Medical Experts
Moser
Smock
Given the high prevalence of thrombotic events in the United States, anticoagulants play 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 regularly used 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 | |||||
PT/INR | No effectc | No effectc | Prolonged | No effect/ prolongedd | Prolongedd/ no effect |
aPTT | Prolonged | No effect/ prolonged | No effect/ prolonged | Prolongedd/ no effect | No effect/ prolongedd |
D-dimer | No effect | No effect | No effect | No effect | No effect |
Fibrinogen | No effectc | No effectc | No effect | No effect/ underestimated | No effect |
Fibrinogen antigen | No effect | No effect | No effect | No effect | No effect |
Reptilase time | No effect | No effect | No effect | No effect | No effect |
Thrombin time | Prolonged | Prolonged/no effect | No effect | Prolonged | No effect |
Anti-Xa assayse (for UFH, LMWH, or anti-Xa DOACs) | Overestimatee | Overestimatee | No effect | No effect | Overestimatee |
Thrombotic Risk Assays | |||||
APC resistance | No effectc | No effectc | No effect | Possible false negative | Possible false negative |
Antithrombin activity, IIa method | No effectf | No effectf | No effectf | Overestimated | No effect |
Antithrombin antigen | No effectf | No effectf | No effectf | No effect | No effect |
Protein C activity, clot based | No effectc/ overestimate | No effectc/ overestimate | Decreased | Overestimated | Overestimated |
Protein C antigen | No effect | No effect | Decreased | No effect | No effect |
Protein S activity | No effectc/ overestimate | No effectc/ overestimate | Decreased | Overestimated | Overestimated |
Protein S free antigen | No effect | No effect | Decreased | No effect | No effect |
Protein S total antigen | No effect | No effect | Decreased | No effect | No effect |
Lupus Anticoagulant Assaysg | |||||
dRVVT | No effectc/ prolonged | No effectc/ prolonged | Prolonged | No effect/ prolongedd | Prolonged/ no effect |
dRVVT confirmatory ratio | No effectc/ false positive | No effectc/ false positive | No effect/ possible false positivef | Possible false positive | Possible false positive or false negative |
Hexagonal phospholipid neutralization | No effectc/ false positive | No effectc/ false positive | No effect/ possible false positivef | Possible false positive | Possible false positive |
Fibrinolytic Assays | |||||
Alpha-2-antiplasmin | No effect | No effect | No effect | No effect | No effect |
Fibrin/fibrinogen degradation products | No effect | No effect | No effect | No effect | No effect |
Plasminogen activator inhibitor-1 | No effect | No effect | No effect | No effect | No effect |
Plasminogen activity | No effect | No effect | No effect | No effect | No effect |
tPA antigen | No effect | No effect | No effect | No effect | No effect |
Soluble fibrin monomer | No effect | No effect | No effect | No effect | No effect |
Other Assays | |||||
ADAMTS13 | No effect | No effect | No effect | No effect | No effect |
Factor assays, clot basedh | No effect/ underestimatei | No effect/ underestimatei | No effect/ decreased vitamin K-dependent factors | Underestimated | Underestimated |
von Willebrand factor antigen and activity | No effect | No effect | No effect | No effect | No effect |
aArgatroban, bivalirudin (Angiomax), and dabigatran (Pradaxa). Only dabigatran is a DOAC; argatroban and bivalirudin are administered parenterally. bRivaroxaban (Xarelto), apixaban (Eliquis), and edoxaban (Savaysa). cReagent contains heparin neutralizer; effect may occur 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, direct factor Xa inhibitor) 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. gThis table indicates the possible effects on LA assays in the absence of anticoagulant neutralizing reagents (such as heparinase, polybrene, or activated charcoal-based DOAC neutralizers). LA assays may also show anticoagulant interference if drug levels exceed the capacity of the neutralizing reagent used by the laboratory. 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. Factor XIII assays are not affected by other anticoagulants. iaPTT-based factor assays (factors VIII, IX, XI, XII) are more likely to demonstrate assay interference and underestimation than PT-based factor 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; LA, lupus anticoagulant; 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 |
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
APC resistance
Electromagnetic Mechanical Clot Detection
Electromagnetic Mechanical Clot Detection/Polymerase Chain Reaction (PCR)/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/Chromogenic Assay
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
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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.