Acquired von Willebrand's disease in the myeloproliferative syndrome

Budde, Ulrich; Schaefer, Gerald; Mueller, Nicolas J.; Egli, H; Dent, Judith A.; Ruggeri, ZM; Zimmerman, Theodore S.

doi:10.1182/blood.v64.5.981.981

Cited by 208 publications

(106 citation statements)

References 17 publications

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“…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).…”

Section: Pathogenesissupporting

confidence: 84%

Thrombosis and haemorrhage in polycythaemia vera and essential thrombocythaemia

2005

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Summary Despite decades of clinical and laboratory research, relatively little has been accomplished concerning the pathogenesis as well as the identification of risk factors for thrombosis and bleeding in myeloproliferative disorders. In polycythaemia vera, the pro‐thrombotic effect of an elevated haematocrit is well established. In contrast, thrombocytosis per se has not been similarly incriminated in essential thrombocythaemia. In both conditions, advanced age and the presence of a prior event identify thrombosis‐prone patients. There is increasing evidence to suggest an additional role by leucocytes that might partly explain the antithrombotic effects of myelosuppressive therapy. A substantial minority of affected patients display reduced levels of high molecular weight von Willebrand protein in the plasma during extreme thrombocytosis and it is believed that this might explain the bleeding diathesis of such patients. Recent controlled studies support the therapeutic value of hydroxyurea and aspirin in essential thrombocythaemia and polycythaemia vera, respectively. The current communication will address the incidence, phenotype, pathogenesis, risk factors, prevention, and treatment of both thrombosis and haemorrhage in these disorders.

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Section: Pathogenesissupporting

confidence: 84%

Thrombosis and haemorrhage in polycythaemia vera and essential thrombocythaemia

2005

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“…However, the presence of MG has not always been evident in several of the haematological and nonhaematological disorders described in association with AVWD. These conditions have included chronic lymphoproliferative (Goudemand et al, 1988) or myeloproliferative disorders (Budde et al, 1984).…”

mentioning

confidence: 99%

Acquired von Willebrand's disease due to aberrant expression of platelet glycoprotein Ib by marginal zone lymphoma cells

Tefferi¹,

Hanson

Kurtin

et al. 1997

Br J Haematol

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Summary.A 69-year-old woman presented with splenic marginal zone lymphoma associated with acquired von Willebrand's disease (AVWD). Laboratory abnormalities included markedly decreased plasma levels of factor VIII coagulant (C) activity (VIII:C 28%), von Willebrand's factor (VWF) antigen (Ag) (vWF:Ag < 6%), and VWF ristocetin cofactor (RCo) activity (VWF:RCo, < 12%). VWF multimer analysis revealed a severe type II defect. Treatment with cryoprecipitate, high-dose gamma globulin or desmopressin given intravenously was unsuccessful. Clinical bleeding and coagulation abnormalities showed transient improvement after replacement therapy with Humate-P concentrate. The coagulation abnormalities improved partially after splenectomy and completely after subsequent chemotherapy. The neoplastic lymphocytes in the blood and spleen strongly expressed platelet glycoprotein Ib (CD42) and VWF but not other platelet-associated antigens.Keywords: acquired von Willebrand's disease, glycoprotein Ib, lymphoma.Acquired von Willebrand's disease (AVWD) is usually associated with autoimmune or clonal proliferative disorders ( Jakway, 1992). The autoimmune disorders have included systemic lupus erythematosus and hypothyroidism. Monoclonal gammopathy of undetermined significance (MGUS) is the most frequently reported clonal disorder associated with AVWD. Furthermore, monoclonal gammopathy (MG) is an essential component of other plasma cell proliferative disorders associated with AVWD, including multiple myeloma and Waldenström's macroglobulinaemia. Similarly, MG is often present in chronic lymphoproliferative disorders that have been associated with AVWD (Mannucci et al, 1984). However, the presence of MG has not always been evident in several of the haematological and nonhaematological disorders described in association with AVWD. These conditions have included chronic lymphoproliferative (Goudemand et al, 1988) or myeloproliferative disorders (Budde et al, 1984).We describe a patient with clinical and histopathologic characteristics of splenic marginal zone lymphoma (SMZL) presenting with a severe bleeding diathesis due to AVWD. Laboratory investigations revealed an aberrant expression of glycoprotein Ib (CD42) and VWF by the neoplastic cells. The possibility of a similar aberrant expression of plateletassociated antigens in related lymphoid disorders was addressed and possible pathogenetic mechanisms for the development of AVWD were considered. CASE REPORTA 69-year-old, 85 kg woman presented with anaemia (haemoglobin 6 . 4 g/dl) and melena. For 4 weeks before presentation she had experienced night sweats, low-grade fever, and recurrent epistaxis. There was no previous history of bleeding diathesis in either the patient or her family. Physical examination revealed multiple areas of ecchymosis and palpable splenomegaly 5 cm below the left costal margin. The initial laboratory studies revealed normal leucocyte and platelet counts and a normal leucocyte differential count.The patient was hospitalized and required transfusion with > 25 unit...

