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Bleeding Disorders
Coagulation Factor Inhibitors
Von Willebrand Disease
Platelet Function: Whole Blood Lumi-aggregometry
Fibrinolysis Assays
Disseminated Intravascular Coagulation (DIC)
Anticoagulant Therapy Monitoring
Complete List of Risk Factors for Venous Thrombosis
Partial List for Patients on Heparin or Warfarin, or for Acute Patients Who Have Had a Thrombotic Event in the Past Ten Days
Lupus Anticoagulant (LA) with Follow-up Assays
Coagulation Mechanism
Coagulation Mechanism Controls


 




Intrinsic pathway assay

  • Partial thromboplastin time (PTT)

Extrinsic pathway assay

  • Prothrombin time (PT) & INR

Common pathway assays

  • Fibrinogen activity
  • Thrombin clotting time (TCT)
  • Reptilase time (not prolonged by heparin)

Factor assays

  • Fibrinogen activity
  • Prothrombin (II), V, VII, or X activity
    VIII, IX, XI, or XII activity
  • Factor XIII activity by urea solubility
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Follow-up to Abnormal PT and/or PTT

  • PTT mixing studies
  • PT mixing studies
Inhibitors

  • Lupus anticoagulant
  • Factor VIII inhibitor (Bethesda)
  • Factor IX inhibitor (Bethesda)
  • Inhibitors to all other factors
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Initial profile

  • Factor VIII activity
  • von Willebrand factor activity
    (AKA ristocetin cofactor)
  • von Willebrand factor antigen

Follow-up tests (when indicated)

  • Ristocetin response curve
  • von Willebrand factor multimers
    (performed in outside laboratory)
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Platelet aggregation and ATP release are measured using thrombin, collagen, arachidonic acid, and ristocetin as stimulators.  Requires at least 9 mL (three tubes) of whole blood with a minimum platelet count of 100   109/L. Specimen must be assayed within 3 hours of collection.

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  • Fibrinogen activity
  • Thrombin time (TCT)
  • Reptilase time
  • Euglobulin clot lysis time (ECLT)
  • Plasminogen activator inhibitor-1 (PAI-1, performed in outside laboratory)
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  • Partial thromboplastin time (PTT)
  • Prothrombin time (PT)
  • Fibrinogen activity
  • Quantitative D-dimer
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Warfarin (Coumadin)

  • Prothrombin time (PT) & INR

Standard heparin

  • Partial thromboplastin time (PTT)
  • Chromogenic anti-Xa heparin assay

LMWH (Enoxaparin, Tinzaparin)

  • Chromogenic anti-Xa heparin assay
Direct thrombin inhibitors: Argatroban, Lepirudin

  • Partial thromboplastin time (PTT)
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  • Lupus anticoagulant
  • Anti-cardiolipin antibody, IgG & IgM
  • Activated protein C resistance (APCR)
    • Factor V Leiden mutation assay if APCR ratio low
  • Prothrombin G20210A mutation
  • Factor VIII activity
  • Fasting homocysteine
  • Protein C activity
    • Antigen assay if low
  • Protein S activity
    • Antigen assay if low
  • Antithrombin activity
    • Antigen assay if low
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  • Lupus anticoagulant
  • Anti-cardiolipin antibody, IgG & IgM
  • Prothrombin G20210A mutation
  • Fasting homocysteine
  • Activated protein C resistance (APCR)
    • Factor V Leiden mutation assay if positive
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Two LA screens are used

  • LA sensitive PTT (PTT-LA)
  • Dilute Russell viper venom time (dRVVT)

Follow-up assays when the LA screen is positive

  • Thrombin time to R/O heparin
  • PTT-LA mixing study
  • StaClot-LA: PTT confirmatory test using hexagonal phase phospholipid neutralization procedure (PNP)
  • dRVVT mixing study
  • dRVVT confirmatory test (dRVVT ratio reported)
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  • Initiation phase on vascular cells: tissue factor (TF) exposed in injury or inflammation binds activated factor VII (VIIa). TF/VIIa activates IX and X (IXa, Xa). This is often called the extrinsic pathway.
  • Propagation phase on activated platelets: Activated XI (XIa) also activates IX. IXa and activated VIII (VIIIa) form VIIIa/IXa, or "tenase" that activates X. This is often called the "intrinsic" pathway.
  • Xa and activated V (Va) form Va/Xa "prothrombinase complex" that activates prothrombin to form thrombin.
  • Thrombin cleaves fibrinogen to form fibrin polymer, polymer is crosslinked by activated XIII (XIIIa). This is sometimes called the "common" pathway.
  • Trace thrombin activates plasma XIII, XI, VIII and V for positive feedback.

Click to enlarge
 




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  • Tissue factor pathway inhibitor (TFPI) neutralizes TF/VIIa.
  • Activated protein C (APC) + protein S inactivate Va and VIIIa.
  • Protein Z-dependent protease inhibitor (ZPI) inactivates Xa.
  • Antithrombin (AT) inactivates at multiple steps, especially Xa and thrombin.

Click to enlarge
 




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Test Interpetation & Therapy Menu:

Reference Intervals for Premature Infants | Reference Intervals for Full-term Infants | Reference Intervals for Children | UAB Reference Intervals For Adults | Biochemical Properties of the Coagulation Proteins | The Coagulation Cascade Mechanism | Dos and Don'ts in Coagulation Testing | Blood Specimen Management | UAB Hemostasis and Coagulation Test Menu | Thrombophilia |Anticoagulant Therapy Monitoring | Management of Bleeding | Management of Platelet Disorders | Glossary of Hemostasis Terms with Abbreviations


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