fibrinolitiktrombolitik, antikoagulan dan antiplatelet

Endang Sulistyowati N, M.Sc., Apt

HemostasisThe process that leads to the stopping of bleeding

Trombosis pembentukan trombus di vaskuler, jika mengalir bersama aliran darah disebut embolus

Hemostasis involves :PlateletsCoagulation/Clotting cascade (include fibrin)Blood vessels (endothelium)Inhibitory/control mechanism

When the endothelium is damaged vasoconstriction and underlying collagen is exposed to circulating platelets.

Platelet membran bind directly to collagen-specific Glycoprotein Ia/IIa and Ib surface receptors and strengthened by von Willebrand factor (vWF) which is bundled in subendothelium.

Three main process of platelets are : adhesion (1 – 3 seconds after injury)activation (platelets release ADP and TXA2 more platelets stimulation and produce new fibrins) aggregation (3 – 7 minutes)

Consist of  : the tissue factor pathway  (the extrinsic pathway) and the contact/surface activation/ amplification pathway  (the intrinsic pathway)

Extrinsic pathway is the initiation of blood coagulation

It was previously thought that coagulation cascade consisted of two pathways of equal importance joined to a common pathway (Fibrin produced)

Protein C is a major physiological anticoagulant

Antithrombin is a serine protease inhibitor (serpin)

Tissue factor pathway inhibitor (TFPI)

Plasminogen plasmin (catalyzed by tissue plasminogen activator/ t-PA) which is synthesized and secreted by endothelium

Prostacyclin (PGI2) activates adenylyl cyclase which synthesizes cAMP that inhibits platelet activation

Negative feed back

a. Parenteral Unfractionated heparin (UFH) LMWH (enoxaparin, nadroparin) Fondaparinux

b. Oral Warfarin, rifaroxaban, dabigatran

Extracted from porcine intestinal mucosa or bovine lung

LMWH lower risk for bleeding and heparin induced trombositopenia, doesn’t cause thrombin inhibition

Administer : SubcutaneousContinuous intravenous infusion

Novel oral factor Xa and direct thrombin (IIa) inhibitors and their respective targets in the coagulation cascade

Cabral, K. P. & Ansell, J. (2012) Oral direct factor Xa inhibitors for stroke prevention inatrial fibrillation

Nat. Rev. Cardiol. doi:10.1038/nrcardio.2012.19

Pharmacokinetic and pharmacodynamic characteristics of oral factor Xa inhibitors

Cabral, K. P. & Ansell, J. (2012) Oral direct factor Xa inhibitors for stroke prevention inatrial fibrillation

Nat. Rev. Cardiol. doi:10.1038/nrcardio.2012.19

Aspirin Inhibit production of Thromboxan A2

Dose : 50 – 320 mg/day Dipiridamol

Increasing cAMP vasodilator Ticlopidin

Inhibition of ADP-activated platelet P2Y1 receptor Dose : 250 mg twice daily

ClopidogrelDose : 75 mg/day, Less leucopenia n trombositopenia

Streptokinase produced by Streptococcus β-hemoliticus

t-PA (tissue plasminogen activator)AlteplaseReteplase

Acute Myocardial Infarction

During CABG, PCI, stent placement

Stroke ischemia

Venous Thromboembolism (VT)

Pulmonary Embolism

Clotting time, Drugs Interaction Antikoagulan heparin aPTT 26 – 33 detik (variatif)

(+kaolin) activated Partial Tromboplastin Time

PTT 12 – 14 detik (+tromboplastin) Prothrombin time

Antikoagulan oral INR (International Normalized Ratio)

Bleeding assest underlying cause Lab : Prolonged PTT/aPTTOthers .. Red/Dark urine or stools, Gums bleed

Antidot tranexamat acid, protamin sulfat

Trombositopenia diganti dgn Bivalirudin