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“…10 Various abnormalities of circulating von Willebrand factor (VWF) have been described in patients with MPNs, usually associated with severe thrombocytosis. [11][12][13] The main abnormalities consisted of loss of larger VWF multimers and high proteolysis of VWF, all associated with thrombocytosis, mostly resulting in bleeding. 11,14,15 In a previous study on ET, we observed a deficiency of VWF activity and selectively of large VWF multimers over a wide range of platelet counts, rather than in patients with severe thrombocytosis only.…”

Section: Introductionmentioning

confidence: 99%

“…[11][12][13] The main abnormalities consisted of loss of larger VWF multimers and high proteolysis of VWF, all associated with thrombocytosis, mostly resulting in bleeding. 11,14,15 In a previous study on ET, we observed a deficiency of VWF activity and selectively of large VWF multimers over a wide range of platelet counts, rather than in patients with severe thrombocytosis only. 16 This acquired VWF deficiency was likely a continuous phenomenon, driven by high ongoing in vivo platelet activation, which is the hallmark of ET, with consequent platelet-dependent VWF consumption.…”

Section: Introductionmentioning

confidence: 99%

Increased von Willebrand factor levels in polycythemia vera and phenotypic differences with essential thrombocythemia

Sacco

Ranalli

Lancellotti

et al. 2020

Research and Practice in Thrombosis and Haemostasis

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Background Acquired von Willebrand factor (VWF) deficiency was described in Philadelphia‐negative myeloproliferative neoplasms, especially in essential thrombocythemia (ET). VWF phenotype in contemporary patients with polycythemia vera (PV) remains less explored. Objectives To characterize the VWF phenotype in PV and to compare VWF phenotype in PV with matched healthy subjects and ET patients. Patients/Methods We studied 48 PV patients, treated according to current recommendations (hematocrit ≤ 45%, on low‐dose aspirin prophylaxis); 48 healthy and 41 subjects with ET, all sex, age, and blood group matched. We measured VWF antigen, activity, multimeric pattern, ADAMTS‐13, and factor VIII (FVIII) antigen. Results In patients with PV, VWF antigen and activity were significantly higher than in healthy subjects (antigen: 119[96‐137] vs 93[79‐107] IU/dL; activity: 114[95‐128] vs 90[79‐107] IU/dL, respectively, medians and interquartile, P < 0.01), with normal multimeric distribution. ADAMTS‐13 levels were similar between patients with PV and healthy subjects. FVIII levels were higher in PV than in healthy subjects (141[119‐169] versus 98[88‐123] IU/dL, respectively, P < 0.01). By multivariable analysis, JAK2‐p.V617F allelic burden, erythrocyte count, and male sex significantly predicted VWF antigen and activity levels. As compared to patients with ET, patients with PV showed similar VWF antigen levels but approximately 40% higher activity (79[49‐104] vs 112[93‐125] IU/dL, respectively, P < 0.01). Conclusions Patients with PV show increased VWF and FVIII levels, predicted by JAK2‐p.V617F burden and erythrocyte count. At variance with ET, acquired VWF defect was not observed in PV. High VWF/FVIII levels may sustain the thrombotic diathesis of PV and may be investigated as biomarkers for risk stratification.

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Acquired von Willebrand's disease in the myeloproliferative syndrome

Cited by 208 publications

References 17 publications

Thrombosis and haemorrhage in polycythaemia vera and essential thrombocythaemia

Thrombosis and haemorrhage in polycythaemia vera and essential thrombocythaemia

Acquired von Willebrand's disease due to aberrant expression of platelet glycoprotein Ib by marginal zone lymphoma cells

Increased von Willebrand factor levels in polycythemia vera and phenotypic differences with essential thrombocythemia

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