(

David E. Eisenbud, MD, Bruce J. Brener, !\ID, Richard Shoenfeld, !\ID, Debra Creighton, ~IS, Robert J.Goldenkranz, MD, Donald K. Brief, ~ID, Jose:ph Alpert, !\ID, Jan Huston, MD, Andrew Novick, ~ID, U. R,

Krishnan, MD, Victor Parsonnet, MD, Jerome Nozick, !\ID, Pedro Cordero, MD, :-.'ewark. Ne" Jersey

This study reviewed 57 patients with 71 vascularocclusions treated with urokinase from 1985 to1988. Of these patients, 89% were candidates forurgent surgery. Tota tisis was achieved in 73%of cases. The success rate rose wit rncreasrng expe-r-:~p <0.05), and recent occlusions had morefavorable outcomes Iban older ones (p <0.05).The length and type of occluded conduit (graft orvessel) , age, sex, other mediéal conditions, andconcurrent use of heparin had no influence on suc-cess. Of 18 cases successfully lysed and not subject-ed to any adjunctive therapy directed at the causeof occlusion, 9 (50%) reoccluded within 1 to 88days (mean: 25 days). Cases successfully treatedwith thrombolysis and surgery or dilation of thecausative stenosis had poor l-year patencies: 17%,20%, and 55% for vein grafts, prosthetic grafts,and native arteries, respectively. With additionalurokinase treatments, surgical operations, and per-cutaneous procedures, l-year patencies were 22%,45%, and 65%, respectively.

too small for surgical thrombectomy may be re-estab-lished. This approach also has appeal because it is lessinvasive than surgery. Because of these considerations,thrombolytic therapy has been used in coronary [1], pe-ripheral vessel and graft [2-6], dialysis graft [7], andvenous [8] occlusions.

There rema in, however, many potential problemswith this approach. Bleeding from the angiographicpuncture site or at distant points such as the retroperiton-eum or intracranial space may occur, with potentiallydisastrous results. The multiple angiograms needed tofollow the course of thrombolysis can cause dye-inducedrenal injury. Ifunsuccessful, the delay of definitive surgi-cal therapy may cause progression to irreversible end-organ ischemia. Finally, the thrombolytic agents are ex-pensive and require considerable material and humanresources for their delivery and monitoring.

Several gro!lps have sought to define the optimal regi-men for delivery of thrombolytic agents. The duration oftherapy, the dosage schedules, and the delivery cathetersare all subjects of investigation. Even less clear is theexact role of thrombolytic therapy in the clinical setting.Does it replace, augment, or merely delay surgery?

We have used thrombolytic therapy in selected pa-tients ayer the past 7 years. Because of the high incidenceof allergic reactions and increased bleeding complicationswith streptokinase [2], we have used urokinase exclusive-ly since 1985. In arder to investiga te the efficacy of uroki-nase and its role in the treatment of vascular occlusions,we have reviewed our experience with 71 infusions in 57patients since 1985.

T be próblem of acute vascular or graft occlusion re-mains a major cballenge to vascular surgeons. Tber-

apy must be addressed not only toward prompt tbrombec-tomy but also toward correction of tbe underlying causeof occlusion. Success also depends on tbe speed witbwbicb tbe problem is solved; delay allows for distal propa-gation of clot and compromises tbe eventual outcomebecause distal iscbemia may become irreversible beforeflow is re-establisbed.

Tbrombolytic tberapy has emerged as an importanttreatment tbat is useful in botb tbe diagnostic and tbera-peutic aspects of tbis problem. By dissolving tbe clot, anunderlying arteriallesion tbat led to tbrombosis may berevealed; at tbe same time, flow in peripheral branches

PATIENTS AND METHODSAll patients receiving urokinase from 1985 through

1988 were included in the study. Factors noted includedstandard demographic and vascular risk factors, usingthe format of Rutherford el al [9]. The degree and dura-tion of ischemia and angiographic features of the occlu-sion (site and length) were recorded. A judgement wasmade concerning the type of surgical procedure thatwould be required if thrombolytic therapy were not at-tempted. Features of the urokinase administration wererecorded, including the duration of therapy, dosage, con-comitant administration ofheparin, fibrinogen levels, andcomplications. Finally, the angiographic and clinical out-comes were noted.

