Hemothorax and retroperitoneal hematoma after anticoagulation with enoxaparin.

ABSTRACT

A 58-year-old woman with chronic obstructive pulmonary disease had spontaneous bilateral hemothorax and a retroperitoneal hematoma after 4 days of anticoagulation therapy with enoxaparin (1 mg/kg subcutaneously every 12 hours) for suspected pulmonary thromboembolism. The patient was successfully managed with red blood cell and plasma transfusions, multiple thoracenteses for evacuation of blood from the pleural space, short-term mechanical ventilation, and administration of bronchodilators, corticosteroids, and antibiotics. This is the first report of spontaneous hemothorax and the third report of spontaneous retroperitoneal hematoma associated with enoxaparin therapy.

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SPONTANEOUS RETROPERITONEAL HEMATOMA is a rare but potentially serious complication of anticoagulation therapy. It has been described in patients treated with warfarin, (1) unfractionated heparin, (2) and the low molecular weight (LMW) heparins dalteparin (3) and enoxaparin. (4,5) A concomitant retroperitoneal hematoma with hemothorax has been described in a patient receiving warfarin and a nonsteroidal anti-inflammatory drug (6) and in patients treated with unfractionated heparin. (7) Spontaneous hemothorax complicating the use of unfractionated heparin was reported in multiple cases. (8) We are reporting the first case of spontaneous hemothorax in a patient receiving enoxaparin.

CASE REPORT

A 58-year-old woman with chronic obstructive pulmonary disease (COPD) and a 60 pack year history of smoking went to another hospital after a 1-week history of cough, progressively worsening dyspnea, and pleuritic chest pain. Two years earlier, she had had right hemicolectomy and left nephrectomy for a gunshot wound to the abdomen. Her vital signs and results of physical examination were reported as normal except for decreased breath sounds and scattered wheezes. Pulse oximetry showed an oxygen saturation of 85% on room air. Complete blood count, international normalized ratio, activated partial thromboplastin time, metabolic profile, and electrocardiographic and chest x-ray findings were reported as normal. After initial evaluation, the patient was treated for a COPD exacerbation with xopenexk and methylprednisolone (SoluMedrol). For possible pneumonia, she received ticarcillin clavulanate, azithromycin, and zanamivir. Enoxaparin therapy, 70 mg subcutaneously every 12 hours, was initiated for suspected pulmon ary thromboembolism. Four days after admission, the patient's respiratory status had improved, and a ventilation/perfusion lung scan was interpreted as showing low probability for pulmonary embolism. Enoxaparin therapy was discontinued after nine doses. On the fifth day, the patient had severe pain in the right lower quadrant. Within 12 hours, she became hypotensive (blood pressure of 80/60 mm Hg). The hemoglobin value dropped to 4.9 g/dL, the blood urea nitrogen level increased from 12 to 49 mg/dL, and the serum creatinine level increased from 1.5 to 2.4 mg/dL. Computed tomography of the abdomen showed a large right-sided retroperitoneal hematoma and left pleural effusion. The patient received transfusion of 9 units of packed red blood cells and 8 units of fresh frozen plasma and then was transferred to the University of South Alabama Medical Center.

On admission to our hospital, she was afebrile with a respiratory rate of 20/min, a heart rate of 92/min and blood pressure of 175/95 mm Hg. The lung examination showed scattered wheezes bilaterally and dullness to percussion over both inferior lung fields. There was a large right flank ecchymosis resembling Turner's sign (Fig 1). Laboratory values were similar to those obtained from the transferring institution except for a hemoglobin value of 10.6 g/dL and a leukocyte count of 15,000/[micro]L with 88% granulocytes. Arterial blood gas values were pH 7.40, [PCO.sub.2] 48 mm Hg, [PO.sub.2] 68 mm Hg, [HCO.sub.3] 29 mEq/L, and oxygen saturation of 92% on supplemental oxygen with an [FIO.sub.2] of 50% delivered via facemask. A chest x-ray film showed bilateral pleural effusions. Computed tomography of the chest and abdomen showed bilateral hemothorax (Fig 2) and large right retroperitoneal hematoma (Fig 3). Thoracentesis yielded sanguineous pleural fluid (red blood cell count of 4,000,000/[micro]L and leukocyte c ount of 3,600/[micro]L). The patient was treated for the COPD exacerbation with ipratropium bromide, albuterol, supplemental oxygen, and intravenous corticosteroids. For possible community-acquired pneumonia, she received ceftriaxone and azithromycin. The patient continued to be hypoxic and required supplemental oxygen ([FIO.sub.2] of 40% to 50%) to maintain an oxygen tension >55 mm Hg. The hypoxemia repeatedly improved after thoracentesis to evacuate blood from the pleural space, but the improvement was only temporary. On the third day after transfer, the patient was electively intubated because of hypercapnea ([PCO.sub.2] of 85 mm Hg) after a failed trial of continuous positive airway pressure support. The patient was extubated 3 days later and was weaned off supplemental oxygen. Hemoglobin levels remained stable and renal function returned to normal.

