Haematology Flashcards
What percentage of blood is plasma and what does this consist of?
55%
Plasma proteins–> e.g. albumin and carrier proteins, coagulation factors (e.g. fibrinogen) and immunoglobulins
Water
What percentage of blood is cells?
45%
RBC + Leukocytes + Platelets
What is serum and what does it contain?
Blood plasma without the clotting factors.
Contains:
Glucose
Electrolytes (sodium and potassium)
Proteins (e.g. immunoglobulins and hormones)
Where do blood cells develop?
Bone marrow
Where is the majority of bone marrow found?
Pelvis, vertebrae, ribs, sternum
What can a pluripotent haematopoietic stem cell differentiate into?
Myeloid stem cell
Lymphoid stem cell
Dendritic cell
What can myeloid stem cells differentiate into?
Megakaryocytes
Erythrocytes
Myeloblasts
What do Megakaryocites produce?
Platelets
What do RBC’s develop from?
Reticulocytes that come from myeloid stem cells.
What is the life span of a:
- platelet?
- RBC?
- 10 days
2. 120 days
What is the role of platelets?
To aggregate (clump together) and plug gaps where blood clots need to form.
What can myeloblasts differentiate into?
Basophil Neutrophil Eosinophil Monocyte Mast cells
What do monocytes differentiate into?
Macrophages
What can lymphoid stem cells differentiate into?
B lymphocytes
T lymphocytes
Natural killer cells
What do B lymphocytes differentiate into?
Plasma cells
Memory B cells
What do T lymphocytes differentiate into?
CD4 cells (T helper cells) CD8 cells (cytotoxic T cells) Natural killer cells
Where do B lymphocytes mature?
Bone marrow
Where to T lymphocytes mature?
Thymus gland
What are reticulocytes?
Immature red blood cells that are slightly larger than standard erythrocytes and still have RNA material in them which has a reticular (mesh-like) appearance.
What is the normal percentage of reticulocytes in the blood and why may it increase?
1% of RBC
Percentage goes up when there is a rapid turnover of RBC’s such as in haemolytic anaemia.
What is anaemia?
Low level of haemoglobin in the blood.
A result of disease-not a disease itself
What is haemoglobin?
A protein found in RBC’s, responsible for picking up oxygen in the lungs and transporting it to the cells of the body.
What should you measure to see if a patient has anaemia?
Haemoglobin levels
Mean cell volume (MCV)
What is the mean cell volume?
The size of their red blood cells
What is the normal haemoglobin and MCV levels in women?
Haemoglobin= 120-165 g/L MCV= 80-100 femtolitres
What is the normal haemoglobin and MCV levels in men?
Haemoglobin= 130-180 g/L MCV= 80-100 femtolitres
What are the 3 types of anaemia (based on size)?
Microcytic
Normocytic
Macrocytic
What is microcytic anaemia?
Low MCV anaemia indicating small RBC’s
What is normocytic anaemia?
Normal MCV indicating normal sized RBCs
What is macrocytic anaemia?
Large MCV indicating large RBC’s
What are the causes of microcytic anaemia?
TAILS: Thalassaemia Anaemia of chronic disease Iron deficiency anaemia Lead poisoning Siderobastic anaemia
What are the main causes of normocytic anaemia?
Acute blood loss Anaemia of chronic disease Aplastic anaemia Haemolytic anaemia Hypothyroidism
What are the two main causes of macrocytic anaemia?
Megaloblastic anaemia
Normoblastic anaemia
What is megaloblastic anaemia?
The result of impaired DNA synthesis preventing the cell from dividing normally. Instead it keeps growing into a larger abnormal cells.
What is the cause of megaloblastic (macrocytic) anaemia?
Vitamin deficiency:
B12 deficiency
Folate deficiency
What are the causes of normoblastic macrocytic anaemia?
Alcohol Reticulocytosis Hypothyroidism Liver disease Drugs (e.g. Azathioprine)
What are the main generic symptoms of anaemia?
Tiredness Shortness of breath Headaches Dizziness Palpitations Worsening of other conditions (e.g. angina, heart failure, PVD)
What are the symptoms specific to iron deficiency anaemia?
Pica
Hair loss
What is pica?
Dietary cravings for abnormal things such as dirt
What are the generic signs of anaemia?
Pale skin
Conjunctival pallor
Tachycardia
Raised respiratory rate
What signs are specific to iron deficiency anaemia?
Koilonychia (spoon shaped nails)
Angular chelitis (red, swollen patches in corners of mouth)
Atrophic glossitis (smooth tongue)
Brittle hair and nails
What are the initial investigations into anaemia?
Haemoglobin MCV B12 Folate Ferritin Blood film
What further investigations could be done to diagnose anaemia?
Oesophago-gastroduodenoscopy (OGD) / colonoscopy to investigate cause of unexplained iron deficiency anaemia.
Bone marrow biopsy if cause unclear/
Under what circumstances may a patient become iron deficient?
Insufficient dietary iron
Iron requirements increase (e.g. pregnancy)
Iron being lost (e.g. slow bleeding in colon cancer)
Inadequate iron absorption
Where is the majority of iron absorbed?
