1. Normal haemostasis

Haemostasis is the process whereby haemorrhage following vascular injury is arrested. It depends on closely linked interaction between: the vessel wall; platelets; coagulation factors. The fibrinolytic system and inhibitors of coagulation ensure coagulation is limited to the site of injury.

Haemorragic diatheses Vasopathies (vessel wall dysfunction) Thrombocytopenias/-pathias Coagulopathies (inherited, aquired) Mixed type (vWD, DIC)

Coagulation factors are proenzymes (serine proteases) and procofactors which are activated sequentially. The cascade has been divided on the basis of laboratory tests into intrinsic, extrinsic and common pathways

Laboratory tests of coagulation.

Screening test (normal range) Abnormalities indicated (prolonged abnormal) Most common cause of disorder Prothrombin time (PT) (10– 14s) Extrinsic and common coagulation pathways Deficiency/inhibition of factor VII, factors X, V, II and fibrinogen Liver disease, Warfarin therapy, DIC Activated partial thromblastin time (APTT or PTTK) (30–40s) Intrinsic and common coagulation pathways Deficiency/inhibition of one or more of factors XII, IX, VIII, X, V, II and fibrinogen Heparin therapy, haemophilia A and B, DIC Thrombin time (14–16s)Deficiency or abnormality of fibrinogen; inhibition of thrombin by heparin or FDPs DIC, heparin therapy, fibrinolytic therapy Fibrin degradation products (<10mg/mL) Accelerated destruction of fibrinogen DIC Platelet aggregation testsAbnormal platelet functionDrugs (e.g. aspirin), uraemia, von Willebrand’s disease

Disorders of coagulation I: inherited

Factor VIII deficiency (haemophilia A)

Clinical features Range from severe spontaneous bleeding, especially into joints (haemarthroses) and muscles, to mild symptoms. Onset in early childhood. Increased risk of postoperative or post-traumatic haemorrhage. Chronic debilitating joint disease caused by repeated bleeds.

Severity Mild (>5% activity of the f.VIII) Moderate (2-5%) Severe (<2%) All the lab tests normalize at the activity level of >10%. Patients with mild form don’t have spontaneous bleeding.

Laboratory features Prolonged activated partial thromboplastin time (APTT), normal prothrombin time (PT), normal bleeding time, Plasma factor VIII reduced Carriers have factor VIII approximately 50% of normal. DNA analysis is helpful in carrier detection and counselling. Von Willebrand factor level is normal.

Treatment Plasma exchange, cryoprecipitate, native plasma concentrate, Infusions of factor VIII concentrate to elevate the patient’s level to 20–50% of normal for severe bleeding. Level is raised to and maintained at 80–100% for elective surgery. Desmopressin, an analogue of vasopressin, leads to a modest rise in endogenous factor VIII which is useful in mild cases. Avoid aspirin, other antiplatelet drugs and intramuscular injections. Patients should be registered with a recognized haemophilia centre and should carry a card with details of their condition.

Complications of treatment HIV and hepatitis C from impure preparations, subsequent AIDS, hepatitis and cirrhosis. Neutralizing antibodies to factor VIII in 15% of severe patients may require immunosuppressive therapy, treatment with porcine factor VIII (during a week - max), Feiba, Novoseven

Von Willebrand’s disease

Is usually autosomal dominant, results from mutations in the von Willebrand factor (vWF) gene. Von Willebrand factor is a large multimeric protein produced by endothelial cells, which carries factor VIII in plasma and mediates platelet adhesion to endothelium. The disease is more frequent than haemophilia A; males and females are affected equally.

Clinical features Bleeding, typically from mucous membranes (mouth, epistaxes, menorrhagia). Excess blood loss following trauma or surgery. Haemarthroses and muscle bleeding are rare.

Diagnosis APTT is prolonged, PT normal. Factor VIII and vWF levels are reduced. Bleeding time is prolonged. Defective platelet function, reduced aggregation with ristocetin. Mild thrombocytopenia may occur.

Treatment Intermediate purity factor VIII concentrate (contains both vWF and factor VIII) for bleeding. Desmopressin is helpful for mild bleeding. Fibrinolytic inhibitors (e.g. tranexamic acid) are helpful.

Disorders of coagulation II: acquired

Vitamin K deficiency (liver disease, mechanical jaundice) Disseminated intravascular coagulation Drugs (warfarin) Acquired coagulation inhibitors

Thank you for your attention. Questions are welcome!