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Heparin plus alteplase compared with heparin alone in patients with submassive pulmonary embolism.

BACKGROUND: The use of thrombolytic agents in the treatment of hemodynamically stable patients with acute submassive pulmonary embolism remains controversial. METHODS: We conducted a study of patients with acute pulmonary embolism and pulmonary hypertension or right ventricular dysfunction but without arterial hypotension or shock. The patients were randomly assigned in double-blind fashion to receive heparin plus 100 mg of alteplase or heparin plus placebo over a period of two hours. The primary end point was in-hospital death or clinical deterioration requiring an escalation of treatment, which was defined as catecholamine infusion, secondary thrombolysis, endotracheal intubation, cardiopulmonary resuscitation, or emergency surgical embolectomy or thrombus fragmentation by catheter. RESULTS: Of 256 patients enrolled, 118 were randomly assigned to receive heparin plus alteplase and 138 to receive heparin plus placebo. The incidence of the primary end point was significantly higher in the heparin-plus-placebo group than in the heparin-plus-alteplase group (P=0.006), and the probability of 30-day event-free survival (according to Kaplan-Meier analysis) was higher in the heparin-plus-alteplase group (P=0.005). This difference was due to the higher incidence of treatment escalation in the heparin-plus-placebo group (24.6 percent vs. 10.2 percent, P=0.004), since mortality was low in both groups (3.4 percent in the heparin-plus-alteplase group and 2.2 percent in the heparin-plus-placebo group, P=0.71). Treatment with heparin plus placebo was associated with almost three times the risk of death or treatment escalation that was associated with heparin plus alteplase (P=0.006). No fatal bleeding or cerebral bleeding occurred in patients receiving heparin plus alteplase. CONCLUSIONS: When given in conjunction with heparin, alteplase can improve the clinical course of stable patients who have acute submassive pulmonary embolism and can prevent clinical deterioration requiring the escalation of treatment during the hospital stay.

Aged↗

Current indications for and results of Greenfield filter placement.

Review of the indications for and results of Greenfield filter placement for protection against thromboembolism in 260 patients shows that the most common indication remains a contraindication to anticoagulation therapy (35%) or recurrent thromboembolism in spite of anticoagulation therapy (31%). Prophylaxis in the absence of embolism is a less common indication (18%), but increasingly favorable experience by others with the filter in place of anticoagulation therapy in the elderly may alter the approach to these patients. Although two patients with massive embolism who had undergone pulmonary embolectomy died postoperatively, no deaths occurred as a result of filter placement. Only one of the remaining 35 patients who died (14%) within 2 weeks of filter placement had suspected recurrent embolism. Follow-up studies in 99 patients extending to 100 months showed only two early and no late occlusions of the filter, for a long-term patency rate of 98%. The recurrent embolism rate of 5% is comparable to that of previously reported experience and appears to be independent of the use of long-term anticoagulation therapy.

Adolescent↗

Malignant melanoma embolus as a cause of acute aortic occlusion: report of a case.

A case of acute aortic occlusion caused by embolization of malignant melanoma tumor fragments is presented. Transfemoral catheter embolectomy restored normal lower extremity circulation. Noncardiac tumor emboli, although rare, originate either from primary pulmonary malignancies or nonpulmonary malignancies with pulmonary metastases and pulmonary vein invasion. Tumor embolization should be considered a possible source of peripheral arterial emboli when there is no other obvious source, such as the fibrillating or infarcted heart. In such cases, early surgical intervention should be considered in preference to therapy with heparin or streptokinase.

Acute Disease↗

Acute renal artery occlusion: when is revascularization justified?

Acute renal artery occlusion is an infrequently encountered entity, with a paucity of literature on which to form clinical decisions. During a 20-year period 35 patients were treated for acute renal artery occlusion as a result of embolism (13 patients), thrombosis of a stenosed vessel (16 patients), or trauma (six patients). Patients were treated operatively in 16 cases and nonoperatively in 19 cases. In patients with embolic occlusion, embolectomy was successful in the relief of hypertension but was ineffective in the restoration of renal function. In patients with thrombotic occlusion, thrombectomy and aortorenal bypass were successful in both the reduction of blood pressure and the retrieval of renal function. In this group, salvage was dependent on the presence of a reconstituted distal renal artery, irrespective of the operative delay. In patients with traumatic renal artery occlusion, return of renal function did not occur, despite reperfusion as early as 6 hours after injury. These data suggest that the period in which function of embolized or traumatized kidneys may be preserved has usually passed by the time the diagnosis of renal artery occlusion has been made. By contrast, operative therapy of thrombotic occlusion frequently results in return of renal function, irrespective of the delay in treatment.

