Detection of Carboxyhemefibrinogen and Methemefibrinogen in a Patient with Thrombosis of a HeartMate II Ventricular Assist Device

Abstract

Ventricular assist device (VAD) thrombosis is a devastating, potentially fatal complication suffered by patients requiring mechanical circulatory support. We present a patient with thrombosis of a HeartMate II VAD with concurrent hemolysis and increased carbon monoxide formation. Using a specialized thrombelastographic assay, we detected marked plasmatic hypercoagulability mediated in part by the formation of carboxyhemefibrinogen.

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].…”

“…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].…”

“…Also of interest, when hematin (an HO-1 inducer) has been administered to treat acute porphyria, phlebitis at the injection site has been noted [81], further when hematin in similar doses was administered to healthy volunteers, a picture of intravascular coagulation occurred, with 45% of the subjects suffering thrombophlebitis [82]. Taken as a whole, in patient populations known to be at risk of thrombotic events, both plasmatic hypercoagulability and COHF formation have been identified [71][72][73][74][75][76], and patients exposed to HO-1 induction also exhibit signs of hypercoagulability [80][81][82].…”

“…4), with methods used to generate these images as previously cited [84][85][86]. Considered together, these investigations involved conditions or disease states wherein increased CO would be expected to be present, resulting in thrombus ultrastructure (e.g., finer or matted fibers) consistent with enhanced clot strength demonstrated in vitro [48,[51][52][53][54][55][56][57]67,68,[70][71][72][73][74][75][76] or in vivo [68,69] following CO exposure.…”