Longer Procoagulant Phospholipid-dependent Clotting Time, Lower Endogenous Thrombin Potential and Higher Tissue Factor Pathway Inhibitor Concentrations Are Associated with Increased VTE Occurrence in Patients with Newly Diagnosed Multiple Myeloma:...

Overview

Journal Blood Cancer J

Date 2018 Nov 9

PMID 30405097

Citations 11

Authors

Despina Fotiou

Theodoros N Sergentanis

Loula Papageorgiou

Kimon Stamatelopoulos

Maria Gavriatopoulou

Efstathios Kastritis

Theodora Psaltopoulou

Stella Salta

Patrick Van Dreden

Rabiatou Sangare

Annette K Larsen

Evangelos Terpos

Ismail Elalamy

Meletios A Dimopoulos

Grigoris T Gerotziafas

Affiliations

Soon will be listed here.

Abstract

Venous thromboembolism (VTE) is a common complication in newly diagnosed symptomatic multiple myeloma (NDMM) patients. We explored cellular and plasma hypercoagulability in NDMM patients to identify relevant biomarkers that can be used in combination with clinical factors in the development of a risk assessment model (RAM) for VTE. Untreated patients (n = 144) with NDMM were prospectively enrolled, baseline biomarkers prior to anti-myeloma treatment and thromboprophylaxis initiation were obtained. These were compared against values in a group of healthy individuals with similar age and sex distribution. The primary study end point was symptomatic VTE occurrence. At 12-month follow-up cumulative VTE rate was 10.4%. NDMM patients showed biological signs of cellular and plasma hypercoagulability and endothelial cell activation. Procoagulant phospholipid clotting time (Procoagulant-PPL) was shorter, P-selectin levels lower and thrombin generation attenuated overall compared to healthy subjects. Longer Procoag-PPL, lower endogenous thrombin potential (ETP), and higher levels of tissue factor pathway inhibitor (TFPI) were associated with VTE occurrence. Multivariate analysis showed that Procoag-PPL and ETP were independent risk factors for VTE. We conclude that Procoag-PPL and ETP can be prospectively incorporated into a RAM for VTE in MM in combination with clinical and disease risk factors.

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References

Syrigos K, Grapsa D, Sangare R, Evmorfiadis I, Larsen A, Van Dreden P . Prospective Assessment of Clinical Risk Factors and Biomarkers of Hypercoagulability for the Identification of Patients with Lung Adenocarcinoma at Risk for Cancer-Associated Thrombosis: The Observational ROADMAP-CAT Study. Oncologist. 2018; 23(11):1372-1381. PMC: 6291320. DOI: 10.1634/theoncologist.2017-0530. View

Huang H, Li H, Li D . Effect of serum monoclonal protein concentration on haemostasis in patients with multiple myeloma. Blood Coagul Fibrinolysis. 2015; 26(5):555-9. DOI: 10.1097/MBC.0000000000000296. View

Perrin J, Depasse F, Lecompte T . Large external quality assessment survey on thrombin generation with CAT: further evidence for the usefulness of normalisation with an external reference plasma. Thromb Res. 2015; 136(1):125-30. DOI: 10.1016/j.thromres.2014.12.015. View

Zamagni E, Brioli A, Tacchetti P, Zannetti B, Pantani L, Cavo M . Multiple myeloma, venous thromboembolism, and treatment-related risk of thrombosis. Semin Thromb Hemost. 2011; 37(3):209-19. DOI: 10.1055/s-0031-1273085. View

Dargaud Y, Wolberg A, Luddington R, Regnault V, Spronk H, Baglin T . Evaluation of a standardized protocol for thrombin generation measurement using the calibrated automated thrombogram: an international multicentre study. Thromb Res. 2012; 130(6):929-34. DOI: 10.1016/j.thromres.2012.07.017. View

Wannez A, Devalet B, Bouvy C, Laloy J, Bihin B, Chatelain B . Eculizumab decreases the procoagulant activity of extracellular vesicles in paroxysmal nocturnal hemoglobinuria: A pilot prospective longitudinal clinical study. Thromb Res. 2017; 156:142-148. DOI: 10.1016/j.thromres.2017.06.013. View

