Bleeding and bruising in patients with Ehlers–Danlos syndrome and other collagen vascular disorders

Abstract

SummaryEasy 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 posttranslational 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.

Periventricular Heterotopia: New Insights into Ehlers-Danlos Syndrome

“…7 The collagens represent a large family of structurally related extracellular matrix proteins essential for development, cell attachment, platelet aggregation and for providing tensile strength to the connective tissues in bone, skin, ligaments and tendons, and blood vessels. 8 Loss of the elasticity and strength of collagen in EDS presumably contributes to the structural failure in connective tissue of the various affected organ systems.…”

“…5,8 When the integrity of the vascular wall is compromised, as in vascular EDS, platelets adhere to subendothelial collagens exposed at the sites of blood vessel injury via the glycoprotein (GP) Ib-V-IX complex and integrin α2β1. 8 This initial platelet entrapment requires the plasma protein von Willebrand factor, which simultaneously binds the GP and integrin complex and facilitates platelet tethering and rolling. More stable binding of collagen to the platelet collagen receptors (namely integrin α2β1 and GPVI) follows this initial interaction.…”

Quantitative nanohistological investigation of scleroderma: an atomic force microscopy-based approach to disease characterization

“…[24][25][26] SEM allowed for surface topographical analysis over a range of magnifications. When the polarized LM images were used, the color changes seen in the SSc sample implied a loss of collagen register.…”

Ehlers-Danlos syndrome associated with cleft lip and palate

“…It is genetically transmitted in an autosomal dominant, recessive or sex-linked fashion with incomplete penetrance. Typical histological findings on skin biopsy show disorderly arranged dermal collagen fibres with a whorled appearance, while laboratory investigations of clotting factors, platelet aggregation and bleeding time are usually within normal limits, as in most connective tissue disorders (1). This is one of the oldest known causes of bruising and bleeding and was first described by Hippocrates in 400 BC.The syndrome is named after Edvard Ehlers, a Danish dermatologist, (1863-1937) and Henri-Alexandre Danlos, a French dermatologist (1844-1912) (2).…”