Adolescent↗

Plasma exchange after revascularization compartment syndrome with acute toxic nephropathy caused by rhabdomyolysis.

A 75-year-old man developed acute, fulminating compartment syndrome of the femoral and crural muscles together with acute toxic nephropathy caused by severe myoglobinemia after uncomplicated embolectomy of the common femoral artery. In addition to fasciotomies and administration of mannitol, sodium hydrogen bicarbonate, and furosemide, we performed plasma exchanges on three occasions. The urine and serum concentrations of myoglobin fell from above 180.0 and 50.0 mg/dl, respectively, to 0.14 and 0.11 mg/dl after the third plasma exchange on the ninth day after admission. The serum creatinine concentration was normal on admission, peaked at 2.85 mg/dl, and returned to normal values at discharge. We suggest that plasma exchange may be considered an adjunct to conventional therapy of compartment syndrome with associated acute toxic nephropathy caused by myoglobinemia.

Aged↗

Massive pulmonary embolism: triple-armed therapy.

Many patients who suffer a massive pulmonary embolus die despite emergent therapy. In these desperately ill patients an aggressive, combined method of management was initiated to improve their chances and quality of survival. During a 5-year period 10 patients were treated with (1) low-dose topical, intrapulmonary thrombolytic therapy to dissolve thrombus, (streptokinase or urokinase); (2) anticoagulation to prevent thrombus propagation (heparin); and (3) the simultaneous insertion of a Greenfield filter to prevent the early, recurrent, and therefore potentially fatal pulmonary embolus--"triple-armed therapy." Thrombolytic therapy was administered through a Swan-Ganz catheter wedged against the pulmonary embolus. During the same interval 10 other patients also sustained massive pulmonary emboli but were treated only with systemic heparin. Serial pulmonary arteriography was performed daily. The patients treated by triple-armed therapy responded favorably with a rapid (less than 6 hours), significant improvement in PaO2, pulmonary artery pressure, cardiac output, pulmonary vascular resistance, and blood pressure, compared with patients treated with continuous heparin alone. Nine patients in the triple-armed therapy group survived whereas only six in the heparin group survived. Two additional patients were treated by triple-armed therapy and had thrombolysis with triple-armed therapy with tissue plasminogen activator; these patients demonstrated the most rapid improvement in cardiorespiratory dynamics and arteriographic clearance of emboli. This management protocol shows promise for patients who sustain a massive pulmonary embolus, because it reduces the morbidity associated with pulmonary embolectomy while avoiding the hazards associated with systemic thrombolytic therapy.

Aged↗

Posterolateral exposure for renal artery reconstruction.

Anterior approaches to the renal arteries are complicated by the intervening renal veins, inferior vena cava, and abdominal viscera. We describe techniques of direct posterolateral access to both right and left renal arteries by use of an extended retroperitoneal exposure. This approach allows for grafting from the aorta or iliac artery on either side and is particularly suitable on the left side for direct retropancreatic splenorenal artery anastomosis, which is described in detail. It is also useful for distal reconstruction of branch renal arteries, renal artery embolectomy, and autotransplantation "bench surgery." We have used this approach in 28 patients with no operative deaths and two reconstructive occlusions.

Humans↗

Endoscopic intravascular surgery removes intraluminal flaps, dissections, and thrombus.

Over the last 3 years angioscopic techniques have been used to guide intraluminal instrumentation in 73 patients undergoing thrombectomy, nine patients with vascular trauma, and 32 patients during laser angioplasty and balloon dilation. After balloon-catheter thromboembolectomy residual, occlusive thrombi tightly adherent to the arterial wall were removed with flexible biopsy forceps in 13 of 73 (18%) patients; underlying intimal flaps were removed in another four. In nine patients traumatic intimal defects caused by iatrogenic cannulation injuries (n = 5) or external trauma (n = 4) were managed by thrombectomy followed by complete or partial intravascular removal of the intimal flap (n = 6) or dissection plane (n = 3) with long flexible forceps and rotating brushes. Traumatic intimal defects observed in two additional patients were judged to be too severe for endoscopic manipulation and required immediate bypass grafting. Inspection after angioplasty in 32 patients revealed wall charring and obvious thermal damage after laser procedures in 28 (87%) and plaque cracking, intimal flaps, and fragmentation in 26 (81%). These defects were underestimated on intraoperative angiography. Large flaps and thrombus were removed endoscopically in three. We conclude that angioscopic study reveals the extent of intimal injury and gives insights into mechanisms of instrumentation. Adherent thrombus after embolectomy by balloon catheter and intimal flaps caused by trauma or angioplasty are common and, if severe, can be successfully treated by endoscopic intravascular manipulation in selected patients.

