Haematology Flashcards
Describe MCV, ferritin, serum iron, transferrin; transferrin saturation in iron deficiency anaemia
All low except transferrin high
Describe MCV, ferritin, serum iron, transferrin; transferrin saturation in anaemia of chronic disease
- MCV, low or normal
- ferritin, high or normal
- serum iron, low
- transferrin; low
- transferrin saturation, low or normal
Name 4 causes microcytic hypochromic anaemia
MCV <80
TICS
- Thalassaemia
- iron deficiency
- Chronic disease anaemia
- Sideroblastic anaemia
Name 9 causes macrocytic hyperchromic anaemia
Megaloblastic
- folate deficiency
- vit B12 deficiency
- Bactrim
Non-megaloblastic ALARMS
- Aplastic anaemia, AZT
- Liver disease
- Alcohol
- Reticulocytosis
- Myxoedema, multiple myeloma
- Smoking
Also hypothyroid
Name normal haemoglobin in females and males
Male: 14-18 g/dL
Female: 11.5- 15.5
How investigate for thalassaemia?
Hb electrophoresis
How test for pernicious anaemia (3)
- Anti-parietal cell antibodies
- anti-intrinsic factor antibodies
- gastroscope with biopsy: atrophic gastritis with significant reduction in parietal cells
Where is b 12 absorbed
Distal ileum
Must first combine with intrinsic factor (secreted by parietal cells) stomach in order to be absorbed
How diagnose anaemia caused by parvovirus B 19
Bone marrow aspirate: giant pronormoblasts
(Pathomnemonic)
Will cause normocytic anaemia with low reticulocyte count
Name 4 risk factors Hodgkin’s lymphoma
- HIV
- EBV
- autoimmune conditions eg ra, sarcoidosis
- family history
Name 3 types non-hodgkin lymphoma
- Diffuse large B cell lymphoma (rapidly growing painless mass in elderly)
- Burkitt lymphoma (ass with EBV, HIV)
- malt lymphoma (around stomach)
Histologic cell found in Hodgkin lymphoma?
Reed-sternberg cell (2 nuclei)
Pentad of TTP
Thrombotic thrombocytopenia purpUra
Fat Cats Make Terrible Ropes
- fever
- fluctuating CNS signs: fits, hemiparesis, decrease consciousness, loss vision
- maha ( microangiopathic hemolytic anaemia) (severe, often with jaundice ).
- thrombocytopenia (severe, often mucosal bleed)
- renal failure.
Name 4 causes target cells on blood smear
Central area of haemoglobinisation.
- liver disease
- thalassaema
- post splenectomy
- haemoglobin c disease
Name 3 causes spherocytes on blood smear
Dense cells, no area of central pallor
- autoimmune haemolytic anemia
- post-splenectomy
- hereditary spherocytosis
Name 2 causes howell-jolly bodies on blood smear
Small round nuclear remnants
- hyposplenism, post-splenectomy
- dyshaematopoeisis
Name 2 causes polychromAsia on blood smear
Young red cells- reticulocytes present
- haemolysis, acute haemorrhage
- increased red cell turnover
Name 2 causes basophilic stippling on blood smear
Abnormal ribosomal RNA appears as blue dots
- lead poisoning
- dyshaematopoeisis
Normal platelets?
150 - 400 x 10^9/l
Normal prothrombin time?
9-12 seconds
Absolute vs relative erythrocytosis?
Aka polycythaemia.
- Haematocrit high both
- Red cell mass high vs normal
- plasma volume normal vs low
Name 4 broad causes absolute polycythaemia with examples
Primary
- myeloproliferative disorder: polycythaemia rubra Vera
Secondary
- high erythropoietin due to tissue hypoxia: high altitude, cardiorespiratory disease
- inappropriately high erythropoietin: renal disease (hydronephrosis, cysts, carcinoma), other tumours ( hepatoma, phaeochromocytoma, bronchogenic carcinoma), exogenous testosterone
- exogenous erythropoietin: performance enhancing drugs in athletes
Name 5 causes relative (low -volume) polycythaemia
- Diuretics
- smoking
- obesity
- alcohol
- Gaisbock’s syndrome
Define polycythaemia
Persistent raised haematocrit about > 0,5
Name 6 broad causes with examples of lymphadenopathy
Miami
- malignancy: primary ( lymphoma, leukemia), secondary ( lung, breast, thyroid, melanoma)
- Infective: bac (strep, tb, brucellosis), viral (ebv, HIV), parasite (toxoplasmosis), fungal (histoplasmosis, coccidiodomycosis )
- autoimmune: connective tissue disorders: ra, SLE
- miscellaneous: sarcoidosis, amyloidosis
- iatrogenic: drugs: phenytoin (antiepileptic)
How differentiate cause of bleeding by site? (2)
- Bleed into muscles, joints, retroperitoreal+ intracranial haemorrhage = coagulation factor defect
- purpurA, prolonged bleed from superficial cut, epistaxis, git haemorrhage, menorrhagia = thrombocytopenia / platelet dysfunction / Von willebrand disease.
