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Upper-extremity deep-vein thrombosis: Thrombolytic therapy with anistrepalase
CASE REPORT anistrepalase deep-vein thrombosis
Thrombosis: U p p e r - EDeep-Vein xtrem ity Thrombolytic Therapy With Anistrepalase From the Division of Cardiovascular Medicine * and Emergency Medicine, l Department of Medicine, University of Massachusetts Medical Center, Worcester. Received for publication July 25, 1992. Accepted for publication October 1, 2992.
Luis A Pires, MD* Gregory Jay, MD, PhD*
A patient with primary axillary vein thrombosis was treated successfully in the emergency department with a single IV bolus of anistrepalase followed by continuous IV heparin. The patient's symptoms resolved quickly, and a repeat venogram 16 hours later showed near-complete resolution of the venous obstruction. We discuss briefly the role of thrombolytic therapy in the treatment of upper-extremity deep-vein thrombosis and the potential advantages of using anistrepalase. [Pires LA, Jay G: Upper-extremity deep-vein thrombosis: Thrombolytic therapy with anistrepalase. Ann EmergMed April 1993;22:748-750.] INTRODUCTION Upper-extremity deep-vein thrombosis is relatively rare and accounts for less than 2% of all deep-vein thrombosis. 1 Although previously thought to be a benign condition,2, 3 more recent evidence suggests that upper-extremity deepvein thrombosis often can lead to disabling symptoms when treated conservatively and with standard anticoagulation therapy.>5 In view of the potential morbidity associated with this condition and reports showing a rise in its incidence,X, 3 emergency physicians should be well aware of its clinical presentation, diagnosis, and current management. We present a case of primary axillary vein thrombosis and discuss the role of thrombolytic therapy, particularly anistrepalase (anisoylated plasminogen streptokinase activator complex [APSAC]), in its management. CASE REPORT A previously healthy, right-handed, 20-year-old man presented to the emergency department with a three-day history of right upper-extremity pain and swelling. He initially complained of arm pain and minimal numbness after a game of golf and later developed swelling of the entire upper extremity. He had a history of right rotator
152/ 748
ANNALS OF EMERGENCY MEDI01NE
22:4
APRIL 1993
DEEP-VEIN THROMBOSIS
Pires & Jay
There are two broad categories of upper-extremity deepvein thrombosis, primary and secondary> Primary deepvein thrombosis, often referred to as "effort" thrombosis or Paget-von Schroetter syndrome, usually is seen in otherwise healthy young adults who engage in vigorous upper-extremity activity. It is believed that repeated injury to the vein leads to a propensity for local thrombosis. Secondary deep-vein thrombosis usually occurs in patients with an underlying predisposition to venous thrombosis (eg, hypercoagulable state, malignancy, indwelling catheter). Whatever the etiology, patients usually complain of pain, swelling, and numbness of the upper extremity, and
in rare cases, patients may present with symptoms of pulmonary embolism. 5 Physical examination is marked by swelling, local tenderness and discoloration of the extremity, and increased superficial venous markings over the ipsilateral anterior chest wall, shoulder, and medial aspect of the upper arm> Diagnosis usually is confirmed by contrast venography, although other modalities such as digital subtraction angiographyr and duplex Doppler sonographyS seem to be equally useful. Prompt diagnosis and treatment are very important to avoid serious complications such as pulmonary embolism, which occurs in up to 12.4% of cases, 3 and can lead to cot pulmonale 9 and even death. 5 Any precipitating cause of deep-vein thrombosis should be identified and treated. 6 Standard anticoagulation therapy with IV heparin followed by oral warfarin has been the mainstay of treatment for upper-extremity deep-vein thrombosis. However, such treatment can result in chronic symptoms of pain and swelling once the patient resumes his or her usual activity,*,4, 5 thus the rationale for early use of thrombolytic treatment. A few patients have been treated successfully with streptokinase and urokinase,lO-16 but to our knowledge, this is the first reported use of APSAC to treat upperextremity deep-vein thrombosis. Our patient remained asymptomatic and without recurrence after one year of follow-up. Patients who receive urokinase or streptokinase, locally or systemically, often require continuous infusion for at least 24 to 48 hours after the initial bolus until the thrombus is resolved 1°-16 and usually are kept for observation in an ICU. For these reasons, their hospital cost can be quite high. APSAC, however, can be given more readily as a single IV bolus of 30 units over two to five minutes, followed by IV heparin once the diagnosis is made,~r, is thus reducing delay in treatment. 19 APSAC has been used to treat acute
Figure 1.
