Hypercoagulable States - Thrombophilia

Primary Author: Smock, Kristi J., MD.

  • Key Points
  • Diagnosis
  • Screening
  • Background
  • Lab Tests
  • References
  • Related Topics

The widespread use of numerous anticoagulants for a variety of diseases, including the newest direct oral anticoagulant agents, has created clinical dilemmas for both anticoagulant monitoring and the interpretation of coagulation testing. Evaluations for thrombophilia may demonstrate interference once heparin and/or warfarin or one of the new direct agents is administered, making interpretation of results difficult. The table below details possible interferences with coagulation parameters based on the specific drug administered.

Anticoagulants and Possible Coagulation Test Interferences

Anticoagulant

Unfractionated Heparin

Low-Molecular-Weight Heparin (LMWH)

Warfarin

Direct Thrombin Inhibitors Argatroban, bivalirudin (Angiomax), dabigatran (Pradaxa)

Direct Factor Xa Inhibitors Rivaroxaban (Xarelto), apixaban (Eliquis), edoxaban (Savaysa)

Common coagulation assays

PT/INR

Prothrombin Time/International Normalized Ratio 0030224

No effect~

No effect~

Prolonged

No effect/prolonged#

Prolonged#/no effect

aPTT

Partial Thromboplastin Time 0030235

Prolonged

No effect/prolonged

No effect/prolonged

Prolonged#/no effect

No effect/prolonged#

D-dimer

D-Dimer 0030057

No effect

No effect

No effect

No effect

No effect

Fibrinogen

Fibrinogen 0030130

No effect~

No effect~

No effect

No effect/underestimate#

No effect

Fibrinogen antigen

Fibrinogen Antigen 0030135

No effect

No effect

No effect

No effect

No effect

Reptilase time

Reptilase Time with Reflex to Reptilase Time 1:1 Mix 0030295

No effect

No effect

No effect

No effect

No effect

Thrombin time

Thrombin Time with Reflex to Thrombin Time 1:1 Mix 0030260

Prolonged

No effect/prolonged

No effect

Prolonged

No effect

Thrombotic risk assays

Activated protein C (APC) resistance

APC Resistance Profile 0030127

OR

APC Resistance Profile with Reflex to Factor V Leiden 0030192

No effect~

No effect~

No effect^

Possible false negative

Possible false negative

Antithrombin activity, IIa method

Antithrombin, Enzymatic (Activity) 0030010

No effect*

No effect*

No effect*

Overestimate#

No effect

Antithrombin antigen

Antithrombin, Antigen 0030015

No effect*

No effect*

No effect*

No effect

No effect

Protein C activity, clot-based

Protein C, Functional 0030113

No effect~/overestimate

No effect~/overestimate

Decreased

Overestimate#

Overestimate#

Protein C antigen

Protein C, Total Antigen 0030111

No effect

No effect

Decreased

No effect

No effect

Protein S activity

Protein S, Functional 0030114

No effect~/overestimate

No effect~/overestimate

Decreased

Overestimate#

Overestimate#

Protein S free antigen

Protein S Free, Antigen 0098894

No effect

No effect

Decreased

No effect

No effect

Protein S total antigen

Protein S, Total Antigen 0030112

No effect

No effect

Decreased

No effect

No effect

Lupus anticoagulants

DRVVT

Preferred test – Lupus Anticoagulant Reflexive Panel 0030181

OR

Dilute Russell Viper Venom Time (dRVVT) with Reflex to dRVVT 1:1 Mix and Confirmation 0030461

No effect~/prolonged

No effect~/prolonged

No effect/prolonged

No effect/prolonged#

Prolonged/no effect

DRVVT confirmatory ratio

Dilute Russell Viper Venom Time (dRVVT) with Reflex to dRVVT 1:1 Mix and Confirmation 0030461

