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Cocaine-Induced Thrombosis of Common Iliac and Popliteal Arteries
Cocaine-Induced Thrombosis of Common Iliac and Popliteal Arteries Raffy Mirzayan, MD, Sue E. Hanks, MD, and Fred A. Weaver, MD, Los Angeles, California
Cocaine-induced thrombosis has been reported in the literature; however, its mechanism is not fully understood. Most cases are of small caliber vessels, such as the coronaries and cerebral vasculature. We report a case of a 36-year-old man with signs and symptoms of acute arterial insufficiency in his right lower extremity. At angiography, the right common iliac artery and the popliteal artery were occluded. The patient was successfully treated with thrombolytic therapy. Cocaine-induced thrombosis should be suspected in a patient with history of cocaine abuse who presents with acute arterial insufficiency in an extremity, without an identifiable source. (Ann Vasc Surg 1998;12:476-481.)
INTRODUCTION It is estimated that over 5 million people in the United States use cocaine on a regular basis.1-3 A 1990 National Household Drug Survey showed that 11% of Americans older than 12 years had used cocaine at least once and 7% of adults between 18 and 34 years had used it the previous year.4 Cocaine, benzoylmethylecgonine, is derived from leaves of the Erythroxylum coca plant, found predominantly in the mountains of Peru, Ecuador, and Bolivia.5 In recent years, ‘‘crack’’ (alkaloid cocaine) has gained popularity over the powder form (cocaine hydrochloride) because of its higher addiction potential, lower cost, and ease of handling.6 Cocaine inhibits the presynaptic reuptake of monoamine transmitters (principally epinephrine, norepinephrine, and dopamine, as well as serotonin),7 which leads to an increased postsynaptic concentration thought to account for the euphoric effects as well as peripheral sympathomimetic effects such as From the Departments of Orthopedic Surgery (R.M.), Radiology (S.E.H.), and Surgery (F.A.W.), University of Southern California School Medicine, Los Angeles County and University of Southern California Medical Center, Los Angeles, CA. Correspondence to: F.A. Weaver, MD, Department of Surgery, USC Health Consultation Center, 1510 San Pablo Street, Suite 514, Los Angeles, CA 90033, USA. 476
tachycardia, hypertension, and vasospasm.8 Routes of administration include oral, vaginal, rectal, sublingual, intranasal, smoking (free-base), subcutaneous, intramuscular, or intravenous injection.2 Myocardial infarctions9-24 and cerebral vascular accidents5,25-27 caused by cocaine have been previously documented in the literature. Vascular spasm and arterial thrombosis due to cocaine are thought to be the main etiologies. However, these reports are of small caliber vessels. We present a case of acute thrombosis of common iliac and popliteal arteries without an identifiable source, which we believe was cocaine induced.
CASE REPORT A 36-year-old African American man complained of a 2-day history of right lower extremity pain. He stated that his symptoms began 1 hour after intranasal cocaine use, and he continued to use cocaine in the 2 days prior to admission. Right hip, thigh, calf, and foot pain was constant, present at rest, and only partially relieved with dependency. He denied any history of claudication, prior similar episodes, left lower extremity pain, chest, or abdominal pain. History of diabetes, hypertension, coronary artery disease (CAD), family history of CAD, sickle cell disease, or myeloproliferative diseases was absent. He admitted to a 40-pack-year history of smoking and 8 years of cocaine and ‘‘crack’’ use. He denied intravenous drug abuse.
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Fig. 1. Digital subtraction abdominal aortagram demonstrates complete occlusion of the right common iliac artery. Fig. 2. Right popliteal arteriogram demonstrates complete occlusion of the popliteal artery at the knee joint with reconstitution of the anterior tibial artery.
