Elevated aPTT in the setting of prophylactic unfractionated subcutaneous heparin administration

Abstract

Abstract Subcutaneous unfractionated heparin or low-molecular-weight heparin is commonly used for venous thromboembolism prophylaxis in hospitalized patients at an increased risk of developing thrombosis. Generally, the prophylactic doses of these medications have poor bioavailability and do not reach therapeutic serum concentration levels to cause coagulopathy. However, there have been some reported cases of heparin-binding proteins becoming saturated. Here, we report a case of a patient who had an elevated aPTT while receiving prophylactic subcutaneous unfractionated heparin for venous thromboembolism. A 75-year-old female presented to our institution with a complete heart block. She had a past medical history of chronic kidney disease stage V, essential hypertension, insulin-dependent diabetes mellitus, and hyperlipidemia. She was started on subcutaneous unfractionated heparin 5000 units TID prophylaxis on hospital day 0. Her baseline aPTT was 33.7 seconds, and INR was 0.99. The patient underwent a dual-chamber pacemaker placement on hospital day 1. Her kidney function continued to worsen throughout her hospitalization, and she developed symptomatic hyponatremia with encephalopathy that was thought to be due to hypervolemia but was not responsive to intravenous diuresis. She was initiated on conventional hemodialysis. On hospital day 7, the patient had a temporary dialysis catheter placed, but before catheter placement, the patient's aPTT was measured at > 150 seconds (normal 23-35 sec). A repeat aPTT 3 hours later confirmed an elevated aPTT > 150 seconds. Her platelet count at the time was 151,000. Her subcutaneous heparin was held, and she had a significant amount of bleeding from her dialysis access site. Therefore, the patient was given intravenous protamine sulfate 50 mg once and received intravenous 0.6 mcg of desmopressin for concerns of uremic bleeding. The patient underwent an extensive coagulopathy workup, including a mixing study, which initially showed an incomplete factor inhibitor, but the patient's aPTT normalized after protamine and discontinuation of heparin, suggesting heparin as the cause of her coagulopathy. We report a case of elevated aPTT levels while receiving unfractionated heparin prophylaxis for VTE. The supratherapeutic aPTT level was > 150 seconds. The time to supratherapeutic laboratory values (aPTT) was 7 days. Both aPTT and anti-Xa assays are used to monitor heparin activity. It is also important to note that our patient never received a bolus of heparin throughout her hospitalization, and this significant rise in aPTT levels was attributed to the unfractionated subcutaneous heparin administration she was receiving. Protamine sulfate is routinely administered to reverse the systemic anticoagulation effects of unfractionated heparin. The need for urgent or emergent heparin reversal is individualized based on the site and severity of bleeding, as well as the degree of anticoagulation. If reversal is required, heparin is discontinued, and protamine sulfate is administered at a dose calculated based on the heparin administered and the elapsed time since the last heparin dose. Protamine sulfate should be ideally administered by slow intravenous infusion, and not to exceed greater than 5 mg/minute, and the total dose should not exceed 50 mg in 10 minutes to avoid adverse effects such as hypotension, anaphylactic reactions, or cardiac collapse. Hemostasis is a complex, tightly regulated balance between bleeding and clotting, which is often deranged in critically ill patients. These critically ill patients have a predisposition to develop coagulopathies and have an elevated risk for thrombotic complications. In our patient, we found several shared characteristics relevant to previously published case reports and case series amongst patients with supratherapeutic laboratory values, which include female gender, age greater than 65, ICU admission, baseline renal dysfunction, and a low albumin level. Therefore, providers should consider therapeutic monitoring in high-risk patients with these characteristics. Critically ill patients are predisposed to a higher baseline bleeding risk due to factors such as platelet dysfunction, coagulation factor deficiencies, more invasive procedures, and mechanical ventilation. Understanding all these factors is a crucial part of decision-making when administering anticoagulation.