DDAVP in acquired von Willebrand syndrome associated with multiple myeloma

Takahashi, Hiroyuki; Nagayama, Reizo; Tanabe, Yuji; Satoh, Ken; Hanano, Manabu; Mito, M; Shibata, Akira

doi:10.1002/ajh.2830220412

Cited by 43 publications

(14 citation statements)

References 33 publications

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“…More recently, it has been shown that vWf fragmentation occurs due to in-vivo proteolysis in the patients with CMPD (Budde et al 1986;Lopez-Fernandez et al 1987), and that abnormal vWf structure was not corrected even if blood was obtained in the presence of protease inhibitors (Lopez-Fernandez et al 1987). It is important to determine whether or not these vWf abnormalities are present in each patient with CMPD, because when bleeding episodes occur, the administration of cryoprecipitate or desmopressin (DDAVP) may be effective, as demonstrated in several patients with acquired vWf abnormalities (Budde et al 1984;Mannucci et al 1984;Takahashi et al 1986b).…”

Section: Discussionmentioning

confidence: 99%

Multimeric composition of plasma von Willebrand factor in chronic myeloproliferative disorders

Tatewaki

Takahashi

Shibata

1988

Clinical &Amp; Laboratory Haematology

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In chronic myeloproliferative disorders (CMPD) thrombohaemorrhagic complications occur occasionally in association with thrombocytosis. We studied the multimeric composition of plasma von Willebrand factor (vWf) in 15 patients with polycythaemia vera (PV), 12 with essential thrombocythaemia (ET) and eight with primary myelofibrosis (PMF). The relative content of large (multimer band greater than or equal to 11) multimers calculated by densitometer scan following SDS-agarose gel electrophoresis was 18.5 +/- 4.4% (mean +/- SD) in normal controls, 8.3 +/- 7.9% in PV, 8.1 +/- 4.6% in ET and 19.6 +/- 6.7% in PMF. The patients with PV and ET but not PMF had a significantly lower percentage of large multimers than normal controls (P less than 0.001). The relative content of large multimers was negatively correlated with WBC and platelet count (P less than 0.02 each) in PV. It was negatively correlated with platelet count (P less than 0.005) and was positively correlated with a ratio of ristocetin cofactor/vWf antigen (RCof/vWf:Ag) (P less than 0.01) in ET. These results indicate that acquired defects of vWf are quite common in PV and ET but not in PMF. In addition, some CMPD patients with high platelet counts completely lacked large multimers. The negative correlation of the relative content of large multimers with platelet count suggests that large multimers may be preferentially consumed during thrombocytosis or degraded by protease(s) from increased blood cells.

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Section: Discussionmentioning

confidence: 99%

Multimeric composition of plasma von Willebrand factor in chronic myeloproliferative disorders

Tatewaki

Takahashi

Shibata

1988

Clinical &Amp; Laboratory Haematology

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“…10 The antibiotic ristocetin promotes binding of the vWF to the platelet receptor glycoprotein Ib.11 Low levels of vWF, abnormal vWF-multimer composition, and defects in the vWF-binding sites all result in an impaired ristocetin-induced platelet aggregation,12-14 which in some cases can be normalized by DDAVP. 15 It has been suggested that DDAVP might be used to reduce the blood loss after cardiac surgery.6"17 To confirm this, a double-blind placebo-controlled clinical trial of DDAVP on postoperative bleeding in 100 patients was initiated. To investigate the mechanisms behind such a possible effect, it was of interest to study not only the levels of vWF: Ag and VIII: C but also platelet function in relation to the treatment.…”

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confidence: 99%

Effects of desmopressin acetate on platelet aggregation, von Willebrand factor, and blood loss after cardiac surgery with extracorporeal circulation.

