Effect of intravenous heparin infusion on thrombin-antithrombin complex and fibrinopeptide A in unstable angina.
BACKGROUND
In unstable angina, the clinical efficacy of heparin is limited in time, and recurrence of adverse events has been reported after discontinuation of the anticoagulant.


METHODS
In 21 episodes of unstable angina, we used the plasma level of fibrinopeptide A (FPA) and of thrombin-antithrombin complex (TAT) to evaluate the pattern of thrombin inhibition by heparin and the effect of stopping heparin and initiating aspirin.


RESULTS
At admission, the plasma level of FPA was increased: median value 3.7 ng/mL compared with 5.5 ng/mL in a control group of 20 patients with early myocardial infarction (not significant). The following findings were observed during a 4-day course of intravenous heparin infusion: (1) FPA decreased significantly 6 hours after the start of therapy; (2) FPA was lower when activated partial thromboplastic time (aPTT) was >1.5 times baseline; (3) there was a significant negative correlation between aPTT and FPA. Twenty-four hours after heparin was discontinued and aspirin initiated, a significant increase in TAT and FPA in plasma was observed.


CONCLUSIONS
The results confirm ongoing fibrin formation in the active phase of unstable angina, indicate incomplete and variable inhibition of thrombin by heparin during continuous infusion, and suggest a risk of re-emergence of thrombosis (in spite of initiating aspirin) 24 hours after withdrawal of heparin. Data demonstrate a better control of thrombin activity when heparin is infused at rates that maintain aPTT at >1.5 times baseline, as currently recommended in unstable angina.
Mombelli
G
G
Ospedale Regionale Locarno, and the Thrombosis Research Laboratory, University of Bern, Switzerland.
Marchetti
O
O
Haeberli
A
A
Straub
P W
PW
D000368:Aged; D000789:Angina, Unstable / Q000097:blood* / Q000188:drug therapy*; D000925:Anticoagulants / Q000008:administration & dosage* / Q000627:therapeutic use; D000990:Antithrombin III / Q000032:analysis*; D001241:Aspirin / Q000008:administration & dosage / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D005260:Female; D005344:Fibrinopeptide A / Q000032:analysis*; D006493:Heparin / Q000008:administration & dosage* / Q000627:therapeutic use; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D010447:Peptide Hydrolases / Q000032:analysis*; D011446:Prospective Studies
D000925:Anticoagulants; D015415:Biomarkers; C046193:antithrombin III-protease complex; D005344:Fibrinopeptide A; D000990:Antithrombin III; D006493:Heparin; D010447:Peptide Hydrolases; D001241:Aspirin