Coagulants and

Anti Coagulants
Venus Eisha L. Barte

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Clinical uses of Anticoagulant
• DVT
• Pulmonary embolism
• Coronary occlusion with acute MI
• Reduces arterial embolism in patients with atrial
fibrillation, mitral stenosis, or prosthetic heart
valve
• Cerebrovascular accidents
• Systemic Coagulopathy
• Cardiovascular operations

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 Coagulation cascade Stage 1

Intrinsic Vascular Injury Extrinsic

-Collagen
Tissue factor III
exposure
exposure
-Contact
activation
involving
VIIa VII
kininogen and
prekallikrein

XII
XIIa X
X1 X1a Membrane Ca VIII

IX
Xa
Ca
IXa Heparin
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 Coagulation cascade Stage 2

Prothrombin Thrombin IIa

XIII
Membrane Ca V
Ca

Heparin
XIIIa
Heparin

Coagulation cascade Stage 3

Fibrinogen Fibrin Cross linked

monomer Ca fibrin

Calcium is needed in every aspect of transformation

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Mechanism of Action
• A. Direct Acting (Systemic) - Parenteral
– Heparin Na
– Blocks Stages:
• 1 = Formation of Factor Xa is inhibited
• 2 = Interferes with the conversion of prothrombin to
thrombin
• 3 = Antagonizes the action of thrombin to
fibrinogen so there is no fibrin formation
• B. Indirect Acting (Oral)
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• B. Indirect Acting (Oral)
– Coumarin (more common) and Indandiones
(Less common)
– Interfere with the uptake of vitamin K responsible
for the manufacture of factor 9 10 7 2 by the
hepatic cells, so there is no synthesis of several
factors such as:
• Factor II – Prothrombin  Hypoprothrombinemia
• Factor VII – Convertin
• Factor IX – Plasma thromboplastin, Christmas factor
• Factor X – Stuart-Prower factor

PTU (Propythiouracil also inhibits) 6

 Drug Trade Name Onset Duration Routes

Direct Acting Heparin Quick Short Oral, IV

infusion,
deep SC
Indirect Acting Slow Long
- Coumarin
- Bishydroxicoumarin Dicumarol 36-48 h 24-108 h PO
- Ethylbiscon Tromexan 18-30 h 36-60 h PO
macetate
- Warfarin Coumadin 35-48 h 84 – 108 h PO
Panwarfarin PO, SC, IV
Indandione
- Diphenadione Dipaxin 48-60 h 96-168 h PO
- Phenandione Hedulin 36-48 h 72-96 h PO
Danilone

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 Drug Trade Name Onset Duration Route

Fibrinolytic
Agents
-Plasmin IV
-Arvin
-Streptokinase
-Urokinase

Most popular

In vitro
-Na Citrate
-Na oxalate

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 Adverse Drug reaction
• Heparin
– Bleeding (most common) from mucous
membranes and open wounds – intracranial
hemorrhage
– With long term use (> 3months) – Osteoporosis
fracture
– Thrombocytopenia
• Induces platelet aggregation
• Production of heparin dependent anti-platelet antibody
– Venous or arterial thrombosis (stroke, gangrene)
– Transplant and reversible alopecia 9
Adverse Drug Reaction
• Warfarin (Indirect)
– Hypoprothrombinemia (associated with
Vitamin K deficiency) – ecchymosis and
hemorrhage
– Alopecia, urticaria, dermatitis
– Abdominal cramps, nausea, LBM
– First 10 weeks of pregnancy (Teratogenic) –
causes Embryopathy nasal hypoplasia and
stippled epiphyses)
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 Anticoagulant Antagonists
DRUG Trade Name Dose and Route Preparation
Direct Acting: 1mg for each 1% sterile
Protamine SO4 100u of Heparin solution (vial
by VERY slow form)
IV
Indirect Acting
Vit K prep:
1. Menadiol Synakyvite 5-10mg PO Tablets,
sodium 5-15 mg IV solutions
diphosphate
2. Menadione Hykinone 2-10mg PO Tabs, caps, oily
1-2 mg IV solution
3. Menadione Monokay 5-10mg oral, IV Tabs, solution
sodium bisulfate
4. Phytonadione Mephyton 5mg PO Tabs, solution
25-250mg IV 11
Drugs that increase effect of
Coumarins
• (Coumarins are INDIRECT / PO coagulants)
– Antibiotics affecting intestinal flora (TCN)
– Clofibrate – Causes displacement
– Chloral hydrate Reduces Vitamin
K Absorption
– Disulfiram – Inhibits biotransformation
– Dextrothyroxine
– Methylphenidate
– Propylthiouracil
– Phenylbutazone
– Salicylates – Inhibits platelet aggregation

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Drugs that decrease effect of
Coumarins
• Barbiturates – through enzyme induction
• Ethchlorvynol
All are PO
• Glutethimide
• Griseofulvin

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 Drugs that enhance PO anticoagulant
activity (Causes more bleeding)

• Decrease vitamin K absorption

– Anitbiotics (TCN – broad spectrum)
– Mineral oil
• Displacement from plasma proteins
– Salicylates (NSAID’s)
– Phenylbutazone
– Chloral hydrate (Sedative hypnotics)
– Clofibrate (Anti cholesterol)
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Drugs that enhance PO anticoagulant
activity (Causes more bleeding)
• Inhibition of biotransformation
– Allopurinol (Anti gout)
– Disulfiram (For alcoholics)
– Metronidazole (Ameobiasis)
– Chloramphenicol (Broad spectrum antibiotic) – for
Typhoid fever
• Inhibition of platelet aggregation(Antiplatelet)
– Aspirin (NSAID’s)
– Epoprosterol (synthetic prostacyclin)
– Ticlopidine
– Clopidogrel (Plavix)
– Dipyridamole 15
Drugs that enhance PO anticoagulant
activity (Causes more bleeding)

• Decreases clotting factors

– Quinidine (Myocardial anti depressant)  anti
arrhythmia

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 Drugs that reduce
PO anticoagulant activity
(But they no anticoagulant activity)
• Enzyme induction
– Barbiturates
– Glutethimide
– Griseofulvin
• Increase clotting factor production
– Vitamin K
– PO contraceptive

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Procoagulants
I. Replacement of deficient clotting factors
A. Anti hemophilic factor
– Factor VIII: Hemophilia A
– Supplied as fresh frozen plasma,
cryoprecipitates or lyophilized concentrate
– Pooled plasma from blood donors
B. Factor IX Complex (Dried Human Plasma
Fraction containing Factors II, VII, IX & X)
– for hemophilia B
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Procoagulants
II. Increased endogenous clotting factors in
the plasma
– Desmopressin – Stimulates the release of
endogenous pools of factor VIII and vWF

III. Inhibition of Natural Fibrinolytic pathway

– competitive inhibitor of plasmin binding to
fibrin
A. Aminocaproic acid
B. Tranexanic acid (Hemostan)
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Coagulants
• Local (Stops capillary bleeding)
– Sterile wax
– Oxidized cellulose
– Absorbable gelatin
– Fibrin foam
– Thrombin
– Microfibrillar collagen Hemostat
• Systemic
– Vitamin K prep (secondary to Warfarin use)
– Tolonium Cl
– Protamine SO4
– Hexadimetrine bromide
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Procoagulants
• 3 inhibition of natural fibrinolytic pathway
competitive inhibitor of plasmin binding to
fibrin
– Aminocaproic acid
– Tranexamic acid (Hemostan)

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Side notes
• Herbal tannins are coagulants
• If profuse bleeding, give IV if no response
to PO therapy
• Aloe vera juice is also good for bleeding

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