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FeedbackGiven the high prevalence of thrombotic events in the United States, anticoagulants have taken on a prominent role in patient care. However, the use of anticoagulants in prophylaxis, emergent care, and long-term management may interfere with associated laboratory testing.
Three general classes of anticoagulants are in regular use today: heparins, including unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH); vitamin K antagonists (VKAs), including warfarin; and direct oral anticoagulants (DOACs), including direct thrombin inhibitors and direct factor Xa inhibitors. Each of these anticoagulants has the potential to interfere with laboratory testing.
| Classes | Heparins | VKAs | DOACs | ||
|---|---|---|---|---|---|
| Anticoagulant | UFH | LMWH | Warfarin | Direct Thrombin Inhibitorsa | Direct Factor Xa Inhibitorsb |
|
Common Coagulation Assays |
|||||
|
No effectc |
No effectc |
Prolonged |
No effect/ |
Prolongedd/ |
|
|
Prolonged |
No effect/ |
No effect/ |
Prolongedd/ |
No effect/ |
|
|
No effect |
No effect |
No effect |
No effect |
No effect |
|
|
No effectc |
No effectc |
No effect |
No effect/ |
No effect |
|
|
No effect |
No effect |
No effect |
No effect |
No effect |
|
|
No effect |
No effect |
No effect |
No effect |
No effect |
|
|
Prolonged |
No effect/ |
No effect |
Prolonged |
No effect |
|
|
Anti-Xa assayse (for UFH, LMWH, or anti-Xa DOACs) |
Possible effect/ |
Possible effect/ |
No effect |
No effect |
Possible effect/ |
|
Thrombotic Risk Assays |
|||||
|
No effectc |
No effectc |
No effectf |
Possible false negative |
Possible false negative |
|
|
No effectg |
No effectg |
No effectg |
Overestimated |
No effect |
|
|
No effectg |
No effectg |
No effectg |
No effect |
No effect |
|
|
No effectc/ |
No effectc/ |
Decreased |
Overestimated |
Overestimated |
|
|
No effect |
No effect |
Decreased |
No effect |
No effect |
|
|
No effectc/ |
No effectc/ |
Decreased |
Overestimated |
Overestimated |
|
|
No effect |
No effect |
Decreased |
No effect |
No effect |
|
|
No effect |
No effect |
Decreased |
No effect |
No effect |
|
|
Lupus Anticoagulant Assays |
|||||
|
No effectc/ |
No effectc/ |
No effect/ |
No effect/ |
Prolonged/ |
|
|
No effectc/ |
No effectc/ |
No effect/ |
Possible false positive |
Possible false positive or false negative |
|
|
No effectc/ |
No effectc/ |
No effect/ |
Possible false positive |
Possible false positive |
|
|
No effectc/ |
No effectc/false positive |
No effect/ |
Possible false positive |
Possible false positive |
|
|
Fibrinolytic Assays |
|||||
|
No effect |
No effect |
No effect |
No effect |
No effect |
|
|
No effect |
No effect |
No effect |
No effect |
No effect |
|
|
No effect |
No effect |
No effect |
No effect |
No effect |
|
|
No effect |
No effect |
No effect |
No effect |
No effect |
|
|
No effect |
No effect |
No effect |
No effect |
No effect |
|
|
No effect |
No effect |
No effect |
No effect |
No effect |
|
|
Other Assays |
|||||
|
No effect |
No effect |
No effect |
No effect |
No effect |
|
|
No effect/ |
No effect/ |
No effect/ |
Underestimated |
Underestimated |
|
|
No effect |
No effect |
No effect |
No effect |
No effect |
|
|
aArgatroban, bivalirudin (Angiomax), dabigatran (Pradaxa). bRivaroxaban (Xarelto), apixaban (Eliquis), edoxaban (Savaysa). cReagent contains heparin neutralizer; effect may be seen with supratherapeutic drug levels. dDrug, concentration, and reagent dependent. eFor accurate drug quantitation, the selected assay must correspond with the specific drug (ie, UFH, LMWH, rivaroxaban, apixaban, edoxaban) that the patient is receiving. Additionally, reported concentrations will be inaccurate (ie, overestimated) when >1 drug with anti-Xa activity is present (eg, when a patient is being bridged between medications). fDrug does not interfere with assay, but presence may affect analyte. gInterference in high concentrations of anticoagulant medication. hPresence of UFH, 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. iaPTT-based factor assays (factors VIII, IX, XI, XII) are more likely to demonstrate assay interference and underestimation than PT-based factors assays (factors II, V, VII, X). The effect is more pronounced with UFH than with LMWH. APC, activated protein C; aPTT, activated partial thromboplastin time; dRVVT, dilute Russell viper venom time; INR, international normalized ratio; PT, prothrombin time; tPA, tissue plasminogen activator Sources: Linkins, 2002 ; Molinaro, 2008 ; Genzen, 2005 ; Hillarp, 2011 ; Adcock, 2015 ; Dale, 2014 ; Tsutsumi, 2015 ; Favaloro, 2019 ; Gosselin, 2018 |
