therapeutic modalities

Brief Reports

Upper Extremity Deep Venous Thrombosis: A Case Report and Review of Current Diagnostic/Therapeutic Modalities MARY J. HUGHES, DO, JOSEPH C. D’AGOSTINO, Upper extremity deep venous thrombosis is a relatively rare clinical entity with potentially grave sequelae. Pathophysiological mechanisms are currently believed to be multifactorial, involving thoracic compressive forces in conjunction with the activation of the coagulation cascades. Diagnostically, venography remains the gold standard, and the combination of phleborheography and Doppler ultrasound approach a 90% specificity and sensitivity. Numerous therapeutic modalities have been described, and long- term venous patency seems to correlate best with local urokinase and concomitant systemic heparin administration followed by oral anticoagulation and decompressive surgery. A case report is described, and a review of the literature follows. CASE REPORT A 24-year-old athletic man with no significant prior medical history initially presented to the emergency department with a chief complaint of swelling and paresthesias of his right upper extremity for one day’s duration. The patient denied any prior or recent history of trauma, antecedent illness, or coagulopathy. On physical examination, vital signs were within normal limits, and there was a noted, welllocalized area of erythema and edema to the biceps region. Distal neurovascular and motor function was intact. With a presumptive diagnosis of acute allergic reaction versus myositis, the patient was treated with antihistamines and steroids being subsequently discharged on nonsteroidal antiinflammatory medication. The patient returned within 36 hours after discharge with progressive, right, upper extremity swelling and pain that tended to exacerbate during exercise. There was an absence of chest pain or shortness of breath, and the history elicited was essentially unremarkable, inclusive of risk factors for thromboembolic disease. On repeat clinical examination, pertinent findings included a minimally larger and erythematous right upper extremity compared with the left, with evidence of superficial venous

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engorgement. Circumferential measurements obtained showed a 1.75 cm and 1 cm discrepancy compared with the left arm above and below the elbow, respectively. There was palpable tenderness to the medial aspect of the axilla without evidence of cord or lymphadenopathy. Distal radial, ulnar, brachial, and axillary pulses were intact. In addition, there were no motor or sensory deficits, and deep tendon reflexes were within normal limits. With a clinical suspicion of upper extremity deep venous thrombosis the patient was admitted, anticoagulated with heparin, and underwent duplex ultrasound imaging that showed right subclavian/axillary vein thrombosis. HOSPITALCOURSE The patient was maintained on heparin for 24 hours while he reported mild improvement in symptomatology. A laboratory profile, including sickle cell prep, coagulation studies, antithrombin 3. and protein C levels, was unremarkable. In an attempt to better delineate the vascular bed, a venogram was performed that showed total occlusion of the right subclavian/axillary vein (Figure 1). The patient was then treated with local urokinase while continued on high therapeutic heparin. Follow-up venogram after 36 hours showed a restoration of subclavian venous flow with residual thrombosis (Figure 2). A subsequent venogram at 46 hours showed complete clot lysis with residual narrowing of the midsubclavian vein believed to be consistent with intimal scarring (Figure 3). An abduction view showed total occlusion of the subclavian vein via first rib compression, raising the question of Paget-Von Schroetter or “effort-related” thrombosis (Figure 4). The patient was subsequently discharged on a combination of subcutaneous heparin therapy of one week’s duration and oral Coumadin (Warfarin sodium, DuPont, Wilmington, DE) while scheduled for follow-up orthopedic evaluation for anticipated decompressive surgery. DISCUSSION

From the Michigan State University Emergency Medicine Residency Program, Lansing, Ml. Manuscript received March 7, 1994; revision accepted April 6, 1994. Address reprint requests to Dr Mary J. Hughes, Osteopathic Program Director, MSU-EM Residency Program, PO Box 30480, Lansing, MI 48909-9986. Key word: Upper extremity deep venous thrombosis. Copyright 0 1994 by W.B. Saunders Company 0735-6757/94/l 206-0005$5.00/O

The incidence of upper extremity deep venous thrombosis (UEDVT) is relatively rare, accounting for approximately 2% of total venous thrombosis. However, it is the most common vascular problem occurring in athletes today.’ Although initially believed to be a relatively benign, selflimiting disorder, there have been numerous studies documenting significant long-term morbidity and occasional catastrophic complications, including limb loss secondary to 631

