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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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Vascular Injury ExtrinsicIntrinsic

-Collagen exposure

-Contact activation involving

kininogen and prekallikrein

XII

XIIaX1 X1a

IX

CaIXa

Tissue factor III exposure

VII VIIa

Membrane Ca VIII

X

Xa

Coagulation cascade Stage 1

Heparin

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Coagulation cascade Stage 2

Prothrombin Thrombin IIaMembrane Ca V

XIII

XIIIa

Ca

Coagulation cascade Stage 3

Fibrinogen Fibrin monomer

Cross linked fibrinCa

Calcium is needed in every aspect of transformation

Heparin

Heparin

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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)

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Drug Trade Name Onset Duration Routes

Direct Acting Heparin Quick Short Oral, IV infusion, deep SC

Indirect Acting- Coumarin- Bishydroxicoumarin- Ethylbiscon

macetate- Warfarin

Indandione- Diphenadione- Phenandione

Dicumarol

Tromexan

Coumadin

Panwarfarin

Dipaxin

Hedulin

Danilone

Slow

36-48 h

18-30 h

35-48 h

48-60 h

36-48 h

Long

24-108 h

36-60 h

84 – 108 h

96-168 h

72-96 h

PO

PO

PO

PO, SC, IV

PO

PO

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Drug Trade Name Onset Duration Route

Fibrinolytic Agents-Plasmin-Arvin-Streptokinase-Urokinase

IV

In vitro-Na Citrate-Na oxalate

Most popular

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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

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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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DRUG Trade Name Dose and Route Preparation

Direct Acting: Protamine SO4

1mg for each 100u of Heparin by VERY slow IV

1% sterile solution (vial form)

Indirect Acting

Vit K prep:

1. Menadiol sodium diphosphate

Synakyvite 5-10mg PO

5-15 mg IV

Tablets, solutions

2. Menadione Hykinone 2-10mg PO

1-2 mg IV

Tabs, caps, oily solution

3. Menadione sodium bisulfate

Monokay 5-10mg oral, IV Tabs, solution

4. Phytonadione Mephyton 5mg PO

25-250mg IV

Tabs, solution

Anticoagulant Antagonists

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Drugs that increase effect of Coumarins• (Coumarins are INDIRECT / PO coagulants)

– Antibiotics affecting intestinal flora (TCN)– Clofibrate – Causes displacement– Chloral hydrate– Disulfiram – Inhibits biotransformation– Dextrothyroxine– Methylphenidate– Propylthiouracil– Phenylbutazone– Salicylates – Inhibits platelet aggregation

Reduces Vitamin K Absorption

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Drugs that decrease effect of Coumarins• Barbiturates – through enzyme induction

• Ethchlorvynol

• Glutethimide

• Griseofulvin

All are PO

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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

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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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ProcoagulantsII. 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