RESUMEN
BACKGROUND: Current treatment of acute peripheral artery or bypass graft occlusion utilizes catheter-directed thrombolysis of a plasminogen activator (PA). Plasmin is a direct-acting thrombolytic with a striking safety advantage over PA in preclinical models. OBJECTIVES: To report the first use of purified plasmin for acute lower extremity arterial or bypass graft thrombosis in a phase I dose-escalation study of a catheter-delivered agent. METHODS: Eighty-three patients with non-embolic occlusion of infrainguinal native arteries or bypass grafts were enrolled (safety population) into seven sequential dose cohorts to receive 25-175 mg of plasmin by intrathrombus infusion over 5 h. Arteriograms were performed at baseline, 2 h, and 5 h, and subjects were monitored for 30 days for clinical outcomes and laboratory parameters of systemic fibrinolysis. RESULTS: Major bleeding occurred in four patients (4.8%), and minor bleeding alone in 13 (15.7%), with no trend towards more bleeding at higher dosages of plasmin. There was a trend towards lower plasma concentrations of fibrinogen, α(2) -antiplasmin and α(2) -macroglobulin with increasing doses of plasmin, but the nadir fibrinogen concentration was > 350 mg dL(-1) at the highest plasmin dose. Individual nadir values were above 200 mg dL(-1) in 82 of 83 subjects, and were not different in patients with or without bleeding. Thrombolysis (≥ 50%) occurred in 79% of subjects receiving 125-175 mg of plasmin, as compared with 50% who received 25-100 mg. CONCLUSIONS: Catheter-delivered plasmin can be safely administered to patients with acute lower extremity arterial occlusion at dosages of 25-175 mg.
Asunto(s)
Arteriopatías Oclusivas/tratamiento farmacológico , Cateterismo Periférico , Fibrinolisina/administración & dosificación , Fibrinolíticos/administración & dosificación , Oclusión de Injerto Vascular/tratamiento farmacológico , Extremidad Inferior/irrigación sanguínea , Terapia Trombolítica/métodos , Enfermedad Aguda , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Arteriopatías Oclusivas/sangre , Arteriopatías Oclusivas/diagnóstico por imagen , Biomarcadores/sangre , Brasil , Cateterismo Periférico/efectos adversos , Relación Dosis-Respuesta a Droga , Europa (Continente) , Femenino , Fibrinógeno/metabolismo , Fibrinolisina/efectos adversos , Fibrinolíticos/efectos adversos , Oclusión de Injerto Vascular/sangre , Oclusión de Injerto Vascular/diagnóstico por imagen , Hemorragia/inducido químicamente , Humanos , Infusiones Intraarteriales , Masculino , Persona de Mediana Edad , Radiografía , Sudáfrica , Terapia Trombolítica/efectos adversos , Factores de Tiempo , Resultado del Tratamiento , Estados Unidos , Adulto Joven , alfa 2-Antiplasmina/metabolismo , alfa-Macroglobulinas/metabolismoRESUMEN
PURPOSE: Occlusive iliofemoral venous thrombosis is associated with morbid short- and long-term consequences. Having been disappointed with standard anticoagulant therapy and systemic fibrinolysis, we embarked on an aggressive multidisciplinary regional approach to treat these patients, with the goals of therapy being (1) to eliminate iliofemoral venous thrombus, (2) to provide unobstructed venous drainage from the affected limb, and (3) to prevent recurrent thrombosis. METHODS: Twelve consecutive patients were treated for extensive iliofemoral venous thrombosis. Each had thrombus from their infrapopliteal veins through their iliofemoral system, and four had vena caval involvement. The conditions of 11 patients failed to improve when the patients were given anticoagulants, and prior systemic fibrinolysis failed in five patients. The treatment strategy includes catheter-directed thrombolysis with intrathrombus infusion of the plasminogen activator or operative thrombectomy or venous bypass with a permanent 4 mm arteriovenous fistula (AVF). RESULTS: Nine of 12 patients had a good or excellent clinical outcome (mean follow-up 25 months), which correlated with restored unobstructed venous drainage from the affected limb. Seven patients had catheter-directed lytic therapy attempted. In five patients the catheters were appropriately positioned, and lysis was successful. Five of the eight patients who underwent operations had successful procedures. Two of the three patients with poor operative outcomes had residual thrombus in their iliac veins or vena cava after thrombectomy (without bypass). The third patient, in whom anticoagulation was contraindicated, had an initially successful thrombectomy and AVF; however, vena caval thrombosis developed 2 months after operation. No patient had symptomatic pulmonary emboli, and routine posttreatment ventilation/perfusion lung scanning was not performed. CONCLUSIONS: An aggressive multidisciplinary regional approach to patients with obliterative iliofemoral venous thrombosis, designed to remove thrombus and provide unobstructed venous drainage, offers substantially better clinical outcome compared with systemic fibrinolysis and standard anticoagulation. Catheter-directed thrombolysis is successful if the catheter is appropriately positioned within the thrombus. Contemporary venous thrombectomy, which includes thrombus removal, completion phlebography, AVF, and cross-pubic bypass when necessary, is associated with high success rates. Failures can be anticipated and avoided in most patients.
