Goldstein, Sheldon

Introduction: Post-Cardiopulmonary Bypass (CPB) coagulopathy results in bleeding, transfusion and re-exploration, and increases morbidity, mortality and cost. Some studies have reported a relationship between individual factor levels and chest tube drainage as a marker of bleeding, but few have reported that relationship for multiple factors. Methods: With IRB approval and informed consent, 98 patients, ages 18 - 85, undergoing cardiac surgery with cardiopulmonary bypass (CPB) were studied. Factor levels measured five minutes post-protamine included fibrinogen (FIB), and factors II, V, VII, VIII, Von Willebrand Factor Antigen (VWF Ag), Ristocetin Cofactor (VWF Activity), IX, X, XI and XIII. Linear regression models examined the relationship between factor levels and post-op chest tube drainage over 24 hours as a surrogate marker for bleeding. An effect size (ES) was calculated so that each factor deficiency multiplied by the ES and the patient's weight in kg would estimate the contribution of that factor to bleeding. Factors were ranked from most to least impact on bleeding. Conversely, said ES would estimate the decrease in bleeding achieved by a percentage increase in a deficient factor level if such factor was known to be deficient. Results: F:II was 1st (most associated with bleeding), ES = -0.137, 95% CI -0.214 - -0.059, p < 0.001; F:X was 2nd, ES = -0.130, 95% CI -0.202 - -0.058, p < 0.001; F:VII ES = -0.121, 95% CI -0.198 - -0.045, p = 0.002; F:XI ES = -0.109, 95% CI -0.16 - -0.058, p < 0.001; F:IX ES = -0.100; 95% CI -0.135 - -0.065, p < 0.001; F:V ES = - 0.065; 95% CI -0.114 - -0.016, p = 0.011; F:XIII ES = - 0.055; 95% CI -0.099 - -0.011, p = 0.016; FIB ES = - 0.042; 95% CI -0.063 - -0.022, p < 0.001; F:VIII ES = - 0.007; 95% CI -0.020 - 0.006, p = 0.318; VWF Ag ES = 0.002; 95% CI -0.016 - 0.019, p = 0.855; VWF Activity ES = 0.004; 95% CI -0.015 - 0.023, p = 0.671. Conclusions: Factors VIII, VWF Ag and Ristocetin Cofactor demonstrated no relationship with bleeding, perhaps because they are elevated as acute-phase reactants. In theory, raising F:II level post-CPB by 30% in an 80 kg patient might decrease bleeding by 328 ml, and raising F:X level post-CPB by 30% in an 80 kg patient might decrease bleeding by 312 ml, etc. A weakness of this study is that the sample size was too small to perform a multi-variate analysis considering all factor levels. Still, the data suggest four-factor prothrombin complex concentrate (PCC) might be a more effective treatment for post-CPB coagulopathy than FFP. The data do not confirm cause and effect; that would require a large study with control and treatment arms. If multiple factor levels could be measured in a rapid and cost-effective manner it might aid in targeted treatment of post-CPB coagulopathy. The data suggest that work should be performed to better elucidate the contribution of coagulation factor deficiencies to post-CPB bleeding, as improved treatment of such factor deficiencies might decrease bleeding and transfusion requirements.

Abstract A device that would provide a rapid evaluation of hemostasis would greatly aid physicians in making scientific decisions regarding transfusion therapy; especially with perioperative bleeding. We performed a prospective in-vitro study with reconstituted, recalcified whole blood (n = 6) separated into samples containing specific deficiencies in platelets, plasma, lyophilized platelets and lyophilized plasma such that the concentrations of the specific platelet or plasma were 0%, 10%, 30%, 50%, and 100%. The whole blood was obtained from consenting healthy volunteers. Samples from the various concentrations of the reconstituted blood were subjected to the following point of care coagulation tests: activated clotting time (ACT), thromboelastogram (TEG), laboratory prothrombin time (PT), laboratory activated partial thromboplastin time (APTT) and Signature+ PT. ACT’s were performed for each of four celite doses (1.5 mg, 3.0 mg, 6.0 mg and 12 mg celite). The four dose celite ACT’s were performed in duplicate and the mean recorded. The TEG was performed in duplicate, and the mean was recorded. The signature+ PT was performed in duplicate, and the mean recorded. The laboratory PT, aPTT, Platelet Count and Fibrinogen were performed once each. ACT values were analyzed within each of the three preparations using analysis of variance. This assessed the strength of the relationship between blood constituent concentration and ACT, and determined whether this relationship differed across varying amounts of celite. Other coagulation parameters including TEG (mA), PT and APTT were analyzed using analysis of variance with a single term for blood constituent concentration. This model determined the strength of the relationship between these coagulation parameters and blood constituent concentration. In addition, the kaolin activated TEG and the signature+ PT was evaluated to determine the strength of the relationship between these tests and the variations in platelet and plasma concentrations. There was a significant correlation between the plasma, platelets and lyophilized plasma concentrations and ACT results (all p < 0.001). There was a significant correlation between plasma platelets and lyophilized plasma and the TEG MA and angle (all p < 0.028). There was a significant correlation between laboratory PT and APTT and plasma, platelets, and lyophilized plasma, lyophilized platelets (all p < 0.001). There was a significant correlation between the Signature+ PT and plasma, lyophilized platelets, and lypholized plasma and platelets (all p < 0.005), (figure 1). A better point of care coagulation device that is based on in-vitro additions of various therapies, and comparison of their effects on coagulation tests may provide better treatment of the bleeding patient. The Signature+ PT could provide the endpoint for such a device whereas the ACT was nonspecific and had a small change in results with large changes in plasma concentration. The additional benefit of lypholized plasma to behave similarly to human plasma may allow such a device to be built. Figure Figure