The patient subsequently required right above-knee and left below-knee amputations. Prolongation of the international normalized ratio (INR), which measured 3.7 after stopping the argatroban, was consistent with the diagnosis of warfarin-associated venous limb gangrene. However, because of a supratherapeutic APTT (116 s), the argatroban was decreased and then held (for 18 h), during which time irreversible ischemic necrosis developed in both lower limbs. After bilateral lower-limb fasciotomies were performed for suspected compartment syndrome, the patient received argatroban, beginning in standard doses (2 μg kg −1 min −1 = 14 mg h −1 for patient weighing 117 kg). The patient developed progressive venous limb ischemia of the right lower limb, as well as new-onset left lower limb swelling despite palpable pulses.
Strong positive testing by commercial anti-PF4/polyanion enzyme-immunoassay supported the diagnosis (4.024 optical density units normal, <0.400 U). Warfarin (7.5 mg) was given on day 8 because of atrial fibrillation, and HIT was diagnosed the following day, with symptomatic right lower-limb deep-vein thrombosis (DVT).
1A) was a 55-year-old male who developed HIT following coronary artery bypass grafting the platelet count nadir was 7 × 10 9 L −1 on day 9.
The clinical course of the following two patients provides support in favor of this recommendation of the ACCP. The reason that coumarin administration could lead to underdosing of DTI therapy is because DTIs are usually monitored using the activated partial thromboplastin time (APTT), and the APTT is typically increased by coumarins, such as warfarin. This advice was based upon two theoretical considerations: reducing the potential for VKA (coumarin)-induced venous limb gangrene in the high-risk setting of HIT, as well as avoiding underdosing of direct thrombin inhibitor (DTI) therapy (lepirudin or argatroban).
Recently, the Seventh American College of Chest Physicians (ACCP) Conference on Antithrombotic and Thrombolytic Therapy advised: ‘for patients receiving vitamin K antagonists (VKAs) at the time of diagnosis of heparin-induced thrombocytopenia (HIT), we recommend use of vitamin K’.
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