On physical examination, his blood pressure was 120/ 70 mmHg and his pulse was 96 beats per min and afebrile. He was in moderate distress secondary to pain. His heart rate and rhythm were regular and no murmurs were auscultated. The abdomen was nondistended and nontender. Bowel sounds were present and no pulsatile masses were palpated. The patient had a cool right lower extremity with dependent rubor and elevation pallor but without trophic hair, skin, or nail changes. There was a 2+ left femoral pulse, 1+ left popliteal pulse, and 2+ left dorsalis pedis and posterior tibialis pulses. The ankle brachial index on the left was 0.87. There were no palpable pulses in his right femoral, popliteal, dorsalis pedis, and posterior tibialis arteries. Bruits were absent over the carotid arteries, the abdomen, or the femoral arteries. No Doppler signal was present over the dorsalis pedis or posterior tibial arteries on the right. There was decreased sensation and motor strength of the right lower extremity. An electrocardiogram revealed normal sinus rhythm. A transthoracic echocardiogram revealed good left ventricular function, normal-sized left atrium, normal valve function, no wall motion abnormalities, and no intracardiac thrombi. A computed tomography scan of the chest and an abdominal ultrasound were performed which did not reveal thoracic or abdominal aortic aneurysms, respectively. The patient was anticoagulated immediately with intravenous heparin and underwent diagnostic arteriography. The aorta, from the root to the trifurcation, was
normal. The right common iliac artery was occluded at the origin, and the right popliteal artery was occluded at the level of the trifurcation (Figs. 1 and 2). A multiside hole infusion catheter was positioned across the right common iliac occlusion and 250,000 units of urokinase was infused (Fig. 3A). An infusion of 120,000 units of urokinase was administered overnight. Follow-up arteriography demonstrated residual clot in the common and external iliac arteries. Therefore, an infusion wire was placed coaxially through the catheter into the external iliac thrombus, and 120,000 units of urokinase was infused into both the catheter and wire, for a total of 240,000 units/hour for 5 hours. The iliac artery was thrombus free at this time, so the popliteal thrombus was then treated by positioning an infusion wire across the occlusion. Another 120,000 units of urokinase was infused overnight. The final arteriogram demonstrated the right common iliac artery to be of normal caliber, free of residual thrombus or underlying stenoses (Fig. 3B). The right popliteal artery had a small residual thrombus, with good flow to the right anterior tibial artery that was patent into the foot (Fig. 4). The posterior tibial artery was occluded proximally, but reconstituted at the midcalf and was patent distally. Subsequently, the patient’s symptoms resolved. His right lower extremity pulses returned and were 2+ throughout. Subsequent hematological work-up including antithrombin III, protein C & S, lupus anticoagulant, activated protein C resistance, antinuclear antibodies, rheumatoid factor, antifactor XA, sickle cell screen, and hu-
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Fig. 3. A Initiation of thrombolytic therapy with initial clot lysis. The filling defect in the proximal common iliac represents residual thrombus. B Following thrombolytic treatment with urokinase, the right common iliac artery is free of thrombus. No underlying stenoses were revealed. Fig. 4. A The right popliteal artery is patent following thrombolytic therapy with a small amount of residual thrombus. B The peroneal and anterior tibial arteries are patent but the posterior tibial artery remains occluded.
man immunodeficiency virus were all negative. The patient was orally anticoagulated and discharged without any residual symptoms. At a 1-year follow-up, the patient remains asymptomatic.
DISCUSSION Cocaine has become the most commonly seen illicit drug in emergency room visits.28,29 The mistaken belief that cocaine is a harmless, nonaddicting recreational drug, as well as the decline in its price over the last decade, have led to an increase in its abuse.2 Although numerous medical complications are as-
sociated with cocaine use, such as acute myocardial infarction10,11,28,30 and cerebrovascular accidents,5,25-27 peripheral arterial complications have rarely been described and mostly involve the enteric organs.31-43 Cocaine-associated arterial or venous thrombosis has been described, but the underlying mechanism has not been entirely defined.44 Platelet aggregation and subsequent release of vasoactive mediators is the dominant theory.45 Using flow cytometric studies detecting P-selectin, found on the surface of activated platelets, Kugelmass et al.46,47 have shown platelet activation of in vitro in human platelets and
