The Effect of Paraprotein on Platelet Aggregation

Đjunić, Irena; Elezović, Ivo; Ilić, Vesna; Milosević-Jovcić, N; Bila, Jelena; Suvajdzic-Vukovic, Nada; Vidovic, Ana; Tomin, Dragica

doi:10.1002/jcla.21658

Cited by 7 publications

(4 citation statements)

References 23 publications

(31 reference statements)

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“…Of interest, IVIg was not able to restore platelet function, indicating a non-immunogenic impairment of ristocetin-induced platelet aggregation. In accordance to Djunic et al who performed systematic mixing studies and showed that adding IVIg to the reaction mixture was not able to restore platelet activity in vitro 15 , we have provided the first corresponding clinical evidence that IVIg fails to significantly change platelet aggregation capacity in paraproteinemic impairment. Platelet function and in-vitro bleeding time however subsequently normalized after high-dose melphalan therapy, presumably due to the general reduction of paraprotein burden.…”

Section: Discussionsupporting

confidence: 84%

Long-Term Remission of Acquired von-Willebrand's Disease and Platelet Dysfunction after High-Dose Melphalan in a Patient with Multiple Myeloma

Stratmann

Gundermann

Geisen

et al. 2019

IJHOSCR

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Background: Autologous stem cell transplantation is considered a standard of care treatment in eligible patients with multiple myeloma, but puts the patient at high risk for infections and bleeding complications. Acquired von-Willebrand's disease (AVWD) and acquired platelet dysfunction are rare bleeding disorders that are associated with lymphoproliferative disorders such as multiple myeloma. Patients with acquired bleeding disorders who are planned for ASCT to treat the underlying condition are considered at highest risk for bleeding complications, and optimal treatment strategies are not known. Materials and Methods: We summarized the diagnostic and therapeutic approach to a patient affected by AVWD and acquired platelet disorder related to multiple myeloma. The patient who was planned for ASCT presented with moderate to severe bleeding symptoms. Results: Acute bleeding episodes were successfully controlled and prevented during induction and consolidation therapy with immunoglobulins, whereas replacement of plasma-derived VW factor showed no clinical improvement. High-dose melphalan-based consolidation therapy supported with autologous stem-cell transplantation led to an immediate and sustainable rise of von-Willebrand antigen and activity and a subsequent normalization of platelet aggregation activity. After a follow-up of 40 weeks, the patient maintained normalized VW levels and platelet aggregation capacity. There were no further signs or symptoms of bleeding. Conclusion: This case report highlights the necessity for combined supportive and causal treatment in patients with AVWD and paraproteinemic PD. High-dose melphalan with autologous stem cell support may function as a treatment option in patients with myeloma-related AVWD.

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Section: Discussionsupporting

confidence: 84%

Long-Term Remission of Acquired von-Willebrand's Disease and Platelet Dysfunction after High-Dose Melphalan in a Patient with Multiple Myeloma

Stratmann

Gundermann

Geisen

et al. 2019

IJHOSCR

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“…In MM and PCD, interference of paraproteins with the platelet VWF receptor (GPIb, CD42b) and collagen binding sites (GPVI, CD36) has been shown to cause a disturbed interplay of platelet cytoadhesive receptors and their ligands. In addition, paraproteins with specificity for GPIIIa have been found and resulted in a significant bleeding diathesis .…”

Section: Discussioncontrasting

confidence: 55%

“…19,20 Although this method was questioned for a lack of sensitivity to detect certain types of platelet disorders (eg, secretion or granula defects), these defects are not typically found in MM. 7 In MM and PCD, interference of paraproteins with the platelet VWF receptor (GPIb, CD42b) and collagen binding sites (GPVI, CD36) 21,22 has been shown to cause a disturbed interplay of platelet cytoadhesive receptors and their ligands. In addition, paraproteins with specificity for GPIIIa have been found and resulted in a significant bleeding diathesis.…”

Section: Discussionmentioning

confidence: 99%

Disease progression and defects in primary hemostasis as major cause of bleeding in multiple myeloma

Hinterleitner

Pecher

Kreißelmeier

et al. 2019

European J of Haematology

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Background and objectives In patients with multiple myeloma (MM), unexpected bleeding complications remain a major issue. Since routine coagulation parameters are often inconspicuous, diagnosis and treatment of the underlying coagulation disorders are challenging. Patients and methods In our single‐center observational study, we analyzed 164 patients with MM for coagulation disorders and bleeding complications. Results Prolonged closure times (CTs), measured by PFA‐100, were the most common, abnormal coagulation test, found in 66% of bleeding patients vs 5% in non‐bleeding, followed by qualitative defects of von Willebrand factor (VWF:CB/VWF:Ag ratios), found in 34% vs 1% in the non‐bleeding group. Increased serum free light chains (SFLC) and SFLC ratios were significantly associated with prolonged CTs and acquired von Willebrand syndrome (AVWS). Prolonged CTs and AVWS were associated with disease progression, determined by dynamics of SFLC ratios (P < .001), serum creatinine level (P = .013), Beta‐2 microglobulin (P = .03), LDH (P = .016), and bone marrow infiltration (P < .001). Of note, response to myeloma therapy was frequently correlated with normalization of coagulation parameters. Conclusions Bleeding complications in MM are predominantly caused by defects in primary hemostasis and associated with disease progression. In a peri‐interventional workup, determination of CTs and VWF:CB/VWF:Ag ratios are of significant importance to assess bleeding risk.

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“…It has been postulated that the paraprotein binds to platelet receptors involved in aggregation. This leads to prolonged bleeding time and, in some patients, causes unexplained mucocutaneous bleeding or bruising or in others can cause severe bleeding, resulting in hematuria or large hematomas [52,53].…”

Section: M-protein Related Bleeding Disordersmentioning

confidence: 99%

Treatment of Patients with Monoclonal Gammopathy of Clinical Significance

Moreno

Rosiñol

Cibeira

et al. 2021

Cancers

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Monoclonal gammopathy of undetermined significance (MGUS) is defined as the presence of a monoclonal protein (M-protein) produced by a small amount of plasma cells. The majority of patients remain asymptomatic; however, a fraction of them develop clinical manifestations related to the monoclonal gammopathy despite not fulfilling criteria of multiple myeloma or other lymphoproliferative disorder. These patients constitute an emerging clinical issue coined as monoclonal gammopathy of clinical significance (MGCS). The mechanisms involved are poorly understood, and literature is scarce regarding management. The clinical spectrum involves symptoms related to renal, neurologic, skin, ocular, or bleeding manifestations, requiring a multidisciplinary approach. Treatment strategies rely on the basis of symptomatic disease and the M-protein isotype. In this review, we focus on MGCS other than renal, as the latter was earliest recognized and better known. We review the literature and discuss management from diagnosis to treatment based on illustrative cases from daily practice.

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The Effect of Paraprotein on Platelet Aggregation

Abstract: Platelet aggregation was not significantly changed was confirmed with addition of human immunoglobulins.

Cited by 7 publications

References 23 publications

Long-Term Remission of Acquired von-Willebrand's Disease and Platelet Dysfunction after High-Dose Melphalan in a Patient with Multiple Myeloma

Long-Term Remission of Acquired von-Willebrand's Disease and Platelet Dysfunction after High-Dose Melphalan in a Patient with Multiple Myeloma

Disease progression and defects in primary hemostasis as major cause of bleeding in multiple myeloma

Treatment of Patients with Monoclonal Gammopathy of Clinical Significance

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