Streptokinase in the vein thrombosis. treatment of subclavian

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1 Streptokinase in the vein thrombosis treatment of subclavian David L. Steed, M.D., Michael F. Teodori, M.D., Andrew B. Peitzman, M.D., Clyde E. McAuley, M.D., Wishwa N. Kapoor, M.D., and Marshall W. Webster, M.D., Pittsburgh, Pa. During the past 2 years, streptokinase has been used to treat subclavian or axillary vein thrombosis in seven patients of whom two were considered "effort" thromboses and five resulted from use of a central venous catheter. All patients had venography performed before treatment to document the thrombosis, and venography was repeated after streptokinase therapy to determine the status of clot dissolution. Streptokinase was given either systemically or in a lowered dose locally, with low-dose therapy chosen whenever a catheter could be threaded up to the clot through an antecubital vein. Although all seven patients had resolution of their clinical symptoms, only one had complete dissolution of the thrombus. The failure of streptokinase to completely dissolve the thrombus suggests that, although apparent clinical improvement can be achieved after streptokinase infusion, treatment of the underlying cause, whenever possible, may be necessary if complete resolution of the thrombus is to occur. (J VASC SURG 1986; 4:28-32.) Thrombosis of the axillary or subclavian vein is uncommon, occurring with an incidence of 1% to 2% of that noted for deep venous thrombosis of the leg. 1-3 Although reported complications are rare and lasting disability is uncommon, 4 recent evidence suggests that as many as 12,6 of patients have significant complications, including pulmonary emboli and venous gangrene, s'6 Recommended treatment modalities include systemic anticoagulation and venous thrombectomy with or without first rib resection, as well as the more conservative therapy consisting of arm elevation and warm compresses. Dissatisfaction with the poor results of these modalities has prompted others to use fibrinolytic agents, but the benefit of fibrinolytic agents in treating this entity is uncertain. The evaluation of results of any treatment by clinical examination is inadequate, because as many as 80% of patients may show clinical improvement even when no treatment is specifically directed at removal of the clot. We herein report the results of streptokinase therapy in the management of seven patients with axillary and subclavian vein thrombosis; the therapeutic efficacy was documented by venography before and after treatment and correlated with the findings on clinical examination. From the Departments of Surgery and Medicine, University of Pittsburgh School of Medicine. Reprint requests: David L. Steed, M.D., 1087 Scaife Hall, University of Pittsburgh, Pittsburgh, PA MATERIAL AND METHODS During the past 2 years, seven patients were treated for axillary or subclavian vein thrombosis. Patients underwent venography in the affected extremity to document the lesion and were then treated either systemically or locally with streptokinase. If the streptokinase was given systemically, the loading dose was 250,000 units followed by 100,000 U/hr. This dose was adjusted on the basis of whether the lyric state had been achieved. The dose was adjusted to keep the prothrombin time and the parial thromboplastin time at twice control. If the streptokinase was infused for local effect, the dose was 5000 U/ hr. There was no effect on clotting function when this dose was given. Local treatment was chosen whenever a catheter could be conveniently placed into the clot through an antecubital vein in the affected extremity. Treatment was then continued until the patient showed resolution of his/her clinical symptoms of pain, edema, and cyanosis. If resolution was not complete within 48 to 72 hours, strcptokinase infusion was discontinued and the patients were given heparin for systemic anticoagulation. Venography was then repeated to document any resolution of the thrombus within the vein. Anticoagulation with warfarin sodium was begun before the heparin was withdrawn. RESULTS Seven patients with axiuary or subclavian vein thrombosis were treated with streptokinase after ve- 28

