Decreased half‐life time of plasma von Willebrand factor collagen binding activity in essential thrombocythaemia: normalization after cytoreduction of the increased platelet count

Abstract

Summary. Patients with essential thrombocythaemia (ET)exhibit a decrease of large von Willebrand factor (VWF) multimers in plasma, which is inversely related to the platelet count. In the present study we investigated whether the decrease of large VWF multimers in plasma with increasing platelet counts is the consequence of increased turnover of large VWF multimers in vivo. To that end we measured the half-life times of endogenously released VWF:Ag and VWF:CBA (collagen binding activity) after intravenous administration of desmopressin (DDAVP) to nine ET patients and nine control subjects (N). In addition, the half-life times of VWF:Ag and VWF:CBA were also measured in four ET patients after cytoreduction of the increased platelet count to normal or nearly normal values. Estimated half-life times of VWF:Ag did not differ between ET patients and normals (11·0 Ϯ 4·0 h v 12·4 Ϯ 2·5 h, P > 0·05). Estimated half-life times of VWF:CBA were significantly lower in ET patients as compared with normal individuals (6·1 Ϯ 2·0 h v 8·4 Ϯ 2·5 h, P < 0·05). After cytoreduction of the increased platelet count to (nearly) normal values in all four ET patients the half-life time of VWF:CBA significantly (P ¼ 0·014) increased from 5·2 Ϯ 1·2 h to 8·7 Ϯ 2·0 h. Our data suggest that platelets may play a role in the homeostasis of circulating von Willebrand factor, which may compromise normal haemostasis at fairly increased platelet counts.

Prevalence of acquired von Willebrand syndrome during essential thrombocythemia: a retrospective analysis of 170 consecutive patients

“…However, according to the literature, determination of VWF:Ag and FVIII levels alone may be insufficient in some cases, 20,30 and some functional assays (eg, VWF:Rco) should be also performed. [31][32][33] Importantly, we have conducted all coagulation tests at least 7 days after discontinuation of platelet aggregation inhibitors to exclude false-positive results, which should be a standard of evaluation for AVWS. 34 While interpreting our findings, potential methodological limitations of the study should be considered, which are primarily related to its retrospective design.…”

Oral, but Not Transdermal, Administration of Estrogens Lowers Tissue-Type Plasminogen Activator Levels in Humans Without Affecting Endothelial Synthesis

“…vWF is an endothelium-derived protein, which is stored in the endothelium in specialized storage sites (ie, Weibel-Palade bodies). Circulating vWF, which has a plasma half-life of 12 hours, 32 should not increase significantly during 10 minutes of venous occlusion in the absence of activation of the endothelium, which has been noted previously. 33 Values of all postocclusion tPA, PAI-1, and vWF levels were corrected for the effects of hemoconcentration by use of the hematocrit (by automated cell counter measurements).…”

Acquired von Willebrand Syndrome

“…Proteolysis of HMW vWF during the course of essential thrombocythemia may be triggered by platelet-released calcium ions, causing the activation of proteases and elastases. In such cases, proteolysis can be confirmed based on the presence of enzymatically-digested fragments of HMW vWF [29]. Excessive pathological proteolysis of HMW vWF may also occur in the course of uremia, pancreatitis, liver cirrhosis, leukemia and after the adminis- tration of some therapeutic agents, e.g.…”