Vol.7, No 1, 2000 pp. 62 -69
UC 612.17;616.12
HEPARIN REBOUND PHENOMENON IN ACUTE CORONARY
SYNDROMES: ADVANTAGE OF LOW MOLECULAR WEIGHT HEPARINS
Goran Koraćević, Sladjana Andrejević, Dejan Sakač, Zoran Stanojević,
Srdjan Stefanović,
Jovan Antović, Danijela Miković, Ankica Jelenković
Department for Cardiovascular Diseases, Clinical Center, and Institute
of Pharmacology,
University School of Medicine, Niš, Yugoslavia
Summary. Heparin rebound phenomenon was named to illustrate unstable
angina pectoris (UAP) reactivation after stopping heparin. Reinfarction
clustering, as well as sharp increase of both thrombin production and activity
in the early hours after heparin abandoning have been described (after
thrombolysis), which has been partially attributed to heparin rebound.
The aim of the study was to show importance of problem of heparin rebound,
to suggest possible directions of its avoidance and to present our own
initial results with low molecular weight heparin (LMWH) Nadroparin in
this context, because data on these topics have been completely lacking
in our literature. Total number of pts analyzed was 45 (27 men, 18 women),
average age 59.4 ? 4.3, all of them with gastric protection with H2 blocker.
With close inhospital follow-up there was no heparin rebound phenomenon
had negative result found, which might be related to the solid duration
of therapy. In addition to careful heart rate and blood pressure control,
adequate antithrombin therapy seem to improve their prognosis. Side effects
were only minor haemorrhages: 5 injection site ecchymoses and 1 gingival
haemorrhage, while 39 pts experienced no manifest bleeding, including 9
pts with ulcer history. There are some practical suggestions to reduce
heparin-rebound phenomenon: 1) to decrease prothrombotic tendencies in
the blood, unrelated to heparin; 2) to improve therapy with standard heparin
and to 3) to use newer antithrombotic drugs.
We conclude that prevalence of heparin rebound can be lowered probably
with adequate duration and dose of standard and LMWH, together with other
suggested actions to decrease coagulation and platelet activation. Literature
and own data suggest low incidence of heparin rebound phenomenon with enough
long LMWH usage. They may be given with easily, with low bleeding rates,
and without a need for aPTT monitoring. Thus, LMWHs for a few weeks seems
justified in pts at high rethrombosis risk.
Key words: Low molecular weight heparin, heparin, rebound, acute
myocardial infarction, unstable angina
FENOMEN "USKRAĆIVANJA" HEPARINA U AKUTNIM
KORONARNIM SINDROMIMA: PREDNOST NISKOMOLEKULSKOG
HEPARINA
Kratak sadržaj: Fenomen "uskraćivanja" ("rebound") je tako nazvan
da ilustruje APNS reaktivaciju nakon prestanka primene heparina. Opisano
je grupisanje reinfarkta i oštar porast stvaranja i delovanja trombina
u prvim časovima nakon obustave heparina (nakon trombolize), što se delimično
pripisuje heparin "rebound" efektu.
Cilj studije je bio da ukaže na značaj malo poznatog problema uskraćivanja
heparina, da sugeriše moguće puteve za njegovo izbegavanje i da prikaže
sopstvene početne rezultate sa niskomolekulskim heparinom nadroparinom
u tom kontekstu, jer podaci o tim temama kompletno nedostaju u našoj literaturi.
Ukupni broj analizovanih pacijenata bio je 45 (27 muškaraca, 18 žena),
prosečne starosti 59,4 ? 4,3 g, a svi su primali H2 blokator u cilju zaštite
želuca.
Preciznim praćenjem nije nadjen heparin "rebound" fenomen, što može
biti povezano sa dužinom terapije. Uz pažljivu kontrolu srčane frekvence
i krvnog pritiska tokom hospitalnog praćenja, adekvatna antitrombinska
terapija izgleda da je poboljšala njihovu prognozu. Neželjeni efekti bili
su minorne hemoragije: u 5 bolesnika ekhimoze na mestu uboda injekcije
u jednog gingivalna hemoragija, dok 39 pacijenata nije imalo krvarenje,
uključujući devet sa anamnezom ulkusa. Ima praktičnih sugestija da se smanji
fenomen uskraćivanja heparina: 1) da se smanje protrombotske tendencije
u krvi, nevezane za heparin; 2) da se popravi terapija standardnim heparinom
i 3) da se koriste noviji antitrombotski lekovi.
Zaključujemo: Prevalenca fenomena "uskraćivanja" heparina verovatno
se može smanjiti adekvatnim trajanjem i dozom standardnog i niskomolekulskog
heparina, uz druge sugestije da se redukuje aktivacija koagulacije i aktivacije
trombocita. Literaturni i sopstveni podaci ukazuju na malu incidencu heparin
rebound fenomena sa dovoljno dugom primenom niskomolekulskih heparina.
Oni se mogu lako davati, uz mali procenat krvarenja, a bez portebe za aPTT
monitoring. Znači, višenedeljna terapija niskomolekulskim heparinom izgleda
da je opravdana u pacijenata koji su na visokom riziku za retrombozu.
Ključne reči: Niskomolekulski heparin, heparin, rebound, akutni
infarkt miokarda, nestabilna angina
