il laboratorio nell’emergenza emorragica tripodi.pdf · il laboratorio nell’emergenza...
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Armando Tripodi Angelo Bianchi Bonomi
Hemophilia and Thrombosis Center Dept. of Clinical Sciences and Community Health
University of Milano
Il laboratorio nell’emergenza emorragica
Usefulness of the laboratory in anticoagulated patients in emergency (1)
• Can Lab tests identify the type of oral anticoagulant being taken by the patient?
‒Vitamin K antagonists ‒Direct oral anticoagulants (Dabi Riva, Api, Edo?)
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Can Lab tests identify the type of oral anticoagulant? Test Drug
VKA Dabi Riva Api Edo
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Can Lab tests identify the type of oral anticoagulant? Test Drug
VKA Dabi Riva Api Edo
PT
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Can Lab tests identify the type of oral anticoagulant? Test Drug
VKA Dabi Riva Api Edo
PT
APTT
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Can Lab tests identify the type of oral anticoagulant? Test Drug
VKA Dabi Riva Api Edo
PT
APTT
Thrombin time
Not affected
Not affected
Not affected
Not affected
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Can Lab tests identify the type of oral anticoagulant? Test Drug
VKA Dabi Riva Api Edo
PT
APTT
Thrombin time
Not affected
Not affected
Not affected
Not affected
Anti-FXa activity
Not affected
Not affected
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Usefulness of the laboratory in anticoagulated patients in emergency (2)
• Measurement of circulating DOAC is useful ‒To establish if bleeding or thrombosis is due to
elevated or low drug levels ‒To assess residual circulating drug before
surgery/invasive procedures ‒To make decision on thrombolysis in stroke patients ‒To make decision on antidotes
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22 out 90 patients (24%) had normal laboratory test (dTT) at study entry Conclusions A significant proportion of patients would receive (unnecessary) antidote if dabigatran is not measured before treatment
20 out 67 patients (30%) had drug concentration <75 ng/mL at study entry Conclusions A significant proportion of patients would receive (unnecessary) antidote if Riva/Api is not measured before treatment
How to measure the DOAC? Basic coagulation tests (i.e, PT, APTT
or TT) are affected by DOAC
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Owing to the between-reagent variability their prolongations are not invariably related to
their circulating concentrations
Hawes EM et al, 2013
Commercial APTT & Dabigatran
• APTT at presentation: 110 seconds (normal range: 20-30) • Dabi at presentation: 2040 ng/mL
• APTT is not entirely representative of the very high Dabi levels
Shapiro S et al, 2016
Clinic A
Clinic B
Clinic C
Clinic D
Dabi (aPTT) 1.67
(1.61-1.75) 1.74
(1.66-1.80) 1.97
(1.82-2.14) 1.68
(1.63-1.75)
Riva (PT) 1.57
(1.54-1.62) 1.88
(1.85-1.94) 1.31
(1.26-1.38) 1.53
(1.49-1.59)
Api (PT) 1.28
(1.25-1.34) 1.29
(1.26-1.36) NA
1.32
(1.21-1.47)
Responsiveness of PT/aPTT at 200 ng/mL DOAC concentration
S. Testa, C Legnani, A. Tripodi et al, 2016
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et al, 2010
Rodgers R et al, 2013
Rivaroxaban & PT
Rodgers R et al, 2013
Rivaroxaban & APTT
Platton S et al, 2016
Rivaroxaban & PT/APTT
Van Veen JJ et al, 2012
Rivaroxaban & PT
Van Veen JJ et al, 2012
Rivaroxaban & PT
Conclusion on DOAC & PT/APTT
• Responsiveness of PT/APTT to DOAC is variable • Their results might be misleading when used as
standalone tests • They could be used only in emergency when
dedicated tests are not availalbe provided their responsiveness to DOAC is known
• Labs should check with reference plasmas which is the least DOAC concentration that prolongs PT/APTT beyond the upper limit of the normal range
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How to measure Dabigatran
• Dilute TT (or Ecarin Test)
Results Expression • Drug-equivalent concentration as ng/mL
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How to measure Rivaroxaban
• Anti- Factor Xa activity
Results expression • Drug-equivalent concentration as ng/mL
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How to measure Apixaban
• Anti- Factor Xa assay
Results expression
• Drug-equivalent concentration as ng/mL
Laboratory & DOAC When to measure
• DOAC reach peak value (Cmax) approximately 2 hours after ingestion
• DOAC reach Ctrough approximately 12h (bid) or 24h (od) after ingestion
• Timing of blood draw is essential for results interpretation
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Alerting values Owing to the inter-individual variability and limited clinical
experience, no accurate alerting values are currently known
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Plasma Concentration [ng/mL (min-max)] at Steady-State Dabigatran
Rivaroxaban
Peak
6 Trough
535 22
239
117 275
61 143
Peak
Trough
Overall Conclusions
• If available in emergency, lab testing may be useful • Although accurate alarming values for DOAC are not
yet defined, it can be assumed that extreme values (>400 or <30 ng/mL) are potentially associated with adverse events
• Results interpretation for DOAC requires knowledge of the time elapsing between the last dose intake and blood drawing
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