Thrombin generation as a predictor of thromboembolic events in multiple myeloma patients

Leiba, Merav; Malkiel, Sarah; Budnik, Ivan; Rozic, Gabriela; Avigdor, Abraham; Duek, Adrian; Nagler, Arnon; Kenet, Gili; Livnat, Tami

doi:10.1016/j.bcmd.2017.03.010

Cited by 31 publications

(47 citation statements)

References 42 publications

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“…With 1 PM TF, no significant difference was found between patients with and controls, which was in agreement with Leiba et al study comparing 13 patients to 14 controls . However, Crowley et al demonstrated an increase in TG in patients with MM, attested by a significantly higher peak thrombin in 8 patients compared with 8 controls …”

Section: Discussionsupporting

confidence: 83%

“…Regarding to the published data, contradictions were noted. Leiba et al found mild but not significant elevations of TG parameters (peak thrombin and ETP) upon initiation of MM treatment in 13 patients . In addition, Tiong et al observed a significant acceleration of TG in 15 patients during treatment, attested by a significant increase in velocity index at 2 months of MM therapy compared with baseline .…”

Section: Discussionmentioning

confidence: 99%

“…It must be emphasized that during follow‐up, no thromboembolic events have been reported, except a symptomatic pulmonary embolism in one patient which occurred at diagnosis. However, the overall rate of thrombotic events during MM treatment varied between 10% and 25% depending on the series despite the thromboprophylaxis …”

Section: Discussionmentioning

confidence: 99%

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The hypercoagulable state in multiple myeloma: The contribution of thrombin generation test

Baccouche

Hadhri

Aissi

et al. 2019

Int J Lab Hematology

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Background Multiple myeloma is a hematologic malignancy which confers a high venous thromboembolic risk. This risk is linked to patient‐related factors, disease‐specific mechanisms, and antimyeloma therapy, especially immunomodulatory drugs. Some studies have suggested that the thrombin generation assay may be a predictive marker of thrombosis. This study aimed to assess the hypercoagulable state in patients with multiple myeloma at diagnosis and after myeloma therapy. Methods Thirty‐one patients with multiple myeloma were included in a prospective study and were compared with 31 matched controls with age and gender. Thrombin generation assay was performed in patients at diagnosis prior to treatment initiation and at the end of myeloma therapy, and in controls. Parameters of lag time, peak thrombin concentration, time to peak, endogenous thrombin potential, and velocity index were analyzed. Results Median age of patients at diagnosis was 58 years (11 men and 20 women). Twenty‐three patients (74%) were classified as high vascular risk and received thromboprophylaxis. No thromboembolic events have been reported during follow‐up, except a symptomatic pulmonary embolism in one patient which occurred at diagnosis. At baseline, patients with myeloma had significantly elevated velocity index as compared to controls (178 vs 128 nmol/L/min; P = .013). High‐risk patients showed an elevation of plasma thrombin generation as compared to low‐risk patients (endogenous thrombin potential = 1244 vs 1052 nmol/L/min; P = .043). Myeloma therapy did not significantly change the thrombin generation parameters. Conclusion Thrombin generation appears to be higher in patients with myeloma compared with controls, especially in high‐risk patients, and does not change significantly after treatment completion.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

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The hypercoagulable state in multiple myeloma: The contribution of thrombin generation test

Baccouche

Hadhri

Aissi

et al. 2019

Int J Lab Hematology

View full text Add to dashboard Cite

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“…We found no significant changes in TG over time. These results contrast with those of two recent studies, in which certain TG parameters (ETP and peak height) were found either to be higher for patients with MM experiencing thromboembolic events compared with those manifesting no events, or to show an increase during 3 months of MM therapy . In our opinion, these results warrant cautious appraisal in view of several methodological issues.…”

Section: Discussionmentioning

confidence: 99%

“…This test evaluates the entire course of thrombin production in adequately stimulated plasma, ie, thrombin generation (TG), and belongs to the class of global coagulation tests assessing the entire coagulation process. Observational studies of patients with cancer have found a higher basal thrombin peak (TP) and/or a higher endogenous thrombin potential (ETP) in patients subsequently manifesting VTE event, compared with patients experiencing no such event . The aim of the present study was to evaluate TG by CAT during the first three cycles of chemotherapy in patients with newly diagnosed MM (nMM), to determine whether changes in coagulability during initial treatment might be associated with thrombotic risk.…”

Section: Introductionmentioning

confidence: 99%

Thrombin generation in newly diagnosed multiple myeloma during the first three cycles of treatment: An observational cohort study

Chalayer

Tardy‐Poncet

Karlin

et al. 2019

Research and Practice in Thrombosis and Haemostasis

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BackgroundMultiple myeloma (MM) is associated with a high risk of thrombosis, particularly during the first months of treatment including immunomodulatory drugs (IMiDs). There is no consensus on prevention of thromboembolic risk in patients with de novo MM, and identification of patients requiring anticoagulant thromboprophylaxis remains challenging. Evaluating coagulability by an in vitro thrombin generation (TG) test might be a way of identifying such patients.ObjectiveTo determine whether TG assessment could reveal an increase in coagulability during the first three chemotherapy cycles.MethodsThis prospective and longitudinal observational study included patients newly diagnosed with MM. TG was determined in platelet‐rich and platelet‐poor plasma using calibrated automated thrombography with a low tissue factor (TF) concentration.ResultsSeventy‐one patients were enrolled, allowing TG analysis during 213 chemotherapy cycles. TG remained unchanged throughout follow‐up irrespective of treatment regimen, but values determined before cycles 2 and 3 were significantly higher in patients receiving iMiDs‐containing regimens. No association was found between TG and its changes and thrombosis occurrence during follow‐up: venous thrombosis in eight patients; no cardiovascular event. A significantly (87%) lower risk of venous thrombosis was observed in patients receiving prophylaxis with a low‐molecular‐weight heparin (LMWH; OR: 0.13 (95% CI: 0.02‐0.76). Neither bortezomib‐ nor dexamethasone‐containing regimens were associated with thrombotic risk. Changes in TG, as studied, were not associated with thrombotic events.ConclusionsThe only factor associated with a reduction in early thrombotic risk was prophylaxis with LMWH. The issue of how to identify patients requiring prophylactic anticoagulation remains unresolved.

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Global coagulation assays in hypercoagulable states

Lim

Donnan

Nandurkar

et al. 2022

J Thromb Thrombolysis

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Thrombin generation as a predictor of thromboembolic events in multiple myeloma patients

Cited by 31 publications

References 42 publications

The hypercoagulable state in multiple myeloma: The contribution of thrombin generation test

The hypercoagulable state in multiple myeloma: The contribution of thrombin generation test

Thrombin generation in newly diagnosed multiple myeloma during the first three cycles of treatment: An observational cohort study

Global coagulation assays in hypercoagulable states

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