Correspondence  |   September 2002
Thrombosis after Deep Hypothermic Circulatory Arrest with Antifibrinolytic Therapy: Is Factor V Leiden the Smoking Gun?
Author Notes
  • Vanderbilt University, Nashville, Tennessee.
Article Information
Correspondence   |   September 2002
Thrombosis after Deep Hypothermic Circulatory Arrest with Antifibrinolytic Therapy: Is Factor V Leiden the Smoking Gun?
Anesthesiology 9 2002, Vol.97, 760-761. doi:
Anesthesiology 9 2002, Vol.97, 760-761. doi:
To the Editor:—
I read with interest the report by Fanashawe et al.  1 describing two cases in which deep hypothermic circulatory arrest (DHCA) with aminocaproic acid was complicated by massive thrombosis once heparin was reversed by protamine. Postmortem studies were conducted to search for occult hypercoagulable states, and one patient turned out to carry factor V Leiden (FVL). The authors assert that FVL was “almost certainly contributory” to the event and suggest consideration of preoperative testing for FVL to guide decision-making in cases in which DHCA is planned. 1 
While I find these cases very interesting, there is no evidence in the present literature to support that FVL “almost certainly” contributed to the thrombotic risk in one of these patients. Although this conclusion is physiologically plausible, FVL does not always carry risk in specific clinical settings. One example is the lack of association of FVL with venous thrombosis after orthopedic surgery. 2,3 Also, most population studies have failed to show an association of FVL with coronary thrombosis and stroke, 4–7 although FVL may increase arterial thrombotic risk in specific patient subgroups. 8,9 A few studies have suggested (but not proven) that FVL may carry clinical significance in cardiac surgery, 10,11 and it is possible that larger studies may characterize this significance in greater detail. However, it is currently pure speculation to suggest that risk of DHCA with aminocaproic acid is increased by the presence of FVL.
It is equally misguided to suggest preoperative screening for FVL and to base patient care decisions on anecdotal reports. No prospective, controlled studies exist to validate the use of preoperative testing for FVL, so it is very unclear how this information should be used. If my next patient is known to carry FVL, what do I do next? Is antifibrinolytic therapy unnecessary? Is it dangerous? Is DHCA safe with aprotinin? Do we need to cross-match fewer units of erythrocytes? Since these genetic studies are becoming widely available, it is concerning that a possible abuse of this test may follow the authors’ suggestions. If the authors themselves had tested their second patient for FVL preoperatively, they may have felt better justified in using aminocaproic acid, only to be dreadfully surprised when they observed a similar thrombotic event.
The risk of FVL in cardiac surgery is presently unclear. The risk of FVL in the presence of cardiac surgery, DHCA, and antifibrinolytic therapy is even less well understood. Fanashawe et al.  perform an important service by reporting a tragic complication of antifibrinolytic therapy and therefore highlight the need to carefully research the possible contributing factors. However, we must be exceedingly cautious not to draw conclusions about genetic risk factors or issue recommendations for patient care based on anecdotal reports. What is needed is a large-scale association study, examining gene-environment interactions, to characterize the role of FVL in cardiac surgery. Only then will we be justified in concluding that FVL is “contributory” toward a particular outcome or in proposing preoperative screening in an effort to reduce risk.
Fanashawe MP, Shore-Lesserson L, Reich DL: Two cases of fatal thrombosis after aminocaproic acid therapy and deep hypothermic circulatory arrest. A nesthesiology 2001; 95: 1525–7Fanashawe, MP Shore-Lesserson, L Reich, DL
Ryan DH, Crowther MA, Ginsberg JS, Francis CW: Relation of factor V Leiden genotype to risk for acute deep venous thrombosis after joint replacement surgery. Ann Intern Med 1998; 128: 270–6Ryan, DH Crowther, MA Ginsberg, JS Francis, CW
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