There were 33 men and 24 women, with an averageage of 60.5 years. Diabetes was present in 39% and hyper-tension in 51 %; 46% were current smokers. Sites of occlu-sion included 27 native arteries (11 popliteal, 4 femoral, 4tibial, 3 iliac, 3 renal, 1 brachial, 1 pedal arch), 2 veins (1superior vena cava, 1 axillary-subclavian), and 42 grafts

From the Departments of Surgery and Radiology, Newark Beth IsraelMedical Center, Newark, New Jersey.

Requests for reprints should be addressed to David E. Eisenbud,MD, Newark Beth Israel Medical Center, 201 Lyons Avenue, Newark,New Jersey 07112.

Presented at the 18th Annual Meeting of the Society for ClinicalVascular Surgery, Palm Desert, California, March 7-11, .1990.

THE AMERICAN JOURNAL OF SURGERY VOLUME 160 AUGUST 1990160

UROKINASE TREATMENT FOR VASCULAR OCCLUSIONS

(17 femoral-popliteal, 11 femoral-tibial, 4 aorto-femoral,10 other). The decision to use urokinase therapy wasmade jointly by the vascular surgeon and the radiologist.Intracerebral neoplasm, recent stroke, recent gastrointes-tina1 bleeding, active coagulopathy, abdominal, chest, orneurologic surgery within the prior 3 weeks, and criticalischemia requiring irnmediate operation were contraindi-cations to the use of urokinase [10].

After angiography defined the site of occlusion, a softguide wire was advanced through the clot. For iliac occlu-sions, this was accomplished retrograde from the ipsilat-eral groin; infrainguinal occlusions were approached an-tegrade from the ipsilateral or contralateral groin. If aguide wire could not be passed, thrombolytic therapy wasnot attempted. A catheter was then red over the wire andpositioned in the most distal point o.r occlusion. A high-dose urokinase regimen, as outlined by McNamara andco-workers [4,11], was instituted. In most cases, this in-volved a bolus of 40,000 units followed by a constantinfusion of 4,000 unitsjminute for 2 hours. During thisinitial period, the course of thrombolysis was followed byfrequent fluoroscopic monitoring; as the clot lysed, thecatheter was repositioned more proximally. Concurrentsystemic heparin therapy was generally not used. Duringthe period of this study, a coaxial catheter became avail-able; this was used to deliver 2,000 unitsjminute simulta-neously-through both proximal and distal ports. At theend of 4 hours, if any clot remained, the infusion wascontinued at 1,000 to 2,000 unitsjminute, and the patientwas monitored in the intensive caTe unit until the follow-ing day. Angiography was conducted at approximately12-hour intervals thereafter until therapy was discontin-ued. Patients were monitored with frequent clinical ex-aminations and measurements of hematocrit and fibrino-gen levels.

Patients who required urgent surgery after thrombo-lytic therapy were brought to the operating room with theangiographic catheter in place infusing heparin. Patientswho underwent total clot lysis, with or without subse-quent adjunctive procedures (surgery or angioplasty),were followed with clinical and Doppler examinations.

Data were entered into the Newark Beth Israel Vas-cular Registry and a computer database. The final clini-cal and angiographic outcomes were classified as success-es or failures, and other parameters were tested for theirinfluence on the success rate using chi-square analysis.Long-term patency of initially successful outcomes wasplotted by the Kaplan-Meier method.

ferences were found between infusion times for arterial,venous, or graft occlusions. Total clot resolution wasachieved in 73% of cases. The success rate rose signifi-cantly during the course of ibis study: 57% in 1985-1986versus 81% in 1987-1988 (p <0.05).