Blood Vessels↗

Percutaneous intraarterial thrombolysis in the treatment of thrombosis of lower extremity arterial reconstructions.

Vascular grafts may be salvaged with thrombolytic therapy after acute occlusion as an alternative to balloon catheter thrombectomy. From October 1987 to May 1990, 15 arterial bypasses to the lower extremity (infrainguinal saphenous vein [n = 7] or expanded polytetrafluoroethylene [n = 6], and Dacron aortofemoral bifurcation graft limbs [n = 2]) were treated for 30 occulsions with intraarterial urokinase (390,000 IU to 5,808,000 IU) infused from 3 to 40 hours. The origins of 15 graft occlusions were morphologic defects (intimal hyperplasia with anastomotic or conduit stricture), pseudoaneurysm, or progression of disease distal to the graft. Two occlusions were attributed to coagulation disorders. A cause could not be identified for 13 occlusions. Patency was initially restored to all grafts with use of thrombolytic therapy, however, adjunctive surgical thrombectomy to remove persistent thrombus from the graft or outflow vessels was required after six thrombolytic infusions. One graft in the series could not be salvaged leading to below-knee amputation. Graft defects were corrected by balloon angioplasty (n = 7) or surgical revision of the conduit (n = 8). Five significant hemorrhagic complications occurred from the catheter insertion site requiring four emergent surgical procedures and resulting in the death of a fifth patient from a myocardial infarction. This technique allows chemical thrombectomy of branch arteries distal to the graft and inaccessible to a balloon embolectomy catheter, and permits diagnosis of abnormal graft morphology that may be the cause of the graft occlusion. Graft reocclusion can be expected if technical defects in the arterial reconstruction are not revised or hypercoagulable states are not treated.

Angioplasty, Balloon↗

Surgical management of severe acute lower extremity ischemia.

Seventy-four patients (70 men [95%], 4 women [5%], mean age, 63 years) with severe, acute lower limb ischemia (acute clinical deterioration and absent pedal Doppler signals) caused by either arterial thrombosis (n = 68) or embolism (n = 6) underwent urgent surgical management consisting of operative revascularization with or without amputation in 67 patients (91%) and primary amputation alone in 7 patients (9%). Sixty-one patients (82%) had severely threatened limb viability, and 13 (18%) had major irreversible ischemic limb changes at presentation. Eighty-six percent of patients were initially anticoagulated with heparin. Seventy percent underwent preoperative angiography. Surgical revascularization included 42 inflow and 20 outflow arterial reconstructions and 9 thrombectomy or embolectomy procedures. Mean follow-up was 17 months (range, 0 to 64). Life-table primary patency at 36 months for arterial reconstructions was 81% for inflow and 78% for outflow procedures. Cumulative limb salvage was 70% at 1 month and 68% at 36 months. Patient survival was 85% at 1 month and 51% at 36 months. No death was directly attributable to complications related to limb reperfusion, and no patient required dialysis for myoglobinuria. We conclude that management of severe, acute lower limb ischemia with early amputation of nonviable limbs and heparinization, angiography, and prompt operative revascularization for threatened but viable extremities minimizes morbidity and mortality rates, while maximizing limb salvage. These results may be useful for comparison with comparable groups of patients treated with thrombolytic or endovascular modalities.

Acute Disease↗

Isolated limb perfusion with urokinase for acute ischemia.

