UW Medicine Alternative Monitoring for Antithrombotic Agents

SUMMARY OF ANTICOAGULATION LAB TESTS AT UWMedicine

Description

Order Code

Specimen Collection

Availability

Turn-Around Time

Anti Xa Based Tests

antiXa for heparin

HIXA

2ml or 3ml blue top tube

24/7

1hr STAT upon receipt of sample at UWMC Lab

4 hrs ROUTINE

antiXa for LMWH

LMWXA

2ml or 3ml blue top tube

24/7

1hr STAT upon receipt of sample at UWMC Lab

4hrs ROUTINE

antiXa for apixaban level

 APIXN1

2ml or 3ml blue top tube

7am to 4pm daily

1hr STAT upon receipt of sample at UWMC Lab

4hrs ROUTINE

Off hours with Lab Medicine Resident approval

anti Xa for fondaparinux level

FNDXT

2ml or 3ml blue top tube

7am to 4pm daily

1hr STAT upon receipt of sample at UWMC Lab

4hrs ROUTINE

Off hours with Lab Medicine Resident approval

antiXa for rivaroxaban level

 RIVAR1

2ml or 3ml blue top tube

7am to 4pm daily

1hr STAT upon receipt of sample at UWMC Lab 

4 hrs ROUTINE

Off hours with Lab Medicine Resident approval

 

Coagulation Based Tests

dabigatran level

DABIGL

2ml or 3ml blue top tube

7am - 4pm Daily

1hr STAT upon receipt of sample at UWMC Lab

4hrs ROUTINE

Off hours with Lab Medicine Resident approval

direct thrombin inhibitor assay

(plasma-diluted thrombin time)

DTI

2ml or 3ml blue top tube

24/7

1hr STAT

4 hrs ROUTINE

modified prothrombin time mPT 2ml or 3ml blue top tube 24/7 only as part of EMERGENCY STROKE PANEL 30 min STAT

Factor X Tests

chromogenic factor X

CHRF10

2ml or 3ml blue top tube

7am - 10pm daily

1hr STAT upon receipt of sample at UWMC Lab

4hrs ROUTINE

factor X level

not used for anticoagulant monitoring

F10

2ml or 3ml blue top tube

7:30am to 3pm Mon-Fri

4 hrs ROUTINE

 

 

 

 

Anti-Xa Activity (Heparin Activity)

a) Anti-Xa Activity for Heparin (HIXA)

Used to monitor heparin as an alternative to PTT in patients with antiphospholipid antibodies that might interfere with PTT, or in patients with presumed heparin resistance as measured by PTT. Click here to see UWMedicine's Heparin Infusion Using AntiXa Monitoring Protocol

Therapeutic range for IV unfractionated heparin: 0.3-0.7 units/mL

b) AntiXa Activity for LMWH (LMWXA)

  • routine monitoring is not recommended - there is no "therapeutic range" for LMWH
  • dosing adjustments to reach a particular target range is not recommended
  • no optimal target range is correlated with efficacy or clinical endpoints
  • if measured, check peak antiXa level 3-4 hours after a dose
  • observed peak antiXa levels for q12h dosing of LMWHs (e.g enoxaparin 1mg/kg q12h) = 0.5 - 1 units/ml
  • observed peak antiXa levels for 1.5mg/kg  q24h dosing of LMWHs (e.g enoxaparin 1.5mg/kg q24h)  = 1-2 units/ml
  • if measured, check trough antiXa level at end of dosing interval (just before next dose)
  • expected trough antiXa levels = < 0.5 units/ml
  • higher troughs suggest impaired clearance - an increased dosing interval may be indicated

 

APIXABAN ASSAY (APIXN1)

Uses chromogenic anti-Xa activity to extrapolate apixaban concentrations in ng/ml.  Lower limit of measurable range is < 20 ng/ml 

Measuring the presence of apixaban may be helpful to:

  • assure absence of drug prior to invasive procedures
  • assure absence of drug prior to use of thrombolytic therapy

Measuring presence of apixaban is less likely to be useful to:

  • assess compliance
  • assess possible over-anticoagulation in cases of hemorrhage
  • assess possible under-anticoagulation in cases of treatment failure

For apixaban,  no “therapeutic range” has been established.  Observed peak and trough concentrations patients exposed to therapeutic dosing are described below*

Apixaban dose Observed Peak Concentration Observed Trough Concentration

VTE Prophylaxis

2.5mg bid

41-146 ng/ml 23-109 ng/ml

VTE Treatment

2.5mg bid

5mg bid

10mg bid

 

30-153 ng/ml

59-302 ng/ml

111-572 ng/ml

 

 

11-90 ng/ml

22-177 ng/ml

41-335 ng/ml

 

Stroke Prevention in AF

2.5mg bid

5mg bid

 

69-221 ng/ml

91-321 ng/ml

 

34-162 ng/ml

41-230 ng/ml

* from http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002148/WC500107728.pdf

 

CHROMOGENIC FACTOR X (CHRF10)

Used instead of INR to monitor warfarin in patients with antiphospholipid antibodies or other inhibitors that might interfere with INR, or in patients on concurrent direct thrombin inhibitors that might interfere with INR.

