Haematology Flashcards
Define polycythaemia
Polycythaemia = increased haemoglobin concentration above the normal for age and sex matched individual
Polycythaemia Vera = A bone marrow neoplasm associated with excessive production of red blood cells. It is characterised by erythrocytosis, thrombocytosis, leukocytosis and splenomegaly.
What is the difference between relative and absolute polycythaemia?
Relative polycythaemia = normal red blood cell mass but decreased blood volume
Absolute polycythaemia = increased red cell mass
Summarise the aetiology of polycythaemia
Polycythaemia Rubra Vera: (Primary Polycythaemia)
Clonal proliferation of myeloid cells
Varied morphologic maturity and haematopoietic efficiency
Mutations in JAK2 tyrosine kinase
Secondary Polycythaemia:
Raised red blood cell production in response to APPROPRIATE increase in erythropoietin: Chronic hypoxia (e.g. chronic lung disease, living at high altitude) - upregulation of erythropoiesis
Raised red blood cell production in response to INAPPROPRIATE increase in erythropoeitin:
Renal (carcinoma, cysts, hydronephrosis)
Hepatocellular carcinoma
Fibroids
Cerebellar hemangioblastoma
Erythropoietin abuse by athletes
Relative Polycythaemia:
Dehydration (e.g. diuretics, burns, enteropathy)
Gaisbock’s syndrome - young male smokers with increased vasomotor tone and hypertension, which results in a decrease in plasma volume and an apparent increase in red cell count
Summarise the epidemiology of polycythaemia
Peak Age 45-60 years
UK Annual Incidence of Polycythaemia Rubra Vera: 1.5 in 100,000
Polycythaemia Vera more common in men
Very rare in children
Incidence increases with age
What are the presenting symptoms of polycythaemia?
Hyperviscosity symptoms - headaches, blurred vision
Fatigue
Plethoric/red face
Aquagenic pruritis - itching particularly after warm bath
Dizziness
Increased sweating
Dyspnoea
Tinnitus (ringing or buzzing in the ears)
Night Sweats
Tenderness & Redness of fingers, palms, heels or toes
Pain from Peptic Ulcer Disease
Angina
Gout
What are the signs on physical examination of polycythaemia?
Plethoric face
Excoriation marks from itching
Splenomegaly
Conjunctival suffusion - red conjunctiva
Retinal venous engorgement
Hypertension
What are the appropriate investigations for polycythaemia?
FBC - high Hb, high haematocrit, low MCV
Isotope Dilution Techniques:
Find plasma volume and red cell mass
Can then distinguish between relative and absolute polycythaemia
Polycythaemia Rubra Vera: High Hb High haematocrit Low MCV High WCC High platelets Low serum erythropoeitin JAK2 mutation Bone marrow trephine and biopsy - erythroid hyperplasia and raised megakaryocytes
Secondary Polycythaemia:
High serum erythropoeiti
Exclude Chronic Lung Disease/Hypoxia
Check for EPO-secreting Tumours (CT Abdo, Brain MRI
Define macrocytic anaemia
A low haemoglobin below which is normal for an sex and age-matched individual in the presence of erythrocytes with a high MV (>100fL).
There are two types: megaloblastic and non-megaloblastic
Summarise the aetiology of macrocytic anaemia
Megaloblastic:
Bone marrow produces unusually large, structurally abnormal immature RBCs
Vitamin B12 deficiency
- Decreased dietary intake (vegans)
- Defective absorption:
1. Gastric atrophy - less HCl, less pepsin, less absorption
2. Gastric bypass - food passes through too quickly to be absorbed
3. Pernicious anaemia - antibodies against intrinsic factor or parietal cells
4. Terminal ileal disease
Folate deficiency
- Decreased dietary intake (little leafy greens or citrus fruit) - alcoholics, elderly, anorexia
- Increased need (pregnancy, lactation, malignancy, chronic inflammation, haemolytic anaemia)
- Impaired absorption
- Jejunal Disease ie coeliac
- Drugs eg phenytoin
Drugs: Methotrexate, Hydroxyurea, Azathioprine, Zidovudine
NON-MEGALOBLASTIC: Alcohol Excess Liver Disease Myelodysplasia Multiple Myeloma Hypothyroidism Haemolysis Drug
Summarise the epidemiology of macrocytic anaemia
Elderly
Females
What are the presenting symptoms of macrocytic anaemia?
Fatigue
Lethargy
Exertional dyspnoea
Shortness of breath
Symptoms of CAUSE:
Weight loss
Diarrhoea
Steatorrhea in coeliac disease
Regular falls and tingling of extremeties in vitamin B12 deficiency
What are the signs on physical examination of macrocytic anaemia?
