il laboratorio nell’emergenza emorragica tripodi.pdf · il laboratorio nell’emergenza...

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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