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ARUP Laboratory Tests
PT/INR
Electromagnetic Mechanical Clot Detection
aPTT
Electromagnetic Mechanical Clot Detection
D-dimer
Immunoturbidimetry
Fibrinogen
Electromagnetic Mechanical Clot Detection
Fibrinogen antigen
Quantitative Immunoturbidimetry
Repitilase time
Electromagnetic Mechanical Clot Detection
Thrombin time
Electromagnetic Mechanical Clot Detection
Anti-Xa assays
Chromogenic Assay
Chromogenic Assay
Chromogenic Assay
Chromogenic Assay
Chromogenic Assay
APC resistance
Electromagnetic Mechanical Clot Detection
Electromagnetic Mechanical Clot Detection/Polymerase Chain Reaction/Fluorescence Monitoring
Antithrombin activity, IIa method
Chromogenic Assay
Antithrombin antigen
Microlatex Particle-Mediated Immunoassay
Protein C activity, clot based
Electromagnetic Mechanical Clot Detection
Protein C antigen
Enzyme Immunoassay
Protein S activity
Electromagnetic Mechanical Clot Detection
Protein S free antigen
Microlatex Particle-Mediated Immunoassay
Protein S total antigen
Microlatex Particle-Mediated Immunoassay
Lupus anticoagulant panel
Electromagnetic Mechanical Clot Detection
dRVVT
Electromagnetic Mechanical Clot Detection
Hexagonal phospholipid neutralization
Qualitative Clotting
Alpha-2-antiplasmin
Chromogenic Assay
Fibrin/fibrinogen degradation products
Latex Agglutination
Plasminogen activator inhibitor-1
Bioimmunoassay
Plasminogen activity
Chromogenic Assay
tPA antigen
Enzyme-Linked Immunosorbent Assay
Soluble fibrin monomer
Qualitative Hemagglutination
ADAMTS13
Chromogenic Assay
Factor assays, clot based
Electromagnetic Mechanical Clot Detection
Electromagnetic Mechanical Clot Detection
Electromagnetic Mechanical Clot Detection
Electromagnetic Mechanical Clot Detection
Electromagnetic Mechanical Clot Detection
Electromagnetic Mechanical Clot Detection
Electromagnetic Mechanical Clot Detection
Electromagnetic Mechanical Clot Detection
Electromagnetic Mechanical Clot Detection
Electromagnetic Mechanical Clot Detection
Chromogenic Assay
Qualitative Solubility Assay
von Willebrand factor antigen and activity
Microlatex Particle-Mediated Immunoassay
Platelet Agglutination
References
-
12479885
Linkins LA, Julian JA, Rischke J, et al. In vitro comparison of the effect of heparin, enoxaparin and fondaparinux on tests of coagulation. Thromb Res. 2002;107(5):241-244.
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18580197
Molinaro RJ, Szlam F, Levy JH, et al. Low plasma fibrinogen levels with the Clauss method during anticoagulation with bivalirudin. Anesthesiology. 2008;109(1):160-161.
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16146819
Genzen JR, Miller JL. Presence of direct thrombin inhibitors can affect the results and interpretation of lupus anticoagulant testing. Am J Clin Pathol. 2005;124(4):586-593.
-
20946166
Hillarp A, Baghaei F, Fagerberg Blixter I, et al. Effects of the oral, direct factor Xa inhibitor rivaroxaban on commonly used coagulation assays. J Thromb Haemost. 2011;9(1):133-139.
-
25981138
Adcock DM, Gosselin R. Direct oral anticoagulants (DOACs) in the laboratory: 2015 review. Thromb Res. 2015;136(1):7-12.
-
25196577
Dale BJ, Ginsberg JS, Johnston M, et al. Comparison of the effects of apixaban and rivaroxaban on prothrombin and activated partial thromboplastin times using various reagents. J Thromb Haemost. 2014;12(11):1810-1815.
-
24963788
Tsutsumi Y, Shimono J, Ohhigashi H, et al. Analysis of the influence of dabigatran on coagulation factors and inhibitors. Int J Lab Hematol. 2015;37(2):225-230.
-
30665674
Favaloro EJ, Mohammed S, Curnow J, et al. Laboratory testing for lupus anticoagulant (LA) in patients taking direct oral anticoagulants (DOACs): potential for false positives and false negatives. Pathology. 2019;51(3):292-300.
-
29433148
Gosselin RC, Adcock DM, Bates SM, et al. International Council for Standardization in Haematology (ICSH) recommendations for laboratory measurement of direct oral anticoagulants. Thromb Haemost. 2018;118(3):437-450.
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