We present a patient with chronic renal insufficiency who developed a massive posttraumatic abdominal wall hematoma after a single therapeutic dose of enoxaparin administered during workup of chest pain. Surgical evacuation of the hematoma was required to control life-threatening hemorrhage. Low-molecular-weight heparin use is not without risk and mandates appropriate indication and accurate dosing. Bleeding can occur at any site during heparin therapy, and abdominal wall hematoma should be considered as a source after traumatic injury.
FOR MORE THAN 40 YEARS, heparin has been standard therapy for the initial treatment or prevention of vascular thrombosis. When used appropriately, heparin prevents recurrent thromboembolism with an acceptable risk of major bleeding. Recently, however, the dominance of unfractionated heparin (UH) in the antithrombotic armamentarium has been overtaken by low-molecular-weight heparin (LMWH).
Unfractionated heparin is a complex glycosaminoglycan isolated and purified from porcine intestinal mucosa or bovine lung. It functions as an anticoagulant by inducing a conformational change in the structure of antithrombin (AT), dramatically augmenting its ability to neutralize thrombin, and to a lesser extent, factor Xa and other serine proteases that participate in the formation of fibrin.1 UH binds to endothelial cells and macrophages, as well as to plasma proteins including platelet factor 4 and von Willebrand factor, explaining the variability in plasma heparin activity observed after parenteral administration.
Low-molecular-weight heparin is prepared from UH by enzymatic or chemical hydrolysis, procedures that substantially alter the biological properties and clinical attributes of the anticoagulant. For example, LMWH inhibits factor Xa more effectively than thrombin, lacks nonspecific plasma protein binding, and has a more stable half- life compared to UH.2 LMWH has a more predictable biological availability and is administered in a subcutaneous dose once or twice daily without the need for laboratory monitoring. Because of these characteristics, LMWH is now being used in the emergency department and inpatient and outpatient settings for the treatment or prevention of deep venous thrombosis, pulmonary embolism, and acute coronary syndrome.3
We present the case of a chronic renal failure patient who developed a posttraumatic abdominal wall hematoma after a single dose of enoxaparin.
Case Report
A 43-year-old female (60 kg) with a history of nondialytic chronic renal failure resulting from malignant hypertension presented to the emergency department with chest pain and a blood pressure of 160/90. The differential diagnosis included possible acute myocardial ischemia versus pulmonary embolism. Pertinent and reviewed laboratory results included serum creatinine 4.1 mg/dL, potassium 3.9 meq/L. hematocrit 31 percent, and international normalized ratio (INR) 1.08. After an elevated D-dimer of 2.2 (normal, 0-0.5), the patient received 60 mg of enoxaparin subcutaneously while awaiting ventilation/perfusion (V/Q) scan. The V/Q scan was low probability for pulmonary embolism. Cardiac evaluation including enzymes, and electrocardiogram was also negative, and the patient was discharged. On her way home, the patient was involved in a low-speed motor vehicle crash as a front- seat passenger restrained by shoulder harness and lap belt. She reported increasing lower abdominal pain immediately after the collision and returned to the emergency department.
She arrived hemodynamically stable with examination revealing a large right lower abdominal wall mass in the distribution of the lap belt (Fig. 1). The overlying skin was taught and shining in appearance. CT scan of the abdomen and pelvis revealed a large subcutaneous hematoma of the abdominal wall with no obvious solid organ injury or traumatic hernia (Fig. 2).
FIG. 1. Abdominal wall mass in the distribution of the lap belt.
The patient was emergently transported to the operating room due to the development of hemodynamic instability and rapid expansion of the hematoma. A preoperative hematocrit was 18 per cent, and a low- molecular-weight heparin level (antiXa level) drawn 13 hours after the enoxaparin dose remained elevated at 0.6 IU/mL (therapeutic range, 0.6 to 1.0 antiXa lU/mL). She received 60 mg of protamine sulfate intravenously immediately prior to surgery, and a low- molecular-weight heparin level after the protamine dose was less than 0.1 IU/mL. Evacuation of the hematoma produced approximately 800 mL of blood. Ligation of an actively bleeding superficial inferior epigastgric artery was performed, the hematoma cavity was packed for additional hemostasis, and the patient was transfused 3 units of packed red blood cells. Postoperatively, no further wound bleeding occurred, and the patient was discharged to home on postoperative day 5, performing daily dressing changes. Outpatient follow-up documented complete wound healing by postoperative day 30.
