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Acute Aortoiliac Thrombosis Due to Cocaine Intake
Acute Aortoiliac Thrombosis Due to Cocaine Intake Carmen Maria Paulin Vera, Alfonso Mateos Colin, Gabriela Calvo Arrojo, and Jose M. Colodro Garcı´a, Lugo, Spain
Cocaine has become one of the most commonly abused recreational drugs, resulting in a significantly increased number of visits to the emergency department due to the acute symptoms caused by its intake. The acute onset of cardiovascular complications, such as myocardial infarction, arrhythmias, stroke, and kidney and spleen infarction, has been described in association with cocaine use, but aortic thrombosis has rarely been studied in this context. We report a case of acute aortoiliac thrombosis in a young male patient with no underlying medical records.
Cocaine intake has led to major health and social problems. Its increased consumption among young people has been described in association with cardiovascular complications such as myocardial infarction (MI), dilated cardiomyopathy, arrhythmias, ruptured aorta, aortic dissection, endocarditis, arterial thrombosis, sudden cardiac death, stroke, and kidney or spleen infarction.1e3 Its toxicity can be explained by its ability to block sodium channels, leading to a local anesthetic or membrane-stabilizing effect and inhibition of the reuptake of norepinephrine and dopamine at the presynaptic cleft. This cathecolamine release can lead to profound hypertension, intense vasoconstriction, and increased cardiac workload.4 Also, platelet activation, a-granule release, and platelet-containing microaggregate formation promote thrombosis and predisposition to ischemic events.5 Although cocaine-induced arterial thrombosis is uncommon, we report a case of acute aortoiliac
Vascular Surgery & Internal Medicine Department, Hospital Lucus Augusti, Lugo, Spain. Correspondence to: Carmen Maria Paulin Vera, MD, Hospital Lucus Augusti, San Cibrao s/n, ZC 27003 Lugo, Spain; E-mail: car_paulinv@ hotmail.com Ann Vasc Surg 2013; 27: 239.e1e239.e4 http://dx.doi.org/10.1016/j.avsg.2012.06.013 Ó 2013 Elsevier Inc. All rights reserved. Manuscript received: June 5, 2011; manuscript accepted: April 16, 2012.
thrombosis in a young male patient with no relevant medical history. A 35-year-old man with no medical disease, a cigarette smoker of 20 packs/year, and a cocaine abuser during the last 10 years, was admitted. He indicated that he had inhaled cocaine 15 days prior to admission. He also stated that for the past 9 months he had numbness, calf pain, and acral coldness, especially while playing football or walking long distances, which progressively worsened and changed his lifestyle. He presented to the emergency department complaining of a sudden onset of left lower limb rest pain associated with acral coldness, pallor, and numbness. On physical examination, bilateral femoral pulses were absent, accompanied by pallor of the legs and diminished sensibility and movement. A computed tomography (CT) angiography scan and three-dimensional rendering reconstruction (Fig. 1) showed a complete obstruction of the subrenal aorta and common iliac arteries, aortic collateral circles, and recanalization of the external iliac artery of the right lower limb and superficial femoral artery of the left. No lesions were found in the thoracic aorta. Normal chest radiography, electrocardiogram, and transthoracic echocardiogram (TTE) findings were obtained. Laboratory testing was within normal limits (Table I). The patient subsequently underwent emergency revascularization surgery in which an aortobifemoral bypass Dacron graft was performed. During the surgery no atherosclerotic changes were
239.e1
239.e2 Case reports
Annals of Vascular Surgery
Table I. Laboratory tests
Fig. 1. Complete obstruction of the subrenal aorta and common iliac arteries with aortic collateral circles and recanalization of the external iliac artery of the right lower limb and superficial femoral artery of the left.
