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

Bleeding Disorders

Coagulation Factor Inibitors

Follow-up to Abnormal PT and/or PTT

Inhibitors

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Von Willebrand Disease

Initial profile

• Ristocetin response curve
• von Willebrand factor multimers
  (performed in outside laboratory)

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Platelet Function: Whole Blood Lumi-aggregometry

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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Fibrinolysis Assays

• 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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Disseminated Intravascular Coagulation

• Partial thromboplastin time (PTT)
• Prothrombin time (PT)
• Fibrinogen activity
• Quantitative D-dimer

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Anticoagulant Therapy Monitoring

Warfarin (Coumadin)

• Partial thromboplastin time (PTT)

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Complete List of Risk Factors for Venous Thrombosis

• 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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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
• 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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Lupus Anticoagulant (LA) with Follow-Up Assays

Two LA screens are used

• 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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Coagulation Mechanism

• 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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Coagulation Mechanism Controls

• 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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