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in vivo in dogs. However, Rezkalla et al.48 demonstrated that human platelets in vitro treated with cocaine became more aggregable only after a nonaggregating low dose of adenosine diphosphate was added. This suggests a theory that cocaine may not directly activate platelets, but sensitizes platelets to some aggregatory stimuli. Another theory implicates arachidonic acid metabolism in the vascular system.49 Since thromboxanes induce thrombosis by stimulating platelet aggregation, and prostacycline counteracts this phenomenon, the imbalance of thromboxane synthesis over that of prostacycline in the presence of cocaine may predispose to thromboses.45,50 These theories of platelet aggregation are supported by autopsy studies that demonstrate acute occlusive thrombi composed mostly of platelets.3,16,51,52 Virmani et al.3 reported a 23year-old woman with a history of chronic use of free-base cocaine (crack) who had experienced sudden cardiac arrest in an emergency room. Postmortem studies revealed that the left anterior descending coronary artery was totally occluded by a platelet thrombus. Stenberg et al.52 reported a 38year-old man with no previous cardiac history, but with a long history of cocaine abuse, who developed acute myocardial infarction 15 min after intravenous injection of cocaine. Postmortem examination revealed acute occlusive thrombi composed predominantly of platelets in the left anterior descending and right coronary arteries. Myocardial infarction due to cocaine use was first described by Coleman53 in 1982. Since then, over 100 cases of cocaine-induced myocardial infarction have been documented.9-24 Minor et al.’s30 comprehensive review of the literature demonstrated that 38% of these cases had normal coronary vessels at angiography or autopsy. In a review of cases of cocaine-associated myocardial events, Rezkalla et al.48 demonstrated that 28% of subjects had normal coronary arteries, 33% had a coronary thrombus, while 39% had coronary atherosclerotic disease. Lange et al.54 have demonstrated significant vasoconstriction of coronary vessels during angiography after administration of cocaine. These and other reports suggest the theory that cocaineinduced coronary vasospasm culminates in thrombosis.15,24,25,30,55 Thrombotic phenomena in the arterial system from cocaine use have been described in other organ systems other than the heart and brain. Ischemia of small bowel and colon is most common with a total of 16 cases reported in the literature.3149 describe a 35-year-old-man who 43 Heng et al. developed skin necrosis 4 min after intravenous injection of cocaine. Wohlman56 and Sharff57 re-
Case reports 479
ported two 32-year-old men with right renal artery thromboembolus that developed 15 and 30 sec, respectively, after each patient injected cocaine intravenously. Reznik et al.58 reported an aortic thrombosis with extension into bilateral renal arteries in a cocaine-exposed neonate (2800 g) after an umbilical artery catheter was placed. Other vascular complications included the rupture of an ascending aorta59 and inadvertent intraarterial cocaine injection into the radial artery that led to complete occlusion of the artery.60 Chen et al.61 reported the only extremity arterial occlusion. A 49-year-old chronic cocaine abuser occluded of the right internal iliac, profunda femoris, and popliteal arteries as well as the celiac axis, splenic, and hepatic arteries. The patient was successfully treated operatively and discharged on long-term warfarin. He had no complications at 12-month follow-up.
CONCLUSIONS Our case of common iliac and popliteal artery thrombosis due to cocaine is only the second reported in such large caliber vessels. The patient had no underlying hypercoagulable state. He responded well to thrombolytic therapy. Cocaine-induced thrombosis should be considered in a patient with a history of cocaine abuse who presents with acute arterial insufficiency in an extremity, without an identifiable source. Thrombolytic therapy is a reasonable first option if the limb is not threatened. Operative intervention should be considered when time is a limiting factor. Postintervention shortterm intravenous and oral anticoagulation are important in preventing rethrombosis. In the long term, cessation of cocaine use and aspirin therapy are important in minimizing further events. REFERENCES 1. Abelson HI, Miller JD. A decade of trends in cocaine use in the household population. DA Res Monogr 1985;61:35-49. 2. Cregler LL, Mark H. Medical complications of cocaine abuse. N Engl J Med 1986;315:1495-1500. 3. Virmani R, Robinowitz M, Smialek JE, et al. Cardiovascular effects of cocaine: an autopsy study of 40 patients. Am Heart J 1988;115:1068-1076. 4. National Institute on Drug Abuse. National Household Survey on Drug Abuse: main findings 1990. Washington, DC: U.S. Department of Health and Human Services. DHHS publication no. (ADM) 91-1788, 1991. 5. Levine SR, Welch KMA. Cocaine and stroke. Stroke 1988; 19:779-783. 6. Washton AM, Gold MS, Pottash AC. ‘‘Crack’’: early report on a new drug epidemic. Postgrad Med J 1986;5:52-58. 7. Rezkalla S, Hale S, Kloner RA. Cocaine-induced heart disease. Am Heart J 1990;120:1403-1408.
