Successful Use of Cangrelor with Heparin in a Chronic Thromboembolic Pulmonary Hypertension Patient with Heparin-Induced Thrombocytopenia Requiring Pulmonary Thromboendarterectomy

Abstract

Anticoagulation in heparin-induced thrombocytopenia (HIT) requiring cardiopulmonary bypass presents a clinical challenge. Platelet activating immunoglobulin G antibodies target heparin-platelet factor-4 complexes, with subsequent platelet aggregation and thrombosis. We report successful use of cangrelor, a P2Y12 platelet receptor antagonist, with heparin during urgent pulmonary thromboendarterectomy (PTE) for chronic thromboembolic pulmonary hypertension (CTEPH). A 30 year-old male with morbid obesity presented with dyspnea and syncope. Chest computed tomography angiography demonstrated large-burden chronic pulmonary embolism with near complete occlusion of the left and right pulmonary arteries (Figure 1). Echocardiogram revealed severe right ventricular enlargement and dysfunction with right ventricular hypertrophy. Heparin infusion lead to a platelet drop from 260K to 66K. Given concern for HIT, he was switched to argatroban and transferred to our institution. Severe HIT was confirmed with an optimal density of 2.185 and a positive serotonin-release assay, mandating alternative anticoagulation. Bivalirudin has not been well-studied in PTE, surgically unique as it warrants cardiopulmonary bypass with deep hypothermia and circulatory arrest. Deep hypothermia delays bivalirudin metabolism by blood proteases, while circulatory arrest promotes stasis. Thus, bivalirudin in PTE significantly increases circuit thrombosis and patient bleeding risks. Cangrelor was used with heparin to minimize platelet aggregation and thrombosis. Cangrelor has advantages due to high-affinity causing almost complete inhibition of platelet aggregation, with a half-life of 2.6 to 3.3 minutes, allowing rapid removal and platelet function restoration. Intraoperatively, platelet reaction units (PRUs) were measured to assess cangrelor activity and ensure P2Y12 antiplatelet effect with the appropriate scale (baseline PRU 194 to 418, post anti-platelet administration 18 to 435). A cangrelor bolus and infusion were given before heparinization; PRU reduced from 293 to 156. Heparin was then safely administered (total 40,000 units) and cardiopulmonary bypass was started once activated clotting time was appropriate. The patient required a second cangrelor bolus to ensure appropriate PRU levels and anti-platelet effect. Total circulatory arrest was 33 minutes, and after discontinuation of cangrelor, protamine was given for heparin neutralization and hemostasis. Extensive clot material was removed with no perioperative complications (Figure 1). Hemodynamics preoperatively (pulmonary artery pressure 86/23 mm Hg, cardiac index 1.8 lpm 2) dramatically improved post-PTE (pulmonary artery pressure 33/10 mm Hg, cardiac index 3.4 lpm 2). This case represents a novel approach of using cangrelor with heparin intraoperatively for a patient with confirmed HIT requiring urgent PTE. Cangrelor use with heparin offers an effective and safe option in CTEPH while minimizing hematologic complications of thrombosis and bleeding.