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.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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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 -