Plasmatic hypercoagulation in patients with breast cancer

Abstract

Breast cancer is an important health threat to women worldwide, and is associated with a 9-14% incidence of thrombophilia. Of interest, patients with breast cancer have been noted to have an increase in endogenous carbon monoxide production via upregulation of heme oxygenase-1 activity. Given that it has been demonstrated that carbon monoxide enhances plasmatic coagulation in vitro and in vivo, we sought to determine whether patients with breast cancer had an increase in endogenous carbon monoxide and concurrent plasmatic hypercoagulability. Breast cancer patients who were not smokers scheduled to undergo partial or complete mastectomy (n = 18) had 15 ml of whole blood collected via an indwelling intravenous catheter and anticoagulated with sodium citrate. Whole blood was centrifuged and citrated plasma assessed with a thromboelastometric method to measure coagulation kinetics and the formation of carboxyhemefibrinogen. Breast cancer patients were determined to have an abnormally increased carboxyhemoglobin concentration of 2.5 ± 1.3%, indicative of heme oxygenase-1 upregulation. Breast cancer patient plasma on average clotted 73% more quickly and had 32% stronger thrombus strength than normal individual (n = 30) plasma. Further, 44% of breast cancer patients had plasma clot strength that exceeded the 95% confidence interval value observed in normal individuals, and 75% of this hypercoagulable subgroup had carboxyhemefibrinogen formation. Future investigation of the role played by heme oxygenase-1-derived carbon monoxide in the pathogenesis of breast cancer-related thrombophilia is warranted.

Carbon monoxide: Anticoagulant or procoagulant?

“…Sixth, in an investigation of 19 patients with thoracic tumors, it was determined that 84% had plasmatic hypercoagulability, 44% of Nielsen et al 15 15 these hypercoagulable patients had COHF formation, and the average COHb concentration was 2.10.6% [76]. In all these clinical situations CO exposure was significant, either as a result of combustion [71] or hemolysis/tumor cell HO-1 upregulation [72][73][74][75][76]. Of particular interest, in the case of exposure of blood to prosthetic biomaterials (e.g., prosthetic heart valves, ventricular assist devices, artificial hearts), there is always the need for anticoagulation, low grade hemolysis is present, and circulating COHb concentrations between 2-3% are observed as recently reviewed [80].…”

“…Specific details concerning the conduct of the thrombelastograph-based assay have been previously described [61,71,[73][74][75]. 13 of CO, acting via a heme-like mechanism [63][64][65][66].…”

“…Utilizing the aforementioned, thrombelastographically-based assay of plasmatic hypercoagulability and COHF formation [61], the role of excessive exogenous or endogenous CO exposure was determined in a variety of settings [71][72][73][74][75]. First, twenty healthy smokers without history of thrombotic illness had their plasmatic coagulation analyzed, with the finding that after smoking two cigarettes within a 90 minute period, 45%…”

“…Second, a patient with a left ventricular assist device presented with gross hemolysis and partial pump thrombosis; the COHb varied between 3.1-3.8% during clinical care, and both hypercoagulability and COHF formation were detected [72]. Third, it was serendipitously noted that a patient undergoing removal of thyroid cancer had plasmatic hypercoagulability; this patient had a COHb of 2.4% and was found to have COHF formation [73]. Fourth, in an investigation involving eighteen patients with breast cancer, it was determined that 44% had plasmatic hypercoagulability, 50% had COHF formation, 33% had both hypercoagulability and COHF formation, and the average COHb concentration was 2.51.3% [73].…”

“…Third, it was serendipitously noted that a patient undergoing removal of thyroid cancer had plasmatic hypercoagulability; this patient had a COHb of 2.4% and was found to have COHF formation [73]. Fourth, in an investigation involving eighteen patients with breast cancer, it was determined that 44% had plasmatic hypercoagulability, 50% had COHF formation, 33% had both hypercoagulability and COHF formation, and the average COHb concentration was 2.51.3% [73]. Fifth, in a similarly designed investigation of twenty patients with brain tumors, it was determined that 50% had plasmatic hypercoagulability, 60% had COHF formation, 25% had both hypercoagulability and COHF formation, and the average COHb concentration was 1.50.3% [75].…”