drinking alcohol. B Symptoms: Systemic symptoms of lymphoma include: Fever Weight loss Night sweats Additional Non-Specific Symptoms: Fatigue Itching Cough Shortness of breath Abdominal pain Recurrent infections

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Lymph Node Biopsy: This is a critical diagnostic investigation for lymphoma. Characteristic Finding in Hodgkin’s Lymphoma: Reed-Sternberg cells, which are large cancerous B lymphocytes with two nuclei and prominent nucleoli, resembling an owl face with large eyes. Imaging Studies: CT Scans: To visualize lymph nodes and assess the extent of disease. MRI: Helpful in evaluating specific areas of involvement. PET Scans: Used for staging and assessing metabolic activity of the lymphoma. HIV test (often performed as this is a risk factor for non-Hodgkin's lymphoma) FBC and blood film (patient may have a normocytic anaemia and can help rule out other haematological malignancy such as leukaemia)

Answer 179

The Lugano classification replaces the older Ann Arbor system and emphasizes the location of affected nodes relative to the diaphragm. Stage 1: Confined to one lymph node or group of nodes. Stage 2: Involvement of more than one group of nodes, but on the same side of the diaphragm (either above or below). Stage 3: Affects lymph nodes on both sides of the diaphragm. Stage 4: Widespread involvement, including non-lymphatic organs (e.g., lungs, liver In addition to these stages, the classification includes the following: A/B Symptom Designation: The absence of significant symptoms is designated as 'A', while the presence of fever, night sweats, or weight loss is designated as 'B'. E: The presence of extranodal disease is denoted by the letter 'E'. S: Involvement of the spleen is denoted by the letter 'S'. X: Bulky disease (large tumor mass) is denoted by the letter 'X'.

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Chemotherapy: Aims to cure the disease but may cause side effects like infections, cognitive impairment, secondary cancers (e.g., leukemia), and infertility. ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine): considered the standard regime BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone): alternative regime with better remission rates but higher toxicity Radiotherapy: Also aims to cure, but can lead to tissue fibrosis, secondary cancers, and infertility.

Answer 181

Management depends on the type and stage and may involve: Watchful waiting Chemotherapy Monoclonal antibodies (e.g., rituximab, targeting B cells) Radiotherapy Stem cell transplantation

Answer 182

Myeloma is a type of cancer that affects plasma cells in the bone marrow. Plasma cells, which are B lymphocytes, produce antibodies. In myeloma, a specific type of plasma cell becomes cancerous, leading to the production of large quantities of a specific paraprotein (or M protein), which is an abnormal antibody or part of an antibody. Most common haematological malignancy

Answer 183

Multiple myeloma is a form of myeloma where the cancer affects multiple areas of the bone marrow throughout the body.

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Plasma cells are B lymphocytes that have developed to produce specific antibodies, also known as immunoglobulins. They play a crucial role in the immune system by recognizing and fighting infections by targeting specific proteins on pathogens.

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Antibodies (immunoglobulins) are complex molecules composed of heavy chains and light chains arranged in a Y shape.

Answer 186

The five types of antibodies are A (IgA), G (IgG), M (IgM), D (IgD), and E (IgE).

Answer 187

Myeloma is a cancer of a single type of plasma cell that undergoes a genetic mutation, causing it to rapidly and uncontrollably multiply. This results in the production of a specific paraprotein (or M protein), which is an abnormal antibody or part of an antibody, often in the form of light chains.

Answer 188

Paraproteinaemia is the condition characterized by an abnormally high level of a specific paraprotein (M protein) in the blood, produced by the malignant plasma cells in myeloma.

Answer 189

Bence Jones proteins refer to free light chains of antibodies that are present in the urine, often associated with multiple myeloma.

Answer 190

The median age at presentation for myeloma is 70 years old.

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Key Symptoms (CRABBI): --> Calcium (Hypercalcaemia): Caused by increased osteoclastic bone resorption due to cytokines released by myeloma cells. Symptoms: Constipation, nausea, anorexia, confusion. --> Renal Impairment: Light chain deposition in renal tubules causes renal damage. Symptoms: Dehydration, increasing thirst. Other causes include amyloidosis, nephrocalcinosis, and nephrolithiasis. --> Anaemia: Bone marrow crowding suppresses erythropoiesis. Symptoms: Fatigue and pallor. --> Bleeding: Thrombocytopenia due to bone marrow crowding increases the risk of bleeding and bruising. --> Bones: Osteoclastic overactivity leads to lytic bone lesions. Symptoms: Bone pain (especially in the back) and increased risk of pathological fractures. --> Infection: Reduced production of normal immunoglobulins leads to increased susceptibility to infections. --> Additional Non-Specific Symptoms: Fatigue Itching Cough Shortness of breath Abdominal pain Recurrent infections Features of amyloidosis (e.g., macroglossia) Carpal tunnel syndrome Neuropathy Hyperviscosity

Answer 192

Myeloma bone disease is caused by increased osteoclast activity and suppressed osteoblast activity, leading to bone resorption exceeding bone formation due to cytokines from abnormal plasma cells. Commonly affected sites include the skull, spine, long bones, and ribs, resulting in osteolytic lesions and pathological fractures (e.g., vertebral fractures). It can also cause hypercalcaemia from calcium reabsorption into the blood. Plasmacytomas are individual tumors formed by cancerous plasma cells, occurring in bones or soft tissues.

