Anticoagulation for Cardiac Surgery

Patients with acute HIT, or recent previous HIT with persisting HIT antibodies, may need to undergo cardiac surgery. UFH is contraindicated during acute HIT, necessitating an alternative anticoagulant for use during CPB. After successful experiments in dogs (Henny et al., 1985a), danaparoid underwent use for CPB anticoagulation in such situations (Magnani, 1993; Wilhelm et al., 1996; Westphal et al., 1997; Christiansen et al., 1998; Fernandes et al., 2000; Olin et al., 2000). Magnani et al. (1997) reported the experience of 47 such evaluable patients. The initial recommended dosing schedule, which consisted of an iv bolus to the patient both before and after thoracotomy plus addition of danaparoid to the priming fluid (and if necessary further iv booster doses during surgery if fibrin formation became a problem), often led to the patient receiving over 16,250 U danaparoid in total. In some patients, attempts were made to prolong the activated clotting time

(ACT) prior to surgery, but since this test is insensitive to danaparoid (Gitlin et al., 1998), it led to serious overdosing. Although two of the 47 operations had to be abandoned because of intra-operative clotting, the biggest problem (22%) was serious postoperative bleeding (Magnani et al., 1997). It seemed that a total dose of > 16,250 U (> 250 U/Kg) danaparoid was more likely to increase postoperative blood loss significantly. Therefore, a new dosing regimen (Table 1) was developed that delivers no more than 232 U/kg of the drug. Continuous intraoperative danaparoid infusion is also recommended, which might reduce the need for a further drug bolus shortly before wound closure, as well as provide therapeutic drug levels throughout CPB.

This new regimen and its modifications were used by Olin and coworkers (2000) and Fernandes et al. (2000). Disappointingly, the new regimen did not reduce postoperative bleeding. Consequently, danaparoid is not recommended for CPB (Buys et al., 2003; see also Chapter 19), unless no other suitable alternative is available.

Advances in surgical method may permit other treatment approaches in selected patients. For example, the off-pump ("beating heart") technique does not utilize CPB, and thus a far lower dose of danaparoid may be feasible for intraoperative anticoagulation. This approach was used successfully to perform multiple coronary artery bypass grafting in a patient with acute HIT and unstable angina (Warkentin et al., 2001). A relatively low target plasma anti-factor Xa level (0.6U/mL) was used, rather than the levels (> 1.5U/mL) sought during CPB (see Chapter 19).

A randomized, double-blind comparison of danaparoid (n = 34) with UFH (n = 37) for off-pump coronary artery bypass grafting in non-HIT patients showed a non-significant trend to greater postoperative blood loss (mean, 264 mL) but a significant increase in patients exposed to homologous blood (53% vs. 27%) with danaparoid. Clinical outcomes appeared similar, and the authors concluded that danaparoid could be a valuable option in patients undergoing off-pump surgery when UFH is contraindicated (Carrier et al., 2003).

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