A SINGLE CENTRE EXPERIENCE MEASURING RIVAROXABAN LEVELS WITH A SPECIFIC ANTI XA ASSAY AND THE EFFECT ON THE STANDARD COAGULATION SCREEN.
(Abstract release date: 05/19/16)
EHA Library. Niblock A. 06/09/16; 135099; PB2199
Dr. Aaron Niblock
Contributions
Contributions
Abstract
Abstract: PB2199
Type: Publication Only
Background
Direct oral anticoagulants drugs are now commonly used in clinical practice. Rivaroxaban inhibits free factor Xa and hence prothrombinase activity as well as clot bound Xa, thus effectively blocking thrombin generation. One main advantage over vitamin K antagonists is that blood coagulation monitoring is not necessary. However introducing a static change into a dynamic cascade always raises concern. The concentration may potentially need to be measured in certain clinical situations. These may include urgent surgery, perioperative management, thromboembolic events, bleeding events and suspected overdose. All routine coagulation screens performed in Northern Ireland are undertaken on a Sysmex Coagulaometer using the Innovin reagent. The Regional Specialty Coagulation Laboratory uses a Stago analyser with the STA Neoplastine CI+ reagent. The effect on the coagulation screen by rivaroxaban is known to vary between analysers making interpretation difficult.
Aims
To assess the effect of rivaroxaban on the current coagulation screen to help aid clinicians in making urgent decisions. To assess the variation of rivaroxaban concentrations between patients invivo rather than a controlled dilutional experiment.
Methods
Recording the dose and time from last drug ingestion we were able to measure the effect on the standard coagulation screen with both analysers. On the same samples the rivaroxaban concentration was measured with the specific anti-Xa rivaroxaban assay. Each recruited patient had their age, renal function and other co prescribed medications recorded to assess variation within these parameters.As a control, healthy volunteers on no anticoagulation had their rivaroxaban levels measured. The volunteers’ rivaroxaban levels ranged from 15-21ug/l and therefore we assume no drug is present when levels fall into, and below, this range.
Results
The effect on the PT and APTT was variable between analysers. The PT, in line with previous publications, was more sensitive than the APTT at smaller drug concentrations. The Neoplastine CI plus reagent on the Stago analyser was more sensitive than the Innovin reagent to rivaroxaban concentrations. The Neoplastine CI PT was prolonged in all samples taken within 17 hours of rivaroxaban ingestion. Our results compare with University Hospital Hotel Dieu (Paris) which found peak concentrations up to 400ug/l and trough concentrations up to160ug/l. However our results demontrated more variation with some patients have a higher rivaroxaban level than expected 600ug/l. These patients were also taking verapamil. We noted the SPC advises rivaroxaban not to be used in patients who are receiving concomitant combined P-gp and moderate CYP3A4 inhibitors unless the potential benefit justifies the potential risk.2There is a positive correlation between rivaroxaban concentration and Neoplastine CI PT reagent with prolongation up to a certain concentration and beyond this the effect on Neoplastine CI PT appears to plateau. The patients with a rivaroxaban concentration in excess of 600ug/l had a similar PT than those with a rivaroxaban concentration of 450ug/l.
Conclusion
The PT, provided it is sensitive to rivaroxaban, is a quick test and may be useful to ascertain rivaroxaban presence or not but given the plateau effect, not necessarily reassurance that rivaroxaban levels are excessive. Although smaller amounts of rivaroxaban (<100ug/l) may still be present when the PT is normal its clinical significance and its anticoagulant needs to be judged on a case by case basis. Rivaroxaban anti Xa assay will quantify the drug concentration however turnaround time is slower. There is significant variation in rivaroxaban when co prescribed with other medications utilising CYP3A4. Although the results demonstrated when used with an inhibitor the elevated rivaroxaban concentration may not necessary have addition anticoagulant effect this raises the concern when the opposite siituation arises. If a patient is found to have a clot while on rivaroxaban it may be appropriate to check the rivaroxaban specific anti Xa to ensure its therapeutic especially when patients have co prescribed CYP3A4 inducers.
Session topic: E-poster
Type: Publication Only
Background
Direct oral anticoagulants drugs are now commonly used in clinical practice. Rivaroxaban inhibits free factor Xa and hence prothrombinase activity as well as clot bound Xa, thus effectively blocking thrombin generation. One main advantage over vitamin K antagonists is that blood coagulation monitoring is not necessary. However introducing a static change into a dynamic cascade always raises concern. The concentration may potentially need to be measured in certain clinical situations. These may include urgent surgery, perioperative management, thromboembolic events, bleeding events and suspected overdose. All routine coagulation screens performed in Northern Ireland are undertaken on a Sysmex Coagulaometer using the Innovin reagent. The Regional Specialty Coagulation Laboratory uses a Stago analyser with the STA Neoplastine CI+ reagent. The effect on the coagulation screen by rivaroxaban is known to vary between analysers making interpretation difficult.