None of the demographic factors analyzed-sex, age,hypertension, diabetes, cardiac disease, and smoking-had a significant influence on the likelihood of completethrombolysis (Table 1). Results in patients with minimalischemia were similar to those in patients with more sig-nificant impairment. On the other hand, duration of theocclusion had an important effect on outcome: occlusionhad been present in the successfully treated patients for41 :i: 90 hours (median: 15 hours) but had been presentfor 187 :i: 359 hours (median: 48 hours; p <0.05) in thepatients in whom treatment failed. The length, site, andtype of the occluded conduit had no effect on the out-come. Autogenous graft material fared as well as pros-thetics.

The cause of vascular occlusion was definitively re-vealed in 52% of cases, and a possible cause was revealedin an additional 23%. The cause was more likely to beclearly defined when clot lysis was complete (p <0.05).Among the 18 of 42 graft thromboses whose causes weredefinitely revealed were 7 polytetrafluoroethylene(PTFE; l inflow and 6 outflow stenoses), 2 reversed sa-

RESULTSSevere ischemia was present in most patients; prior to

urokinase infusion, 89% of patients were judged to becandidates for urgent surgery. Among these, the plannedsurgical procedures were 36 bypass grafts, 18 thrombec-tomies, 3 graft revisions, 3 nephrectomies, 3 below-kneeamputations, and 1 above-knee amputation. Only eightpatients, including the two with venous occlusions, wouldprobab1y not have required any surgery.

Infusion times ranged from 15 minutes to 110 hours(mean: 23 hours; median: 18 hours). No significant dif-

THE AMERICAN JOURNAL OF SURGERY VOLUME 160 AUGUST 1990 161

f;ISENBUD ET AL

,..

.,-, ~

100

90

80

70~

~60~ 50

~40~30

20

10

8

lative

5

3 40%AulogenousAutogenous

~-

'.' 22%2 "" Proslhetic 1

".".'.""".' 10%17""10~

12TIME (monlhs )

12TIME (mon1hs)

Figure 1. Patency of aneries, vein gratIs, and prosthetic gratIsafter successful thrombolysis and subsequent adjunctive proce-dures (dilatation or surgery) during the same hospitalizatíon.

-Figure 2. Patency of arteries, vein grafts, aro prosthetic graftsafter successful thrombolysis and subsequent adjunctive mea-sures (repeated thrombolysis, dilatation, or surgery) at any pointafterwards.

versus 268 ::1: 80 mgjdL; p <0.01). Two patients hadfibrinogen levels measured below 100 mgjdL; one bledand the other did noto The extra time r~uired to deliverthrombolytic therapy, resulting in a delay in bringing thepatient to surgery, was harrnful in two patients and mildlydetrimental in another two; unsuccessful thrombolysisperrnitted distal ischemia to progress. One patient whounderwent multiple angiograms during a 5-day course ofurokinase therapy experienced irreversible renal failurer~uiring dialysis.

The median and mean fo1low-up was 5.3 and 10months, respectively. One-year patency rates after initial-ly successful thrombolysis (and adjunctive proceduresduring the same hospitalization) were 17%, 20%, and55% for vein grafts, prosthetic grafts, and arteries, respec-tively (Figure 1). Secondary patencies, allowing for mul-tiple interventions with thrombolysis, surgery, or percuta-neous dilatation, raised the patency rates somewhat: 22%,45%, and 65% for vein grafts, prosthetic grafts, and arter-ies, respectively (Figure 2).