et al. 1990

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The effects of desmopressin acetate (DDAVP) on platelet aggregation and the von Willebrand factor antigen (vWF: Ag) were studied in 19 patients undergoing cardiac surgery with extracorporeal circulation. The patients represented one of five blocks in a randomized double-blind placebo-controlled parallel group trial on the effects of DDAVP on postoperative bleeding after uncomplicated coronary artery bypass operations. After termination of extracorporeal circulation, DDAVP (0.3 jig/kg body wt) or its vehicle was infused into a peripheral vein throughout 15 minutes. The increase in factor VIII coagulant activity after infusion did not differ between the groups but there was a significantly larger increase in vWF: Ag levels in DDAVP-treated patients. The aggregatory response to adenosine-diphosphate (ADP) and ristocetin showed a normal pattern and was not significantly different between the two groups. As compared with placebo, DDAVP did not decrease the bleeding time or the postoperative blood loss. We conclude that DDAVP causes an increase in vWFF:Ag levels but does not alter platelet aggregation, bleeding time, or blood loss in uncomplicated coronary artery bypass patients. (Circulation 1990;81:872-878) Acommon problem in cardiac surgery is increased bleeding tendency after cardiopulmonary bypass. The hemostatic defect can be caused by several factors such as a decrease in plasma coagulation factors, increased fibrinolytic activity, inadequate reversal of heparinization, or reduced platelet count as well as defects in platelet function.1,2Desmopressin acetate (DDAVP) can reduce bleeding in patients with mild hemophilia A and most types of von Willebrand's disease. It also seems to be effective in some patients with congenital or acquired platelet function defects,34 including abnormalities associated with uremia5 and intake of aspirin.6 Infusion of DDAVP is known to increase From the

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“…The additional mechanisms, although appearing to be implausible, remain to be investigated as follows: (1) the Ig preparation used may have anti-idiotypic antibodies or a direct effect on antibodyproducing cells [1][2][3][4], or (2) the Ig preparation may have an activity in stimulating endothelial cells, thus producing and releasing more VWF [1][2][3][4]. In contrast, for AVWS of the nonantibody type, another mechanism, such as the selective absorption of VWFMs on clonal lymphocytes or plasma cells [22][23][24], has been postulated, because some clonal cells in those patients may express platelet glycoprotein Ib, a VWF receptor, on their surface. However, this is not the case in our patient.…”

Section: Discussionmentioning

confidence: 99%

Low-Dosage Intravenous Immunoglobulin in the Management of a Patient with Acquired von Willebrand Syndrome Associated with Monoclonal Gammopathy of Undetermined Significance

Hayashi

Yano²,

Suzuki³

et al. 2002

Pathophysiol Haemos Thromb

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We report herein the case of a 69-year-old Japanese man with acquired von Willebrand syndrome associated with monoclonal gammopathy of undetermined significance who developed IgG1-ĸ antibodies against von Willebrand factor (VWF). The patient was urged to undergo tooth extractions because of alveolar pyorrhea, and a low-dosage intravenous immunoglobulin (IV-Ig) therapy (0.3 g of IgG/kg/day for 3 days) was chosen for him. On the 4th day after the infusion, VWF antigen and VWF ristocetin cofactor increased to 40 and 78% of the control, respectively, and dental extractions were performed successfully. On the 7th day, these values reached a maximum, i.e. 95 and 160% of the control, respectively. Then, they quickly decreased to 35 and 75% on the 10th day, and 6 months later, they became 16 and <3% of the control, respectively. Upon analysis of plasma VWF multimers (VWFMs) in this patient, those with large to medium molecular masses more selectively disappeared before the IV-Ig infusion than did those with small molecular masses. On the 4th day, the pattern of VWFMs was completely normalized and appeared to persist until the 10th day. Six months later, a small amount of large to medium-sized VWFMs was still present, but at 7–8 months, the pattern of VWFMs became almost the same as that before infusion. Throughout the patient’s clinical course, the activity of plasma VWF-cleaving protease, which specifically cleaves the Tyr842-Met843 bond of the subunit and reduces its multimeric sizes, was quite normal (95–119%). These results provided consistent evidence that the selective absence of VWFMs with large to medium molecular masses in this patient is caused by the heightened clearance of a complex of IgG inhibitor and VWFMs from the circulation, presumably through IgG binding to the Fc receptor of macrophages. Furthermore, these results also indicated that a low-dosage IV-Ig therapy is effective enough for hemostatic management for programmed surgery.

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DDAVP in acquired von Willebrand syndrome associated with multiple myeloma

Cited by 43 publications

References 33 publications

Multimeric composition of plasma von Willebrand factor in chronic myeloproliferative disorders

Multimeric composition of plasma von Willebrand factor in chronic myeloproliferative disorders

Effects of desmopressin acetate on platelet aggregation, von Willebrand factor, and blood loss after cardiac surgery with extracorporeal circulation.

Low-Dosage Intravenous Immunoglobulin in the Management of a Patient with Acquired von Willebrand Syndrome Associated with Monoclonal Gammopathy of Undetermined Significance

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