2 Volume 4 Number 1 July 1986 Streptokinase to treat subclavian vein thrombosis 29 Table I. Streptokinase treatment and results in seven patients with subclavian and axillary vein thrombosis Venogram Treatment Venogram Patient Age Sex Cause before treatment (route, duration) a~er treatment 1 29 M Effort Occlusion of left Systemic, 48 hr Partial resolution SVC + AXV 2 22 M Effort Occlusion of right SCV Systemic, 48 hr Patent SCV with and partial occlusion some thrombus right AXV remaining 3 46 F CVP catheter Occlusion of left Systemic, 48 hr Patent AXV + SCV AXV + SCV 4 47 F Chemotherapy Near total occlusion of Systemic, 72 hr; catheter Partial resolution catheter right AXV + SCV not removed 5 69 M Chemotherapy Occlusion of right Systemic, 72 hr Near complete catheter AXV + SCV resolution 6 65 M TPN catheter Near-total occlusion of Local, 12 hr Partial resolution right SCV 7 64 M CVP catheter Occlusion of left SCV Local, 48 hr Near complete resolution SCV = subclavian vein; AXV = axillary vein; CVP = central venous pressure; TPN = total parenteral nutrition, nography documented the presence of a thrombus. There were three men and four women ranging in age from 22 to 69 years (Table I). Two patients had "effort" thrombosis whereas five had venous occlusion resulting from an indwelling central venous catheter placed for pressure monitoring (two patients), chemotherapy (two patients), or total parenteral nutrition (one patient). In all seven cases, patients were evaluated and treatment initiated within 48 hours of the onset of symptoms. The two patients with "effort" thrombosis were treated with streptokinase systemically for 48 hours. Both patients had complete resolution of their clinical symptoms, yet on follow-up venography, both had significant thrombus remaining within the axillary and subclavian veins (Figs. 1 and 2). At 2-year follow-up, one patient is free of symptoms whereas the other patient has vague discomfort in his arm with prolonged exertion. Neither patient has any swelling or signs of venous obstruction. Five patients had thrombosis resuking from use of a central venous catheter. After venography was performed to document that thrombosis, the catheter was removed before fibrinolytic therapy was begun in four of the five patients. Three patients were treated with streptokinase systemically, whereas two patients were given streptokinase locally in a lowered dose. All symptoms resolved within 72 hours in the three patients who received streptokinase systemically. However, on repeat venography, only one of the three patients had complete dissolution of the thrombus. In the patient in whom the central venous catheter was not removed before treatment, there was only minimal clot dissolution (Figs. 3 and 4). This patient died 2 months later. The other two patients have no signs or symptoms of venous obstruction. Two patients were given low-dose streptokinase directly into the thrombus by placement of an intravenous catheter near the clot through an antecubital vein. Although both patients had complete resolution of their clinical symptoms, there was only partial dissolution of the thrombus seen with venography (Figs. 5 and 6). One patient died 6 months later. The other patient has no evidence of venous obstruction. DISCUSSION The natural history of a major venous thrombosis occurring in an upper extremity has been well described. Although resolution of most acute symptoms commonly occurs within a few days, residual disability may be present in as many as 74% of patients. 7 Serious complications of this entity, including pulmonary embolus or venous gangrene, were once thought to be uncommon, yet Adams, McEvoy, and DeWeese s reported that 12% of patients with thrombosis of the upper extremity had pulmonary emboli. In addition, Warden, Wilmore, and Pruitt 8 noted upper extremity venous thrombosis to be the source of more than half of the pulmonary emboli found at autopsy in burn patients. Although some clinicians have managed this entity with little more than rest, arm elevation, and warm compresses, significant long-term disability often occurs in these patients and a more aggressive approach has evolved. 9 Treatment of a venous thrombosis of the upper extremity now generally includes anticoagulation, venous thrombectomy with or without first rib resection, or fibrinolytic therapy. Anti-

