DETERMINATION OF PROTHROMBOTIC PHENOTYPE IN PATIENTS WITH MULTIPLE MYELOMA ON IMMUNOMODULATORY THERAPY BY THE CALIBRATED AUTOMATED THROMBOGRAM.
(Abstract release date: 05/19/16)
EHA Library. Shmeleva V. 06/09/16; 132862; E1313
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Dr. Veronika Shmeleva
Contributions
Contributions
Abstract
Abstract: E1313
Type: Eposter Presentation
Background
Patients with multiple myeloma (MM) have an increased risk of venous thromboembolism (VTE), particularly when immunomodulatory therapy is used. It is of great importance to choose proper thrombosis prophylaxis in these patients. Resistance to activated protein C (APCR) is proposed to be one of the pathogenic mechanism underlying thrombotic complications in MM patients. The Calibrated Automated Thrombography (CAT) determines the action of both procoagulant and anticoagulant factors and is now considered to reflect patient’s phenotype better than traditional coagulation tests. When thrombomodulin (TM) is used CAT becomes sensitive to all disorders of the protein C (PC) system. Clinical utility of CAT in MM patients needs further elucidation.
Aims
Aim of our study was to evaluate the prevalence of APCR and determine prothrombotic phenotype in MM patients by an integrated approach with CAT made in parallel with and without TM.
Methods
The study involved 63 patients (M/F 23/40, mean age 62,0±14,0 yr) with MM and 30 age and sex matched controls. Patients and controls gave informed consent. We divided patients in 3 groups: 30 patients with IgA associated MM, 20 patients with IgG associated MM and 13 patients with MM associated with IgG on lenalidomide treatment with prophylaxis of VTE by aspirin. CAT was done according to Hemker et al. at 5 pM TF and 4 μM phospholipids in platelet poor plasma (PPP) with PPP plasma+/-TM reagent. The procedure was carried out on an automated fluorometer (Fluoroscan Ascent, Thermolab system, Finland). Thrombin generation curves were calculated using the Thrombinoscope software (Thrombinoscope BV, The Netherlands). Lupus anticoagulants (LA), activities of FVIII, protein C and S and antithrombin were also measured. STATISTICA 6.1 was used.
Results
Importantly endogenous thrombin potential (ETP) and peak thrombin (PT) in MM patients on lenalidomide were within the normal range. Increased ETP were defined as values above 95th percentile measured in controls (i.e. >2114 nMmin in the absence of TM and >1433 nMmin in the presence of TM). Normal ranges of ETP and PT inhibition calculated in controls were 22-62% and 15-51% respectively, means values of ETP and PT inhibition were 45% and 33% respectively. Abnormalities of inhibition were more pronounced in IgA associated MM compared to IgG group without lenalidomide (41% vs 64% for ETP and 25% vs 53% for PT). The most significant changes in the protein C system activities were found in IgG group on lenalidomide (mean inhibition of ETP 36% and 24% of PT). Values below 22% for ETP inhibition and/or 15% for PT inhibition (i.e. APRC) were found in 3 (23%) of patients on lenalidomide. Though ETP and PT inhibition showed significant correlation with PC activity (R=0,51 and R=0,63 respectively), all these patients had protein C and S activities as well as FVIII activity within the normal range and no one demonstrated LA.
Conclusion
An integrated approach defining an individual’s phenotype could help in identifying patients with higher risk for thrombotic event. We suggest APCR detected by CAT to be important marker of thrombotic risk in MM patients. Whether these patients would benefit from more active primary thromboprophylaxis need further elucidation.
Session topic: E-poster
Keyword(s): Immunomodulatory thalidomide analog, Multiple myeloma, Thrombin generation, Thromboembolism
Type: Eposter Presentation
Background
Patients with multiple myeloma (MM) have an increased risk of venous thromboembolism (VTE), particularly when immunomodulatory therapy is used. It is of great importance to choose proper thrombosis prophylaxis in these patients. Resistance to activated protein C (APCR) is proposed to be one of the pathogenic mechanism underlying thrombotic complications in MM patients. The Calibrated Automated Thrombography (CAT) determines the action of both procoagulant and anticoagulant factors and is now considered to reflect patient’s phenotype better than traditional coagulation tests. When thrombomodulin (TM) is used CAT becomes sensitive to all disorders of the protein C (PC) system. Clinical utility of CAT in MM patients needs further elucidation.
