PubMed1991
Congenital bleeding disorders comprise a heterogeneous group of diseases that reflect abnormalities of blood vessels, coagulation proteins and platelets. Studies of these diseases, many of which are rare and several of which result in a mild bleeding diathesis only, have significantly increased our understanding of normal haemostasis. Two lessons have been learned. First, quantitative abnormalities of coagulation proteins and platelets are an important, but not the only, cause of significant haemorrhage; some cases of inherited bleeding disorders reflect synthesis of a dysfunctional coagulation protein or production of abnormal platelets. Diagnostic tests that reflect qualitative abnormalities are therefore important in the evaluation of selected patients with inherited bleeding disorders. Second, in occasional patients the inherited disorder is complex and reflects combined abnormalities of coagulation proteins alone or in association with platelet disorders. In clinical practice it is useful to distinguish disorders that cause significant clinical bleeding from those that cause few or no symptoms. Examples of the former include severe deficiencies of factors VIII and IX, and the homozygous forms of factor II, V, VII, X, XI, XIII, fibrinogen and von Willebrand factor. Comparable platelet disorders include the inherited thrombocytopenias with platelet counts less than 20 x 10(9) litre-1 and the homozygous forms of Bernard-Soulier syndrome and Glanzmann's thrombasthenia. The most frequently encountered mild haemostatic abnormalities include type I von Willebrand's disease, the platelet storage pool deficiency syndromes and the mild and moderate forms of haemophilia A and B; occasionally heterozygous or homozygous forms of the rarer coagulation disorders, e.g. factor XI deficiency, may present with a mild bleeding diathesis. Finally, some disorders are entirely asymptomatic, e.g. factor XII deficiency and deficiencies of other contact coagulation factors. Management of patients with inherited bleeding disorders should reflect knowledge of the specific disorder to be treated plus careful consideration of the clinical circumstance for which therapy is proposed. In all cases, once a decision to treat has been made, the safest efficacious therapy should be given (for example DDAVP in the treatment of patients with mild haemophilia A or type I von Willebrand's disease). Although blood products are now much safer and the risk of blood transmitted viral infections is low, there still remains a risk that transfusion of any blood product may be associated with serious side-effects. As a result, therapy should be given only after careful consideration of the risk: benefit ratio and not merely to treat an abnormal laboratory result.(ABSTRACT TRUNCATED AT 400 WORDS)