COMMENTSOur experience with urokinase demonstrates that 73%

of thrombi can be lysed completely. This result is compa-rable with that reported from other centers, where throm-bolysis rates of40%to 90% have been found [2-6,12-16].The factors that influence the speed and degree of clotlysis have not been established completely. The onIy fac-tor on which there is agreement is the duration of occlu-sion; fresh clots are more likely to lyse iban older ones[3,4]. In some cases, however, clots that are months oldwill still respond to urokinase infusion. It has been pro-posed [3] that thrombolysis of grafts should be moresuccessful iban arteries, presumab.1y beca use arterieshave sirle branches that can siphon off the urokinase,leaving less agent to act on the thrombus. In our study,however, grafts and native vessels farro equally well,perhaps because patients with clotted grafts presentedthemselves for therapy earlier iban those with collateral-ized arterial obstructions. In addition, although others[3,4] have found site-specific differences in success rates,we found no differences in the results at the suprain-guinal, thigh, and infrageniculate levels.

phenous veins (both with anastomotic stenoses), 5 nonre-versed saphenous veins (2 outllow and 3 midgraft steno-ses), and 1 inflow stenosis of a Dacron graft. There were22 arteria1 thromboses, including 12 in situ thromboses ofdiseased iliac, femoral, or popliteal segments; 6 immedi-ate postangioplasty thromboses (5 renal and 1 other); and2 popliteal aneurysrns. The remaining seven patients hadfive emboli and two venous thromboses.

Adjunctive therapy was required in 47 (66%) cases;tbis was accomplished within 1 day of completion ofthrombolytic therapy in 29 cases (62%). Additional ther-apy included 18 percutaneous transluminal angioplasties,17 bypass grafts, 2 patch angioplasties, 3 thrombecto-mies, 2 graft revisions, 2 below-knee amputations, 1 sym-pathectomy, and 1 pacemaker insertion. Among the 36patients who would have requireda vascular graft beforeurokinase, only 15 underwent such a procedure after-wards; 10 had no surgery, 3 underwent thrombectomy,and 8 had transluminal angioplasty. The magnitude ofthe procedures required was reduced in 33% of patients.Many patients who would have required bypass graftinginstead uriderwent local surgical or percutaneous angio-plasties. In general, patients requiring bypass surgerywere those with incomplete thrombolysis, while thosetreated with angioplasty or local revisions had totallysisbeforehand. In 27% of cases, the outcome was judged tobe favorably influenced by the improved selection of graftinflow and outllow sites and a clearer outllow tract afterurokinase dissolution of obscuring clot.

Adjunctive therapy was not used in 24 cases (34%).Six of these patients had thrombosis during angioplastyand, after successful thrombolysis, underwent completionof their angioplasties. Among the other 18 patients, 9(50%) had reocclusion at an average of 25 days (range: 1to 88 days).

Complications were noted in 41 % of cases. Most ofthese related to bleeding from the angiographic puncturesite. Significant internal hemorrhage requiring transfu-sion was seen in 11 patients (15%). One intracranialbleeding episode was fatal; all other cases of bleedingresolved without adversely affecting the patient. Patientswith hemorrhagic complications had lower fibrinogenlevels iban those without complications (198 :f: 76 mgj dL

VOLUME ] 60 AUGUST 1990162 THE AMERICAN JOURNAL OF SURGER y

~

UROKINASE TREATMENT FOR VASCULAR OCCLUSIONS

Figure 3. Angiogram demonstrating an acute popliteal occlusion. Figure 4. Angiogram after complete clot Iysis by urokinase. dem-onstrating an irregular popliteal artery; a sonogram showed asmall popliteal aneurysm (same patient as in Figure 3).

We have noted a significant increase in OUT rate ofsuccessful thrombolysis ayer the past 4 years. This im-provement can be attributed to several factors. First, asthe study progressed, we were less reluctant to use higherclases of urokinase. Currently, we employ the high-doseregimen of McNamara and co-workers [4,17]-a bolusclase of 40,000 units followed by an infusion of 4,000unitsjminute, supplemented by bolus clases of 20,000 to40,000 units as needed. Secand, patient selection hasimproved. Patients with old clots that will not permitpassage of a soft guide wire are no longer selected forthrombolytic therapy. In addition, various technical im-provements have made passage of the required catheterseasier. For example, during bypass surgery, we mark thelocation of all vascular anastomoses in the operatingroom with radiopaque clips to facilitate fluoroscopic vis u-alization in case of later graft thrombosis. Softer guidewires that are more easily steered around curves have alsofacilitated urokinase administration.

