Skip to main content
Log in

The evolving hemostatic profile of patients with myeloma receiving treatment

  • Brief Communication
  • Published:
Comparative Clinical Pathology Aims and scope Submit manuscript

Abstract

Thrombosis is a well-described complication of myeloma and the drugs used to treat it. The causes are multifactorial. Traditional screening tests of coagulation, such as the prothrombin time and the activated partial thromboplastin time, are known to be poor at assessment of thrombosis risk. It has been suggested that global measures of haemostasis, such as thromboelastography, may have a role to play in the assessment of this risk. The aim of this study was to look at traditional measures of haemostasis, that measure certain parts of the coagulation cascade, as well as thromboelastography, to see if a coagulation profile of patients with myeloma could be established. Sixteen consecutive patients with symptomatic myeloma were recruited and had their coagulation parameters measured at baseline and following four consecutive cycles of treatment. IgG was the most common subtype of myeloma. Almost two thirds received an immunomodulatory agent and the majority of patients (13/16) received some form of thromboprophylaxis. The median FVIII:C level was elevated at baseline. It significantly increased after one cycle of chemotherapy (p = 0.02). This pattern was replicated with VWF:Ag (p = 0.039). Thromboelastography demonstrated a significant shortening of the mean k time (p = 0.015) and a mean increase in the alpha angle (p = 0.032) between baseline and after two cycles of treatment consistent with increasing hypercoagulability. Markers of hypercoagulability are increased in patients with myeloma and further increase when they commence treatment. There is a suggestion that after this initial increase, as the burden of myeloma decreases, so do these markers of hypercoagulability.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

References

  • Arkel YS, Ku DH, Thurston AL (2003) The effect of thalidomide on tissue factor activity in Mono Mac 6 cells and the relationship to tumor necrosis factor (TNF)-alpha-stimulated cells. JTH 1(12):2691–2692

    CAS  PubMed  Google Scholar 

  • Blom JW, Doggen CJ, Osanto S, Rosendaal FR (2005) Malignancies, prothrombotic mutations, and the risk of venous thrombosis. JAMA 293(6):715–722

    Article  CAS  PubMed  Google Scholar 

  • Bottles KD, Morrissey JH (1993) Dexamethasone enhances agonist induction of tissue factor in monocytes but not in endothelial cells. Blood Coagul Fibrinolysis 4(3):405–414

    Article  CAS  PubMed  Google Scholar 

  • Bowbrick VA, Mikhailidis DP, Stansby G (2000) The use of citrated whole blood in thromboelastography. Anesth Analg 90(5):1086–1088

    Article  CAS  PubMed  Google Scholar 

  • Catovsky D, Ikoku NB, Pitney WR, Galton DA (1970) Thromboembolic complications in myelomatosis. BMJ 3(5720):438–439

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Crowley MP, Quinn S, Coleman E, Eustace JA, Gilligan OM, O’Shea SI (2015) Differing coagulation profiles of patients with monoclonal gammopathy of undetermined significance and multiple myeloma. J Thromb Thrombolysis 39(2):245–249

    Article  PubMed  Google Scholar 

  • van Giezen JJ, Brakkee JG, Dreteler GH, Bouma BN, Jansen JW (1994) Dexamethasone affects platelet aggregation and fibrinolytic activity in rats at different doses which is reflected by their effect on arterial thrombosis. Blood Coagul Fibrinolysis 5(2):249–255

    Article  PubMed  Google Scholar 

  • Golder M, Mewburn J, Lillicrap D (2013) In vitro and in vivo evaluation of the effect of elevated factor VIII on the thrombogenic process. Thromb Haemost 109(1):53–60

    Article  CAS  PubMed  Google Scholar 

  • Gomperts ED, Shulman G, Lynch SR (1976) Factor VIII and factor-VIII-related antigen in multiple myelomatosis and related conditions. Br J Haematol 32(2):249–255