Duodenum and jejenum
How is absorbed iron kept in the soluble ferrous (Fe2+) form?
Due to acid in the stomach
What happens when the acid levels drop?
Ferrous iron changes to the insoluble ferric (Fe3+) form
How do medications such as proton pump inhibitors interfere with iron absorption?
Reduce the stomach acid, meaning it stays in the soluble ferrous form for less time
What can cause inadequate iron absorption?
Medications such as proton pump inhibitors
Conditions that cause inflammation of the duodenum/ jejunum (e.g. Coeliac or Crohn’s disease)
What are the most common causes of iron deficiency anaemia?
- Blood loss –> most common cause in adults
- Dietary insufficiency–> most common cause in growing children
- Poor iron absorption
- Increased requirements during pregnancy
What are the most common causes of iron deficiency anaemia due to blood loss?
Monorrhagia (heavy period) Loss from the GI tract: - Gi tract cancer - Oesophagitis -Gastritis -IBD
How does iron travel around the blood?
As ferric ions (Fe3+) bound to transferrin (carrier protein)
What is total iron binding capacity (TIBC)?
The total space on the transferrin molecule for iron to bind.
What is the transferrin saturation?
The proportion of transferring molecules that are bound to iron/
How is the transferrin saturation calculated?
Serum iron/ Total iron binding capacity
What form does iron take when it is deposited and stored in cells?
Ferritin (Fe2+)
What causes raised blood ferritin?
Extra ferritin is released from cells in inflammation (E.g. infection or cancer)
What does low blood ferritin suggest?
Iron deficiency
Why is serum iron not a very useful measure?
It varies significantly throughout the day. (e.g. in the morning and after meals)
What happens to TIBC/ transferrin levels in iron deficiency?
The levels increase
What measurement gives the best indication of the total iron in the body?
Transferrin
What is the normal transferrin level in adults?
30%
Normal range= 15-50%
What blood tests are used to diagnose iron deficienct anaemia/ iron overload?
Serum ferritin
Serum iron
Total iron binding capacity
Transferrin saturation
What is the normal range of serum ferritin?
41-400 ug/L
What is the normal range of serum iron?
12-30 μmol/L
What is the normal range of TIBC?
45-80 μmol/L
What factors can give the impression of iron overload?
Iron supplementation
Acute liver damage (lots of iron is stored in the liver)
What are the 3 main methods of management for iron deficient anaemia?
- Blood transfusion
- Iron infusion
- Oral iron
What are the benefits/ risks of using a blood transfusion to treat iron deficiency anaemia?
Immediately corrects the anaemia and is very quick.
Does not treat underlying iron deficiency and carries risks.
What are the benefits/ risks of using an iron infusion to treat iron deficiency anaemia?
Very quickly corrects the iron deficiency
Small risk of anaphylaxis and should be avoided during sepsis
What is given as oral iron to treat iron deficiency anaemia and how much?
Ferrous sulfate 200mg three times a day
What are the benefits/ risks of oral iron to treat iron deficiency anaemia?
Least invasive.
Slowly corrects the deficiency.
Causes constipation and black coloured stools.
By how much could you expect haemoglobin to rise when correcting iron deficiency anaemia?
10 grams/ litre per week
What is pernicious anaemia?
An autoimmune condition where antibodies form against the parietal cells or intrinsic factor, preventing the absorption of B12 and causing B12 deficiency anaemia
What are the causes of B12 deficiency anaemia?
caused by insufficient dietary intake or by pernicious anaemia
Where in the body is B12 absorbed and what does it need in order to be absorbed?
Ileum
Needs intrinsic factor produced by the parietal cells of the stomach.
What are the main symptoms caused by B12 deficiency?
Neurological symptoms:
- Peripheral neuropathy–> numbness or paraesthesia (pins and needles)
- Loss of proprioception/ vibration sense
- Visual changes
- Mood/ cognitive changes
How is pernicious anaemia diagnosed?
Testing for autoantibodies:
Intrinsic factor antibody
Gastric parietal cell antibody
How can B12 dietary deficiency be treated?
Oral replacement (Cyanocobalamin)
Why can oral B12 replacement not be used to treat pernicious anaemia?
Because the problem is with absorption not intake.
How can pernicious anaemia be treated?
1mg of intramuscular hydroxycobalamin (B12) 3 times weekly for 2 weeks, then every 3 months.
What is haemolytic anaemia?
Anaemia caused by destruction of red blood cells (haemolysis)
What inherited conditions cause haemolytic anaemia and how?
Cause RBC’s to be more fragile and break down faster than normal:
- Hereditary Spherocytosis
- Hereditary Elliptocytosis
- Thalassaemia
- Sickle Cell Anaemia
- G6PD Deficiency
What acquired conditions cause haemolytic anaemia and how?
Lead to increased breakdown of RBC’s:
- Autoimmune haemolytic anaemia
- Alloimmune haemolytic anaemia (transfusions reactions and haemolytic disease of newborn)
- Paroxysmal nocturnal haemoglobinuria
- Microangiopathic haemolytic anaemia
- Prosthetic valve related haemolysis
What does an abnormal rate of RBC destruction cause?
