Effectivity of a joint didactic intervention by School for Patients on inappropriate control prothrombin time anticoagulated patients. Protocol for developing a randomized and controlled clinical trial.

Abstract Background Oral anticoagulant drugs represent an essential tool in thrombo-embolic events prevention. Most used are vitamin K antagonists, whose plasma level is monitored by measuring prothrombin time using the International Normalized Ratio. If it takes values out of the recommended range, the patient will have a higher risk of suffering from thromboembolic or hemorrhagic complications. Previous research has shown that about 33% of total patients keep values on inappropriate level. The purpose of the study is to improve International Normalized Ratio control figures by a joint didactic intervention based on the Junta de Andalucía School for Patients method that will be implemented by anticoagulated patients themselves. Methods A randomized clinical trial was carried out at primary care centers from one healthcare area in Málaga (Andalusia, Spain). Study population: patients included in an oral anticoagulant therapy program consisting in using vitamin K antagonists. First step detection of patients on oral anticoagulation program with International Normalized Ratio control on therapeutic level during 65% or less over total time. Second step: patients with inappropriate International Normalized Ratio control were included in two groups: Group 1 or Joint Intervention Group: patients were instructed a joint didactic intervention “from peer to peer”, by a previously trained and expert anticoagulated patient. Group 2 or Control Group: Control group performed usual clinical practice: people were schedule by nurses about one time per month, except cases in which controls were inappropriate; in those circumstances patients were schedule before that period expired. In order to built the study group and the control group, 312 individuals were required (156 in each group) to detect differences in INR figures equal or higher than 15% between both groups. Study variables time on therapeutic levels before and after intervention, sociodemographic variables, vital signs, existence of cardiovascular risk factors or accompanying diseases in the clinical records, laboratory test including complete blood count, bleeding time, and prothrombin time or partial thromboplastin time and blood chemistry, other prescribed drugs, and social support. Almost-experimental analytic study with before-after statistical analysis of the intervention were made. Lineal regression models were applied on main variables results (International Normalized Ratio value, time on therapeutic level) inputting sociodemographic variables, accompanying diseases and social support.

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New artificial intelligence prediction model using serial prothrombin time international normalized ratio measurements in atrial fibrillation patients on vitamin K antagonists: GARFIELD-AF

European Heart Journal - Cardiovascular Pharmacotherapy ◽

10.1093/ehjcvp/pvz076 ◽

2019 ◽

Vol 6 (5) ◽

pp. 301-309 ◽

Cited By ~ 2

Author(s):

Shinichi Goto ◽

Shinya Goto ◽

Karen S Pieper ◽

Jean-Pierre Bassand ◽

Alan John Camm ◽

...

Keyword(s):

Neural Network ◽

Artificial Intelligence ◽

Atrial Fibrillation ◽

Prothrombin Time ◽

Clinical Outcomes ◽

Vitamin K ◽

Vitamin K Antagonists ◽

International Normalized Ratio ◽

One Dimensional ◽

Major Bleed

Abstract Aims Most clinical risk stratification models are based on measurement at a single time-point rather than serial measurements. Artificial intelligence (AI) is able to predict one-dimensional outcomes from multi-dimensional datasets. Using data from Global Anticoagulant Registry in the Field (GARFIELD)-AF registry, a new AI model was developed for predicting clinical outcomes in atrial fibrillation (AF) patients up to 1 year based on sequential measures of prothrombin time international normalized ratio (PT-INR) within 30 days of enrolment. Methods and results Patients with newly diagnosed AF who were treated with vitamin K antagonists (VKAs) and had at least three measurements of PT-INR taken over the first 30 days after prescription were analysed. The AI model was constructed with multilayer neural network including long short-term memory and one-dimensional convolution layers. The neural network was trained using PT-INR measurements within days 0–30 after starting treatment and clinical outcomes over days 31–365 in a derivation cohort (cohorts 1–3; n = 3185). Accuracy of the AI model at predicting major bleed, stroke/systemic embolism (SE), and death was assessed in a validation cohort (cohorts 4–5; n = 1523). The model’s c-statistic for predicting major bleed, stroke/SE, and all-cause death was 0.75, 0.70, and 0.61, respectively. Conclusions Using serial PT-INR values collected within 1 month after starting VKA, the new AI model performed better than time in therapeutic range at predicting clinical outcomes occurring up to 12 months thereafter. Serial PT-INR values contain important information that can be analysed by computer to help predict adverse clinical outcomes.