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FIGURE I. Venogram of a patient with primary axillary vein thrombosis showing total occlusion of the right axillary/ subclavian vein.

gangrene and death caused by pulmonary embolic phenomena.2,3 Traditionally, UEDVT has been classified into two categories, primary and secondary, based on cause, although there is some variation encountered. With greater use of invasive cardiac monitoring, an iatrogenic classification has evolved. Independent of classification, the pathogenesis of each subgroup can be related to combinations of the classic triad of the factors determinant of thrombosis: hypercoagulability, intimal changes, and venous stasis.4.5 Primary, spontaneous, or “effort” thrombosis, initially described by S. James Paget and Von Schroetter, is believed

to occur as a result of repetitive external compressive forces such as those that may occur in thoracic outlet syndrome in conjunction with an endothelial intimal defect involving a release of thrombogenic substances that, in turn, activates the intrinsic and extrinsic coagulation cascades.4.6 Numerous compressive anatomic anomalies, including hypertrophied scalenus anterior muscle, axillary lipomas, and cervical ribs have been implicated in causing an intimal defect, resulting in thrombus formation either by occlusion and/or release of thrombogenic substances.7.8 Secondary thrombosis includes those patients in which a primary or secondary

FIGURE 2. After 36 hours, local urokinase and systemic heparin in the same patient as in Figure 1, with restoration of Row around residual thrombus (arrow) noted.

FIGURE 3. Follow-up venogram at 46 hours showing residual narrowing of the midsubclavian vein believed to be consistent with intimal scarring caused by repetitive compressive forces.

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FIGURE 4. Stress venography (right shoulder abduction) at discharge shows total occulation of the subclavian vein consistent with “effort-related” or primary thrombosis.

hypercoagulable state is present. Examples of primary disorders include antithrombin 3 and protein C and S deficiencies, whereas secondary disorders include malignancy, congestive heart failure, and polycythemia. Iatrogenic causality, occasionally listed with secondary thrombosis, is believed to occur as a result of traumatic manipulation of the vascular endothelium that occurs with central venous catheterization or indwelling catheters in conjunction with alteration of venous flow, ie, turbulence resulting in platelet aggregation and release of procoagulants.4 Subclavian catheters are the most common cause of catheter related UEDVT.9 The gauge of the catheter, its composition, and the type of infusion have been correlated with incidence of thrombosis, and approximately 28% of subclavian catheter-related UEDVT have venous thrombosis develop, often subclinically.‘~‘O~” Of note, a recent article reports a disproportionate number of UEDVT attributed to intravenous drug abuse, and pathogenesis is attributed to concomitant injection of vasoactive substances.” Epidemiologically, primary thrombosis has a male predisposition, occurs most commonly in the third decade of life, and has a right hand predilection, which is probably secondary to a greater incidence of right hand dominance. Eightyfive percent of cases present within 24 hours after physical activity, and complaints usually include pain, swelling, and occasionally paresthesias of the involved extremity.13 In rare incidences, no discomfort has been reported.14 Pain is usually described as a dull ache, more common distally and typically exacerbated with activity and relieved with rest. The inciting mechanism is usually repetitive use, and the patient often reports easy fatigability. The presentation may be either acute, subacute, or chronic. Physical examination usually shows a firm, nonpitting, circumferential edema and superficial venous engorgement. A mottled, cyanotic appearance to the skin is occasionally present, and variations in limb temperature have been reported (presumably based on the presence of coexistent arterial spasm). A palpable axillary cord is an inconsistent finding, and hypoesthesia

