Efficacy of anticoagulants and platelet inhibitors in cancer-induced thrombosis.
The efficacy of anticoagulants, low-molecular-weight heparins (LMWHs), the antiplatelet glycoprotein IIb/IIIa antagonist, or combinations on cancer-activated thrombosis was determined using thromboelastography. The LMWHs tinzaparin and enoxaparin (0.179, 1.79, 17.9 microg) were incubated in human citrated whole blood (n = 4) and then activated by calcium chloride (11 mmol/l) or Colo205 (cell count 10). Concentrations of 9.9, 17.9 and 179 microg glycoprotein IIb/IIIa antagonist, XV454, and combinations with each LMWH were carried out and activated under the same conditions. The experiment was repeated with tissue factor substituting for the Colo205 to induce platelet/fibrin clot formation. Parameters tested in the thrombelastography analysis included clotting time, rate of clot formation due to fibrin formation, clot kinetics, and clot strength related to platelet count (maximum amplitude). Tinzaparin (1.79 microg), enoxaparin (1.79 microg), and XV454 (17.9 microg) significantly reduced the angle by 64, 26 and 27%, respectively, in cancer-induced clotting. Significant reductions in the maximum amplitude occurred in tinzaparin 1.79 microg (31%), enoxaparin 1.79 microg (11%), and XV454 17.9 microg (59%). An overall antithrombotic additive effect occurred when each LMWH (1.79 microg) was combined with XV454 (17.9 microg). The results between cancer-activated and tissue factor-activated blood were similar. The study concludes that an additive effect is present between LMWHs and a glycoprotein IIb/IIIa antagonist in reducing cancer-mediated thrombosis.
Cloonan
Melissa E
ME
Pharmaceutical Research Institute at Albany College of Pharmacy, 106 New Scotland Avenue, Albany, NY 12208, USA.
DiNapoli
Marianne
M
Mousa
Shaker A
SA
D000409:Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D004359:Drug Therapy, Combination; D017984:Enoxaparin / Q000494:pharmacology*; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology*; D006801:Humans; D009369:Neoplasms / Q000097:blood*; D010080:Oxazoles / Q000494:pharmacology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D013916:Thrombelastography; D013925:Thromboplastin / Q000502:physiology; D013927:Thrombosis / Q000517:prevention & control*; D000078222:Tinzaparin
D017984:Enoxaparin; D006495:Heparin, Low-Molecular-Weight; D010080:Oxazoles; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; C116340:XV 454; D000078222:Tinzaparin; D013925:Thromboplastin; D000409:Alanine