Answer 193

Hyperviscosity syndrome is a condition where plasma viscosity exceeds normal levels (1.3 to 1.7 times that of water) due to increased protein levels, such as paraproteins in myeloma. It is considered an emergency and can lead to complications, including: Bleeding: Nosebleeds and bleeding gums Visual Symptoms: Retinal hemorrhages and other eye changes Neurological Complications: Stroke Heart Failure

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Older Age Male Gender Black Ethnic Origin Family History Obesity

Answer 195

Key presenting features include: Persistent Bone Pain (e.g., spinal pain) Pathological Fractures Unexplained Fatigue Unexplained Weight Loss Fever of Unknown Origin Hypercalcaemia Anaemia Renal Impairment

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--> Full Blood Count: - Findings: Anaemia --> Peripheral Blood Film: - Findings: Rouleaux formation --> Urea and Electrolytes: - Findings: Renal failure --> Bone Profile: - Findings: Hypercalcaemia --> Protein Electrophoresis: - Findings: Raised concentrations of monoclonal IgA/IgG in serum; Bence Jones proteins in urine -->Bone Marrow Aspiration: - Confirmatory: Significantly raised plasma cells --> Imaging: - Historical: Skeletal survey for bone lesions - Recommended: Whole-body MRI (2016 NICE guidelines) - X-rays: 'Rain-drop skull' appearance (dark spots); similar to 'pepperpot skull' in primary hyperparathyroidism - lytic lesions - punched out appearance

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Induction Therapy: Combination of Drugs: Targeted drugs: Thalidomide, Lenalidomide, Bortezomib, Daratumumab Chemotherapy: Cyclophosphamide, Melphalan Steroids: Prednisolone, Dexamethasone Choice of combination depends on the patient's eligibility for autologous hematopoietic cell transplantation. Autologous Hematopoietic Cell Transplantation: Process: Removal of the patient’s own stem cells before chemotherapy, replaced afterward. Benefits: Prolongs event-free and overall survival; suitable for younger, healthier patients. Allogenic Hematopoietic Cell Transplantation: Use: Not commonly used due to high mortality rates and graft versus host disease. Management of myeloma bone disease may involve:

Answer 198

Management of complications includes: Pain: Use analgesia based on the WHO analgesic ladder. Pathological Fractures: Administer Zoledronic Acid to prevent/manage osteoporosis and fragility fractures. Infection: Annual Influenza Vaccinations. Consider Immunoglobulin Replacement Therapy. Venous Thromboembolism Prophylaxis: Implement strategies to reduce the risk of blood clots. Fatigue: Address all possible underlying causes. If symptoms persist, consider using an Erythropoietin Analogue.

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--> Haemophilia A: Caused by a deficiency of Factor VIII. Inherited bleeding disorder leading to severe bleeding episodes. --> Haemophilia B (Christmas Disease): Caused by a deficiency of Factor IX. Also an inherited bleeding disorder, similar in severity to Haemophilia A.

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X-linked recessive

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Clinical Manifestation: Haemophilia A and B present similarly; however, disease severity impacts symptoms. Severe cases: More likely to present with spontaneous bleeding and at an earlier age, often during the first two years of life as mobility increases. Symptoms and Signs: --> Haemarthrosis: Bleeding into joints (up to 80% of hemorrhages). Painful, erythematous, stiff, and swollen joints (commonly knees, ankles, elbows). --> Easy Bruising: Ecchymosis often without clear trauma. --> Prolonged Bleeding: After dental procedures (days of oozing after tooth extraction). --> Muscular Haematomas: 15% of hemorrhages, commonly in leg muscles (e.g., quadriceps, calves). Risk of compartment syndrome from increased pressures. --> Epistaxis: Frequent nosebleeds. --> Gastrointestinal Symptoms: Melaena or haematemesis more common in older patients. Neonatal Presentation: Significant portion present in the neonatal period (40%): Prolonged bleeding after circumcision. Intracranial bleeding (up to 5% in severe cases) due to delivery trauma (e.g., forceps). Prolonged bleeding after heel prick testing. Female Carriers: May experience mild symptoms similar to mild male cases, often unnoticed until challenged by trauma or surgery.

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Clinical Suspicion: Haemophilia should be suspected in younger patients with prolonged hemorrhage, ecchymosis, or haemarthrosis. Blood Tests: Full Blood Count (FBC): Assesses for thrombocytopenia to rule out platelet dysfunction. Clotting Studies: Activated Partial Thromboplastin Time (aPTT): Prolonged aPTT is a hallmark of haemophilia, indicating a delay in the intrinsic coagulation pathway. Prothrombin Time (PT): A normal PT helps rule out extrinsic and common pathway issues (e.g., liver disease, vitamin K deficiency, disseminated intravascular coagulation). --> Liver Function Tests (LFTs): To rule out liver synthesis dysfunction affecting clotting factors. --> Factor VIII and IX Assays: Compare with normal levels to determine specific deficiencies. --> Mixing Studies: Mix patient plasma with normal plasma for two hours; a corrected aPTT suggests a clotting factor deficiency. APTT will not correct in cases of acquired haemophilia (due to antibodies against clotting factors). --> Von Willebrand Factor Antigen Testing: To assess for von Willebrand disease, which can present similarly.

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Von Willebrand Disease: Affects both genders; more mucous membrane involvement than haemophilia. Platelet Dysfunction Disorders: Rare but significant; ruled out with normal platelet count and aggregation studies. Other Coagulation Factor Deficiencies: Consider deficiencies of other clotting factors. Scurvy: Vitamin C deficiency leading to bleeding disorders. Ehlers-Danlos Syndrome: Connective tissue disorder with bleeding tendencies. Disseminated Intravascular Coagulation (DIC): Acquired disorder causing bleeding due to systemic activation of coagulation. Child Abuse: In young patients, consider inconsistent stories, delayed presentation, or signs of neglect.

Answer 204

Factor Replacement Therapy: Haemophilia A: Replace factor VIII. Haemophilia B: Replace factor IX. Varying concentrations based on hemorrhage severity. Factor Inhibitors: Antibodies can develop against replacement factors, requiring higher doses. More common in Haemophilia A (up to 30%) than in Haemophilia B (up to 3%). Desmopressin (DDAVP): Used for mild Haemophilia A to promote von Willebrand factor function. Coagulation factor concentrates if bleeding persists. Prophylactic Treatment: Severe disease requires regular infusions (1-3 times/week) to maintain factor levels (30-50% of normal) for at least 45 weeks/year. Supportive Care: Analgesia: Paracetamol, opioids for pain. RICE (Rest, Ice, Compression, Elevation) for injuries. Physiotherapy for rehabilitation. Antifibrinolytic Agents: Considered in cases of severe hemorrhage. Lifestyle Modifications: Avoid contact sports. Avoid aspirin and NSAIDs: Increased bleeding risk.