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8. Hueter DC. Cardiovascular effects of cocaine. JAMA 1987; 257:979. 9. Ascher EK, Stauffer JC, Gaasch WH. Coronary artery spasm, cardiac arrest, transient electrocardiographic Q waves and stunned myocardium in cocaine-associated acute myocardial infarction. Am J Cardiol 1988;61:939-941. 10. Cregler LL, Mark H. Myocardial infarction associated with cocaine abuse: a case report. Tex Heart Inst J 1986;13:174. 11. Cregler LL, Mark H. Relation of acute myocardial infarction to cocaine abuse. Am J Cardiol 1985;56:794. 12. Gould L, Gopalaswamy C, Patel C, et al. Cocaine-induced myocardial infarction. NY State J Med 1985;85:660-661. 13. Hadjimiltiades S, Covalesky V, Manno BV, et al. Coronary arteriographic findings in cocaine abuse-induced myocardial infarction. Cathet Cardiovasc Diagn 1988;14:33-36. 14. Howard RE, Hueter DC, Davis GJ. Acute myocardial infarction following cocaine abuse in a young woman with normal coronary arteries. JAMA 1985;254:95-96. 15. Isner JM, Estes NAM III, Thompson PD, et al. Acute cardiac events temporally related to cocaine abuse. N Engl J Med 1986;315:1438-1443. 16. Kossowsky WA, Lyon AF. Cocaine and acute myocardial infarction: a probable connection. Chest 1984;86:729-731. 17. Pasternack PF, Colvin SB, Baumann FG. Cocaine-induced angina pectoris and acute myocardial infarction in patients younger than 40 years. Am J Cardiol 1985;55:847. 18. Rod JL, Zucker RP. Acute myocardial infarction shortly after cocaine inhalation. Am J Cardiol 1987;59:161. 19. Rollinger JM, Belzberg AS, Macdonald IL. Cocaine-induced myocardial infarction. Can Med Assoc J 1986;135:45-46. 20. Schachne JS, Roberts BH, Thompson PD. Coronary-artery spasm and myocardial infarction associated with cocaine use. N Engl J Med 1984;310:1665-1666. 21. Smith HWB III, Liberman HA, Brody SL, et al. Acute myocardial infarction temporally related to cocaine use: clinical, angiographic, and pathophysiologic observations. Ann Intern Med 1987;107:13-18. 22. Weiss RJ. Recurrent myocardial infarction caused by cocaine abuse. Am Heart J 1986;111:793. 23. Wilkins CE, Mathur VS, Ty RC, et al. Myocardial infarction associated with cocaine abuse. Texas Heart Inst J 1985;12: 385-387. 24. Zimmerman FH, Gustafson GM, Kemp HG. Recurrent myocardial infarction associated with cocaine abuse in a young man with normal coronary arteries: evidence for coronary artery spasm culminating in thrombus. J Am Coll Cardiol 1987;9:964-968. 25. Konzen JP, Levine SR, Garcia JH. Vasospasm and thrombus formation as possible mechanisms of stroke related to alkaloidal cocaine. Stroke 1995;26:1114-1118. 26. Levine SR, Brust JCM, Futrell N, et al. Cerebrovascular complications of the use of the ‘‘crack’’ form of alkaloidal cocaine. N Engl J Med 1990;323:699-704. 27. Petty GW, Brust JCM, Tatemichi TK, et al. Embolic stroke after smoking ‘‘crack’’ cocaine. Stroke 1990;21:1632-1635. 28. Brody SL, Slovis CM, Wrenn KD. Cocaine-related medical problems: consecutive series of 233 patients. Am J Med 1990;88:325-331. 29. MacDonald DI. Cocaine leads ED drug visits. JAMA 1987; 258:2029. 30. Minor RL, Scott BD, Brown DD, et al. Cocaine-induced myocardial infarction in patients with normal coronary arteries. Ann Intern Med 1991;115:797-806. 31. Brown DN, Rosenholtz MJ, Marshall JB. Ischemic colitis re-
Annals of Vascular Surgery