No effect~/false positive

No effect~/false positive

No effect/possible false positive^

Possible false positive

Possible false positive

Hexagonal phospholipid neutralization

Preferred test – Lupus Anticoagulant Reflexive Panel 0030181

OR

Hexagonal Phospholipid Neutralization 0030064

No effect~/false positive

No effect~/false positive

No effect/possible false positive^

Possible false positive

Possible false positive

Platelet neutralization procedure

Preferred test – Lupus Anticoagulant Reflexive Panel 0030181

No effect~/false positive

No effect~/false positive

No effect/possible false positive^

Possible false positive

Possible false positive

Fibrinolytic assays

Alpha-2-antiplasmin

Alpha-2-Antiplasmin, Activity 0098727

No effect

No effect

No effect

No effect

No effect

Fibrin/fibrinogen degradation products

Fibrin/Fibrinogen Degradation Split Products, Plasma 2006491

No effect

No effect

No effect

No effect

No effect

Plasminogen activator inhibitor-1

Plasminogen Activator Inhibitor 1, Activity 0098781

No effect

No effect

No effect

No effect

No effect

Plasminogen activity

Plasminogen Activity 0030190

No effect

No effect

No effect

No effect

No effect

tPA antigen

Tissue Plasminogen Activator, Antigen 0099187

No effect

No effect

No effect

No effect

No effect

Soluble fibrin monomer

Soluble Fibrin Monomer 0030126

No effect

No effect

No effect

No effect

No effect

Other assays

ADAMTS-13

ADAMTS13 Activity 0030056

No effect

No effect

No effect

No effect

No effect

Factor assays, clot-based$

Factor II, Activity (Prothrombin) 0030007

Factor V, Activity 0030075

Factor VII, Activity 0030080

Factor VIII, Activity 0030095

Factor VIII Activity with Reflex to Bethesda Quantitative, Factor VIII 0030026

Factor IX, Activity 0030100

Factor IX Activity with Reflex to Bethesda Quantitative, Factor IX 0030032

Factor X, Activity 0030105

Factor XI, Activity 0030110

Factor XII, Activity 0030115

Factor XIII Activity 2006182

Factor XIII, Qualitative, with Reflex to Factor XIII 1:1 Mix 2002819

No effect/underestimate+

No effect/underestimate+

No effect/decreased vitamin K-dependent factors

Underestimate#

Underestimate#

von Willebrand factor antigen and activity

von Willebrand Factor Antigen 0030285

von Willebrand Factor Activity (Ristocetin Cofactor) 0030250

No effect

No effect

No effect

No effect

No effect

* Drug does not interfere with assay, but presence may affect analyte

^ Interference in high concentrations of anticoagulant medication

~ Reagent contains heparin neutralizer; effect may be seen with supratherapeutic drug levels

# Drug, concentration, and reagent-dependent

+ aPTT-based factor assays (factors 8, 9, 11, 12) are more likely to demonstrate assay interference and underestimation than PT-based factors assays (factors 2, 5, 7, 10). The effect is more pronounced with unfractionated heparin than with LMWH.

$ Presence of unfractionated heparin, LMWH, direct thrombin inhibitors, and direct Xa inhibitors may produce inhibitory patterns and may prevent accurate quantitation (underestimation) of factor activity. May also interfere with and cause false-positive Bethesda assays (false-positive coagulation factor inhibitor). Chromogenic Factor XIII activity may also be falsely decreased in the presence of direct thrombin inhibitors.

Sources: Linkins, L, 2002; Molinaro, R, 2008; Genzen, J, 2005; Hillarp, A, 2010; Adcock, DM, 2015; Dale, BJ, 2014; Tsutsumi, Y, 2014

Indications for Testing

  • Patient with new or recurrent venous thromboembolism (VTE) without obvious risk factors (see Differential Diagnosis, below)
    • Abnormalities may be identified in a significant number of patients; however, identification of an abnormality may not predict risk of recurrence or alter therapeutic plan
    • Use when the results will impact management of the patient or patient family members
    • Do not order testing for first DVT in the setting of known etiology (ASCP's Pathology-Related Choosing Wisely Recommendations, 2015 [Society for Vascular Medicine])
    • Do not test during acute episode – results do not alter therapy and some results may be inaccurate
  • Situations where testing should be considered (College of American Pathologists [CAP], American College of Medical Genetics [ACMG])
    • Idiopathic thrombosis in patient ≤50 years of age
    • Recurrent thrombosis
    • Unusual sites of thrombosis in the absence of risk factors
    • First-degree relatives with thromboses
    • Thrombotic event during pregnancy, or while taking oral contraceptives or hormone replacement therapy