The diagnostic value of thrombolysis is high in situa-tions that are not clinically obvious, such as the acutepopliteal occlusion (Figures 3 and 4). In this case, thereare several possible causes-embolus, in situ thrombosis,aneurysm, entrapment, and cystic adventitial disease-and the optimal treatment varies according to the diagno-sis. In addition, thrombolysis may be preferable to sur-

gery in occluded vein grafts, which may be damaged bythe passage of Fogarty catheters.

The therapeutic role of urokinase is less well defined.In our patients, 89% of whom were candidates for urgentsurgical operation before the urokinase treatment, sometype of invasive therapy was still required in 66% of casesafter treatment. This is not unexpected, since in the ma-jority of our patients, graft or vessel thrombosis was sec-ondary to underlying atheromatous plaque or neointimalhyperplasia. In fact, most patients who did not receivesome sort of adjunctive therapy after urokinase proceed-ed to experience re-occlusion within weeks. Others havereported similar experiences. Pernes el al [3] found that 8of 13 patients with initially complete lysis of thrombosedgrafts had re-occlusion within 1 week. McNamara andBomberger [4] reported that of arteries and grafts openedwith thrombolytic therapy and demonstrating residualstenosis over 50%, only 8% remained patent at 6 months.Others describe a re-thrombosis rate of 25% to 50% forgrafts untreated after they were opened with urokinase[5,6,18].

When we reviewed the adjunctive measures requiredin our patients, an interesting trend emerged. One third ofcases that were initially judged to need surgery eventuallyrequired an operation of lesser magnitude after thrombo-lytic therapy. Many of the procedures in this group were

163THE AMERICAN JOURNAL OF SURGERY VOLUME 160 AUGUST 1990

EISENBUD ET AL,--- --,--

confined to percutaneous transluminal or open surgicalangioplasty of the distal anastomoses of grafts, or limiteddistal extensions of grafts. In addition, our re~ew indi-cates that 27% of cases involved outtlow beds that wouldnot have been amenable to Fogarty catheter thrombec-tomy; in these cases, clearing the outtlow tract with uroki-fiase materially increased the chance for long-term paten-

cy.Despite the encouraging early results with thromboly-

sis, we have noted disappointing long-term patencies forboth grafts and native vessels (Figure 1). Although thesepatencies are somewhat higher with repeated urokinasetreatments, percutaneous interventions, and surgical op-erations (Figure 2), nearly balE of the arteries and themajority of grafts still reocclude within the first year.These results are similar to the few reports of long-termfollow-up after thrombolysis [4,18-20]. Motarjeme [19]found 1-, 2-, and 3-year patencies of 44%, 22%, and 17%,respectively, for occluded femoral-popliteal grafts aftersuccessful thrombolysis and dilatation. Using a tissueplasminogen activator to open occluded infrainguinalgrafts, Graor el al [20] found a 1-year patency of 200/0,which was similar to the result in a comparable group ofpatients treated with surgical thrombectomy. The rea-sons for such low patency after apparently successfulthrombolysis or thrombectomy have not been clarified;however, it has been demonstrated that the outcome forrevised grafts is much poorer if the reintervention is doneafter, rather than before, graft thrombosis [21].

In conclusion, experience with 71 intra-arterial uroki-nase treatments of acute vascular occlusions over the past4 years has revealed a primary success Tale of 73%. TheTale of successful thrombolysis has improved in the laterstages of the study because of advances in patient selec-tion, catheter technology, and dosing' regimens. The inci-dence of serious complications was low. The underlyingpathologic condition leading to thrombosis was elucidat-ed in m¡tny cases using urokinase, facilitating and oftenreducing the magnitude of further procedures needed toassure long-term patency. Though 1-year patencies werelow, we continue to use thrombolysis in selected patientsfor whom the alternative options are limited.

