Læknablaðið - 15.10.1993, Blaðsíða 11

LÆKNABLAÐIÐ
303
úrókínasa og APSAC, sem valda einnig miklu
leysiástandi, verður lítil storkuleysing in vitro
við svo lítinn styrk plasmínógens (9) og því
má leiða líkum að því, að þannig sé því einnig
varið með virkni streptókínasa. Sambandið
á milli niðurbrots fíbrínógens og niðurbrots
plasmínógens (mynd 5) gerir mögulegt
að áætla þéttni plasmínógens út frá þéttni
fíbrínógens meðan á streptókínasagjöf stendur.
Mæling fíbrínógens er bæði mun einfaldari
og fljótlegri en mæling plasmínógens. Þetta
samband kann því að hafa hagnýta þýðingu ef
áætlun á þéttni plamínógens reynist hjálpleg
meðan á segaleysandi meðferð stendur.
Sé tekið mið af áðurnefndum
glasarannsóknum og niðurstöðum núverandi
rannsóknar má leiða líkur að því, að
segaleysing hafi minnnkað verulega eftir
fyrstu 10-20 mínútur SK-meðferðar vegna
skorts á plasmínógeni í plasma. Ef það reynist
rétt má ætla að lengri gjöf lyfsins þjóni litlum
tilgangi í núverandi skömmtum. Sú spurning
vaknar hvort þörf sé breytinga á meðferðinni
til þess að draga úr plasmínógeneyðingunni.
Ef til vill næðust sömu segaleysiáhrif með
gjöf 500.000 eininga af SK á 20 mínútum
eða jafnvel enn minni skammti gefnum
á lengri tíma. Þá er hugsanlegt að meiri
storkuleysiáhrif rt-PA in vitro (8,9) og in vivo
miðað við lyf sent valda miklu leysiástandi
og eyðingu plasmínógens (SK, UK, APSAC)
(6,9) skýrist af plasmínógensparandi áhrifum.
Niðurstöðurnar vekja einnig upp þá spurningu
hvort bæta megi árangur meðferðar með
gjöf plasmínógens ásamt segaleysandi lyfi.
Frekari rannsókna er þó þörf áður en meðferð
á sjúklingum verður breytt.
ÞAKKIR
Höfundar færa læknum og
hjúkrunarfræðingum bráðavakta og
hjartadeilda Landspítala og Borgarspítala bestu
þakkir fyrir veitta aðstoð við öflun blóðsýna.
Einnig sérstaklega Guðmundi Þorgeirssyni og
Gesti Þorgeirssyni.
SUMMARY
Thrombolytic therapy is associated with the
development of a lytic state manifested by
depletion of fibrinogen, coagulation factors V and
VIII, plasminogen and antiplasmin to a varying
degree. The severity of the lytic state is dependent
on the type and dose of plasminogen activator
applied and is frequently considered desirable
during treatment as a measurable indicator of
effective in vivo fibrinolysis and an important
hypocoagulable condition preventing reocclusion
after thrombolytic therapy. However, in vitro data
indicate that more clot can be lysed using rt-PA
which causes less lytic state than urokinase (tcu-
PA, UK) which induces a more pronounced lytic
state and that this may possibly be explained in
part by depletion of circulating (rather than clot-
bound) plasminogen. Based on this hypothesis
we have investigated the speed and intensity
of lytic state formation in 6 patients treated
with 1.500.000 units of streptokinase over one
hour for acute myocardial infarction by drawing
blood at consecutive early timepoints during
infusion. Already after 10 minutes of infusion
the plasminogen concentration had decreased to
47±6% of initial, 24±4% after 20 minutes and
<15% after 40 and 80 minutes. Antiplasnrin
was 53±11% after 5 minutes, I9±5% after
10 minutes and about 5% at 20 minutes and
therafter. Fibrinogen degradation was also rapid:
72±8% of initial at 10 minutes, 19±9% at 20
nrinutes and 6±1% after 40 and 80 minutes.
A curvilinear relationship was found between
the concentration changes of fibrinogen and
plasminogen during therapy (R:=.94) making it
possible to predict plasminogen concentration
based on fibrinogen levels. It is concluded that
near maximum lytic state developes within 10-20
minutes of streptokinase infusion for myocardial
infarction. Although further study is needed it
can be hypothesized based on these results and
others’ in vitro data that the rapid development of
an intense lytic state may limit therapeutic success.
HEIMILDIR
1. Marder VJ, Sherry S. Thrombolytic Therapy: Current
Status. N Engl J Med 1988; 318: 1512-20; 1585-95.
2. Collen D. Basic and clinical aspects of fibrinolysis
and thrombolysis. Blood 1991; 78: 3114-24.
3. Rao AK, Pratt C, Berke A, et al. Thrombolysis
in myocardial infarction (TIMI) trial - Phase I:
Hemorrhagic manifestations and changes in plasma
(ibrinogen and the fibrinolytic system in patients
trealed with recombinant tissue plasminogen activator
and streptokinase. J Am Coll Cardiol 1988; 11: 1-11.
4. Burket MW, Smith MR, Walsh TE, Brewster PS,
Fraker TD. Relation of effectiveness of intracoronary
thrombolysis in acute myocardial infarction to
systemic thrombolytic state. Am J Cardiol 1985; 56:
441-4.
5. Marder VJ. Rothbard RL, Fitzpatrick PL, Francis
CW. Rapid lysis of coronary artery thrombi with
anisolated p!asminogen:streptokinase activator
complex. Treatment by bolus intravenous injection.
Ann Int Med 1986; 104: 304-10.
6. Collen D. Coronary thrombolysis: Streptokinase or
recombinant tissue-type plasminogen activator? Ann
Int Med 1990; 112: 529-38.
7. Alkjaersig N, Fletcher AP, Sherry S. The mechanism