Figure 2.
cuff injury but denied any recent trauma, use of IV drugs and indwelling catheters, or history of thromboembolism. On examination, the circumference of the right upper arm measured 8 cm more than the left. Increased superficial venous markings were noted over the ipsilateral anterior chest wall and shoulder. Arterial pulses were intact, and there was no evidence for sensory deficit. Clotting studies, hematocrit, chest radiograph, and a computed tomography scan of the chest were normal. Venography showed occlusion of the axillary vein (Figure 1). The patient received a single bolus of 30 units IV APSAC followed by IV heparin at 1,000 U/hr. The patient's symptoms and venous congestion of the chest wall diminished significantly within 90 minutes of treatment. Sixteen hours later, the patient was asymptomatic, and a repeat venography showed near-complete resolution of the thrombus (Figure 2). He experienced no bleeding complications and soon was discharged on warfarin. At one-year follow-up, the patient was asymptomatic with no restriction on his activity. DISCUSSION
Venograph7 before treatment showing complete occlusion of axillary vein and increased collaterals
Yenography 16 hours after treatment showing near-
complete resolution of ax~llary vein occlusion
(magnification higher than in Figure 1)
APRIL 1993 22:4
ANNALS OF EMERGENCY MEDICINE
7 49/1
53
DEEP-VEIN THROMBOSIS Pires &day
myocardial infarction,iF, 18 seems to be as effective as tissue plasminogen activator and streptokinase, 20 and causes no serious side effects such as hemorrhage. 17,20 APSAC also has been used to treat pulmonary embolism. 21 However, these agents have not been compared with one another in the treatment of deep-vein thrombosis, and no controlled study has compared standard anticoagulation therapy with thrombolytic agents in treating upper-extremity deep-vein thrombosis. In lower-extremity deep-vein thrombosis, streptokinase is more effective than heparin in the lysis of clot, but the risk of bleeding is higher. 22 Whether the same is true for upper-extremity deep-vein thrombosis is unclear, but there is no reason to suspect otherwise. The use of heparin alone would not be expected to result in such quick resolution of symptoms and lysis of thrombus, as noted in our patient. 2o SUMMARY
It would appear that APSAC is a reasonable alternative for treating deep-vein thrombosis of the upper extremity. Once the correct diagnosis is made, provided there is no contraindication to thrombolytic therapy, it can be given quickly in the ED, followed by continuous IV heparin for at least 24 hours until repeated venography shows resolution of thrombus. Patients should be monitored closely for bleeding complication. We treated only one patient and, therefore, cannot make more specific treatment recommendations.