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may be found in a nondermatomal distribution. Neurological examination is otherwise usually normal.8.‘5 Differential diagnoses include contusion, lymphedema, sprain, cellulitis, arteriovenous fistula, septic arthritis. hematoma, and postphlebitic syndrome.’ Diagnostically, numerous noninvasive modalities have been described. To date, venography remains the gold standard, although it is not without attendant risk. Routine Doppler ultrasound initially was found to be unreliable because of poor differentiation of collateral venous circulation.16 Knudson et al, using color-flow Doppler, showed a sensitivity and specificity of 18% and 92%, respectively, when evaluating UEDVT, when correlated with venography/CT imaging. ” Limitations involve poor proximal central vein delineation and occasional distorted anatomy. One false positive was reported as a result of external compression of the subclavian vein. Prospectively comparing magnetic resonance imaging (MRI) with contrast venography, Erdman et al showed a 90% and 100% sensitivity and specificity when evaluating the central venous system, with reported greater delineation of chronicity using MRI.18 Occlusion straingauge plethysmography has been used to detect acute versus chronic thrombosis with a fair degree of accuracy.” An investigational method used to diagnose UEDVT is light reflection rheography, which measures venous pressure changes as recorded from the subdermal capillary plexus with a reported sensitivity/specificity of 92%/100%, respectively. Similar to Doppler studies. this technique is limited in its delineation of the central venous system,although it does not require the same degree of operator expertise and is helpful in identifying chronic occlusion.*’ Phleborheography (PRG) measures segmental volume changes and, indirectly, venous flow. It has been found to have various sensitivities and specificities ranging from 84% to 88% and 75% to 90%, respectively. When used in combination with Doppler ultrasound the values of sensitivity and specificity approach 90%. False negatives were encountered in patient’s with extensive collaterals and with existent thrombosis.‘6.2’.22 Although originally considered a rare complication of UEDVT, pulmonary embolism is now believed to be more common and has been a reported cause of death in several patients with secondary thrombosis.3,23 Kerr et al reported a 25% case fatality incidence in an 8% subgroup of patients with documented pulmonary embolism and coexistent UEDVT.24 Monreal et al showed a 15% incidence in pulmonary embolism in a retrospective study. Of note, all of the patients in the study had been placed on full-dose heparin at the time of diagnosis, and the subset of patients that were with the highest risk seemed to be catheter related.25 Several studies have reported similar findings.4*‘2~‘3 Delay in diagnosis has resulted in several instances of gangrene that required amputation.26.‘7 It is important to note that the aforementioned patients had significant concomitant illness that increased their tendency to a hypercoagulable state. The treatment of UEDVT has evolved from conservative modalities including elevation, rest, and heat to the current local thrombolytic therapy. Previous studies documented a 50% to 74% incidence of long-term morbidity, ie, pain/ swelling in patients treated by systemic anticoagulation and/ or decompressive surgery with or without thrombecretomy.4’2,28 D.L. Steed, using systemic streptokinase,

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ported complete symptomatic resolution in 72% of patients with primary thrombosis. However, only 14.2% had complete resolution of thrombus on follow-up venography.29 Becker et al showed venous patency in four patients with primary thrombosis using local urokinase or streptokinase and achieved good short-term results in two patients that required decompressive surgery. They also described an area of luminal irregularity at the site of the thrombus in each case.3o Variable success has been reported using local fibrinolytic therapy with venous balloon dilatation and/or surgical decompression in a small group of patients with primary thrombosis.28 A recent isolated case report involving the use of systemic anistreptalase emergently followed by heparin resulted in near resolution of thrombus and no symptoms at 1 year follow-up.“’ Taylor et al showed successful short-term outcome in two patients treated with local thrombolytic therapy followed by first rib resection.32 In a recent study involving 50 patients with primary thrombosis by Machleder. long-term venous patency seemed to correlate with initial use of local urokinase. Interestingly, predecompressive angioplasty resulted in a high rate of reocclusion. Those patients who underwent decompressive surgery after thrombolysis showed a 64% versus 44% venous patency rate at 3 year follow-up. Additionally, an overall 93% and 64% asymptomatic status was reported on 3 year follow-up venography in patients with patent versus occluded veins, respectively.33 CONCLUSION Although a relatively rare clinical entity. the diagnosis and treatment of UEDVT presents a formidable challenge. Because of the occasional atypical presentation in conjunction with variability in clinical findings, suboptimal noninvasive diagnostic techniques, and potential complications, it behooves the physician to maintain a relatively high index of suspicion of this disorder. Pathogenesis is now considered to be multifactorial involving both external compressive forces in conjunction with intimal defects causing thrombogenic tendencies. Noninvasive modalities of diagnosis are suboptimal, although the combination of color-flow Doppler and PRG approaches a 90% sensitivity and specificity. However, venography remains the gold standard. Avoidable long-term sequelae seem to be related to initial aggressive therapy with local thrombolytics, with concomitant heparin administration followed by a period of oral anticoagulation, and decompressive surgery in those patients with evidence of anatomic anomalies or cessation of venous flow on stress radiography. In patients with postsurgical recurrent thrombus, balloon dilatation has shown to be beneficial.