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Critical Role of Factors II and X During Coumarin Anticoagulation and Their Combined Measurement with a New Prothrombin Time Variant (Fiix-PT),

Blood ◽

10.1182/blood.v118.21.3354.3354 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3354-3354

Author(s):

Pall T. Onundarson ◽

Brynja R. Gudmundsdottir ◽

Charles W. Francis

Keyword(s):

Prothrombin Time ◽

Vitamin K ◽

Vitamin K Antagonists ◽

Critical Role ◽

Patent Application ◽

Maximum Velocity ◽

Coagulation Factors ◽

Clot Formation ◽

Normal Platelet ◽

Anticoagulated Patients

Abstract Abstract 3354 Introduction: Vitamin K antagonists (VKA) are monitored with prothrombin time (PT) based assays that are equally sensitive to reductions in factors II, VII or X. However, previous studies suggest that the anticoagulant effect of VKA depends primarily on reductions in factors II and X and not VII. Aim and methods: We compared the effect of vitamin K dependent (VKD) coagulation factors on PT (Quick and Owren methods) and also on rotational thromboelastometric (ROTEM) parameters. The experiments used normal platelet poor plasma (PPP) and PPP selectively immunodepleted of individual VKD factors, with and without added platelet phospholipid or washed platelets. Results: The PT was equally sensitive to reductions in factors II, VII or X. However, ROTEM parameters correlated poorly with the PT in anticoagulated patients` plasmas. ROTEM experiments showed that the clotting time, maximum velocity of clot formation and the maximum clot firmness were more affected by reductions in FII or FX than by FVII or FIX concentrations which had little influence except at very low concentrations. We developed a modified PT that was sensitive only to reductions in factors II and X by using factor II and X (Fiix) depleted plasma in the PT system. The Fiix-PT (Fiix-INR) correlated well with PT (INR) but the Fiix-INR fluctuated less than the INR in anticoagulated patients reflecting its insensitivity to FVII. Conclusion: The ROTEM results suggest that mild to moderate reductions in factors II or X are more important in clot formation than factors VII or IX at therapeutically relevant factor concentrations. Reductions in FII and X may therefore better reflect anticoagulation with VKA than FVII or IX. FVII may be a confounding source of unwanted variation in PT-INR. The new Fiix-PT that is sensitive only to FII and FX may more accurately reflect the degree of therapeutic anticoagulation in patients treated with VKA than do the current PT assays which may overestimate the fluctuation in anticoagulation. Disclosures: Onundarson: See i. other: Patent application for Fiix method in process. Gudmundsdottir:Other, see i: patent applicaiton filed for Fiix method.

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Should we Test the Prothrombin Time in Anticoagulated Epistaxis Patients?

Allergy & Rhinology ◽

10.2500/ar.2013.4.0049 ◽

2013 ◽

Vol 4 (1) ◽

pp. ar.2013.4.0049 ◽

Cited By ~ 3

Author(s):

Michael B. Soyka ◽

David Holzmann

Keyword(s):

Prothrombin Time ◽

Vitamin K ◽

Oral Anticoagulation ◽

Vitamin K Antagonists ◽

International Normalized Ratio ◽

Increased Risk

Epistaxis is one of the most frequent emergencies in rhinology. Patients using anticoagulative medication are at increased risk for epistaxis. We evaluated the prothrombin time and the international normalized ratio (INR) in anticoagulated epistaxis patients. Patients suffering from epistaxis were prospectively included in a database and results from prothrombin testing were analyzed in the context of anticoagulation. One hundred sixteen of 591 epistaxis cases were identified to be on oral anticoagulation. The INR was found to be above therapeutic levels in 19 (16%) of these cases. We strongly recommend prothrombin time and INR testing in all epistaxis patients taking any sort of vitamin K antagonists.