Pallor
Tachycardia
Dyspnoea
Signs of pernicious anaemia: Jaundice Glossitis Angular stomatitis Weight loss
Signs of B12 deficiency: Peripheral neuropathy Subacute combined degeneration of the spinal cord Ataxia Optic atrophy Dementia
What are the appropriate investigations for macrocytic anaemia?
Bloods:
FBC: increased MCV, low Hb, pancytopenia in megaloblastic
LFTs: increased bilirubin (due to ineffective erythropoiesis or haemolysis)
Serum Vitamin B12 - low if due to B12 deficiency
Red Cell Folate - low if due to folate deficiency
Anti-parietal cell AND anti-intrinsic factor antibodies - if pernicious anaemia causing B12 deficiency
Serum protein electrophoresis – looking for dense band in Myeloma
ESR, TFT (hypothyroidism can cause non-megaloblastic)
Peripheral blood film:
Large erythrocytes
Megaloblastic: Megaloblasts, Hyper segmented Neutrophil Nuclei (>5 lobes)
Schilling Test: Method of testing for pernicious anaemia B12 will only be absorbed when given with intrinsic factor
Bone Marrow Biopsy (megaloblast, myelodysplastic changes)
What is the management of macrocytic anaemia?
Vitamin B12 deficiency:
Must be treated first!!
IM hydroxocobalamin for life
Folate Deficiency:
Oral folic acid
What are the possible complications of macrocytic anaemia?
Pernicious Anaemia: increased risk of Gastric Cancer
Pregnancy: folate deficiency increases risk of neural tube defects
Summarise the prognosis of macrocytic anaemia
Majority are treatable if there are no complications
Define microcytic anaemia
Haemoglobin lower than expected for an age and sex matched individual with a low MCV <80fL.
Summarise the aetiology of microcytic anaemia
Defects in haem synthesis:
Iron deficiency anaemia
- Chronic blood loss (heavy menstrual period, bleeding gastric ulcer, blood loss from colon cancer)
- Lack of absorption - gastrectomy, IBD, coeliac
- Increased demand - pregnancy
- Malnutrition
Lead poisoning
Sideroblastic Anaemia
Defects in globin synthesis:
Thalassemia
Summarise the epidemiology of microcytic anaemia
It is the most common form of anaemia worldwide
What are presenting symptoms of microcytic anaemia?
Tiredness Lethargy Fatigue Shortness of breath Pallor
Lead Poisoning: Anorexia Nausea/Vomiting Abdominal Pain Constipation Peripheral Nerve Lesions
What are the signs on physical examination of microcytic anaemia?
Pallor
Brittle nails and hair
Iron deficiency:
Koilonychia
Glossitis
Thalassemia: Hepatosplenomegaly Mild jaundice Peripheral nerve lesions (wrist or foot drop) Glossitis – atrophy of lung papillae Angular Stomatitis
Lead poisoning: Blue gum line Convulsions Altered consciousness Encephalopathy
What are the appropriate investigations of microcytic anaemia?
Peripheral blood smear
Iron deficiency anaemia: Microcytic, Hypochromic (central pallor <1/3 cell size), Anisocytosis (variable cell size), Poikilocytosis (variable cell shape)
Sideroblastic anaemia: Dimorphic blood film, Hypochromic microcytic cells
Lead poisoning: Basophilic stippling (coarse dots represent condensed RNA in cytoplasm)
Iron studies:
Iron deficiency - iron and ferritin low, transferrin and TIBC high
Sternoblastic - iron and ferritin high, transferrin and TIBC normal/low
Haemoglobin electrophoresis
Checking for Hb variants and thalassemia
If > 40 years and post-menopausal and no obvious cause of blood loss:
Upper GI endoscopy
Colonoscopy
Investigations for haematuria
Summarise the management of microcytic anaemia
Iron deficiency:
Oral iron supplements
Sideroblastic:
Treat the cause
If inherited: pyridoxine
If no response: blood transfusion and iron chelation
Lead poisoning:
Chelating agents
Dimercaprol
D-penicillinamine
Thalassemia:
Blood transfusions
What are the possible complications of microcytic anaemia?
High Output Cardiac Failure
Complications related to the CAUSE
What is the prognosis of microcytic anaemia?
Depends on the cause
Define aplastic anaemia
A type of anaemia which results in panyctopenia with hypocellular bone marrow without any abnormal cells, usually due to autoimmune destruction of haematopoeitic stem cells.