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Definition: Uncontrolled proliferation of a single type of stem cell in the bone marrow; considered a slow-progressing cancer with potential transformation into acute myeloid leukaemia. Key Disorders: Primary Myelofibrosis Cell Line: Haematopoietic stem cells Blood Findings: Low haemoglobin, variable white cell and platelet counts Polycythaemia Vera Cell Line: Erythroid cells Blood Findings: High haemoglobin Essential Thrombocythaemia Cell Line: Megakaryocyte Blood Findings: High platelet count Genetic Mutations:

Answer 206

Commonly Associated Genes: JAK2 MPL CALR Key Mutation to Remember: JAK2 (Treatment may involve JAK2 inhibitors, such as ruxolitinib)

Answer 207

Definition: Myelofibrosis can arise from primary myelofibrosis, polycythaemia vera, or essential thrombocythaemia, characterised by bone marrow fibrosis due to the proliferation of a single cell line. Pathophysiology: Bone marrow is replaced by scar tissue in response to cytokines (e.g., fibroblast growth factor) released from proliferating cells. This fibrosis impairs blood cell production, leading to: Low haemoglobin (anaemia) Low white blood cells (leukopenia) Low platelets (thrombocytopenia) Extramedullary Haematopoiesis: Blood cell production occurs in the liver and spleen, leading to: Hepatomegaly Splenomegaly Portal hypertension Potential spinal cord compression if occurring around the spine Blood Film Findings: Teardrop-shaped red blood cells Anisocytosis (varying sizes of red blood cells) Blasts (immature red and white cells)

Answer 208

Asymptomatic Patients: Approximately 20% may be asymptomatic. Common Features: Severe Fatigue Hepatosplenomegaly: Splenomegaly may be profound, extending past the midline into the pelvis; present in almost all patients. Hepatomegaly occurs in about 50% of patients. 'B Symptoms' (20%): Weight loss Fever Night sweats These symptoms are associated with neoplasms of the haematopoietic system. Signs of Anaemia: Pale conjunctiva Thromboembolic Events: Secondary to thrombocytosis. Unexplained Bleeding: Secondary to thrombocytopenia. Extramedullary Haematopoiesis Symptoms: Symptoms vary by localization, including: Seizures Paralysis Ascites Pericardial, abdominal, or pleural effusions Raised intracranial pressure Lymphadenopathy Severe Bony Pain: Due to periosteal inflammation and osteosclerosis. The liver and spleen are the most common sites of extramedullary haematopoiesis.

Answer 209

Blood Tests: May show pancytopenia (low levels of red blood cells, white blood cells, and platelets). Presence of teardrop-shaped red blood cells. Bone Marrow Aspirate: May yield a dry tap, indicating difficulty in obtaining a sample due to fibrosis. Bone Marrow Biopsy: Necessary to assess for fibrosis and abnormal megakaryocytes. Genetic Testing: Essential for diagnosis; JAK2 mutation is the most common association with myelofibrosis.

Answer 210

Polycythaemia Vera: Elevated red blood cells; JAK2 mutations present. Essential Thrombocythaemia: Mature megakaryocytes on bone marrow biopsy; JAK2 mutations present. Myelodysplastic Syndrome (MDS): No splenomegaly; hypercellular marrow with ringed sideroblasts. Acute Myeloid Leukaemia (AML): Peripheral smear shows Auer rods and blasts; rapid progression. Acute Lymphoblastic Leukaemia (ALL): Blasts on smear and bone marrow infiltration; surface markers assist diagnosis. Chronic Myeloid Leukaemia (CML): Confirmed with BCR-ABL fusion testing; may have similar symptoms. Non-Haematologic Causes of Myelofibrosis: Hyperparathyroidism Systemic lupus erythematosus Vitamin D deficiency Systemic sclerosis

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symptomatic Patients: No treatment required; routine follow-up recommended. Symptomatic Patients: Curative Option: Haematopoietic Stem Cell Transplant: Only curative treatment; eligibility depends on patient fitness and shown to delay/prevent progression to acute myeloid leukaemia. Symptomatic Management (Palliative): Splenomegaly Management: - Ruxolitinib: JAK2 inhibitor for managing splenomegaly and symptoms, effective regardless of JAK2 mutation status. - Hydroxyurea and Interferon-alpha: Alternative options. - Splenectomy or Splenic Irradiation: Considered if splenomegaly causes significant pain. Management of Anemia: - Blood Transfusions: Mainstay treatment for anemia. - Thalidomide and Prednisone: Adjunctive therapies. - Investigate and Manage Deficiencies: Iron, B9, and B12 deficiencies. Pain from Extramedullary Haematopoiesis: Irradiation of Painful Foci: Effective for pain management. Management of Hyperuricaemia: Allopurinol: Used to control uric acid levels. Preventing Thromboembolic Events: Aspirin: May be used for prevention.

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Definition: Polycythaemia vera (PV) is a myeloproliferative disorder characterized by the clonal proliferation of a marrow stem cell, leading to an increase in red cell volume, often accompanied by overproduction of neutrophils and platelets. Peaks in the sixth decade of life.

Answer 213

A mutation in the JAK2 gene is present in approximately 95% of patient

Answer 214

--> JAK2 Mutation: The JAK2 V617F mutation leads to constitutive activation of the JAK-STAT pathway, causing: - Abnormal erythropoiesis: Increased red blood cell production independent of EPO. - Myeloproliferation: Overproduction of white blood cells and platelets. --> Hyperviscosity and Complications: - Thrombosis risk: Deep vein thrombosis, pulmonary embolism, stroke, and myocardial infarction. - Organ engorgement: Hepatomegaly, splenomegaly. - Haemorrhagic complications: Epistaxis, gastrointestinal bleeding due to abnormal platelet function.

Answer 215

--> Hyperviscosity: Increased blood thickness, leading to complications like thrombosis. --> Pruritus: Itching, typically worsened after a hot bath. --> Splenomegaly: Enlarged spleen. --> Haemorrhage: Bleeding due to abnormal platelet function. --> Plethoric appearance: Reddened or flushed skin, especially the face. --> Hypertension: Present in about a third of patients.

