TY - JOUR
T1 - Rebound increase in thrombin generation and activity after cessation of intravenous heparin in patients with acute coronary syndromes
AU - Granger, Christopher B.
AU - Miller, Julie M.
AU - Bovill, Edwin G.
AU - Gruber, Andras
AU - Tracy, Russell P.
AU - Krucoff, Mitchell W.
AU - Green, Cindy
AU - Berrios, Eric
AU - Harrington, Robert A.
AU - Ohman, E. Magnus
AU - Califf, Robert M.
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 1995/4/1
Y1 - 1995/4/1
N2 - Background: The abrupt cessation of heparin and other thrombin inhibitors when used to treat acute coronary syndromes has been accompanied by a clustering of thrombotic events. It is unknown whether these events are the result of inadequate antithrombin therapy or whether they represent a rebound increase in thrombin activity. This study was designed to determine whether there is a true rebound, as defined by an increase followed by a subsequent decrease, in thrombin activity after discontinuation of intravenous heparin therapy. Methods and Results: Thirty-five patients with recent acute myocardial infarction or unstable angina who had received at least 48 hours of intravenous heparin were studied. Patients underwent ST-segment monitoring, and blood samples for determination of thrombin generation and activity were drawn at 0, 3, 6, 10, and 24 hours after heparin discontinuation. Median a PTT was 65 seconds before heparin discontinuation. Median fibrinopeptide A increased from 9.5 to 16.9 ng/mL at 3 hours (P<.0004) and returned to 10.5 by 24 hours. Prothrombin fragment 1.2 likewise transiently increased, from 0.34 to 0.51 nmol/L at 6 hours (P<.0002). Modified antithrombin III decreased over time (P<.002), and activated protein C increased from 2.3 to 4.5 ng/mL at 3 hours (P<.001). Although there were no clinical thrombotic events in the first 24 hours, 4 patients had evidence of ischemia by ST-segment monitoring at a median of 12 hours after heparin discontinuation. The degree of increase in fibrinopeptide A and prothrombin fragment 1.2 was not found to be associated with baseline diagnosis, duration of heparin therapy, baseline level of antithrombin III, or activated protein C. Conclusions: This study demonstrates a transient rebound increase in thrombin activity as well as in activated protein C upon abrupt discontinuation of intravenous heparin. Clinicians should be vigilant for associated thrombotic events. Further investigation of the significance, mechanism, and possible prevention of this rebound phenomenon is needed.
AB - Background: The abrupt cessation of heparin and other thrombin inhibitors when used to treat acute coronary syndromes has been accompanied by a clustering of thrombotic events. It is unknown whether these events are the result of inadequate antithrombin therapy or whether they represent a rebound increase in thrombin activity. This study was designed to determine whether there is a true rebound, as defined by an increase followed by a subsequent decrease, in thrombin activity after discontinuation of intravenous heparin therapy. Methods and Results: Thirty-five patients with recent acute myocardial infarction or unstable angina who had received at least 48 hours of intravenous heparin were studied. Patients underwent ST-segment monitoring, and blood samples for determination of thrombin generation and activity were drawn at 0, 3, 6, 10, and 24 hours after heparin discontinuation. Median a PTT was 65 seconds before heparin discontinuation. Median fibrinopeptide A increased from 9.5 to 16.9 ng/mL at 3 hours (P<.0004) and returned to 10.5 by 24 hours. Prothrombin fragment 1.2 likewise transiently increased, from 0.34 to 0.51 nmol/L at 6 hours (P<.0002). Modified antithrombin III decreased over time (P<.002), and activated protein C increased from 2.3 to 4.5 ng/mL at 3 hours (P<.001). Although there were no clinical thrombotic events in the first 24 hours, 4 patients had evidence of ischemia by ST-segment monitoring at a median of 12 hours after heparin discontinuation. The degree of increase in fibrinopeptide A and prothrombin fragment 1.2 was not found to be associated with baseline diagnosis, duration of heparin therapy, baseline level of antithrombin III, or activated protein C. Conclusions: This study demonstrates a transient rebound increase in thrombin activity as well as in activated protein C upon abrupt discontinuation of intravenous heparin. Clinicians should be vigilant for associated thrombotic events. Further investigation of the significance, mechanism, and possible prevention of this rebound phenomenon is needed.
KW - angina
KW - heparin
KW - thrombosis
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U2 - 10.1161/01.CIR.91.7.1929
DO - 10.1161/01.CIR.91.7.1929
M3 - Article
C2 - 7895349
AN - SCOPUS:0028962819
SN - 0009-7322
VL - 91
SP - 1929
EP - 1935
JO - Circulation
JF - Circulation
IS - 7
ER -