3 30 Steed et al. Journal of VASCULAR SURGERY Fig. 1. Case 2: Venogram of 22-year-old man with clot in right axillary and subclavian veins from "effort" thrombosis (arrow). Fig. 3. Case 4: Venogram of 47-year-old woman demonstrates thrombosis of right axillary and subclavian veins resulting from use of central venous pressure catheter (arrow). Fig. 2. Case 2: Although patency returned after systemic streptokinase infusion, thrombus remains within subclavian vein (arrows). coagulation with heparin has yielded satisfactory resuits with minimal morbidity and mortality. However, it has proved to be most effective in those patients with "effort" or spontaneous thrombosis, and anticoagulation provides less than satisfactory long-term benefit in patients with extrinsic compression of the axiuary or subclavian vein. l Operative therapy, including venous thrombectomy and accompanying first rib resection, has been recom- mended by some because of dissatisfaction with more conservative methods of therapy. Unfortunately, the results are not significantly better and operation is not without risk. 912 Venous thrombosis is often a multifactorial process, accounting in part for the poor results accompanying current therapy) s Venous intimal damage can result from medications given intravenously, radiographic dyes, trauma, indwelling catheters, pacemaker leads, venipuncture, or repeated compression of the vein by muscular contraction. Abnormal coagulation can occur in patients with malignancy, estrogen therapy, or biochemical abnormality, all having been documented in patients with subclavian vein thrombosis? 4 Extrinsic compression of the vein can be caused by subclavius or anterior scalene muscle abnormalities, a cervical rib, narrowing of the costodavicular space from muscle hypertrophy, tumor, or voluminous callus formation after a clavicular fracture. Because the possible causes of subclavian or axillary vein thrombosis are so varied, proper therapy may be directed at resolution of the thrombus and also correction of any underlying anatomic abnormalities that might have contributed to the thrombosis. We believe streptokinase to be preferable to thrombectomy in that it avoids the risks of operation and the possibility of intimal damage resulting from the use of an embolectomy catheter. All the patients in this series had venography performed to document not only the diagnosis of axillary or subclavian vein thrombosis but also to determine the extent of

4 Volume 4 Number 1 July 1986 Streptokinase to treat subclavian vein thrombosis 31 Fig. 5. Case 7: Venogram of 64-year-old man shows clot in left subclavian vein resulting from central venous pressure catheter (arrow). Fig. 4. Case 4: Catheter (see Fig. 3) was not removed (black arrows) and there is only partial improvement after streptokinase systemic therapy (open arrows)~." obstruction. Five of the seven patients in our series had subclavian vein thrombosis from an indwelling central venous catheter, supporting the findings of Warden, Wilmore, and Pruitt s who noted that the invasion of axillary and subclavian veins with monitoring or treatment catheters is an increasingly common cause for subsequent subclavian vein thrombosis. The other two cases were spontaneous or "effort" thrombosis in the dominant arms of young men. The treatment in each case was directed at lysis of the clot in view of the presumptive underlying cause. The central venous catheter was removed in four of the five patients. However, one patient was receiving chemotherapy and the catheter was not removed since venous access was difficult. There was minimal dissolution of the thrombus in this patient (Figs. 3 and 4). Since 80% of patients have spontaneous improvement in symptoms even without specific treatment, clinical evaluation alone is not adequate to evaluate clot dissolution. In fact, although all seven patients in our series had complete resolution of their symptoms within 72 hours, only one of the seven had complete dissolution of thrombus. Therefore, to adequately evaluate clot dissolution after streptokinase therapy, venography was performed in all patients when the streptokinase infusion was completed. Previous studies that failed to use venog- Fig. 6. Case 7: Venogram shows near-total resolution of thrombus with low-dose streptokinase therapy infused locally (arrow). raphy before and after streptokinase infusion do not fully answer questions regarding the usefulness of this medication, because clot lysis cannot be determined by clinical examination alone. Rubenstein and Creger is reported the use of streptokinase for 72 hours to dissolve a subclavian vein thrombosis in a patient receiving long-term parenteral nutrition through a Hickman catheter by subclavian vein. The catheter was removed before treat-