11, O'Leary MR, Smith MS, Drury EM: Diegnositic and therapeutic approachto axillary-subclavian vein thrombosis. Ann EmergMed 1987;16:889~893. 12. Drury EM, Trout HH, GiordanoJM, et ah Lytic therapy in the treatment of axillary and subclavian vein thrombosis. J VascSurg1985;2:821-827. 13. Rubensteio M, CregerWP: Successful streptokinase therapy for catheter-induced subclavian vein thrombosis. ArchInternMefl 1980;140:1370-1371 14. BeckerGJ, Holden RW, Rabe FE, et al: Local thrombolytic therapy for subclavian and axil/ary vein thrombosis. Radiology1983;149:419-423. 15. LandscasperJ, Gall W, FischerM, et ah Thrombolytic therapy of axillary-subciavian vein thrombosis. Arch Surg1987;122:1072-1075. 18, Fraschini G, Jadeja J, Lawson M, et ah Local infusion of urokinasefor rysis of thrombosis associated with permanent central venous catheters in cancer patients. J Cfin Oncol 1987;5:672-678. 17, Pacouret G, Charbenoier8, Curien NO, et ah Invasive reperfusion study. II. Multicentre Europeanrandomizedtrial of anistrepalase vs streptokinase in acute myocardial infarction. Eur HeartJ1991;12:179-185. 18. Held PH, Teo KK, Yusuf S: Effects of tissue-type plasminogen activator and anisoylated plasminegon streptokinase activator complex on mortality in acute myocardial infarction. Circulation 1990;82:1668-1674. 19. MacOallum AG, Stafford PJ, Jones C, et ah Reduction in hospital time to thrombolytic therapy by audit of policy guidelines. EurHeartJ 19g0;1l(suppl F):48-52. 20. ISIS-3 (Third Internation Study of Infarct Survival} Collaborative Group:A randomized comparison of streptokinase vs tissue plasminogen activator vs anistreplase and of aspirin plus heparin vs aspirin alone among 41,299 cases of suspectedacute myocardial infarction. Lancet 1992;339:753-770. 21. Santo ME, da Silva G, PimentaA: Pulmonaryembolism. A case treated with APSAC (Portuguese).RoyPortugueseCardio11991;10:339-342. 22. GoldheberSZ, Budng JE, Lipnick RJ, et ah Pooledanalysis of randomizedtrials of streptokinase and hoparin in phlebographica/lydocumented acute deep venous thrombosis. Am J Med 1984;76:393-397.
Address for reprints:
Luis A Pires, MD Division of Cardiovascular Medicine University of Massachusetts Medical Center
REFERENCES
55 Lake Avenue North
1. Swinton NW Jr, Edgett JW Jr, Hall RJ: Primarysubclavian-axillary vein thrombosis. Circulation 1968;38:737-745.
Worcester, Massachusetts 01655
2. Horattas MC, Wright DJ, FentonAN, et al: Changingconcepts of deep venous thrombosis of the upper extremity--Report of a series and review of the literature. Surgery1988;104:581~567. 3. DonayreCE, White GEl,Mehringer SM, et el: Pathogenesisdetermines later morbidity of axiJlo-subclavianvein thrombosis. Am J Surg1986;152:179-184. 4. Tilney NL, Griffiths JG, Edwards EA: Natural history of major venous thrombods of the upper extremity. Arch Surg1970;101:792-796. 5. Campbell CB, ChandlerJG, Tegmeyer CJ, et ah Axillary, subclavian, and brachycephalicvein obstruction. Surgery1977;82:816-826. 6. Bo/giano EB, Foxwetl NM, Browne BJ, et ah Deep venous thrombosis of the upper extremity: Diagnosisand treatment. J EmergMed 1990;8:85-91. 7. Kinnison ML, Kaufman SL, Chang R, et ah Upper extremity venography using digital subtraction angiography. CardivascInterventRadio11986;9:106-108. 8. Falk RL, Smith DF: Thrombosis of upper extremity thoracic inlet veins: Diagnosiswith duplex Doppler sonography.Am J Radio/1987;149:677-682.
ERRATUM
9. Falicov RE, BesnekovL, PetasnickJ: Progressivepulmonaryvascular obstruction and cor pulmonale due to repeated embolism from axillary vein thrombosis. Ann InternMed 1970;73:429-431.
In the article "Utility of Serum Interleukin-6 for Diagnosis of Invasive
10. Taylor LM, McAllister WR, Dennis DL, eta]: Thrombolytic therapy followed by first rib resection for spontaneous("effort"} subclavian vein thrombosis. Am J Surg1985;146:644-647.
1 5 4 / 7 50
Bacterial Disease in Children" [December 1992;21:1413-1417], the name of one of the authors was misspelled. The correct spelIing is George R Siber, not Sflber.
