Haematology Flashcards
Commonest cause of sideroblastic anaemia?
Primary acquired sideroblastic anaemia (myelodysplasia)
Congenital cause of sideroblastic anaemia?
X-linked defect in haem synthesis key enzyme (ALA-S mutation, delta-amino laevulinic acid synthase)
What is sideroblastic anaemia?
Ringed sideroblasts (erythroblasts with perinuclear Fe-engorged mitochondria). Inadequate marrow use of Fe for Haem synthesis despite enough/raised Fe. Cannot incorporate Fe into protoporphyrin.
Causes of acquired sideroblastic anaemias?
Myelodysplastic syndrome
Drugs: chloramphenicol, cycloserine, isoniazid, linezolid, pyrazinamide
Toxins: EtOH, Pb.
Pyridoxine or copper deficiency.
Management of acute iron poisoning?
Gastric lavage (within 1-2h), ?whole bowel irrigation. IV desferrioxamine (chelates Fe and reduces risk of liver damage)
Features of Pb poisoning?
Clinically: abdo pain, constipation, anaemia, peripheral neuropathy, blue line of gums.
Bloods: punctate basophilia (undegraded RNA), haemolysis signs. Marrow ringed sideroblasts.
Management of sideroblastic anaemia?
Symptomatic. Regular transfusion and Fe chelation.
Inherited form: ?respond to pyridoxine (Vit B6), cofactor for ALA-S.
For myelodysplastic syndromes (esp with Ch5q deletion) -> lenalidomide.
Clinical manifestations of Sickle cell disease?
SICKLE Swellings and splenic sequestration
Infections and infarctions
Chronic haemolysis, Crises (vaso-occlusive, aplastic, cholelithiasis)
Kidneys
Lungs
Eyes, Erection
Causes of G6PD deficiency crises?
Acidosis (DKA)
Infections
Oxidant drugs (antimalarial, sulfonamides, synthetic Vit K, nitrofurans)
Fava beans
What are heinz bodies? How do you see them
Precipitate of oxidised, denatured Hb. Need an extra stain to see them (e.g. New methylene blue or bromocresol green)
Causes of heinz bodies?
NADPH deficiency G6PD deficiency crisis Chronic liver disease Alpha-thalassaemia Hyposplenism/asplenia.
Investigations for haemolytic anaemia?
FBC + MCV
Reticulocyte count
Peripheral blood film
Urine dip for haemoglobinuria, haemosiderinuria
?LFTs conj v unconj bilirubin. Gallstones?
What are iron studies?
Ferritin
Serum Fe
Transferrin/TIBC
Transferrin saturation
What is RDW?
Red cell distribution width. Increased if anisocytosis (commonly due to nutritional deficiencies)
Hb 110, MCV 110, RDW raised. What is the likely diagnosis?
Macrocytic anaemia due to megaloblastic. E.g. B12/folate def.
Normal RDW = all other macrocytoses.
Hb 110, MCV 70, RDW raised. What is the likely diagnosis?
Fe deficient anaemia. Microcytic anaemia with RDW normal would indicate heterozygote thalassaemia (or HbE trait, or ACD)
Causes of raised RDW?
Folate and B12 def. Immune haemolytic anaemia, myelodysplastic syndromes, (liver disease)
Fe def. Sickle cell.
Dimorphic anaemia
How to distinguish ACD v Fe def anaemia?
TIBC/transferrin: up in Fe def, low in ACD (don't want circ Fe) Serum ferritin (=Fe stores): low in Fe def; up in ACD
How to differentiate sideroblastic anaemia from other microcytic anaemias?
High serum Fe, high transferrin sats %, high serum ferritin (stores). Low TIBC/transferrin.
How to distinguish thalassaemia from other microcytic anaemias?
Most of iron studies are normal (ferritin, transferrin, transferrin sats, serum Fe) RDW likely to be normal.
RBC count is raised.
Film: target cells and Howell-jolly bodies.
What happens to iron in acute inflammation?
Acute phase proteins (APP): ferritin and hepcidin (store Fe, decrease intake)
Negative APP: transferrin.
Decrease in circ Fe > decrease of transferrin.
What is Plumber Vincent Syndrome?
Oesophageal strictures seen in Fe def.
What does hepcidin do?
Stops absorption of Fe from gut. (Via inhibition of ferroportin on BM of enterocytes) also inhibit Fe uptake by transferrin.
How to diagnose haemochromatosis?
Liver biopsy showing evidence of heavy Fe deposition and hepatic fibrosis. OR genetic testing
Complications of haemochromatosis?
Diabetes mellitus, cirrhosis, DCM, hypogonadism (?pituitiary), pseudogout, impotence,
How to distinguish B12 from folate deficiency?
