Antikoagulační léčba doc. MUDr. Jaromír Chlumský, PhD.

1. Antitrombotická léčba = ACP, ticlodipin, clopidogrel 2 1.Antitrombotická léčba = ACP, ticlodipin, clopidogrel 2.Trombolytická léčba = streptokináza, TPA 3.Antikoagulační léčba =heparin, warfarin

% of Patients Having Stroke, MI, or Vascular Death Antiplatelet Trialists’ Collaboration Efficacy in Prevention of Ischemic Events Odds Reduction* 22% 0% 5% 10% 15% 20% 25% Antiplatelet Therapy Control 25% 29% 27% 25% % of Patients Having Stroke, MI, or Vascular Death 32% Prior Stroke/TIA Acute MI Prior MI Other High Risk High Risk All Patients *OR = Odds reduction, a percentage reduction of an outcome measure comparing treatment to control group. Antiplatelet Trialists’ Collaboration. BMJ. 1994;308:81–106.

ASA – 7 dní, indobufen- 12 hodin ticlopidin - neutropenie clopidogrel- rezistence prasugrel

Coagulation Cascade Intrinsic Pathway (surface contact) Extrinsic Pathway (tissue factor) XIIa VIIa XIa Heparin / aLMWH (AT-III dependent) IXas Hirudin/Hirulog (direct antithrombin) Xa aPTT Thrombin (IIa) PTa Thrombin-Fibrin Clot Courtesy of VTI

Activation of Platelets The Procoagulant State in Thrombolysis Vascular Injury Activation of Platelets And Coagulation Amplification Xa Thrombin (IIa)

Role of Platelets in Thrombus Formation in Acute Ischemic Events Lipid Core Atherosclero tic Vessel Plaque Rupture Platelet Adhesion, Activation, and Aggregation Thrombus Formation Thrombotic Occlusion MI Stroke Vascular Death Vessel wall injury  Plaque rupture  Exposure of subendothelial collagen and other platelet-adhering ligands Schafer AI. Am J Med. 1996;101:199–209.

Inactivation of Thrombin by Heparin-AT Complexes Fibrin Heparin AT Thrombin H F S C When thrombin binds to fibrin, it becomes resistant to inactivation by heparin.

Differential inhibitory activity against factor Xa and IIa activity Unfractionated Heparin LMWH Thrombin (IIa) H F S C Thrombin (IIa) H F S C AT AT By binding to AT, most UH and LMWH can inhibit Xa activity. Fewer than half the chains of LMWH are of sufficient length to also bind factor IIa, therefore has decreased anti-IIa activity.

DUS

Délka antikoagulační léčby doživotně HŽT + AT III def., homozygot aPC, kombinované TF, životohrožující příhoda 6-18 měsíců HŽT+ nádor, protein C nebo S deficience, žilní insuficiencie 6 měsíců HŽT + věk do 45 let, recidiva nebo RA, PE 3 měsíce HŽT po operaci doživotně HŽT + AT III def., homozygot aPC, kombinované TF, životohrožující příhoda 6-18 měsíců HŽT+ nádor, protein C nebo S deficience, žilní insuficiencie 6 měsíců HŽT + věk do 45 let, recidiva nebo RA, PE 3 měsíce HŽT po operaci

Physiologic Fibrinolytic System (plasmin - key to fibrinolysis) Plasminogen synthesized in the liver circulates in high concentrations significant homology with LP(a) Plasminogen Activator t-Pa and u-PA released by endothelium converts plaminogen to plasmin fibrin surface facilitates fibrinolysis by providing the binding site for the formation of plasminogen-tPA complex free floating t-PA has low activity Fibrinolytic Inhibitor PAI-1 is the main inhibitor of tPA & uPA Plasminogen activators (t-PA, u-PA) Plasminogen activator inhibitors (PAI-1, PAI-2) Plasmin Plasminogen 2-Antiplasmin Fibrin FDP

Streptokináza: 250 000 j bolus Trombolytická léčba Streptokináza: 250 000 j bolus dále 1 250 000 j /l hod Nebo 100 000 j/ hod 24-48 hod tPA: 15 mg bolus, 50 mg l hod, 35 mg l hod

Indikace IM plicní embolie lokálně – embolie či trombosy