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Hemostasis
The process that leads to the stopping of
bleeding
Trombosis pembentukan trombus di
vaskuler, jika mengalir bersama aliran darah
disebut embolus
Hemostasis involves :
Platelets
Coagulation/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 (PGI
2
) activates adenylyl cyclase which
synthesizes cAMP that inhibits platelet activation
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, doesnt
cause thrombin inhibition
Administer :
Subcutaneous
Continuous 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 in
atrial 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 in
atrial 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
Clopidogrel
Dose : 75 mg/day, Less leucopenia n trombositopenia
Streptokinase produced by Streptococcus
-hemoliticus
t-PA (tissue plasminogen activator)
Alteplase
Reteplase
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/aPTT
Others .. Red/Dark urine or stools, Gums bleed
Antidot tranexamat acid, protamin sulfat
Trombositopenia diganti dgn Bivalirudin