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HEMATOLOGY

Coagulation cascade

Intrinsic pathway (components already present in the blood)
• Minor role in clotting
• Subendothelial damage e.g. collagen
• Formation of the primary complex on collagen by high-molecular-weight kininogen (HMWK), prekallikrein, and
Factor 12
• Prekallikrein is converted to kallikrein and Factor 12 becomes activated
• Factor 12 activates Factor 11
• Factor 11 activates Factor 9, which with its co-factor Factor 8a form the tenase complex which activates Factor
10

Extrinsic pathway (needs tissue factor released by damaged tissue)
• Tissue damage
• Factor 7 binds to Tissue factor
• This complex activates Factor 9
• Activated Factor 9 works with Factor 8 to activate Factor 10

Common pathway
• Activated Factor 10 causes the conversion of prothrombin to thrombin
• Thrombin hydrolyses fibrinogen peptide bonds to form fibrin and also activates factor 8 to form links between
fibrin molecules
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burns.5.9. on contact ē injured vascular basement membrane.10 Vitamin K dependent Factors 2.11 Liver disease Factors 1. dissecting aortic aneurysm • Liver disease 2 . VIII conc. But some are Glycoproteins – V & VIII Transglutaminase – XIII ● Hageman factor (XII). activates both collagen sequence & kinin system.8.g.2. ultimately leading to bleeding Causes include: • Infection • Malignancy • Trauma e.9. Abnormal coagulation Cause Factors affected Heparin Prevents activation factors 2.12 Extrinsic pathway Increased PT Factor 7 Common pathway Increased APTT & PT Factors 2.10 Von Willebrand Disease (clinically resembles hemophilia) RX : Desmopressin (DDAVP-RX of choice) Cryoprecipitate (I. Desmopressin.10 DIC Factors 1.10.7.2.7.5.5.Fibrinolysis Plasminogen is converted to plasmin to facilitate clot resorption Intrinsic pathway Increased APTT Factors 8. XIII.10 ● Coagulation factors are generally serine proteases. The most useful test in practice is to do the VwB Antigen and activity(RICOF) Disseminated intravascular coagulation Simultaneous coagulation and haemorrhage caused by initially formation of thrombi which consume clotting factors (factors 5.. shock.11.11 Warfarin Affects synthesis of factors 2.9. vWF).8) and platelets.9. major surgery.9.7. VIII.

Acute liver disease : All rises.Immune complexes S . thrombocytopenia.Dx: D dimer I . IX. APTT. IXa. PT rises ● Intrinsic Pathway.binds ē antithrombin→Heparin-antithrombin complex → (-) IIa. colon.Neoplasms A .Snakebite. prostate.Dead fetus (retained) ● Platelet function disorder : All (N) ● Extrinsic Pathway. lung. decreased fibrinogen. (And also in PE) ** DIC shows rise of all except Platelet + fibrinogen** *** APTT indicate intrinsic pathway and PT indicate extrinsic pathway*** ● DVT pt.Endotoxins (bacterial) D .Acute promyelocytic leukemia T .XII) deficiency : All (N). (VIII. BT rise (F VIIIc abnormal) ● Vitamin K deficiency : All (N). + anticardiolipin & lupus anticoagulant ab (+)ve = underlying cz antiphospholipid syndrome. Heparin.(-) Xa (indirect inactiv of Xa) n ● HMWH: . Haemophilia. Platelet. then platelets) * DIC : D – dimer may be elevated due to endothelial cell injury *.Infections: viral and bacterial N .SLE E . • Obstetric complications Key points • Clinically bleeding is usually a dominant feature. increased fibrinogen degradation products • Treat the underlying cause and supportive management D-I-S-S-E-M-I-N-A-T-E-D D . Xa (indirect inactiv of thrombin) n ● Both unfractionated and low-molecular weight heparin can cz hyperkalaemia.Tumor products: Tissue Factor (TF) and TF-like factors released by carcinomas of pancreas. stomach E . heatstroke S . VII deficiency : All (N). DIC. ● Recurrent DVT = Factor V Leiden. ischaemia and organ failure • Blood tests: prolonged clotting times. APTT. PT rise ● Common Pathway.Massive tissue damage I . Protein C. shock. It caused by inhibit of aldosterone n secret 3 . Warferin Rx. Protein S test to be done Heparin n ● LMWH (and also Fondaperinux) :. APTT rises ● VWD : All (N). Hb reduce (Initially factor V & VIII are consumed. HELLP syndrome M .Eclampsia. bruising.

