Distinct mechanisms account for acquired von Willebrand syndrome in plasma cell dyscrasias

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Distinct mechanisms account for acquired von Willebrand syndrome in plasma cell dyscrasias. / Dicke, Christina; Schneppenheim, Sonja; Holstein, Katharina; Spath, Brigitte; Bokemeyer, Carsten; Dittmer, Rita; Budde, Ulrich; Langer, Florian.

In: ANN HEMATOL, Vol. 95, No. 6, 05.2016, p. 945-57.

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@article{832ae9f52e8744a89bdae2fcb419dd89,
title = "Distinct mechanisms account for acquired von Willebrand syndrome in plasma cell dyscrasias",
abstract = "Acquired von Willebrand syndrome (AVWS) is a rare bleeding disorder that may cause life-threatening hemorrhages in patients with plasma cell dyscrasias (PCDs). Early diagnosis and treatment require a thorough understanding of its underlying pathophysiology. Two patients with IgG MGUS presented with dramatically decreased plasma von Willebrand factor (VWF) and a severe type-1 pattern on multimer analysis. A prompt response to intravenous immunoglobulins (IVIG), but not to VWF/FVIII, was consistent with accelerated immunologic clearance of plasma VWF. Another IgG MGUS patient showed a type-2 pattern and a less pronounced response to IVIG, suggesting that additional mechanism(s) contributed to AVWS evolution. In a patient with Waldenstr{\"o}m's macroglobulinemia and severe depletion of plasma VWF, multimer analysis indicated association of the IgM paraprotein with VWF before, but not after plasmapheresis, resulting in destruction of the agarose gel and a characteristically distorted band structure of VWF multimers. A type-2 pattern with highly abnormal VWF triplets and laboratory evidence of excessive fibrinolytic activity suggested that plasmin-mediated VWF degradation contributed to AVWS in a patient with multiple myeloma (MM) and AL amyloidosis. Finally, in a patient with IgG MM, maximally prolonged PFA-100{\textregistered} closure times and a specific defect in ristocetin-induced platelet agglutination, both of which resolved after remission induction, indicated interference of the paraprotein with VWF binding to platelet GPIb. Importantly, in none of the six patients, circulating autoantibodies to VWF were detected by a specific in-house ELISA. In summary, when evaluating PCD patients with severe bleeding symptoms, AVWS due to various pathogenic mechanisms should be considered.",
keywords = "Aged, Autoantibodies, Female, Humans, Immunoglobulins, Intravenous, Male, Middle Aged, Paraproteinemias, von Willebrand Diseases, von Willebrand Factor, Case Reports, Journal Article",
author = "Christina Dicke and Sonja Schneppenheim and Katharina Holstein and Brigitte Spath and Carsten Bokemeyer and Rita Dittmer and Ulrich Budde and Florian Langer",
year = "2016",
month = may,
doi = "10.1007/s00277-016-2650-x",
language = "English",
volume = "95",
pages = "945--57",
journal = "ANN HEMATOL",
issn = "0939-5555",
publisher = "Springer",
number = "6",

}

RIS

TY - JOUR

T1 - Distinct mechanisms account for acquired von Willebrand syndrome in plasma cell dyscrasias

AU - Dicke, Christina

AU - Schneppenheim, Sonja

AU - Holstein, Katharina

AU - Spath, Brigitte

AU - Bokemeyer, Carsten

AU - Dittmer, Rita

AU - Budde, Ulrich

AU - Langer, Florian

PY - 2016/5

Y1 - 2016/5

N2 - Acquired von Willebrand syndrome (AVWS) is a rare bleeding disorder that may cause life-threatening hemorrhages in patients with plasma cell dyscrasias (PCDs). Early diagnosis and treatment require a thorough understanding of its underlying pathophysiology. Two patients with IgG MGUS presented with dramatically decreased plasma von Willebrand factor (VWF) and a severe type-1 pattern on multimer analysis. A prompt response to intravenous immunoglobulins (IVIG), but not to VWF/FVIII, was consistent with accelerated immunologic clearance of plasma VWF. Another IgG MGUS patient showed a type-2 pattern and a less pronounced response to IVIG, suggesting that additional mechanism(s) contributed to AVWS evolution. In a patient with Waldenström's macroglobulinemia and severe depletion of plasma VWF, multimer analysis indicated association of the IgM paraprotein with VWF before, but not after plasmapheresis, resulting in destruction of the agarose gel and a characteristically distorted band structure of VWF multimers. A type-2 pattern with highly abnormal VWF triplets and laboratory evidence of excessive fibrinolytic activity suggested that plasmin-mediated VWF degradation contributed to AVWS in a patient with multiple myeloma (MM) and AL amyloidosis. Finally, in a patient with IgG MM, maximally prolonged PFA-100® closure times and a specific defect in ristocetin-induced platelet agglutination, both of which resolved after remission induction, indicated interference of the paraprotein with VWF binding to platelet GPIb. Importantly, in none of the six patients, circulating autoantibodies to VWF were detected by a specific in-house ELISA. In summary, when evaluating PCD patients with severe bleeding symptoms, AVWS due to various pathogenic mechanisms should be considered.

AB - Acquired von Willebrand syndrome (AVWS) is a rare bleeding disorder that may cause life-threatening hemorrhages in patients with plasma cell dyscrasias (PCDs). Early diagnosis and treatment require a thorough understanding of its underlying pathophysiology. Two patients with IgG MGUS presented with dramatically decreased plasma von Willebrand factor (VWF) and a severe type-1 pattern on multimer analysis. A prompt response to intravenous immunoglobulins (IVIG), but not to VWF/FVIII, was consistent with accelerated immunologic clearance of plasma VWF. Another IgG MGUS patient showed a type-2 pattern and a less pronounced response to IVIG, suggesting that additional mechanism(s) contributed to AVWS evolution. In a patient with Waldenström's macroglobulinemia and severe depletion of plasma VWF, multimer analysis indicated association of the IgM paraprotein with VWF before, but not after plasmapheresis, resulting in destruction of the agarose gel and a characteristically distorted band structure of VWF multimers. A type-2 pattern with highly abnormal VWF triplets and laboratory evidence of excessive fibrinolytic activity suggested that plasmin-mediated VWF degradation contributed to AVWS in a patient with multiple myeloma (MM) and AL amyloidosis. Finally, in a patient with IgG MM, maximally prolonged PFA-100® closure times and a specific defect in ristocetin-induced platelet agglutination, both of which resolved after remission induction, indicated interference of the paraprotein with VWF binding to platelet GPIb. Importantly, in none of the six patients, circulating autoantibodies to VWF were detected by a specific in-house ELISA. In summary, when evaluating PCD patients with severe bleeding symptoms, AVWS due to various pathogenic mechanisms should be considered.

KW - Aged

KW - Autoantibodies

KW - Female

KW - Humans

KW - Immunoglobulins, Intravenous

KW - Male

KW - Middle Aged

KW - Paraproteinemias

KW - von Willebrand Diseases

KW - von Willebrand Factor

KW - Case Reports

KW - Journal Article

U2 - 10.1007/s00277-016-2650-x

DO - 10.1007/s00277-016-2650-x

M3 - SCORING: Journal article

C2 - 27040683

VL - 95

SP - 945

EP - 957

JO - ANN HEMATOL

JF - ANN HEMATOL

SN - 0939-5555

IS - 6

ER -