5 32 Steed et al. Journal of VASCULAR SURGERY ment. Zimmerman et al.16 reported a 48-hour urokinase infusion in 18 patients with subclavian vein thrombosis and demonstrated the return of vein patene T in 82% of cases. A study reported by Theiss and Wirtzfeld ~7 in the German literature with both streptokinase and urokinase therapy demonstrated improvement in 94% of patients, yet complete resolution of the clot occurred in only 57%. Taylor et al.x8 reported the successful use of streptokinase to dissolve clots in two patients who had "effort" thrombosis and followed this with first rib resection. Our study, which used streptokinase as well as venography both before and after treatment, is in agreement with the findings of these reports. Two of our patients received low-dose streptokinase locally, delivered directly into the clot through an intravenous catheter. Nearly complete resolution of the thrombus occurred in one of the two patients (Figs. 5 and 6). Becker et al..9 reported success with this technique, although in all four patients, urokinase was utimately used to dissolve the clot and two of the four went on to have operative procedures for subclavian vein thrombosis. The concept of low-dose local streptokinase infusion is appealing, since it should be possible to reduce the risk of a therapeutic complication, especially hemorrhage. Webb and Kerstein 2 reported success with low-dose local streptokinase infusion in one patient with subclavian vein thrombosis. REFERENCES 1. Coon WW, Willis PW. Thrombosis ofaxillary and subclavian veins. Arch Surg 1966; 94: Barker NW, Nygard KK, Waiters W, Priestly JT. A statistical study of postoperative venous thrombosis and pulmonary embolism. Mayo Clin Proc 1941; 16: Ochsner A, DeBakey ME, DeCamp RT, da Rocha E. Thrombo-embolism; Analysis of cases at the Charity Hospital in New Orleans over a 12-year period. Ann Surg 1951; 134: Hughes ES. Venous obstruction in the upper extremity (Pa- get-schrotter syndrome): Review of 320 cases. Int Abstr Surg 1949; 88: Adams JT, McEvoy RK, DeWeese JA. Primary deep venous thrombosis of the upper extremity. Arch Surg 1965; 91: Adams JT, DeWeese JA. "Effort" thrombosis of the axillary and subclavian veins. J Trauma 1971; 11: Tilney NL, Grifliths HJG, Edwards EA. Natural history of major venous thrombosis of the upper extremity. Arch Surg 1970; 101: Warden GD, Wilmore DW, Pruitt BA. Central venous thrombosis: A hazard of medical progress. J Trauma 1973; 13: Swinton NW, Edgett JW, Hall RJ. Primary subclavian-axillary vein thrombosis. Circulation 1968; 38: Campbell CB, Chandler JG, Tegtmeyer CJ, Bernstein EF. Axillary, subclavian, and brachiocephalic vein obstruction. Surgery, 1977; 82: Inahara T. Surgical treatment of "effort" thrombosis of the axillary and subclavian veins. Am Surg 1968; 34: Daskalakis E, Bouhoutsos J. Subclavian and axillary vein compression of musculoskeletal origin. Br J Surg 1980; 67: Rutherford RB. Vascular surgery. Philadelphia: WB Saunders Co, 1984; Sundqvist SB, Hedner U, Kullenbcrg HKE, Bergentz SE. Deep vein thrombosis of the arm: A study of coagulation and fibrinolysis. Br Med J 1981; 283: Rubenstein M, Creger WP. Successful streptokinase therapy for catheter-induced subclavian vein thrombosis. Arch Int Med 1980; 140: Zimmerman R, Morl H, Harenbcrg J, Gerhardt P, Kuhn HM, Wahl P. Urokinase therapy of subclavian-axillary vein thrombosis. Klin Wochenschr 1981; 59: Theiss W, Wirtzfeld A. Fibrinolytische Behandlung yon akuten nnd subakuten Thrombosen der tiefen Venen des Schultergiirtels. Dtsch Med Wochenschr 1982; 107: Taylor LM, McAllister WR, Dennis DL, Porter LM. Thrombolytic therapy followed by first rib resection for spontaneous ("effort") subclavian vein thrombosis. Am J Surg 1985; 149: Becker GJ, Holden RW, Rabe FE, Castaneda-Zuniga WR, Sears N, Dilley RS, Glover IL. Local thrombolytic therapy for subclavian and axillary vein thrombosis. Radiology 1983; 149: Webb GL, Kerstein MD. Management of effort thrombosis with low dose streptokinase. Vasc Surg 1985; 19:200-5.