Skip to main content
Erschienen in: Comparative Clinical Pathology 3/2017

11.04.2017 | Brief Communication

The evolving hemostatic profile of patients with myeloma receiving treatment

verfasst von: Maeve P. Crowley, Shane Quinn, Eoin T. Coleman, Susan I. O’Shea, Oonagh M. Gilligan

Erschienen in: Comparative Clinical Pathology | Ausgabe 3/2017

Einloggen, um Zugang zu erhalten

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.
Literatur
Zurück zum Zitat 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):2691–2692PubMed 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):2691–2692PubMed
Zurück zum Zitat Blom JW, Doggen CJ, Osanto S, Rosendaal FR (2005) Malignancies, prothrombotic mutations, and the risk of venous thrombosis. JAMA 293(6):715–722CrossRefPubMed Blom JW, Doggen CJ, Osanto S, Rosendaal FR (2005) Malignancies, prothrombotic mutations, and the risk of venous thrombosis. JAMA 293(6):715–722CrossRefPubMed
Zurück zum Zitat Bottles KD, Morrissey JH (1993) Dexamethasone enhances agonist induction of tissue factor in monocytes but not in endothelial cells. Blood Coagul Fibrinolysis 4(3):405–414CrossRefPubMed Bottles KD, Morrissey JH (1993) Dexamethasone enhances agonist induction of tissue factor in monocytes but not in endothelial cells. Blood Coagul Fibrinolysis 4(3):405–414CrossRefPubMed
Zurück zum Zitat Bowbrick VA, Mikhailidis DP, Stansby G (2000) The use of citrated whole blood in thromboelastography. Anesth Analg 90(5):1086–1088CrossRefPubMed Bowbrick VA, Mikhailidis DP, Stansby G (2000) The use of citrated whole blood in thromboelastography. Anesth Analg 90(5):1086–1088CrossRefPubMed
Zurück zum Zitat 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):245–249CrossRefPubMed 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):245–249CrossRefPubMed
Zurück zum Zitat 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):249–255CrossRefPubMed 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):249–255CrossRefPubMed
Zurück zum Zitat 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):53–60CrossRefPubMed 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):53–60CrossRefPubMed
Zurück zum Zitat 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):249–255CrossRefPubMed 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):249–255CrossRefPubMed
Zurück zum Zitat 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):127–133CrossRefPubMed 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):127–133CrossRefPubMed
Zurück zum Zitat 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):152–155CrossRefPubMed 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):152–155CrossRefPubMed
Zurück zum Zitat 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):933–939CrossRefPubMed 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):933–939CrossRefPubMed
Zurück zum Zitat 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):1078–1084CrossRefPubMed 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):1078–1084CrossRefPubMed
Zurück zum Zitat 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):445–449CrossRef 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):445–449CrossRef
Zurück zum Zitat 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):29–37CrossRefPubMed 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):29–37CrossRefPubMed
Zurück zum Zitat 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):145–151CrossRefPubMed 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):145–151CrossRefPubMed
Zurück zum Zitat 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):3574–3580CrossRefPubMedPubMedCentral 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):3574–3580CrossRefPubMedPubMedCentral
Zurück zum Zitat 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):619–626PubMed 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):619–626PubMed
Zurück zum Zitat 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 133:667–670CrossRefPubMed 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 133:667–670CrossRefPubMed
Zurück zum Zitat 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):3303–3311CrossRefPubMed 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):3303–3311CrossRefPubMed
Metadaten
Titel
The evolving hemostatic profile of patients with myeloma receiving treatment
verfasst von
Maeve P. Crowley
Shane Quinn
Eoin T. Coleman
Susan I. O’Shea
Oonagh M. Gilligan
Publikationsdatum
11.04.2017
Verlag
Springer London
Erschienen in
Comparative Clinical Pathology / Ausgabe 3/2017
Print ISSN: 1618-5641
Elektronische ISSN: 1618-565X
DOI
https://doi.org/10.1007/s00580-017-2465-8

Weitere Artikel der Ausgabe 3/2017

Comparative Clinical Pathology 3/2017 Zur Ausgabe

Neu im Fachgebiet Pathologie