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Systemic thrombolysis in the early postoperative period can cause fatal hemorrhage. Systemic thrombolysis is often considered contraindicated after major vascular procedures; thus, experience with this scenario is limited. A 67-year-old man experienced massive pulmonary embolization after his abdominal aortic aneurysm was repaired with a bifurcated, woven Dacron graft. Because systemic thrombolysis was the only option for our patient's survival, he underwent this procedure with recombinant tissue-type plasminogen activator just 2 weeks after the Dacron graft repair of his abdominal aortic aneurysm. After clinical stabilization, abdominal and pelvic computed tomography showed no periprosthetic graft hemorrhage. The successful systemic thrombolysis suggests that this therapy may prove useful in extreme situations.
Thrombolytic agents are used in an increasing number of clinical scenarios. They are used clinically to treat acute ischemic stroke, myocardial infarction, acute arterial occlusion, and venous thromboembolism. However, a wide variation in the use of thrombolytic agents was documented in a recent survey of perceived contraindications in several medical conditions.
Such perceived contraindications are often based on qualitative concerns, not quantitative analysis, of the clinician, and should be defined as relative contraindications. The risk of hemorrhage resulting from thrombolysis after surgery has limited the use of systemic thrombolytic therapy after major vascular procedures.
Hemorrhage or contrast extravasation can occur after local or systemic thrombolysis with knitted
grafts. We describe a patient who underwent successful thrombolytic therapy after sustaining massive pulmonary embolization after the repair of an abdominal aortic aneurysm and concomitant aortocaval fistula. Previous conventional therapy with anticoagulation and the placement of a Greenfield filter failed to influence the clinical course of the patient.
REPORT OF A CASE
A 67-year-old man presented with sudden onset of sharp chest and abdominal pain. The pain woke the patient from sleep and was associated with severe shortness of breath. Examination of the patient revealed tachycardia, hypotension, a pulsatile abdominal mass, and a machinery thrill over the abdomen. Abdominal and pelvic computed tomography (CT) revealed a 7-cm-diameter infrarenal aortic aneurysm and an 8-cm-diameter right common iliac aneurysm. The left common femoral vein was also enlarged. A small amount of fluid in the culdesac was also noted.
The patient underwent emergent replacement of the aneurysms with a bifurcated, woven, double-velour Dacron graft with distal anastomoses to the left common iliac artery and to the right common femoral artery, excluding the right common iliac aneurysm. An aortocaval fistula was noted on exploration and was repaired with a filamentous velour Dacron patch. The abdomen was too tense to be closed initially and the incision was approximated with a 2-mm polytetrafluorethylene patch.
The patient had an initially stable postoperative convalescence. Delayed closure of the abdomen was performed on postoperative day 6. The patient, however, developed left lower extremity edema on postoperative day 9. A Doppler ultrasound confirmed deep venous thrombosis, and systemic heparinization was initiated. On postoperative day 12, the patient developed an acute hemodynamic compromise associated with persistent hypoxia. Pulmonary angiography showed multiple large peripheral emboli bilaterally. The main pulmonary arterial pressure level was 62/41 mm Hg (mean, 50 mm Hg). A thrombus was noted in the inferior vena cava, which extended to 5 cm below the renal veins. A Greenfield filter was placed into the inferior vena cava.
Management with systemic heparin anticoagulation was maintained (activated partial thromboplastin time [APTT] range, 50.8-93.5 seconds; prothrombin time, 13.6 seconds). Despite paralysis and full ventilatory support (assistcontrol mode; rate, 18 breaths per minute; tidal volume, 800 mL; positive end-expiratory pressure, 7.5 cm water; fraction of inspired oxygen, 100%), the patient could not be adequately ventilated or oxygenated (arterial pH, 7.43; Pco2, 47 mm Hg; Po2, 54 mm Hg; oxygen saturation, 86%). Pulmonary thromboembolectomy was not believed to be an option because of the technical challenge presented by multiple peripheral emboli. No interim improvement was noted during the subsequent 2 days. Proceeding with systemic thrombolysis was the only available option for the patient's survival. Consequently, recombinant tissue-type plasminogen activator (r-tPA) was infused through a central venous catheter, 100 mg over 2 hours, a large dosage compared with the literature.
Fibrinogen levels measured after infusion ranged from 404 to 773 mg/dL (reference range, 175-350 mg/dL) after r-tPA administration. The APTT did not vary substantially after r-tPA infusion (APTT range, 66.4-98.1 seconds), nor did the prothrombin time (12.3-13.5 seconds). Rapid improvements in both ventilation and oxygenation were observed. The patient's recovery continued, and extubation was performed 5 days after lytic therapy.
After the initiation of lytic therapy, the patient required transfusions of 4 U of red blood cells during the ensuing 24 hours. An abdominal wall hematoma arose, likely representing the entire volume of transfused blood, and was evacuated at the bedside. There was no other evidence of bleeding. An abdominal CT obtained the week after lytic therapy showed no evidence of hemorrhage in the retro- peritoneum (Figure 1).
