Haematology Flashcards
Anaemia
<120 females, <140 males
Erythropoiesis
Takes place in bone marrow. Reticulocytes stay in bone marrow for 3 days before released into circulation. After 1d, form mature RBCs which circulate for 120d and then removed by macrophages. Anaemia develops when rate of RBC production decreases, or rate of RBC destruction increases.
Sx: fatigue, SOB
Signs: pallor of conjunctivae, increased HR, flow murmurs
Classification Low MCV <80 (microcytic) IDA Anaemia of chronic disease Thalassaemia
Normal MCV (80-100)
Acute blood loss
Anaemia of chronic disease
Bone marrow failure (if WCC or platelets low) e.g. myeloma
High MCV >100 (macrocytic)
Megaloblastic: B12 deficiency , Folate
Non-megaloblastic: Alcohol, Pernicious anaemia, hypothyroidism
IDA
Most common anaemia Causes: Blood loss e.g. menorrhagia, GI bleed Poor diet Malabsorption e.g. coeliac
Signs: Koilonocyhia, atrophic glossitis, angular stomatitis, oesophageal webs (Plummer vinson Syndrome)
Ix: FBC, Blood film (microcytic, hypochromic)
Iron panel:
Serum Fe decreased
Ferritin decreased (stores iron. Acute phase protein so can increase in inflammation)
Transferrin increased (binds to iron to deliver to tissues. So as there is less iron there will more transferrin)
TIBC increased
Coeliac - IgA TTG
Gastroscopy/Colonoscopy (males/non-menstruating females - IDA = GI bleed until proven otherwise)
Tx: ferrous sulphate SE: abdo pain, black stools ferrous gluconate IV iron (if intolerant or oral, renal anaemia)
Anaemia of chronic disease
Commonest cause of anaemia in hospital
Causes: infection, inflammation (vasculitis, RA), malignancy
Arises from increased production of hepcidin (decreases absorption of Fe from gut and stores into macrophages,liver cells)
Ix: FBC, blood film (microcytic/normocytic)
Serum Fe decreased (as body trying to keep as little iron in blood as possible)
Ferritin N/increased (as body trying to store as much iron)
Transferrin decreased
TIBC decreased
Tx: treat underlying cause. EPO
Sideroblastic anaemia
Ineffective erythropoiesis, increase iron absorption and iron deposition in marrow
Causes: X-linked or acquired e.g. myelodysplastic diseases, chemo, anti-TB drugs
Ix: Hypochromic blood film, ferritin increased, ring sideroblasts in marrow (ring of iron granules around nucleus)
Tx: Pyridoxine
When do you see increased reticulocytes?
Immature RBCs with RNA (indicates active erythropoiesis)
Increased in haemolysis, haemorrhage
B12 or folate deficiency
B12
Meat
Binds to IF (made by gastric parietal cells)
Absorbed in terminal ileum
Stored: years
Causes of deficiency: diet (vegans), malabosorption (pernicious anaemia - lack of IF, coeliac)
Sx: yellow tinge skin (mix of pallor and jaundice (due to haemolysis), angular stomatitis (red, painful tongue), dementia, peripheral neuropathy
Sub-acute combined degeneration of SC (triad of postive extensor plantar reflex (UMN), absent knee and ankle jerk (LMN). Pain and temp remain intact. Joint/vibration sense lost first then ataxia.
Folate
Green veg
Absorbed in duodenum
Causes of deficiency: poor diet (alcoholics), malabsorption (coeliac)
Ix: LFTs (include gamma GT), serum B12, folate, bone marrow biopsy
Tx: folic acid
Ix: FBC, Reticulocytosis, blood film (hypersegmented neurotriphils), TFTs (hypothyroidism), vit B12, folate.
BM examination in myelodysplastic syndrome
Pernicious anaemia
Autoimmune condition in which atrophic gastritis leads to destruction of parietal cells in stomach and less IF secretion
Associated with other autoimmune disorders
Usually >40 yrs (if under 40 think malabsorption)
2-3x increased risk of gastric ca.
Ix: Serum B12, Blood film (macrocytic), bone marrow (hypersegmented neutrophils), parietal cell antibodies, IF antibodies
Tx: Hydroxocobalamin
Haemolytic anaemia
Pre-mature breakdown of RBCs before their normal lifespan of 120d
Causes;
Hereditary
Glucose 6-phosphate dehydrogenase (X-linked- male) - Sx: acute anaemia and jaundice
Causes: ceftiaxone, anti-malarials
Ix: Heinz bodies (denatured Hb), bite cells
Pyruvate kinase deficiency (ARecessive) - neonatal jaundice, splenomegaly
Acquired:
Autoimmune haemolytic anaemia (warm or cold) - both direct Coombs +ve
Autoimmune hepatitis (Direct -ve)
Malaria
Occurs in Intravascular (in circulation) or Extravascular (RES - spleen, liver, bone marrow
Ix: Anaemia (N or increased MCV), Increased unconjugated bilirubin, urobilinogen, LDH (released from RBCs)
Intravascular Mechanical trauma (mechanical heart valve, HUS), incompatible blood transfusion, malaria, IgM cold autoantibodies
Causes of cold AIHA:
Idiopathic, Mycoplasma pneumonia, infectious mononucleosis, lymphoma
Ix: Increased free plasma haemaglobin (released from RBCs)
Decreased haptoglobin (binds to free Hb as is removed)
Increased haemoaglobinuria
Extravascular
IgG antibodies attach to antigen of RBC which becomes spherocytic and phagocytosed by RES esp. spleen. So spleen enlarges - Splenomegaly }
Causes of warm haemolytic anaemia:
Idiopathic, CLL, Non-Hodkin’s lymphoma, SLE, drugs (Ceftriaxone)
Tx: Corticosteroids, blood transfusion, splenectomy
Hx: family history, dark urine, jaundice, drugs, travel
Examination: hepatosplenomegaly, gallstones (pigmented as increased bilirubin)
Ix: Positive direct Coombs test
bilirubin, LDH, haptoglobin, thick/thin blood film
Difference between direct and indirect Coombs test
Direct - measures antibodies or complement proteins on RBC. Indicates immune mechanism involved.