Aims
Aim of our study was to evaluate the prevalence of APCR and determine prothrombotic phenotype in MM patients by an integrated approach with CAT made in parallel with and without TM.
Methods
The study involved 63 patients (M/F 23/40, mean age 62,0±14,0 yr) with MM and 30 age and sex matched controls. Patients and controls gave informed consent. We divided patients in 3 groups: 30 patients with IgA associated MM, 20 patients with IgG associated MM and 13 patients with MM associated with IgG on lenalidomide treatment with prophylaxis of VTE by aspirin. CAT was done according to Hemker et al. at 5 pM TF and 4 μM phospholipids in platelet poor plasma (PPP) with PPP plasma+/-TM reagent. The procedure was carried out on an automated fluorometer (Fluoroscan Ascent, Thermolab system, Finland). Thrombin generation curves were calculated using the Thrombinoscope software (Thrombinoscope BV, The Netherlands). Lupus anticoagulants (LA), activities of FVIII, protein C and S and antithrombin were also measured. STATISTICA 6.1 was used.
Results
Importantly endogenous thrombin potential (ETP) and peak thrombin (PT) in MM patients on lenalidomide were within the normal range. Increased ETP were defined as values above 95th percentile measured in controls (i.e. >2114 nMmin in the absence of TM and >1433 nMmin in the presence of TM). Normal ranges of ETP and PT inhibition calculated in controls were 22-62% and 15-51% respectively, means values of ETP and PT inhibition were 45% and 33% respectively. Abnormalities of inhibition were more pronounced in IgA associated MM compared to IgG group without lenalidomide (41% vs 64% for ETP and 25% vs 53% for PT). The most significant changes in the protein C system activities were found in IgG group on lenalidomide (mean inhibition of ETP 36% and 24% of PT). Values below 22% for ETP inhibition and/or 15% for PT inhibition (i.e. APRC) were found in 3 (23%) of patients on lenalidomide. Though ETP and PT inhibition showed significant correlation with PC activity (R=0,51 and R=0,63 respectively), all these patients had protein C and S activities as well as FVIII activity within the normal range and no one demonstrated LA.
Conclusion
An integrated approach defining an individual’s phenotype could help in identifying patients with higher risk for thrombotic event. We suggest APCR detected by CAT to be important marker of thrombotic risk in MM patients. Whether these patients would benefit from more active primary thromboprophylaxis need further elucidation.
Session topic: E-poster
Keyword(s): Immunomodulatory thalidomide analog, Multiple myeloma, Thrombin generation, Thromboembolism
Abstract: E1313
Type: Eposter Presentation
Background
Patients with multiple myeloma (MM) have an increased risk of venous thromboembolism (VTE), particularly when immunomodulatory therapy is used. It is of great importance to choose proper thrombosis prophylaxis in these patients. Resistance to activated protein C (APCR) is proposed to be one of the pathogenic mechanism underlying thrombotic complications in MM patients. The Calibrated Automated Thrombography (CAT) determines the action of both procoagulant and anticoagulant factors and is now considered to reflect patient’s phenotype better than traditional coagulation tests. When thrombomodulin (TM) is used CAT becomes sensitive to all disorders of the protein C (PC) system. Clinical utility of CAT in MM patients needs further elucidation.
Aims
Aim of our study was to evaluate the prevalence of APCR and determine prothrombotic phenotype in MM patients by an integrated approach with CAT made in parallel with and without TM.
Methods
The study involved 63 patients (M/F 23/40, mean age 62,0±14,0 yr) with MM and 30 age and sex matched controls. Patients and controls gave informed consent. We divided patients in 3 groups: 30 patients with IgA associated MM, 20 patients with IgG associated MM and 13 patients with MM associated with IgG on lenalidomide treatment with prophylaxis of VTE by aspirin. CAT was done according to Hemker et al. at 5 pM TF and 4 μM phospholipids in platelet poor plasma (PPP) with PPP plasma+/-TM reagent. The procedure was carried out on an automated fluorometer (Fluoroscan Ascent, Thermolab system, Finland). Thrombin generation curves were calculated using the Thrombinoscope software (Thrombinoscope BV, The Netherlands). Lupus anticoagulants (LA), activities of FVIII, protein C and S and antithrombin were also measured. STATISTICA 6.1 was used.