PURPOSE: Isolated limb perfusion with urokinase was used to salvage an acutely ischemic lower limb. METHODS: Isolated limb perfusion with urokinase over a 90-minute period was used in the treatment of a 69-year-old female patient with acute ischemia of the left leg after thrombosis of a femoral artery bypass graft. Previous balloon embolectomy and heparin therapy had failed. The flow rate was able to be increased progressively without rise in the line pressure during the course of the perfusion, indicating an increase in capacity of the peripheral arterial bed. Fibrinogen and plasminogen levels in the isolated circulation remained low throughout the perfusion. The concentration of cross-linked fibrin degradation particles (d. dimer) rose progressively in the isolated circulation but remained at normal levels in the systemic circulation during perfusion. RESULTS: Completion angiography demonstrated clearance of thrombus in the popliteal artery and appearance of arteries not seen on preperfusion films. Clinical improvement paralleled the angiographic appearances, with restoration of limb viability. CONCLUSION: We concluded that isolated limb perfusion with use of urokinase is safe and worthy of further investigation.

Acute Disease↗

Management of symptomatic and asymptomatic popliteal venous aneurysms: a retrospective analysis of 25 patients and review of the literature.

OBJECTIVE: Popliteal venous aneurysms (PVAs) are an uncommon but potentially life-threatening disease because they can be a source for pulmonary emboli (PE). With the widespread use of venous duplex scanning, PVAs are increasingly found in patients with deep or superficial vein insufficiency, and questions have arisen as to the management of these aneurysms. The purpose of this study was to review our experience in the management of PVAs diagnosed in patients with PE and in patients with chronic venous diseases. METHODS: Twenty-five patients with PVAs were treated in two centers between 1985 and 1999. There were 20 women and five men, with an average age ranging from 33 to 79 years (mean age, 59 years). Twenty-four percent (6/25) presented with PE, and 76% (19/25) of PVAs were discovered during investigation for chronic venous disease (varicosities, n = 13; post-thrombotic symptoms, n = 6). The diagnosis of PVA was achieved in all cases with venous duplex scanning and phlebography. Aneurysms were located in the proximal popliteal vein (n = 17) and at the saphenopopliteal junction (n = 8). Seventy-two percent (18/25) of PVAs were saccular, and 40% (10/25) had an intraluminal thrombus. Two patients with PE underwent cardiac arrest, with one requiring a pulmonary embolectomy. The Fisher exact test showed a statistically significant correlation between PE and the presence of thrombus (50% vs 7% without thrombus, P =.02). Aneurysms were treated with tangential aneurysmectomy and lateral venorrhaphy (n = 19), resection with end-to-end anastomosis (n = 2), resection with interposition of the greater saphenous vein (n = 2) or the superficial femoral vein (n = 1), and resection with vein transposition (n = 1). Two patients who experienced a PE had an inferior vena cava filter placement before surgical repair of the PVA. RESULTS: Mean follow-up was 63 months (range, 11-168 months). No operative deaths occurred, and no patient had evidence of a recurrent PE. Postoperative minor complications (20%) included transient common peroneal nerve palsy (n = 2), postoperative hematoma (n = 2), and wound infection (n = 1). Postoperative thrombosis of the surgical repair occurred in three patients, and patency was restored with anticoagulation therapy. CONCLUSION: Despite its rarity, PVAs should be ruled out with venous duplex scanning in patients with PE and in patients presenting with chronic venous diseases. Because of the unpredictable risk of thromboembolic complications, surgical treatment that is accompanied by a low morbidity rate is indicated in all PVAs. Tangential aneurysmectomy with lateral venorrhaphy is the procedure of choice.

Adult↗

Arterial tumor embolism caused by metastatic melanoma: case report and literature review.

Arterial tumor embolization is a rare complication of neoplasms. This report describes a 64-year-old female with metastatic melanoma and acute arterial embolization to the left lower extremity. With surgical embolectomy, a clot was retrieved that had an atypical bland solid lead point. Pathologic examination confirmed metastatic melanoma. Further echocardiography revealed an intracardiac mass consistent with metastatic disease. The patient was seen a month later with embolization to the right middle cerebral artery.

Diagnosis, Differential↗

Pulmonary thromboembolism. 2. New trends in prophylaxis and therapy.

Although low-dose heparin therapy is the technique most commonly used for prophylaxis of pulmonary thromboembolism, its usefulness is being questioned. Platelet deaggregation prophylaxis with either aspirin or dipyridamole, or both, apparently is a reasonable alternative, but further studies are needed. For treatment of pulmonary thromboembolism, continuous conventional-dose heparin therapy is the approach of choice. It has the highest therapeutic/toxic ratio and is the most effective technique for prevention of clot propagation. The patient's fibrinolytic network must be intact, however, if clot degradation is to occur. Fibrinolytic therapy with urokinase or streptokinase should be restricted to use in patients with massive pulmonary embolism in whom hemodynamics are unstable. Caval interruption and pulmonary embolectomy have lower benefit/risk ratios than do the medical alternatives and are rarely used for pulmonary thromboembolism.