Laboratory Testing

  • Based on family and patient history – nongenetic tests may be altered by anticoagulant therapy or acute phase reaction due to clot
  • Children are at very low risk for thrombophilia and should only have testing performed in consultation with hematologist (ACMG)
  • Consider acquired disorders such as antiphospholipid syndrome
  • If testing pursued, consider the following combination (ACMG)
    • Activated protein C resistance (with or without reflex to factor V Leiden [FVL] mutation); factor V R2 A4070G mutation
    • Prothrombin mutation
    • Antithrombin (AT) activity
    • Protein C activity
    • Free protein S
    • Testing for less-common disorders may be considered if results are uninformative and additional testing is considered necessary
  • The following tests are not recommended
    • Factor VIII activity (testing other factor activities such as FVIII and FIX is controversial and not currently recommended)
    • Factor XIII (F13A1) V34L variant – presence of variant associated with decreased/reduced risk for deep vein thrombosis, myocardial infarction and coronary artery disease in Caucasians
  • Before making a definitive diagnosis of an inherited thrombophilia, consider repeating abnormal functional or antigenic testing
    • False positives and false negatives may encourage inappropriate therapies or follow-up planning
    • Low results can be obtained due to patient condition/biologic variability, medications, and assay variability or interference
    • Normal ranges vary by age and gender and must be considered when interpreting results

Differential Diagnosis

  • Acquired thrombophilia is more common than inherited thrombophilia and its causes and should be considered when evaluating patients with thrombosis
  • Population testing is not recommended for unselected patients

Hypercoagulable states may be acquired or inherited. Hereditary thrombophilia is a genetically determined increased risk for thrombosis and thromboembolism.

Epidemiology

  • Adults
    • Incidence – 30-500/10,000 for all disorders
    •  Ethnicity – slightly higher among African Americans; lower in Asian and Native Americans
  • Pediatrics
    • Incidence – 0.05-14/100,000
    • Sex – M<F
    • Age – peak in neonates and infants <1 year
      • Second peak in puberty

Etiologies

Most common thrombophilias

  • Factor V Leiden
    • Genetics and pathophysiology
      • Factor V Leiden (FVL) mutation of the F5 gene is the most common inherited thrombophilia
        • Accounts for more than 90% of patients with activated protein C resistance (APC-R)
          • During normal hemostasis, APC limits clot formation by proteolytic inactivation of factors Va and VIIIa
          • FVL prevents inactivation of factor Va by APC at the normal rate, increasing the risk for thrombosis
        • Functional tests for APC-R are generally used to screen for FVL
          • DNA tests are used to confirm positive screening tests and to differentiate between heterozygotes and homozygotes
      • Autosomal dominant inheritance
        • Heterozygotes have a five- to tenfold increased risk
        • Homozygotes have a 50- to 100-fold increased risk
    • Clinical presentation
      • Venous thromboembolism (VTE) is the most common type of thrombotic event
        • Recurrent VTE (pulmonary embolism, DVT) is uncommon in heterozygotes unless additional risk factors are present
        • Increased risk of recurrent VTE in homozygotes
      • Pregnancy complications – recurrent miscarriage in the second trimester
    • Additional risk factors
      • Presence of F5 R2 (A4070G) mutation with FVL increases risk of thrombotic event tenfold
      • Patients with FVL mutation and recurrent episodes of thrombosis often have more than one genetic risk factor (eg, concomitant prothrombin G20210A mutation of F2, protein C deficiency, homocystinemia)
      • Acquired factors such as pregnancy, oral contraceptives, hormone replacement therapy, and immobilization increase the risk​
  • Prothrombin G20210A
    • Genetics and pathophysiology
      • Prothrombin G20210A mutation of the F2 gene is the second most common inherited thrombophilia
        • Results in elevated levels of plasma prothrombin leading to hypercoagulability (gain of function)
        • Detected using DNA tests
          • Factor II (prothrombin) activity testing may not identify the disease and should not be used for diagnosis
      • Autosomal dominant inheritance
        • Variable penetrance
          • Many patients who are either heterozygous or homozygous for G20210A do not experience VTE
        • Heterozygosity causes a two- to fourfold increase in thrombotic risk
        • Homozygosity is rare and increases thrombotic risk above that observed in G20210A heterozygotes
    • Clinical presentation
      • VTE
      • Pregnancy complications – preeclampsia, placental abruption
    • Additional risk factors
      • Combined heterozygosity for both prothrombin G20210A and FVL mutations leads to thrombophilia with earlier onset, higher rate of recurrence, and more severe thrombotic events than either mutation alone
      • Increased risk of thrombosis associated with oral contraceptive use and pregnancy