Results
Importantly endogenous thrombin potential (ETP) and peak thrombin (PT) in MM patients on lenalidomide were within the normal range. Increased ETP were defined as values above 95th percentile measured in controls (i.e. >2114 nMmin in the absence of TM and >1433 nMmin in the presence of TM). Normal ranges of ETP and PT inhibition calculated in controls were 22-62% and 15-51% respectively, means values of ETP and PT inhibition were 45% and 33% respectively. Abnormalities of inhibition were more pronounced in IgA associated MM compared to IgG group without lenalidomide (41% vs 64% for ETP and 25% vs 53% for PT). The most significant changes in the protein C system activities were found in IgG group on lenalidomide (mean inhibition of ETP 36% and 24% of PT). Values below 22% for ETP inhibition and/or 15% for PT inhibition (i.e. APRC) were found in 3 (23%) of patients on lenalidomide. Though ETP and PT inhibition showed significant correlation with PC activity (R=0,51 and R=0,63 respectively), all these patients had protein C and S activities as well as FVIII activity within the normal range and no one demonstrated LA.
Conclusion
An integrated approach defining an individual’s phenotype could help in identifying patients with higher risk for thrombotic event. We suggest APCR detected by CAT to be important marker of thrombotic risk in MM patients. Whether these patients would benefit from more active primary thromboprophylaxis need further elucidation.
Session topic: E-poster
Keyword(s): Immunomodulatory thalidomide analog, Multiple myeloma, Thrombin generation, Thromboembolism
Type: Eposter Presentation
Background
Patients with multiple myeloma (MM) have an increased risk of venous thromboembolism (VTE), particularly when immunomodulatory therapy is used. It is of great importance to choose proper thrombosis prophylaxis in these patients. Resistance to activated protein C (APCR) is proposed to be one of the pathogenic mechanism underlying thrombotic complications in MM patients. The Calibrated Automated Thrombography (CAT) determines the action of both procoagulant and anticoagulant factors and is now considered to reflect patient’s phenotype better than traditional coagulation tests. When thrombomodulin (TM) is used CAT becomes sensitive to all disorders of the protein C (PC) system. Clinical utility of CAT in MM patients needs further elucidation.
Aims
Aim of our study was to evaluate the prevalence of APCR and determine prothrombotic phenotype in MM patients by an integrated approach with CAT made in parallel with and without TM.
Methods
The study involved 63 patients (M/F 23/40, mean age 62,0±14,0 yr) with MM and 30 age and sex matched controls. Patients and controls gave informed consent. We divided patients in 3 groups: 30 patients with IgA associated MM, 20 patients with IgG associated MM and 13 patients with MM associated with IgG on lenalidomide treatment with prophylaxis of VTE by aspirin. CAT was done according to Hemker et al. at 5 pM TF and 4 μM phospholipids in platelet poor plasma (PPP) with PPP plasma+/-TM reagent. The procedure was carried out on an automated fluorometer (Fluoroscan Ascent, Thermolab system, Finland). Thrombin generation curves were calculated using the Thrombinoscope software (Thrombinoscope BV, The Netherlands). Lupus anticoagulants (LA), activities of FVIII, protein C and S and antithrombin were also measured. STATISTICA 6.1 was used.
Results
Importantly endogenous thrombin potential (ETP) and peak thrombin (PT) in MM patients on lenalidomide were within the normal range. Increased ETP were defined as values above 95th percentile measured in controls (i.e. >2114 nMmin in the absence of TM and >1433 nMmin in the presence of TM). Normal ranges of ETP and PT inhibition calculated in controls were 22-62% and 15-51% respectively, means values of ETP and PT inhibition were 45% and 33% respectively. Abnormalities of inhibition were more pronounced in IgA associated MM compared to IgG group without lenalidomide (41% vs 64% for ETP and 25% vs 53% for PT). The most significant changes in the protein C system activities were found in IgG group on lenalidomide (mean inhibition of ETP 36% and 24% of PT). Values below 22% for ETP inhibition and/or 15% for PT inhibition (i.e. APRC) were found in 3 (23%) of patients on lenalidomide. Though ETP and PT inhibition showed significant correlation with PC activity (R=0,51 and R=0,63 respectively), all these patients had protein C and S activities as well as FVIII activity within the normal range and no one demonstrated LA.
Conclusion
An integrated approach defining an individual’s phenotype could help in identifying patients with higher risk for thrombotic event. We suggest APCR detected by CAT to be important marker of thrombotic risk in MM patients. Whether these patients would benefit from more active primary thromboprophylaxis need further elucidation.
Session topic: E-poster
Keyword(s): Immunomodulatory thalidomide analog, Multiple myeloma, Thrombin generation, Thromboembolism
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