Vascular haemostasis.
While the majority of this session will deal with selected inherited vascular abnormalities that may manifest as a haemorrhagic disorder, the initial discussion by Dr Key will focus on the interplay between the vessel wall and components of the coagulation system, with a focus on haemophilia A and B. Although it is generally accepted that physiological haemostasis is triggered by contact of blood with tissue factor (TF), there remains some controversy regarding the cellular origin of TF in vivo. In addition, the initiation and propagation of thrombin generation are highly dependent on the balance of pro- and anticoagulant functions of endothelium, a profile that varies significantly throughout the vasculature. Drs De Paepe and Malfait address heritable collagen disorders such as the Ehlers-Danlos syndromes (EDS), a heterogeneous group of diseases involving the skin, ligaments and joints, blood vessels and internal organs. Most EDS subtypes are caused by mutations in genes encoding fibrillar collagens, or in genes coding for enzymes involved in posttranslational modifications of collagens. Accurate biochemical and molecular testing is now available for most EDS subtypes and can direct genetic counselling and medical management for these disorders. Dr Shovlin reviews recent developments in hereditary haemorrhagic telengiectasia (HHT), a frequently undiagnosed disorder characterized by arteriovenous malformations in multiple organs. These abnormal blood vessels are the result of mutations in one of a number of genes whose protein products influence TGF-beta signalling in vascular endothelial cells. Several HHT management guidelines have been published and are discussed.
Key
N S
NS
Harold R Roberts Comprehensive Hemophilia Diagnostic and Treatment Center, University of North Carolina, Chapel Hill, NC, USA. nigel_key@med.unc.edu
DE Paepe
A
A
Malfait
F
F
Shovlin
C L
CL
D003094:Collagen / Q000378:metabolism; D003095:Collagen Diseases / Q000503:physiopathology*; D003937:Diagnosis, Differential; D004535:Ehlers-Danlos Syndrome / Q000175:diagnosis / Q000503:physiopathology*; D042783:Endothelial Cells / Q000502:physiology; D004727:Endothelium / Q000502:physiology; D004844:Epistaxis / Q000235:genetics; D006467:Hemophilia A / Q000150:complications*; D002836:Hemophilia B / Q000150:complications*; D006487:Hemostasis; D006801:Humans
D003094:Collagen