Test ID: THRMP
Thrombophilia Profile

Evaluating patients with thrombosis or hypercoagulability states

Detecting a lupus-like anticoagulant; dysfibrinogenemia; disseminated intravascular coagulation/intravascular coagulation and fibrinolysis

Detecting a deficiency of antithrombin, protein C, or protein S

Detecting activated protein C resistance (and the factor V R506Q [Leiden] mutation if indicated)

Detecting the prothrombin G20210A mutation

Initial testing includes: prothrombin time (PT); activated partial thromboplastin time (APTT); dilute Russells viper venom time (DRVVT); thrombin time (bovine); fibrinogen; D-dimer; soluble fibrin monomer; antithrombin activity; protein C activity; protein S antigen, free; prothrombin G20210A mutation; activated protein resistance V; and, if appropriate, special coagulation interpretation.

If PT is > or =14 seconds, PT mix will be performed.

If APTT is >36 seconds, APTT mix will be performed.

If APTT mix is >36 seconds with no evidence of heparin in samples, platelet neutralization procedure will be performed.

If DRVVT ratio is > or =1.2, DRVVT mix will be performed.

If DRVVT mix ratio is > or =1.2, DRVVT confirmation will be performed.

If thrombin time is >23 seconds, reptilase time will be performed.

If protein S antigen, free is <65% for males and females > or =50 years of age and <50% for females <50 years of age, protein S antigen, total will be performed.

If protein C activity is <70% with no evidence for an acquired decrease in protein C activity, protein C antigen may be performed.

If antithrombin activity is <80% with no evidence of an acquired decrease in antithrombin activity, antithrombin antigen will be performed.

If activated protein C resistance (APC) ratio is <2.3 or baseline APC APTT is prolonged, factor V leiden (R506Q) mutation analysis will be performed.

If appropriate, protein S activity, plasminogen, coagulation factor assays, or Staclot LA will be performed at an additional charge to clarify significant abnormalities in the screening clotting times.

If factor VIII result is <55%, the factor VIII inhibitor screen may be performed along with the Bethesda titering assay, if inhibitor screen is positive.

See Thrombophilia Profile algorithm in Special Instructions.

• Coagulation Studies
• Informed Consent for Genetic Testing
• Coagulation Patient Information Sheet
• Thrombophilia Profile

PTC/6599, PTMX/9053, APTTB/6548, APTTM/9118, DRVT/80340, TT/9059, RPTL/9078, STLA/82756, APCRV/81967, DRVTM/32467, DRVTC/32468: Clot-Based Assay

FIBC/80343: Clauss Methodology

DIRM/6625, PSF/80338, PST/80994, ATTI/9031: Automated Latex Immunoassay (LIA)

SFM/6600: Immunoturbidimetric

ATTF/9030, CFX/9339: Chromogenic Assay

PSGN/9079: Amidolysis of Chromogenic Substrate

S_FX/80775: Clot-Based End point Thromboplastin (APTT) Test System

F5DNA/81419, PTNT/81742: Direct Mutation Analysis

PNP/8866: Activated Partial Thromboplastin Time (APTT) Mixing Test

F_2/9121, FACTV/9054, F_7/9055, F_10/9066: Prothrombin Clot-Based Assay

F8A/9070, F_9/9065, F_11/9067, F_12/9069: Activated Partial Thromboplastin Time Clot-Based Assay

PCAG/9127: Enzyme Linked Immunosorbent Assay (ELISA)

IBETH/7288, F8IS/7289: Clot-Based Assay

See Coagulation Studies in Special Instructions.

Forms:

1. Coagulation Patient Information Sheet (Supply T675) in Special Instructions

2. New York Clients-Informed consent is required. Please document on the request form or electronic order that a copy is on file. An Informed Consent for Genetic Testing (Supply T576) is available in Special Instructions.

Blood and plasma are required.

Specimen Type: Whole blood

Container/Tube: 

Preferred: Yellow top (ACD)

Acceptable: EDTA, sodium citrate

Specimen Volume: 6 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Do not transfer blood to other containers.

3. Label specimen as whole blood.

Specimen Type: Platelet-poor plasma

Collection Container/Tube: Light-blue top (citrate)

Submission Container/Tube: Plastic vials

Specimen Volume: 6 mL in 6 plastic vials each containing 1 mL

Collection Instructions:

1. Specimen must be drawn prior to factor replacement therapy.

2. Spin down, remove plasma, and spin plasma again.

3. Freeze specimens immediately at < or =-40 degrees C, if possible.

4. Label specimens as plasma.

5. Send specimens in the same shipping container.

Additional Information:

