Coagulation Lecture 2 Flashcards
What 2 things are used in Anticoagulation Therapy?
- Heparin
2. Coumadin
Heparin (Natural)
- Naturally present in the body in low concentrations
- produced by mast cells and basophils
- produced as heparin and “heparin like” molecules
Heparin (Artificial)
- Artificially derived from mucosal tissues of pig intestine (porcine) and cow lung (bovine)
- Unfractionated heparin
- Average molecular size 12,000-13,000 daltons
- Administered by IV and subcutaneously
Low Molecular Weight heparin
- Prepared from unfractionated heparin
- Average Molecular size is 5,000 daltons
- Administered subcutaneously
When is Therapeutic drug monitoring necessary?
Patients with:
-unusually low or high body weight
- renal failure
- pediatric patients
- patients with medical conditions that may influence heparin metabolism
What does heparin do?
- prevents the formation of clots and growth of existing blood clots
- will not destroy clots that have already formed
Describe heparin’ actions
- Binds with the enzyme inhibitor anti-thrombin
- acts as a catalyst; accelerates the action of antithrombin
- antithrombin must be present for heparin to work
- half life of 4 hrs
- monitored with APPT
- heparin bound antithrombin irreversibly binds to factors XIIa, XIa, IXa and II; inhibits their activity
Vitamin K action (before Coumadin)
- Vitamin K facilitates The binding and acceleration of the action of carboxylase
- carboxylase add a carboxyl group onto coagulation factors II, VII, IX and X
- Extra carboxyl grp makes these factors biologically active
- 1 Vit K molecule can be reused for carboxylation of multiple molecules
Coumadin (anti vitamin k action)
- interferes with the recycling of Vit K
- 1 Vit K molecule helps add a carboxyl grp to only 1 factor rather than being able to modify several factors through its recycling
• Coumadin is not a True anticoagulant, it leads to the production of dysfunctional factors with impaired coagulant activity
• inhibits vitamin K dependent factors:
II, VII, IX and X
Coumadin contd
- VII is affected the most due to shortest half life
- oral administration
- Coumadin half life: 31-58 hrs
- takes 5-7 days of therapy to maintain stable anticoagulant effect
- Aspirin, barbiturates, oral hypoglycemic agents and anti-inflammatory drugs may react with Coumadin and adversely affect therapy
- therapy is monitored with the PT and INR
Prothrombin time (PT) Principle
When an optimal amount of calcium and an excess of thromboplastin are added to decalcified plasma, the rate of coagulation depends on the concentration of prothrombin in the plasma
What is Prothrombin time
Prothrombin Time (PT) is the time required for plasma to clot after an excess of thromboplastin and an optimal concentration of calcium have been added
What does PT measure the functional activity of?
Extrinsic and Common Pathways
**also method of choice for monitoring anticoagulant therapy by vit K antagonists
What does PT test for?
- Generation of thrombin
- conversion of fibrinogen to fibrin
- screens for deficiencies of Factors I, II, VII and X
What are Coumadin and Warfarin used for?
-Used to prevent thrombosis and pulmonary embolism
Increased PT = fatal hemorrhage
Decreased PT = embolism