DISCUSSION

Despite many advantages over unfractionated heparin, enoxaparin is associated with a comparable rate of major bleeding complications. (5,9,10) In most cases, major bleeding syndromes are procedure-related, but bleeding may also occur spontaneously (5,9,10) and may cause fatal complications such as intracranial hemorrhage (5) or retroperitoneal hematoma. (4,5) Risk factors for LMW heparin-induced hemorrhage are thought to be similar to those already linked to hemorrhage induced by unfractionated heparin: recent surgery or trauma, concomitant use of aspirin, thrombolysis, concurrent glycoprotein IIb/IIIa inhibitor use, and age >70 years. (11,12) The optimal dosage of LMW heparins has not been established for extremes of body weight, renal insufficiency, pregnancy, or children.

Almost half of all enoxaparin-related major bleeding complications occur within 3 days of therapy. (5) Our patient had hemothorax and retroperitoneal hematoma on the fifth day (after nine doses) of a standard therapeutic dose of enoxaparin (1 mg/kg of body weight subcutaneously every 12 hours). (9) Interestingly, evacuation of blood from the pleural spaces with repeated thoracenteses resulted in only temporary respiratory improvement. Postextubation computed tomography showed only a small decrease in the size of the pleural effusions, despite evacuation of 1.5 L of blood (combined from three thoracenteses) and with no change in serum hemoglobin levels. These findings suggest the possibility of a communication between the retroperitoneal hematoma and the pleural spaces. Whether anatomic changes caused by previous operations involving the retroperitoneum contributed to retroperitoneal bleeding or its possible progression to the pleural space remains unknown. The effect of enoxaparin may also have been influence d by the presence of only one functioning kidney. In our patient, hemothorax itself probably did not cause respiratory failure but may have contributed to decreased functional lung capacity already hampered by the COPD exacerbation.

Retroperitoneal hematoma has been reported twice previously in patients treated with enoxaparin. (4, 5) Spontaneous hemothorax has not been previously reported in patients receiving a therapeutic dose of enoxaparin and should be added to the list of potential complications of administration of LMW heparin.

References

(1.) Ananthasubramaniam K, Beattie JN, Rosman HS, et al: How safely and for how long can warfarin therapy be withheld in prosthetic heart valve patients hospitalized with a major hemorrhage? Chest 2001; 119:478-484

(2.) Katz R, Admon D, Pode D: Life-threatening retroperitoneal hematoma caused by anticoagulant therapy for myocardial infarction after SWL. J Endourol 1997; 11:23-25

(3.) Albada J, Nieuwenhuis HK, Sixma JJ: Treatment of acute venous thromboembolism with low molecular weight heparin (Fragmin). results of a double-blind randomized study. Circulation 1989; 80:935-940

(4.) Montoya JP, Pokala N, Melde SL: Retroperitoneal hematoma and enoxaparin. Ann Intern Med 1999; 131:796-797

(5.) Antman EM, McCabe CH, Gurfinkel EP, et al: Enoxaparin prevents death and cardiac ischemic events in unstable angina/non-Q-wave myocardial infarction, results of the Thrombolysis in Myocardial Infarction (TIMI) 11B Trial. Circulation 1999; 100:1593-1601

(6.) Dzielski T, Nowicka D, Pasz P, et al: Hemothorax and retroperitoneal hematoma with the secondary posthemorrhagic anemia as a complication of oral anticoagulant and nonsteroidal anti-inflammatory drug therapy. Pol Merkuriusz Lek 2000; 8:335-336

(7.) Moskovitz B, Braner B, Engel A, et al: Multifocal bleeding due to anticoagulant therapy. Urol Int 1988; 43:53-55

(8.) Bragg FE: Hemothorax complicating anticoagulation for pulmonary embolus. a report of 2 patients. J Maine Med Assoc 1975; 66:274-275

(9.) Cohen M, Demers C, Gurfinkel EP, et al: A comparison of low-molecular-weight heparin with unfractionated heparin for unstable coronary artery disease. Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events Study Group. N Engl J Med 1997; 337:447-452

(10.) Noble S, Peters DH, Goa KL: Enoxaparin. a reappraisal of its pharmacology and clinical applications in the prevention and treatment of thromboembolic disease. Drugs 1995; 49:388-410

(11.) Dose-ranging trial of enoxaparin for unstable angina: results of TIMI IIA. The Thrombolysis in Myocardial Infarction (TIMI) IIA Trial Investigators. J Am Coll Cardiol 1997; 29:1474-1482

(12.) Levine MN, Raskob G, Landefeld S, et al: Hemorrhagic complications of anticoagulant treatment. Chest 2001; 119:108S-121S

RELATED ARTICLE: KEY POINTS

* In our patient, computed tomography of the chest and abdomen showed bilateral hemothorax and large right retroperitoneal hematoma.

* Risk factors for LMW heparin-induced hemorrhage are thought to be similar to those already linked to hemorrhage induced by unfractionated heparin: recent surgery or trauma, concomitant use of aspirin, thrombolysis, concurrent glycoprotein IIb/IIIa inhibitor use, and age >70 years.

* Spontaneous hemothorax should be added to the list of potential complications of administration of LMW heparin.

From the Department of Internal Medicine, University of South Alabama College of Medicine, Mobile.

Reprint requests to Martin A. Alpert, MD, University of South Alabama Medical Center, 2451 Fillingim St, Suite 10-C, Mobile, AL 36617.