Auto-immune haemolytic anaemia
Drug-induced (penicillin)
Indirect - measures antibodies in serum. Used for pre-natal test (haemolytic disease of newborn), blood transfusion
Positive in: Automimmune hepatitis, hep B/C, drugs: rituximab
Sickle-cell anaemia
Autosomal recessive
Abnormal RBCs causing vaso-occlusive crisis
Due to amino acid substituion in gene encoding B chain leading to HbS rather than HbA
Hb S polymerises when deoxygenated forming sickle cells which haemolyse and block small blood vessels.
Sickle cell crisis:
triggered by infection, deoxygenation
Sx: pain, anaemia, acute chest syndrome (SOB, pulmonary infiltrates)
Tx: Analgesia, blood cultures, IV fluids, O2 <95%
Ix: FBC (low), reticulocytes (high), cross-match
Thalassaemia
Underproduction (or none) of B globin chain. These damage RBCs causing haemolysis whilst in bone marrow.
B-thalassaemia minor - asymptomatic
B-thalassaemia intermedia - moderate anaemia, not requiring transufiosns
B-thalassaemia major - severe anaemia, failure to thrive ,RBCs made elsewhere causing skull bossing, hepatosplenomegaly
Tx: transfusions, iron chelators (desferrioxamine), splenectomy, bone marrow transplant
Alpha thalassaemias (2 alpha genes on each chromosome) If 4 genes deleted - death in utero If 3 genes deleted - HbH disease. Mod anaemia, hepatosplenomegaly, jaundice If 2 genes deleted - asymptomatic. Decreased MCV Target cells on blood film (looks like mexican hat)
Bleeding disorders
Platelet disorders, von Willebrand abnormalities - bleeding from cuts, skin (easy bruising, purpura), mucous membranes (epistaxis, menorrhagia)
Coagulation disorders - bleeding into joints, muscles
Platelet;
Decreased marrow production: Aplastic anaemia, leukaemia, myeloma
Excess destruction: Immune thrombocytopenia, drugs - heparin (heparin induced thrombocytopenia), thrombotic thrombocytopenic pupura
Sx: prolonged epistaxis, easy bruising, menorrhagia
Coagulation:
Congenital: Von Willebrand, Haemophilia
Acquired: Anticoagulants, DIC, liver disease
Sx:
Joint haemorrhages, muscle haematomas, intracranial bleeding
Platelet disorders
Immune thrombocytopenia (idiopathic thrombocytic pupura)
Antiplatelet autoantibodies
Children or women
Sx: bleeding, purpura, epistaxis. No splenomegaly
Ix: antiplatelet autoantibodies
Tx: prednisolone, IV immunoglobulin
Thrombotic thromcytopenic pupura:
Haemolytic anaemia, decreased platelets, AKI, neuro symptoms
Loss of von Willebrand cleaving enzyme causing large von Willebrand complexes causing thrombocytopenia
Tx: haematological emergency. Plasma exchange
Coagulation disorders
Von Willebrand disease
Missing/defect vWF, which aids platelet aggregration. Binds Factor 8 and prolongs its half life
Sx: mucosal bleeding
Ix: Reduced vWF, Factor VIII, prolonged APTT
Haemophilia A Deficiency in Factor VIII X-linked recessive Male Sx: presents early in life, bleeding into joints, muscle haematomas Ix: Increased APTT, decreased Factor 8 Tx: Desmopressin. Recombiant factor VIII
Haemophilia B X-linked rec: males Deficiency in Factor IX Sx: similar to haemophilia A Tx: recombiant factor 9
Acquired;
Warfarin (INR/PT high), APTT (high as affects factor 9,11)
Tx: Stop warfarin. Vit K, prothombin complex
Liver disease
Poor coag factor synthesis, absorption of vit K, reduced platelets (as decreased thrombopoietin)
Ix: APTT, PT: high
DIC
Activation of coagulation cascade leading to deposition of fibrin - microthrombi, and depletion of coag factors - bleeding
Causes: sepsis, malignancy, massive haemorrhage
Ix: PT (high), APTT (high), D-dimers (high) (as fibrin degradation product), platelets (low)
Tx: Treat cause. FFP +/- platelets
When is PT prolonged?
Tests factors 7, 10, 5, 2, 1
Warfarin, liver disease, DIC
