Coagulation Lecture 2 Flashcards

1
Q

What 2 things are used in Anticoagulation Therapy?

A
  1. Heparin

2. Coumadin

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2
Q

Heparin (Natural)

A
  • Naturally present in the body in low concentrations
  • produced by mast cells and basophils
  • produced as heparin and “heparin like” molecules
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3
Q

Heparin (Artificial)

A
  • 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
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4
Q

Low Molecular Weight heparin

A
  • Prepared from unfractionated heparin
  • Average Molecular size is 5,000 daltons
  • Administered subcutaneously
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5
Q

When is Therapeutic drug monitoring necessary?

A

Patients with:
-unusually low or high body weight

  • renal failure
  • pediatric patients
  • patients with medical conditions that may influence heparin metabolism
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6
Q

What does heparin do?

A
  • prevents the formation of clots and growth of existing blood clots
  • will not destroy clots that have already formed
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7
Q

Describe heparin’ actions

A
  • 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
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8
Q

Vitamin K action (before Coumadin)

A
  • 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
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9
Q

Coumadin (anti vitamin k action)

A
  • 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

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10
Q

Coumadin contd

A
  • 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
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11
Q
Prothrombin time (PT) 
Principle
A

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

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12
Q

What is Prothrombin time

A

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

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13
Q

What does PT measure the functional activity of?

A

Extrinsic and Common Pathways

**also method of choice for monitoring anticoagulant therapy by vit K antagonists

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14
Q

What does PT test for?

A
  • Generation of thrombin
  • conversion of fibrinogen to fibrin
  • screens for deficiencies of Factors I, II, VII and X
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15
Q

What are Coumadin and Warfarin used for?

A

-Used to prevent thrombosis and pulmonary embolism

Increased PT = fatal hemorrhage
Decreased PT = embolism

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16
Q

Reagents used in PT test

A

Calcium Chloride –usually combined with thromboplastin reagent

17
Q

What is ISI and what is it used for?

A

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
18
Q

PT controls

A
  • 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
19
Q

What specimen is used for PT test

A
  • 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
20
Q

how much anticoagulant should PT tube (blue) have in it?

A
  • 3.2% sodium citrate (1:9 citrate to blood)
21
Q

PT Specimen processing

A
  • 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
22
Q

Normal PT values

A

10-13 seconds

23
Q

INR (international normalized ratio)

A
  • 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
24
Q

INR Con’t

A
  • 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

25
Q

INR normal range

A

0.85-1.15

26
Q

INR Formula

A

INR = (patient PT result ÷ mean normal PT) ^ISI

**INR is a better method for reporting all PT values

27
Q

Activated Partial Thromboplastin TIme (APPT) Principle

A

An activator is mixed with a platelet substitute (thromboplastin) before the addition of the plasma being tested; only a partial component of thromboplasti is used

** Based on the observation that when whole thromboplastin is used, the times obtained for hemophillic plasma are the same as for normal plasma

***With partial thromboplastin or platelet substitute, the times obtained for hemophilic plasma are much longer

28
Q

APTT

A
  • Best procedure for detection of deficiencies in the Intrinsic and common coag pathways
  • used to manage pts on heparin anticoag therapy
  • Measure deficiencies in factors VIII, IX, XI, and XII but can detect deficiencies in all factors except VII and XIII
29
Q

What reagents are used for APTT

A
  • Partial thromboplastin (phospholipid substitute)
  • Kaolin (ensures activation of coag factors)
  • CaCl (used by some manufacturers instead of KAolin for activation of coag factors)

Controls, specimen, specimen prep all same as PT

30
Q

APTT normal values

A

25 to 40 seconds