FIG. 2. CT scan revealing subcutaneous abdominal wall hematoma.
Discussion
Rates of serious hemorrhage with UH or LMWH therapy approximate 2 to 6 per cent per patient episode of treatment in clinical trials of acute coronary syndrome and deep venous thrombosis treatment.4, 5 Bleeding occurs more frequently in patients with risk factors including recent surgery or trauma, renal insufficiency, active peptic ulcer disease, hypertension, recent intracranial hemorrhage or stroke, and history of bleeding diathesis.6
If bleeding is severe, protamine sulfate can be used for immediate neutralization of anticoagulant. When the heparin has been given recently, 1 mg of protamine neutralizes approximately 100 IU of UH. The relative prolongations of the activated partial thromboplastin time (PTT) and low-molecular-weight heparin level (antiXa level) are useful for estimating the quantity of circulating heparin and the need for protamine.7
Protamine sulfate is less effective in neutralizing LMWH. One approach is to administer 1 mg of protamine for every 1 mg or 10 antiXa units of LMWH, producing an approximate 50 per cent neutralization of LMWH. Given the longer half-life of LMWH, 4 hours, one-half of this dose can be repeated in 4 hours if necessary.8
Enoxaparin is a LMWH with an average molecular weight of 4-5 kDa compared to 12-15 kDa for UH. It is rapidly absorbed after subcutaneous administration and has a linear dose relationship for antiXa activity over the dose range 20-80 mg. The sustained biological activity of enoxaparin allows less frequent administration than that required for UH, and it is predominantly eliminated by the kidney.9 With a LMWH level within the therapeutic range 13 hours after the emergency department dose, this patient clearly had an impaired clearance and prolonged therapeutic effect of enoxaparin.
After a therapeutic weight-adjusted dose of LMWH is administered by subcutaneous injection, the antiXa activity peaks at approximately 4 hours, and this is the recommended time to perform monitoring assays.2 It should be noted that the measured peak antiXa activity varies among individual LMWH preparations given in the same antiXa dose, due to individual variations in pharmacokinetics. A conservative therapeutic range for peak effect with twice-daily administration of enoxaparin is 0.6 to 1.0 IU/mL for patients being treated for venous thromboembolism.10 In order to avoid an increased risk of bleeding, levels >1.0 IU/mL should be avoided if the appropriateness of the dose is in question in patients with renal impairment.11
The safety of administering standard doses of LMWH to patients with severe renal insufficiency has not been clearly established. Large contemporary randomized controlled trials of LMWH have generally excluded patients with severe renal insufficiency. However, pharmacokinetic and clinical data have become available that allow reasonable conclusions to be made regarding the use of LMWH in these patients. Pharmacokinetic studies have demonstrated that the clearance of the antiXa effect of LMWH is strongly correlated with creatinine clearance (CrCl). This relationship has been shown in single-dose studies of enoxaparin at a CrCl rate of
Evidence-based guidelines from the 7th Annual American College of Chest Physicians Conference on Antithrombotic Therapy recommends using UH to provide full therapeutic anticoagulation therapy in patients with severe renal insufficiency (CrCl
Thromboprophylactic LMWH in patients with renal insufficiency requires separate consideration. Although increased antiXa activity was observed in patients with renal failure who received multiple thromboprophylactic doses of enoxaparin (40 mg daily), the mean peak antiXa level was only 0.6 IU/mL and the trough was
Bleeding can occur at any site during heparin therapy, and abdominal wall hematom\a should be considered as a source after traumatic injury. CT scan of the abdomen can be useful in differentiating subcutaneous from intramuscular abdominal wall hematoma, the latter rarely requiring operative intervention.13 Surgical evacuation of an abdominal wall hematoma may be required to control ongoing hemorrhage or preserve skin viability.
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ROBERT L. WEINSHEIMER, M.D.,* EDWARD LIBBY, M.D.,[dagger] THOMAS R. HOWDIESHELL, M.D.*
From the Departments of * Surgery and [dagger] Medicine, University of New Mexico Health Sciences Center, Albuquerque, New Mexico
Address correspondence and reprint requests to Thomas R. Howdieshell, M.D., F.A.C.S., Trauma/Surgical Critical Care, Department of Surgery, University of New Mexico HSC, Albuquerque, NM 87131.
Copyright The Southeastern Surgical Congress Feb 2005
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