ANNALS OF EMERGENOY MEDICINE
22:4
APRIL 1993
Thrombosis: U p p e r - EDeep-Vein xtrem ity Thrombolytic Therapy With Anistrepalase From the Division of Cardiovascular Medicine * and Emergency Medicine, l Department of Medicine, University of Massachusetts Medical Center, Worcester. Received for publication July 25, 1992. Accepted for publication October 1, 2992.
Luis A Pires, MD* Gregory Jay, MD, PhD*
A patient with primary axillary vein thrombosis was treated successfully in the emergency department with a single IV bolus of anistrepalase followed by continuous IV heparin. The patient's symptoms resolved quickly, and a repeat venogram 16 hours later showed near-complete resolution of the venous obstruction. We discuss briefly the role of thrombolytic therapy in the treatment of upper-extremity deep-vein thrombosis and the potential advantages of using anistrepalase. [Pires LA, Jay G: Upper-extremity deep-vein thrombosis: Thrombolytic therapy with anistrepalase. Ann EmergMed April 1993;22:748-750.] INTRODUCTION Upper-extremity deep-vein thrombosis is relatively rare and accounts for less than 2% of all deep-vein thrombosis. 1 Although previously thought to be a benign condition,2, 3 more recent evidence suggests that upper-extremity deepvein thrombosis often can lead to disabling symptoms when treated conservatively and with standard anticoagulation therapy.>5 In view of the potential morbidity associated with this condition and reports showing a rise in its incidence,X, 3 emergency physicians should be well aware of its clinical presentation, diagnosis, and current management. We present a case of primary axillary vein thrombosis and discuss the role of thrombolytic therapy, particularly anistrepalase (anisoylated plasminogen streptokinase activator complex [APSAC]), in its management. CASE REPORT A previously healthy, right-handed, 20-year-old man presented to the emergency department with a three-day history of right upper-extremity pain and swelling. He initially complained of arm pain and minimal numbness after a game of golf and later developed swelling of the entire upper extremity. He had a history of right rotator
152/ 748
ANNALS OF EMERGENCY MEDI01NE
22:4
APRIL 1993
DEEP-VEIN THROMBOSIS
Pires & Jay
There are two broad categories of upper-extremity deepvein thrombosis, primary and secondary> Primary deepvein thrombosis, often referred to as "effort" thrombosis or Paget-von Schroetter syndrome, usually is seen in otherwise healthy young adults who engage in vigorous upper-extremity activity. It is believed that repeated injury to the vein leads to a propensity for local thrombosis. Secondary deep-vein thrombosis usually occurs in patients with an underlying predisposition to venous thrombosis (eg, hypercoagulable state, malignancy, indwelling catheter). Whatever the etiology, patients usually complain of pain, swelling, and numbness of the upper extremity, and
in rare cases, patients may present with symptoms of pulmonary embolism. 5 Physical examination is marked by swelling, local tenderness and discoloration of the extremity, and increased superficial venous markings over the ipsilateral anterior chest wall, shoulder, and medial aspect of the upper arm> Diagnosis usually is confirmed by contrast venography, although other modalities such as digital subtraction angiographyr and duplex Doppler sonographyS seem to be equally useful. Prompt diagnosis and treatment are very important to avoid serious complications such as pulmonary embolism, which occurs in up to 12.4% of cases, 3 and can lead to cot pulmonale 9 and even death. 5 Any precipitating cause of deep-vein thrombosis should be identified and treated. 6 Standard anticoagulation therapy with IV heparin followed by oral warfarin has been the mainstay of treatment for upper-extremity deep-vein thrombosis. However, such treatment can result in chronic symptoms of pain and swelling once the patient resumes his or her usual activity,*,4, 5 thus the rationale for early use of thrombolytic treatment. A few patients have been treated successfully with streptokinase and urokinase,lO-16 but to our knowledge, this is the first reported use of APSAC to treat upperextremity deep-vein thrombosis. Our patient remained asymptomatic and without recurrence after one year of follow-up. Patients who receive urokinase or streptokinase, locally or systemically, often require continuous infusion for at least 24 to 48 hours after the initial bolus until the thrombus is resolved 1°-16 and usually are kept for observation in an ICU. For these reasons, their hospital cost can be quite high. APSAC, however, can be given more readily as a single IV bolus of 30 units over two to five minutes, followed by IV heparin once the diagnosis is made,~r, is thus reducing delay in treatment. 19 APSAC has been used to treat acute
Figure 1.