Name 5 causes purpura
- Most common = thrombocytopenia /platelet dysfuction / Von willebrand disease!
- Henoch schonlein purpura (autoimmune)
- vasculitis
- purpura fulminanS eg in DIC 2° to sepsis
- senile purpura (sun exposure)
- factitious (inflicted by patients )
- paraproteinaemias
Name 4 causes pancytopenia with examples
- Bone marrow failure: hypoplastic/aplastic anaemia inherited/viral/ drugs / idiopathic
- Bone marrow infiltration: acute leukemia, lymphoma, myelodysplastic syndromes
- ineffective haematopaeisis: megaloblastic anaemia, AIDS
- peripheral pooling/destruction: SLE, hypersplenism (pht, felty, malaria, myelofibrosis)
Name 5 indications heparin/lmwh/ fondaparinux
- Prevent + treat VTE
- post thrombolysis for mi
- percutaneous coronary intervention
- unstable angina pectoris
- acute peripheral arterial occlusion
- cardiopulmonary bypass
- haemodialysis + haemofiltration
- non q-wave mi
Name 5 indications warfarin (coumarin)
- Prevent + treat VTE
- arterial embolism
- dilated cardiomyopathy
- afib with specific risk factors for stroke
- mechanical prosthetic cardiac valve
- mobile mural thrombus post mi; extensive anterior mi,
- Cardioversion
- ischaemic stroke in antiphospholipid syndrome
- mitral stenosis + mitral regurgitation with afib
Name 2 indications rivaroxaban/ dabigatran/ apixaban/ edoxaban
- Prevent VTE ( except edoxaban)
- treat VTE (except dabigatran, apixaban)
- afib with risk factors for stroke
Name 4 antiplatelet drugs and their moa
- Cox inhibition: aspirin
- ADP receptor inhibition: clopidogrel
- glycoprotein 2b/3a inhibition: abciximab, tirofiban
- phosphodiesterase inhibition: dipyridamole
Name 3 oral anticoagulant drugs and their moa
- Vitamin K antagonist: warfarin (coumarin)
- direct thrombin inhibition: dabigatran
- direct 10a inhibition: rivaroxaban, apixaban, edoxaban
Name 3 injectable anticoagulant drugs and their moa
- Antithrombin -dependent inhibition of thrombin and 10a: heparin, lmwh
- antithrombin dependent inhibition of 10a: fondaparinux
- direct thrombin inhibition: argatraban
Antidote to warfarin
Prothrombin complex concentrate + iv vitamin K
Target INR for patients on warfarin?
2-3
Target INR for patients on warfarin and recurrent VTE on warfarin or mechanical prosthetic heart valve?
2,5 - 3,5
Name 3 causes iron deficiency anaemia with examples
- Blood loss, esp git : From malignancy, gastritis, peptic ulcer, IBD, diverticulitis, polyps, hookworm, schistosomiasis, angiodysplastic lesions, aspirin, NSAID. Also menstruation, pregnancy
- malabsorption: deficient intake; lack gastric acid (need to release fe from food + keep iron in soluble ferrous state) eg PPI, achlorhydria in elderly, gastric surgery; Coeliac disease (absorbed in upper small intestine)
- physiological demands: infancy, puberty, pregnancy, breadfeeding
Dose iron for fe deficiency anaemia?
Ferrous sulphate 200 mg 3x daily for 3-6 months.
Pathogenesis anaemia of chronic disease?
Hepcidin protein excess due to inflammation → keeps iron trapped in ferritin.