Asunto(s)
Vena Femoral , Vena Ilíaca , Trombectomía , Terapia Trombolítica , Trombosis/terapia , Enfermedad Aguda , Adulto , Cateterismo Periférico , Terapia Combinada , Femenino , Vena Femoral/cirugía , Humanos , Vena Ilíaca/cirugía , Masculino , Persona de Mediana Edad , Terapia Trombolítica/métodos , Trombosis/tratamiento farmacológico , Trombosis/cirugíaRESUMEN
Two new cases of popliteal venous aneurysm are reported and added to the 22 other cases of popliteal venous aneurysm available for review. Both patients were first seen with acute pulmonary embolism and were treated with thrombolytic therapy followed by anticoagulation. Each had recurrent venous thromboembolism before discovery of the popliteal venous aneurysm. One popliteal venous aneurysm was diagnosed with phlebography and the second with venous duplex imaging, confirmed with phlebography. Both were surgically corrected with tangential aneurysmectomy and lateral venorrhaphy. Twenty-four cases of popliteal venous aneurysm are now available for review. Seventy-one percent (17 of 24) presented with pulmonary embolism, 88% (21 of 24) were saccular, and 96% (23 of 24) were located in the proximal popliteal vein. All but two were diagnosed by ascending phlebography. Three patients received no treatment: in two of these the outcome was not documented and the third had occasional pain. Two patients received anticoagulation without subsequent operative repair and both died of recurrent pulmonary emboli. Operative correction resulted in a 75% patency rate with 21% complications, most of which were related to postoperative anticoagulation. No patient who was operated on had subsequent pulmonary embolism, and there were no operative deaths. We suggest that all patients who have pulmonary embolism have lower-extremity venous duplex imaging. All popliteal venous aneurysms should be surgically repaired, inasmuch as nonoperative therapy results in recurrent thromboembolism and an unacceptably high mortality rate. Tangential aneurysmectomy with lateral venorrhaphy is the recommended procedure.
Asunto(s)
Aneurisma/patología , Vena Poplítea , Adulto , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Embolia Pulmonar/patología , Trombosis/patologíaRESUMEN
Acute deep venous thrombosis (DVT) continues to be a common clinical problem requiring objective evaluation. Hemodynamic testing for acute DVT has been popular, but is inadequate for evaluating asymptomatic patients and symptomatic patients with isolated calf vein thrombi. Venous duplex imaging (VDI) has rapidly gained in popularity, and is generally accepted to be the noninvasive technique of choice for the evaluation of patients with acute DVT. Twenty-five reports evaluate gray-scale venous duplex imaging versus ascending phlebography in 2,781 symptomatic patients. The sensitivity for proximal DVT and calf DVT is 96 and 80%, respectively. Seven reports review the use of VDI for surveillance in 857 asymptomatic patients, with an overall sensitivity of 76% for proximal DVT and of 11% for isolated calf vein thrombosis. The results of color-flow duplex appear to be somewhat better; however, the numbers are considerably smaller. The results for identification of calf vein thrombosis in asymptomatic surveillance patients continue to be poor. VDI appears to be the best noninvasive diagnostic test for acute DVT, and may challenge ascending phlebography as the best diagnostic test for proximal DVT in symptomatic patients, although it will miss 20% of isolated calf DVT. VDI appears to be the best noninvasive screening technique for high-risk asymptomatic patients under surveillance; however, additional correlative studies with ascending phlebography are required. The addition of color Doppler images appears to have improved results, although these higher sensitivities may be the consequence of improved experience as much as the addition of color to the image.
