Prophylaxis of Thromboembolism in Spinal Patients·
Cord~lnJured
David Gnren, M.D., Ph.D.
T
he selection and implementation of optimal thromboprophylaxis in patients with spinal cord injury is a daunting task. In addition to choosing the most appropriate method for thrombus prevention, one must also consider when to institute treabnent, how to interrupt therapy should surgery or other invasive procedures become necessary, and when the patient is no longer at risk for thrombosis and prophylaxis can be safely discontinued. In this communication, we shall attempt to provide some answers to these questions based on our experience and a review of the relevant literature. WHEN TO INmATE PROPHYLAXIS
While initiation of thromboprophylaxis as soon as possible after injury would seem to be ideal, there are many problems with this approach. First, patients are being constantly shuttled between the intensive care unit, radiology suite, and operating room, so that it is very difficult to maintain compression devices. Second, the use of anticoagulants is usually contraindicated in the presence of acute spinal column injury and other trauma and because of concurrent operative procedures. Third, studies of patients within the first 3 days after injury have shown that deep vein thrombosis (OVT) is very infrequent at this time. For example, of 65 patients studied with the fibrinogen uptake test, none had any evidence of a OVf within 72 h after injury, but 4 had positive tests, and the presence of thrombi confirmed by venography at 72 to 144 hours,' In another study only 1 of 87 patients was found to have a DVf by venous How examiantions within the first 72 h after injury" On the other hand, aU 9 patients studied by Myllynen et al3 had thrombosis detected on average 5 days after accident. Therefore, if at all possible, thromboprophylaxis should begin on day 3 postinjury. CHOICE OF PROPHYLACfIC AGENT
There are 4 modalities currently in clinical use for the prevention of thromboembolism in spinal cord-injured patients. They are compression devices, warfarin, standard heparin, and the new low molecular weight heparins. Compression Devices
External pneumatic compression (EPC) devices are designed to provide sequential compression of the veins of the lower extremities to reduce the venous stasis associated with immobility They may be applied to the calf alone or the calf and thigh, and use variable pressures and cycle lengths. The *From the Atherosclerosis Program, Rehabilitation Institute, and the Division of Hematology/Oncology, Department of Medicine, Northwestern University Medical School, Chicago. Reprint requests: Dr. Green, 345 East Superior Street, Rm 1407, Chicago 60611
effectiveness of these devices in groups of surgical patients recently has been reviewed by Caprini et al. 4 These authors observed that most of the published trials used pressures in the 35 to 55 mm Hg range, inflation periods of 10 to 25 s, and deflation periods of 60 s, and were most successful if prophylaxis was continued until the patient was fully ambulatory The EPC was significantly more effective than no prophylaxis in preventing DVfs in patients undergoing neurosurgery, orthopedic surgery, and urologic or gynecologic procedures. The EPC would seem to be ideally suited for patients with spinal cord injury, in that it does not provoke bleeding. In one published trial, 1 27 patients were managed with either EPC alone (15 patients) or with EPC plus aspirin and dipyridamole (12 patients). The EPC was started 72 h after injury and continued for 30 days, and OVf was detected by the fibrinogen uptake test and confirmed by venography Nine patients, 6 in the EPC alone group and 3 in the aspirin! dipyridamole group, had clots. One patient receiving aspirin had major bleeding. The overall rate of thrombosis, 33%, represented a significant improvement over no prophylaxis, 78%, but is still unacceptably high, and adding aspirin conferred little added benefit. Also worrisome was the observation that 3 patients free of clots during the 30 days of the trial had thromboses in the week following the cessation of the prophylaxis. This was not unexpected, since the observations of Caprini et al4 indicated that resumption of ambulation was necessary to prevent thrombosis after discontinuation of EPC. In the patient with spinal cord injury and complete motor paralysis, EPC would most likely have to be continued for several months. This would impact on the patient's rehabilitation program and is probably not feasible. Thus, EPC, while an attractive modality for thromboprophylaxis in spinal cord injury, has important drawbacks. Whether greater efficacy would result from combining EPC with low doses of anticoagulants rather than aspirin during initial therapy, and then continuing the anticoagulants alone for long-term protection, has not been evaluated. Warfarin
Warfarin administration has provided effective prophylaxis in patients undergoing elective hip surgery and in patients with hip fractures. S A two-step regimen, described by Francis et al,6 has become popular. A low dose is started 10 to 14 days prior to surgery and then escalated postoperatively to prolong the prothrombin time to 1.5 times the control value. In patients with spinal cord injury, the low dose along with Ef'C could be used during the first weeks after injury, when the risk of bleeding is high, and then the higher dose implemented and continued for several months, until rehabilitation is well underway In an early trial of warfarin prophylaxis, Silver" reported good efficacy but a CHEST I 102 I 6 I DECEMBER, 1992 I Supplement
649S
high incidence of bleeding. This would provide the rationale for using lower doses initially: A disadvantage of warfarin regimens is the need for constant surveillance with prothrombin times, given that the spinal cord-injured patient is likely to be deficient in vitamin K due to poor dietary intake and antibiotic therapy and therefore, very sensitive to warfarin.