g. therefore give with vitamin K 4. Human Prothrombin Complex (reversal within 1 hour) -Bereplex 50 u/kg -Rapid action but factor 6 short half life. This results in a temporary procoagulant state after initially starting warfarin.: amiodarone. X. XI ) to be given ● Antistatin: direct factor Xa inhibitor 4 . e. Thrombosis may occur in venules leading to skin necrosis… ● Protein-C is used as co-factor in activation of thrombomodulin ● Blood products used in warfarin reversal Immediate or urgent surgery in patients taking warfarin(steps 1 & 2): 1. IX and X (mnemonic = 1972) and protein C) Factors that may potentiate warfarin • Liver disease • P450 enzyme inhibitors. inhibit vitamin K –to become active hydroquinone form (hydroquinone form acts as co-factor in the formation of factor II. VII. ciprofloxacin • Cranberry juice • Drugs which displace warfarin from plasma albumin. **If question says Bleeding due to Excessive Warferinisation then Factor IX concentrate (IX. therefore give with vitamin K **Massive bleeding= stop warin.g. NSAIDs • Inhibit platelet function: NSAIDs Side-effects • Haemorrhage • Teratogenic • Skin necrosis: when warfarin is first started biosynthesis of protein C is reduced. Fresh frozen plasma …Used less commonly now as 1st line warfarin reversal -1 -30ml/kg -Need to give at least 1L fluid in 70kg person (therefore not appropriate in fluid overload) -Need blood group -Only use if human prothrombin complex is not available 4. Stop warfarin 2. if available). Human Prothrombin Complex Concentrate (reversal within 1 hour) -Bereplex 50 u/kg -Rapid action but factor 6 short half life. normally avoided by concurrent heparin administration. Vitamin K (reversal within 4-24 hours) -IV takes 4-6h to work (at least 5mg) -Oral can take 24 hours to be clinically effective 3. IV vitamin K & either PCC or FFP (PCC preferable.WARFERIN ALL ● Warferin. e.

fits. TIBC high Fe deficiency : S.ferritin raised TIBC low Haemolytic : S. S. obstruction of microvessels and infarction • Sickling is precipitated by: dehydration. B12 def.) Autoimmune haemolytic : Direct coomb’s test positive (& also in Reynaud’s disease) ● Vit B12 deficiency macrocytic anaemia and thrombocytopenia Sickle cell anaemia Disorder of varying degrees. infection. Autosplenectomy occurs • Autosomal recessive • Single base mutation • Deoxygenated cells become sickle in shape • Causes: short red cell survival. splenic infarcts. pleuritic pain. Typical infarctive sickle crises (Vasoactive crisis. TIBC high Megaloblastic : Not assoc. ferritin low. pernicious. Fe not low Chr. aplastic crisis. In the older patient. Indian • Diagnosis: Hb electrophoresis Sickle crises • Bone pain • Pleuritic chest pain: acute sickle chest syndrome commonest cause of death • CVA. Fe low. and priapism. unless there is • Aplasia: parvovirus • Acute sequestration • Haemolysis Long-term complications • Infections: Streptococcus pnemoniae • Chronic leg ulcers 5 .dis : S. It may present in childhood with anaemia and mild jaundice. Fe low S. vaso- occlusive problems occur due to sickling in the small vessels of any organ. seizures • Papillary necrosis • Splenic infarcts • Priapism • Hepatic pain Hb does not fall during a crisis. ferritin low. hypoxia • Manifest at 6 months age • Africans.● Hirudin+ Argatroban: Direct inactivation of thrombin Anaemias Chr. SpO2 low. Blood loss : S. mimicking many medical and surgical emergencies. sequestration crisis) includes bone pain. with Fe metabolism (gastritis. hemiparesis. Middle East.