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lated to cocaine abuse. Am J Gastroenterol 1994;89:15581561. Endress C, Gary DGK, Wollschlaeger G. Bowel ischemia and perforation after cocaine use. AJR Am J Roentgenol 1992; 159:73-75. Fishel R, Hamamoto G, Barbul A, et al. Cocaine colitis. Is this a new syndrome? Dis Colon Rectum 1985;28:264-266. Freudenberger RS, Cappell MS, Hutt DA. Intestinal infarction after intravenous cocaine administration. Ann Intern Med 1990;113:715-716. Garfia A, Valverde JL, Borondo JC, et al. Vascular lesions in intestinal ischemia induced by cocaine-alcohol abuse: report of a fatal case due to overdose. J Forensic Sci 1990;35:740745. Hazanas FH, Torres CP, Delgado FI. Multiorgan failure and intestinal ischemia after cocaine intoxication [letter]. Intensive Care Med 1993;19:239-240. Hon DC, Salloum LJ, Hardy HW III, et al. Crack induced enteric ischemia. N Engl J Med 1990;87:1001-1002. Martin TJ. Cocaine-induced mesenteric ischemia. N C Med J 1991;52:429-430. Mizrahi S, Laor D, Stamler B. Intestinal ischemia induced by cocaine abuse. Arch Surg 1988;123:394. Mustard R, Gray R, Maziak D, et al. Visceral infarction caused by cocaine abuse: a case report. Surgery 1992;112: 951-955. Myers SI, Clagett P, Valentine RJ, et al. Chronic intestinal ischemia caused by intravenous cocaine use: Report of two cases and review of the literature. J Vasc Surg 1996;23:724729. Nalbandian H, Sheth N, Dietrich R, et al. Intestinal ischemia caused by cocaine ingestion: report of two cases. Surgery 1985;97:374-376. Yang RD, Han MW, McCarthy JH. Ischemic colitis in a crack abuser. Dig Dis Sci 1991;36:238-240. Kolodgie FD, Virmani R, Cornhill F, et al. Increase in atherosclerosis and adventitial mast cells in cocaine abusers: an alternative mechanism of cocaine-associated coronary vasospasm and thrombosis. J Am Coll Cardiol 1991;17:15531560. Togna G, Tempesto E, Togna AR, et al. Platelet responsiveness and biosynthesis of thromboxane and prostacycline in response to in vitro cocaine treatment. Hemostasis 1985;15: 100-107. Kugelmass AD, Oda A, Monahan K, et al. Activation of human platelets by cocaine. Circulation 1993;88:876-883. Kugelmass AD, Shannon RP, Yeo EL, et al. Intravenous cocaine induces platelet activation in the conscious dog. Circulation 1995;91:1336-1340. Rezkalla SH, Mazza JJ, Kloner RA, et al. Effects of cocaine platelets in healthy subjects. Am J Cardiol 1993;72:243-246. Heng MCY, Haberfeld G. Thrombotic phenomena associated with intravenous cocaine. J Am Acad Dermatol 1987;16: 462-468. Moncada S, Gryglewski RJ, Bunting S, et al. A lipid peroxide inhibits the enzyme in blood vessel microsomes that generate from prostaglandin endoperoxides the substance (prostaglandin X) which prevents platelet aggregation. Prostaglandins 1976;12:715-737. Simpson RW, Edwards WD. Pathogenesis of cocaineinduced ischemic heart disease. Arch Pathol Lab Med 1986; 110:479-484. Stenberg RG, Winniford MD, Hillis LD, et al. Simultaneous acute thrombosis of two major coronary arteries following intravenous cocaine use. Arch Pathol Lab Med 1989;113: 521-524.
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53. Coleman DL, Ross TF, Naughton JL. Myocardial ischemia and infarction related to recreational cocaine use. West J Med 1982;136:444-446. 54. Lange RA, Cigarroa RG, Yancy CW, Jr. Cocaine-induced coronary-artery vasoconstriction. N Engl J Med 1989;321: 1557-1562. 55. Vincent GM, Anderson JL, Marshall HW. Coronary spasm producing coronary thrombosis and myocardial infarction. N Engl J Med 1983;309:220-223. 56. Wohlman RA. Renal artery thrombosis and embolization associated with intravenous cocaine injection. South Med J 1987;80:928-930. 57. Sharff JA. Renal infarction associated with intravenous cocaine use. Ann Emerg Med 1984;13:1145-1147.