Anaemia
Splenomegaly–> Spleen becomes filled with destroyed RBCs
Jaundice–> Bilirubin is released during the destruction
What investigations can be done to diagnose haemolytic anaemia?
Full blood count
Blood film–> Shows schistocytes (fragments of RBC’s)
Direct Coombs test (shows autoimmune causes)
What is hereditary spherocytosis?
The most common inherited haemolytic anaemia.
Autosomal dominant condition that causes sphere shaped RBCs that are fragile and break down easily when passing through the spleen.
How is hereditary spherocytosis haemolytic anaemia treated?
With folate supplementation and splenectomy
What is hereditary elliptocytosis?
Same as hereditary spherocytosis except RBCs are ellipse shaped instead of spheres.
What is G6PD Deficiency?
Type of haemolytic anaemia caused by a defect in the RBC enzyme G6PD.
What are the two types of Autoimmune Haemolytic Anaemia (AIHA)?
-Warm type
-Cold type
Based on the temperatures at which the auto-antibodies function to cause destruction of RBCs
What is Alloimmune Haemolytic Anaemia?
When there are foreign RBCs or antibodies circulating in the patients blood causing an immune reaction that destroys them.
What causes Alloimmune Haemolytic Anaemia?
Blood transfusion reactions
Haemolytic disease of the newborn
What is Paroxysmal Nocturnal Haemoglobinuria?
Rare condition that occurs when a specific genetic mutation in the haematopoeitic stem cells in the bone marrow results in a loss of proteins on the surface of RBCs that inhibit the complement cascade.. This results in its activation and therefore the destruction of RBCs
What is Microangiopathic Haemolytic Anaemia (MAHA)?
Where the small blood vessels have structural abnormalities that cause haemolysis of the blood cells travelling through them. Usually secondary to an underlying condition
What is Prosthetic Valve Haemolysis?
Haemolytic anaemia caused by turbulence around the valve and collision of red blood cells with the implanted valve. ( Valve churns up the cells and they break down.)
Where in the body is folate absorbed and what does it do?
Absorbed in the jejunum.
Essential for DNA synthesis and RBC formation.
What happens if the body does not have enough folic acid?
The body makes abnormally large RBCs that don’t work properly and there is decreased RBC production in the bone marrow.
What are the main causes of folate deficiency?
Poor folate diet
Malabsorption
Pregnancy
Anti-folate drugs (e.g. mehtotrexate)
What foods are high in folat?
Green vegetables
How can you differentiate B12 and folate deficiency anaemia based on symtpoms?
Unlike B12, there is no neuropathy
What investigations can be done to diagnose folate deficiency anaemia?
FBC
Blood film - show macrocytic anaemia
Serum and erythrocyte folate levels
How is folate deficiency anaemia treated?
Treat underlying cause
Folic acid supplementation (particularly consider during pregnancy)
What is the structure of haemoglobin?
2 alpha and 2 beta-globin chains
What is thalassaemia?
Anaemia caused by an autosomal recessive genetic defect in the protein chains that make up haemoglobin.
What causes alpha thalassaemia?
Genetic defects in alpha-globin chains
What causes beta thalassamia?
Genetic defects in beta-globin chains
What happens to RBCs in thalassaemia?
They are more fragile and break down more easily
What happens to the spleen in thalassaemia?
The spleen collects all the destroyed RBCs and swells, causing splenomegaly
What happens to the bone marrow in thalassaemia?
It expands to produce extra red blood cells for the chronic anaemia.
What does bone marrow expansion in thalassaemia cause?
Susceptibility to fractures and prominent features such as a pronounced forehead and malar eminences
What are the potential signs and symptoms of thalassaemia?
Microcytic anaemia Fatigue Pallor Jaundice Gallstones Splenomegaly Poor growth and development Pronounced forehead/ cheekbones
How is thalassaemia diagnosed?
Full blood count–> Shows microcytic anaemia
Haemoglobin electrophoresis–> diagnoses globin abnormalities
DNA testing–> Looks for genetic abnormalities
(Pregnant women offered screening)
Why is important to monitor serum ferritin levels in thalassaemia?
Iron overload can occur
Why does iron overload occur in thalassaemia?
As a result of faulty creation of blood cells, recurrent transfusions and increased absorption of iron in response to anaemia.
What are the effects of iron overload?
Fatigue Liver cirrhosis Infertility and impotence Heart failure Arthritis Diabetes Osteoporosis/ joint pain
How is iron overload managed?
Limit transfusions
Iron chelation
What chromosome contains the gene that codes for alpha-globin chains?
Chromosome 16
What chromosome contains the gene that codes for beta-globin chains?
Chromosome 11
How is alpha-thalassaemia managed?
Monitor full blood count Monitor complications Blood transfusions Splenectomy Bone marrow transplant
What are the 3 types of beta-thalassaemia and what are they based on?
