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Fibrinolytic therapy: Clinical and laboratory management
ARSTRAC'TS Ol- A N N I J A L MEII'I'IN(;
1980 383
should be noted. Medical factors such a s C . C , t . . limb paralysis 01-iinmobllizatioli~ocatrogcn contal1iIng Ihcrap?. probably repre\ent additi\e risk l'kxors. At surgery. the age 01' the patient. t h e duratlon ol' s ~ ~ r g e rpresc~ice ). of' nialignnncy and the nature a n d s i t e o f i u r g e r ) . the expected degree oftissue t r a u m a 'lnd durnrioit ofp"\t-"perat'\e immobilization all need to be taken into account. The adLent ol'a relat~vel! bafe. e;i\11y ,tdministered and cfl'ectibe prophylaxi\ of low dose heparin m i t h o r without a n antiplatelet agent o r dtli~drocrgotalnineI ~ O M ohllge the individual physician o r \urgeon to be more highly iiuiii-e o f these risk factors a i i d include \uch i i n ;I rout ine procedure PREVENTION OF ARTERIAL AND VENOUS THROMBOEMBOLISM
A. S. GAI1.1,s H ( / c , i ~ i t i t i i / ( ~ C ~ .ti/. i / ,F//i/d(,/.\ . 2 . l ( ~ t / i c ~ i(i'/< , t i / r ( , .A t / < , / ( i i < k ~ BCC~ILI\C venous thromhoembolism Lend\ t o complicate .high-risk. illnesse\ 111 .htgI1-rhk. p;iticnt\. cll'rcti\e prophylaxi\ applied t o selected patients s h o u l d substantially I-cdnccIhe prcvnleiicc o I ' I h i \ contplicitiroi) Hot", . a \ prophylactic methods arc not ccl~iallyeffcctivc i n all situations. pi-evention s l i o t i l d be tiiilo!-ed to the needs ol'the patient. Low-dose heparin prophylaxis remains the method of choice i n grvioru/ \iii.,yc,ri . but 111c1.cI\ Incl-enslllg evidence t h a t venous H o u acceleration may be equall! effective. a i d that both ;ippi-oacher togethei- m a y he moIc ell'rcti\e t h a n either alone. Combined prophylaxi\ may be o n e anauci- t o the pi-oblcm in i)rrhi)p(/rdi[\i/i.,qc,rl'. M here 10%-dore heparin is relativelq ineffective, and oral anticoagulants are unaccept;iblc to m o s t surgeons. 011t h e o t h c ~h a n d . or~11 anticoagulant treatment seems t o be the most rational approach whene\,ci- t h e illin i11'1e1-i u ) ' i ) i uri/rii/ i i ! / i / i i,/io/i15 t o p r a e n t both pulmonary and systemic emboltam. In arterial thromboembolism. interest ha\ recently su ung from the 01-illtiiitiec)iigtilaiits t o ;intiplatelet drugs. Early treatment with sulphinpyi-azone sub\tantiallq reduced the risk D I \lidden death during t h e l i n t 7 mth alter iiiroc.trr(/ici/infurcriiiii in one study. but was ineffective in patient\ with rru/i\iiwr i.r,rc,h~.ii/is( /l(ii,/iiiii 111 another. By contrast. aspirin appears t o reduce the likelihood o f further ischaemic episodes including \troke i n lncn with transient cerebral ischaemia. but its value after myocardial infarction remains uncei-tain. l2a\t1q. tlicrc i\ e\ideiice that both dipyridamole and aspirin further reduce the risk 01' systemic emboli\m i n patient\ 11-eated filth oi-al anticoagulants because they have ;I prosthetic heart val\e. FlBRlNOLYTlC THERAPY. CLINICAL AND LABORATORY MANAGEMENT
C . N.C H ~I ~SK M A N I 'il~/or.itr
[ ' r i i i v i . . c i f J . of
.Llc/houm, Dcprrr/ricvir of l.l(dii //i(', .Si I . / / i w i i r ' 5
t/o.\piii//. b'i/:iw I
.
