Supranormal von Willebrand factor multimers in scleroderma

Abstract

Platelet adhesion-aggregation reactions play an early and pivotal role in the pathogenesis of systemic sclerosis in scleroderma, but the mechanisms are incompletely understood. We determined whether or not plasma from 11 consecutive patients with scleroderma contained a subset of larger than normal (“supranormal”) multimers of von Willebrand factor (vWF) that are potent inducers of platelet aggregation and adhesion. Supranormal multimers were found in all patients on at least one of two different occasions 9 to 12 months apart, whatever the duration and severity of the disease, but in none of the normal controls. Administration of low-dose aspirin (40 mg) to five of the 11 patients for ten days to inhibit the platelet release reaction slightly reduced the amounts of supranormal multimers suggesting that they might originate in part from platelets. Supranormal multimers may contribute to the pathogenesis of systemic sclerosis by inducing platelet aggregation and enhancing adhesion to subendothelium under the conditions of elevated shear stress occurring in the partially occluded vessels of the arterial microcirculation of scleroderma.

Pathogenic role of platelets in rheumatoid arthritis and systemic autoimmune diseases

“… 33 On the other hand, plasma samples from patients with SSc contain a supranormal subset of von Willebrand factor, which can induce platelet aggregation and adhesion to the subendothelium. 34 Interestingly, SSc platelets were recently found to over-express a specific receptor for type I collagen. 35 Platelets have surface receptors for collagen I and collagen III.…”

Assessment of endothelial damage and dysfunction: observations in relation to heart failure

“…24 In addition, high vWF predicts the development of thromboembolic events and poor prognosis in patients with rheumatoid arthritis and systemic sclerosis. [25][26][27][28][29][30] In unstable coronary artery disease, an early increase of vWF in 48 h is an independent predictor of adverse clinical outcome at 14 and 30 days. 31 In a substudy of the ESSENCE (Efficacy and Safety of Subcutaneous Enoxaparin in Non Q Wave Coronary Events) trial, patients who were allocated to enoxaparin compared to unfractionated heparin had a smaller increase in vWF over 48 h, and this was associated with a lower composite end-point of death, myocardial infarction, recurrent angina or revascularization.…”

Acquired von Willebrand Syndrome: from Pathophysiology to Management

“…The second most common groups of disorders associated with AvWS is neoplasia such as Wilms tumors (52)(53)(54)(55)(56)(57) and carcinomas (58-60), followed by immunological diseases, most notable being systemic lupus erythematosus (SLE) (5,61,62) and hypothyroidism (63)(64)(65)(66)(67)(68)(69)(70)(71)(72)(73)(74). Various other clinical conditions (Table 1) such as rare immunological disorders (75)(76)(77)(78), uremia (79)(80)(81), cardiac diseases (82)(83)(84)(85)(86), gastrointestinal angiodysplasia (87)(88)(89)(90)(91)(92)(93), viral (94) and parasitical (95) infections, rare congenital syndromes (96)(97)(98) and treatments using antibiotics (99)(100)…”