Standard Heparin
Standard heparin has been recommended for the prevention of venous thromboembolism in patients having elective hip surgery, in doses that prolong the activated partial thromboplastin time to the upper half of the normal range." Lesser doses of heparin (3,500 U every 8 h) were Significantly less effective. 9 Trials using various regimens of fixed and adjusted dose standard heparin have also been reported in patients with spinal cord injury: An early study by Frisbie and Sasahara'" compared 5,000 U of heparin every 12 h with no specific prophylaxis in 17 and 15 patients, respectively: There was only one episode of venous thrombosis in each group, perhaps because the criteria for entry did not limit eligibility to just those patients with complete motor paralysis, and only impedance plethysmography was used to detect venous thrombosis. In another study Merli et al" examined 48 patients within 2 weeks of injury and used the fibrinogen uptake test to detect thrombosis, and venography to confirm the diagnosis. In addition, all patients with negative fibrinogen tests during the 28-day study had bilateral venography at the conclusion of the trial. Eight of 17 patients receiving no specific prophylaxis had venous thrombosis, as compared to 8 of 16 treated with 5,000 U of heparin every 8 h (difference not significant). However, repetitive 23 hour-a-day electric stimulation of the calf muscles of a third group of heparin-treated patients lowered the thrombosis rate to only 1 of 15. This study strongly suggested that low-dose heparin alone was inadequate for thromboprophylaxis in the spinal cord-injured patient. A similar conclusion was reached by Green et al, II who compared fixed vs adjusted-dose heparin in 58 patients with complete motor paralysis. One half the patients were randomized to receive 5,000 U of heparin twice daily; the remainder received sufficient heparin (on average 13,200 U every 12 h) to prolong their activated partial thromboplastin times to 1.5 times the normal control value. Nine patients receiving the fixed dose but only 2 receiving the adjusted dose developed venous thrombosis (p
Cord~lnJured
David Gnren, M.D., Ph.D.
T
he selection and implementation of optimal thromboprophylaxis in patients with spinal cord injury is a daunting task. In addition to choosing the most appropriate method for thrombus prevention, one must also consider when to institute treabnent, how to interrupt therapy should surgery or other invasive procedures become necessary, and when the patient is no longer at risk for thrombosis and prophylaxis can be safely discontinued. In this communication, we shall attempt to provide some answers to these questions based on our experience and a review of the relevant literature. WHEN TO INmATE PROPHYLAXIS
While initiation of thromboprophylaxis as soon as possible after injury would seem to be ideal, there are many problems with this approach. First, patients are being constantly shuttled between the intensive care unit, radiology suite, and operating room, so that it is very difficult to maintain compression devices. Second, the use of anticoagulants is usually contraindicated in the presence of acute spinal column injury and other trauma and because of concurrent operative procedures. Third, studies of patients within the first 3 days after injury have shown that deep vein thrombosis (OVT) is very infrequent at this time. For example, of 65 patients studied with the fibrinogen uptake test, none had any evidence of a OVf within 72 h after injury, but 4 had positive tests, and the presence of thrombi confirmed by venography at 72 to 144 hours,' In another study only 1 of 87 patients was found to have a DVf by venous How examiantions within the first 72 h after injury" On the other hand, aU 9 patients studied by Myllynen et al3 had thrombosis detected on average 5 days after accident. Therefore, if at all possible, thromboprophylaxis should begin on day 3 postinjury. CHOICE OF PROPHYLACfIC AGENT
There are 4 modalities currently in clinical use for the prevention of thromboembolism in spinal cord-injured patients. They are compression devices, warfarin, standard heparin, and the new low molecular weight heparins. Compression Devices
External pneumatic compression (EPC) devices are designed to provide sequential compression of the veins of the lower extremities to reduce the venous stasis associated with immobility They may be applied to the calf alone or the calf and thigh, and use variable pressures and cycle lengths. The *From the Atherosclerosis Program, Rehabilitation Institute, and the Division of Hematology/Oncology, Department of Medicine, Northwestern University Medical School, Chicago. Reprint requests: Dr. Green, 345 East Superior Street, Rm 1407, Chicago 60611
