Laboratory Assessment of Familial, Nonthrombocytopenic Mucocutaneous Bleeding: A Definitive Diagnosis Is Often Not Possible

Abstract

Patients with inherited mucocutaneous bleeding (MCB) pose frequent and significant diagnostic challenges. Bleeding symptoms are frequent among the otherwise healthy population, and the clinical distinction between normal subjects and patients with genuine bleeding disorders is complex. Screening or global laboratory assays are nonspecific and have low sensitivity to detect mild bleeding disorders. Moreover, there are inherent difficulties in diagnosing von Willebrand disease and platelet function defects, the best-characterized and most frequent disorders of primary hemostasis. On the other hand, some patients with moderate to severe clotting factor deficiencies and those with increased fibrinolysis usually present with MCB. Finally, in a significant proportion of patients, the definitive diagnosis is not possible even after an extensive laboratory workup. This article reviews the clinical and laboratory approach to the diagnosis of patients presenting with MCB, the limitations of the available methodologies to evaluate the clinical significance of bleeding, and the diagnostic yield of global and specific hemostasis tests used to investigate these patients.