Coagulants and Anti Coagulants
Transcript of Coagulants and Anti Coagulants
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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