The defect can either consist of abnormal copies that retain some function or deletion genes where there is no function in beta-globin at all. This leds to 3 types:
Thalassaemia minor
Thalassaemia intermedia
Thalassaemia major
What is thalassaemia minor?
Carriers of abnormally functioning beta globin gene- have one abnormal and one normal gene.
Causes mild microcytic anaemia and does not usually require active treatment.
What is thalassaemia intermedia?
When patients have two abnormal copies of the beta-globin gene. Can either be two defective genes of one defective gene and one deletion gene.
Causes more significant microcytic anaemia and patients require monitoring and occasional blood transfusions.
What is thalassaemia major?
Patient sare homozygous for deletion genes. This means they have no functioning beta-globin genes at all. This usually presents with sever anaemia and failure to thrive in early shildhood.
What does thalassaemia major cause?
Severe microcytic anaemia
Splenomegaly
Bone deformities
What is sickle cell anaemia?
A genetic condition that causes sickle (crescent) shaped red blood cells which are more fragile and easy to destroy, leading to haemolytic anaemia
What happens to fetal haemogloin (HbF) at 6 weeks of age?
It is replaced by HbA
What kind of haemoglobin do sickle cell patients have and what does it cause?
Abnormal variant: HbS
Causes RBCs to have an abnormal sickle shape
What causes sickle cell anaemia?
Autosomal recessive condition caused by an abnormal gene for beta-globin on chromosome 11.
What does having only one copy of the abnormal haemoglobin gene lead to?
Sickle-cell trait- usually asymptomatic.
What are the benefits of having sickle-cell trait
Reduces the severity of malaria.
How is sickle cell anaemia diagnosed?
- Pregnant women at risk of being carriers are offered testing during pregnancy.
- Newborn screening heel prick test at 5 days old.
What are the complications of sickle cell disease?
Anaemia Increased risk of infection Stroke Avascular necrosis Pulmonary hypertension Painful and persistent penile erection Chronic kidney disease Sickle cell crises Acute chest syndrome
How is sickle cell anaemia managed?
Avoid triggers of crises (e.g. dehydration) Ensure vaccines are up to date Antibiotic prophylaxis Hydroxycarbamide Blood transfusion for severe anaemia Bone marrow transplant
What is the benefit of hydroxycarbamide in sickle cell anaemia treatment?
It can be used to stimulate the production of fetal haemoglobin (HbF)- HbF does not lead to sickling of RBCs so has a protective effect against sickle cell crises
What are sickle cell crises?
A range of acute crises linked to sickle cell disease
that can range from mild to life threatening.
What are the main triggers of sickle cell crises?
Spontaneous Infection Dehydration Cold Significant life events
How are sickle cell crises managed?
No specific treatment, just support:
- Treat any infection
- Keep warm
- Keep well hydrated
- Simple analgesia
What are some examples of sickle cell crises?
Vaso-occlusive crisis
Splenic sequestration crisis
Aplastic crisis
Acute chest syndrome
What is a vaso-occlusive crisis?
Pain and fever caused by sickle cells clogging capillaries and causing distal ischaemia.
It can cause dehydration, raised haematocrit and priapism.
What is priapism and how is it treated?
Painful prolonged erection caused by blood being trapped in the penis.
Treated with aspiration of blood from the penis.
What is a splenic sequestration crisis?
When red blood cells block blood flow in the spleen, causing an acutely enlarged and painful spleen, severe anaemia and hypovolaemic shock.
How is splenic sequestration crisis treated?
Supportive management with blood transfusions and fluid resuscitation.
Splenectomy used in cases of recurrent crises.
What is an aplastic crisis?
When there is a temporary loss of the creation of new blood cells- usually resolves within a week
What triggers an aplastic crisis?
Infection with parvovirus B19.
What is acute chest syndrome?
Fever or respiratory symptoms with new infiltrates in chest X-ray, caused by sickling in the small blood vessels in the lungs.
What can cause acute chest syndrome?
Infection (e.g. pneumonia or bronchiolitis) or non-infective causes (e.g. pulmonary vaso-occlusion or fat emboli)
How is acute chest syndrome managed
Antibiotics or antivirals to treat infection.
Blood transfusions
Incentive spirometry
Artifical ventilation.
What is laukaemia?
Cancer of a line of bone marrow stem cells.
How are leukaemias classified?
By how rapidly the progress (chronic or acute)
By the cell line that is affected (myeloid or lymphoid)
What are the 4 main types of leukaemia?
Acute myeloid leukaemia
Acute lymphoblastic leukaemia
Chronic myeloid leukaemia
Chronic lymphocytic leukaemia
What causes leukaemia?
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. This leads to suppression of production other cell lines, resulting in pancytopenia
What is pancytopenia?
Combination of low red blood cells (anaemia), low white blood cells (leukopenia) and low platelets (thrombocytopenia).
What are the progressive ages of the different leukaemias?
‘ALL CeLLmates have CoMmon AMbitions’
- Under 5 and over 45 – acute lymphoblastic leukaemia (ALL)
- Over 55 – chronic lymphocytic leukaemia (CeLLmates)
- Over 65 – chronic myeloid leukaemia (CoMmon)
- Over 75 – acute myeloid leukaemia (AMbitions)
What are the typical features of leukeamia?
