Elevated platelet count as a cause of abnormal von Willebrand factor multimer distribution in plasma

Abstract

Twelve of 19 patients with myeloproliferative disorders showed a decrease of absence of the largest multimers of plasma von Willebrand factor (vWF) that correlated with elevated platelet counts but not with leukocyte counts. This suggested that platelets, rather than leukocytes, may be associated with the pathogenesis of the acquired vWF abnormality seen in these patients. To examine the hypothesis further, we studied 12 patients with reactive thrombocytosis after splenectomy. Increased platelet count (> 5 x 10(11)/L) after splenectomy was associated with vWF abnormalities indistinguishable from those detected in patients with myeloproliferative disorders. Accordingly, there was an inverse correlation between proportion of large vWF multimers and platelet, but not leukocyte, number: normalization of the platelet count was accompanied by restoration of a normal vWF multimeric pattern. These findings suggest that an increase in the number of platelets circulating in blood may favor the adsorption of larger vWF multimers onto the platelet membrane, resulting in their removal from the circulation and subsequent degradation.

Thrombosis and haemorrhage in polycythaemia vera and essential thrombocythaemia

“…This phenomenon is not restricted to MPD and has also been described in patients with reactive thrombocytosis, suggesting a primary effect of absolute platelet number as opposed to dysfunctional clonal platelets (Budde et al, 1993). This would be consistent with the observed resolution of the specific laboratory abnormality with platelet cytoreduction (Budde et al, 1984;Budde et al, 1993;van Genderen et al, 1997b;Michiels et al, 2001).…”

“…On the other hand, the assays used to assess VWF function, including collagen binding activity (VWF:CBA) and ristocetin cofactor activity (VWF:RCoA), show that VWF function declines with increasing platelet counts (van Genderen et al, 1996bGenderen et al, , 1997bFavaloro, 2000). This phenomenon is not restricted to MPD and has also been described in patients with reactive thrombocytosis, suggesting a primary effect of absolute platelet number as opposed to dysfunctional clonal platelets (Budde et al, 1993). This would be consistent with the observed resolution of the specific laboratory abnormality with platelet cytoreduction (Budde et al, 1984;Budde et al, 1993;van Genderen et al, 1997b;Michiels et al, 2001).…”

“…In view of the clonal derivation of the platelet in MPD, a dysfunctional platelet has long been assumed to be the main culprit in the haemorrhagic manifestations. However, increasing data indicate that this may only indirectly be the case, as thrombocytosis may cause an acquired von Willebrand Syndrome (AVWS), that may account for a significant proportion of reported bleeding episodes (Budde et al, 1993;Budde & van Genderen, 1997). Furthermore, the general lack of correlation between platelet function abnormalities and clinical bleeding suggest alternate mechanisms might be involved (Schafer, 1984).…”

Type 2A (IIH) von Willebrand disease is due to mutations that affect von Willebrand factor multimerization

“…Lane NP shows normal plasma VWF. Multimers were visualized using a luminescence method[20]. Multimer analysis of wild-type and mutated recombinant von Willebrand factors (rVWFs) as expressed in COS-7 cells.…”

Target hematologic values in the management of essential thrombocythemia and polycythemia vera

“…Aspirin significantly aggravates the risk of hemorrhage (14,15). A correlation between the loss of larger vWF multimers and increase in platelet count has been demonstrated in MPN patients as well as in those with reactive thrombocytosis (22). Normalization of the platelet count resulted in restoration of a normal vWF multimeric pattern (22).…”