Anticoagulants
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Transcript of Anticoagulants
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Thrombosis and Anticoagulation
Ahmed ElshebinyAhmed ElshebinyUniversity of MenoufyiaUniversity of Menoufyia
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Thrombosis Arterial Venous Risk factors Thrombophilia
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VTE, PE 10% of hospital deaths may be due to PE PE is the most common preventable cause of
death in hospitals Thromboprophylaxis is highly effective and
cost – effective All medical and surgical admitted patients
must be assessed for thrombotic risk and given appropriate thromboprophylaxis
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Risk factors for VTE Patients
factors Disease or
surgical procedure
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Coagulation factors
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Coagulation
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Coagulation cascade
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Fibrin formation
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Investigations of coagulation system Coagulation tests use citrate as anticoagulant Adding tissue factor(thromboplastin and calcium) …… PT…
measures VII , X, V, prothrombin and fibrinogen Adding a surface activator like Kaolin (phospholipid) to
mimic platelet membrane and calcium….. PTT…..VIII, IX,X,XI,V , in addition to prothrmbin and fibrinogen( Classic Intrinsic)
Adding Thrmbin…. Thrombin Time TT Correction tests Factor assays Fibrinogen and FDPs
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Natural inhibitors of coagulation Antithrombin Activated
protein C Protein S Others
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Antithrombin and its deficiency Action Hereditary and acquired Concentrates available
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Acquired antithrombin difficiency Neonates Pregnancy and its states Trauma , major surgery Liver disease Kidney disease (NS) Sepsis Consumptive coagulopathies Bone marrow transplantation (Veno-occlusive
disease) Drugs (heparin, oral contraceptives, asparaginase)
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Hereditary antithrombin difficiency Early onset of thrombosis Types (I and II) Different gene mutations and antithrombin
activities
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Protein C and S
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DIC
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Anticoagulants
Anticoagulants
Indirect thrombin Inhibitors Direct thrombin inhibitors
Heparin LMW heparin Fondaparinux Parentral oral
Vitamin k antagonists
Classic oral
Warfarin
PhendionPhenendionee
Hirudin
Lepirudin
Bivalirudin
Enoxparin
Dalteparin
danaparinoiDanaparoidd
Dabigatran
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Anticoagulants
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Heparin 1937 Heterogenous mixture of sulfated MPs Its binds to endothelial cell surface and plasma
proteins Its activity depends on endogenous antithrombin Heparin functions as a cofactor for the antithrombin-
protease reaction without being consumed Monitor heparin Has Antidote
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Adverse effects of Heparin Bleeding Allergy Increased loss of hair and reversible alopecia Long term use is associated with osteoporosis
and spontaneous fractures and minralocorticoid deficiency
Heparin induced thrombocytopenia (HIT)
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Heparin induced Thrombocytopenia(HIT) A hypercoagulable state in in 1-4 % of patients
treated with UFH for a minimum of 7 days More in surgical patients , less in pregnant, more
with bovine heparin than porcine Lower in LMW heparins Morbidity and mortality due to thrombotic events In all patients receiving heparin ------ monitor
platelets ---if decreased in the time frame of immune cause ---- stop heparin and add direct thrombin inhibitor or fondaparinux
Don’t introduce warfarin alone
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Contra-indications of heparin HIT, hypertension (severe), hemophilia Erosions (ulcers of GIT) Purpura Active bleeding- active T.B., abortion (threatened),
advanced liver and kidney disease- visceral cancer Recent surgery in brain, eye, spinal cord (planned
Lumbar puncture) or renal biopsy Infective endocarditic Never administer IM
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LMW heparins Enoxparin(clexane) Daltparin(fragmin)
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LMW heparin characteristics Duration Bleeding Control of dosing
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Doses of Heparins UFH bolus 80-100 U/ kg then 15-22/Kg/hr Enoxparin ( 30 mg / 12 or 40 mg /d prophylactic ….
If therapeutic 1 mg /kg /12 hr or 1.5 mg/kg/ d in selected patients)
Dalataparin( prophylactic dose 5000 U/d…. Full dose is 200 U/kg / d for venous or 120 U/kg /12 hr in ACS)
Use LMW with caution in renal insufficiency and in patients > 150 kg ….. Monitor with anti-Xa level
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Reversal of the action of heparin Discontinue heparin Protamine sulfate Avoid excess protamine Protamine can’t reverse fondaparinux What about LMW ?
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Fondaparinux Synthetic pentasaccharide Long acting, once daily Effective Acts through antithrombin resulting in
efficient inactivation of factor Xa Appears not to cross react with HIT
antibodies
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factor Xa inhibitors Fondaparinux Rivaroxaban (oral)
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Indirect thrombin inhibitors
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Direct Thrombin inhibitors Hirudin
Lepirudin (kidney) Bivalirudin (reversible), less bleeding Argatroban (Liver) Monitor by PTT
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Vitamin K antagonists Coumarins (Warfarin) ( Marevan) Inandiones (phenendione) ( Dindevan)
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Target INR and Indications 2.5 3.5
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Bleeding during anticoagulation INR 3-6 4-6 6-8 without bleeding or minor > 8 without bleeding or minor > 8 major bleeding
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Anticoagulation during pregnancy
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New orally active anti-coagulant drugs Direct thrombin Xa inhibitors
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References Current diagnosis and treatment (Medicine) 2010 Kumar and Clark’s Clinical Medicine 2009 E-medicine- online textbook/Hematology Specialty Harrison’s online textbook 2008 Zehnder James L, "Chapter 34. Drugs Used in
Disorders of Coagulation" Katzung BG: Basic & Clinical Pharmacology, 11e
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