Non-specific:
- Fatigue
- Fever
- Failure to thrive
- Pallor
- Petechiae/ abnormal bruising
- Abnormal bleeding
- Lymphadenopathy
- Hepatosplenomegaly
What is petechiae?
Tiny purple, red or brown spots that appear on the skin as a result of bleeding. (non-blanching rash)
What causes bruising and petechiae?
Thrombocytopenia (low platelets)
What are the differential diagnosis of petechiae?
Leukaemia Meningococcal septicaemia Vasculitis HSP Idiopathic Non-accidental injury (abuse)
How is leukaemia diagnosed?
Full blood count Blood film Lactase dehydrogenase blood test Bone marrow biopsy Chest X ray Lymph node biopsy Lumbar puncture CT/ MRI/ PET scan
What are the different types of bone marrow biopsy?
Bone marrow aspiration–> Liquid sample full of cells taken from within bone marrow
Bone marrow trephine–>Solid core sample of bone marrow taken to assess cells and structure
Bone marrow biopsy–> Taken from iliac crest under local anaesthetic with a specialist needle.
What happens in acute lymphoblastic leukaemia?
When a malignant change in a lymphocyte precursor cell causes acute proliferation of a single line of lymphocyte (usually B), causing them to replace the other cell types being created leading to pancytopenia.
What is the epidemiology of acute lymphoblastic leukaemia?
Most common cancer in children and peaks around 2-4 years. Can also affect adults over 45.
Associated with Down’s syndrome and Philadelphia chromosome translocation.
What would a blood film show in Acute Lymphoblastic Leukaemia?
Blast cells
What is the pathophysiology of Chronic Lymphocytic Leukaemia?
When there is a chronic proliferation of a single type of well differentiated lymphocyte (usually B).
What are the presentations of Chronic Lymphocytic Leukaemia?
Over 55 Often asymptomatic Can present with: -Infections -Anaemia -Bleeding -Weight los.s. -Warm autoimmune haemolytic anaemia.
What is Richter’s transformation?
When Chronic Lymphocytic Leukaemia transforms into a high-grade lymphoma
What does a blood film show in Chronic Lymphocytic Leukaemia?
Smear or smudge cells- caused during the preperation of the film where aged or fragile white blood cells rupture and leave a smudge.
What are the three phases of Chronic Myeloid Leukaemia?
- Chronic phase
- Accelerated phase
- Blast phase
What happens during the chronic phase of Chronic Myeloid Leukaemia?
Lasts around 5 years and is often asymptomatic/ diagnosed incidentally with raised white cell count.
What happens during the accelerated phase of Chronic Myeloid Leukaemia?
When the abnormal blast cells take up a high proprtion of cells in the bone marrow and blood (10-20%). Patients become more symptomatic, develop anaemia and thrombocytopenia and become immunocompromised.
What happens in the blast phase of Chronic Myeloid Leukaemia?
Abnormal blast cells make up >30% of bone marrow and blood cells. Has sever symtpoms and pancytopenia. Is often fatal.
What genetic change is indicative of chronic myeloid leukaemia?
Philadelphia chromosome: Translocation of genes between chromosome 9 and 22 (t(9:22) translocation)
What is acute myeloid leukaemia?
Cancer of the myeloid cells- many different types with slightly different cytogenetic differences and presentations.
What can cause acute myeloid leukaemia?
Transformation from a myeloproliferative disorder (e.g. polycythaemia ruby era or myelofibrosis)
What will a blood film show in acute myeloid leukaemia?
High proportion of blast cells with Auer rods (rods inside the blast cell cytoplasms)
Which is the most common leukeamia in adults overall?
Chronic lymphocytic leukeamia
What is the most common acute adult leukaemia?
Acute myeloid leukaemia
How is leukaemia primarily treated?
With chemotherapy and steroids. Can also use radiotherapy, bone marrow transplant and surgery
What are the complications of chemotherapy?
- Failure
- Stunted growth/ development
- Infections due to immunodeficiency
- Neurotoxicity
- Infertility
- Secondary malignancy
- Cardiotoxicity
- Tumour lysis syndrome
What is tumour lysis syndrome?
Caused by the release of uric acid from cells that are destroyed in chemotherapy. Uric acid forms crystals in the interstitial tissue and tubules of the kidneys and causes acute kidney injury.
What are lymphomas?
A group of cancers that affect the lymphocytes inside the lymphatic system., causing lymphadenopathy (abnormally large lymph nodes)
What are the two main categories of lymphoma?
Hodgkin’s lymphoma
Non-Hodgkin’s lymphoma
What is Hodgkin’s lymphoma?
Specific disease caused by proliferation of lymphocytes
What proportion of lymphomas are Hodgkin’s and what is the age distribution?
1 in 5
Bimodal age distribution (peaks around 20 and 75)
What are the risk factors for lymphoma?