Answer 216

Initial investigations after history and examination: --> Full blood count and blood film: Raised haematocrit, with neutrophils, basophils, and platelets raised in ~50% of cases. --> JAK2 mutation test --> Serum ferritin --> Renal and liver function tests If JAK2 mutation is negative and no secondary cause is found: Red cell mass Arterial oxygen saturation Abdominal ultrasound Serum erythropoietin level

Answer 217

JAK2-positive PV Requires both: --> High haematocrit (>0.52 in men, >0.48 in women) OR raised red cell mass --> JAK2 mutation --> JAK2-negative PV Requires A1 + A2 + A3 + either another A or two B: A1: High haematocrit OR raised red cell mass A2: No JAK2 mutation A3: No secondary cause of high red cell mass B criteria (any 2): --> Thrombocytosis (high platelets) --> Neutrophilia (high neutrophils) --> Splenomegaly --> Low erythropoietin

Answer 218

Aspirin – reduces risk of blood clots. Venesection (first-line) – reduces red cell mass. Hydroxyurea – used when venesection is insufficient; slight risk of secondary leukaemia. Phosphorus-32 therapy – for selected patients, especially older adults.

Answer 219

--> Thrombotic events are a significant cause of morbidity and mortality in PV patients. --> 5-15% of patients may progress to myelofibrosis. --> 5-15% of patients may progress to acute leukaemia, with the risk increased in those treated with chemotherapy.

Answer 220

Haemochromatosis is an autosomal recessive genetic condition that leads to iron overload, with excessive total body iron and its deposition in tissues. It is an iron storage disorder.

Answer 221

The majority of haemochromatosis cases are due to C282Y mutations in the HFE gene, located on chromosome 6. Since haemochromatosis is an autosomal recessive condition, mutations in both copies of the gene are required. The HFE gene regulates iron metabolism.

Answer 222

Haemochromatosis usually presents after age 40 and later in females due to menstruation. Symptoms include: Chronic tiredness Joint pain Bronze skin pigmentation Testicular atrophy Erectile dysfunction Amenorrhoea (in women) Cognitive symptoms (memory and mood disturbances) Hepatomegaly (enlarged liver)

Answer 223

Initial Investigation: Serum ferritin Causes of raised ferritin: Haemochromatosis Infections (acute phase reactant) Chronic alcohol consumption Non-alcoholic fatty liver disease Hepatitis C Cancer Transferrin Saturation: High Transferrin Saturation: Indicates iron overload. Normal Transferrin Saturation: Suggests other causes of raised ferritin. Genetic Testing: For mutations in the HFE gene when both serum ferritin and transferrin saturation are high. Liver Biopsy with Perl’s Stain: Used to establish iron concentration in the liver but may not be necessary due to genetic testing. MRI: Provides detailed imaging and quantifies liver iron concentration, avoiding the need for a biopsy.

Answer 224

--> Secondary Diabetes: Iron overload affects pancreatic function. --> Liver Cirrhosis: Chronic liver damage due to iron deposition. --> Endocrine and Sexual Problems: Hypogonadism Erectile dysfunction Amenorrhea (absence of menstruation) Reduced fertility --> Cardiomyopathy: Iron deposits can affect heart function. --> Hepatocellular Carcinoma: Increased risk of liver cancer. --> Hypothyroidism: Iron can deposit in the thyroid gland. --> Chondrocalcinosis: Calcium pyrophosphate deposits in joints leading to arthritis

Answer 225

General Management: Advice: - Avoid iron and iron-containing supplements. - Avoid vitamin C supplements (except in iron chelation therapy). - Limit or avoid alcohol. - Consider hepatitis A and B vaccinations. Specific Management by Stage: Stage 0: Criteria: Normal transferrin saturation and ferritin; no clinical symptoms. Management: Monitor iron labs and symptoms every 3 years. Stage 1: Criteria: Transferrin saturation > 45%; normal ferritin; no clinical symptoms. Management: Monitor iron labs and symptoms every year. Stage 2, 3, 4: Criteria: Transferrin saturation > 45%; raised ferritin and/or clinical symptoms. Management: Phlebotomy (venesection). Phlebotomy Process: Induction: Weekly sessions until iron levels are <50% transferrin saturation (under specialist guidance). Maintenance: Infrequent (less than monthly) sessions to maintain normal iron levels. Iron Chelation Therapy: Indicated for patients with contraindications to phlebotomy (e.g., anaemia, cardiac disease). Options include oral (Deferasirox) and parenteral (Desferrioxamine) agents. Liver Transplantation: Candidates for patients with end-stage cirrhotic liver disease due to haemochromatosis (transplant outcomes are poorer compared to other causes of cirrhosis).

Answer 226

Febrile neutropenia is characterized by the presence of a fever > 38°C and an absolute neutrophil count of <1.0 × 10^9/L.

Answer 227

--> Patients may be considered to have febrile neutropenia with a recorded fever and recent chemotherapy (usually within the last 2 weeks), even if the neutrophil count is not low. --> Neutropenia occurs due to bone marrow suppression, common with chemotherapy and other causes (e.g., anemias, genetic defects, drugs, infections). --> Patients with neutropenia are at high risk for life-threatening bacterial infections and sepsis.

Answer 228

Suspect febrile neutropenia in patients receiving chemotherapy who develop a fever (>38°C) or appear systemically unwell.

Answer 229

Assess if the patient is in a high-risk group (e.g., renal failure). Inquire about the timing of the last chemotherapy cycle. Ask about any recent blood products or intravascular devices. Check past microbiology results for any history of resistant organisms.

Answer 230

Check for cardiac and respiratory symptoms, pyrexia, skin rashes, lymphadenopathy, and potential foci of infection. Conduct ENT examination, fundoscopy, and assess the GI tract, respiratory system, genitourinary tract, and neurological signs (e.g., signs of meningism).

Answer 231

--> Full blood count (FBC) to check neutrophil levels. --> Two blood cultures from a peripheral vein and any indwelling venous catheters. --> Radiological investigations if needed. --> Additional tests: blood film, renal and liver function tests, CRP, CXR, coagulation screen, and viral serology.

Answer 232

Administer empiric IV broad-spectrum antibiotics according to local policy, ideally within 60 minutes. Provide supportive measures, such as IV fluids if necessary.

Answer 233

Oral antibiotics may be prescribed for some low-risk febrile neutropenia patients who are hemodynamically stable and do not have severe complications (e.g., pneumonia, acute leukaemia, evidence of organ failure).

Answer 234

NICE suggests that all patients requiring IV treatment should start on β-lactam monotherapy, such as piperacillin-tazobactam. Aminoglycosides should be avoided for initial empirical therapy unless there are specific reasons.

Answer 235

Hyposplenism refers to a reduced or absent splenic function, which can lead to increased susceptibility to infections and certain hematological disorders.