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58. Reznick VM, Anderson J, Griswold WR, et al. Successful fibrinolytic treatment of arterial thrombosis and hypertension in a cocaine-exposed neonate. Pediatrics 1989;84:735738. 59. Barth CW III, Bray M, Roberts WC. Rupture of the ascending aorta during cocaine intoxication. Am J Cardiol 1986; 57:496. 60. Klabacha ME, Miller SH, Pav JM, et al. Inadvertent intraradial arterial injection of cocaine. Ann Plast Surg 1984;13:6062. 61. Chen JC, Hsiang YN, Morris C, et al. Cocaine-induced multiple vascular occlusions: a case report. J Vasc Surg 1996;23: 719-723.
Cocaine-induced thrombosis has been reported in the literature; however, its mechanism is not fully understood. Most cases are of small caliber vessels, such as the coronaries and cerebral vasculature. We report a case of a 36-year-old man with signs and symptoms of acute arterial insufficiency in his right lower extremity. At angiography, the right common iliac artery and the popliteal artery were occluded. The patient was successfully treated with thrombolytic therapy. Cocaine-induced thrombosis should be suspected in a patient with history of cocaine abuse who presents with acute arterial insufficiency in an extremity, without an identifiable source. (Ann Vasc Surg 1998;12:476-481.)
INTRODUCTION It is estimated that over 5 million people in the United States use cocaine on a regular basis.1-3 A 1990 National Household Drug Survey showed that 11% of Americans older than 12 years had used cocaine at least once and 7% of adults between 18 and 34 years had used it the previous year.4 Cocaine, benzoylmethylecgonine, is derived from leaves of the Erythroxylum coca plant, found predominantly in the mountains of Peru, Ecuador, and Bolivia.5 In recent years, ‘‘crack’’ (alkaloid cocaine) has gained popularity over the powder form (cocaine hydrochloride) because of its higher addiction potential, lower cost, and ease of handling.6 Cocaine inhibits the presynaptic reuptake of monoamine transmitters (principally epinephrine, norepinephrine, and dopamine, as well as serotonin),7 which leads to an increased postsynaptic concentration thought to account for the euphoric effects as well as peripheral sympathomimetic effects such as From the Departments of Orthopedic Surgery (R.M.), Radiology (S.E.H.), and Surgery (F.A.W.), University of Southern California School Medicine, Los Angeles County and University of Southern California Medical Center, Los Angeles, CA. Correspondence to: F.A. Weaver, MD, Department of Surgery, USC Health Consultation Center, 1510 San Pablo Street, Suite 514, Los Angeles, CA 90033, USA. 476
tachycardia, hypertension, and vasospasm.8 Routes of administration include oral, vaginal, rectal, sublingual, intranasal, smoking (free-base), subcutaneous, intramuscular, or intravenous injection.2 Myocardial infarctions9-24 and cerebral vascular accidents5,25-27 caused by cocaine have been previously documented in the literature. Vascular spasm and arterial thrombosis due to cocaine are thought to be the main etiologies. However, these reports are of small caliber vessels. We present a case of acute thrombosis of common iliac and popliteal arteries without an identifiable source, which we believe was cocaine induced.
CASE REPORT A 36-year-old African American man complained of a 2-day history of right lower extremity pain. He stated that his symptoms began 1 hour after intranasal cocaine use, and he continued to use cocaine in the 2 days prior to admission. Right hip, thigh, calf, and foot pain was constant, present at rest, and only partially relieved with dependency. He denied any history of claudication, prior similar episodes, left lower extremity pain, chest, or abdominal pain. History of diabetes, hypertension, coronary artery disease (CAD), family history of CAD, sickle cell disease, or myeloproliferative diseases was absent. He admitted to a 40-pack-year history of smoking and 8 years of cocaine and ‘‘crack’’ use. He denied intravenous drug abuse.
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Fig. 1. Digital subtraction abdominal aortagram demonstrates complete occlusion of the right common iliac artery. Fig. 2. Right popliteal arteriogram demonstrates complete occlusion of the popliteal artery at the knee joint with reconstitution of the anterior tibial artery.