The patient also sustained multiple cerebrovascular emboli due to a previously unknown patent foramen ovale. Seizures were noted on postoperative day 12 at the time of pulmonary embolization and responded to benzodiazepine therapy. High-resolution head CT subsequently showed infarcts in the right posterior cerebral artery distribution. No intracranial hemorrhage was identified. The left hemiparalysis resolved in time, but a left hemianopsia persisted. Three weeks after the appearance of the massive pulmonary embolism, the patient was transferred to the inpatient rehabilitation unit and was dismissed home after a 110-day hospitalization.
The patient is fully independent 7 years after the event. Two years after his initial presentation, he underwent a Stoppa repair of a ventral hernia; 3 years after his initial presentation, he underwent a right inguinal herniorrhaphy. Surveillance CT performed annually showed no delayed complications of his aortic reconstruction; in particular, no anastomotic aneurysm was documented. He is maintained on long-term oral anticoagulant medication.
Massive pulmonary embolism is a recognized, albeit infrequent, complication of surgical intervention. High-risk groups include patients who have sustained major trauma and those undergoing orthopedic, neurosurgical, and intraabdominal general surgical procedures. Information is lacking on the incidence after emergent noncardiac vascular surgery. However, the incidence of deep venous thrombosis after elective aortic reconstruction varies from 4.3% to 20.5%,
These reported frequencies of embolism likely underestimate the true frequency. Autopsy analysis in one study confirmed pulmonary embolization in 74.9% of patients with documented venous thromboembolism.
In 70% of patients with pulmonary embolization, the pulmonary embolus was believed to be fatal or contributory to death. Our patient had not only an emergent repair of a ruptured abdominal aortic aneurysm, but also an aortocaval fistula closed with a Dacron patch. Both of these predisposing factors are likely contributory and may have potentiated each other in lessening the prophylactic benefits of the sequential compression devices that were used in this patient.
Systemic thrombolysis has been extensively investigated in the treatment of massive pulmonary embolism. Recombinant tissue-type plasminogen activator is an exogenous stimulator of the fibrinolytic system, catalyzing the conversion of the inactive plasminogen into active plasmin. Plasmin is a nonspecific proteolytic enzyme that catalyzes the degradation of fibrin, fibrinogen, prothrombin, factor V, and factor VIII. Because the circulation contains a large concentration of plasmin inhibitor to neutralize the plasmin's effect, the action of plasmin is relatively specific to fibrin clots. Despite the relative specificity for active fibrin clots, bleeding complications are the most common adverse reactions to systemic thrombolysis. Approximately one third of patients receiving thrombolytic therapy for pulmonary embolism experience clinical bleeding; one quarter have hematocrit decreases of more than 5%.
Interestingly, fibrinogen levels were not lowered below the normal range in our patient after thrombolytic therapy. A recent serologic evaluation of patients presenting with a ruptured abdominal aortic aneurysm showed a prothrombotic and hypofibrinolytic status,
perhaps caused by increased plasmin inhibitor levels. This altered state presumably limited fibrinolysis to the emboli and thus protected against massive hemorrhage in the early postoperative period. Nonetheless, administration of r-tPA in our patient was associated with dramatic hemodynamic and ventilatory changes.
An interesting issue is whether thrombolytic therapy delivered locally to the pulmonary arteries would be safer after major vascular procedures. Indeed, catheter administration of r-tPA has been described previously in case series.
Periprosthetic graft hemorrhage was described previously with thrombolysis with 1 woven and 8 knitted Dacron aortic grafts (Table 1). The integrity of the loose- weave knitted grafts depends largely on the mural thrombus; therefore, these grafts understandably account for most cases of hemorrhaging reported to date. In addition, at least one previously reported case involved a graft pseudoaneurysm.
Interestingly, an interval of 3 months to 8 years transpired between graft implantation and thrombolysis. In contrast to these reported problems with knitted Dacron grafts or complications in the anastomoses, a woven Dacron graft was used in our patient, and he had no pseudoaneurysm. The single previous case involving a woven Dacron graft resulted in hemoperitoneum.
Unfortunately, localization of the hemorrhage by angiography or CT was unavailable (N. J. London, oral communication); therefore, hemorrhaging may have occurred secondary to anastomotic incompetence or pseudoaneurysm. Clinical follow-up in that patient is unavailable. Animal studies suggest that woven Dacron grafts can be exposed to thrombolytic agents as early as 3 weeks after implantation.
In our patient, systemic thrombolytic therapy did necessitate the administration of blood transfusions to maintain acceptable hemoglobin levels. The associated abdominal wall hematoma represented a component of this transfusion requirement. However, abdominal and pelvic CT performed after clinical stabilization documented no evidence of periprosthetic graft hemorrhage. In particular, only minimal fluid surrounded the graft, consistent with postoperative changes. Possibly, a component of this perigraft fluid represented blood extravasation; however, no intravascular contrast was noted in this fluid.
In conclusion, we report a successful case of systemic r-tPA infusion for fulminant pulmonary embolization 2 weeks after woven Dacron repair of an abdominal aortic aneurysm. Although not recommended as first-line therapy, systemic thrombolysis may prove useful in extreme situations unresponsive to more conventional treatments.
Perceived contraindications to thrombolytic treatment in acute myocardial infarction: a survey at a teaching hospital.