Aspirin↗

Management of arterial emboli. Gleanings from 20 years of experience.

Arterial embolism is usually caused by cardiac disease, and atherosclerotic coronary vascular disease is the primary precursor. Other cardiac states, as well as several uncommon causes, are part of the etiologic spectrum. The earliest signs are pain, paresthesias, pallor, and pulselessness. Severe ischemia is indicated by paralysis, a late feature. Arterial embolism and acute thrombosis can be difficult to distinguish, and deep venous thrombosis may also be suspected in the differential diagnosis. To restore arterial flow, anticoagulation treatment with heparin (Lipo-Hepin, Liquaemin) is given and surgical embolectomy is performed. Heparin infusion is continued until the patient is ambulatory, and then warfarin sodium (Coumadin, Panwarfin) is given over the long term. Fibrinolysis has also been used to treat acute arterial occlusion. Complications of embolism must be carefully guarded against, and additional procedures are sometimes necessary.

Arterial Occlusive Diseases↗

Heparin-associated thrombocytopenia: an update.

The use of heparin may be complicated by two types of thrombocytopenia (HAT): type I occurs early, is transient, and has no clinical relevance, while type II may lead to very severe manifestations (arterial or venous thromboses and more rarely bleedings), that are still underestimated by some clinicians. HAT-type II most frequently develops after use of therapeutic doses of unfractionated heparin (UH) but has also been described less frequently after use of very low doses of UH, of low molecular weight heparins (LMWH), and even of polysulfated glycosaminoglycosans devoid of anticoagulant action. The estimation of the incidence of HAT-type II and of related thromboses is a very difficult matter. Recent observations suggest that thromboses (notably venous) may be more frequent than previously estimated. HAT-type II pathophysiology includes the formation of immune complexes at the surface of platelets; the antigen has been shown to be most often platelet factor 4 bound to heparin while the antibody is recognized by platelet Fc gamma RII receptors. Thromboses result most probably from activation of both platelets (leading to the formation of microparticles) and endothelial cells. Several biological tests are presently available for diagnosing HAT-type II but none of them has been shown to be ideal. The prevention of HAT-type II requires history taking preference of LMWH to UH, early start of oral anticoagulation, and platelet monitoring from the fifth day of heparin therapy. The therapy of HAT-type II implies immediate discontinuation of heparin and avoidance of platelet transfusions, unless severe bleeding occurs. If further antithrombotic treatment is deemed necessary (probably in all cases), several options are possible but presently, the most recommended ones are Org 10172 or Ancrod; embolectomy or thrombolysis may also be required if a new thrombotic event has developed. A very difficult dilemma concerns patients previously sensitized to heparin and who present a clinical situation that theoretically mandates re-exposure to UH, such as by-pass surgery; prostacyclin analogues may be successfully used in such cases. Recent developments in the therapy of HAT-type II include recombinant hirudin or synthetic analogs, or use of some intravenous immunoglobulin preparations. Possible candidates are the heparin synthetic pentasaccharide and recombinant tissue factor pathway inhibitor.

Ancrod↗

Intraoperative diagnosis and treatment of massive pulmonary embolism complicating surgery on the abdominal aorta.

Massive pulmonary embolism associated with total cardiovascular collapse occurred during the surgical repair of a ruptured abdominal aortic aneurysm with an aortocaval fistula. Pulmonary artery pressure monitoring permitted immediate diagnosis whereas central venous pressures did not reflect the obstruction to right ventricular outflow. Pulmonary embolectomy without cardiopulmonary bypass was performed successfully.

Aorta, Abdominal↗

Cardiopulmonary bypass in patients with malignant renal neoplasms.

A case report of a patient with malignant renal neoplasm who underwent emergency pulmonary embolectomy during operation is presented. Knowledge of degree of venous extension, appropriate operative positioning of the patient and consideration of elective cardiopulmonary bypass are suggested ways to reduce morbidity and mortality from massive pulmonary emboli in these patients.

Carcinoma, Renal Cell↗