Name 5 clinical signs megaloblastic anaemia
Proliferating cells exhibit megaloblastosis causing clinical changes:
- smooth tongue
- angular cheilosis
- vitiligo
- skin pigmentation
- heart failure
- pyrexia
Lab results megaloblastic anaemia? (6)
- Hb low
- MCv high
- erythrocyte, reticulocyte, leukocyte, platelet count low
- ferritin high
- LDH high! (High proliferation rate in marrow → ineffective erythropoiesis → haemolysis)
- blood film: neutrophil hypersegmentation!, oval macrocytosis, poikilocytosis, red cell fragmentation
- bone marrow: high Iron stores!, pathological non-ring sideroblasts, giant metamyelocytes…
Name 4 causes b12 deficiency
- Dietary deficiency: vegan
- gastric pathology: hypochlorydia in elderly, gastric surgery
- pernicious anaemia: atrophy gastric mucosa → loss parietal cells → IF deficiency
- small bowel pathology: mobility disorders/ hypogammaglobulinaemia → bacterial overgrowth; Chron’s disease
Name 4 causes folate deficiency
- Diet: poor vegetable intake
- malabsorption: coeliac disease, small bowel surgery
- increased demand: pregnancy!, cell proliferation eg haemolysis
- drugs: methotrexate, phenytoin, contraceptive pill
Diagnosis folate deficiency anaemia
Low red cell folate levels (not plasma folate)
Treatment b12 deficiency?
Hydroxycobalamin 1000 micrograms IM for 6 doses 2 or 3 days apart, then
Maintenance 1000 micrograms every 3 days for life
Describe and name 3 indications for direct Coombs test
Detect presence of antibody bound to red cell surface
- autoimmune haemolytic anaemia
- haemolytic disease of the newborn
- transfusion reactions
Describe and name 2 indications for indirect Coombs test
Detect antibodies in plasma
- antibody screen in pre-transfusion testing
- screening in pregnancy for antibodies that may cause haemolytic disease of the new born
Classic precipitant of haemolysis in patients with G6PD deficiency
Consumption of Fava beans causing favism
Blood film features of G6PD deficiency haemolysis? (3)
- Bite cellS
- blister cells
- polychromasia reflecting the reticulocytosis
- denatured hb visible as Heinz bodies within red cell cytoplasm with methyl violet stain
- irregularly shaped small cells
Blood film of pyruvate kinase deficiency?
Prickle cells (resemble holly leaves)
(Red cell enzyme defect)
Name 4 precipitating factors of sickle cell crisis
- Hypoxia
- acidosis
- dehydration
- infection
Name 5 clinical features of sickle cell crisis
- Painful vasO- occlusive crisis: acute severe bone pain (most common)
- stroke
- sickle chest syndrome: follows vaso-occlusive crisis → bone marrow infarction → fat emboli to lungs → ventilatory failure (most common cause death)
- sequestration crisis: thrombosis of venous outflow from organ → loss function + painful enlargement eg spleen, liver, priapism
- aplastic crisis: infection with parvo B19 → severe red cell aplasia → anemia → Hf
Define thalassaemia
Inherited Impairment of hb production with partial/complete failure to synthesise a specific type of globin chain eg beta or alpha chains
Define leukemia
Malignant disorders of haematopoeitic stem cell compartment, characteristically associated with increased no of while cells in bone marrow andor peripheral blood.
Name 5 risk factors leukaemia
- Ionising radiation: radiotherapy, diagnostic xr of foetus in pregnancy
- cytotoxic drugs
- retroviruses
- genetic: Down’s syndrome
- immunological deficiency eg hypogammaglobulinaema
Name 4 types leukemia
Acute: failure of cell maturation → accumulation primitive cells → take up marrow space at expense of normal cells.
- Acute lymphoblastic leukemia (all) (b and t cells)
- acute myeloid leukemia (AML) (other lineages: red cells, granulocytes, monocytes,platelets) (more common in adults)
Chronic
- chronic lymphocytic leukemia (Cll) (most common leukemia, B lymphocytes)
- chronic myeloid leukemia (CML) (predominantly granulocytes )
Name 5 complications of acute leukaemia
- Anaemia (give rcc)
- thrombocytopenia Bleeding (give platelets)
- infection due to neutropenia eg S aureus, staph epidermis, E. coli, pseudomonas, klebsiella, pneumocystis jirovecii in ALL, candida, HsV + hzv reactivation
- metabolic: diarrhoea → anorexia + electrolyte loss,
- psychological
Defining genetic characteristic of CML?
