Impacts of Common Anticoagulants on Coagulation Testing

Last Literature Review: February 2024 Last Update:

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
Chief Medical Director, ARUP Institute for Clinical and Experimental Pathology
Medical Director, Hemostasis/Thrombosis, ARUP Laboratories

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.

Anticoagulants and Possible Coagulation Test Interferences
ClassesHeparinsVKAsDOACs
AnticoagulantUFHLMWHWarfarinDirect Thrombin InhibitorsaDirect Factor Xa Inhibitorsb
      

Common Coagulation Assays

PT/INRNo effectcNo effectcProlongedNo effect/
prolongedd
Prolongedd/
no effect
aPTTProlongedNo effect/
prolonged
No effect/
prolonged
Prolongedd/
no effect
No effect/
prolongedd
D-dimerNo effectNo effectNo effectNo effectNo effect
FibrinogenNo effectcNo effectcNo effectNo effect/
underestimated
No effect
Fibrinogen antigenNo effectNo effectNo effectNo effectNo effect
Reptilase timeNo effectNo effectNo effectNo effectNo effect
Thrombin timeProlongedProlonged/no effectNo effectProlongedNo effect
Anti-Xa assayse (for UFH, LMWH, or anti-Xa DOACs)OverestimateeOverestimateeNo effectNo effectOverestimatee

Thrombotic Risk Assays

APC resistanceNo effectcNo effectcNo effectPossible false negativePossible false negative
Antithrombin activity, IIa methodNo effectfNo effectfNo effectfOverestimatedNo effect
Antithrombin antigenNo effectfNo effectfNo effectfNo effectNo effect
Protein C activity, clot basedNo effectc/
overestimate
No effectc/
overestimate
DecreasedOverestimatedOverestimated
Protein C antigenNo effectNo effectDecreasedNo effectNo effect
Protein S activityNo effectc/
overestimate
No effectc/
overestimate
DecreasedOverestimatedOverestimated
Protein S free antigenNo effectNo effectDecreasedNo effectNo effect
Protein S total antigenNo effectNo effectDecreasedNo effectNo effect

Lupus Anticoagulant Assaysg

dRVVTNo effectc/
prolonged
No effectc/
prolonged
ProlongedNo effect/
prolongedd
Prolonged/
no effect
dRVVT confirmatory ratioNo effectc/
false positive
No effectc/
false positive
No effect/
possible false positivef
Possible false positivePossible false positive or false negative
Hexagonal phospholipid neutralizationNo effectc/
false positive
No effectc/
false positive
No effect/
possible false positivef
Possible false positivePossible false positive

Fibrinolytic Assays

Alpha-2-antiplasminNo effectNo effectNo effectNo effectNo effect
Fibrin/fibrinogen degradation productsNo effectNo effectNo effectNo effectNo effect
Plasminogen activator inhibitor-1No effectNo effectNo effectNo effectNo effect
Plasminogen activityNo effectNo effectNo effectNo effectNo effect
tPA antigenNo effectNo effectNo effectNo effectNo effect
Soluble fibrin monomerNo effectNo effectNo effectNo effectNo effect

Other Assays

ADAMTS13No effectNo effectNo effectNo effectNo effect
Factor assays, clot basedhNo effect/
underestimatei
No effect/
underestimatei
No effect/
decreased vitamin K-dependent factors
UnderestimatedUnderestimated
von Willebrand factor antigen and activityNo effectNo effectNo effectNo effectNo 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

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

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

References