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Abnormal structure of von Willebrand factor in myeloproliferative syndrome is associated to either thrombotic or
M F López-Fernández1, C López-Berges, R Martín
1Department of Hematology, Hospital Clinico, Universidad de Salamanca, Spain.
Abstract:
The multimeric and subunit patterns of plasma von Willebrand factor (vWF) were analyzed in eight patients with myeloproliferative syndrome (MS) in order to investigate the possible existence of heterogeneity in the "in vivo" proteolytic cleavage of the protein, previously observed in this entity. Six patients lacked large vWF multimers, five of them having normal bleeding times (BT) and clinically documented episodes of thrombotic origin, whereas one patient had long BT and bleeding symptoms. Seven patients showed a relative increase in the 176 kDa subunit fragment while the 189 kDa polypeptide was increased in only one. In addition, another patient (and prior to any therapy) showed the presence of a new fragment of approximately 95 kDa which disappeared after Busulfan therapy. The collection of blood from these patients with proteinase inhibitors did not correct the abnormalities. The infusion of DDAVP to two patients with abnormal vWF was accompanied by: the appearance of larger vWF multimers which disappeared rapidly from plasma; an increase in the relative proportion of the satellite bands of each multimer and a further increase of the 176 kDa fragment. These data point to some heterogeneity in the vWF abnormality present in MS which may be related in part to a variable degree of proteolysis of vWF occurring "in vivo" rather than "in vitro", and which may be associated to either a thrombotic or a bleeding diathesis. They also suggest that despite the presence of abnormal, already proteolyzed vWF, DDAVP-enhanced proteolysis occurs in MS to a similar extent to what is described in normal individuals.
Insights
Myeloproliferative syndrome (MS) shows varied von Willebrand factor (vWF) proteolysis, impacting thrombotic or bleeding risks. DDAVP infusion in MS patients revealed enhanced vWF proteolysis, similar to healthy individuals.
Area of Science:
- Hematology
- Molecular Biology
- Protein Chemistry
Background:
- Myeloproliferative syndromes (MS) are characterized by abnormal blood cell proliferation.
- Von Willebrand factor (vWF) plays a crucial role in hemostasis.
- Previous studies suggested heterogeneity in vWF proteolytic cleavage in MS.
Purpose of the Study:
- To investigate the heterogeneity of in vivo proteolytic cleavage of von Willebrand factor (vWF) in patients with myeloproliferative syndrome (MS).
- To explore the relationship between vWF abnormalities and clinical manifestations (thrombosis or bleeding) in MS.
- To assess the effect of DDAVP on vWF multimer structure and proteolysis in MS patients.
Main Methods:
- Analysis of plasma vWF multimeric and subunit patterns in eight MS patients.
- Assessment of bleeding times (BT) and clinical history of thrombotic or bleeding episodes.
- Evaluation of vWF changes following DDAVP infusion and in vitro studies with proteinase inhibitors.
Main Results:
- Six patients lacked large vWF multimers; five had normal BT with thrombotic episodes, one had prolonged BT with bleeding.
- Seven patients exhibited increased 176 kDa vWF subunit fragments.
- A novel 95 kDa fragment was observed in one patient, disappearing after Busulfan therapy; proteinase inhibitors did not correct abnormalities.
- DDAVP infusion led to transient appearance of larger vWF multimers, increased satellite bands, and further 176 kDa fragment elevation.
Conclusions:
- vWF abnormalities in MS exhibit heterogeneity, potentially due to variable in vivo proteolysis.
- These vWF alterations may correlate with either thrombotic or bleeding diatheses in MS patients.
- DDAVP enhances vWF proteolysis in MS patients similarly to healthy individuals, despite pre-existing abnormal vWF.