1987; 243-7.7. Davis GB, Dowd CF, Bookstein JJ, Maroney TP, Lang EV,Halasz N. Thrombosed dialysis grafts: efficacy of intrathromboticdeposition of concentrated urokinase, clot maceration, and angio-plasty. AJR 1987; 149: 177-81.8. Putnam JS, Uchida BT, Antonovic R, el al. Superior vena cavasyndrome associated with massive thrombosis: treatment with ex-pandable wire stents. Radiology 1988; 167: 727-8.9. Rutherford RB, Flanigan DP, Gupta SK, el al. Suggested sta n-dards for reports dealing with lower extremity ischemia. J VascSurg 1986; 4: 80-94.10. Belkin M, Belkin B, Bucknam CA, Straub JJ, Lowe R. Intra-arterial fibrinolytic therapy: efficacy of streptokinase vs. urokinase.Arch Surg 1986; 121: 769-73.11. McNamara TO, Fischer JR. Thrombolysis of peripheral arteri-al and graft occlusions: improved results using high-~e urokinase.AJR 1985; 144: 769-75.12. Dotter CT, Rosch J, Seaman AJ. Selective clot Iysis with low-dose streptokinase. Radiology 1974; 111: 31-7.13. Traughber PD, Cook PS, Miclos TJ, Miller FJ. Intraarterialfibrinolytic therapy for popliteal and tibial artery obstruction: com-parison of streptokinase and urokinase. AJR 1987; 149: 453-6.14. Gurewich V, Pannell R, Louie S, el al. Effective and fibrin-specific clot Iysis by a zymogen precursor form of urokinase (pro-urokinase). A study in vilro and in two animal species. J Clin Invest1984; 73: 1731-9. ,15. Graor RA, Risius B, Young JR, el al. Peripheral artery andbypass graft tbrombolysis with recombinant human tissue-typeplasminogen activator. J Vasc Surg 1986; 3: 115-24.16. Katzen BT, Van Breda A. The current status of catheterdirected fibrinolysis in the treatment of arterial and graft occlu-sions. In: Bergan JJ, Yao JST, eds. Arterial surgery: new diagnosticand operative techniques. Orlando: Grune & Stratton, 1988; 119-134.17. McNamara TO, Fischer JR. Thrombolysis of peripheral arteri-al and graft occlusions: improved results using high-dose urokinase.AJR 1985; 144: 769-75.18. Gardiner GA, Harrington DP, Koltun W, Whittemore A,Mannick JA, Levin DC. Salvage of occluded arterial bypass bymeans of thrombolysis. J Vasc Surg 1989; 9: 426-31.19. Motarjeme A. Thrombolytic therapy in arterial occlusion andgraft thrombosis. Semin Vasc Surg 1989; 2: 155-78.20. Graor RA, Risius B, Young JR, el al: Thrombolysis of periph-eral arterial bypass grafts: surgical thrombectomy compared withthrombolysis. J Vasc Surg 1988; 7: 347-55.21. Ascer E, Collier P, Gupta SK, Veith FJ. Reoperation forpolytetrafluoroethylene bypass failure: the importante of distal out-flow site and operative technique in determining outcome. J VascSurg 1987; 5: 298-310.

DISCUSSIONAnthony J. Comerota (Philadelphia, PA): Once lysis

was complete, adjunctive therapy was rcquired in only66% of cases. The most common adjunctive procedurewas percutaneous transluminal angioplasty. Dr. Eisen-bud, do you think that operative correction of the under-lying lesion would offer better long-term results thantransluminal angioplasty?