Answer 236

--> Splenectomy - surgical removal of the spleen. --> Sickle Cell Disease - leads to splenic infarcts and loss of function. --> Coeliac Disease - causes lymphocytic infiltration of the spleen. --> Dermatitis Herpetiformis - associated with coeliac disease, contributing to hyposplenism. --> Graves' Disease - autoimmune condition affecting splenic function. --> Systemic Lupus Erythematosus (SLE) - autoimmune processes impairing splenic function. --> Amyloidosis - deposition of amyloid in the spleen impairs its function.

Answer 237

--> Relative Polycythaemia --> Primary Polycythaemia (Polycythaemia Rubra Vera) --> Secondary Polycythaemia

Answer 238

Dehydration Stress (Gaisbock syndrome)

Answer 239

Polycythaemia Rubra Vera

Answer 240

Chronic Obstructive Pulmonary Disease (COPD) High Altitude Obstructive Sleep Apnoea Excessive Erythropoietin: Cerebellar haemangioma Hypernephroma (Renal Cell Carcinoma) Hepatoma Uterine Fibroids*

Answer 241

Red Cell Mass Studies: True polycythaemia: Total red cell mass in males > 35 ml/kg and in females > 32 ml/kg.

Answer 242

Malaria is an infectious disease caused by members of the Plasmodium family of protozoan parasites, which are single-celled organisms.

Answer 243

Plasmodium falciparum is the most severe and dangerous type of malaria, accounting for about 80% of malaria cases in the UK.

Answer 244

--> Malaria is spread through bites from female Anopheles mosquitoes that carry the disease.

Answer 245

Plasmodium falciparum Plasmodium vivax Plasmodium ovale Plasmodium malariae

Answer 246

Plasmodium falciparum causes nearly all episodes of severe malaria.

Answer 247

Plasmodium vivax is the most common and causes 'benign' malaria

Answer 248

--> Sickle-cell trait, which inhibits parasite survival in red blood cells. --> G6PD deficiency, reducing parasite survival in red blood cells. --> HLA-B53, associated with an enhanced immune response. --> Absence of Duffy antigens, which prevents Plasmodium vivax from entering red blood cells.

Answer 249

--> Malaria is spread by female Anopheles mosquitoes, typically at night. --> The mosquito ingests infected blood, where the Plasmodium parasites reproduce in its gut, forming sporozoites. --> When the mosquito bites a person, sporozoites are injected and travel to the liver. --> P. vivax and P. ovale can remain dormant in the liver as hypnozoites. --> In the liver, parasites mature into merozoites, which enter the bloodstream and infect red blood cells. --> Red blood cells rupture, releasing merozoites, leading to haemolytic anaemia. --> P. vivax and P. ovale cause tertian malaria (fever spikes every 48 hours). --> P. falciparum causes more frequent or irregular fever spikes, while P. malariae causes quartan malaria (fever spikes every 72 hours).

Answer 250

Symptoms: Fever (up to 41ºC) with sweats and rigors Fatigue Myalgia (muscle aches) Headache Nausea and vomiting Signs on examination: Pallor (due to anaemia) Hepatosplenomegaly Jaundice (from bilirubin release during red blood cell rupture) The most characteristic symptom is a fever that spikes every 48 hours. In a patient with unexplained fever, always consider recent or past travel to malaria-endemic areas.

Answer 251

Gold standard: Blood film (should be repeated if diagnosis is unclear) Thick film: More sensitive Thin film: Determines species Rapid diagnostic tests: Detect plasmodial histidine-rich protein 2, with sensitivities of 77-99% and specificities of 83-98% for falciparum malaria. Three negative samples taken over three consecutive days are required to exclude malaria due to the parasites being released from red blood cells into the blood every 48-72 hours.

Answer 252

All patients with falciparum malaria are admitted, and the local infectious diseases team will advise on management. Oral options for uncomplicated malaria: Artemether with lumefantrine (Riamet) - usual first choice Quinine plus doxycycline or clindamycin Proguanil with atovaquone (Malarone) Chloroquine (resistance is increasing) Primaquine (can cause severe haemolysis in G6PD deficiency) Severe or complicated malaria: Admission to HDU or ICU Intravenous options: Artesunate - usual first choice (common side effect: haemolysis) Quinine dihydrochloride

Answer 253

Cerebral malaria Seizures Reduced consciousness Acute kidney injury Pulmonary oedema Disseminated intravascular coagulopathy (DIC) Severe haemolytic anaemia Multi-organ failure and death

Answer 254

General advice: No method is 100% effective alone Use mosquito spray (e.g., 50% DEET) Use mosquito nets and barriers Seek medical advice if symptoms develop Take antimalarial medication as recommended Antimalarial medications: Proguanil with atovaquone (Malarone): Least side effects, taken from 2 days before until 7 days after travel Doxycycline: Causes photosensitivity, taken from 2 days before until 4 weeks after travel Mefloquine: Risk of psychiatric side effects, taken weekly from 2 weeks before until 4 weeks after travel Chloroquine with proguanil: Less used due to resistance

Answer 255

--> Chronic liver disease with portal hypertension (later stages of cirrhosis associated with a small liver) --> Infections: glandular fever, malaria, hepatitis --> Lymphoproliferative disorders --> Myeloproliferative disorders (e.g., CML) --> Amyloidosis

Answer 256

Myelofibrosis Chronic myeloid leukaemia Visceral leishmaniasis (kala-azar) Malaria Gaucher's syndrome Other causes (in addition to the above): Portal hypertension (e.g., secondary to cirrhosis) Lymphoproliferative diseases (e.g., CLL, Hodgkin's) Haemolytic anaemia Infections: hepatitis, glandular fever Infective endocarditis Sickle-cell disease (note: most adults with sickle-cell have an atrophied spleen due to repeated infarction) Thalassaemia Rheumatoid arthritis (Felty's syndrome)

Answer 257

--> Inability to Remove Abnormal RBCs: Loss of splenic tissue leads to the inability to readily remove immature or abnormal red blood cells. - Red Cell Count: Does not alter significantly. - Cytoplasmic Inclusions: Howell-Jolly bodies may be seen in the blood. --> Early Changes Post-Splenectomy (First Few Days): - Target cells, siderocytes, and reticulocytes appear in circulation. - Granulocytosis: Mainly composed of neutrophils immediately after surgery. --> Changes Over Following Weeks: - Transition from granulocytosis to lymphocytosis and monocytosis. - Increased Platelet Count: Often persistent; some patients may require oral antiplatelet agents.

