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Effect of activated protein C on plasma plasminogen activator inhibitor activity in patients with acute myocardial infarction treated with alteplase

Comparison with unfractionated heparin

Tomohiro Sakamoto, MD^*,*, Hisao Ogawa, MD^*, Keiji Takazoe, MD^*, Michihiro Yoshimura, MD^*, Hideki Shimomura, MD, Yasushi Moriyama, MD, Hidekazu Arai, MD and Kenji Okajima, MD

^* Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
Laboratory Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
Division of Cardiology, Fukuoka Tokushukai Hospital, Kasuga, Japan

View larger version (14K): [in a new window]   Figure 1 Schematic summarization of the study protocol. All patients were treated with a bolus injection of 100 U/kg heparin followed by a drip infusion of recombinant tissue-type plasminogen activator (alteplase). The patients were then randomly assigned to receive heparin or activated protein C intravenously for 48 h. AMI = acute myocardial infarction.

View larger version (16K): [in a new window]   Figure 2 Serial changes in plasma levels of activated protein C (APC) between the two conjunctive treatment groups. During infusion of APC, the plasma levels were maintained at 5 to 10 times its control level. *p < 0.05 vs. pre in both treatment groups. p < 0.05 and p < 0.01 between the two groups at each sampling point. The center lines in the columns show the median value, and the box plots show the ranges between the 25th and 75th percentile values. The bars attached to the columns show the ranges between the 10th and 90th percentile values. Solid columns = APC group; open columns = heparin group.

View larger version (19K): [in a new window]   Figure 3 Serial changes in activated partial thromboplastin time (aPTT) between the two conjunctive treatment groups. The aPTT was significantly prolonged in the heparin group, though not in the activated protein C (APC) group. *p < 0.05 vs. pre in the heparin treatment group. p < 0.01 between the two groups at each sampling point. The center lines in the columns show the median value, and the box plots show the ranges between the 25th and 75th percentile values. The bars attached to the columns show the ranges between the 10th and 90th percentile values. Solid columns = APC group; open columns = heparin group.

View larger version (22K): [in a new window]   Figure 4 Serial changes in plasma levels of plasminogen activator inhibitor (PAI) activity between the two conjunctive treatment groups. There is a significant difference in the time course of PAI activity between the two groups. Activity of PAI was increased similarly until 8 h in both groups. Then the level kept increasing until 24 h in the heparin group, although it was decreasing in the APC group. *p < 0.05 vs. pre in both treatment groups. p < 0.05 between the two groups at each sampling point. The center lines in the columns show the median value, and the box plots show the ranges between the 25th and 75th percentile values. The bars attached to the columns show the ranges between the 10th and 90th percentile values. Solid columns = APC (activated protein C) group; open columns = heparin group.

View larger version (18K): [in a new window]   Figure 5 Serial changes in plasma levels of t-PA antigen. The level was higher at 24 and 48 h in the heparin group. *p < 0.05 vs. pre in both treatment groups. p < 0.05 and p < 0.01 between the two groups at each sampling point. The center lines in the columns show the median value, and the box plots show the ranges between the 25th and 75th percentile values. The bars attached to the columns show the ranges between the 10th and 90th percentile values. Solid columns = APC (activated protein C) group; open columns = heparin group.

View larger version (13K): [in a new window]   Figure 6 Correlations between changes in plasma PAI activity from the pretreatment levels and those of plasma activated protein C (APC) levels at each of six sampling points after thrombolysis in the APC group.