Post-Cardiac Catheterization Access Site Complications and Low-Molecular-Weight Heparin Following Cardiac Catheterization

No consensus has emerged on the periprocedural anticoagulation regimen of patients receiving long-term oral anticoagulation.1 Enoxaparin, a low molecular weight heparin (LMWH), is often used following percutaneous invasive procedures in patients on long-term anticoagulation who undergo temporary periprocedural discontinuation of warfarin. From 1993 through 1998, the Food and Drug Administration (FDA) received reports of 43 patients who developed spinal or epidural hematomas following the use of enoxaparin in the setting of neuraxial blockade.2 Many of these patients developed severe neurologic impairment. Because of concern that adverse events might occur with other procedures, the post-procedure clinical course for enoxaparin-treated patients who underwent cardiac catheterization or percutaneous coronary intervention was evaluated. Methods Patients with left ventricular thrombi, atrial fibrillation, or who were chronically anticoagulated for other reasons, received enoxaparin preprocedure following coumadin discontinuation. Enoxaparin was discontinued the evening prior to the procedure and restarted 12–24 hours post-procedure if no vascular or bleeding complications occurred. All patients who received subcutaneous enoxaparin (> 50 mg dose) following cardiac catheterization between June 8, 2000 and April 9, 2001 were identified by cross referencing the cardiac catheterization database with the hospital pharmacy database. All enoxaparin-treated patients who developed major or minor hematoma-related complications following cardiac catheterization were identified by reviewing data from the monthly quality management conference for the cardiac procedures unit. A major complication included any hematoma >= 5 cm, bleeding that required transfusion of red blood cells, a new pseudoaneurysm diagnosed by ultrasound, or uncontrollable bleeding that required vascular surgical intervention. Results During the 6-month observation period, a total of 119 patients underwent cardiac catheterization procedures for evaluation of coronary and valvular heart disease and received post-procedure subcutaneous enoxaparin (1 mg/kg). Five patients developed severe delayed hemorrhage or vascular complications following procedures utilizing 7 French (Fr) venous sheaths (n = 4) and 6 Fr (n = 3) or 7 Fr (n = 2) arterial sheaths through a percutaneous femoral approach (Table 1). Patient 1 had a history of chronic atrial fibrillation. Thirty hours after left heart catheterization and placement of a coronary artery stent, enoxaparin (80 mg subcutaneous every 12 hours), aspirin and clopidogrel were initiated. On the 11th post-procedure day while at home, a 4 cm x 4 cm hematoma developed. An ultrasound identified a 1 cm x 2 cm pseudoaneurysm. Two units of packed red blood cells were transfused. The pseudoaneurysm was treated with an ultrasound-guided injection of thrombin. Patient 2 had a history of chronic atrial fibrillation. Twelve hours after left and right heart catheterization, enoxaparin (80 mg subcutaneous every 12 hours) was started. Three days later, a 30 cm x 20 cm hematoma developed. Shortly thereafter, the patient was hypotensive and subsequently suffered a cardiac arrest. Cardiopulmonary resuscitation and electrical cardioversion for ventricular tachycardia were successfully carried out. Four units of packed red blood cells and two units of fresh frozen plasma were transfused. Emergency surgical repair of the femoral artery was performed. Visual inspection indicated that all bleeding occurred from the single anterior puncture site. Patient 3 had a history of chronic atrial fibrillation. Twenty-four hours after left heart catheterization, enoxaparin (60 mg subcutaneous every 12 hours) and warfarin were started. Four days later, leg pain was noted and the patient was readmitted to the hospital. Six units of packed red blood cells were transfused. A pseudoaneurysm was identified by ultrasound. Over the next 2 weeks, persistent bleeding into the pseudoaneurysm was noted. The pseudoaneurysm was surgically repaired 17 days after catheterization. Upon visual inspection, no laceration of the femoral artery was noted. Patient 4 had a history of left ventricular thrombus. Twenty-four hours after left and right heart catheterization, enoxaparin injections (90 mg subcutaneous every 12 hours) and warfarin were started. Four days after the procedure, a 10 cm x 10 cm hematoma developed, followed by hypotension requiring hospitalization. Three units of packed red blood cells and 1 unit of fresh frozen plasma were transfused. Patient 5 underwent left and right heart catheterization, which identified a left ventricular thrombus. One day later, a ventricular biopsy was performed. Two days after the catheterization, enoxaparin (80 mg subcutaneous every 12 hours) and warfarin were started. Six days after the catheterization, a 4 cm x 3 cm hematoma developed. Ultrasound identified a 1 cm x 1 cm pseudoaneurysm. No blood products were transfused. Repeat ultrasound several days later demonstrated resolution of the pseudoaneurysm without intervention. Discussion Following invasive procedures, enoxaparin-associated complications can be life threatening. Among 43 patients reported to the FDA with severe enoxaparin-associated bleeding complications following neuraxial anesthesia procedures, sixteen were permanently paralyzed.2 At our hospital, during a 10-month period, three patients with chronic atrial fibrillation and 2 patients with left ventricular thrombi developed pseudoaneurysms, profound hypotension and severe hemorrhages into a femoral arterial puncture site between 3 and 11 days after cardiac catheterization. For all 5 patients, enoxaparin was started more than 12 hours after the procedure as a “bridge” until warfarin could achieve a therapeutic level of anticoagulation. Two patients required emergency surgical repair of the puncture site and 1 patient required cardiopulmonary resuscitation with electrical cardioversion following a cardiac arrest. Of note, predisposing factors identified in the previous report on enoxaparin and neuraxial anesthesia procedures (i.e., female gender, age greater than seventy years and concomitant administration of medications known to increase bleeding) were also apparent in our patients.2 Renal insufficiency is also an important consideration when using enoxaparin following cardiac procedures, as contrast media induced nephrotoxicity occurs in 5% or more.3 Contrast media induced nephrotoxicity occurred in 1 of our patients and may have led to increased plasma levels of the renally excreted enoxaparin. There is uncertainty over the appropriate “bridge” anticoagulant treatment following cardiac procedures. In the Enoxaparin Restenosis Trial, patients who received enoxaparin 40 mg subcutaneously once daily following angioplasty had a statistically significant increased rate of overall bleeding than placebo patients (48% versus 34%; p

1. Hirsh J, Anand S, Halperin J, Fuster V. Guide to anticoagulant therapy: Heparin. A Statement for Healthcare Professionals from the American Heart Association. Circulation 2001;103:2994–3018. 2. Wysowski DK, Talarico L, Bacsanyi J, Botstein P. Spinal and epidural hematoma and low-molecular-weight heparin (letter). N Engl J Med 1998;338:1774. 3. Davidson CJ, Hlatky M, Morris K, et al. Cardiovascular and renal toxicity of a nonionic radiographic contrast agent after cardiac catheterization. Ann Intern Med 1989;110:119–124. 4. Faxon D, Spiro T, Minor S, et al., for the ERA Investigators. Low molecular weight heparin in prevention of restenosis after angioplasty — Results of the Enoxaparin Restenosis (ERA) Trial. Circulation 1994;90:908–914. 5. Cairns JA, Gill J, Morton B, et al., and the EMPAR Collaborators. Fish oils and low-molecular-weight heparin for the reduction of restenosis after percutaneous transluminal coronary angioplasty —The EMPAR Study. Circulation 1996;94:1553–1560.