Thromholytic drugs remain a unique approach t o occlusive vascular disease beins the \ole non-rurglcal mciltis 01' dissolution ofintravascular thrombi The t w o d r ~ i g acurrently i n use are rtreptokin;isc and ui-okimsc. 'These dl-ugs have proven useful i n a limited number ofpatients with thromboernbolic dihense. There IS i~clciirci~\cI'or their \aluc in acute massive and submassive pulmonary embolisin and in defined ciises of deep \ciii thrombo\is 'The ~ a l u c01' lea\ certain but depends u p o n the expel-tise of those ti\ing the drugs and thrombolgtic treatment o f arterial dise cooperation between ular surgeon and phyhiciiin. Outside these conditions indicat!on< Ibr throinbolytic therapy are less clear. Despite a continuing growth o f information ahout the tise of streptokinase 111 m)ocardial infarction. in common with anticoagulant drugs. t h e \ittiation IS not clear. I t s x m s highl! likel! that there 15 21 gr-oup o f patients % i t h acute myocardial infarction who should benefit from thrombolyllc therap!. I t I\ dil'ficult to make ii practical rccommcndatton however. o n the basis of aLailablc kiiobletlge Because 01' t l i e potenti:il dnngcr ol' thrombolytic therapy. particularly cerebral haeniorrhage, eiidencc l o r their value mu\( be strong before undertaking their use. Continued experimentation 01' dosage rCgiines and siinultancou\ LIW 01' o t l i e l Cotmis 01' thernpq. e.g. plasininogen infusion m a y increase the thcrxpcutic index. Such rCgiinc\ itre based on ;I greater understanding o f the rnechanisrna tiiiderlying tlironibolysis which has dcwlopcd ovci- the pa\t f>u year\. CHROMOGENIC SUBSTRATE ASSAYS PRESENT AND POTENTIAL APPLICATIONS
H. G. F I K K I .kfonti.sh ~ I k p u ~f i i i w i r
of ,Mct/i(.im,, A / / r ( ~Ho,$pir(//. l Prii/iroii, 1 il,rorii/
Chromogenic substrates are now available for the study of many aspect\ of blood coiigulalion ;ind relilted e n l q me reaction\ in blood. These substrates have opened up lieu vistas. ~ncludinge i i w o l c o n t r o l o l ' r o ~ ~antico;igulant t~~~e therapy. The overall impact on routine haemostatic testing will prob;ihl> he i n i n i c n ~ \ince e a u t o m a t c d sg\tems ma) be ~iscdas a n initial screen f o r patients with haenio\ta\is problems. 7 his applieh not onl) t o t h e coagulation hut aI\u for related systems such a s the fibrinolytic pathway. The major point o n e must remembei- i n their use IS t h a t activity directed against these substrates maq not be identical with the biological ;ICII\ 11) one %islies to examine T h l \ must
1980 383
should be noted. Medical factors such a s C . C , t . . limb paralysis 01-iinmobllizatioli~ocatrogcn contal1iIng Ihcrap?. probably repre\ent additi\e risk l'kxors. At surgery. the age 01' the patient. t h e duratlon ol' s ~ ~ r g e rpresc~ice ). of' nialignnncy and the nature a n d s i t e o f i u r g e r ) . the expected degree oftissue t r a u m a 'lnd durnrioit ofp"\t-"perat'\e immobilization all need to be taken into account. The adLent ol'a relat~vel! bafe. e;i\11y ,tdministered and cfl'ectibe prophylaxi\ of low dose heparin m i t h o r without a n antiplatelet agent o r dtli~drocrgotalnineI ~ O M ohllge the individual physician o r \urgeon to be more highly iiuiii-e o f these risk factors a i i d include \uch i i n ;I rout ine procedure PREVENTION OF ARTERIAL AND VENOUS THROMBOEMBOLISM
A. S. GAI1.1,s H ( / c , i ~ i t i t i i / ( ~ C ~ .ti/. i / ,F//i/d(,/.\ . 2 . l ( ~ t / i c ~ i(i'/< , t i / r ( , .A t / < , / ( i i < k ~ BCC~ILI\C venous thromhoembolism Lend\ t o complicate .high-risk. illnesse\ 111 .htgI1-rhk. p;iticnt\. cll'rcti\e prophylaxi\ applied t o selected patients s h o u l d substantially I-cdnccIhe prcvnleiicc o I ' I h i \ contplicitiroi) Hot", . a \ prophylactic methods arc not ccl~iallyeffcctivc i n all situations. pi-evention s l i o t i l d be tiiilo!