Coagulation Factors and Disorders
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Prolonged APTT with normal PT and TT | Deficiency of Factor XII, XI, IX, VIII
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Prolonged PT with normal APTT and TT | Factor VII deficiency
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Prolongation of APTT and PT with normal TT | Factor X, V or II deficiency, patients receiving Warfarin or with liver disease
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Prolongation of APTT, PT and TT | Heparin therapy (activated antithrombin III) or a complex deficiency state (DIC, abnormal fibrinogen, fibrinogen deficiency)
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Dense platelet granules contain... | Calcium and ADP
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Alpha granules | Secondary mediators of coagulation
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Primary platelet activation | Platelet monolayer attached to vWF or collagen on the subendothelial layer
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Secondary platelet activation | Release of calcium, ADP and synthesis of thromboxane A2 to activate surrounding platelets.
Cross-linking with fibrinogen
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Von Willebrand's Factor | Large multimeric protein found in the subendothelium, made by the endothelium. Carrier for FVIII in the blood
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Desmopressin | Releases vWF from endothelial cells for the treatment of vWF deficiency
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Factor V and VIII | Clotting cofactors
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Coagulation cascade: Initiation | Release of TF, binds FVII in blood, activates FX which causes the production of a small amount of thrombin
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Coagulation cascade: Amplification | Positive feedback by thrombin activates extrinsic pathway
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Coagulation cascade: Clot Formation | Large amounts of thrombin are present, fibrinogen is broken down to fibrin monomers.
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Antithrombin III | Directly inactivates thrombin and FX
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Tissue plasminogen activator | Released when a clot is formed, or conditions that promote clotting (stasis, hypoxia). Converts plasminogen to plasmin
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Mucocutaneous bleeding | vWF deficiency, platelet dysfunction
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Haemarthrosis | Haemophilia
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Purpura | Thrombocytopenia
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Bleeding into hair follicles, gingival bleeding | Scurvy
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Telangiectasia | Vascular abnormality (hereditary haemorrhagic telangiectasia)
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Venous thrombosis | Fibrin based (surgery, trauma, pregnancy, cancer)
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Arterial thrombosis | Platelet based (smoking, diabetes, hyperlipidaemia, obesity)
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Venous stasis eczema | Complication of deep vein thrombosis and varicose veins
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Normal prothrombin time | 12-13 seconds
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Normal INR | 1
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Normal INR on patient on warfarin | 2-3.5
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Mildly prolonged APTT | vWF deficiency (FVIII low)
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50:50 plasma mix does not correct APTT | Clotting factor inhibitor
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Binding site of unfractionated heparin | Thrombin and Xa
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Binding site of LMWH | Factor Xa
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Factors that decrease effectiveness of warfarin | High intake of green leafy vegetables, administration of vitamin K
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Factors that inctrase effectiveness of warfarin | Poor diet, antibiotics (roxithromycin), NSAIDs, liver disease or congestion
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Dabigatron | Thrombin inhibitor
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Haemophilia A | X-linked recessive deficiency of Factor VIII
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Haemophilia B | X-linked recessive deficiency of Factor IX
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Severe haemophilia | <1% of normal factor levels
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Mild haemophilia | >5% of normal factor levels
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Moderate/severe haemophilia | 3-5% of normal factor levels
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Treatment of mild haemophilia A | Desmopressin
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vWF Disease | Autosomal dominant inheritance (not complete penetrance) in 1% of population.
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Delayed bleeding | Clotting factor deficiency (haemophilia), chronic liver disease, warfarin or heparin therapy
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Immediate bleeding | Platelet problem - thrombocytopenia, vWF deficiency, NSAID, corticosteroid use (vascular fragility)
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Transexamic acid | Anti-fibrinolytic drug that stabilises clots. Used for dental surgery in high risk patients, menorrhagia in vWF disease, trauma
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Clotting factors made in the liver | I, II, V, VII, IX, X, XII
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Thrombocytopenia in liver disease | Toxic effect of alochol on megakaryocytes
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Pulmonary embolism | Dyspnoea, pleuritic chest pain
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Decreased platelet count with deficiency of all clotting factors | Disseminated intravascular coagulopathy
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D-dimers | Breakdown products of fibrin, marker of fibrin formation in vivo and its subsequent breakdown by plasmin
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Risk of spontaneous coagulation | INR>5
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