HIV
Epstein-Barr Virus
Autoimmune conditions
Family history
What is the key presenting symptoms in Hodgkin’s lymphomas?
Lymphadenopathy–> englarged lymph node that feel rubbery.
May be painful when drinking alcohol
Where are the lymph nodes?
Neck, axilla and ingual region
What are the B symptoms of lymphoma?
Systemic symptoms: Fever, weight loss, night sweats
What are other symptoms of Hodgkin’s lymphoma?
Fatigue Itching Cough S.O.B Abdominal pain Recurrent infections
What investigations can be done to diagnose lymphoma?
Lactase dehydrogenase (LGH) bloofd test
Lymph node biopsy
CT/ MRI/ PET scan
What is the key lymph node biopsy finding in patients with Hodgkin’s lymphoma?
Reed-Sternberg cell- abnormally large B cells that have multiple nuclei and nucleoli inside them. (owl-like appearance)
What is the Ann Arbor staging system?
Classifies lymphomas as to whether they are above or blow the diaphragm
What is a stage 1 lymphoma?
Confined to one region of lymph nodes
What is a stage 2 lymphoma?
In more than one region but on the same side of the diaphragm (either above or below)
What is a stage 3 lymphoma?
Affects lymph nodes both above and below the diaphragm
What is a stage 4 lymphoma?
Widespread involvement including non-lymphatic organs such as the lungs or liver
What are the key treatments of lymphoma?
Chemotherapy and radiotherapy
What is Non-Hodkins lymphoma?
Very large group of lymphomas including Burkitt, MALT and Diffuse large B cell lymphoma.
What are the risk factors for non-Hodgkin’s lymphomas?
HIV Epstein-Barr Virus H. pylori Hep. B or C Exposure to pesticides or trichloroethylene Family history
How are Hodgkin’s and non-Hodgkin’s lymphomas differentiated?
Lymph node bipsy
What is myeloma?
A cancer of the plasma cells.
What is the pathophysiology of myeloma?
Genetic mutation in a specific type of plasma cell, resulting in large quantities of a single type of antibody being produced.
What is multiple myeloma?
Where the myeloma affects multiple areas of the body
What is MGUS?
Monoclonal gammopathy of undetermined significance- An excess of a single type of antibody without other features of cancer/ myeloma
What is a smouldering myeloma?
Where there is progression of MGUS with higher levels of antibodies or antibody components- premalignant and more likely to progress into myeloma.
What is Waldenstrom’s macroglobulinemia?
A type of smouldering myeloma where there is excessive IgM specifically
What is the most likely antibody to be in excess in myeloma?
IgG 50% of the time. (monoclonal paraprotein)
Why does myeloma lead to anaemia?
Cancerous plasma cells invade the bone marrow (infiltration), causing suppression of the development of other blood cell lines leading to anaemia, neutropenia and thrombocytopenia.
What is myeloma bone disease?
When myeloma results in the abnormal breakdown of bone.
What causes myeloma bone disease
A result of increased osteoclast acitivty and suppressed osteoblast activity, resulting in the metabolism becoming imbalances and more bone being reabsorbed than constructed.
What causes myeloma bone disease?
Cytokines released from plasma cells (and stromal cells when they are in contact with plasma cells)
Where are the most common places for myeloma bone disease to happen?
Skull, spine, long bones, ribs.
What are osteolytic lesions?
The areas of bone that become very thin due to myeloma bone disease and can lead to fractures
What are plasmacytomas?
Individual tumours made up of cancerous plasma cells that can occur in the bones or soft tissue.
What does myeloma cause?
Anaemia
Myeloma Bone disease
Myeloma renal disease
Why do patients with myeloma get renal impairment?
- High levels of antibodies block the flow through the tubules
- Hypercalcaemia impairs renal function
- Dehydration
- Medications used to treat it can be harmful
What is the normal plasma viscosity compared to water?
1.3-1.7 X that of water
When does plasma viscosity increase?
When there are more proteins in the blood (e.g. immunoglobulins and fibrinogen)
What does raised plasma viscosity cause?
- Easy bruising
- Easy bleeding
- Reduced or loss of sight
- Purple discolouration of extremities
- Heart failure
4 features of myeloma- CRAB?
Calcium (elevated)
Renal failure
Anaemia
Bone lesions/ pain
What patients would you suspect myeloma in?
Over 60 with persistent bone pain, back pain or unexplained fractures
What are the initial investigations into suspected myeloma?
FBC (low white cell count in myeloma)
Calcium (Raised in myeloma)
ESR (Raised in myeloma)
Plasma viscosity (Raised in myeloma)
What tests would be done if and of the initial myeloma investigations were positive?
An urgent serum protein electrophoresis and urine Bence-Jones protein test.
(BLIP: Bence-Jones protein test L- serum-free Light chain assay I- Serum Immunoglobulins P- Serum Protein electrophoresis)
Bone Marrow biopsy
Imagine
What would be found on an X-ray of a myeloma patient?
Punched out lesions
Lytic lesions
Raindrop skill
What are the aims of the management of myeloma?
To control the disease and improve quality of life
What is the first line treatment of myeloma?