On physical examination, his blood pressure was 120/ 70 mmHg and his pulse was 96 beats per min and afebrile. He was in moderate distress secondary to pain. His heart rate and rhythm were regular and no murmurs were auscultated. The abdomen was nondistended and nontender. Bowel sounds were present and no pulsatile masses were palpated. The patient had a cool right lower extremity with dependent rubor and elevation pallor but without trophic hair, skin, or nail changes. There was a 2+ left femoral pulse, 1+ left popliteal pulse, and 2+ left dorsalis pedis and posterior tibialis pulses. The ankle brachial index on the left was 0.87. There were no palpable pulses in his right femoral, popliteal, dorsalis pedis, and posterior tibialis arteries. Bruits were absent over the carotid arteries, the abdomen, or the femoral arteries. No Doppler signal was present over the dorsalis pedis or posterior tibial arteries on the right. There was decreased sensation and motor strength of the right lower extremity. An electrocardiogram revealed normal sinus rhythm. A transthoracic echocardiogram revealed good left ventricular function, normal-sized left atrium, normal valve function, no wall motion abnormalities, and no intracardiac thrombi. A computed tomography scan of the chest and an abdominal ultrasound were performed which did not reveal thoracic or abdominal aortic aneurysms, respectively. The patient was anticoagulated immediately with intravenous heparin and underwent diagnostic arteriography. The aorta, from the root to the trifurcation, was
normal. The right common iliac artery was occluded at the origin, and the right popliteal artery was occluded at the level of the trifurcation (Figs. 1 and 2). A multiside hole infusion catheter was positioned across the right common iliac occlusion and 250,000 units of urokinase was infused (Fig. 3A). An infusion of 120,000 units of urokinase was administered overnight. Follow-up arteriography demonstrated residual clot in the common and external iliac arteries. Therefore, an infusion wire was placed coaxially through the catheter into the external iliac thrombus, and 120,000 units of urokinase was infused into both the catheter and wire, for a total of 240,000 units/hour for 5 hours. The iliac artery was thrombus free at this time, so the popliteal thrombus was then treated by positioning an infusion wire across the occlusion. Another 120,000 units of urokinase was infused overnight. The final arteriogram demonstrated the right common iliac artery to be of normal caliber, free of residual thrombus or underlying stenoses (Fig. 3B). The right popliteal artery had a small residual thrombus, with good flow to the right anterior tibial artery that was patent into the foot (Fig. 4). The posterior tibial artery was occluded proximally, but reconstituted at the midcalf and was patent distally. Subsequently, the patient’s symptoms resolved. His right lower extremity pulses returned and were 2+ throughout. Subsequent hematological work-up including antithrombin III, protein C & S, lupus anticoagulant, activated protein C resistance, antinuclear antibodies, rheumatoid factor, antifactor XA, sickle cell screen, and hu-
478
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Fig. 3. A Initiation of thrombolytic therapy with initial clot lysis. The filling defect in the proximal common iliac represents residual thrombus. B Following thrombolytic treatment with urokinase, the right common iliac artery is free of thrombus. No underlying stenoses were revealed. Fig. 4. A The right popliteal artery is patent following thrombolytic therapy with a small amount of residual thrombus. B The peroneal and anterior tibial arteries are patent but the posterior tibial artery remains occluded.
man immunodeficiency virus were all negative. The patient was orally anticoagulated and discharged without any residual symptoms. At a 1-year follow-up, the patient remains asymptomatic.
DISCUSSION Cocaine has become the most commonly seen illicit drug in emergency room visits.28,29 The mistaken belief that cocaine is a harmless, nonaddicting recreational drug, as well as the decline in its price over the last decade, have led to an increase in its abuse.2 Although numerous medical complications are as-
sociated with cocaine use, such as acute myocardial infarction10,11,28,30 and cerebrovascular accidents,5,25-27 peripheral arterial complications have rarely been described and mostly involve the enteric organs.31-43 Cocaine-associated arterial or venous thrombosis has been described, but the underlying mechanism has not been entirely defined.44 Platelet aggregation and subsequent release of vasoactive mediators is the dominant theory.45 Using flow cytometric studies detecting P-selectin, found on the surface of activated platelets, Kugelmass et al.46,47 have shown platelet activation of in vitro in human platelets and
