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
Reagents used in PT test
Calcium Chloride –usually combined with thromboplastin reagent
What is ISI and what is it used for?
ISI = International Sensitivity Index
- Used to standardize PT results
- Enables comparison of PT results
- ISI is an indicator of the responsiveness of the PT testing system to Vit K deficiencies
PT controls
- Lab establishes reference range
- limits vary with brand used
- controls detect the deterioration of reagents and improper incubation temp
- at LEAST 2 levels of controls used
- Controls are run in duplicate and must agree within specific limits established for the rest
What specimen is used for PT test
- clean, rapid venipuncture must be used to prevent the sample from being contaminted with tissue thromboplastin which can alter results
- hemolysis must be avoided
- silicon coated glass tube or plastic tube used
- temp affects labile factors V and VIII
how much anticoagulant should PT tube (blue) have in it?
- 3.2% sodium citrate (1:9 citrate to blood)
PT Specimen processing
- Specimens must be centrifuged nd separated from the cells within 1 hr of collection
- Hemolyzed specimens must be rejected
- can be refrigerated for 4 hrs but if testing is delayed more than 4 hrs, frozen may be kept up to 1 week
Normal PT values
10-13 seconds
INR (international normalized ratio)
- used to report standardized results for PT assays for pts who are receiving oral anticoagulant therapy
- Devised by WHO to ensure that pts on long term anticoag. therapy that had PT testing performed in different labs would yield comparable results
INR Con’t
- INR becomes elevated with deficiencies in the extrinsic pathway
**deficiencies most commonly results from use of nanticoag. therapy (depletes Vit K dep. factors) and liver disease
