Labile heparin response in a pre-operative cardiac surgery patient: Unmasking predisposition for post-operative coagulopathy

Abstract Candidacy for coronary artery bypass grafting (CABG) is generally dependent on the extent of atherosclerotic burden within coronary vasculature. One of the main indications is at least two-vessel coronary artery disease (CAD) with >70% stenosis involving the LAD as determined by SYNTAX scoring which is used to guide individualized revascularization strategy. Anticoagulation in these patients is individualized pre-operatively, then generalized in the peri-operative period. Patients with high thrombotic risk such as a history of malignancy would require systemic pre-operative anticoagulation. Labile Partial Thromboplastin Time (PTT) in patients receiving heparin infusion pre-operatively may serve as a presenting sign of underlying coagulopathy, especially in patients with a history of cancer. Malignancy is one such factor that can contribute to heparin resistance, as noted by the American College of Chest Physicians' Evidence Based Clinical Practice Guidelines (2012). While this most likely indicates a level of heparin resistance, causes of such a finding such as Anti-thrombin III deficiency would warrant further elucidation. A 54-year-old man with a history of alcohol abuse, testicular cancer post chemotherapy and orchiectomy of right testes presented for CABG evaluation after he was found to have multi-vessel coronary artery disease. Per protocol, he was started on IV heparin prior to surgery. However, titration was challenging with his PTT dancing between 70 and 130 seconds with small adjustments in the heparin rate. Heparin was discontinued on the morning of the surgery. PTT was 37 seconds, and the procedure was successfully completed on hospital day 4. The patient returned to ICU vitally stable but quickly began to decompensate. Profuse bleeding from his chest tubes was noted with hypotension. His hematologic history was only notable for occasional, mild epistaxis. There was no personal or family history of easy bruising or bleeding. He was taken back to the OR for evaluation, but no clear source of bleeding was identified. He was given multiple units of platelets, fresh frozen plasma (FFP), desmopressin and packed red blood cells. Initial concern was for disseminated intravascular coagulation, D-dimer was 586 and fibrinogen was 200, expected post-op. Peripheral smear demonstrated the presence of thrombocytopenia without schistocytes or clumping, decreasing the likelihood of thrombotic thrombocytopenic purpura. Although heparin had since been discontinued, this presentation also raised suspicion for heparin induced thrombocytopenia (HIT). The platelet count had dropped from 141 to 102, but HIT antibody optical density returned at 0.18, which was not consistent with HIT. Factor V, VIII, and XIII levels could not be properly interpreted given recent blood products. Throughout the patient's 11-day hospital course, his clinical status stabilized, and he was continued on DAPT with resumption of prophylactic heparin. When reviewing the patient data, a slightly elevated INR was noted, which may have indicated liver dysfunction in addition to labile PTT. His previous history of alcohol abuse and malignancy likely played a central role in this post-operative coagulopathy. This case demonstrates how utilizing labile PTT control can prime further evaluation, elevating clinical suspicion of an underlying hematological disorder. High-risk patients undergoing cardiac surgery will require IV heparin prior to the procedure. Heparin response can be used as a marker to prompt further investigation into an underlying coagulopathy. If the procedure is not critical, a hematologic work up may be indicated prior to surgical intervention. If surgery is emergent or cannot be delayed, this abnormality should prompt caution in the immediate post-operative hours. The blood bank can be notified to prepare blood products such as FFP, cryoglobulin or desmopressin which can take longer to obtain in large quantities. This should lead to further evaluation into medications, toxins or biologic causes for the labile response to heparin which may mitigate adverse outcomes. Although the incidence of heparin resistance is rare, performing a clinical study in the future may determine if some of these interventions would be beneficial to patient care.