Asunto(s)
Embolia Pulmonar/diagnóstico por imagen , Tromboflebitis/diagnóstico por imagen , Enfermedad Aguda , Color , Presentación de Datos , Estudios de Evaluación como Asunto , Humanos , Métodos , Flebografía , Valor Predictivo de las Pruebas , Sensibilidad y Especificidad , UltrasonografíaRESUMEN
Intraoperative venodilation in veins distant from the site of operation has been shown to occur in animals and has been directly correlated with focal venous endothelial damage. This exposure of subendothelial collagen could serve as initiation sites for thrombus formation. This study tests the hypothesis that human beings (1) significant operative venodilation occurs and that it correlates with postoperative deep venous thrombosis (DVT); (2) operative venodilation can be pharmacologically controlled; and (3) this control reduces the incidence of postoperative DVT. Twenty-one patients undergoing total hip replacement had their contralateral cephalic vein continuously monitored with modified ultrasonographic instrumentation, with a continuous on-line recorder graphing venous diameter. Patients were randomly assigned to receive 0.5 mg of dihydroergotamine and 5000 U of heparin (DHE/Hep) for prophylaxis or placebo, with investigators "blinded" Postoperatively, all patients underwent ascending phlebography. Patients in whom postoperative DVT developed (11) had a mean operative venodilation of 28.9% +/- 3.93%, and those in whom DVT did not develop (10) had a mean venodilation of 11.6% +/- 1.55% (p = 0.001). Only 17% (2/12) dilating less than 20% baseline diameter had DVT compared with 100% (9/9) dilating greater than 20% of baseline diameter (p = 0.002). Patients receiving venotonic agent DHE had significantly less venodilation and DVT (p less than 0.001) compared with patients receiving the placebo. Patients who had DVT and whose veins dilated greater than 20% were older than patients who did not have DVT and whose veins minimally dilated: p = 0.04 and p = 0.07, respectively. Although there was a trend toward increased venoconstriction in patients receiving DHE/Hep (p = 0.09), there was no correlation of venoconstriction with ultimate thrombotic outcome. Maximal venodilation occurs during handling of soft tissue (muscle), and this occurs significantly sooner than maximal venoconstriction, which occurs during bone manipulation. We conclude that excessive operative venodilation is a new and important etiologic factor that leads to postoperative DVT. Operative venodilation can be pharmacologically controlled with the venotonic agent DHE. The combination DHE/Hep reduces postoperative DVT by the reduction of operative venodilation in the presence of low doses of an anticoagulant. These findings offer a new approach for predicting postoperative DVT and an object rationale for developing effective prophylaxis.
Asunto(s)
Articulación de la Cadera/cirugía , Prótesis de Cadera , Complicaciones Posoperatorias , Tromboflebitis/etiología , Vasodilatación , Venas/fisiopatología , Anciano , Dihidroergotamina/uso terapéutico , Heparina/uso terapéutico , Humanos , Estudios Prospectivos , Tromboflebitis/prevención & controlRESUMEN
This is a prospective analysis of 351 patients in two distinct groups undergoing ascending phlebography, impedance plethysmography (IPG), and/or phleborheography (PRG) within the same 24-hour period. One hundred twenty patients also had a 125I-fibrinogen uptake test (RFUT). The two patient groups consisted of the following: those patients evaluated because of suspicion of deep vein thrombosis (DVT) (diagnostic) and those patients at high risk for postoperative DVT (total joint replacement) who had routine noninvasive testing and ascending phlebography (surveillance). The overall sensitivities for IPG and PRG were significantly better in the diagnosis group (71% [69 of 97 patients] and 78% [82 of 105], respectively) compared with the surveillance group (20% [14 of 71] and 27% [17 of 63], respectively) (p less than 0.0001). The sensitivities for IPG and PRG detecting proximal (A/K) thrombi was 83% (68 of 82 patients) and 92% (79 of 86) in the diagnosis group compared with 32% (11 of 34) and 33% (9 of 27) in the surveillance group (p less than 0.0001). Although there was no difference in overall incidence of DVT between the diagnosis group (56%, 118 of 212 patients) and the surveillance group (55%, 76 of 139), the results can be explained by the difference in A/K thrombi (84% [99 of 118] and 47% [36 of 76]) (p less than 0.001) and occlusive A/K thrombi (84% [58 of 69] and 23% [7 of 31]) (p less than 0.0001), respectively. Of the patients with A/K thrombi, 97% (67 of 69) in the diagnosis group had hemodynamically detectable thrombi compared with only 48% (12 of 25) in the surveillance group (p less than 0.001). Combining the RFUT with the noninvasive studies for surveillance significantly improved the sensitivity for both A/K and distal thrombi. Patient selection also appears to have a significant influence on the results of the combination of IPG and RFUT when the current surveillance group is compared with similarly performed studies in a previously reported diagnosis group. The location and magnitude of thrombi in any patient population can be skewed depending on indications and timing of testing, thereby significantly affecting the sensitivity of noninvasive tests. IPG and PRG are reliable for evaluating patients with suspected DVT. However, patients with postoperative DVT have a high incidence of nonocclusive thrombi. Because noninvasive hemodynamic tests cannot identify accurately postoperative DVT, they cannot be used to generate epidemiologic data or as end points for studies evaluating efficacy of prophylaxis in patients undergoing total joint replacement, and anatomic studies of the deep venous system continue to be required.