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Management of Oral Anticoagulant-associated Intracerebral Hemorrhage

Journal of Stroke Medicine ◽

10.1177/2516608518821745 ◽

2018 ◽

Vol 1 (2) ◽

pp. 114-125

Author(s):

Corina Epple ◽

Thorsten Steiner

Keyword(s):

Vitamin K ◽

Oral Anticoagulant ◽

Anticoagulant Activity ◽

Oral Anticoagulant Therapy ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Clinical Problem ◽

International Normalized Ratio ◽

Bleeding Management ◽

Number Of Patients

Introduction: Oral anticoagulant-associated intracerebral hemorrhages (OAC-ICHs) account for nearly 20% of all ICH and are associated with high mortality. The number of patients with an indication for oral anticoagulant therapy (OAT) is increasing with the aging population; therefore, despite the improved safety profile of non-vitamin K oral anticoagulants (NOACs), the number of patients with OAC-ICH will increase. OAT was simplified with the introduction of NOACs, which are easy to handle and show a favorable risk-benefit profile. The rate of ICH is lower than for vitamin K antagonists (VKA) and routine coagulation testing is not required. Nevertheless, OAC-ICH does occur and is still a devastating disease, thus representing the most feared complication in OAT, irrespective of treatment with VKA or NOAC. Purpose: The aim of this article is to address the clinical problem of bleeding management in patients with ICH due to OAC and will consider anticoagulation with NOAC and VKA. Recommendations: Restoring coagulation as soon as possible is the main goal and, therefore, knowledge of the actual coagulation status is essential. In VKA-associated ICH, the international normalized ratio (INR) should be lowered to below 1.3. However, laboratory measurement of anticoagulant activity in NOAC patients is more complex, rendering OAC-ICH treatment more complicated. The best assays are specialized and not widely available, whereas more accessible tests such as prothrombin time and activated partial thromboplastin time have important limitations. For VKA-ICH, prothrombin complex concentrate (PCC) should be administered to reverse the INR. For dabigatran-related ICH, 5 g idarucizumab should be administered. For factor Xa inhibitors, PCC is recommended in the absence of andexanet alfa as soon as an OAC-related ICH evolves. Resuming OAC after ICH should be considered, depending on risk factors and a risk-benefit evaluation.

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Management of anticoagulated patients in dentoalveolar surgery: a retrospective study comparing bridging with heparin versus unpaused vitamin K antagonist medication

BMC Oral Health ◽

10.1186/s12903-021-01464-9 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Mayte Buchbender ◽

Felix Rößler ◽

Marco R. Kesting ◽

Gesche Frohwitter ◽

Werner Adler ◽

...

Keyword(s):

Retrospective Study ◽

Prothrombin Time ◽

Vitamin K ◽

Tooth Extraction ◽

Postoperative Bleeding ◽

Vitamin K Antagonist ◽

Control Group ◽

Risk For Bleeding ◽

Tooth Removal ◽

Anticoagulated Patients

Abstract Background The aim of this study was to investigate the occurrence of postoperative bleeding following dentoalveolar surgery in patients with either continued vitamin K antagonist medication or perioperative bridging using heparin. Methods A retrospective study was performed analyzing patients who underwent tooth extraction between 2012 and 2017. Patients were retrospectively allocated into two comparative groups: un-paused vitamin K antagonist medication versus bridging using heparin. A healthy, non-anticoagulated cohort with equivalent surgery served as a control group. Main outcome measures were: the occurrence and frequency of postoperative bleeding, the number of removed teeth, the surgical technique of tooth removal (extraction/osteotomy/combined extraction and osteotomy) and the prothrombin time. Results In total, 475 patients were included in the study with 170 patients in the group of un-paused vitamin K antagonist medication VG, 135 patients in the Bridging group BG and 170 patients in the control group CG. Postoperative bleeding was significant: CG versus VG p = 0.004; CG versus BG p < 0.001, BG versus VG p < 0.001. A significant correlation of number of the extracted teeth in the BG (p = 0.014) and no significance in VG (p = 0.298) and CG (p = 0.210) and in the BG versus VG and CG with p < 0.001 in terms of surgical intervention extraction. No difference observed in terms of prothrombin time. Conclusions Bridging with heparin increases the risk for bleeding compared to un-paused vitamin K antagonist medication. The perioperative management of anticoagulated patients requires a well-coordinated interdisciplinary teamwork to minimize or at best avoid both: postoperative bleeding and thromboembolic incidences.

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Management of anticoagulated patients in dentoalveolar surgery: a retrospective study comparing Bridging with heparin versus unpaused vitamin K antagonist medication.

10.21203/rs.3.rs-55563/v2 ◽

2021 ◽

Author(s):

Mayte Buchbender ◽

F Rößler ◽

Marco Kesting ◽

Gesche Frohwitter ◽

Werner Adler ◽

...