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in vivo in dogs. However, Rezkalla et al.48 demonstrated that human platelets in vitro treated with cocaine became more aggregable only after a nonaggregating low dose of adenosine diphosphate was added. This suggests a theory that cocaine may not directly activate platelets, but sensitizes platelets to some aggregatory stimuli. Another theory implicates arachidonic acid metabolism in the vascular system.49 Since thromboxanes induce thrombosis by stimulating platelet aggregation, and prostacycline counteracts this phenomenon, the imbalance of thromboxane synthesis over that of prostacycline in the presence of cocaine may predispose to thromboses.45,50 These theories of platelet aggregation are supported by autopsy studies that demonstrate acute occlusive thrombi composed mostly of platelets.3,16,51,52 Virmani et al.3 reported a 23year-old woman with a history of chronic use of free-base cocaine (crack) who had experienced sudden cardiac arrest in an emergency room. Postmortem studies revealed that the left anterior descending coronary artery was totally occluded by a platelet thrombus. Stenberg et al.52 reported a 38year-old man with no previous cardiac history, but with a long history of cocaine abuse, who developed acute myocardial infarction 15 min after intravenous injection of cocaine. Postmortem examination revealed acute occlusive thrombi composed predominantly of platelets in the left anterior descending and right coronary arteries. Myocardial infarction due to cocaine use was first described by Coleman53 in 1982. Since then, over 100 cases of cocaine-induced myocardial infarction have been documented.9-24 Minor et al.’s30 comprehensive review of the literature demonstrated that 38% of these cases had normal coronary vessels at angiography or autopsy. In a review of cases of cocaine-associated myocardial events, Rezkalla et al.48 demonstrated that 28% of subjects had normal coronary arteries, 33% had a coronary thrombus, while 39% had coronary atherosclerotic disease. Lange et al.54 have demonstrated significant vasoconstriction of coronary vessels during angiography after administration of cocaine. These and other reports suggest the theory that cocaineinduced coronary vasospasm culminates in thrombosis.15,24,25,30,55 Thrombotic phenomena in the arterial system from cocaine use have been described in other organ systems other than the heart and brain. Ischemia of small bowel and colon is most common with a total of 16 cases reported in the literature.3149 describe a 35-year-old-man who 43 Heng et al. developed skin necrosis 4 min after intravenous injection of cocaine. Wohlman56 and Sharff57 re-
Case reports 479
ported two 32-year-old men with right renal artery thromboembolus that developed 15 and 30 sec, respectively, after each patient injected cocaine intravenously. Reznik et al.58 reported an aortic thrombosis with extension into bilateral renal arteries in a cocaine-exposed neonate (2800 g) after an umbilical artery catheter was placed. Other vascular complications included the rupture of an ascending aorta59 and inadvertent intraarterial cocaine injection into the radial artery that led to complete occlusion of the artery.60 Chen et al.61 reported the only extremity arterial occlusion. A 49-year-old chronic cocaine abuser occluded of the right internal iliac, profunda femoris, and popliteal arteries as well as the celiac axis, splenic, and hepatic arteries. The patient was successfully treated operatively and discharged on long-term warfarin. He had no complications at 12-month follow-up.
CONCLUSIONS Our case of common iliac and popliteal artery thrombosis due to cocaine is only the second reported in such large caliber vessels. The patient had no underlying hypercoagulable state. He responded well to thrombolytic therapy. Cocaine-induced thrombosis should be considered in a patient with a history of cocaine abuse who presents with acute arterial insufficiency in an extremity, without an identifiable source. Thrombolytic therapy is a reasonable first option if the limb is not threatened. Operative intervention should be considered when time is a limiting factor. Postintervention shortterm intravenous and oral anticoagulation are important in preventing rethrombosis. In the long term, cessation of cocaine use and aspirin therapy are important in minimizing further events. REFERENCES 1. Abelson HI, Miller JD. A decade of trends in cocaine use in the household population. DA Res Monogr 1985;61:35-49. 2. Cregler LL, Mark H. Medical complications of cocaine abuse. N Engl J Med 1986;315:1495-1500. 3. Virmani R, Robinowitz M, Smialek JE, et al. Cardiovascular effects of cocaine: an autopsy study of 40 patients. Am Heart J 1988;115:1068-1076. 4. National Institute on Drug Abuse. National Household Survey on Drug Abuse: main findings 1990. Washington, DC: U.S. Department of Health and Human Services. DHHS publication no. (ADM) 91-1788, 1991. 5. Levine SR, Welch KMA. Cocaine and stroke. Stroke 1988; 19:779-783. 6. Washton AM, Gold MS, Pottash AC. ‘‘Crack’’: early report on a new drug epidemic. Postgrad Med J 1986;5:52-58. 7. Rezkalla S, Hale S, Kloner RA. Cocaine-induced heart disease. Am Heart J 1990;120:1403-1408.
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