observed, no aortic biopsy was taken, and no previous aortic thrombectomy was detected. The postoperative course was uneventful, with recovery of distal pulses, and after 1 week he was discharged without complications. Anticoagulation based on low-molecular-weight heparin and antiplatelet therapy was given. Despite medical therapy, 1 week later he returned with similar ischemic symptoms. A new CT scan was performed showing an abundant thrombus with an irregular surface against the proximal anastomosis of the previous bypass (Fig. 2); in addition, a further TTE was obtained, showing no evidence of residual thrombus or other alterations. An emergency attempt at revascularization was then performed via left transfemoral thrombectomy and local thrombolysis with urokinase, achieving excellent results by regaining distal pulses. No further complications were observed during the postoperative course. Medical therapy with anticoagulants and antiplatelet drugs was continued. As part of outpatient follow-up, another CT scan was performed 2 months later. The scan showed mural thrombus on the posterior aortic wall contiguous to the proximal anastomosis. We decided to
Autoimmune profile (a) Antinuclear antibodies (b) Antithyroid antibodies (c) Perinuclear and classical antineutrophil cytoplasmatic antibodies (d) Rheumatoid factor Coagulation profile (a) a2-plasmin inhibitor (b) Anticardiolipin antibodies (c) Factor V Leiden (1691) (d) Homocysteine (e) Lupus-type anticoagulant (f) Plasminogen (g) Protein C and S activity (h) Prothrombin (G20210A) gene mutations Conventional blood chemistry Endocrine profile (a) Cortisol levels (b) Thyroid and parathyroid hormones Hemogram Proteinogram Routine urine analysis Serology (a) HIV (b) Hepatitis B and C virus Tumor markers (a) a-fetoprotein (b) Carbohydrate antigen 19.9 (c) Carcinoembryonic antigen (d) Prostate-specific antigen
continue with surveillance and medical therapy. The patient has remained asymptomatic.
DISCUSSION Cocaine has become among the most commonly abused recreational drugs. Its use has been responsible for increased visits to the emergency department due to the acute cardiovascular events caused by overdose. MI and stroke are the most frequent complications associated to cocaine intake.1 Cocaine-induced myocardial ischemia has been documented even in patients with normal coronary arteries and is unrelated to the dose, route, or frequency of use. Coronary ischemic symptoms related to thrombosis are seen relatively rapidly after cocaine use (60 minutes), whereas peripheral arterial thrombosis is seen hours after usage and likely a consequence of critical vasoconstriction. It is believed that coronary vasoconstriction is induced by a-adrenergic stimulation. Lange et al. found that subjects with atherosclerotic disease
Vol. 27, No. 2, February 2013
Fig. 2. Abundant thrombus with irregular surface against the proximal aortic anastomosis of previous bypass.
who had narrowed coronary segments had a greater reduction in cross-sectional areas than in the nondiseased segments, suggesting that these patients are at greater risk of having an ischemic event in response to cocaine.4 Acute arterial thrombosis of the lower limb affecting various segments, such as iliac, popliteal, and distal arteries, have been described previously. Such cases have been treated successfully with surgical thrombectomy or thrombolytic agents.6e8 There have been only a few reported cases of acute aortic thrombosis due to cocaine intake in young patients who inhaled crack. The appropriate management of such cases remains uncertain. Two of the reported cases were resolved nonoperatively and the patients were anticoagulated with heparin sodium, and in the other case the patient underwent thrombectomy with excellent results.9,10 The exact mechanism by which cocaine can induce arterial thrombosis is undetermined. Various mechanisms have been proposed as causes of vasoconstriction and thrombus formation. Heesch et al.5 demonstrated that cocaine exposure causes platelet activation, a-granule release, and platelet-containing microaggregate formation. Their findings suggest that these may be important mechanisms contributing to ischemic events in the setting of acute cocaine intoxication. Also, their data support that chronic use of cocaine could accelerate the development of atherosclerosis by stimulating the release of growth factors from platelets, which explains why they recommend use of platelet-inhibiting agents such as aspirin in the setting of cocaine-related ischemic syndromes. Havranek et al.11 affirmed that a dysfunctional endothelium in cocaine users may participate in the genesis of ischemic vascular accidents due to
Case reports 239.e3
an impairment of nitric oxide release leading to failure of platelet aggregation and an increase of vasoconstrictor factors such as thromboxane A2, serotonin, and endothelin. We have described the case of a young man with a history chronic cocaine and tobacco use who presented to the emergency department with sudden onset of lower limb resting pain. Although this was an acute presentation, we believe that the patient had chronic alterations based on the presence of aortic collateral circles on CT scan and clinical findings that included intermittent claudication. This evidence leads us to consider a possible superimposed mechanismdchronic aortic partial occlusion complicated by new aortic thrombi. It is speculative to affirm that in this case, platelet aggregation mechanisms outweigh vasospasm as the cause of the aortic thrombi development. There has been no consensus on how or whether to manage these occlusions. In our case, we did not hesitate to proceed with aortic bypass graft surgery due to the threat of diminished viability of the limbs. We believe that given the extensive use of cocaine among young people, it is important to consider possible aortic thrombosis, even in patients with chronic symptoms. Proper management should be based on clinical findings.
