Basic Data Related to Thrombolytic Therapy For Venous Thrombosis

Basic data underlying decision making in clinical vascular suraerv Section Editor- John M. Porter, MD (Portland, Oregon)

Basic Data Related to Thrombolytic Therapy For Venous Thrombosis Timothy Pilla, MD, and Anthony J. Comerota, MD, Philadelphia, Pennsylvania

KEY WORDS: Thrombolytic therapy; venous thrombosis.

Fibrinolytic therapy for acute venous thrombosis is controversial in the minds of many physicians. Intuitively, they agree that thrombus in the deep venous system is bad and that elimination of the thrombus is beneficial. Deep venous thrombosis (DVT) leads to pulmonary embolism and the postthrombotic syndrome. Important questions are: Can the incidence of pulmonary embolism be reduced? Can the postthrombotic syndrome be avoided? Can the risk of recurrent episodes of DVT be reduced? Is the costeffectiveness ratio of therapy (both in dollars and avoidance of complications) favorable? While the question regarding prevention of pulmonary emboli is unlikely to be answered in light of the effective protec-

tion offered by anticoagulant therapy, answers to the other questions are currently being investigated. Clouding the data are studies reporting patient entry at variable times remote from the onset of DVT, incomplete follow-up, follow-up which obscures the influence of intercurrent events, and failure to appreciate the physiologic benefit of lysis versus nonlysis. The rapid advances in noninvasive vascular technology are allowing complete, accurate and repetitive evaluations of the deep venous system. The ongoing studies promise to provide definitive information regarding the long-term function of the venous system in patients suffering deep vein thrombosis who are offered fibrinolytic therapy compared to standard anticoagulation. Until these definitive answers are obtained, the data provided in the tables which follow may assist the clinician in making therapeutic decisions. The basic data describing lysis rates, symptomatic consequences, and complications of fibrinolytic therapy for acute deep venous thrombosis are listed.

From the Section of Vascular Surgery, Temple University School of Medicine, Philadelphia, Pennsylvania. Reprinf requests: Anthony J . Comerota, MD, Section of Vascular Surgery, Temple University School of Medicine, Philadelphia, Pennsylvania 19140. 81

THROMBOLYTIC THERAPY FOR VENOUS THROMBOSIS

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ANNALS OF VASCULAR SURGERY

TABLE I.-Radiographic lysis, pulmonary embolism and bleeding complications

Significant or complete phlebographlc clearance of DVT

Ref 192 3 4 4 5 6 7 8,13 8,13 9,15 10 11,34 12 14 16 18 19a 20 21 22 23 24 25 26 27 28 29 30 31 32 35 36 37 38 39 40 41 42 42 49 50

Duration of clot (days) <4 <5 < 14 <3 < 14 <7 <8 < 14 <3 <5 < 21 <4 >6 mean > 7 0 - > 14 < 14 < 14 <4 < 14

< 10 0->7 < 5b mean 16 < 16 <4 <4 <6 >7 < 10

Heparin 219 1/15 1I26 0113 11125 1117 0125 4114 011 1 5111 015 117 4/42 0112 7/24 217 16/91 601108

<

UKt

t PA

Heparln

SK

Major Bleeding

Heparin

1I26

SK 1/10 4119 6123

5/25

3/26 7121

2121

2/21

217

6117

1/10 1115

1/17 2125

5/42

1I8 015 3114 2116e

1120 4120

7193

2159

< 21 < 15 <5

< 42

'SK = streptokinase +UK = urokinase TPA = tissue plasminogen activator a = pooled analysis b = no initial phiebogram c = jaundice, liver function tests d = sub-therapeutic doses e = Ancrod f = all initial therapy with heparin g = followed by impedance plethysmography h = post-thrombectomyrethrombosis i = concurrent heparin

2110

8/57

16/108 1/10

1140

l h

mean 4

t PA

1/15

31108

415 5114 9113 518 016 8114 15118 7114 18/41 11/20 10129 416 24/30

UK

1118

6110 34/40 15119 315

>5 <7 2-21' 0-> 79 1 7

SK* 619 10119 6123 318 11/21 8118 17/23 411 1 6111 15/21 315 519 62/93 5112 17/25 7114 59196

FatallMajor Pulmonary embollsm

5/40 3119

115 1I14c 2113

118 1118

2112 1/18

2/41 3/64 8116 25/30 316 4/21 34/50' 12/41 8113

5/64 5/30

1111 0130

0150 0141 0113 212 5112

012 1/12

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TABLE 11.-Long-term results of thrombolytic therapy for DVT Ref

Length of follow-up

2 5,13 15 17 23 -

6-12 4-18 41-106 14-57 6-50

7 15 17 18

months months months months months

19 months mean 41-106 months 6-51 months 8-10 years

Normal phlebogram Heparin

After therapy Streptokinase

1118 1112 8118

417 6115 7117 0128 8115

Asymptomatiac Heoarin

After therapy Streotokinase

2/25 6118

12113 13117 9/35 317

212

Normal phlebogram Heparin 16 17 18 31 35

24 months 6-51 months 8-10 years 8-53 months 5-10 years

After therapy Streptokinase

212

1I5 2/35 1I6 315 11/12

TABLE Ill.-Significant or complete phelbographic clearance of subclavian-axillary DVT Ref

Duration of clot

43 44 45 46,47 48

? ? < 24 hours < 9 days < 7 days

Streptokinase

Urokinase

719 417b 212

014'

Maior Bleed16 Streptokinase Urokinase 019a

012

0/11a

11/11 15/18

a = low dose, local therapy b = all patients symptomatically improved c = streptokinase stopped due to fever or rethrombosis

TABLE IV.-Pooled results-significant or complete clearance with lytic therapy References 1-42,49,50 1-37,38,40 37-42 49,50 1-1 9,24,27,29,35

43-48 46-48 43-47

Total patients

Lysis-DVT

995 817 164 14 431

58% 59% 52% 50% 16%

all streptokinase urokinase tissue plasminogen activator heparin

Lysis-axillary subclavian DVT

Comment

51 29 22

76% 90% 59%

Comment

all urokinase StreDtOkinaSe

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THROMBOLYTIC THERAPY FOR VENOUS THROMBOSIS

TABLE V.-Major References 1-4,7-9,11,13, 15,19-23,26,28, 30,32,34,36,38 4,8,9,11,13,15, 19,28,34 49,50 37,38,41,42

43,45,46,47

bleeding compllcatlons"

Total patients

Bleeding DVT

654

14%

146 14 132

9% 7%

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ANNALS OF VASCULAR SURGERY

Therapy streptokinase heparin tissue plasminogen activator urokinase

0.8% Bleeding axillary subbclavian DVT 0

Therapy all but #45--low dose, local therapy

'resulting in discontinuance of therapy, blood transfusion, or death

TABLE VI.-Fatal or major pulmonary embolus therapy References 1-3,6,7,12,24 6,12,20,22,30,36

Total patients 114 341

Fatal or major pulmonary embolism 10%

5O/o

Therapy heparin streptokinase

TABLE VII.-Long-term results following Initial slgnificant complete lysis References 2,5,13,15,17,23 2 5 13,15

Total patients 82 48

Normal follow-up phlebogram 30% 4%

Therapy streptokinase heparin

72 43

Normal clinlcal exam; patients asymptomatic 51O/o 19%

Therapy streptokinase heparin

~

7,15,17,18 7.15

The tables also summarize the currently available literature.

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