Thrombin generation and activity during thrombolysis and concomitant heparin therapy in patients with acute myocardial infarction.
OBJECTIVE
This prospective study investigated the behavior of thrombin generation and activity during thrombolysis and concomitant heparin administration.


BACKGROUND
It has been shown that during thrombolytic therapy there is an increase in thrombin generation and activity. Increased thrombin activity is suppressed by concomitant intravenous heparin, but it is unknown whether thrombin generation is also affected.


METHODS
Thrombin generation was assessed by measuring prothrombin fragment 1 + 2 and thrombin-antithrombin complex plasma levels and thrombin activity by measuring fibrinopeptide A plasma levels. Serial blood samples were obtained before and at 90 min and 24 and 48 h after the administration of streptokinase (15 patients), recombinant tissue-type plasminogen activator (15 patients) or anistreplase (13 patients). An intravenous bolus of heparin (5,000 IU) was administered before the start of thrombolytic therapy, followed by an infusion of 1,000 U/h to maintain an activated partial thromboplastin time > 1.5 times baseline.


RESULTS
During thrombolytic and concomitant heparin therapy, there was an increase in the plasma levels of prothrombin fragment 1 + 2 (baseline 1.08 vs. 2.73 nmol/liter, p < 0.001) and thrombin-antithrombin complex (baseline 6.5 vs. 17.1 micrograms/ml, p < 0.01) at 90 min, whereas no change was observed in fibrinopeptide A at 90 min (baseline 2.8 vs. 3.0 nmol/liter, p = NS).


CONCLUSIONS
During thrombolytic therapy with both fibrin-specific and non-fibrin-specific drugs, there is an increase in thrombin generation despite concomitant administration of intravenous heparin.
Merlini
P A
PA
Second Division of Cardiology, Ca' Granada Niguarda Hospital, Milan, Italy.
Bauer
K A
KA
Oltrona
L
L
Ardissino
D
D
Spinola
A
A
Cattaneo
M
M
Broccolino
M
M
Mannucci
P M
PM
Rosenberg
R D
RD
D000368:Aged; D000990:Antithrombin III / Q000032:analysis; D004359:Drug Therapy, Combination; D005260:Female; D005344:Fibrinopeptide A / Q000032:analysis; D006493:Heparin / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000188:drug therapy*; D010447:Peptide Hydrolases / Q000032:analysis; D011446:Prospective Studies; D011516:Prothrombin / Q000032:analysis; D012008:Recurrence; D013917:Thrombin / Q000032:analysis / Q000096:biosynthesis* / Q000187:drug effects; D015912:Thrombolytic Therapy; D013997:Time Factors
C046193:antithrombin III-protease complex; D005344:Fibrinopeptide A; D000990:Antithrombin III; D011516:Prothrombin; D006493:Heparin; D010447:Peptide Hydrolases; D013917:Thrombin