Low-dosage intravenous immunoglobulin in the management of a patient with acquired von Willebrand syndrome associated with monoclonal gammopathy of undetermined significance.
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-kappa 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.
Hayashi
T
T
Division of Internal Medicine, Tokyo Metropolitan Police Hospital, Tokyo, Japan.
Yagi
H
H
Suzuki
H
H
Nonaka
Y
Y
Nomura
T
T
Sakurai
Y
Y
Shibata
M
M
Matsumoto
M
M
Yamamoto
Y
Y
Fujimura
Y
Y
D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; D000368:Aged; D019468:Disease Management; D006470:Hemorrhage / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage*; D007518:Isoantibodies / Q000097:blood; D008297:Male; D008666:Metalloendopeptidases / Q000097:blood / Q000187:drug effects; D008998:Monoclonal Gammopathy of Undetermined Significance / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology; D014081:Tooth Extraction / Q000009:adverse effects / Q000379:methods; D014842:von Willebrand Diseases / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology; D014841:von Willebrand Factor / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous; D007518:Isoantibodies; D014841:von Willebrand Factor; D051722:ADAM Proteins; D008666:Metalloendopeptidases; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human