Increased thrombin levels during thrombolytic therapy in acute myocardial infarction. Relevance for the success of therapy.

Gulba, Dietrich C.; Barthels, Monika; Westhoff-Bleck, M.; Jost, Stefan; Rafflenbeul, W.; Daniel, Werner G.; Hecker, Hartmut; Lichtlen, Paul R.

doi:10.1161/01.cir.83.3.937

Cited by 174 publications

(61 citation statements)

References 41 publications

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“…The use of alteplase reveals similar findings: Levels of TAT complexes, prothrombin fragment 1ϩ2, and fibrinopeptide A 3,6,8,10,11,18 are higher, along with a reduction in fibrinogen and an increase in D-dimers. High thrombin activation markers are reported to be associated with failure of lysis 18 but not with worse clinical outcome.…”

Section: Comparison Of Data On Coagulation and Fibrinolysis With The mentioning

confidence: 60%

“…[12][13][14][15][16][17] In patients with AMI and thrombolytic therapy, markedly increased thrombin activation was associated with failure to open the occluded coronary artery and with a high reocclusion rate. 18 As one pathway of thrombin stimulation of thrombolytics, activation of the contact phase of the coagulation by plasmin has been found in vitro. 19 A recent clinical study measuring indirect plasmin markers proved the activation of the kallikrein-contact-phase system after streptokinase in patients with AMI, 13 but no direct data on plasmin activation are available.…”

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confidence: 99%

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Thrombolytic Therapy in Acute Myocardial Infarction

et al. 1998

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Background-Thrombolytic therapy in patients with acute myocardial infarction (AMI) is hampered by procoagulant effects. In vitro studies have indicated that plasmin stimulation activates the kallikrein-contact-phase system, resulting in thrombin activation. This prospective comparative study was designed to examine the procoagulant effects of streptokinase or alteplase in AMI. Methods and Results-Sixty-one patients with AMI received 1.5 million U of streptokinase or front-loaded alteplase (up to 100 mg) and systemic heparin. Twenty-four patients with AMI and no thrombolytic therapy and 30 control subjects were examined for comparison. Molecular markers of thrombin, plasmin activation, and coagulation activities were determined before therapy and serially for up to 10 days. Streptokinase and alteplase increase TAT to 50Ϯ17 and 51Ϯ18 g/L at 3 hours and to 50Ϯ17 and 33Ϯ14 g/L at 6 hours, respectively (PϽ0.01). Kallikrein activity is elevated (PϽ0.01) to 76Ϯ5 and 71Ϯ7 U/L at 3 hours and 64Ϯ6 and 47Ϯ5 U/L by streptokinase and alteplase, respectively, at 6 hours. Reductions in fibrinogen and increases in D-dimers and plasmin-antiplasmin complexes are more marked (PϽ0.05 and 0.01) after streptokinase versus alteplase. Correlations were found among TAT, kallikrein activity, and plasmin activation (PϽ0.01). Conclusions-The data indicate a more marked procoagulant action of the streptokinase regimen compared with front-loaded alteplase, thus supporting the hypothesis of a plasmin-mediated kallikrein activation with consecutive procoagulant action in vivo.

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Section: Comparison Of Data On Coagulation and Fibrinolysis With The mentioning

confidence: 60%

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confidence: 99%

Thrombolytic Therapy in Acute Myocardial Infarction

et al. 1998

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“…2,3 In patients with AMI, markers of elevated thrombin generation predict poorer clinical outcomes, failure to reperfuse, and increased hemorrhagic events. 7,8,10 We found a surge of thrombin generation after rtPA therapy for AIS. High thrombin generation at 24 hours is associated with a higher overall odds of mortality.…”

Section: Thrombin Generationmentioning

confidence: 82%

“…5, 6 The usefulness of hemostatic markers in affecting clinical outcomes after thrombolysis has been investigated more extensively in patients with acute myocardial infarction (AMI). 4,[7][8][9][10] We undertook to investigate in the National Institute of Neurological Diseases and Stroke (NINDS) rtPA Stroke Trial 1 (1) the extent of altered markers of endogenous fibrinolysis, thrombin generation, and endothelial injury in AIS; and (2) the relationship of these markers to outcomes, including response to intravenous rtPA. We hypothesized that markers of impaired endogenous fibrinolysis, increased thrombin generation, and microvascular injury may be linked to poorer stroke outcome and may blunt the clinical response to rtPA therapy.…”

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confidence: 99%

Hemostatic Activation and Outcome After Recombinant Tissue Plasminogen Activator Therapy for Acute Ischemic Stroke