Aims
To assess the effect of rivaroxaban on the current coagulation screen to help aid clinicians in making urgent decisions. To assess the variation of rivaroxaban concentrations between patients invivo rather than a controlled dilutional experiment.
Methods
Recording the dose and time from last drug ingestion we were able to measure the effect on the standard coagulation screen with both analysers. On the same samples the rivaroxaban concentration was measured with the specific anti-Xa rivaroxaban assay. Each recruited patient had their age, renal function and other co prescribed medications recorded to assess variation within these parameters.As a control, healthy volunteers on no anticoagulation had their rivaroxaban levels measured. The volunteers’ rivaroxaban levels ranged from 15-21ug/l and therefore we assume no drug is present when levels fall into, and below, this range.
Results
The effect on the PT and APTT was variable between analysers. The PT, in line with previous publications, was more sensitive than the APTT at smaller drug concentrations. The Neoplastine CI plus reagent on the Stago analyser was more sensitive than the Innovin reagent to rivaroxaban concentrations. The Neoplastine CI PT was prolonged in all samples taken within 17 hours of rivaroxaban ingestion. Our results compare with University Hospital Hotel Dieu (Paris) which found peak concentrations up to 400ug/l and trough concentrations up to160ug/l. However our results demontrated more variation with some patients have a higher rivaroxaban level than expected 600ug/l. These patients were also taking verapamil. We noted the SPC advises rivaroxaban not to be used in patients who are receiving concomitant combined P-gp and moderate CYP3A4 inhibitors unless the potential benefit justifies the potential risk.2There is a positive correlation between rivaroxaban concentration and Neoplastine CI PT reagent with prolongation up to a certain concentration and beyond this the effect on Neoplastine CI PT appears to plateau. The patients with a rivaroxaban concentration in excess of 600ug/l had a similar PT than those with a rivaroxaban concentration of 450ug/l.
Conclusion
The PT, provided it is sensitive to rivaroxaban, is a quick test and may be useful to ascertain rivaroxaban presence or not but given the plateau effect, not necessarily reassurance that rivaroxaban levels are excessive. Although smaller amounts of rivaroxaban (<100ug/l) may still be present when the PT is normal its clinical significance and its anticoagulant needs to be judged on a case by case basis. Rivaroxaban anti Xa assay will quantify the drug concentration however turnaround time is slower. There is significant variation in rivaroxaban when co prescribed with other medications utilising CYP3A4. Although the results demonstrated when used with an inhibitor the elevated rivaroxaban concentration may not necessary have addition anticoagulant effect this raises the concern when the opposite siituation arises. If a patient is found to have a clot while on rivaroxaban it may be appropriate to check the rivaroxaban specific anti Xa to ensure its therapeutic especially when patients have co prescribed CYP3A4 inducers.
Session topic: E-poster
Abstract: PB2199
Type: Publication Only
Background
Direct oral anticoagulants drugs are now commonly used in clinical practice. Rivaroxaban inhibits free factor Xa and hence prothrombinase activity as well as clot bound Xa, thus effectively blocking thrombin generation. One main advantage over vitamin K antagonists is that blood coagulation monitoring is not necessary. However introducing a static change into a dynamic cascade always raises concern. The concentration may potentially need to be measured in certain clinical situations. These may include urgent surgery, perioperative management, thromboembolic events, bleeding events and suspected overdose. All routine coagulation screens performed in Northern Ireland are undertaken on a Sysmex Coagulaometer using the Innovin reagent. The Regional Specialty Coagulation Laboratory uses a Stago analyser with the STA Neoplastine CI+ reagent. The effect on the coagulation screen by rivaroxaban is known to vary between analysers making interpretation difficult.
Aims
To assess the effect of rivaroxaban on the current coagulation screen to help aid clinicians in making urgent decisions. To assess the variation of rivaroxaban concentrations between patients invivo rather than a controlled dilutional experiment.
Methods
Recording the dose and time from last drug ingestion we were able to measure the effect on the standard coagulation screen with both analysers. On the same samples the rivaroxaban concentration was measured with the specific anti-Xa rivaroxaban assay. Each recruited patient had their age, renal function and other co prescribed medications recorded to assess variation within these parameters.As a control, healthy volunteers on no anticoagulation had their rivaroxaban levels measured. The volunteers’ rivaroxaban levels ranged from 15-21ug/l and therefore we assume no drug is present when levels fall into, and below, this range.
Results
The effect on the PT and APTT was variable between analysers. The PT, in line with previous publications, was more sensitive than the APTT at smaller drug concentrations. The Neoplastine CI plus reagent on the Stago analyser was more sensitive than the Innovin reagent to rivaroxaban concentrations. The Neoplastine CI PT was prolonged in all samples taken within 17 hours of rivaroxaban ingestion. Our results compare with University Hospital Hotel Dieu (Paris) which found peak concentrations up to 400ug/l and trough concentrations up to160ug/l. However our results demontrated more variation with some patients have a higher rivaroxaban level than expected 600ug/l. These patients were also taking verapamil. We noted the SPC advises rivaroxaban not to be used in patients who are receiving concomitant combined P-gp and moderate CYP3A4 inhibitors unless the potential benefit justifies the potential risk.2There is a positive correlation between rivaroxaban concentration and Neoplastine CI PT reagent with prolongation up to a certain concentration and beyond this the effect on Neoplastine CI PT appears to plateau. The patients with a rivaroxaban concentration in excess of 600ug/l had a similar PT than those with a rivaroxaban concentration of 450ug/l.
