Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis
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Blood Coagul. Fibrinolysis · Dec 2011
Egyptian experience of reliability of 4T's score in diagnosis of heparin induced thrombocytopenia syndrome.
To evaluate the utility of the 4Ts clinical scoring system as a pretest probability method for detection of heparin-induced thrombocytopenia (HIT). Medical and surgical inpatients and outpatients at Kasr El Eini hospital. This single-centre series of 50 HIT testing referrals assessed combination of clinical score (thrombocytopenia, timing, thrombosis, other causes of thrombocytopenia not evident; 4T's), Heparin platelet factor 4 (H-PF4) rapid particle gel immunoassay (PaGIA) and 14C serotonin release assay (SRA) to develop a practical and well tolerated diagnostic strategy for HIT. ⋯ The negative predictive value of a low 4T's score was 100%, effectively ruling out HIT. A low 4Ts score supports low probability of HIT based on the results of the PaGIA and SRA. Overall, the interrater reliability of the scoring system was fair.
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Blood Coagul. Fibrinolysis · Dec 2011
Carbon monoxide and nitric oxide modulate α₂-antiplasmin and plasmin activity: role of heme.
Cigarette smoke and carbon monoxide (CO) released from tricarbonyldichlororuthenium (II) dimer (CORM-2) attenuate fibrinolysis. The purpose of the present study was to determine whether CO diminished fibrinolysis by enhancement of α₂-antiplasmin via a putative heme group. Plasma, isolated α₂-antiplasmin and isolated plasmin were exposed to CO released from CORM-2 and nitric oxide (NO) via a NO donor to induce carboxyheme and metheme states, respectively. ⋯ CO elicits hypofibrinolysis by enhancing α₂-antiplasmin activity and decreasing plasmin activity. On the basis of the responses to NO and LC-MS/MS data, it is highly likely that both enzymes are modulated by attached heme groups. Efforts to develop methods to detect CO-mediated hypercoagulability are ongoing, with the goal of identifying populations at risk of thrombotic morbidity secondary to cigarette smoking.
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Blood Coagul. Fibrinolysis · Dec 2011
Carbon monoxide-releasing molecule-2 enhances coagulation in rabbit plasma and decreases bleeding time in clopidogrel/aspirin-treated rabbits.
Administration of carbon monoxide derived from carbon monoxide-releasing molecules has been demonstrated to enhance coagulation in vitro at small concentrations (100-200 μmol/l) in human and rabbit plasma. We sought to determine if carbon monoxide-releasing molecule-2 [tricarbonyldichlororuthenium (II) dimer, CORM-2] would improve coagulation in rabbit plasma in vitro via thrombelastography and in an in vivo preclinical rabbit model of ear bleeding time following administration of clopidogrel (20 mg/kg) with aspirin (10 mg/kg) via gavage. Addition of 100 μmol/l CORM-2 to rabbit plasma significantly improved coagulation. ⋯ Bleeding time significantly decreased to 2.6 ± 0.6 min, 5 min after administration of CORM-2 (10 mg/kg; 279 μmol/l 'best-case' instantaneous concentration) intravenously. CORM-2 enhances plasmatic coagulation in a manner similar to that of human plasma in vitro, and plasmatic coagulation is enhanced in vivo by CORM-2 as well. Additional preclinical investigation of the effects of CORM-2 on coagulopathy (e.g. heparin or hemodilution mediated) utilizing this rabbit model is planned.
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Blood Coagul. Fibrinolysis · Dec 2011
Multicenter StudyObservational study of fibrinogen concentrate in massive hemorrhage: evaluation of a multicenter register.
In acute hemorrhage, a critical decrease in fibrinogen often induces acquired coagulopathy. Fibrinogen concentrate has been used to supplement fibrinogen during massive hemorrhage. However, there are limited data on the utilization of fibrinogen concentrate in this setting. ⋯ Clinical application of fibrinogen concentrate in bleeding patients is included within a multimodal therapeutic concept. High levels of fibrinogen are necessary in order to reach therapeutic goals. In bleeding patients, higher plasma fibrinogen might be associated with higher rates of survival.
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Blood Coagul. Fibrinolysis · Dec 2011
Redox-based thrombelastographic method to detect carboxyhemefibrinogen-mediated hypercoagulability.
Cigarette smoking is associated with plasmatic hypercoagulability, and carbon monoxide has been demonstrated to enhance coagulation by binding to a fibrinogen-bound heme. Our objective was to design and test a redox-based method to detect carboxyhemefibrinogen. Normal, pooled, citrated plasma was exposed to 0-100 μmol/l carbon monoxide releasing molecule-2 (tricarbonyldichlororuthenium (II) dimer; CORM-2) before or after exposure to the organic reductant phenylhydroxylamine (PHA, 0-30 mmol/l), a compound that rapidly converts Fe(+2) to Fe(+3) in heme. ⋯ Conversion of fibrinogen-bound to the metheme state alone decreased G by 34.3-38.9% following exposure to 10-30 mmol/l PHA. Conversion of fibrinogen-bound heme Fe(+2) to Fe(+3) with PHA abrogated carbon monoxide-mediated increases in clot strength. Clinical trials are planned to investigate smoking individuals to mechanistically link carboxyhemefibrinogen formation with in-vitro hypercoagulability.