Heparin

INTRODUCTION:
  • Heparin is an anticoagulant (blood thinner) that prevents the formation of blood clots.
  • Heparin is used to treat and prevent blood clots in the veins, arteries, or lung. Heparin is also used before surgery to reduce the risk of blood clots
  • Heparin is heterogeneous of unbranched polysaccharide chains
  • Alternating monosaccaride units of L-iduronic acid and D-glucosamine
  • one third of the polysaccharide chain contain a specific antithrombin binding pentasaccharide sequence
  • Calcium is recomended as dietary supplements is recommended for a pregnant lady on Heparin
  • Preparation from porcine and bovine intestinal mucous
  • Preparation from bovine lung
  • Drug used in heparin overdose is Protamine sulphate
  • Heparin Requires aPTT monitoring in patient
MECHANISM OF ACTION:
  • Heparin exerts parts of its anticoagulant activity through interaction with antithrombin III
  • Antithrombin binds specifically to a pentsaccharide in heparin
  • Heparin Releases Lipoprotein Lipase & Non Teratogenic
  • Heparin inhibits the active form of factor X, XI, XII
  • Binding to heparin induced a conformational change in the antithrombin , which accelerate enzyme inhibition
  • Protamine sulfate is a specific heparin antagonist 1 mg of which neutralizes approximately 100 mg of heparin by chemical antagonism
FORMS OF HEPARIN:
  • Unfractionated heparin (UF)
  • Low molecular weight heparin (LMW)
INDICATION & USES:
  • Prophylaxis and treatment of venous thrombosis and it extensions
  • Osmotic fragility test
  • Pulmonary embolism (PE), mesenteric vein thrombosis, peripheral arterial embolism, and atrial fibrillation with embolization.
  • Treatment of acute and chronic consumption coagulopathies (disseminated intravascular coagulation[DIC]
  • Prevention of postoperative deep venous thrombosis
  • Heparin is strongest organic acid present in body, so it can decrease pH.
  • Pregnant patient with prosthetic valve should be switched to heparin in 36 weeks
  • Also used to maintain catheter patency and as an anticoagulant in blood transfusions, extracorporeal circulation, dialysis, and laboratory samples.
ADVERSE EFFECT:
  • Bleeding
  • Hypersensitivity
  • Heparin induced thrombocytopenia
  • Reversible alopecia
  • Osteoporosis
  • Hyperaldosteronism
  • Thrombocytopenic purpura
  • Infective endocarditis.
  • Threatened abortion.
  • Haemophilia.
DRUG INTERACTIONS:
  • Propylthiouracil and valproic acid may cause hypoprothrombinemia and increase the risk of bleeding; monitor patient for signs of bleeding.
  • Oral anticoagulants (i.e., warfarin)and Heparin are given together, each may contribute to an increase in PT and APTT should be taken into account.
  • Probenecid also increase and prolong the anticoagulant action of heparin.
  • OCP causes a hypercoaguable state.
  • Salicylates, other nonsteroidal anti-inflammatory agents, dextran, dipyridamole and ticlopidine interfere with platelet aggregation which increases the risk of bleeding. Use with caution and monitor patients for signs of hemorrhage.
CONTRAINDICATIONS:
  • Severe thrombocytopenia
  • Patients in whom suitable blood coagulation tests cannot be performed.
  • Hypersensitivity to heparin or any other product ingredients.
Advantages of LMWH over Heparin
  • Low molecular weight heparin inhibits Factor Xa
  • PT; aPTT monitoring is not required in LMWH
  • LMWH (Low Molecular Weight Heparin) has more favorable pharmacokinetics
Advantage Consequence
Better bioavailability and longer half-life after subcutaneous injection Can be given subcutaneously once or twice daily for both prophylaxis and treatment
Dose-independent clearance Simplified dosing
Predictable anticoagulant response Coagulation monitoring is unnecessary in most patients
Lower risk of heparin-induced thrombocytopenia Safer than heparin for short- or long-term administration
Lower risk of osteoporosis Safer than heparin for extended administration
HEPARIN INDUCED THROMBOCYTOPENIA
  • After exposure to heparin for 5-14 days; occurs before 5 days in those who were sensitized to heparin (PF4 antibodies disappear from circulation by -100 days following exposure) Usually not severe, counts rarely Not associated with bleeding
  • Laboratory monitoring of anti-factor Xa activity required
  • Formation of IgG antibodies to heparin-platelet factor 4 (PF4) complexes
  • More common after unfractionated heparin (UFH) therapy than low-molecular-weight heparin (LMWH)
  • 4 t's in HIT
  • Thrombocytopenia
  • Timing of platelet count drop
  • Thrombosis (Venous and arterial)
  • Other causes of thrombocytopenia not evident
  • HIT is diagnosed clinically; antibodies can be detected by ELISA
Treatment:
  1. Discontinue heparin
  2. Direct thrombin inhibitors argatroban and lepirudin are effective in HIT thrombosis
  3. Patients can be transitioned to warfarin, with treatment usually for 3-6 months
  4. Warfarin is contraindicated as initial treatment of HIT 
Exam Question
  • Protamine antagonism for heparin is Chemical
  • Pregnant patient with prosthetic valve should be switched to heparin in 36 weeks
  • Drug used in heparin overdose is Protamine sulphate
  • Lepirudin is recommended for the treatment of Heparin Induced thrombocytopenia
  • Haemorrhage secondary to heparin administration can be corrected by the administration of Protamine sulfate
  • NSAIDS have increased effect when given with heparin
  • Heparin causes Alopecia
  • Heparin Releases Lipoprotein Lipase & Non Teratogenic
  • LMWH shouldn't be used for treatment of Heparin Induced Thrombocytopenia (HIT) syndrome
  • Heparin Induced Thrombocytopenia (HIT) syndrome causes both arterial and venous thrombosis
  • Heparin Induced Thrombocytopenia (HIT) syndrome Occurs commonly in about a week of heparin therapy
  • Calcium is recomended as dietary supplements is recommended for a pregnant lady on Heparin
  • In Heparin induced thrombocytopenia (HIT) Thrombocytopenia is not severe usually & will not lead to bleeding. Marked thrombocytopenia < 20,000 is rare.
  • The antibody responsible for heparin induced thrombocytopenia is Antiheparin / PF4 antibody
  • The best suited anticogulant for osmotic fragility test is heparin
  • Heparin is a mucopolysacchride
  • Heparin Acts by activating anti-thrombin III
  • Heparin Requires aPTT monitoring in patient
  • Most commercial preparations of heparin now utilize pig intestinal slimes
  • For treatment of Deep vein thrombosis with heparin Activated partial thromboplastin time is monitored to adjust dosage
  • Low molecular weight heparin inhibits Factor Xa
  • Low molecular weight heparin therapy is associated with Less chances of bleeding & given as single dose per day
  • Low molecular weight heparin has Easy filterability by glomerular capillaries
  • As compared to unfractionated heparin, low molecular weight heparin Are absorbed more uniformly when given subcutaneously
  • LMWH (Low Molecular Weight Heparin) has higher and predictable bioavailability
  • PT; aPTT monitoring is not required in LMWH
  • LMWH (Low Molecular Weight Heparin) has more favorable pharmacokinetic
  • Heparin interferes with pH of ABG
  • Heparin is given in mesenteric vein thrombosis
  • For prophylaxis of deep vein thrombosis used is Heparin
  • Heparin inhibits the active form of factor X, XI, XII
  • Laboratory monitoring ofAnti-factor Xa activity is desirable with low molecular weight heparin therapy
  • Parameter which should be tested before starting heparin therapy is Activated partial thromboplastin time
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