Anne De Paepe and
Article first published online: 20 OCT 2004
Easy bruising and bleeding are not only characteristic manifestations of clotting and platelet disorders, they are also prominent features in some heritable collagen disorders, such as the Ehlers–Danlos syndromes (EDS). The EDS comprise a heterogeneous group of connective tissue diseases sharing clinical manifestations in skin, ligaments and joints, blood vessels and internal organs. Most EDS subtypes are caused by mutations in genes encoding the fibrillar collagens type I, III and V, or in genes coding for enzymes involved in the post-translational modification of these collagens. Easy bruising is, to a variable degree, present in all subtypes of EDS, and is because of fragility of the capillaries and the perivascular connective tissues. Vascular fragility affecting medium-sized and large arteries and veins is typically observed in the vascular subtype of EDS, caused by a molecular defect in collagen type III, an important constituent of blood vessel walls and hollow organs. Extensive bruising, spontaneous arterial rupture, leading to severe internal bleeding or premature death, and rupture of hollow organs, such as the intestine or the gravid uterus are predominant features of this subtype. Haematological studies including evaluation of clotting factors, platelet aggregation and bleeding time are usually normal in patients with EDS, except for the Hess test (Rumple–Leede test), which may be abnormal, indicating capillary fragility. In some forms of EDS confirmation of the clinical diagnosis and subtype is possible with biochemical and molecular studies.
Excessive bruising and an increased bleeding diathesis are important features of many disorders of coagulation and/or platelets, such as haemophilia A and B, and von Willebrand disease, and the many disorders of platelet number and function. They can, however, be prominently present in another group of diseases, the heritable collagen disorders, a heterogeneous group of genetic diseases that are caused by mutations in structural collagen genes or in genes coding for enzymes involved in their post-translational modification. Although individually rare disorders, together they represent an important category among the heritable disorders of connective tissue. Whereas the prototype collagen type I disorder Osteogenesis Imperfecta (OI) or ‘brittle bone disease’ mainly affects the hard connective tissues, the Ehlers–Danlos syndromes (EDS) typically affect soft connective tissues. The EDS comprise a clinically and genetically heterogeneous group of conditions of which the main features are skin hyperextensibility, joint hypermobility, easy bruising, and generalized connective tissue fragility (Steinman et al, 2002). Prominent bruising and bleeding is seen in all subtypes of EDS (Table I). There is, however, a wide range of severity in bleeding diathesis, comprising mild to severe bruising, subcutaneous haematomas, bleeding of the gums, and life-threatening internal bleeding because of arterial rupture. ‘Easy bruising’, which means the tendency to develop ecchymoses either spontaneously or upon minimal trauma, is seen in all subtypes of EDS, and can be explained by capillary fragility. Fragility of medium-sized and large arteries and veins is seen typically in the vascular subtype of EDS (EDS type IV) and occasionally in the rare kyphoscoliotic subtype (EDS type VI).
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