Keyword(s):

Retrospective Study ◽

Prothrombin Time ◽

Vitamin K ◽

Tooth Extraction ◽

Postoperative Bleeding ◽

Vitamin K Antagonist ◽

Control Group ◽

Risk For Bleeding ◽

Tooth Removal ◽

Anticoagulated Patients

Abstract Background: The aim of this study was to investigate the occurrence of postoperative bleeding following dentoalveolar surgery in patients with either continued vitamin K antagonist medication or perioperative bridging using heparin. Methods: A retrospective study was performed analyzing patients who underwent tooth extraction between 2012 and 2017. Patients were retrospectively allocated into two comparative groups: un-paused vitamin K antagonist medication versus bridging using heparin. A healthy, non-anticoagulated cohort with equivalent surgery served as a control group. Main outcome measures were: the occurrence and frequency of postoperative bleeding, the number of removed teeth, the surgical technique of tooth removal (extraction/ osteotomy/ combined extraction and osteotomy) and the prothrombin time. Results: In total, 475 patients were included in the study with 170 patients in the group of un-paused vitamin K antagonist medication VG, 135 patients in the Bridging group BG and 170 patients in the control group CG. Postoperative bleeding was significant: CG vs.VG p=0.004; CG vs. BG p<0.001, BG vs.VG p<0.001. A significant correlation of number of the extracted teeth in the BG (p=0.014) and no significance in VG (p=0.298) and CG (p=0.210) and in the BG vs. VG and CG with p<0.001 in terms of surgical intervention extraction. No difference observed in terms of prothrombin time. Conclusion: Bridging with heparin increases the risk for bleeding compared to un-paused vitamin K antagonist medication. The perioperative management of anticoagulated patients requires a well- coordinated interdisciplinary teamwork to minimize or at best avoid both: postoperative bleeding and thromboembolic incidences. Key words:

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Absence of Interactions between Denosumab and Warfarin in Women with Osteoporosis

Reports ◽

10.3390/reports1030020 ◽

2018 ◽

Vol 1 (3) ◽

pp. 20

Author(s):

Vincenzo Polimeni ◽

Gianluca Sottilotta ◽

Fabiola Branca ◽

Nadia Mammone ◽

Antonio Panuccio

Keyword(s):

Monoclonal Antibody ◽

Bone Resorption ◽

Prothrombin Time ◽

Therapeutic Range ◽

Oral Anticoagulant ◽

International Normalized Ratio ◽

Prevention And Treatment ◽

Anticoagulated Patients

The monoclonal antibody denosumab reduces bone resorption. Warfarin is an oral anticoagulant used in the prevention and treatment of thrombosis. To date, there have been no studies on the interaction between warfarin and denosumab. The aim of the present study was to assess the maintenance of the Prothrombin Time International Normalized Ratio (INR) in the therapeutic range (TTR) in women under treatment with warfarin and denosumab, in order to evaluate the pharmacological interference of denosumab. No variations of the median TTR were found after undergoing treatment with denosumab: this shows that the intake of denosumab does not require additional checks in anticoagulated patients.

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Management of Anticoagulated Patients in Dentoalveolar Surgery: A Retrospective Study Comparing Bridging Versus Unpaused Vitamin K Antagonist Medication.

10.21203/rs.3.rs-55563/v1 ◽

2020 ◽

Author(s):

Mayte Buchbender ◽

F Rößler ◽

Marco Kesting ◽

Gesche Frohwitter ◽

Werner Adler ◽

...

Keyword(s):