Urine methylmalonic acid increased in B12 and normal in folate.
Should you correct B12 or folate alone?
You can do BUT DO NOT give folate before checking if the B12 is not. B12 BEFORE FOLATE. Or risk SCDC
What is the cause and effect of increased plasma homocysteine?
B12 and/or folate def.
Increased vasc plaques, and thrombosis
How to differentiate causes of B12 def?
Schilling test +/- corrected for IF.
Pernicious anaemia v intestinal disease.
Pentad of TTP?
Thrombocytopaenia Renal failure Fever CNS def MAHA
Cause of TTP?
ADAMTS13-14 def.
Triad of HUS
Renal failure MAHA, thrombocytopaenia
Causes of thrombocytopaenia
Increased destruction: immune, non-immune
Decreased production
Causes of decreased production of platelets:
Marrow failure
Aplastic anaemia
B12 def
Infx (parvovirus B19)
Causes of women with ?haemophilia
severe vWD?
Parental haemophilia
X-inactivation
Causes of thrombocytopaenia?
Increased destruction: immune (infx, auto, allo) ; non-immune
Decreased production: I AM BACK
Immune causes of platelet destruction?
Infection: HIV, EBV, dengue fever
Allo: transfusion, heparin induced, HDN
Auto: primary ITP; secondary SLE, cancer, PNH
Nonimmune causes of increased platelet destruction?
DIC
HUS and TTP
Causes of decreased platelet production?
Infections Parvovirus B19 Aplastic Marrow failure B12 def Alcohol Cirrhosis/liver failure Kidney failure
Acquired Coagulation disorders
DIC Liver failure Warfarin Vit K def Autoantibodies: ITP, SLE, cancer, PNH?
Hereditary coagulation disorders
Haemophilia or vWD
Which factors in Vit K involved in action?
II, VII, IX, X
All problems of blood transfusions
GOT A BAD UNIT Graft v Host Overload (volume) Thrombocytopaenia Alloimmune BP unstable Acute haemolytic transfusion reaction (AHTR) Delayed haemolytic transfusion reaction (DHTR) Urticaria Neutrophilia Infection TRALI (transfusion related acute lung injury)
Problems after transfusing 1 unit of blood?
Don't Forget To Ask About Getting Itchy Delayed haemolytic transfusion reaction Febrile non-haemolytic transfusion reaction TRALI Acute haemolytic transfusion reaction Allergic reaction Graft v host disease Infection: Hep B/C/E; HIV; malaria; CMV; syphilis; vCJD
Problems after massive transfusion
BACK CHaT Bleeding Acidosis (lysis) Ca low (chelators) K up (lysis) Circulation overload Haemochromatosis All the immune stuff (AHTR/DHTR/TRALI/GvH/allergic) Thermia (hypothermia)
Causes of normocytic anaemia?
<3% reticulocytes: BREAM >3% reticulocytes: haemolytic anaemia Blood loss (early) Renal (RDW wide) due to low EPO Early Fe def anaemia/ACD Aplastic anaemia Malignancy
Causes of haemolytic anaemia?
Intrinsic to RBC - inherited: Hb, metabolism, membrane - acquired: PNH, infx Extrinsic to RBC - sequestration - immune (allo, auto, drugs) - mechanical (macro, micro)
Causes of aplastic anaemia
Congenital: Fanconi’s anaemia, TAR, dyskeratosis congenita etc
Acquired:
- idiopathic
- secondary: post-chemo/radio; idiosyncratic; drug related (carbimazole); chemical (benzene); infections (EBV, parvovirus B19, viral hepatitis)
- asn with malignancy e.g. ALL, thymoma
- PNH
Drugs that cause aplastic anaemia
Carbamizole Chloramphenicol Sulphonamides Chlorpromazine Gold
Causes of intrinsic inherited haemolytic anaemias?
Inherited
- Hb: HbS, HbC
- metabolism: G6PD, PKD
- membrane (MCH up): spherocytosis or elliptocytosis
Causes of intrinsic acquired haemolytic anaemias?
PNH: PIGA def
Infections: malaria, clostridia, viral, babesiosis
Causes of mechanical haemolytic anaemia?
Macro: - valves (AS or replacement/metallic); - March; - Burns/hyperthermia Micro: DIC, TTP, HUS
Causes of immune mediated haemolytic anaemia?
Drug related: penicillin, quinine, methyl-DOPA
Auto: warm (IgG); cold (IgM)
Allo: transfusion, haemolytic disease of newborn (Rh/ABO)
Causes of microcytic anaemia?
TAILS Thalassaemia Anaemia of chronic disease Iron def Lead poisoning Sideroblastic
