Impacts of Common Anticoagulants on Coagulation Testing

Given 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.

Anticoagulants and Possible Coagulation Test Interferences
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

No effect/
prolonged

No effect

Prolonged

No effect

Anti-Xa assayse (for UFH, LMWH, or anti-Xa DOACs)

Possible effect/
overestimatee

Possible effect/
overestimatee

No effect

No effect

Possible effect/
overestimatee

Thrombotic Risk Assays

APC resistance

No effectc

No effectc

No effectf

Possible false negative

Possible false negative

Antithrombin activity, IIa method

No effectg

No effectg

No effectg

Overestimated

No effect

Antithrombin antigen

No effectg

No effectg

No effectg

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 Assays

dRVVT

No effectc/
prolonged

No effectc/
prolonged

No effect/
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

Platelet neutralization procedure

No effectc/
false positive

No effectc/false positive

No effect/
possible false positived

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), 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 

ARUP Laboratory Tests

Common Coagulation Assays

PT/INR

aPTT

D-dimer

Fibrinogen

Fibrinogen antigen

Repitilase time

Thrombin time

Anti-Xa assays

Thrombotic Risk Assays

APC resistance

Antithrombin activity, IIa method

Antithrombin antigen

Protein C activity, clot based

Protein C antigen

Protein S activity

Protein S free antigen

Protein S total antigen

Lupus Anticoagulant Assays

Lupus anticoagulant panel

dRVVT

Hexagonal phospholipid neutralization

Fibrinolytic Assays

Alpha-2-antiplasmin

Fibrin/fibrinogen degradation products

Plasminogen activator inhibitor-1

Plasminogen activity

tPA antigen

Soluble fibrin monomer

Other Assays

ADAMTS13

Factor assays, clot based

von Willebrand factor antigen and activity

Medical Experts

Contributor

Moser

Karen A. Moser, MD
Associate Professor of Pathology (Clinical), University of Utah
Medical Director, Hemostasis/Thrombosis, ARUP Laboratories
Contributor

Smock

Kristi J. Smock, MD
Professor of Pathology (Clinical), University of Utah
Medical Director, Hemostasis/Thrombosis, ARUP Laboratories

References