Management of the Patient with a Low or Intermediate Probability of HIT Pending Results of HIT Antibody Testing

In patients with HIT without thrombosis, the risk of major bleeding with therapeutic-dose DTI therapy per patient day has been reported to be as high as 1.0% for lepirudin (i.e., 14.3% major bleeding over a mean treatment period of 13.9 days) (Lubenow et al., 2004) and for argatroban it was 0.6% and 1.0% (3.1% and 5.3% major bleeding over a mean treatment period of 5.3 and 5.1 days, respectively) (Lewis et al., 2001, 2003). In the large case series of HIT patients treated with danaparoid (Magnani and Gallus, 2006), the risk for major bleeding was 0.4% for prophylactic-dose therapy (3.2% major bleeding over a median treatment duration of 6 days) (personal communication, Dr H. Magnani).

These relatively high risks for bleeding (especially with DTIs) should be contrasted with the much lower expected rate of thrombosis (~0.3-0.5% per patient day) among all patients investigated for HIT by ordering laboratory testing for HIT antibodies. This calculation is based upon the estimated initial thrombotic event-rate per day (~5%) multiplied by the relatively low overall risk of obtaining a positive test result using a functional test for platelet-activating heparin-depen-dent antibodies (~6-10%) (Warkentin and Sheppard, 2006; Greinacher et al., 2007). Thus, the high risk of bleeding with therapeutic-dose anticoagulation suggests that such therapy is justified only if the clinical likelihood is judged to be at least intermediate, if not high, based upon the clinical picture, prior to obtaining the results of laboratory testing for HIT antibodies. Unless otherwise dictated by the patient's clinical condition, the use of an alternative anticoagulant in prophylactic doses might be safer in this situation. This could be achieved in several ways: e.g., danaparoid 750 U t.i.d. sc, a dosing regimen that is approved for prophylaxis of new thrombosis in several jurisdictions. Another potential option is prophylactic-dose fondaparinux (2.5 mg once-daily sc), although there is less experience in this setting with fondaparinux than with danaparoid.

Recommendation. In a patient with a low probability for HIT (e.g., 4T's score <3) pending the results of laboratory testing for HIT antibodies, we suggest either continuing the use of heparin or using alternative, non-heparin anticoagulation in prophylactic, rather than in therapeutic, doses (assuming there is no other reason for therapeutic-dose anticoagulation) (Grade 1C).

Recommendation. In a patient with an intermediate probability for HIT (e.g., 4T's score of 4 or 5), who has an alternative explanation for thrombocytopenia and who does not require therapeutic-dose anticoagulation for other reasons, we suggest alternative anticoagulation in prophylactic, rather than in therapeutic, doses (Grade 2C).

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