proliferative retinopathy Surgical complications • Bowel ischaemia • Cholecystitis • Avascular necrosis Management • Supportive • Hydroxyurea • Repeated transfusions pre operatively • Exchange transfusion in emergencies Sickle cell trait • Heterozygous state • Asymptomatic • Symptoms associated with extreme situations ie anaesthesia complications • Protective against Plasmodium falciparum Drugs causing Aplastic Anaemia Indomethacin Sulphonamides Penicillamine ● Chronic Alcoholic develops Megalolblastic Anaemia (↓Hb & ↑MCV) Thrombocytopenia Causes of severe thrombocytopenia • ITP • DIC • TTP • haematological malignancy Causes of moderate thrombocytopenia • heparin induced thrombocytopenia (HIT) • drug-induced (e. • Gallstones: haemolysis • Aseptic necrosis of bone • Chronic renal disease • Retinal detachment. HIV. diuretics. quinine. thiazides) • alcohol • liver disease • hypersplenism • viral infection (EBV. hepatitis) 6 .g. sulphonamides. aspirin.

In older patients an intercurrent illness may increase the rate of red cell destruction resulting in more acute symptoms. oral antiplatelet agents may b needed. Severe cases may benefit from splenectomy Some PBF Findings AML : Blast cells with Auer bodies CML. Myelofibrosis : Philadelphia chromosome (due to long arm deletion in chr-22) CLL : Numerous small. Thalassemia. Clover leaf morphology(Pb poisoning) Sickle cell. (Monospot test +ve) DIC : Schistocyte(RBCs undergoing fragmentation) Splenectomy** : Howell-Jolly bodies. • pregnancy • SLE/antiphospholipid syndrome • vitamin B12 deficiency Hereditary Spherocytosis Most common disorder of the red cell membrane. Irregular contracted erythrocytes(siderotic granules) Hairy Cell Leukaemia : Hairy cell Pb poison. Hemolytic : Traget cell st ** In 1 few days after splenectomy target cells. Ashkenazi Jews are sufferer ● Presence of Lupus anticoagulant: Antiphospholipid Syndrome WHOLE BLOOD FRACTIONS Fraction Key points Packed red cells Used for transfusion in chronic anaemia and cases where infusion of large volumes of fluid may 7 . mature lymphocytes Infectious Mono. it has an incidence of 1 in 5000. Platelet count is usually raised & this may b persistent. Anaemia. Pappenheimer bodies. Septicaemia : Basophilic Stippling. This can result in hyperbilirubinaemia. The abnormally shaped erythrocytes are prone to splenic sequestration and destruction. siderocytes and reticulocytes will appear in circulation. jaundice and splenomegaly. ● XI deficiency is called Haemophilia – C. Immediately following splenectomy a granulocytosis (mainly neutrophils) is seen. : Atypical Lymphocytosis. Poikilocytes (Target cells). it is replaced by lymphocytosis & monocytosis over following weeks.

• Usually used in correcting clotting deficiencies in patients with hepatic synthetic failure who are due to undergo surgery. result in cardiovascular compromise. • Allows large concentration of factor VIII to be administered in small volume. 8 . • It should not be used as first line therapy for hypovolaemia. • Unit is usually 200 to 250ml. albumin and immunoglobulin. It is plasma obtained by low speed centrifugation. concentrate Fresh frozen • Prepared from single units of blood. Product obtained by centrifugation of whole blood. ● BAINBRIDGE REFLEX release Aldosterone to increase HR mediated via atrial stretch receptors that occurs following rapid infusion of blood. • Rich source of Factor VIII and fibrinogen. Cryoprecipitate • Formed from supernatant of FFP. clotting factors and platelets should be considered. plasma • Contains clotting factors. -1 • Usual dose is 12-15ml/Kg . Thereafter whole blood is preferred. Platelet rich Usually administered to patients who are thrombocytopaenic and are bleeding or require surgery. After 8 units. Platelet Prepared by high speed centrifugation and administered to patients with thrombocytopaenia. SAG-Mannitol Removal of all plasma from a blood unit and substitution with: Blood • Sodium chloride • Adenine • Anhydrous glucose • Mannitol Up to 4 units of SAG M Blood may be administered.