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Anticoagulants

Hemostasis

The mechanisms involved to stop bleeding are known as hemostasis. This includes four processes:

  1. Vasoconstriction
  2. Platelet plug formation
  3. Coagulation/Clot formation
  4. Clot becomes fibrous, remains as such, or dissolves

The injury is repaired, limiting blood loss and maintaining the patency of vessels.

This process can go the pathological way either leading to:

  1. Increased bleeding tendency
  2. Thromboembolic phenomenon

The blood fluidity is maintained by four factors:

  1. Circulation –continuous motion. Stasis may lead to coagulation disorders
  2. Smooth endothelial lining of blood vessels and negatively charged glycocalyx
  3. Naturally occurring anticoagulants and thrombolytics:
  1. Thrombomodulin binds endothelial vessels
  2. Binds thrombin and inactivates it
  3. Activates natural anticoagulant, protein C
  4. Presence of antithrombin III in blood, which inactivates many of the clotting factors II, IX, X, XI and XII and to some extent VII.
  5. Tissue plasminogen activator, released in endothelial injury, acts on plasminogen converting it to plasmin. Plasmin acts on fibrin and breaks it, thus having thrombolytic activity.

Endogenous anticoagulants include:

  1. Antithrombin
  2. Protein C –proteolysis of Va
  3. Protein S –proteolysis of VIII a

Blood Coagulation

Blood coagulation is maintained by clotting factors, inactive proteins present in the blood, which are activated in cascade manner.

Anticoagulants

Drugs preventing clotting (pathological thrombosis) by reducing coagubility of blood, are called anticoagulants.

Thrombosis

Thrombus is inappropriate activation of haemostatic mechanisms.

Arterial –main component platelet, fibrin less (anti-platelets preferred)

Venous –main component fibrin, platelet less (anti-coagulants preferred)

Fibrinolysis

Process of fibrin digestion by plasmin.

Plasminogen and plasmin have special kringles that bind exposed lysines or fibrin clot.

Inhibition of fibrinolysis

Endothelial cells synthesize and release plasminogen activator inhibitor (PA-1) which inhibits tissue plasminogen activator. Alpha 2 antiplasmin in blood binds to non-clot bound proteins, inactivating them.

Treatment of clotting abnormalities
  1. Drugs that interfere with clotting of blood
  2. Drugs that interfere with platelet aggregation
  3. If thrombosis, fibrinolytics

Classification

According to Use

Used In Vitro

1. Heparin

2. Ca+2 complexing agents / Ca+2 chelators

a. Na+ / K citrate

b. Na+ / K+ oxalate

c. EDTA (ethylenediamine tetra-acetic acid)

Used In Vivo

 

According to route of administration
Parenteral
1. Indirect Thrombin inhibitors

a. Unfractionated heparin

b. Low molecular weight heparin

–        Enoxaparin

–        Daltaparin

–        Tinzaparin

c. Synthetic heparin derivatives

–        Fondaparinux

d. Haparinoids

–        Heparan sulfate

–        Danaparoid

2. Direct Thrombin Inhibitors (DTIs)

–        Hirudin

–        Lepirudin

–        Bivalirudin

–        Argatroban

–        Melagatran

Oral
1. Vitamin K antagonists

a. Coumarin derivatives

–        Warfarin

–        Dicoumarol

–        Acenocumarol

b. Indandione derivatives

–        Phenindione

–        Diphendione

–        Anisindione

2. Direct Thrombin Inhibitors (DTIs)

–        Ximelagatran

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