Among 18 patients who did not have adjunctive pro-cedures, 50% had rethrombosis within 25 days. Was anyattention given to an underlying hypercoagulable state?What was the raJe of anticoaguJation in the Jong-termmanagement ofthese patients? Did you find that patientswith coagulopathy and reduced fibrinogen !evels had agreater risk of bJeeding? Was there a difference in long-

REFEREi\'CESl. Hartman J, McKeever L, Teran J, el al. Prolonged infusion ofurokinase for recanalization of chronically occluded aortocoronarybypass grafts. Aro J Cardiol1988; 61: '89-94.2. Van Breda A, Katzen BT, Deutsch AS. Urokinase versus strep-tokinase in Jocal thromboJysis. Radiology 1987; 165: 109- 1 l.3. Pernes JM, Vitoux JF, Brenoit P, el al. Acute peripheraJ arterialand graft occlusion: treatment with seJective infusion of urokinaseand lysyJ plasminogen. Radiology 1986; 158: 481-5.4. McNamara TO, Bomberger RA. Factors affecting initial and 6month patency Tales after intraarterial thromboJysis with high doseurokinase. Aro J Surg 1986; 152: 709-12.5. Fiessinger JN, Vitoux JF, Pernes JM, Roncato M, Aiach M,Gaux JC. CompJications ofintraarterial urokinase-Iys-plasminogeninfusion therapy in arterial ischemia oflower limbs. AJR 1986; 146:157-9.6. O'Hara PJ, Graor RA. Fibrinolytic therapy in acutely throm-bosed lower extremity arteries and grafts. In: Ernst CB, Stanley JC,eds. Current therapy in vascular surgery. Toronto: BC Decker Inc,

THE AMERICAN JOURNAL OF SURGERY VOLUME 160 AUGUST 1990164

UROKINASE TREATMENT FOR VASCULAR OCCLUSION~

term results in autogenous grafts following correction ofan identifiable lesion?

We have found that these cases have the best long-term patency and have observed that patients who havethrombosis of their bypasses within 12 to 15 months havea poor prognosis, either owing to a poor conduit, pooroutflow, or both. In contrast, those patients who havethrombosis of bypasses after 3 years tend to have a morelocalized, potentially correctable lesiono Has this beenyour experience?

Did improved patient selection leád to better results inthe last 2 years of your study? Finally, do you and yourcolleagues have any suggestions to reduce complicationsduring infusion? In particular, do you think that the highincidence of ipsilateral arterial puncture contributed tothe 41% complication rate?

Toshio Inohara (PortIand, OR): With regard to theinability to pass the guide wire, wouId you, at that time,take the patient to surgery?

tions. Arnong the most significant complications was anintracerebral bleeding episode leading to the death of thepatient. We also had a case of renal failure. We stop theinfusion ifthe fibrinogen level falls below 100. We do notuse heparin concurrently with the urokinase. Anothercomplication is progression of ischemia, which we moni-tor with Doppler and clinical examination. With regardto OUT improving results over the years, patient selectiondoes playa roleo If we are unable to pass a guide wirethrough a lesion, we do not attempt thrombolysis, thusimproving OUT success rateo

If we cannot identify a lesion causing thrombosis, weinvestiga te the coagulability of the patient's blood. Wehave not identified any patient in a hypocoagulable sta te.Generally speaking, this group has rethrombosis within 2to 3 weeks unless anticoagulants are given.

I do think that surgical correction of lesions identifi-able after thrombolysis is more fruitful iban transluminalangioplasty, and OUT prior results with autogenous veingrafts reflect that early experience.

Dr. Inohara, if we can 't pass the guide wire, we believethat thrombolysis will not be successful, and we thenconsider the surgical option.

David Eisenbud (closing): Dr. Comerota, a low ti-brinogen level correlates directly \\ith bleeding complica-

THE AMERICAN JOURNALOFSURGERY VOLUME 160 AUGUST 1990 165