Haemostasis

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Heparin-Induced Thrombocytopenia
Activated partial thromboplastin time
Prothrombin Time
Thrombin Time
Clotting Abnormalities in Liver Disease
Disseminated Intravascular Coagulation
Essential Thombocythaemia
Factor V Leiden
Haemophilia A
Haemophilia B
Thrombotic Thrombocytopenic Purpura
Vitamin K
Von Willebrands Disease

Basic Mechanism

Two pathways equivalent to two phases of activation

• Extrinsic pathway / Activation phase

  • activated by exposure to tissue factor

    • expressed on most cells other than endothelial cells - can be expressed on monocytes/macrophages

  • factor VII / VIIa (activated factor VII)) then acts on factor X

• Intrinsic pathway / Propagation phase

  • so that a small amount of thrombin produces large bolus of fibrin

  • requires platelets as phospholipid surface for reaction to happen on

  • Thrombin splits XI→XIa

  • Factors IX → IXa using Factor VIIIa-von Willebrand factor as cofactors

  • acts on factor X

The two pathways combine by activating factor X

• using factor Va as cofactor,

• prothrombin  (factor II)→ thrombin (IIa) which produces positive feedback into intrinsic pathway via activation factor XI

• fibrinogen (aka factor I)→ fibrin

Regulators

• Protein C and Protein S turn off factors VIII and V

• Antithrombin - X and VII

• Tissue factor pathway inhibitor (TPFI) - tissue factor

Fibrinolysis

convert plasminogen to plasmin which breaks down fibrin to fibrin degradation products (FDPs or d-dimers)

• tissue-plasminogen activator (tPA)

• urine plasminogen activator (uPA)

  • prevents clots blocking urinary outflow

Tests of clotting system function

• Prothrombin time (PT)

  • normal range 12-16 secs (varies by laboratory)

  • measure extrinsic and common pathway function

• Activated Partial Thromboplastin Time (APTT)

  • 28-38 secs (again varies by laboratory)

  • measures intrinsic and common pathways

• Thrombin Time - only useful when patient heparinised

• Reptilase time - to distinguish heparin-induced reduction  in clotting (does NOT prolong reptilase time) from other causes

Once clotting abnormality discovered

• Mixing studies

  • 50:50 test plasma : reference

  • if clotting partially restored then test plasma is deficient in something

  • if clotting remains abnormal then test plasma contains an inhibitor (e.g. an antibody)

• Antiphospholipid tests

  • lupus anticoagulant

  • anti-phospholipid antibodies

Disorders

Inherited

• von Willebrands Disease

• Haemophilia A

• Haemophilia B

Acquired

• Liver disease

  • ↑ PT, ↑ APTT,  N/↑ TT,  ↓ platelets

• Disseminated Intravascular Coagulation (DIC)

  • ↑ PT, ↑ APTT,  ↑ TT,  ↓ platelets

• Vitamin K deficiency

  • ↑ PT, ↑/normal APTT,  normal TT,  normal platelets

• Massive Transfusion

  • ↑PT, ↑APTT,  normal TT,  ↓ platelets

• Oral Anticoagulants

  • ↑ PT, ↑ APTT,  normal TT, normal platelets

• Heparin

  • ↑ PT, ↑ APTT,  ↑ TT,  normal platelets

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