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J Thorac Cardiovasc Surg 1996;111:493-494
© 1996 Mosby, Inc.

Letters to the Editor

Individualized patient heparinization and protamine reversal

Departments of Anesthesiology,
Internal Medicine, Pathology, and Surgery
Washington University School of Medicine,
St. Louis, MO 63110

Reply to the Editor:

We support Martin and colleagues' recommendation that clinicians reexamine the anticoagulation protocols at their institutions. This contention is supported not only by our study ¹ but also by the recent study of Jobes and coworkers. ² In response to the question regarding the role of heparin as a cause of bleeding, we agree that residual heparin may be a potential cause of excessive bleeding after cardiopulmonary bypass and should be evaluated with a sensitive assay (we used the heparinase activated clotting time). We do not believe that heparin was the cause of bleeding in the control group (C) however, because these patients actually received much less heparin than did patients in our intervention group (I). In patients with demonstrated excessive intraoperative bleeding (n = 101), our laboratory-based thrombin time assay, which is exquisitely sensitive to heparin (measurements prolonged to >120 seconds with heparin concentrations of 0.1 U/ml), did not demonstrate significant amounts of residual heparin in either group after arrival at the intensive care unit (C 24 ± 15, I 27 ± 23 seconds, p = 0.40). The greater prolongations in whole blood prothrombin time and activated partial thromboplastin time assays therefore almost certainly reflected greater reductions in coagulation factors in the control group.

We recently explored this issue further in a subgroup of patients at high risk for excessive blood loss after extracorporeal circulation (n = 31). ³ This study demonstrated that consumable coagulation factors V, VIII, and fibrinogen were preserved in patients in the intervention group in the setting of normal thrombin time results (C 22 ± 5, I 20 ± 4 seconds, p = 0.11). In addition, maintenance of higher heparin concentrations in our intervention group resulted in reduced activation of coagulation and fibrinolysis, as demonstrated by lower fibrinopeptide A levels (p = 0.0002), lower D-dimer (p = 0.03) levels, and a trend toward lower prothrombin fragment 1.2 (p = 0.06) levels in specimens obtained before discontinuation of cardiopulmonary bypass. ³ This confirms previous published data indicating that fibrinopeptide A levels are indirectly related to heparin concentration. ^4,5 Although the potential role of optimized protamine doses on reduced blood product use was not fully addressed, our data provide evidence that maintenance of higher, patient-specific heparin concentrations had a major impact on preservation of coagulation in our intervention group and reduced transfusion requirements.

We look forward to the outcome of the studies initiated by Martin and associates concerning the effects of reduced heparin-protamine complexes on sensitive markers of hemostasis. By characterizing these effects, these studies will better define the potential benefits of optimized protamine doses on the incidence and severity of postoperative bleeding and transfusion requirements.

References

1. Despotis GJ, Joist JH, Hogue CW, et al. The impact of heparin concentration and activated clotting time monitoring on blood conservation: a prospective, randomized evaluation in patients undergoing cardiac operation. J THORAC CARDIOVASC SURG1995;110:46-54.
   
2. Jobes DR, Schaffer GW, Aitken GL. Increased accuracy and precision of heparin and protamine dosing reduces blood loss and transfusion in patients undergoing primary cardiac operations. J THORAC CARDIOVASC SURG1995;110:36-45.
   
3. Despotis GJ, Joist JH, Hogue CW, et al. The effect of higher heparin concentrations on preservation of hemostasis in cardiac surgical patients [Abstract]. Anesthesiology 1995;83:91.
   
4. Gravlee GP, Haddon WS, Rothberger HK, et al. Heparin dosing and monitoring for cardiopulmonary bypass: a comparison of techniques with measurement of subclinical plasma coagulation. J THORAC CARDIOVASC SURG1990;99:518-27.
   
5. Hashimoto K, Yamagishi M, Sasaki T, Nakano M, Kurosawa H. Heparin and antithrombin III levels during cardiopulmonary bypass: correlation with subclinical plasma coagulation. Ann Thorac Surg 1995;58:799-805.[Abstract]
   

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