1. Double-centrifuged specimen is critical for accurate results as platelet contamination may cause spurious results.

2. Patient should not be receiving Coumadin or heparin.

3. If priority specimen, mark request form, give reason, and request a call-back.

Thrombophilia is defined as an acquired or familial disorder associated with thrombosis. The clinical presentation of an underlying thrombophilia may include venous thromboembolism (deep vein thrombosis, pulmonary embolism, superficial vein thrombosis), recurrent miscarriage, and complications of pregnancy (eg, severe preeclampsia, abruptio placentae, intrauterine growth restriction, stillbirth). Other possible clinical presentation includes arterial thrombosis (especially among patients <50 years of age with no other risk factors for atherosclerotic arterial occlusive disease (diabetes mellitus, hypercholesterolemia, hypertension, or tobacco smoking) and aseptic necrosis of bone (eg, femoral head mandible). Demographic or environmental exposures that compound the risk of venous thromboembolism among persons with a thrombophilia include increasing age, male gender, obesity, surgery, trauma, hospitalization for medical illness, malignant neoplasm, prolonged immobility during travel (eg, prolonged airplane travel), oral contraceptive use, estrogen therapy (both oral and transdermal), tamoxifen and raloxifene therapy, and infertility drugs. Central venous catheters and transvenous pacemaker wires increase the risk for upper extremity deep vein thrombosis; this risk is unrelated to thrombophilia.

Inherited thrombophilias include:

-Deficiency due to reduced plasma protein level or dysfunctional protein of:

 - Antithrombin

 - Protein C

 - Protein S

-Dysfibrinogenemias (rare)

-Activated protein C resistance due to the factor V R506Q (Leiden) mutation

-Prothrombin G20210A mutation

Acquired thrombophilias include a lupus-like anticoagulant (antiphospholipid antibodies) and disseminated intravascular coagulation/intravascular coagulation and fibrinolysis (DIC/ICF). DIC/ICF may cause thrombotic as well as hemorrhagic events. Positive tests for DIC/ICF can also occur as consequences of thrombosis.

Acquired deficiencies of fibrinogen, protein C, protein S, and antithrombin may be found in conjunction with liver disease (they are produced by the liver) or DIC/ICF and are of uncertain significance with respect to thrombosis risk.

Acquired deficiencies of protein C and protein S are also found in liver patients treated with oral anticoagulants (eg, warfarin, Coumadin) since both of these proteins are dependent upon the action of vitamin K for normal function.

Acquired protein S deficiency also occurs in thrombotic thrombocytopenic purpura, pregnancy or estrogen therapy, nephrotic syndrome, and sickle cell anemia. In acute illness, the level of acute-phase reactants rise (including C4b binding protein, which binds and inactivates protein S in the plasma) and the portion of bound protein S also rises leaving a lower proportion of free protein S. The significance of acquired protein S deficiency with respect to thrombosis risk is unknown.

An interpretive report will be provided.

An interpretive report will be provided.

To obtain the most useful information, this testing is best performed in medically stable patients who are not receiving oral vitamin K inhibitor (eg, warfarin, Coumadin), heparin, low-molecular-weight heparin, hirudin (Refludan), argatroban, fibrinolytic agents (eg, streptokinase, tissue plasminogen activator), or platelet GPIIbIIIa (alpha IIb beta3) inhibitors (abxicimab [ReoPro], tirofiban, aggrastat). However, useful information can be obtained in patients receiving anticoagulation therapy.

College of American Pathologists Consensus Conference XXXVI: diagnostic issues in thrombophilia. Arch Pathol Lab Med. 2002;126:1277-1433

See individual test IDs.

Monday through Friday

81240-F2 (prothrombin, coagulation factor II) (eg, hereditary hypercoagulability) gene analysis, 20210G->A variant

85300-AT activity

85303-Protein C activity

85306-Protein S antigen, free

85307-Activated protein resistance V

85366-Soluble fibrin monomer

85379-D-Dimer

85384-Fibrinogen

85390-26-Special coagulation interpretation

85610-PT       

85613-DRVVT

85670-Thrombin time

85730-APTT

81241-F5 (coagulation factor V) (eg, hereditary hypercoagulability) gene analysis, Leiden variant (if appropriate)

85210-Factor II (if appropriate)

85220-Factor V (if appropriate)

85230-Factor VII (if appropriate)

85240-Factor VIII (if appropriate)

85250-Factor IX (if appropriate)

85260-Factor X (if appropriate)

85270-Factor XI (if appropriate)

85280-Factor XII (if appropriate)

85301-Antithrombin antigen (if appropriate)

85302-Protein C antigen (if appropriate)

85305-Protein S antigen, total (if appropriate)

85306-Protein S activity (if appropriate)

85335-Bethesda titer (if appropriate)

85335-Factor VIII inhibitor screen (if appropriate)

85420-Plasminogen activity (if appropriate)

85597-Platelet neutralization for lupus inhibitor (if appropriate)

85598-Staclot LA (if appropriate)

85611-PT mix 1:1 (if appropriate)

85613-DRVVT mix (if appropriate)

85613-DRVVT confirmation (if appropriate)

85635-Reptilase time (if appropriate)

85732-APTT mix 1:1 (if appropriate)