Less common thrombophilias

  • Increased clotting factors
    • Elevated factor VIII (FVIII) levels are often found in patients with venous thrombosis, but routine testing is controversial
  • Protein C deficiency
    • Genetics and pathophysiology
      • Protein C is a vitamin K-dependent plasma anticoagulant activated to APC by thrombin-thrombomodulin, which then inactivates factors Va and VIIIa
      • Inherited protein C deficiency is uncommon
        • Two forms
          • Type I – quantitative
          • Type II – qualitative
      • Autosomal dominant inheritance
        • Highly variable phenotypic expression
      • Functional assays preferred for diagnosis (rather than antigenic assays)
        • Protein C levels vary with age
      • Decreased levels in acute thrombotic states, disseminated intravascular coagulation (DIC), liver diseasemalnutrition (vitamin K deficiency), and with warfarin therapy
      • Increased levels in diabetes, nephrotic syndrome, pregnancy, and with oral contraceptive use
        • Elevated FVIII levels may result in falsely decreased values for some functional assays
        • Heparin and direct thrombin inhibitors may result in falsely elevated values for some functional assays
    • Clinical presentation
      • Additional risk factors likely necessary to provoke thrombosis (eg, infection – VZV, meningococcal)
      • VTE in heterozygotes
      • Neonatal purpura fulminans (DIC) in homozygous infants – widespread thromboses with hemorrhagic skin necroses
      • Warfa​rin-induced skin necrosis is rarely seen
  • Protein S deficiency
    • Genetics and pathophysiology
      • Protein S is a vitamin K-dependent plasma anticoagulant that acts as a cofactor for activated protein C and exists in two forms
        • Free protein S – 40% of the total; physiologically active
        • Bound protein S (attached to C4b-binding protein) – 60% of the total; no anticoagulant activity
      • Inherited protein S deficiency is uncommon
        • Three forms
          • Type I – quantitative
          • Type II – qualitative
          • Type III (also called type IIa) – quantitative with normal levels of total protein S
        • Autosomal dominant inheritance
        • Antigenic tests for free protein S preferred for diagnosis
          • Free protein S values are higher in males than in females
      • Decreased levels in acute thrombotic states, nephrotic syndrome, inflammatory syndromes (due to increased C4b-binding protein), DIC, liver disease, malnutrition (vitamin K deficiency), pregnancy, and with estrogen and warfarin therapy
        • Elevated FVIII levels and/or APC resistance may result in falsely decreased values in some functional assays
        • Increased levels in heparin and direct thrombin inhibitors for some functional assays
    • Clinical presentation
      • Additional risk factors likely necessary to provoke thrombosis
      • VTE most common; arterial thrombosis may occur
      • Neonatal purpura fulminans (DIC) in homozygous infants
      • Warfarin-induced skin necrosis (rare)
  • Hyperhomocysteinemia (acquired or inherited)
    • Acquired
      • Independent risk factor for thromboembolic events
      • Most patients with hyperhomocysteinemia have no genetic mutations or polymorphisms
      • Acquired hyperhomocysteinemia is the result of defective homocysteine metabolism and may be the result of  vitamin B6, B12, or folic acid deficiency
      • Thrombotic risk most closely associated with increased fasting plasma homocysteine levels regardless of underlying etiology
        • Plasma homocysteine testing is recommended over DNA-based tests
    • Inherited
      • Homocysteine metabolism defects caused by variants in of the MTHFR gene
        • Most common variants – c.665C>T (p.Ala222Val) (previously designated C677T) and c.1286A>C (p.Glu429la) (previously designated A1298C)
          • Only homozygotes for the c.665C>T variant have been significantly associated with elevated plasma homocysteine levels
      • Autosomal recessive inheritance
      • Elevated plasma homocysteine level may be a risk factor for atherosclerotic vascular disease and venous thrombosis independent of MTHFR status
      • Inherited hyperhomocysteinemia rare
  • Antithrombin deficiency
    • Genetics and pathophysiology
      • Antithrombin (AT) – plasma anticoagulant; inactivates thrombin, factor Xa, and other activated clotting factors
        • AT activity enhanced by heparin-like glycosaminoglycans on the endothelial surface and by pharmaceutical heparin
        • Synthesized in the liver
      • Two forms of inherited antithrombin deficiency
        • Type I – quantitative
        • Type II – qualitative
      • Autosomal dominant inheritance
        • Functional assays preferred for diagnosis
        • Homozygous state is embryonic lethal
      • Decreased levels occurs in acute thrombotic states, liver disease, DIC, nephrotic syndrome, and heparin therapy; mild decreases may be seen in pregnancy or with oral contraceptive use
      • Increased levels may occur with long-term warfarin therapy
    • Clinical presentation
      • VTE
      • Recurrent thrombosis may occur even in the absence of additional risk factors
      • Some deficient patients are resistant to heparin therapy
  • Impaired clot lysis (dysfibrinogenemia, abnormal fibrinolysis)​