Figure 2.
cuff injury but denied any recent trauma, use of IV drugs and indwelling catheters, or history of thromboembolism. On examination, the circumference of the right upper arm measured 8 cm more than the left. Increased superficial venous markings were noted over the ipsilateral anterior chest wall and shoulder. Arterial pulses were intact, and there was no evidence for sensory deficit. Clotting studies, hematocrit, chest radiograph, and a computed tomography scan of the chest were normal. Venography showed occlusion of the axillary vein (Figure 1). The patient received a single bolus of 30 units IV APSAC followed by IV heparin at 1,000 U/hr. The patient's symptoms and venous congestion of the chest wall diminished significantly within 90 minutes of treatment. Sixteen hours later, the patient was asymptomatic, and a repeat venography showed near-complete resolution of the thrombus (Figure 2). He experienced no bleeding complications and soon was discharged on warfarin. At one-year follow-up, the patient was asymptomatic with no restriction on his activity. DISCUSSION
Venograph7 before treatment showing complete occlusion of axillary vein and increased collaterals
Yenography 16 hours after treatment showing near-
complete resolution of ax~llary vein occlusion
(magnification higher than in Figure 1)
APRIL 1993 22:4
ANNALS OF EMERGENCY MEDICINE
7 49/1
53
DEEP-VEIN THROMBOSIS Pires &day
myocardial infarction,iF, 18 seems to be as effective as tissue plasminogen activator and streptokinase, 20 and causes no serious side effects such as hemorrhage. 17,20 APSAC also has been used to treat pulmonary embolism. 21 However, these agents have not been compared with one another in the treatment of deep-vein thrombosis, and no controlled study has compared standard anticoagulation therapy with thrombolytic agents in treating upper-extremity deep-vein thrombosis. In lower-extremity deep-vein thrombosis, streptokinase is more effective than heparin in the lysis of clot, but the risk of bleeding is higher. 22 Whether the same is true for upper-extremity deep-vein thrombosis is unclear, but there is no reason to suspect otherwise. The use of heparin alone would not be expected to result in such quick resolution of symptoms and lysis of thrombus, as noted in our patient. 2o SUMMARY
It would appear that APSAC is a reasonable alternative for treating deep-vein thrombosis of the upper extremity. Once the correct diagnosis is made, provided there is no contraindication to thrombolytic therapy, it can be given quickly in the ED, followed by continuous IV heparin for at least 24 hours until repeated venography shows resolution of thrombus. Patients should be monitored closely for bleeding complication. We treated only one patient and, therefore, cannot make more specific treatment recommendations.