Answer 258

Hyposplenism is the loss of splenic function due to conditions such as splenic artery embolization or splenectomy. Diagnosis: Diagnosis is challenging; peripheral markers like Howell-Jolly bodies are unreliable. Most Sensitive Test: Radionucleotide-labelled red cell scan.

Answer 259

Significantly increases the risk of post-splenectomy sepsis, especially from encapsulated organisms. This increased risk is due to the spleen's role in detecting and responding to these pathogens.

Answer 260

Administer Pneumococcal, Haemophilus type b, and Meningococcal type C vaccines two weeks before or after splenectomy. Schedule: Men C and Hib: Two weeks post-splenectomy. MenACWY: One month later. Children under 2 may need a booster at 2 years. Annual influenza vaccination for all patients.

Answer 261

Penicillin V: Typically continued for at least 2 years or until age 16, though many patients may require lifelong prophylaxis.

Answer 262

Use both pharmacological and mechanical protection when traveling to malaria-endemic areas.

Answer 263

--> Serum Iron: Iron Deficiency Anaemia: Low (< 8 µg/dL) Anaemia of Chronic Disease: Low (< 15 µg/dL) --> TIBC (Total Iron Binding Capacity): Iron Deficiency Anaemia: High Anaemia of Chronic Disease: Low --> Transferrin Saturation: Iron Deficiency Anaemia: Low Anaemia of Chronic Disease: Low --> Ferritin: Iron Deficiency Anaemia: Low Anaemia of Chronic Disease: High

Answer 264

--> Characteristics: - Pancytopenia (low counts of red cells, white cells, and platelets) - Hypoplastic Bone Marrow (reduced cellularity) - Peak incidence of acquired cases at 30 years old Features: - Normochromic, normocytic anaemia - Leukopenia (white blood cell deficiency), with lymphocytes relatively spared - Thrombocytopenia (low platelet count) - May present as acute lymphoblastic or myeloid leukaemia - A minority may develop paroxysmal nocturnal haemoglobinuria or myelodysplasia later --> Causes: - Idiopathic - Congenital: Fanconi anaemia, dyskeratosis congenita - Drugs: Cytotoxics, chloramphenicol, sulphonamides, phenytoin, gold - Toxins: Benzene - Infections: Parvovirus, hepatitis - Radiation

Answer 265

--> Cytotoxic Agents --> Antibiotics: Trimethoprim Chloramphenicol --> Anti-Rheumatoid Medications: Gold Penicillamine --> Carbimazole --> Anti-Epileptics: Carbamazepine --> Sulphonylureas: Tolbutamide

Answer 266

Dabigatran is an oral anticoagulant that works as a direct thrombin inhibitor and does not require regular monitoring like warfarin.

Answer 267

--> Prophylaxis of venous thromboembolism following hip or knee replacement surgery. --> Prevention of stroke in non-valvular atrial fibrillation patients with risk factors such as previous stroke, low LVEF, heart failure, or older age with other conditions.

Answer 268

The major adverse effect is haemorrhage. Doses should be reduced in chronic kidney disease, and dabigatran should not be prescribed if creatinine clearance is < 30 ml/min.

Answer 269

Idarucizumab can be used for rapid reversal of the anticoagulant effects of dabigatran.

Answer 270

The RE-ALIGN study showed significantly higher bleeding and thrombotic events in patients with recent mechanical heart valve replacement. Dabigatran is now contraindicated in such patients.

Answer 271

--> Prevention of stroke in non-valvular atrial fibrillation (AF) with risk factors. --> Prevention of venous thromboembolism (VTE) following hip or knee surgery. --> Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE). Note: Risk factors for stroke prevention generally include prior stroke or TIA, age 75 or older, hypertension, diabetes mellitus, and heart failure.

Answer 272

Mechanism of Action: Direct thrombin inhibitor. Excretion: Majority renal. Reversal Agent: Idarucizumab.

Answer 273

Mechanism of Action: Direct factor Xa inhibitor. Excretion: Majority liver. Reversal Agent: Andexanet alfa.

Answer 274

Mechanism of Action: Direct factor Xa inhibitor. Excretion: Majority faecal. Reversal Agent: Andexanet alfa.

Answer 275

Mechanism of Action: Direct factor Xa inhibitor. Excretion: Majority faecal. Reversal Agent: No authorised reversal agent; andexanet alfa has been studied.

Answer 276

--> Unfractionated (standard) heparin: Activates antithrombin III, forming a complex that inhibits thrombin, factors Xa, IXa, XIa, and XIIa. --> Low molecular weight heparin (LMWH): Activates antithrombin III, increasing its action specifically on factor Xa.

Answer 277

Bleeding Thrombocytopenia Osteoporosis and increased risk of fractures Hyperkalaemia (due to inhibition of aldosterone secretion)

Answer 278

Administration: Standard Heparin: Intravenous LMWH: Subcutaneous Duration of Action: Standard Heparin: Short LMWH: Long Mechanism of Action: Standard Heparin: Inhibits thrombin and multiple factors (Xa, IXa, XIa, XIIa) LMWH: Inhibits factor Xa Side Effects: Standard Heparin: Bleeding, HIT, osteoporosis LMWH: Bleeding (lower risk of HIT and osteoporosis) Monitoring: Standard Heparin: Activated partial thromboplastin time (APTT) LMWH: Anti-Factor Xa (routine monitoring not required) Notes: Standard Heparin: Rapid anticoagulation termination; useful in renal failure LMWH: Standard for managing venous thromboembolism treatment and prophylaxis, and acute coronary syndromes

Answer 279

Heparin overdose may be reversed by protamine sulphate, but this only partially reverses the effect of LMWH.

Answer 280

Parenteral anticoagulants are used for the prevention of venous thromboembolism and in the management of acute coronary syndrome.

Answer 281

Fondaparinux is an anticoagulant that activates antithrombin III, which potentiates the inhibition of coagulation factor Xa. It is administered subcutaneously.

Answer 282

Direct thrombin inhibitors, such as bivalirudin, are anticoagulants that inhibit thrombin directly. They are generally given intravenously.