  • Therapeutic range for warfarin:    INR 2-3.5 ~ CFX 35% - 25% 

  

 

 

 

 

 

 

 

 

 

 

 

 

 

DABIGATRAN ASSAY (DABIGL)

Uses plasma dilute thrombin time (see below) to extrapolate dabigatran concentrations in ng/ml. Lower limit of  measurable range is < 50 ng/ml

Measuring the presence of dabigatran may be helpful to:

  • assure absence of drug prior to invasive procedures
  • assure absence of drug prior to use of thrombolytic therapy

Measuring presence of dabigatran is less likely to be useful to:

  • assess compliance
  • assess possible over-anticoagulation in cases of hemorrhage
  • assess possible under-anticoagulation in cases of treatment failure

For Dabigatran no “therapeutic range” has been established.  Observed peak and trough concentrations in patients exposed to therapeutic dosing are outlined below.

In patients receiving dabigatran 150mg bid

Observed Serum concentrations1

Peak values

64 – 443 ng/ml

Trough values

31 – 225 ng/m

1  van Ryn J, et al. Dabigatran etexilate – a novel reversible oral direct thrombin inhibitor: interpretation of coagulation assays and reversal of anticoagulant activity.  Thromb Haemost 2010; 103: 1116-1127.

 

DIRECT THROMBIN INHIBITOR ASSAY (DTI) 1

(Plasma-Diluted Thrombin Time)

Used instead of aPTT to monitor injectable DTI therapy. Preferred over aPTT due to better sensitivity, and is not affected by antiphospholipid antibodies. Cost, turn-around time and 24/7 availability at UWMC are similar to aPTT.

  • Therapeutic range for DTIs administered by continuous infusion

    • For argatroban: 60-100 seconds

    • For bivalirudin: 60-90 seconds

    • For lepirudin: 90-160 seconds

1 Love JE, et al Monitoring direct thrombin inhibitors with a plasma diluted thrombin time. Thromb Haemost. 2007 Jul;98(1):234-42.

FONDAPARINUX ASSAY (FNDXT)

Uses chromogenic antiXa activity to extrapolate serum concentrations of fondaparinux in mcg/ml.

There is no “therapeutic range” for fondaparinux, and dosing adjustments to reach a particular target or goal range are not recommended.  Observed peak and trough levels from clinical trials, based on dose administered, are described below.

Fondaparinux dose

Observed Peak concentrations
(3 hours after dose)

Observed Trough  concentrations
(24 hours after dose)

VTE Prophylaxis
2.5mg

Mean (1): 0.39 and 0.5 mcg/ml
Range (2): < 0.042-1.161 mcg/ml

Mean (1): 0.14 and 0.19 mcg/ml
Range (2): <0.042-0.569 mcg/ml

VTE Treatment

 

5mg (< 50kg)
7.5mg (50-100 kg)
10mg (> 100 kg)

Mean (3): 1.2 and 1.26 mcg/ml
 

Ranges (4):
0.685 - 1.522 mcg/ml
0.206 - 2.95 mcg/ml
0.582 -1.713 mcg/ml

Mean (3): 0.46 and 0.62 mcg/ml
 

Ranges (4):
0.242 - 1.003 mcg/ml
0.048 – 2.023 mcg/ml
0.0.081 – 1.041 mcg/m

 

(1) mean concentrations in PENTHIFRA and PENTATHLON clinical trials, as noted in package insert
(2) range of concentration values from these trials (data on file, GSK)
(3) mean concentrations in MATISSE DVT and MATISSE PE trials, as noted in package insert
(4) range of concentration values from these trials (data on file, GSK)

 

INR POINT-OF-CARE TESTING (Rapid INR; PRORPD)

Whole blood INR testing using point-of-care devices is available for eligible patients at UW Neighborhood Clinics.  Home INR testing devices using similar technology are available for eligible patients through certain third party companies. 