Acquired thrombophilic state

Tests generally appear in the order most useful for common clinical situations. Click on number for test-specific information in the ARUP Laboratory Test Directory.

APC Resistance Profile with Reflex to Factor V Leiden 0030192
Method: Electromagnetic Mechanical Clot Detection/Polymerase Chain Reaction/Fluorescence Monitoring

Limitations

APC resistance profile may be affected by heparin levels above 2 IU/mL, direct thrombin inhibitors, and low factor V activity levels (<50%)

Perform PCR testing as first-line test if these are present

APC resistance due to a cause other than a factor V mutation will not be detected

Thrombotic Risk, Inherited Etiologies (Uncommon) 0030177
Method: Electromagnetic Clot Detection/Microlatex Particle-Mediated Immunoassay/Chromogenic Assay

Limitations

See individual components

Follow Up

See individual components

Protein C, Functional with Reflex to Protein C, Total and Protein S, Free with Reflex to Protein S, Total 2003386
Method: Electromagnetic Mechanical Clot Detection/Enzyme-Linked Immunosorbent Assay/Microlatex Particle-Mediated Immunoassay

Protein S, Free Antigen with Reflex to Protein S, Total Antigen 2002269
Method: Microlatex Particle-Mediated Immunoassay

Thrombotic Risk (Acquired) Reflexive Panel 0030268
Method: Electromagnetic Clot Detection/Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Immunoturbidimetry/Quantitative Enzymatic

Limitations

See individual components

Follow Up

Interpretation provided in test report

Thrombotic Risk, Inherited Etiologies (Most Common) with Reflex to Factor V Leiden 0030133
Method: Electromagnetic Clot Detection/Quantitative Enzymatic/Polymerase Chain Reaction/Fluorescence Monitoring

Limitations

See individual components

Follow Up

See individual components

Related Tests

Guidelines

American College of Medical Genetics and Genomics. Choosing Wisely - Five Things Patients and Providers Should Question. An initiative of the ABIM Foundation. [Initial posting Jul 2015; Accessed: Nov 2015]

American College of Obstetricians and Gynecologists Women's Health Care Physicians. ACOG Practice Bulletin No. 138: Inherited thrombophilias in pregnancy. Obstet Gynecol. 2013; 122(3): 706-17. PubMed

American Society for Clinical Pathology. Choosing Wisely - Pathology-Related Choosing Wisely Recommendations. An initiative of the ABIM Foundation. [Initial posting Feb 2015; Accessed: Nov 2015]

Baglin T, Gray E, Greaves M, Hunt BJ, Keeling D, Machin S, Mackie I, Makris M, Nokes T, Perry D, Tait RC, Walker I, Watson H, British Committee for Standards in Haematology. Clinical guidelines for testing for heritable thrombophilia. Br J Haematol. 2010; 149(2): 209-20. PubMed

De Stefano V, Rossi E. Testing for inherited thrombophilia and consequences for antithrombotic prophylaxis in patients with venous thromboembolism and their relatives. A review of the Guidelines from Scientific Societies and Working Groups. Thromb Haemost. 2013; 110(4): 697-705. PubMed

Harris E. Guidelines for Thrombophilia Testing. National Health Service Foundation Trust. England [Review date Apr 2013; Accessed: Aug 2015]

Hickey SE, Curry CJ, Toriello HV. ACMG Practice Guideline: lack of evidence for MTHFR polymorphism testing. Genet Med. 2013; 15(2): 153-6. PubMed

Varga EA, Kujovich JL. Management of inherited thrombophilia: guide for genetics professionals. Clin Genet. 2012; 81(1): 7-17. PubMed

VTE, thrombophilia, antithrombotic therapy, and pregnancy: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines . American College of Chest Physicians - Medical Specialty Society. 2001 January (Revised 2012 February). NGC: 008939