Summarise the aetiology of aplastic anaemia
Most often IDIOPATHIC (> 40%):
May be due to destruction or suppression of stem cells via autoimmune mechanisms
Acquired:
Drugs (e.g. chloramphenicol, sulphonamides, methotrexate)
Chemicals (e.g. benzene, DDT, insecticides)
Radiation
Viral infection (e.g. parvovirus B19, EBV, HIV)
Paroxysmal nocturnal haemoglobinuria (PNH)
Inherited: Fanconi’s anaemia - pancytopenia, short stature, microcephaly, developmental delay, cafe-au-lait spots, predisposition to malignancy, absent or hypoplastic thumbs Dyskeratosis congenita (rare, progression bone marrow failure syndrome)
Summarise the epidemiology of aplastic anaemia
Equal between males and females (perhaps slightly more common for males)
Biphasic distribution - 10-25 years and >60 years old peak
Fanconi anaemia is one of the most common congenital causes
What are the presenting symptoms of aplastic anaemia?
Can be slow or rapid onset: Fatigue Pallor Dyspnoea Recurrent infections Mucosal bleeding Easy bruising Bleeding gums Epistaxis
What are the signs on physical examination of aplastic anaemia?
Anaemia signs: pallor
Thrombocytopenia signs: bruises, petechiae
NO HEPATOSPLENOMEGALY OR LYMPHADENOPATHY
What are the appropriate investigations of aplastic anaemia?
FBC - low Hb - normocytic anaemia, thrombocytopenia, leukopenia
Serum erythropoeitin - elevated
Reticulocyte count - decreased
Bone marrow biopsy - hypocellular (low haematopoeitic stem cells), no abnormal cells, dry tap
Fanconi’s Anaemia: Check for the presence of increased chromosomal breakage in lymphocytes cultures in the presence of DNA cross-linking agents.
Define disseminated intravascular coagulation
An acquired syndrome characterised by widespread activation of coagulation pathways, resulting in the formation of intravascular thrombi. This can lead to organ ischaemia, necrosis and failure, but also uses up clotting factors and platelets which can lead to spontaneous bleeding.
Acute overt form where there is bleeding and depletion of platelets and clotting factors
Chronic non-overt form where thromboembolism is accompanied by generalised activation of the coagulation system
Summarise the aetiology of disseminated intravascular coagulation
Sepsis
Malignancy
Obsteteric complications - Missed miscarriage, severe pre-eclampsia, amniotic emboli, Placental abruption
Trauma
Intravascular haemolysis
Immunological reactions - blood transfusion reactions, organ transplant rejection
Severe organ destruction or failure (severe pancreatitis, acute hepatic failure)
Vascular disorders (Kasabach-Merritt syndrome or giant haemangiomas, large aortic aneurysms)
Severe toxic reactions
Summarise the epidemiology of disseminated intravascular coagulation
Seen in severely ill patients
What are the presenting symptoms of disseminated intravascular coagulation?
Patients severely unwell with symptoms of underlying disease
Oligouria - suggests circulatory collapse
Dsypnoea
Cough
Confusion/delirium
Evidence of Bleeding - epistaxis, gingivial bleeding
What are the signs on physical examination of disseminated intravascular coagulation?
Signs of underlying disease
Fever
Evidence of shock - hypotension, tachycardia
Acute DIC:
Petechiae, purpura, ecchymoses
Bleeding: Epistaxis, Mucosal bleeding, Overt haemorrhage, haematuria
Signs of end organ damage – local infarction or gangrene
Oliguria due to renal failure
Respiratory distress
Delirium and coma
Chronic DIC:
Signs of deep vein and arterial thrombosis or embolism
Superficial venous thrombosis
What are the appropriate investigations for disseminated intravascular coagulation?
Serum platelets - low Serum fibrinogen - low D-dimer - high Fibrin degradation products - elevated Prolonged PT Prolonged PTT Hb - decreased
Peripheral Blood Film:
Schistocytes (red blood cell fragments)
Define myelofibrosis
A progressive myeloproliferative disorder in which the bone marrow gets replaced by fibrosis and extramedullary haematopoiesis occurs, resulting in splenomegaly. It is also associated with pancytopenia.
Summarise the aetiology of myelofibrosis
Primary myelofibrosis: due to mutation in haematopoietic stem cells - often JAK2 mutation
Primary stem cell defect is UNKNOWN - results in increased numbers of abnormal megakaryocytes which release growth factors resulting in fibrosis
Seconary myelofibrosis: caused by essential thrombocthaemia or polycythaemia vera - 30% of patients have a history of one of these
Summarise the epidemiology of myelofibrosis
Occurs in adults More common in White patients More common in males Median age at diagnosis is 65 years old RARE Peak onset = 50-70
