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