Correspondence  |   August 2006
Systemic Thromboses after Cardiopulmonary Bypass: Is It Thrombin or Antithrombin?
Author Affiliations & Notes
  • Kenichi A. Tanaka, M.D.
  • †Emory University School of Medicine, Atlanta, Georgia.
Article Information
Correspondence   |   August 2006
Systemic Thromboses after Cardiopulmonary Bypass: Is It Thrombin or Antithrombin?
Anesthesiology 8 2006, Vol.105, 428. doi:
Anesthesiology 8 2006, Vol.105, 428. doi:
To the Editor:—
We read with interest two case reports of fatal thrombotic complications after cardiopulmonary bypass.1,2 However, there are several unclear issues that the readers should become aware of. First, it is not clear whether adequate heparin levels were maintained during cardiopulmonary bypass (CPB) because activated clotting time (greater than 400–600 s1) does not necessarily reflect the efficacy of heparin anticoagulation.3 
Heparin insensitivity due to antithrombin deficiency may be masked by thrombocytopenia, hypofibrinogenemia, or other coagulation factor defects. At our institution, we administer hourly bolus doses of 100 U/kg heparin during CPB to prevent the decrease of plasma heparin levels. Furthermore, we frequently replete antithrombin during prolonged CPB (approximately 3 h) in suspected antithrombin-deficient cases by adding fresh frozen plasma or antithrombin concentrate (Thrombate III®; Talecris Biotherapeutics, Research Triangle Park, NC). We have previously shown that reduced antithrombin levels greatly enhance the rate and peak level of thrombin generation.4 In patients with endocarditis, prolonged CPB, or both, plasma antithrombin levels may become critically low.5 Intravascular fluidity, however, may be maintained by the balance between low procoagulant (fibrinogen, platelet) and low anticoagulant levels (antithrombin, protein C and S, thrombomodulin). Under such conditions consistent with disseminated intravascular coagulopathy, one may observe bleeding tendency. In both cases that the authors described, the administration of hemostatic blood products, platelet concentrate,1 and cryoprecipitate2 after heparin reversal seemed to have triggered thrombotic complications. Rapid extensions of thrombi suggest that uncontrolled “thrombin generation” occurred, and it is questionable whether thrombi could have been quickly dissolved by endogenous fibrinolytic system even in the absence of aprotinin or other antifibrinolytic agents.6 In the case of afibrinogenemia referenced by the authors, it is possible that normal anticoagulant function and short CPB time (36 min) limited thrombus formation locally (i.e.  , graft occlusion) without systemic thrombus extension.7 
To further stress the importance of adequate anticoagulation, the incidence of deep venous thromboses does not seem to be increased with intraoperative use of aprotinin in the orthopedic surgery when prophylaxis for deep venous thromboses (e.g.  , low-molecular-weight heparin) is implemented.8 These two catastrophic cases highlight the importance of balancing procoagulant and anticoagulant components of coagulation to achieve localized hemostasis while avoiding thrombotic complications. Further clinical trials must be conducted to improve our current anticoagulant strategy.9 
†Emory University School of Medicine, Atlanta, Georgia.
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