L08: Haemostasis 3 – Tests and Bleeding Disorders

A systematic approach to a patient with abnormal bleeding begins with interpreting coagulation screening tests in combination with the clinical history and examination findings. The pattern of abnormalities on platelet count, PT, and APTT guides subsequent specific factor assays.

A prolonged PT with a normal APTT points to factor VII deficiency or early warfarin effect (since FVII is the only extrinsic-pathway-specific factor). A prolonged APTT with a normal PT suggests deficiency of an intrinsic-pathway factor: FVIII (haemophilia A), FIX (haemophilia B), FXI, or FXII. A prolonged mixing study (patient plasma mixed 1:1 with normal pooled plasma) that corrects suggests factor deficiency; failure to correct suggests an inhibitor (e.g., lupus anticoagulant or acquired factor antibody). Both PT and APTT prolonged indicates a common-pathway defect (FX, FV, FII, or fibrinogen) or multiple factor deficiencies (liver disease, DIC, warfarin toxicity).

The fibrinogen assay is a thrombin-based functional assay measuring time to clot formation; reference interval is approximately 1.8–4.0 g/L. Fibrinogen is consumed in DIC and may be elevated as an acute phase reactant in inflammation.

Haemophilia A is caused by deficiency or dysfunction of factor VIII. It is X-linked recessive, affecting approximately 1 in 5000 male births. FVIII is the cofactor for FIXa in the tenase complex; its absence dramatically impairs intrinsic pathway activity, prolonging the APTT with a normal PT. Haemophilia A severity is classified by residual FVIII activity: severe (<1%), moderate (1–5%), and mild (5–40%). Bleeding is deep: haemarthroses (joint bleeds causing arthropathy), muscle haematomas, and intracranial haemorrhage. Treatment is recombinant FVIII concentrate or emicizumab, a bispecific monoclonal antibody that mimics FVIII by bridging FIXa and FX.

Haemophilia B (Christmas disease) is caused by FIX deficiency. It is also X-linked recessive, clinically indistinguishable from haemophilia A, and treated with recombinant FIX or non-factor replacement therapies.

Vitamin K deficiency causes combined deficiency of factors II, VII, IX, and X (and Protein C and S). It occurs in newborns (low gut flora, low breast milk content), malabsorption (fat-soluble vitamin), liver disease, and prolonged antibiotic use. Treatment is vitamin K supplementation or, in acute haemorrhage, prothrombin complex concentrate (PCC) or fresh frozen plasma (FFP).

Disseminated intravascular coagulation (DIC) is a life-threatening syndrome of simultaneous widespread thrombin generation and fibrinolysis. Triggers include sepsis (the most common cause), obstetric catastrophe (amniotic fluid embolism, placental abruption), major trauma, and malignancy. Massive thrombin generation consumes clotting factors and platelets, producing paradoxical haemorrhage. Laboratory findings: prolonged PT and APTT, thrombocytopenia, low fibrinogen, elevated D-dimers. Management is directed at the underlying cause; supportive replacement with FFP (factors), cryoprecipitate (fibrinogen), and platelet transfusions is used for active bleeding.