Tanné

Macko

Yang

et al. 2006

Stroke

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for the NINDS rtPA Stroke Study Group Background and Purpose-Early thrombolytic therapy with intravenous recombinant tissue plasminogen activator (rtPA) improves clinical outcome in acute ischemic stroke (AIS), but impaired endogenous fibrinolysis, thrombin generation, and vascular injury may hamper the efficacy of thrombolysis. We investigated in an exploratory, post hoc analysis the relationship between hemostatic markers and clinical outcomes among patients included in the National Institute of Neurological Disorders and Stroke (NINDS) rtPA Stroke Study. Methods-Tissue plasminogen activator (tPA) antigen, thrombin-antithrombin complex (TAT), soluble thrombomodulin, and fibrinogen levels were measured in patients with AIS included in the NINDS rtPA Stroke Study from plasma samples collected at baseline, at 2 hours after treatment, and after 24 hours. Results-TAT and tPA antigen levels peaked at 2 hours selectively in the rtPA treatment group, whereas fibrinogen levels dropped at 2 hours and remained low after 24 hours (PϽ0.0001 for interaction effects between time and treatment). At 24 hours, higher levels of tPA antigen were associated with a lower chance of favorable outcome (odds ratio [OR]ϭ0.34; 95% CI, 0.14 to 0.82) selectively in the rtPA group, and higher levels of TAT (ORϭ1.72; 95% CI, 1.26 to 2.34) in the entire cohort and of thrombomodulin selectively in the rtPA group (ORϭ4.45; 95% CI, 1.26 to 15.67) were associated with higher 3-month mortality. Conclusions-Hemostatic activation after AIS appears to be independently associated with clinical outcome in patients treated with rtPA. However, because we have tested for multiple associations, some may have been identified by chance alone and require further confirmatory studies. On the basis of this exploratory analysis, there is a rationale to investigate the safety and efficacy of protocols in which rtPA is complemented by agents that are antithrombotic and enhance fibrinolysis. (Stroke. 2006;37:1798-1804.)

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“…After enrollment of 302 patients, the trial was stopped after an increased rate of intracranial bleeding was observed in the hirudin group (5 of oronary artery reperfusion by thrombolysis in patients with acute myocardial infarction (AMI) has proved to be a major advance in cardiac medicine, leading to improvement in left ventricular ejection fraction1,2 and to a reduction in mortality.34 Nevertheless, current thrombolytic therapy is limited by the fact that despite adequate adjunctive heparin therapy, fewer than 60% of patients achieve optimal early reperfusion, and of reperfused vessels, 10% to 20% reocclude during the hospital stay.5 Both failure to achieve complete early reperfusion and coronary artery reocclusion are associated with increased morbidity and mortality.67 Ongoing thrombin formation during thrombolysis, even in the presence of intravenous heparin therapy, is a significant predisposing factor for reocclusion. 8,9 Recently, a number of experimental studies investigating the direct thrombin inhibitor hirudin have shown promising results.10~12 148, 3.4%) compared with the heparin group (0 of 154). The overall stroke rate was 3.4% in the hirudin group and 1.3% in the heparin group.…”

mentioning

confidence: 99%

Safety observations from the pilot phase of the randomized r-Hirudin for Improvement of Thrombolysis (HIT-III) study. A study of the Arbeitsgemeinschaft Leitender Kardiologischer Krankenhausärzte (ALKK)

et al. 1994

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Background Adjunctive therapy for thrombolysis in acute myocardial infarction consists of platelet inhibition with aspirin and thrombin inhibition with heparin. Thrombin inhibition may be improved by the use of hirudin as indicated by experimental and phase II clinical studies. The randomized, double-blind phase III r-Hirudin for Improvement of Thrombolysis study (HIT III) compared a recombinant hirudin (HBW 023) with heparin. The primary end point was the incidence of death or reinfarction.Methods and Results Seven thousand patients with acute myocardial infarction and a duration of symptoms of less than 6 hours were to be randomized to receive intravenous heparin

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Increased thrombin levels during thrombolytic therapy in acute myocardial infarction. Relevance for the success of therapy.

Cited by 174 publications

References 41 publications

Thrombolytic Therapy in Acute Myocardial Infarction

Thrombolytic Therapy in Acute Myocardial Infarction

Hemostatic Activation and Outcome After Recombinant Tissue Plasminogen Activator Therapy for Acute Ischemic Stroke

Safety observations from the pilot phase of the randomized r-Hirudin for Improvement of Thrombolysis (HIT-III) study. A study of the Arbeitsgemeinschaft Leitender Kardiologischer Krankenhausärzte (ALKK)

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