Coagulation Tests

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Coagulation Tests

• "Coagulation." In Jacobs DS et al, ed. The
  Laboratory Test Handbook, 5th Edition. 2001
  327-358.
• Ri ???

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Coagulation Cascade
PT
VIIIa
PTT
Heparin
Hirudin, Argatroban
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Coagulation and Fibrinolysis
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Coagulation Tests in NTUH

• Screen test
• Bleeding Time (Duke method, Template method),
  Thrombin Time, PT, PTT
• Antiphospholipid syndrome
• Dilute Russell Viper Venom Time (dRVVT),
  Anti-Cardiolipin Ab, ACA, IgG, Anti-Phospholipid
  Ab, APA, IgG, Anti-Cardiolipin Ab, ACA, IgM
• Coagulation factor
• Factor I (Fibrinogen), II, V, VII, VWF, VIII,
  IX, X, Urea solubility test,

• Other coagulation inhibitor Study, VIII, XI, XII
• DIC profile
• Fibrinogen, FDP, 3P Test, D-dimer
• Fibrinolysis
• Euglobulin clot lysis time, Plasminogen activator
  inhibitor, Alpha2-antiplasmin
• PLT function
• Platelet aggregation
• Thrombosis
• APC Resistance, Protein S, Antithrombin III,
  Protein C, Plasminogen

NTUH portal website
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Activated Partial Thromboplastin Time (aPTT)

• Clotting time from factor XII to fibrin
  clot?intrinsic and common pathways
• aPTT? factor deficiency (VIII, IX, XI, XII),
  inhibitor (lupus anticoagulant, heparin, hirudin,
  or argatroban)
• Container blue top (3.2 citrate) tube

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Activated Partial Thromboplastin Time (aPTT)

• Collection Deliver tubes immediately to the
  laboratory
• ? factor VIII may degrade?PTT?
• ? platelets release platelet factor 4 (PF4) which
  neutralizes heparin ?PTT?
• ? from a peripheral vein, avoiding the heparin,
  hirudin, or argatroban infusion site

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Activated Partial Thromboplastin Time (aPTT)

• Causes for Rejection Specimen received more than
  4 hours after collection, tubes not filled,
  clotted specimens, visible hemolysis
• Turnaround Time lt1 day often lt1 hour if
  requested stat. The PT and PTT are the most
  readily available coagulation tests.

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Activated Partial Thromboplastin Time (aPTT)

• Reference Interval 20-25 to 32-39 seconds.
  Prolong in newborns. Up to 55 seconds at birth,
  and gradually decreases into the adult normal
  range by the age of 6 months. However, newborns
  and infants do not normally experience bleeding,
  because a balance between procoagulants and
  natural anticoagulants is maintained.
• Critical Values gt100-150 seconds

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Activated Partial Thromboplastin Time (aPTT)

• Limitations
• ? single factor deficiency, below 15 to 45
  before the PTT prolongs
• ? more sensitive to intrinsic pathway factor
  deficiency than to common pathway factor
  deficiency
• ? very high doses of heparin (cardiac bypass
  surgery) activated coagulation time (ACT) instead

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Activated Partial Thromboplastin Time (aPTT)

• Methodology
• ? reagent (phospholipid with an activator such as
  silica, celite, kaolin, ellagic acid) and calcium
  are added
• ? measure clot formation time
• ? partial phospholipid without tissue factor

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Prothrombin Time (PT)

• Clotting time from factor VII to fibrin
  clot?extrinsic and common pathways
• PT? fibrinogen or factors II, V, VII, or X
  deficiency, therapeutic anticoagulants (heparin,
  hirudin, or argatroban)
• Container Blue top (3.2 sodium citrate) tube

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Prothrombin Time (PT)

• Collection heparin prolongs the PT to a lesser
  extent than PTT. Hirudin and argatroban prolong
  the PT and PTT.
• ? directly from a peripheral vein, avoiding the
  heparin, hirudin or argatroban infusion site.
• Causes for Rejection Specimen received more than
  24 hours after collection, tube not filled,
  clotted specimen, visible hemolysis

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Prothrombin Time (PT)

• Reference Interval 10-12 to 12-14 seconds.
  Prolong in newborns. Up to 16 seconds at birth,
  and gradually shortens into the adult normal
  range by the age of 6 months.
• Critical Values gt30 seconds

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Prothrombin Time (PT)

• Limitations single factor deficiency
• Methodology Reagent called thromboplastin
  (phospholipid with tissue factor and calcium)
  added, measure clot formation time.
• Vitamin K trial may be performed with an
  unexplained PT prolongation. If vitamin K
  deficiency, the PT becomes normal or
  significantly shorter within 12-24 hours after
  vitamin K administration.

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Prothrombin Time (PT)

• Monitoring warfarin international normalized
  ratio (INR), therapeutic goal is an INR of 2-3.
• ? INR patient PT/normal PTISI
• ? international sensitivity index (ISI), varies
  in reagents

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Effects of Factor Deficiencies on PT and PTT

• PTT Prolonged, PT Normal Deficiencies of factor
  VIII, IX, XI, and/or XII (intrinsic pathway)
• PT Prolonged, PTT Normal Deficiency of factor
  VII (extrinsic pathway), mild-to-moderate
  deficiencies of factor II, V, X, and/or
  fibrinogen (common pathway)
• Both PT and PTT Prolonged Deficiencies of factor
  II, V, X, and/or fibrinogen (common pathway),
  Multiple factor deficiencies

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Disseminated Intravascular Coagulation(DIC)
Screen

• D-dimer or fibrin degradation products (FDP),
  prothrombin time (PT), activated partial
  thromboplastin time (PTT), platelet count, and
  fibrinogen. These tests are not specific for DIC.
• Specimen Plasma (and whole blood for platelet
  count and peripheral blood smear)

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Disseminated Intravascular Coagulation(DIC) Screen

• Limitation D-dimer and FDP() with physiologic
  clot formation, lysis, and liver disease
• DIC is a common acquired coagulation disorder
  resulting from excessive activation of the
  coagulation system, usually due to massive tissue
  injury, sepsis, or certain pregnancy
  complications.

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Disseminated Intravascular Coagulation(DIC) Screen

• disseminated microvascular thrombi ?consumes
  platelets, coagulation factors, and natural
  anticoagulants ?PT, PTT prolongations, bleeding
• Reference value FDPlt 5.0 ug/ml, D-Dimerlt324 ug/L

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D-Dimers and Fibrin Degradation Products (FDP)

• Plasmin degrades fibrin clots into D-dimers and
  fibrin degradation products (FDP).
• Limitations elevate whenever the coagulation and
  fibrinolytic systems are activated. High
  rheumatoid factor (RF) levels may cause
  false-positive result.

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Coagulation and Fibrinolysis
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D-Dimers and Fibrin Degradation Products (FDP)

• Methodology semiquantitative or quantitative
  immunoassays
• D-dimer is a specific FDP formed only by plasmin
  degradation of fibrin, not of intact fibrinogen.
• D-Dimer and FDP() DIC or thrombosis (DVT, PE
  and MI), liver disease, postoperatively,
  significant bleeding, hemodialysis, eclampsia,
  sickle cell crisis, cancer, pregnancy

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Thanks for your attention!