UWMedicine Anticoagulation Services does not routinely use whole blood INR testing, and does not recommend whole blood INR testing in the following circumstances:

  • patients initiating warfarin who have not yet reached steady-state and a stable maintenance dose
  • patients with variable response to warfarin and/or frequent warfarin dose adjustments
  • patients with goal INR upper limit greater than 3.5
  • patients with known HCT< 30.0 (INRatio/Alere) or HCT < 25.0 (Coaguchek/Roche) or HCT > 55.0
  • patients with ventricular assist devices (LVAD)
  • patients undergoing weekly INR testing prior to/following cardioversion or ablation
  • patients with end stage renal disease and/or on hemodialysis or peritoneal dialysis
  • patients with chronic inflammatory conditions (eg: rheumatoid arthritis, Crohns disease, ulcerative colitis, hepatitis, diabetic nephropathy, glomerulonephritis)
  • patients with acute inflammatory conditions (for example: acute viral infection, acute bacterial infection including sepsis)
  • patients with advanced malignancy
  • patients with known chronic elevated fibrinogen for any reason
  • patients with known antiphospholipid antibodies (lupus anticoagulant, anti -beta-2-glycoprotein I, anticardiolipin antibody)
  • patients exposed to an injectable direct thrombin inhibitor in the last 24 hours (argatroban, bivalirudin)
  • patients exposed to an injectable heparin product in the last 48 hours (heparin, dalteparin, enoxaparin)
  • patients exposed to an injectable factor Xa inhibitor in the that 5 days (fondaparinux)
  • patients transitioning between warfarin and any direct oral anticoagulant (apixaban, dabigatran, edoxaban, rivaroxaban
  • self testing in patients during the first three months of warfarin therapy
  • self-testing in patients who are non-compliant with followup or non-adherent to medication administration

 

MODIFIED PROTHROMBIN TIME (mPT)

Uses a highly sensitive prothrombin time reagent to detect the presence of most anticoagulants.  Available rapidly, and measured in seconds.  This test can only be used to screen for the presence of anticoagulants as part of the Emergency Stroke Panel. 

Measuring mPT may be helpful to:

  • assure absence of drugs prior to invasive procedures
  • assure absence of drugs prior to use of thrombolytic therapy

Measuring mPT is less useful to:

  • detect the presence of LMWH
  • detect the presence of intrinsic clotting factor deficiencies (VIII, IX, X, XII)

Drug Present

mPT

No anticoagulant present normal
intrinsic clotting factor deficiency normal
vitamin K deficiency/warfarin prolonged
lupus anticoagulant prolonged
unfractionated heparin prolonged
low molecular weight heparin (> 0.4 antiXa units/ml) normal or prolonged
direct thrombin inhibitors (argatroban, bivalirudin, dabigatran, lepirudin) prolonged
direct factor Xa inhibitors (apixaban, rivaroxaban) prolonged
low ionized calcium prolonged

 

RIVAROXABAN ASSAY (RIVAR1)

Uses chromogenic anti-Xa activity to extrapolate rivaroxaban concentrations in ng/ml.  Lower limit of  measurable range is < 25 ng/ml

Measuring the presence of rivaroxaban may be helpful to:

  • assure absence of drug prior to invasive procedures
  • assure absence of drug prior to use of thrombolytic therapy

Measuring presence of rivaxoxaban is less likely to be useful to:

  • assess compliance
  • assess possible over-anticoagulation in cases of hemorrhage
  • assess possible under-anticoagulation in cases of treatment failure

For rivaroxaban no “therapeutic range” has been established. Observed peak and trough concentrations in patients exposed to therapeutic dosing are outlined below 1,2

 

Stroke Prevention in AF

(20mg daily)

VTE Treatment

(20mg daily)

VTE Prevention

(10mg daily)

Peak values

160 – 360 ng/ml

175 – 360 ng/ml

91 – 196 ng/ml

Trough values

4 – 96 ng/ml

19 – 60 ng/ml

1.3 – 38 ng/ml

1.  Mueck W et al.  Population pharmacokinetics and pharmacodynamics of once- and twice-daily rivaroxaban for the prevention of venous thromboembolism in aptients undergoing total hip replacement.  Thromb Haemost 2008; 100:453-61
2.  Buller HR et al.  A dose-ranging study evaluating once-daily oral administration of the factor Xa inhibitor rivaroxaban in the treatment of patients with acute symptomatic deep vein thrombosis.  The Einstein DVT Dose Ranging Study.  Blood 2008; 112:2242-2247.