11, O'Leary MR, Smith MS, Drury EM: Diegnositic and therapeutic approachto axillary-subclavian vein thrombosis. Ann EmergMed 1987;16:889~893. 12. Drury EM, Trout HH, GiordanoJM, et ah Lytic therapy in the treatment of axillary and subclavian vein thrombosis. J VascSurg1985;2:821-827. 13. Rubensteio M, CregerWP: Successful streptokinase therapy for catheter-induced subclavian vein thrombosis. ArchInternMefl 1980;140:1370-1371 14. BeckerGJ, Holden RW, Rabe FE, et al: Local thrombolytic therapy for subclavian and axil/ary vein thrombosis. Radiology1983;149:419-423. 15. LandscasperJ, Gall W, FischerM, et ah Thrombolytic therapy of axillary-subciavian vein thrombosis. Arch Surg1987;122:1072-1075. 18, Fraschini G, Jadeja J, Lawson M, et ah Local infusion of urokinasefor rysis of thrombosis associated with permanent central venous catheters in cancer patients. J Cfin Oncol 1987;5:672-678. 17, Pacouret G, Charbenoier8, Curien NO, et ah Invasive reperfusion study. II. Multicentre Europeanrandomizedtrial of anistrepalase vs streptokinase in acute myocardial infarction. Eur HeartJ1991;12:179-185. 18. Held PH, Teo KK, Yusuf S: Effects of tissue-type plasminogen activator and anisoylated plasminegon streptokinase activator complex on mortality in acute myocardial infarction. Circulation 1990;82:1668-1674. 19. MacOallum AG, Stafford PJ, Jones C, et ah Reduction in hospital time to thrombolytic therapy by audit of policy guidelines. EurHeartJ 19g0;1l(suppl F):48-52. 20. ISIS-3 (Third Internation Study of Infarct Survival} Collaborative Group:A randomized comparison of streptokinase vs tissue plasminogen activator vs anistreplase and of aspirin plus heparin vs aspirin alone among 41,299 cases of suspectedacute myocardial infarction. Lancet 1992;339:753-770. 21. Santo ME, da Silva G, PimentaA: Pulmonaryembolism. A case treated with APSAC (Portuguese).RoyPortugueseCardio11991;10:339-342. 22. GoldheberSZ, Budng JE, Lipnick RJ, et ah Pooledanalysis of randomizedtrials of streptokinase and hoparin in phlebographica/lydocumented acute deep venous thrombosis. Am J Med 1984;76:393-397.
Address for reprints:
Luis A Pires, MD Division of Cardiovascular Medicine University of Massachusetts Medical Center
REFERENCES
55 Lake Avenue North
1. Swinton NW Jr, Edgett JW Jr, Hall RJ: Primarysubclavian-axillary vein thrombosis. Circulation 1968;38:737-745.
Worcester, Massachusetts 01655
2. Horattas MC, Wright DJ, FentonAN, et al: Changingconcepts of deep venous thrombosis of the upper extremity--Report of a series and review of the literature. Surgery1988;104:581~567. 3. DonayreCE, White GEl,Mehringer SM, et el: Pathogenesisdetermines later morbidity of axiJlo-subclavianvein thrombosis. Am J Surg1986;152:179-184. 4. Tilney NL, Griffiths JG, Edwards EA: Natural history of major venous thrombods of the upper extremity. Arch Surg1970;101:792-796. 5. Campbell CB, ChandlerJG, Tegmeyer CJ, et ah Axillary, subclavian, and brachycephalicvein obstruction. Surgery1977;82:816-826. 6. Bo/giano EB, Foxwetl NM, Browne BJ, et ah Deep venous thrombosis of the upper extremity: Diagnosisand treatment. J EmergMed 1990;8:85-91. 7. Kinnison ML, Kaufman SL, Chang R, et ah Upper extremity venography using digital subtraction angiography. CardivascInterventRadio11986;9:106-108. 8. Falk RL, Smith DF: Thrombosis of upper extremity thoracic inlet veins: Diagnosiswith duplex Doppler sonography.Am J Radio/1987;149:677-682.
ERRATUM
9. Falicov RE, BesnekovL, PetasnickJ: Progressivepulmonaryvascular obstruction and cor pulmonale due to repeated embolism from axillary vein thrombosis. Ann InternMed 1970;73:429-431.
In the article "Utility of Serum Interleukin-6 for Diagnosis of Invasive
10. Taylor LM, McAllister WR, Dennis DL, eta]: Thrombolytic therapy followed by first rib resection for spontaneous("effort"} subclavian vein thrombosis. Am J Surg1985;146:644-647.
1 5 4 / 7 50
Bacterial Disease in Children" [December 1992;21:1413-1417], the name of one of the authors was misspelled. The correct spelIing is George R Siber, not Sflber.
ANNALS OF EMERGENOY MEDICINE
22:4
APRIL 1993