REFERENCES 1. Restrepo CS, Rojas CA, Martinez S, et al. Cardiovascular complications of cocaine: imaging findings. Emerg Radiol 2009;16:11e9. 2. Phillips K. Cocaine use is associated with a number of lifethreatening cardiovascular complications that require careful treatment. Drugs Ther Perspect 2010;26: 1e4. 3. Daniel JC, Huynh TT, Zouh W, et al. Acute aortic dissection associated with use of cocaine. J Vasc Surg 2007;46:427e33. 4. Lange RA, Cigarroa JE, Hills LD, Theodore E. Woodward award: cardiovascular complications of cocaine abuse. Trans Am Clin Climatol Assoc 2004;115:99e111. 5. Heesch CM, Wilhelm CR, Ristich J, Adnane J, Bontempo FA, Wagner WR. Cocaine activates platelets and increases the formation of circulating platelet containing microaggregates in humans. Heart 2000;83:688e95. 6. Coughlin PA, Mavor AI. Arterial consequences of recreational drug use. Eur J Vasc Endovasc Surg 2006;32: 389e96. 7. Collins CG, Seoighe D, Ireland A, Bouchier-Hayes D, McGrath F. Cocaine-associated lower limb ischemia. Vascular 2008;16:297e9. 8. Mirzayan R, Hanks SE, Weaver FA. Cocaine-induced thrombosis of common iliac and popliteal arteries. Ann Vasc Surg 1998;12:476e81.
239.e4 Case reports
9. Weber H, Kline RA, Lucas CE. Aortic thrombosis associated with cocaine use: report of two cases. Ann Vasc Surg 1999;113:302e4. 10. Mochizuki Y, Zhang L, Golestaneh S, Thananart S, Coco M. Acute aortic thrombosis and renal infarction in acute
Annals of Vascular Surgery
cocaine intoxication: a case report and review of literature. Clin Nephrol 2003;60:130e3. 11. Havranek EP, Nademanee K, Grayburn PA, Eichhorn EJ. Endothelium dependent vasorelaxation is impaired in cocaine arteriopathy. J Am Coll Cardiol 1996;28:1168e74.
Cocaine has become one of the most commonly abused recreational drugs, resulting in a significantly increased number of visits to the emergency department due to the acute symptoms caused by its intake. The acute onset of cardiovascular complications, such as myocardial infarction, arrhythmias, stroke, and kidney and spleen infarction, has been described in association with cocaine use, but aortic thrombosis has rarely been studied in this context. We report a case of acute aortoiliac thrombosis in a young male patient with no underlying medical records.
Cocaine intake has led to major health and social problems. Its increased consumption among young people has been described in association with cardiovascular complications such as myocardial infarction (MI), dilated cardiomyopathy, arrhythmias, ruptured aorta, aortic dissection, endocarditis, arterial thrombosis, sudden cardiac death, stroke, and kidney or spleen infarction.1e3 Its toxicity can be explained by its ability to block sodium channels, leading to a local anesthetic or membrane-stabilizing effect and inhibition of the reuptake of norepinephrine and dopamine at the presynaptic cleft. This cathecolamine release can lead to profound hypertension, intense vasoconstriction, and increased cardiac workload.4 Also, platelet activation, a-granule release, and platelet-containing microaggregate formation promote thrombosis and predisposition to ischemic events.5 Although cocaine-induced arterial thrombosis is uncommon, we report a case of acute aortoiliac
Vascular Surgery & Internal Medicine Department, Hospital Lucus Augusti, Lugo, Spain. Correspondence to: Carmen Maria Paulin Vera, MD, Hospital Lucus Augusti, San Cibrao s/n, ZC 27003 Lugo, Spain; E-mail: car_paulinv@ hotmail.com Ann Vasc Surg 2013; 27: 239.e1e239.e4 http://dx.doi.org/10.1016/j.avsg.2012.06.013 Ó 2013 Elsevier Inc. All rights reserved. Manuscript received: June 5, 2011; manuscript accepted: April 16, 2012.