effectiveness of these devices in groups of surgical patients recently has been reviewed by Caprini et al. 4 These authors observed that most of the published trials used pressures in the 35 to 55 mm Hg range, inflation periods of 10 to 25 s, and deflation periods of 60 s, and were most successful if prophylaxis was continued until the patient was fully ambulatory The EPC was significantly more effective than no prophylaxis in preventing DVfs in patients undergoing neurosurgery, orthopedic surgery, and urologic or gynecologic procedures. The EPC would seem to be ideally suited for patients with spinal cord injury, in that it does not provoke bleeding. In one published trial, 1 27 patients were managed with either EPC alone (15 patients) or with EPC plus aspirin and dipyridamole (12 patients). The EPC was started 72 h after injury and continued for 30 days, and OVf was detected by the fibrinogen uptake test and confirmed by venography Nine patients, 6 in the EPC alone group and 3 in the aspirin! dipyridamole group, had clots. One patient receiving aspirin had major bleeding. The overall rate of thrombosis, 33%, represented a significant improvement over no prophylaxis, 78%, but is still unacceptably high, and adding aspirin conferred little added benefit. Also worrisome was the observation that 3 patients free of clots during the 30 days of the trial had thromboses in the week following the cessation of the prophylaxis. This was not unexpected, since the observations of Caprini et al4 indicated that resumption of ambulation was necessary to prevent thrombosis after discontinuation of EPC. In the patient with spinal cord injury and complete motor paralysis, EPC would most likely have to be continued for several months. This would impact on the patient's rehabilitation program and is probably not feasible. Thus, EPC, while an attractive modality for thromboprophylaxis in spinal cord injury, has important drawbacks. Whether greater efficacy would result from combining EPC with low doses of anticoagulants rather than aspirin during initial therapy, and then continuing the anticoagulants alone for long-term protection, has not been evaluated. Warfarin
Warfarin administration has provided effective prophylaxis in patients undergoing elective hip surgery and in patients with hip fractures. S A two-step regimen, described by Francis et al,6 has become popular. A low dose is started 10 to 14 days prior to surgery and then escalated postoperatively to prolong the prothrombin time to 1.5 times the control value. In patients with spinal cord injury, the low dose along with Ef'C could be used during the first weeks after injury, when the risk of bleeding is high, and then the higher dose implemented and continued for several months, until rehabilitation is well underway In an early trial of warfarin prophylaxis, Silver" reported good efficacy but a CHEST I 102 I 6 I DECEMBER, 1992 I Supplement
649S
high incidence of bleeding. This would provide the rationale for using lower doses initially: A disadvantage of warfarin regimens is the need for constant surveillance with prothrombin times, given that the spinal cord-injured patient is likely to be deficient in vitamin K due to poor dietary intake and antibiotic therapy and therefore, very sensitive to warfarin.
Standard Heparin
Standard heparin has been recommended for the prevention of venous thromboembolism in patients having elective hip surgery, in doses that prolong the activated partial thromboplastin time to the upper half of the normal range." Lesser doses of heparin (3,500 U every 8 h) were Significantly less effective. 9 Trials using various regimens of fixed and adjusted dose standard heparin have also been reported in patients with spinal cord injury: An early study by Frisbie and Sasahara'" compared 5,000 U of heparin every 12 h with no specific prophylaxis in 17 and 15 patients, respectively: There was only one episode of venous thrombosis in each group, perhaps because the criteria for entry did not limit eligibility to just those patients with complete motor paralysis, and only impedance plethysmography was used to detect venous thrombosis. In another study Merli et al" examined 48 patients within 2 weeks of injury and used the fibrinogen uptake test to detect thrombosis, and venography to confirm the diagnosis. In addition, all patients with negative fibrinogen tests during the 28-day study had bilateral venography at the conclusion of the trial. Eight of 17 patients receiving no specific prophylaxis had venous thrombosis, as compared to 8 of 16 treated with 5,000 U of heparin every 8 h (difference not significant). However, repetitive 23 hour-a-day electric stimulation of the calf muscles of a third group of heparin-treated patients lowered the thrombosis rate to only 1 of 15. This study strongly suggested that low-dose heparin alone was inadequate for thromboprophylaxis in the spinal cord-injured patient. A similar conclusion was reached by Green et al, II who compared fixed vs adjusted-dose heparin in 58 patients with complete motor paralysis. One half the patients were randomized to receive 5,000 U of heparin twice daily; the remainder received sufficient heparin (on average 13,200 U every 12 h) to prolong their activated partial thromboplastin times to 1.5 times the normal control value. Nine patients receiving the fixed dose but only 2 receiving the adjusted dose developed venous thrombosis (p
