Preoperative platelet dysfunction increases the benefit of aprotinin in cardiopulmonary bypass.

BACKGROUND: This study was designed to determine the benefit of aprotinin therapy in reducing bleeding during and after cardiopulmonary bypass in patients with preoperative platelet dysfunction. Platelet function involvement in the mechanism by which aprotinin acts was also investigated. METHODS: In a double-blind, randomized study, patients received high-dose aprotinin (n = 54) or placebo (n = 52). Whole blood aggregation was measured preoperatively. Platelet function and activation in both groups were assessed intraoperatively and postoperatively at five times. RESULTS: Aprotinin significantly reduced perioperative bleeding and postoperative blood transfusion. Placebo-treated patients with reduced preoperative platelet aggregation bled more postoperatively, but aprotinin reduced the bleeding in patients with normal or reduced platelet function to similar levels. Any cardiopulmonary bypass-induced changes in platelet aggregation, platelet activation as measured by P-selectin expression, and von Willebrand factor antigen and function were similar in aprotinin-treated and placebo-treated groups. CONCLUSIONS: The mechanism by which aprotinin reduced bleeding was independent of any effect on platelet function. However, aprotinin produced a greater reduction in bleeding among patients whose condition was hemostatically compromised by preoperative platelet dysfunction.

Relationship of platelet aggregation to bleeding after cardiopulmonary bypass.

Excessive bleeding after cardiopulmonary bypass operations is a persistent problem. This study assessed the influence of platelet function on blood loss for 134 patients undergoing cardiopulmonary bypass. Platelet function was measured by platelet aggregation in platelet-rich plasma and whole blood using collagen as the agonist. Adenosine triphosphate release was assessed concurrently. Measurements were made 1 day before operation and 1 hour after the cessation of cardiopulmonary bypass. Three important findings were made. First, statistically significant correlations were shown between preoperative and postoperative platelet aggregation and blood drainage for the first 3 hours postoperatively. Second, correlations were greatest when preoperative measurement was performed on whole blood and postoperative measurement was performed on platelet-rich plasma. Third, patients with reduced postoperative platelet aggregation in platelet-rich plasma had significantly greater transfusion requirements in the first 24 hours postoperatively. In defining the 16 patients who bled excessively among the 134 patients studied, the preoperative aggregation in whole blood had a sensitivity of 62%, specificity of 75%, positive predictive value of 26%, and negative predictive value of 94%. The postoperative aggregation in platelet-rich plasma had a sensitivity of 86%, specificity of 69%, positive predictive value of 28%, and negative predictive value of 97%. These results indicate that preoperative and postoperative measurement of platelet aggregation may provide a rationale for the prophylaxis or treatment of patients to reduce blood loss after cardiopulmonary bypass.

The effect of oral anticoagulant therapy on APTT results from a bedside coagulation monitor.

OBJECTIVE: The Ciba Corning 512 coagulation monitor (CC512) can be used to monitor heparin therapy by performing an activated partial thromboplastin time (APTT) at the patient's bedside. This study was designed to compare the CC512 results to results using the laboratory system. The relative sensitivities of both systems to the effect of oral anticoagulant therapy also was investigated. METHODS: Activated partial thromboplastin times were performed with both the CC512 and laboratory system on 74 specimens from patients receiving i.v. heparin therapy, and on 14 specimens from patients on warfarin only. Heparin assays were performed on 43 of the specimens from the heparinized patients. RESULTS: When a patient was receiving heparin only, the APTT results of the CC512 proved to be similar to existing laboratory methods. The CC512 APTT results of patients on warfarin only were markedly prolonged, whereas the laboratory APTTs were only slightly affected. CONCLUSION: The CC512 results were comparable to the laboratory system. However, the CC512 APTT was more sensitive to the effect of warfarin than the laboratory APTT system used in this study. CC512 APTT results on a patient receiving both oral and intravenous anticoagulation could be misleading.

A low volume specimen container suitable for monitoring the aPTT of heparinized patients.

Differences in the activated partial thromboplastin time (aPTT) were shown when blood taken from patients receiving intravenous heparin therapy was collected into 5 ml and 1 ml citrate containers. Mean aPTTs were 27% shorter with the plasma from the 1 ml citrate containers (n = 23). These results were paralleled by a 37% reduction in the mean heparin concentration (n = 11) and a 77% increase in the mean platelet factor 4 (PF4) concentration (n = 7). This phenomenon is due to increased platelet activation and subsequent increased heparin neutralization in the 1 ml citrate container. In an attempt to overcome this, the citrate was removed from a 1 ml container and replaced with a buffered tri-sodium citrate solution containing theophylline, adenosine and dipyridamole anticoagulant (CTAD). Blood from heparinized patients taken into both 5 ml citrate and 1 ml CTAD showed a correction of the shortening artefact in the low volume container. The mean aPTT of plasmas from the 1 ml CTAD container showed an increase of 10% compared with the 5 ml citrate. There was no significant difference in the mean heparin or PF4 concentrations of blood taken into either container. The 1 ml CTAD tube described is a suitable collection container for monitoring heparin in neonates or patients who are difficult to venepuncture and overcomes the neutralization of heparin in part filled low volume containers.