thrombosis in a young male patient with no relevant medical history. A 35-year-old man with no medical disease, a cigarette smoker of 20 packs/year, and a cocaine abuser during the last 10 years, was admitted. He indicated that he had inhaled cocaine 15 days prior to admission. He also stated that for the past 9 months he had numbness, calf pain, and acral coldness, especially while playing football or walking long distances, which progressively worsened and changed his lifestyle. He presented to the emergency department complaining of a sudden onset of left lower limb rest pain associated with acral coldness, pallor, and numbness. On physical examination, bilateral femoral pulses were absent, accompanied by pallor of the legs and diminished sensibility and movement. A computed tomography (CT) angiography scan and three-dimensional rendering reconstruction (Fig. 1) showed a complete obstruction of the subrenal aorta and common iliac arteries, aortic collateral circles, and recanalization of the external iliac artery of the right lower limb and superficial femoral artery of the left. No lesions were found in the thoracic aorta. Normal chest radiography, electrocardiogram, and transthoracic echocardiogram (TTE) findings were obtained. Laboratory testing was within normal limits (Table I). The patient subsequently underwent emergency revascularization surgery in which an aortobifemoral bypass Dacron graft was performed. During the surgery no atherosclerotic changes were
239.e1
239.e2 Case reports
Annals of Vascular Surgery
Table I. Laboratory tests
Fig. 1. Complete obstruction of the subrenal aorta and common iliac arteries with aortic collateral circles and recanalization of the external iliac artery of the right lower limb and superficial femoral artery of the left.
observed, no aortic biopsy was taken, and no previous aortic thrombectomy was detected. The postoperative course was uneventful, with recovery of distal pulses, and after 1 week he was discharged without complications. Anticoagulation based on low-molecular-weight heparin and antiplatelet therapy was given. Despite medical therapy, 1 week later he returned with similar ischemic symptoms. A new CT scan was performed showing an abundant thrombus with an irregular surface against the proximal anastomosis of the previous bypass (Fig. 2); in addition, a further TTE was obtained, showing no evidence of residual thrombus or other alterations. An emergency attempt at revascularization was then performed via left transfemoral thrombectomy and local thrombolysis with urokinase, achieving excellent results by regaining distal pulses. No further complications were observed during the postoperative course. Medical therapy with anticoagulants and antiplatelet drugs was continued. As part of outpatient follow-up, another CT scan was performed 2 months later. The scan showed mural thrombus on the posterior aortic wall contiguous to the proximal anastomosis. We decided to
Autoimmune profile (a) Antinuclear antibodies (b) Antithyroid antibodies (c) Perinuclear and classical antineutrophil cytoplasmatic antibodies (d) Rheumatoid factor Coagulation profile (a) a2-plasmin inhibitor (b) Anticardiolipin antibodies (c) Factor V Leiden (1691) (d) Homocysteine (e) Lupus-type anticoagulant (f) Plasminogen (g) Protein C and S activity (h) Prothrombin (G20210A) gene mutations Conventional blood chemistry Endocrine profile (a) Cortisol levels (b) Thyroid and parathyroid hormones Hemogram Proteinogram Routine urine analysis Serology (a) HIV (b) Hepatitis B and C virus Tumor markers (a) a-fetoprotein (b) Carbohydrate antigen 19.9 (c) Carcinoembryonic antigen (d) Prostate-specific antigen
continue with surveillance and medical therapy. The patient has remained asymptomatic.
DISCUSSION Cocaine has become among the most commonly abused recreational drugs. Its use has been responsible for increased visits to the emergency department due to the acute cardiovascular events caused by overdose. MI and stroke are the most frequent complications associated to cocaine intake.1 Cocaine-induced myocardial ischemia has been documented even in patients with normal coronary arteries and is unrelated to the dose, route, or frequency of use. Coronary ischemic symptoms related to thrombosis are seen relatively rapidly after cocaine use (60 minutes), whereas peripheral arterial thrombosis is seen hours after usage and likely a consequence of critical vasoconstriction. It is believed that coronary vasoconstriction is induced by a-adrenergic stimulation. Lange et al. found that subjects with atherosclerotic disease
Vol. 27, No. 2, February 2013
Fig. 2. Abundant thrombus with irregular surface against the proximal aortic anastomosis of previous bypass.
