A case of heparin resistance or a case of inadequacy of anticoagulation monitoring?

Abstract

Introduction Despite during cardiopulmonary bypass (CPB) inhibiting coagulation is essential, the clinical management of heparin based anticoagulation is still not standardized. Heparin resistance (HR) is a reported feature (10-20%), but there is not a unique definition universally accepted. Methods An 80 years old woman was listed for elective CABG and aortic valve replacement. She had no recognized risk-factors for HR; her pre-op laboratory tests (platelet count, coagulation, liver function) were within normal range. After induction of general anesthesia the baseline ACT was 137sec. 20000IU bolus of unfractionated heparin (300IU/kg) was administered and ACT reached 250sec. Other 10000IU bolus of heparin and 1000IU of AT-III were administered, but ACT remained inadequate (254sec). A ROTEM test showed prolonged INTEM-CT and normal HEPTEM-CT; laboratory tests revealed aPTT >220sec and plasmatic heparin >3IU/mL. According to these results, CPB was started. During CPB anticoagulation was monitored with both ACT and laboratory tests: ACT has never been concordant with aPTT neither ACT increased after further 5000IU bolus of heparin. At the end of CPB, heparin was neutralized with protamine 350mg and tranexamic-acid 2g was administered: the final ACT was 143sec. Nevertheless, the patient was still bleeding and she needed RBC transfusion: a second ROTEM test showed very prolonged INTEM-CT and HEPTEM-CT and normal FIBTEM parameters, thus the patient was efficaciously treated with prothrombin-complex concentrate. Later, in ICU the first laboratory tests revealed normal aPTT and plasmatic heparin below the sensibility range; a third ROTEM test ran totally normal. Results According to common definitions of HR (failure to reach therapeutic ACT despite high doses of heparin), this case should identify an HR situation. However, both ROTEM and laboratory tests (aPTT, plasmatic heparin) confirmed the patient was properly anticoagulated. Conversely, after protamine administration ACT indicated the return to a normal coagulation state, while clinical evidence, aPTT and ROTEM test showed the contrary. These discordant results may be due to the different activators used in ROTEM-INTEM, aPTT and ACT (respectively ellagic-acid, kaolin and celite). Discussion A new unanimous definition for HR is needed to develop a standardized management. ACT is useful to monitor bedside anticoagulation, but second-line tests should always be available and adopted to characterize doubtful cases and verify HR.