Conclusion
The PT, provided it is sensitive to rivaroxaban, is a quick test and may be useful to ascertain rivaroxaban presence or not but given the plateau effect, not necessarily reassurance that rivaroxaban levels are excessive. Although smaller amounts of rivaroxaban (<100ug/l) may still be present when the PT is normal its clinical significance and its anticoagulant needs to be judged on a case by case basis. Rivaroxaban anti Xa assay will quantify the drug concentration however turnaround time is slower. There is significant variation in rivaroxaban when co prescribed with other medications utilising CYP3A4. Although the results demonstrated when used with an inhibitor the elevated rivaroxaban concentration may not necessary have addition anticoagulant effect this raises the concern when the opposite siituation arises. If a patient is found to have a clot while on rivaroxaban it may be appropriate to check the rivaroxaban specific anti Xa to ensure its therapeutic especially when patients have co prescribed CYP3A4 inducers.
Session topic: E-poster
Type: Publication Only
Background
Direct oral anticoagulants drugs are now commonly used in clinical practice. Rivaroxaban inhibits free factor Xa and hence prothrombinase activity as well as clot bound Xa, thus effectively blocking thrombin generation. One main advantage over vitamin K antagonists is that blood coagulation monitoring is not necessary. However introducing a static change into a dynamic cascade always raises concern. The concentration may potentially need to be measured in certain clinical situations. These may include urgent surgery, perioperative management, thromboembolic events, bleeding events and suspected overdose. All routine coagulation screens performed in Northern Ireland are undertaken on a Sysmex Coagulaometer using the Innovin reagent. The Regional Specialty Coagulation Laboratory uses a Stago analyser with the STA Neoplastine CI+ reagent. The effect on the coagulation screen by rivaroxaban is known to vary between analysers making interpretation difficult.
Aims
To assess the effect of rivaroxaban on the current coagulation screen to help aid clinicians in making urgent decisions. To assess the variation of rivaroxaban concentrations between patients invivo rather than a controlled dilutional experiment.
Methods
Recording the dose and time from last drug ingestion we were able to measure the effect on the standard coagulation screen with both analysers. On the same samples the rivaroxaban concentration was measured with the specific anti-Xa rivaroxaban assay. Each recruited patient had their age, renal function and other co prescribed medications recorded to assess variation within these parameters.As a control, healthy volunteers on no anticoagulation had their rivaroxaban levels measured. The volunteers’ rivaroxaban levels ranged from 15-21ug/l and therefore we assume no drug is present when levels fall into, and below, this range.
Results
The effect on the PT and APTT was variable between analysers. The PT, in line with previous publications, was more sensitive than the APTT at smaller drug concentrations. The Neoplastine CI plus reagent on the Stago analyser was more sensitive than the Innovin reagent to rivaroxaban concentrations. The Neoplastine CI PT was prolonged in all samples taken within 17 hours of rivaroxaban ingestion. Our results compare with University Hospital Hotel Dieu (Paris) which found peak concentrations up to 400ug/l and trough concentrations up to160ug/l. However our results demontrated more variation with some patients have a higher rivaroxaban level than expected 600ug/l. These patients were also taking verapamil. We noted the SPC advises rivaroxaban not to be used in patients who are receiving concomitant combined P-gp and moderate CYP3A4 inhibitors unless the potential benefit justifies the potential risk.2There is a positive correlation between rivaroxaban concentration and Neoplastine CI PT reagent with prolongation up to a certain concentration and beyond this the effect on Neoplastine CI PT appears to plateau. The patients with a rivaroxaban concentration in excess of 600ug/l had a similar PT than those with a rivaroxaban concentration of 450ug/l.
Conclusion
The PT, provided it is sensitive to rivaroxaban, is a quick test and may be useful to ascertain rivaroxaban presence or not but given the plateau effect, not necessarily reassurance that rivaroxaban levels are excessive. Although smaller amounts of rivaroxaban (<100ug/l) may still be present when the PT is normal its clinical significance and its anticoagulant needs to be judged on a case by case basis. Rivaroxaban anti Xa assay will quantify the drug concentration however turnaround time is slower. There is significant variation in rivaroxaban when co prescribed with other medications utilising CYP3A4. Although the results demonstrated when used with an inhibitor the elevated rivaroxaban concentration may not necessary have addition anticoagulant effect this raises the concern when the opposite siituation arises. If a patient is found to have a clot while on rivaroxaban it may be appropriate to check the rivaroxaban specific anti Xa to ensure its therapeutic especially when patients have co prescribed CYP3A4 inducers.
Session topic: E-poster
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