who had narrowed coronary segments had a greater reduction in cross-sectional areas than in the nondiseased segments, suggesting that these patients are at greater risk of having an ischemic event in response to cocaine.4 Acute arterial thrombosis of the lower limb affecting various segments, such as iliac, popliteal, and distal arteries, have been described previously. Such cases have been treated successfully with surgical thrombectomy or thrombolytic agents.6e8 There have been only a few reported cases of acute aortic thrombosis due to cocaine intake in young patients who inhaled crack. The appropriate management of such cases remains uncertain. Two of the reported cases were resolved nonoperatively and the patients were anticoagulated with heparin sodium, and in the other case the patient underwent thrombectomy with excellent results.9,10 The exact mechanism by which cocaine can induce arterial thrombosis is undetermined. Various mechanisms have been proposed as causes of vasoconstriction and thrombus formation. Heesch et al.5 demonstrated that cocaine exposure causes platelet activation, a-granule release, and platelet-containing microaggregate formation. Their findings suggest that these may be important mechanisms contributing to ischemic events in the setting of acute cocaine intoxication. Also, their data support that chronic use of cocaine could accelerate the development of atherosclerosis by stimulating the release of growth factors from platelets, which explains why they recommend use of platelet-inhibiting agents such as aspirin in the setting of cocaine-related ischemic syndromes. Havranek et al.11 affirmed that a dysfunctional endothelium in cocaine users may participate in the genesis of ischemic vascular accidents due to
Case reports 239.e3
an impairment of nitric oxide release leading to failure of platelet aggregation and an increase of vasoconstrictor factors such as thromboxane A2, serotonin, and endothelin. We have described the case of a young man with a history chronic cocaine and tobacco use who presented to the emergency department with sudden onset of lower limb resting pain. Although this was an acute presentation, we believe that the patient had chronic alterations based on the presence of aortic collateral circles on CT scan and clinical findings that included intermittent claudication. This evidence leads us to consider a possible superimposed mechanismdchronic aortic partial occlusion complicated by new aortic thrombi. It is speculative to affirm that in this case, platelet aggregation mechanisms outweigh vasospasm as the cause of the aortic thrombi development. There has been no consensus on how or whether to manage these occlusions. In our case, we did not hesitate to proceed with aortic bypass graft surgery due to the threat of diminished viability of the limbs. We believe that given the extensive use of cocaine among young people, it is important to consider possible aortic thrombosis, even in patients with chronic symptoms. Proper management should be based on clinical findings.
REFERENCES 1. Restrepo CS, Rojas CA, Martinez S, et al. Cardiovascular complications of cocaine: imaging findings. Emerg Radiol 2009;16:11e9. 2. Phillips K. Cocaine use is associated with a number of lifethreatening cardiovascular complications that require careful treatment. Drugs Ther Perspect 2010;26: 1e4. 3. Daniel JC, Huynh TT, Zouh W, et al. Acute aortic dissection associated with use of cocaine. J Vasc Surg 2007;46:427e33. 4. Lange RA, Cigarroa JE, Hills LD, Theodore E. Woodward award: cardiovascular complications of cocaine abuse. Trans Am Clin Climatol Assoc 2004;115:99e111. 5. Heesch CM, Wilhelm CR, Ristich J, Adnane J, Bontempo FA, Wagner WR. Cocaine activates platelets and increases the formation of circulating platelet containing microaggregates in humans. Heart 2000;83:688e95. 6. Coughlin PA, Mavor AI. Arterial consequences of recreational drug use. Eur J Vasc Endovasc Surg 2006;32: 389e96. 7. Collins CG, Seoighe D, Ireland A, Bouchier-Hayes D, McGrath F. Cocaine-associated lower limb ischemia. Vascular 2008;16:297e9. 8. Mirzayan R, Hanks SE, Weaver FA. Cocaine-induced thrombosis of common iliac and popliteal arteries. Ann Vasc Surg 1998;12:476e81.
239.e4 Case reports
9. Weber H, Kline RA, Lucas CE. Aortic thrombosis associated with cocaine use: report of two cases. Ann Vasc Surg 1999;113:302e4. 10. Mochizuki Y, Zhang L, Golestaneh S, Thananart S, Coco M. Acute aortic thrombosis and renal infarction in acute
Annals of Vascular Surgery
cocaine intoxication: a case report and review of literature. Clin Nephrol 2003;60:130e3. 11. Havranek EP, Nademanee K, Grayburn PA, Eichhorn EJ. Endothelium dependent vasorelaxation is impaired in cocaine arteriopathy. J Am Coll Cardiol 1996;28:1168e74.