-ed to the needs ol'the patient. Low-dose heparin prophylaxis remains the method of choice i n grvioru/ \iii.,yc,ri . but 111c1.cI\ Incl-enslllg evidence t h a t venous H o u acceleration may be equall! effective. a i d that both ;ippi-oacher togethei- m a y he moIc ell'rcti\e t h a n either alone. Combined prophylaxi\ may be o n e anauci- t o the pi-oblcm in i)rrhi)p(/rdi[\i/i.,qc,rl'. M here 10%-dore heparin is relativelq ineffective, and oral anticoagulants are unaccept;iblc to m o s t surgeons. 011t h e o t h c ~h a n d . or~11 anticoagulant treatment seems t o be the most rational approach whene\,ci- t h e illin i11'1e1-i u ) ' i ) i uri/rii/ i i ! / i / i i,/io/i15 t o p r a e n t both pulmonary and systemic emboltam. In arterial thromboembolism. interest ha\ recently su ung from the 01-illtiiitiec)iigtilaiits t o ;intiplatelet drugs. Early treatment with sulphinpyi-azone sub\tantiallq reduced the risk D I \lidden death during t h e l i n t 7 mth alter iiiroc.trr(/ici/infurcriiiii in one study. but was ineffective in patient\ with rru/i\iiwr i.r,rc,h~.ii/is( /l(ii,/iiiii 111 another. By contrast. aspirin appears t o reduce the likelihood o f further ischaemic episodes including \troke i n lncn with transient cerebral ischaemia. but its value after myocardial infarction remains uncei-tain. l2a\t1q. tlicrc i\ e\ideiice that both dipyridamole and aspirin further reduce the risk 01' systemic emboli\m i n patient\ 11-eated filth oi-al anticoagulants because they have ;I prosthetic heart val\e. FlBRlNOLYTlC THERAPY. CLINICAL AND LABORATORY MANAGEMENT
C . N.C H ~I ~SK M A N I 'il~/or.itr
[ ' r i i i v i . . c i f J . of
.Llc/houm, Dcprrr/ricvir of l.l(dii //i(', .Si I . / / i w i i r ' 5
t/o.\piii//. b'i/:iw I
.
Thromholytic drugs remain a unique approach t o occlusive vascular disease beins the \ole non-rurglcal mciltis 01' dissolution ofintravascular thrombi The t w o d r ~ i g acurrently i n use are rtreptokin;isc and ui-okimsc. 'These dl-ugs have proven useful i n a limited number ofpatients with thromboernbolic dihense. There IS i~clciirci~\cI'or their \aluc in acute massive and submassive pulmonary embolisin and in defined ciises of deep \ciii thrombo\is 'The ~ a l u c01' lea\ certain but depends u p o n the expel-tise of those ti\ing the drugs and thrombolgtic treatment o f arterial dise cooperation between ular surgeon and phyhiciiin. Outside these conditions indicat!on< Ibr throinbolytic therapy are less clear. Despite a continuing growth o f information ahout the tise of streptokinase 111 m)ocardial infarction. in common with anticoagulant drugs. t h e \ittiation IS not clear. I t s x m s highl! likel! that there 15 21 gr-oup o f patients % i t h acute myocardial infarction who should benefit from thrombolyllc therap!. I t I\ dil'ficult to make ii practical rccommcndatton however. o n the basis of aLailablc kiiobletlge Because 01' t l i e potenti:il dnngcr ol' thrombolytic therapy. particularly cerebral haeniorrhage, eiidencc l o r their value mu\( be strong before undertaking their use. Continued experimentation 01' dosage rCgiines and siinultancou\ LIW 01' o t l i e l Cotmis 01' thernpq. e.g. plasininogen infusion m a y increase the thcrxpcutic index. Such rCgiinc\ itre based on ;I greater understanding o f the rnechanisrna tiiiderlying tlironibolysis which has dcwlopcd ovci- the pa\t f>u year\. CHROMOGENIC SUBSTRATE ASSAYS PRESENT AND POTENTIAL APPLICATIONS
H. G. F I K K I .kfonti.sh ~ I k p u ~f i i i w i r
of ,Mct/i(.im,, A / / r ( ~Ho,$pir(//. l Prii/iroii, 1 il,rorii/
Chromogenic substrates are now available for the study of many aspect\ of blood coiigulalion ;ind relilted e n l q me reaction\ in blood. These substrates have opened up lieu vistas. ~ncludinge i i w o l c o n t r o l o l ' r o ~ ~antico;igulant t~~~e therapy. The overall impact on routine haemostatic testing will prob;ihl> he i n i n i c n ~ \ince e a u t o m a t c d sg\tems ma) be ~iscdas a n initial screen f o r patients with haenio\ta\is problems. 7 his applieh not onl) t o t h e coagulation hut aI\u for related systems such a s the fibrinolytic pathway. The major point o n e must remembei- i n their use IS t h a t activity directed against these substrates maq not be identical with the biological ;ICII\ 11) one %islies to examine T h l \ must