Answer 283

Dabigatran is an oral direct thrombin inhibitor that is often grouped alongside direct oral anticoagulants (DOACs).

Answer 284

Warfarin is an oral anticoagulant that was first-line for managing venous thromboembolism and reducing stroke risk in patients with atrial fibrillation. It has largely been replaced by direct oral anticoagulants (DOACs), which require less monitoring.

Answer 285

Warfarin inhibits epoxide reductase, preventing the reduction of vitamin K to its active form, which is necessary for the carboxylation of clotting factors II, VII, IX, and X (mnemonic: 1972) and protein C.

Answer 286

Warfarin is indicated for patients with mechanical heart valves (with target INR varying by valve type and location), and as a second-line treatment after DOACs for venous thromboembolism (target INR = 2.5, 3.5 if recurrent) and atrial fibrillation (target INR = 2.5).

Answer 287

Patients are monitored using the INR (International Normalized Ratio), which compares the patient's prothrombin time to normal. Achieving a stable INR can take several days, and various loading regimens and software are used to adjust doses.

Answer 288

Factors include liver disease, P450 enzyme inhibitors (e.g., amiodarone, ciprofloxacin), cranberry juice, drugs that displace warfarin from plasma albumin (e.g., NSAIDs), and drugs that inhibit platelet function (e.g., NSAIDs).

Answer 289

Side effects include hemorrhage, teratogenic effects (though safe for breastfeeding), skin necrosis (due to reduced protein C biosynthesis leading to a temporary procoagulant state), and purple toes.

Answer 290

Antiepileptics: phenytoin, carbamazepine Barbiturates: phenobarbitone Rifampicin St John's Wort Chronic alcohol intake Griseofulvin Smoking (affects CYP1A2)

Answer 291

Antibiotics: ciprofloxacin, clarithromycin/erythromycin Isoniazid Cimetidine, omeprazole Amiodarone Allopurinol Imidazoles: ketoconazole, fluconazole SSRIs: fluoxetine, sertraline Ritonavir Sodium valproate Acute alcohol intake Quinupristin

Answer 292

Stop warfarin. Give intravenous vitamin K 5 mg. Administer prothrombin complex concentrate; if not available, give fresh frozen plasma (FFP). For INR > 8.0.

Answer 293

Stop warfarin. Administer intravenous vitamin K 1-3 mg. Repeat the dose of vitamin K if INR is still too high after 24 hours. Restart warfarin when INR < 5.0. For INR > 8.0.

Answer 294

Stop warfarin. Give vitamin K 1-5 mg by mouth (using the intravenous preparation orally). Repeat the dose of vitamin K if INR is still too high after 24 hours. Restart warfarin when INR < 5.0.

Answer 295

Withhold 1 or 2 doses of warfarin. Reduce the subsequent maintenance dose.

Answer 296

Clopidogrel Prasugrel Ticagrelor Ticlopidine

Answer 297

ADP is a key platelet activation factor mediated by G-coupled receptors P2Y1 and P2Y12. ADP receptor inhibitors primarily target the P2Y12 receptor, which is crucial for sustained platelet aggregation and stabilizing the platelet plaque.

Answer 298

Studies have shown that combining aspirin with prasugrel or ticagrelor results in a significant reduction in short- and long-term ischemic events compared to clopidogrel and aspirin in moderate- to high-risk ACS patients.

Answer 299

Start dual antiplatelet treatment (DAPT) with aspirin (75 mg daily) and ticagrelor (90 mg twice daily) for 12 months. For patients undergoing PCI, use aspirin (75-100 mg daily) with either prasugrel (10 mg daily) or ticagrelor (90 mg twice daily), or clopidogrel (75 mg daily if others are unsuitable) for 12 months, followed by aspirin alone.

Answer 300

Ticagrelor may cause dyspnoea due to impaired clearance of adenosine.

Answer 301

Clopidogrel interacts with proton pump inhibitors, particularly omeprazole and esomeprazole, which can reduce its antiplatelet effects.

Answer 302

Prior stroke or transient ischemic attack High risk of bleeding Hypersensitivity to prasugrel

Answer 303

High risk of bleeding History of intracranial hemorrhage Severe hepatic dysfunction Caution in patients with acute asthma or COPD (due to higher rates of dyspnoea)

Answer 304

Aspirin blocks the action of cyclooxygenase-1 and cyclooxygenase-2, which are responsible for the synthesis of prostaglandins, prostacyclin, and thromboxane. This reduces thromboxane A2 formation in platelets, decreasing their ability to aggregate.

Answer 305

Low-dose aspirin is widely used to reduce platelet aggregation in patients with established cardiovascular disease. However, recent guidelines have changed, and not all patients with established cardiovascular disease automatically take aspirin if there are no contraindications.

Answer 306

The Aspirin for Asymptomatic Atherosclerosis trial and the Antithrombotic Trialists Collaboration have cast doubt on the effectiveness of aspirin for primary prevention, although guidelines have not yet been updated.

Answer 307

Aspirin is recommended as first-line treatment for patients with ischemic heart disease.

Answer 308

Aspirin can potentiate the effects of: Oral hypoglycemics Warfarin Steroids

Answer 309

Aspirin should not be used in children under 16 due to the risk of Reye's syndrome. An exception is made for Kawasaki disease, where the benefits are considered to outweigh the risks.

Answer 310

There is a conflict in guidelines: recent Royal College of Physician (RCP) guidelines support clopidogrel as first-line treatment for TIAs, while older NICE guidelines recommend aspirin in combination with dipyridamole, which the RCP describes as "illogical."

Answer 311

Clopidogrel is an antiplatelet agent used to manage cardiovascular disease, particularly in patients with acute coronary syndrome, and is now first-line following an ischemic stroke and for peripheral arterial disease.

Answer 312

Clopidogrel belongs to a class of drugs known as thienopyridines.

Answer 313

Other thienopyridines include prasugrel, ticagrelor, and ticlopidine.

Answer 314

Clopidogrel acts as an antagonist of the P2Y12 adenosine diphosphate (ADP) receptor, inhibiting the activation of platelets.

Answer 315

The concurrent use of proton pump inhibitors (PPIs) may reduce the effectiveness of clopidogrel. The MHRA has indicated concerns particularly with omeprazole and esomeprazole, although other PPIs like lansoprazole are considered safer.