Philadelphia chromosome ( shortened chromosome 22)
Name 3 phases CML
- Chronic phase: responsive to treatment, easily controlled (give imatinib)
- accelerated phase
- blast crisis: transform to acute leukaemia relatively refractory to treatment. Main cause of death.
What chemo is given for lymphoma
ABVD regimen
- doxorubicin
- bleomycin
- vinblastine
- dacarbazine
What is multiple myeloma (3)
Malignant proliferation of plasma cells (from B cells)→ produce paraprotein
Appears in urine as Bence Jones proteinuria
Need 2 out of 3:
- Increased malignant plasma cells on bone marrow aspiration
- serum and/or urine m-protein on electrophoresis
- skeletal lytic lesions on bane scan
Name 7 broad clinical and lab features of multiple myeloma with examples
Neoplasm of plasma cells in bone marrow
- Amyloid: “panda” eyes, nephrotic syndrome, carpal tunnel, bone pain/#, lytic lesions skull
- hyper viscosity: retinal bleeds, bruising, cerebral ischaemia, Hf
- Renal failure due to paraprotein deposition, hyper Ca, infection, NSAIDs, amyloid
- abnormal blood tests: macrocytic anaemia, pancytopenia, high ESR, hyper ca, renal impair, paraproteinaemia
- Bence Jones proteinuria
- bone marrow: plAsmacytosis > 10%
- spinal cord compression: bony collapse, extradural mass
CRAB = Calcium elevated, Renal disease, Anemia, Bone lesions
Define aplastic anaemia
Bone marrow failure with pancytopenia, low reticulocyles, macrocytosis
Name 6 causes secondary aplastic anaemia
- Drugs: cytotoxicS, sulphonamides, indomethacin, carbimazole, anticonvulsants, azathioprine
- chemicals: glue sniffing, insecticides
- radiation
- pregnancy
- viral hepatitis
- paroxysmal nocturnal haemoglobinaria
How classify bleeding disorders (8)
Disorders of primary haemostasis (forming initial platelet plug)
- thrombocytopenia
- Von willebrand disease
- platelet function disorders
> acquired: iatrogenic ( aspirin, clopidrogel), - vessel wall abnormalities
> congenital: hereditary haemorrhagic telangiectasia, ehlers Danlos disease
> acquired: vasculitis, scurvy ( vit C deficiency)
Coagulation disorders
- congenital
> haemophilia a+b
> Von willebrand disease - acquired
> under production: liver failure, vitamin K deficiency
> increased consumption: DIC
> inhibition of function of coagulation factors: heparin
Define ITP
Immune-mediated (autoantibodies) against platelet membrane glycoprotein 2b/3a → sensitise platelet → premature removal from circulation by cells of reticulo-endothelial system. → thrombocytopenia
Name 4 clinical manifestations of antiphospholipid syndrome
- Adverse pregnancy outcome: 3 or more first trimester abortion, unexplained death of normal foetus after 10 weeks gestation, severe early pre-eclampsia
- Vte
- ate
- livedo reticularis, catastrophic APS, transverse myelitis, shin necrosis, chorea
Name 4 conditions associated with secondary antiphospholipid syndrome
- SLE
- ra
- temporal arteritis
- Sjögren’s syndrome
- systemic sclerosis (scleroderma)
- BehCet’s disease
What is DIC
Systemic activation of pathways involved in coagulations + its regulation
- Intra vascular fibrin clots → multi-organ failure
- simultaneous coagulation factor + platelet consumption → bleeding
Name 8 causes DIC
- Infection/sepsis !
- obstetric eg amniotic fluid embolism, placental abruption, pre-eclampsia
- Trauma
- severe liver failure
- malignancy eg solid tumours, leukaemias
- tissue destruction eg pancreatitis, burns
- toxic/immunological eg Abo incompatibility, snake bites, drugs
- vascular abnormalities eg vascular aneurysms, liver haemangiomas
Diagnosis DIC? (6)
Isth scoring system
- must have associated disorder eg sepsis
- platelets X10^9/ L
> > 100 = o
> <100 = 1
> <50 = 2 - Elevated fibrin degeneration products
> no increase = o
> moderate = 2
> strong =3 - prolonged prothrombin time
> <3 sec = O
> >3 - <6 sec =1
> >6 sec = 2 - fibrinogen
> > 1=0
> <1 = 1
Score 5 or more = overt DIC
<5 = repeat monitoring over 1-2 days