A Study of a Caucasian Family with Variant von Willebrand’s Disease in Association with Vascular Telangiectasia and Haemoglobinopathy

Abstract

SummaryA family was identified which carries multi-haematological disorders including Type IIA von Willebrand’s disease, vascular telangiectasia, and a haemoglobinopathy (haemoglobin S trait). In the affected individuals, the von Willebrand’s disease varies in its expression from an asymptomatic form to a severe form especially in those patients with telangiectasia. Some patients have vascular telangiectasia in the mucous membranes of the mouth and lips. In two patients endoscopy disclosed telangiectasia in the mucous membranes of the gastrointestinal tract. All of the patients who had telangiectasia also had von Willebrand’s disease. An incidental finding was the presence of an abnormal haemoglobin (haemoglobin S) in some family members. The pattern of inheritance of the haemoglobinopathy was unrelated to the inheritance pattern of von Willebrand’s disease. The presence of haemoglobin S did not interfere with the aggregation of platelets in response to ristocetin.

Hereditary Hemorrhagic Telangiectasia: Analysis of Platelet Aggregation and Fibrinolytic System in Seven Patients

“…The various abnormalities in in vitro platelet function published in the literature by several authors [12][13][14][15] have not been found neither by us nor by others [16]. No quantitative abnormali ties in von Willebrand factor ristocetin cofactor activ ity suggesting a possible von Willebrand disease could be demonstrated, although some groups have evidenced the coexistence of both pathologies in several members from a single kindred [17,18]. Von Willebrand's disease is a relatively common disease, and its association with HHT or different platelet aggregation abnormalities could have only been coin cidental.…”

“…Although the severity of bleeding is highly variable from one patient to another, in some patients, the frequent and continuous requirement of red blood cell transfusions occasionally leads to the development of secondary effects from chronic blood administration [2], No ef fective therapy has been found to stop or, at least, to lessen recurrent bleeding [2,26,27], Fragility of the vessel wall was firstly implicated in the bleeding tendency of these patients [9] but more recently, alterations in platelet function [12][13][14][15], asso ciation between HHT and von Willebrand's disease [17,18] and analytical evidence of compensated dis seminated intravascular coagulation syndrome [10], have been considered in the pathophysiology of this disorder. Fibrinolytic activators have also been impli cated in it [11].…”

“…Abnormalities in in vitro platelet aggregation and adhesion have been reported by several groups [12][13][14] but not by others [16], Moreover, there has been found an association between HHT and von Willebrand's disease in some families [17,18]: the ab normal function of vascular endothelial cells may re sult in defective production and release of von Willebrand factor (vWF) and, in some patients, telangiec tatic lesions.…”

Gastrointestinal and Hepatic Manifestations of Hereditary Hemorrhagic Telangiectasia

“…Both AVM and telangiectasia are surrounded by a cuff of fibrous tissue which prevents vessel contraction following injury, and which promotes the hemorrhagic manifestations of the disease [22]. In addition to the obvious vascular malformations, patients with HHT also have abnormalities of blood coagulation, including the presence of von Willebrand factor (vWF), and factor VIII deficiency, as well as defects of fibrinolysis and platelet function [24][25][26][27][28][29]. These may further affect the severity and the chronicity of bleeding.…”

“…These may further affect the severity and the chronicity of bleeding. It has been postulated that an endothelial cell defect may result in telangiectasia and impaired production of factor VIII and vWF [28,29].…”