1. Scotta RP: Vascular problems in the proximal tremity. Clin Sports Med 1990;9:382-388

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4. Donayre CE, White GH, Mehringer SN, et al: Pathogenesis determines late morbidity of axillosubclavian vein thrombosis. Am J Surg 1986;152:179-184 5. Horattas MC, Wright DJ, Fenton AH, et al: Changing concepts of deep venous thrombosis of the upper extremitiesReport of a series and review of literature. Surgery 1988;104: 561-567 6. Paget J: Clinical Lectures and Essays. London, ,Longmans, Green and Co, 1875

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7. Campbell CB, Chandler JG, Tegtmeyer CJ, et al: Axillary, subclavian and basilic cephalic vein obstruction. Surgery 1977; 82:816-825 8. Machleder H: Veno-occlusive disorders tremity. Curr Probl Surg 1988;XXV:44-61

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9. Painter TD, Kerpf M: Deep venous thrombosis of the upper extremity: Five years experience at a university hospital. Angiology 1984;35:743-749 10. Welch GW, McKee1 DW, Silverstein catheter composition in the development Surg Gynecol Obstet 1974;138:421-424

P, et al: The role of of thrombophlebitis.

11. Dicostanzo J, Sastre B, Choux R, et al: Experimental approach to the prevention of catheter related central venous thrombosis. J Paren Enter Nutr 1984;8:293-297 12. Lisse JR, Davis CP, Thurmond-Aderle M: Upper extremity deep venous thrombosis: Increased prevalence due to cocaine abuse. Am J Med 1989;87:457-460 13. Adams JT, DeWeese JA: “Effort” thrombosis of the axillary and subclavian veins. J Trauma 1971 ;11:923-930 14. Skerker RS, Flandery FC: Case presentation: Painless arm swelling in a high school baseball player. Med Sci Sports Exer 1992;21:1185-1189 15. Cromwell DL: Effort thrombosis of the subclavian and axillary vein: Review of the literature and case report with followup with venography. Ann Intern Med 1960;52:1137-1143 16. Pollack EW, Walsch J: Subclavian - axillary vein thrombosis: Role of non-invasive diagnostic methods. South Med J 1980; 7311503-l 506 17. Knudson GJ, Wiedmeyer DA, Erickson SJ, et al: Color doppler sonographic imaging in the assessment of upper extremity deep venous thrombosis. AJR Am J Roentgen01 1990; 154:399-403 18. Erdman WA, Jayson HT, Redman HC, et al: Deep venous thrombosis of the extremities: Role of MR imaging in the diagnosis. Radiology 1990;174:425-431 19. Zuffery P, Pararos C, Monti M, et al: Assessment of acute and old venous thrombosis of the upper extremity by venous strain gauge plethysmography. Vasa 1992;21:263-267 20. Mukherjee D, Anderson CA, Bertoglio MC: Use of light reflection rheography for diagnosis of axillary or subclavian venous thrombosis. Am J Surg 1991;161:651-656 21. Sullivan ED, Reece Cl: Phleborheography extremity. Arch Surg 1983;118:1134-1136

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22. Sottiurai VS, Towner K, McDonnel AE, et al. Diagnosis of upper extremity deep thrombosis using non-invasive techniques. Surgery 1982;91:582-585 23. Tilney NR, Griffith MB, Edwards EA: Natural history of major venous thrombosis of the upper extremity. Arch Surg 1970;101:792-796 24. Kerr TM, Lutter KS, Moeller DM, et al: Upper extremity thrombosis diagnosed by duplex scanning. Am J Surg 1990;160: 202-206

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Thrombolytic therapy with anistrepalase. Ann Emerg Med 1993; 22:748-750 32. Taylor LM, McAllister, Dennis DL: Thrombolytic therapy followed by first rib resection for spontaneous (“effort”) subclavian vein thrombosis. Am J Surg 1985;149:644-647 33. Machleder HI: Evaluation of a new treatment strategy for Paget-Schroetter syndrome: Spontaneous thrombosis of the axillary/subclavian vein. J Vast Surg 1993;17:305-317