Answer 316

The increase in comorbidity, such as established cardiovascular disease requiring antiplatelet therapy and conditions like atrial fibrillation, venous thromboembolism, or valvular heart disease requiring anticoagulant therapy.

Answer 317

The combination therapy increases the risk of bleeding and may not be necessary in all cases.

Answer 318

All patients should be prescribed an antiplatelet. If an indication for anticoagulant exists (e.g., atrial fibrillation), anticoagulant monotherapy is preferred without adding antiplatelet therapy.

Answer 319

Patients typically receive triple therapy (2 antiplatelets + 1 anticoagulant) for 4 weeks to 6 months, followed by dual therapy (1 antiplatelet + 1 anticoagulant) to complete 12 months.

Answer 320

The duration can vary based on individual risk factors for stroke in patients with atrial fibrillation.

Answer 321

They are likely to be prescribed anticoagulants for 3-6 months. An ORBIT score should be calculated to assess bleeding risk.

Answer 322

Patients with a low risk of bleeding may continue antiplatelets, while those with intermediate or high risk of bleeding should consider stopping antiplatelets.

Answer 323

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 324

Features: Fever, chills (1-2% for red cell transfusion, 10-30% for platelet transfusion) Management: Slow or stop the transfusion, administer paracetamol, monitor the patient.

Answer 325

Features: Pruritus, urticaria Management: Temporarily stop the transfusion, administer antihistamine, monitor the patient.

Answer 326

Features: Hypotension, dyspnoea, wheezing, angioedema Management: Stop the transfusion, administer IM adrenaline, provide ABC support, oxygen, and fluids.

Answer 327

Cause: ABO-incompatible blood (often due to human error) Features: Fever, abdominal pain, hypotension Management: Stop the transfusion, confirm diagnosis, check patient identity, send blood for direct Coombs test, provide supportive care and fluid resuscitation.

Answer 328

Features: Hypoxia, pulmonary infiltrates on chest X-ray, fever, hypotension Management: Stop the transfusion, provide oxygen and supportive care.

Answer 329

Cause: Excessive rate of transfusion, pre-existing heart failure Features: Pulmonary oedema, hypertension Management: Slow or stop the transfusion, consider intravenous loop diuretics (e.g., furosemide) and oxygen.

Answer 330

--> Red Blood Cells (RBCs): Viral (HIV, HBV, HCV) and possible bacterial contamination. --> Platelets: Higher risk for bacterial contamination (e.g., Staphylococcus epidermidis). --> Prions: Risk of vCJD transmission, mitigated by leucodepletion and importing plasma derivatives.

Answer 331

Potential complications include disseminated intravascular coagulation (DIC) and renal failure.

Answer 332

RBC structural membrane proteins connect the lipid bilayer to the underlying cytoskeleton, providing structural support. Mutations lead to the loss of RBC structure, causing them to become spherical (spherocytes) with reduced deformability. Spherocytes are selectively removed and destroyed by the spleen during passage through the reticuloendothelial system, leading to extravascular hemolysis. This process significantly reduces RBC lifespan. The severity of hemolysis and associated disease varies among individuals, depending on the type and extent of membrane disruption.

Answer 333

--> Hereditary Spherocytosis (HS) is an inherited condition that affects the structure of red blood cells (RBCs). --> It is the most common cause of hemolytic anemia due to a defect in the RBC membrane, although it is rare. --> The defect leads to a high destruction rate of abnormal RBCs, resulting in clinical symptoms and signs of hemolytic anemia, such as fatigue, pallor, and jaundice.

Answer 334

Mild (20-30% of cases): Asymptomatic; may have incidental findings on blood tests. Haemolysis is compensated; no clinical anemia or jaundice. Commonly presents with unexplained splenomegaly (of little clinical significance). Moderate (60-75% of cases): Usually presents in childhood. Symptoms include anemia, fatigue, pallor, dyspnoea, and jaundice. Splenomegaly is also present. Severe (5% of cases): Typically presents with a dramatic drop in hemoglobin after the first week of life. Symptoms include significant anemia, splenomegaly, and neonatal jaundice.

Answer 335

Full Blood Count (FBC): Low Hemoglobin: May be normal in compensated mild cases. Elevated Mean Corpuscular Hemoglobin Concentration (MCHC): Highly suggestive of HS if >36 g/dL due to spherocytes' reduced surface area to volume ratio. Low Mean Corpuscular Volume (MCV): Supports diagnosis but is less reliable due to reticulocytosis. Elevated Red Cell Distribution Width (RDW): Reflects reticulocytosis, supports diagnosis when considered with other parameters. Peripheral Blood Film: Spherocytes: RBCs exhibit loss of central pallor and normal biconcave shape. Evidence of reticulocytes may also be present. Tests for Hemolysis: Elevated Unconjugated Bilirubin: Normal levels may occur in mild cases. Elevated LDH. Low Haptoglobin. Elevated Reticulocyte Count: Normal in aplastic anemia. Direct Coombs Test: Negative in HS; performed to exclude immune-mediated hemolysis.

Answer 336

Main Aim: Prevent and minimize complications from chronic hemolysis and anemia. Monitoring: Regular follow-up blood tests depend on disease severity; not needed if baseline results are acceptable. All patients should be educated about their diagnosis and the risk of transient aplastic crisis. General Supportive Measures: Folic Acid Supplementation: Indicated for moderate to severely affected individuals or pregnant patients to prevent megaloblastic anemia due to increased RBC production. Red Cell Transfusions: Indicated in severely affected individuals or during certain clinical scenarios (e.g., pregnancy or aplastic anemia). Not ongoing due to iron overload risk; transfusion thresholds consider age, comorbidities, and clinical scenario. Erythropoietin: May reduce transfusion needs in young infants until they can mount an adequate hematopoietic response. Splenectomy: Significantly reduces hemolysis and complications; indicated for severely affected cases (transfusion-dependent or with severe symptoms). Total splenectomy is usually delayed until age 6 to reduce post-splenectomy sepsis risk; partial splenectomy may be recommended if delay is not possible. Post-splenectomy management includes immunizations and antibiotic prophylaxis against encapsulated bacteria. Gallstones: Symptomatic gallstones may require concomitant cholecystectomy during splenectomy. Considerations: Splenectomy may be contraindicated in some HS subtypes due to increased venous thrombosis risk; proper subtype identification by hematologists is crucial.