M. Galvani et al., FAILURE OF FIXED-DOSE INTRAVENOUS HEPARIN TO SUPPRESS INCREASES IN THROMBIN ACTIVITY AFTER CORONARY THROMBOLYSIS WITH STREPTOKINASE, Journal of the American College of Cardiology, 24(6), 1994, pp. 1445-1452
Objectives. This study was designed to define the extent of inhibition
of thrombin activity achieved with conjunctive fixed dose intravenous
sodium heparin compared with fixed dose subcutaneous calcium heparin
in patients receiving intravenous streptokinase for acute myocardial i
nfarction. Background. The role of heparin therapy during coronary thr
ombolysis with streptokinase is controversial, in part because the eff
icacy of different conjunctive heparin regimens in inhibiting early in
creases of thrombin activity is not known. Methods. Twenty eight patie
nts treated with 1.5 million U of streptokinase and 165 mg of aspirin
for acute myocardial infarction were randomly assigned to receive fixe
d dose subcutaneous heparin therapy (12,500 U every 12 h delayed until
4 h after the end of streptokinase therapy [n = 14]) or fixed dose in
travenous heparin (5,000-U bolus followed by 1,000-U/h infusion [n = 1
4]) Anticoagulation was assessed with serial measurements of activated
partial thromboplastin time, and thrombin activity by measuring fibri
nopeptide A and thrombin-antithrombin III complex levels. Plasma conce
ntrations of creatine kinase (CK) MM isoforms were measured for 3 h to
determine recanalization (increase in activity >0.18%/min). Results.
Recanalization occurred in 27%, 64% and 79% of patients given subcutan
eous heparin versus 43%, 76% and 86% of those given intravenous hepari
n at 1, 2 and 3 h, respectively (p = 0.6). Concentrations of fibrinope
ptide A (mean +/- SEM) at 1 h were higher in patients without (n = 5)
than in those with (n = 23) CK-MM isoform criteria for recanalization
(76.4 +/- 25.7 vs. 25.2 +/- 5.2 nmol/liter, p = 0.02), and at 1, 2 and
3 h were significantly lower with fixed dose intravenous heparin (18.
4 +/- 4.8 vs. 46.7 +/- 10.2 nmol/liter at 1 h, p = 0.004) than without
heparin. After fixed dose subcutaneous heparin at 4 h, fibrinopeptide
A levels were similar in both groups despite lower activated partial
thromboplastin times in patients who received fixed dose subcutaneous
heparin. However, fibrinopeptide A was not consistently suppressed in
either group (fixed dose subcutaneous heparin 8.7 +/- 1.8 nmol/liter v
s. fixed dose intravenous heparin 11.8 +/- 5.2 nmol/liter) at 48 h (p
= 0.4). No significant changes in the concentration of thrombin-antith
rombin In complexes were found between the two groups. Conclusions. Fi
xed dose intravenous heparin attenuates increases in fibrinopeptide A
early after streptokinase. Subsequent fixed dose intravenous and subcu
taneous heparin have similar effects but are relatively ineffective in
suppressing thrombin activity, suggesting a role for more potent anti
thrombin agents during coronary thrombolysis with streptokinase.