Palumbo A, Rajkumar S, Dimopoulos M, Richardson P, San Miguel J, Barlogie B . Prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma. Leukemia. 2007; 22(2):414-23. DOI: 10.1038/sj.leu.2405062. View

Mannucci P, Cattaneo M, Canciani M, Maniezzo M, Vaglini M, Cascinelli N . Early presence of activated ('exhausted') platelets in malignant tumors (breast adenocarcinoma and malignant melanoma). Eur J Cancer Clin Oncol. 1989; 25(10):1413-7. DOI: 10.1016/0277-5379(89)90098-9. View

Auwerda J, Yuana Y, Osanto S, de Maat M, Sonneveld P, Bertina R . Microparticle-associated tissue factor activity and venous thrombosis in multiple myeloma. Thromb Haemost. 2010; 105(1):14-20. DOI: 10.1160/TH10-03-0187. View

10.

Bagot C, Leishman E . Establishing a reference range for thrombin generation using a standard plasma significantly improves assay precision. Thromb Res. 2015; 136(1):139-43. DOI: 10.1016/j.thromres.2015.04.020. View

11.

Khorana A, Kuderer N, Culakova E, Lyman G, Francis C . Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood. 2008; 111(10):4902-7. PMC: 2384124. DOI: 10.1182/blood-2007-10-116327. View

12.

Gerotziafas G, Depasse F, Busson J, Leflem L, Elalamy I, Samama M . Towards a standardization of thrombin generation assessment: the influence of tissue factor, platelets and phospholipids concentration on the normal values of Thrombogram-Thrombinoscope assay. Thromb J. 2005; 3:16. PMC: 1291409. DOI: 10.1186/1477-9560-3-16. View

13.

Ay C, Simanek R, Vormittag R, Dunkler D, Alguel G, Koder S . High plasma levels of soluble P-selectin are predictive of venous thromboembolism in cancer patients: results from the Vienna Cancer and Thrombosis Study (CATS). Blood. 2008; 112(7):2703-8. DOI: 10.1182/blood-2008-02-142422. View

14.

Falanga A, Marchetti M . Venous thromboembolism in the hematologic malignancies. J Clin Oncol. 2009; 27(29):4848-57. DOI: 10.1200/JCO.2009.22.8197. View

15.

De Stefano V, Za T, Rossi E . Venous thromboembolism in multiple myeloma. Semin Thromb Hemost. 2014; 40(3):338-47. DOI: 10.1055/s-0034-1370793. View

16.

Spronk H, Dielis A, De Smedt E, Van Oerle R, Fens D, Prins M . Assessment of thrombin generation II: Validation of the Calibrated Automated Thrombogram in platelet-poor plasma in a clinical laboratory. Thromb Haemost. 2008; 100(2):362-4. View

17.

Terpos E, Kleber M, Engelhardt M, Zweegman S, Gay F, Kastritis E . European Myeloma Network guidelines for the management of multiple myeloma-related complications. Haematologica. 2015; 100(10):1254-66. PMC: 4591757. DOI: 10.3324/haematol.2014.117176. View

18.

Seigneur M, Constans J, Blann A, Renard M, Pellegrin J, Amiral J . Soluble adhesion molecules and endothelial cell damage in HIV infected patients. Thromb Haemost. 1997; 77(4):646-9. View

19.

Dimopoulos M, Palumbo A, Attal M, Beksac M, Davies F, Delforge M . Optimizing the use of lenalidomide in relapsed or refractory multiple myeloma: consensus statement. Leukemia. 2011; 25(5):749-60. DOI: 10.1038/leu.2011.3. View

20.

Rousseau A, Favier R, Van Dreden P . Elevated circulating soluble thrombomodulin activity, tissue factor activity and circulating procoagulant phospholipids: new and useful markers for pre-eclampsia?. Eur J Obstet Gynecol Reprod Biol. 2009; 146(1):46-9. DOI: 10.1016/j.ejogrb.2009.06.001. View