    Article  CAS  PubMed  Google Scholar 

  • Kerachian MA, Cournoyer D, Harvey EJ, Chow TY, Neagoe PE, Sirois MG et al (2009) Effect of high dose dexamethasone on endothelial hemostatic gene expression and neutrophil adhesion. J Steroid Biochem Mol Biol 116(3–5):127–133

    Article  CAS  PubMed  Google Scholar 

  • Koster T, Blann AD, Briet E, Vandenbroucke JP, Rosendaal FR (1995) Role of clotting factor VIII in effect of von Willebrand factor on occurrence of deep-vein thrombosis. Lancet 345(8943):152–155

    Article  CAS  PubMed  Google Scholar 

  • Larocca A, Cavallo F, Bringhen S, Di Raimondo F, Falanga A, Evangelista A et al (2012) Aspirin or enoxaparin thromboprophylaxis for patients with newly diagnosed multiple myeloma treated with lenalidomide. Blood 119(4):933–939

    Article  CAS  PubMed  Google Scholar 

  • van Marion AM, Auwerda JJ, Lisman T, Sonneveld P, de Maat MP, Lokhorst HM et al (2008) Prospective evaluation of coagulopathy in multiple myeloma patients before, during and after various chemotherapeutic regimens. Leuk Res 32(7):1078–1084

    Article  PubMed  Google Scholar 

  • Minnema MC, Fijnheer R, De Groot PG, Lokhorst HM (2003) Extremely high levels of von Willebrand factor antigen and of procoagulant factor VIII found in multiple myeloma patients are associated with activity status but not with thalidomide treatment. Journal of thrombosis and hemostasis : JTH 1(3):445–449

    Article  CAS  Google Scholar 

  • Rajkumar SV, Jacobus S, Callander NS, Fonseca R, Vesole DH, Williams ME et al (2010) Lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone as initial therapy for newly diagnosed multiple myeloma: an open-label randomised controlled trial. The lancet oncology 11(1):29–37

    Article  CAS  PubMed  Google Scholar 

  • Reddy KV, Bhattacharjee G, Schabbauer G, Hollis A, Kempf K, Tencati M et al (2004) Dexamethasone enhances LPS induction of tissue factor expression in human monocytic cells by increasing tissue factor mRNA stability. J Leukoc Biol 76(1):145–151

    Article  CAS  PubMed  Google Scholar 

  • Robak M, Trelinski J, Chojnowski K (2012) Hemostatic changes after 1 month of thalidomide and dexamethasone therapy in patients with multiple myeloma. Med Oncol 29(5):3574–3580

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Swystun LL, Shin LY, Beaudin S, Liaw PC (2009) Chemotherapeutic agents doxorubicin and epirubicin induce a procoagulant phenotype on endothelial cells and blood monocytes. JTH. 7(4):619–626

    CAS  PubMed  Google Scholar 

  • Trelinski J, Misiewicz M, Robak M, Smolewski P, Chojnowski K (2014) Assessment of rotation thromboelastometry (ROTEM) parameters in patients with multiple myeloma at diagnosis. Thromb Res 133:667–670

    Article  CAS  PubMed  Google Scholar 

  • Woodley-Cook J, Shin LY, Swystun L, Caruso S, Beaudin S, Liaw PC (2006) Effects of the chemotherapeutic agent doxorubicin on the protein C anticoagulant pathway. Mol Cancer Ther 5(12):3303–3311

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Maeve P. Crowley.

Ethics declarations

Funding

This study was funded (in part) by an unrestricted educational grant that Maeve P Crowley received.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Conflict of interest

Maeve P Crowley received an unrestricted educational grant from Leo Pharmaceuticals. Shane Quinn, Eoin Coleman, Susan I O Shea and Oonagh M Gilligan have no conflicts of interest to declare.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Crowley, M.P., Quinn, S., Coleman, E.T. et al. The evolving hemostatic profile of patients with myeloma receiving treatment. Comp Clin Pathol 26, 713–717 (2017). https://doi.org/10.1007/s00580-017-2465-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00580-017-2465-8

Keywords

Navigation