Combination of chemotherapy with:
Bortezomid, Thalidomise or Dexamethasone
How is myeloma bone disease managed?
- Bisphosphates: suppress osteoclast activity
- Radiotherapy to bone lesions
- Orthopaedic surgery can stabilise bones
- Cement augmentation- injecting cement into fractures/ lesions to improve stability
What are myeloproliferative disorders?
Type of bone marrow cancer that consists of a group of conditions that occur due to uncrontrolled proliferation of a single type of stem cell.
What are the three main myeloproliferative disorders?
Primary myelofibrosis
Polycythaemia vera
Essential thrombocythaemia
What is stem cell line mutation causes primary myelofibrosis?
Hematopoietic stem cells
What is stem cell line mutation causes Polycythaemia vera?
Erythroid cells
What is stem cell line mutation causes essential thrombocythaemia?
Megakaryocytes
What can myeloproliferative disorders progress/ transform into?
Acute myeloid leukaemia
What mutations are myeloproliferative disorders associated with?
JAK2 *
MPL
CALR
What is myelofribrosis?
Where proliferation of the cell line leads to fibrosis of the bone marrow- it is replaced by scar tissue
Why does myelofibrosis occur?
As a response to cytokines that are released from proliferating mutated stem cells. (e.g. Fibroblast growth factor)
What does myelofibrosis cause?
- Affects the production of blood cells, leading to anaemia and leukopenia
- Haematopoiesis starts to happen in other areas such as the liver and spleen, causing hepato and splenomegaly and portal hypertension
What are the main systemic presentations of myeloproliferative disorders?
Fatigue
Weight loss
Night sweats
Fever
What signs and symptoms might there by in myeloproliferative disorders?
- Anaemia
- Splenomegaly/ Hepatomegaly
- Portal hypertension
- Low platelets
- Thrombosis
- Raised RBCs
- Low white blood cells
What are the three common signs of polycythaemia vera?
Conjunctival plethora (excessive redness to eyes)
Ruddy complexion
Splenomegaly
What is the test of choice to diagnose myeloproliferative disorders?
Bone marrow biopsy (dry bone marrow aspiration)
How is primary myelofibrosis managed?
- May just be monitored
- Allogenic stem cell transplantation
- Chemotherapy
- Supportive management of associated conditions (e.g. anaemia, splenomegaly)
How is polycystaemia vera managed?
Venesection (keeps haemoglobin in normal range)
Aspirin
Chemotherapy
How is essential thrombocythaemia managed?
Aspirin
Chemotherapy
What is myelodysplastic syndrome?
Group of symptoms caused by the myeloid bone marrow cells not maturing properly and therefore not producing healthy blood cells.
What is thrombocytopenia?
A low platelet count ( <150 X 10^9/L)
What are the main causes of thrombocytopenia due to problems with production?
Sepsis B12 or folic acid deficiency Liver failure (causes reduced thrombopoietin production) Leukaemia Myelodysplastic syndrome
What are the main causes of thrombocytopenia due to problems with destruction?
Medications Alcohol Immune thrombocytopenic purpura Thrombotic thrombocytopenic purpura Heparin-induced thrombocytopenia Haemolytic-uraemic syndrome
How does mild thrombocytopenia present?
Asymptomatic- found incidentally on FBC
How do platelet counts below 50 x 10^9/L present?
Easy/ spontaneous bruising and prolonged bleeding times (e.g. nosebleeds, bleeding gums, heavy periods, easy bruising, blood in urine or stools)
How do platelet counts below 10 x 10^9/L present?
High risk for spontaneous bleeding (e.g. intracranial haemorrhage or GI bleeds)
What are some differential diagnoses of abnormal/ prolonged bleeding?
Thrombocytopenia (low platelets)
Haemophilia A and haemophilia B
Von Willebrand Disease
Disseminated intravascular coagulation (usually secondary to sepsis)
What is purpura?
Purple blood spots/ skin hemorrhages.
What is immune thrombocytopenic purpura (/autoimmune/ idiopathic/ primary TP)?
Condition where antibodies are created against platelets, causing an immune response against them and resulting in their destruction
How can Immun thrombocytopenic purpura be managed?
Steroids (prednisolone)
IV immunoglobulins
Monoclonal antibodies (Rituximab)
Splenectomy
What is thrombotic thrombocytopenic purpura?
Condition where tiny blood clots develop throughout the small vessels of the body, using up platelets and causing thrombocytopaenia.
Why does microangiopathy occur in thrombotic thrombocytopenic purpura?
Blood clots develop due to a shortage of ADAMTS13 protein which normally inactivates von Willebrand factor and reduces platelet adhesion to vessel walls and clot formation.
What is Heparin induced thrombocytopenia?
The development of antibodies against platelets in response to exposure to heparin.
What is Von Willebrand Disease?
The most common inherited cause of abnormal bleeding.
What causes Von Willebrand disease?
Genetic (autosomal dominant) causes cause a deficiency, absence or malfunctioning of von Willebrand factor.
What is von Willebrand factor?
