Direct thrombin inhibitors: a case indicating benefit from 'plasmapheresis' in toxicity: a call for establishing "guidelines" in overdose and to find an "antidote"!

Patient presented with passage of fresh blood mixed with clots per rectum. In the ER, she was found to have bright red blood per rectum with clots, with frank blood on nasogastric tube. She was on dabigatran for atrial fibrillation and aspirin, with intermittent intake of ibuprofen. Vitals were positive for orthostatic hypotension. The pertinent findings in the physical examination were altered mental status with orientation*1, weak peripheral pulses, irregularly irregular heart rate, and bilateral pitting edema 2+ in bilateral lower extremities. Patient was intubated and put on mechanical ventilation. A massive transfusion protocol was followed. Laboratories and imaging: hemoglobin/hematocrit, 7.2/22.1; white blood cells, 7.7, platelet, 210; international normalized ratio, 2.5; prothrombin time, 19.2; activated partial thromboplastin time, 88.2; CMP was WNL; BNP, 621; fibrinogen, 500 mg/dL. Electrocardiogram showed atrial fibrillation with inferolateral ischemia. Ultrasonography of the liver and gallbladder showed no acute pathology. Echocardiogram showed an EF of 70% with hyperdynamic LV. Patient was transferred to the intensive care unit. Dabigatran, aspirin, and nonsteroidal anti-inflammatory drugs were discontinued, and antihypertensives were held. She was given blood and FFPs. Hemoglobin, hematocrit, and coagulation profile was monitored every 6 hours. Gastroenterology, general surgery, interventional radiology, and hematology services were called stat. IR placed a double-lumen, power central venous catheter. In gastroenterology, EGD and colonoscopy was performed, which showed active bleed at distal esophagus, stopped with local epinephrine. No active bleed seen on colonoscopy. The patient was put on Nexium drip. Hematology service recommended thrombin time (>200) and factors 2, 5, 7, 9, 10-41(l), 80, 68, 48(l), 61. Prothrombin time and activated partial thromboplastin time mixing studies were done, which indicated the presence of thrombin inhibition. Prothrombin complex concentrate at 50 U/kg was started to reverse the effect of dabigatran, and platelets were transfused to reverse the effect of aspirin. They also discussed that the half-life of dabigatran being 17 hours, and the drug would not be toxic at this point, as the patient was already 24-hour inpatient by now. The hemoglobin trend: 7.4→6.4→8.2→7.5→6.6. At this point, the need for further intervention in form of hemodialysis or plasmapheresis was considered. The patient was given plasmapheresis and hemoglobin and hematocrit stabilized. The patient was kept on continued mechanical ventilator support for the night and extubated next day. The hemodynamics stabilized and the patient was transferred to the general medical floors after 1 day of observation, after extubation.