Microparticle-linked tissue factor activity and increased thrombin activity play a potential role in fibrinolysis failure in ST-segment elevation myocardial infarction.
Fibrinolysis for acute ST-segment elevation MI achieves early recanalisation of the infarct artery in approximately 60% of cases. The aim of the study was to determine whether failure to achieve recanalisation was associated with differences in haemostasis biomarkers compared to patients with successful fibrinolysis. Fourty-three patients were prospectively enrolled in a case-control study. All patients had received tenecteplase (TNK-tPA) together with aspirin (500 mg) and heparin (5,000 IU). Emergency angiography within 90 minutes of bolus TNK-tPA identified 13 TIMI 0-2 patients (cases) and 30 TIMI 3 patients (controls). Blood samples were collected before angiography to determine tissue factor activity associated with microparticles (TF-MP); soluble platelet glycoprotein V (sGPV) and thrombin-antithrombin complexes (TAT) as markers of thrombin generation; tissue plasminogen activator (endogenous tPA+ TNK-tPA), plasminogen activator inhibitor (PAI-1) and plasmin-antiplasmin complexes (PAP) as markers of plasmin generation. The baseline characteristics of the two patients' groups were similar with respect to sex, age, and risks factors. Cases differed from controls by higher TF-MP levels (1.9 [1-13] vs. 1 [0.6-1.3] pM), sGPV (67 [51-126] vs. (48 [39-72] ng/ml), p = 0.039 and TAT (10 [4-37.5] vs. 4 [2.9-7.2] ng/ml), p = 0.035. TAT correlated with TF-MP (r = 0.51, p = 0.0064) and sGPV (r = 0.51, p = 0.0018). No significant difference was observed in tPA or PAI-1 levels. PAP were lower in cases (18.83 [14.83-40.43] mug/ml) than in controls (35.83 [27.9-43.94] mug/ml), p = 0.045. In conclusion, fibrinolysis failure in AMI is characterised by a higher procoagulant state associated with TF-MP and a lower plasmin generation.
Huisse
Marie-Geneviève
MG
Department of Haematology, AP-HP, Hôpital Bichat, Paris, France. marie-genevieve.huisse@bch.aphp.fr
Ajzenberg
Nadine
N
Feldman
Laurent
L
Guillin
Marie-Claude
MC
Steg
Philippe Gabriel
PG
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015906:Angioplasty, Balloon, Coronary; D000925:Anticoagulants / Q000008:administration & dosage; D001241:Aspirin / Q000008:administration & dosage; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D055252:Cell-Derived Microparticles / Q000187:drug effects* / Q000378:metabolism; D017023:Coronary Angiography; D003326:Coronary Circulation; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004638:Emergency Treatment; D005260:Female; D005341:Fibrinolysin / Q000378:metabolism; D005343:Fibrinolytic Agents / Q000008:administration & dosage*; D006487:Hemostasis / Q000187:drug effects*; D006493:Heparin / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage; D011446:Prospective Studies; D013917:Thrombin / Q000378:metabolism*; D015912:Thrombolytic Therapy; D013925:Thromboplastin / Q000378:metabolism*; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage*; D017211:Treatment Failure
D000925:Anticoagulants; D015415:Biomarkers; D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; D006493:Heparin; D013925:Thromboplastin; D013917:Thrombin; C104096:TNK-tissue plasminogen activator; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin; D001241:Aspirin