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Hemostasis requires a fine balance between

procoagulant and regulatory factors

BLOOD COAGULATION,
ANTICOAGULANTS, Coagulation
Proteins/ PC
Thrombosis
PS
FIBRINOLITYC & Deficiency Platelets/
Vessel wall ATIII…

ANTITHROMBOTIC DRUGS Deficiency/

Abnormality

Bleeding
B. Dian Novita, dr., MKed.
diannovitakrisdianto@yahoo.co.id
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The Coagulation
and
Fibrinolytic
Pathways

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Factors Regulating Homeostasis Antithrombotic Drugs Used for

and Thrombosis Venous Thrombosis (1)

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Antithrombotic Drugs Used for

Venous Thrombosis (2)

ANTICOAGULANT DRUGS

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ANTICOAGULANT DRUG • Unfractionated(UFH)

HEPARIN
TARGETS • Low molecular
weight(LMWH)
• HEPARIN

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UNFRACTION HEPARIN (UFH)…1 UNFRACTION HEPARIN (UFH)…2

Pharmacokinetics : Monitoring :
• not reliably absorbed P.O due to molecular size • whole blood clotting time
and anionic structure • activated partial thromboplastin time (aPTT)
• bioavailability and biologic activity is limited by its • activated clotting time (ACT)
propensity to bind to plasma proteins, platelet • antifactor Xa activity
factor 4 (PF4), macrophages, fibrinogen,
• Plasma heparin concentrations
lipoproteins, and endothelial cells
Reduce The Dose
Adverse Effect :
This may explain the substantial inter- and intra- Discontinue The Drug
patient variability observed in the anticoagulation • Bleeding Protamine Sulfate
response • Thrombocytopenia Transfusion
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Low-Molecular-Weight Heparins FONDAPARINUX,

Indications Enoxaparin Dalteparin Tinzaparin IDRAPARINUX
Hip-replacement surgery √ √ (post op)
(prophylaxis) • Pentasaccharides
Knee-replacement surgery √
(prophylaxis) • anticoagulants that selectively inhibits factor Xa
Abdominal surgery (prophylaxis) √ √ activity
• rapidly and completely absorbed by subcutaneous
Acute medical illness √ √
(prophylaxis) administration (100%)
Deep vein thrombosis treatment √ √ • contraindicated in patients with severe renal
(with or without pulmonary
embolism) function impairment
Venous thromboembolism √
treatment in patients with cancer

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FONDAPARINUX Risk Factors for Major Bleeding While

Taking Anticoagulation Therapy
• Anticoagulation intensity
• Initiation of therapy (first few days and weeks)
• Unstable anticoagulation response
• Age >65 years
• Concurrent antiplatelet drug use
• Concurrent nonsteroidal antiinflammatory drug use
• History of gastrointestinal bleeding
• Recent surgery or trauma
• High risk for fall/trauma
• Heavy alcohol use
• Renal failure
• Cerebrovascular disease
• Malignancy
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Contraindications
• Active major bleeding
• Hemophilia or other hemorrhagic tendencies Direct Thrombin
• Severe liver disease with elevated baseline PT
• Severe thrombocytopenia (platelet count <20,000 Inhibitors
mm3)
• Malignant hypertension
• Inability to meticulously supervise and monitor
treatment
• hypersensitive

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DIRECT THROMBIN (IIa) Mechanism of

Action of Direct
INHIBITORS Thrombin
Inhibitors as
Compared with
Heparin

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WARFARIN ...1
Pharmacokinetics :
ORAL ANTI • racemic mixture of R and S isomers
COAGULANT • S isomer 2.7 to 3.8x > potent than R isomer
• bioavailability > 90%
• 99% bound to plasma proteins
Dose adjustment :
Warfarin
• advanced age (>65 years old)
(Vitamin K • elevated baseline INR
Antagonist) • poor nutritional status, liver disease
• Hyperthyroidism
• genetic polymorphisms in CYP2C9 and VKOR
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• concurrent use of medications 22
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Warfarin Drug Interactions Warfarin-Food Interaction (Vit.K)

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WARFARIN ... 2 WARFARIN MANAGEMENT

Adverse Effect : INR excessive,not bleeding - adjust dose
• bleeding
BLEEDING
• hemorrhagic complications
stop warfarin
Contraindication : transfuse
• Pregnancy  fetal hemorrhage & teratogenic give prothrombin complex(clotting factors)
give vitamin K1
complications

INR subtherapeutic
increase warfarin dose slowly
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Warfarin clinical Use

Prevention of thrombo-embolism : ANTIPLATELET DRUGS
• DVT/PE
• MI, Ischemic
• CHF
• Atrial fibrillation Aspirin Abciximab
w/ Valvular heart disease Clopidogrel Prasurgrel
w/ Acute myocardial infarction Clopidogrel
w/ Prosthetic heart valves
w/ Recurrent systemic embolization
NOT for stroke or peripheral
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ASPIRIN
• Complete inactivation of platelet COX-1 is
achieved with a daily aspirin dose of 75 mg

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CLOPIDOGREL
TICLOPIDINE
• an irreversible inhibitor of platelet P2Y12 receptors
• Ticlopidine is a thienopyridine prodrug inhibits the • more potent and has a more favorable toxicity profile
P2Y12 receptor in platelets than Ticlopidine
• prodrug with a slow onset of action
Adverse Effects :
• better than aspirin in the secondary prevention of
• Common : nausea, vomiting, and diarrhea. stroke
• The most serious is severe neutropenia • combination of clopidogrel + aspirin use for
prevention of recurrent ischemia in patients with
unstable angina, after angioplasty & coronary stent
implantation. The combination should be continued
for at least 4-6 weeks in patients with a bare metal
stent and for at least 1 year in those with a drug-
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GLYCOPROTEIN IIb/IIIa
RECEPTOR ANTAGONISTS

THROMBOLYTIC AGENTS

Adverse Effect : • a2 – Antiplasmin

• Bleeding • Streptokinase
• Tissue Plasminogen Activator

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ADVERSE EFFECT OF
THROMBOLYTIC AGENTS
Hemorrhagic toxicity :
• the lysis of fibrin in hemostatic plugs at sites of
vascular injury,
• the systemic lytic state that results from systemic
plasmin generation, which produces
fibrinogenolysis and degradation of other
coagulation factors (especially factors V and
VIII).

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