Retrospective Study ◽

Prothrombin Time ◽

Vitamin K ◽

Tooth Extraction ◽

Postoperative Bleeding ◽

Vitamin K Antagonist ◽

Control Group ◽

Risk For Bleeding ◽

Tooth Removal ◽

Anticoagulated Patients

Abstract Objectives: The aim of this study was to investigate the occurrence of postoperative bleeding following dentoalveolar surgery in patients with either continued vitamin K antagonist medication or perioperative bridging using heparin. Study design: A retrospective study was performed analyzing patients who underwent tooth extraction between 2012 and 2017. Patients were retrospectively allocated into two comparative groups: un-paused vitamin K antagonist medication versus bridging using heparin. A healthy, non-anticoagulated cohort with equivalent surgery served as a control group. Main outcome measures were: the occurrence and frequency of postoperative bleeding, the number of removed teeth, the surgical technique of tooth removal (extraction/ osteotomy/ combined extraction and osteotomy) and the prothrombin time.Results: In total, 475 patients were included in the study with 170 patients in the group of un-paused vitamin K antagonist medication VG, 135 patients in the Bridging group BG and 170 patients in the control group CG. Postoperative bleeding was significant: CG vs.VG p=0.004; CG vs. BG p<0.001, BG vs.VG p<0.001. A significant correlation of number of the extracted teeth in the BG (p=0.014) and no significance in VG (p=0.298) and CG (p=0.210) and in the BG vs. VG and CG with p<0.001 in terms of surgical intervention extraction. No difference observed in terms of prothrombin time.Conclusion: Bridging increases the risk for bleeding compared to un-paused vitamin K antagonist medication. The perioperative management of anticoagulated patients requires a well- coordinated interdisciplinary teamwork to minimize or at best avoid both: postoperative bleeding and thromboembolic incidences.

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Relationship Between Total Prothrombin, Native Prothrombin and the International Normalized Ratio (INR)

Thrombosis and Haemostasis ◽

10.1055/s-0038-1656342 ◽

1992 ◽

Vol 68 (02) ◽

pp. 160-164 ◽

Cited By ~ 3

Author(s):

P J Braun ◽

K M Szewczyk

Keyword(s):

Anticoagulant Therapy ◽

Oral Anticoagulant ◽

Inverse Relationship ◽

Low Dose ◽

Oral Anticoagulant Therapy ◽

International Normalized Ratio ◽

Antigen Assay ◽

Dose Oral ◽

Anticoagulated Patients ◽

Sensitive Method

SummaryPlasma levels of total prothrombin and fully-carboxylated (native) prothrombin were compared with results of prothrombin time (PT) assays for patients undergoing oral anticoagulant therapy. Mean concentrations of total and native prothrombin in non-anticoagulated patients were 119 ± 13 µg/ml and 118 ± 22 µg/ml, respectively. In anticoagulated patients, INR values ranged as high as 9, and levels of total prothrombin and native prothrombin decreased with increasing INR to minimum values of 40 µg/ml and 5 µg/ml, respectively. Des-carboxy-prothrombin increased with INR, to a maximum of 60 µg/ml. The strongest correlation was observed between native prothrombin and the reciprocal of the INR (1/INR) (r = 0.89, slope = 122 µg/ml, n = 200). These results indicated that native prothrombin varied over a wider range and was more closely related to INR values than either total or des-carboxy-prothrombin. Levels of native prothrombin were decreased 2-fold from normal levels at INR = 2, indicating that the native prothrombin antigen assay may be a sensitive method for monitoring low-dose oral anticoagulant therapy. The inverse relationship between concentration of native prothrombin and INR may help in identification of appropriate therapeutic ranges for oral anticoagulant therapy.

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Spectrophotometric Assays of Prothrombin in Plasma of Patients Using Oral Anticoagulants

Thrombosis and Haemostasis ◽

10.1055/s-0038-1657025 ◽

1979 ◽

Vol 42 (04) ◽

pp. 1296-1305 ◽

Cited By ~ 29

Author(s):

R M Bertina ◽

W van der Marel-van Nieuwkoop ◽

E A Loeliger

Keyword(s):

Prothrombin Time ◽

Vitamin K ◽

Oral Anticoagulation ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Factor Xa ◽

Factor V ◽

Anticoagulant Treatment ◽

Factor Ii ◽

K Deficiency

SummaryTwo spectrophotometric assays for prothrombin have been developed and compared with a one stage coagulant and an immunological assay. One of these assays (called the XAPC assay) uses a combination of factor Xa, phospholipid, Ca2+ and factor V as activator of prothrombin, and measures only normal prothrombin. The second (the ECAR assay) uses Echis carinatus venom as activator. This assay measures both normal prothrombin and PIVKA II (protein induced by vitamin K antagonists/absence). Combination of the results obtained by the XAPC and ECAR assays provides rapid and reliable information on the degree of “subcarboxylation” of prothrombin (oral anticoagulation, vitamin K deficiency).For patients on long term anticoagulant treatment the prothrombin time (Thrombotest) shows better correlation with the ratio prothrombin/prothrombin plus PIVKA II (XAPC/ ECAR) than with the factor II concentration. For patients starting the anticoagulant treatment there is no correlation between the Thrombotest time and the XAPC/ECAR ratio.It seems doubtful that (a) spectrophotometric factor II assay(s) will be as useful as the prothrombin time in the control of oral anticoagulation.

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