Diagnostic approach to inherited bleeding disorders

The appropriate development of hemostasis encompasses a delicate equilibrium between anti- and prothrombotic forces developing during three distinct phases (primary hemostasis, coagulation and fibrinolysis) that are closely linked to each other and precisely regulated to close vessel wounds, promote vascular healing and maintain vessel patency. Imbalance in each of these systems produces either hemorrhagic orthrombotic disorders. Inherited bleeding disorders, caused by quantitative or qualitative alterations of either platelets or plasma proteins involved in blood coagulation and fibrinolysis, may lead to serious and lifelong bleeding conditions, the severity of which is inversely associated with the degree of the underlying defect. Rapid and reliable identification of these pathologies is worthy of focus to allow the adoption of appropriate substitutive or supportive antihemorrhagic therapies. Evaluation of the hemorrhage-prone patient requires careful recording of the medical history, attention to pertinent physical findings and the discretionary use of laboratory resources. Owing to the low diagnostic efficiency of clinical history and examination, an appropriate and reliable laboratory approach, encompassing first- and second-line testing, is essential to screen, diagnose and monitor patients with bleeding diatheses. As both the analytical sensitivity and responsiveness of traditional coagulation assays to different abnormalities differ widely, each laboratory should establish individual guidelines based on field experience and on reagent and instrument characteristics. Emerging evidence indicates that the implementation of global coagulation tests, such as the thrombin generation assay and clot waveform analysis, would provide additional information for clinical decision-making for patients with inherited bleeding disorders.