General References

Adcock DM, Gosselin R. Direct Oral Anticoagulants (DOACs) in the Laboratory: 2015 Review Thromb Res. 2015; 136(1): 7-12. PubMed

Anderson JA M, Weitz JI. Hypercoagulable states. Clin Chest Med. 2010; 31(4): 659-73. PubMed

Dale BJ, Ginsberg JS, Johnston M, Hirsh J, Weitz JI, Eikelboom JW. Comparison of the effects of apixaban and rivaroxaban on prothrombin and activated partial thromboplastin times using various reagents. J Thromb Haemost. 2014; 12(11): 1810-5. PubMed

Favaloro EJ, McDonald D, Lippi G. Laboratory investigation of thrombophilia: the good, the bad, and the ugly. Semin Thromb Hemost. 2009; 35(7): 695-710. PubMed

Favaloro EJ. The futility of thrombophilia testing. Clin Chem Lab Med. 2014; 52(4): 499-503. PubMed

Franchini M. The utility of thrombophilia testing. Clin Chem Lab Med. 2014; 52(4): 495-7. PubMed

Hillarp A, Baghaei F, Blixter F, Gustafsson KM, Stigendal L, Sten-Linder M, Strandberg K, Lindahl TL. Effects of the oral, direct factor Xa inhibitor rivaroxaban on commonly used coagulation assays J Thromb Haemost. 2011; 9(1): 133-9. PubMed

Hossain N, Paidas MJ. Inherited thrombophilia: diagnosis and anticoagulation treatment in pregnancy. Clin Lab Med. 2013; 33(2): 377-90. PubMed

Johnson NV, Khor B, Van Cott EM. Advances in laboratory testing for thrombophilia. Am J Hematol. 2012; 87 Suppl 1: S108-12. PubMed

Lindhoff-Last E, Luxembourg B. Evidence-based indications for thrombophilia screening. Vasa. 2008; 37(1): 19-30. PubMed

Linkins LAnn, Julian JA, Rischke J, Hirsh J, Weitz JI. In vitro comparison of the effect of heparin, enoxaparin and fondaparinux on tests of coagulation Thromb Res. 2002; 107(5): 241-4. PubMed

Lippi G. Thrombophilia testing. Useful or hype? Clin Chem Lab Med. 2014; 52(4): 467-9. PubMed

Middeldorp S. Evidence-based approach to thrombophilia testing. J Thromb Thrombolysis. 2011; 31(3): 275-81. PubMed

Molinaro RJ, Szlam F, Levy JH, Fantz CR, Tanaka KA. Low plasma fibrinogen levels with the Clauss method during anticoagulation with bivalirudin Anesthesiology. 2008; 109(1): 160-1. PubMed

Samama MMichel, Martinoli J, LeFlem L, Guinet C, Plu-Bureau G, Depasse F, Perzborn E. Assessment of laboratory assays to measure rivaroxaban--an oral, direct factor Xa inhibitor. Thromb Haemost. 2010; 103(4): 815-25. PubMed

Trampus-Bakija A. Pediatric thrombosis. Clin Chem Lab Med. 2010; 48 Suppl 1: S97-S104. PubMed

Tsutsumi Y, Shimono J, Ohhigashi H, Ito S, Shiratori S, Teshima T. Analysis of the influence of dabigatran on coagulation factors and inhibitors. Int J Lab Hematol. 2015; 37(2): 225-30. PubMed

van Ommen H, Middeldorp S. Thrombophilia in childhood: to test or not to test. Semin Thromb Hemost. 2011; 37(7): 794-801. PubMed

Walker P, Gregg AR. Screening, testing, or personalized medicine: where do inherited thrombophilias fit best? Obstet Gynecol Clin North Am. 2010; 37(1): 87-107, Table of Contents. PubMed

Whitlatch NL, Ortel TL. Thrombophilias: when should we test and how does it help? Semin Respir Crit Care Med. 2008; 29(1): 25-39. PubMed

Yang JY K, Chan AK C. Pediatric thrombophilia. Pediatr Clin North Am. 2013; 60(6): 1443-62. PubMed

References from the ARUP Institute for Clinical and Experimental Pathology®

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Chandler WL, Rodgers GM, Sprouse JT, Thompson AR. Elevated hemostatic factor levels as potential risk factors for thrombosis. Arch Pathol Lab Med. 2002; 126(11): 1405-14. PubMed

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Medical Reviewers

Last Update: July 2016