A blood glycoprotein involved in hemostasis.
What are the key presentations of von Willebrand disease?
History of easy, prolonged or heavy bleeding: Bleeding gums Nose bleeds Heavy menstrual bleeding Family history of VWD
How is von Willebrand disease diagnosed?
Based on a history of anbormal bleeding, family history, bleeding assessment and lab investigations
Why is there no easy definitive von Willebrand disease investigation?
Wide range of genetic causes
How and when is von Willebrand disease managed?
Only needs managing in response to major bleeding or trauma or in preparation for operations:
Desmopressin
VWF
Factor VIII
What is haemophilia?
Inherited severe bleeding disorders
What is Haemophilia A caused by?
A deficiency in factor VIII
What is Haemophilia B caused by?
Deficiency in factor IX
What type of inheritance pattern is haemophilia and therefore who does it affect?
X linked recessive Mostly men (as they only have one X chromosome)
What are patients with haemophilia at risk of?
Excessive bleeding in response to minor trauma
Spontaneous haemorrhage without traume
How can haemophilia present in neonates?
Intracranial haemorrhage
Haematomas
Cord bleeding
What are the main presentations of haemophilia?
Spontaneous bleeding into joints (haeemoathrosis) Spontaneous bleeding into muscles Abnormal bleeding in: -Gums -GI tract -Urinary tract -Retroperitoneal space -Intracranial
How is haemophilia diagnosed?
Based on bleeding scores, coagulation factor assays and genetic testing
How is haemophilia managed?
Affected clotting factors (VIII or IX) replaced by IV infusion.
Treatment of acute bleeding episodes.
What is venous thromboembolism?
Common condition where blood clots (thrombosis) develop in the circulation
Why does venous thromboembolis occur?
Secondary to stagnation of blood and hyper-coagulable states
What is it called when a thrombosis develops in the venous circulation?
Deep vein thrombosis
What is the key concern in venous thromboembolism?
That the thrombus will embolise and travel to the right side of heart/ lungs and become a pulmonary embolism.
What are the risk factors for DVT?
Immobility Recent surgery Long haul flights Pregnancy Hormone therapy with oestrogen Malignancy Polycythaemia Systemic lupus Thrombophilia
What are thrombophilias?
Conditions that predispose patients to develop blood clots. e.g.:
Antiphospholipid syndrome, Antithrombin deficiency e.t.c.
What should every patient admitted to hospital be assessed for and what should they recieve?
Should be assessed for their risk of VTE and receive prophylaxis if they are at increased risk/
How does DVT present?
Unilateral calf/ leg swelling Dilated superficial veins Tenderness over site Oedema Colour change to leg
What is the Wells score?
Test to predict the risk of a patient presenting with symptoms having a DVT or pulmonary embolism, accounting for risk factors such as recent surgery and clinical findings.
How is DVT diagnosed?
D-dimer blood test.
Ultrasound doppler of leg
What is the initial management of DVT?
Low molecular weight heparin (anticoagulant)
Should be started before confirming diagnosis.
What are options for longer term anticoagulant to treat DVT?
Warfarin
NOAC/ DOACs
LMWH
How long should anticoagulation be continued for?
3 months if obvious reversible cause
> 3 months if cause unclear, recurrent VTE or irreversible cause (thrombophilia0
6 months in active cancer
What are inferior vena cava filters?
Devices inserted into the inferior vena cava to filter our blood clots travelling from the venous system to the heart and lungs.
What is polycythaemia?
An increase in red blood cell mass, making blood thicker and less able to travel through blood vessels and organs.
What is absolute Polycythaemia and what are the two types?
Caused by an increase in RBC mass.
Primary: Abnormality in bone marrow cells that produce RBCs
Secondary: Underlying condition causes more erythropoietin to be produced, stimulating excess RBC production
What is the main cause of primary absolute polycythaemia?
polycythaemia vera
What are the main causes of secondary polycythaemia?
COPD, Sleep apnoea, kidney disease, high altitude (hypoxia or inapprotiately high erythropoietin secretion)
What is relative polycythaemia and what causes it?
When there is a normal RBC mass but decreased plasma volume. Caused by apparent polycythaemia and dehydration
What are the main causes of apparent polycythaemia?
Obesity, smoking, excess alcohol intake, certain medicines
What treatments can be used for polycythaemia?
Venesection Chemotherapy to slow production of RBCs Medicines to prevent blood clots Treat underlying cause Lifestyle changes to prevent clots
What are the main complications of polycythaemia vera?
Thrombosis (pulmonary embolisms, DVT) and haemorrhage
What is polycythaemia vera?
When an acquired mutation in the JAK2 gene causes bone marrow cells to produce too many RBCs.
What hormone is in control of platelet production and where is it released from?
Thrombopoietin
Liver (and kidneys)
What are the main reasons for platelet dysfunction?
Reduced platelet number–> Decrease in production of increase in destruction
Normal numbers but reduced function–> Congenital abnormality, Medication, von Willebrand disease, uraemia.
What is thrombocytopenia?
Deficiency of platelets in blood.
