Spectrophotometric Assays of Prothrombin in Plasma of Patients Using Oral Anticoagulants

1979 ◽  
Vol 42 (04) ◽  
pp. 1296-1305 ◽  
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.

Direct Anticoagulants Versus Vitamin K Antagonists in Patients Aged 80 Years or Older With Atrial Fibrillation in a “Real-world” Nationwide Registry: Insights From the FANTASIIA Study

2020 ◽  
Vol 25 (4) ◽  
pp. 316-323
Author(s):  
Martín Ruiz Ortiz ◽  
Javier Muñiz ◽  
María Asunción Esteve-Pastor ◽  
Francisco Marín ◽  
Inmaculada Roldán ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K ◽  
Real World ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Left Ventricular ◽  
Anticoagulant Treatment ◽  
Cancer History

Objective: To describe major events at follow up in octogenarian patients with atrial fibrillation (AF) according to anticoagulant treatment: direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs). Methods: A total of 578 anticoagulated patients aged ≥80 years with AF were included in a prospective, observational, multicenter study. Basal features, embolic events (stroke and systemic embolism), severe bleedings, and all-cause mortality at follow up were investigated according to the anticoagulant treatment received. Results: Mean age was 84.0 ± 3.4 years, 56% were women. Direct oral anticoagulants were prescribed to 123 (21.3%) patients. Compared with 455 (78.7%) patients treated with VKAs, those treated with DOACs presented a lower frequency of permanent AF (52.9% vs 61.6%, P = .01), cancer history (4.9% vs 10.9%, P = .046), renal failure (21.1% vs 32.2%, P = .02), and left ventricular dysfunction (2.4% vs 8.0%, P = .03); and higher frequency of previous stroke (26.0% vs 16.6%, P = .02) and previous major bleeding (8.1% vs 3.6%, P = .03). There were no significant differences in Charlson, CHA2DS2VASc, nor HAS-BLED scores. At 3-year follow up, rates of embolic events, severe bleedings, and all-cause death (per 100 patients-year) were similar in both groups (DOACs vs VKAs): 0.34 vs 1.35 ( P = .15), 3.45 vs 4.41 ( P = .48), and 8.2 vs 11.0 ( P = .18), respectively, without significant differences after multivariate analysis (hazard ratio [HR]: 0.25, 95% confidence interval [CI]: 0.03-1.93, P = .19; HR: 0.88, 95% CI: 0.44-1.76, P = .72 and HR: 0.84, 95% CI: 0.53-1.33, P = .46, respectively). Conclusion: In this “real-world” registry, the differences in major events rates in octogenarians with AF were not statistically significant in those treated with DOACs versus VKAs.

scholarly journals The Severity of Intracranial Hemorrhages Measured by Free Hemoglobin in the Brain Depends on the Anticoagulant Class: Experimental Data

2017 ◽  
Vol 2017 ◽  
pp. 1-4 ◽  
Author(s):  
Kyle M. Ware ◽  
Douglas L. Feinstein ◽  
Israel Rubinstein ◽  
Prudhvi Battula ◽  
Jose Otero ◽  
...  
Keyword(s):  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Hemoglobin Concentration ◽  
Thrombin Inhibitor ◽  
Free Hemoglobin ◽  
Intracranial Hemorrhages ◽  
The Brain

Background and Purpose. Anticoagulant therapy is broadly used to prevent thromboembolic events. Intracranial hemorrhages are serious complications of anticoagulation, especially with warfarin. Direct oral anticoagulants reduce but do not eliminate the risk of intracranial hemorrhages. The aim of this study is to determine the degree of intracranial hemorrhage after application of anticoagulants without additional triggers. Methods. Rats were treated with different anticoagulant classes (vitamin K antagonists, heparin, direct thrombin inhibitor, and factor Xa inhibitor). Brain hemorrhages were assessed by the free hemoglobin concentration in the brain parenchyma. Results. Vitamin K antagonists (warfarin and brodifacoum) significantly increased free hemoglobin in the brain. Among direct oral anticoagulants, thrombin inhibitor dabigatran also significantly increased free hemoglobin in the brain, whereas treatment with factor Xa inhibitor rivaroxaban did not have significant effect on the free hemoglobin concentration. Conclusions. Our data indicates that the severity of brain hemorrhages depends on the anticoagulant class and it is more pronounced with vitamin K antagonists.

The NOACs: clinical pharmacology

ESC CardioMed ◽  
2018 ◽  
pp. 268-272
Author(s):  
Jeffrey Weitz
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K ◽  
Active Site ◽  
Randomized Clinical Trials ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Factor Xa ◽  
Vitamin K Antagonist ◽  
Phase Iii ◽  
High Affinity

The limitations of vitamin K antagonists prompted the development of new oral anticoagulants that could be administered in fixed doses without routine coagulation monitoring. Focusing on thrombin and factor Xa because of their prominent roles in coagulation, structure-based design led to the development of small molecules that bind to the active site pockets of these enzymes with high affinity and specificity. Four non-vitamin K antagonist oral anticoagulants are now licensed: dabigatran, which inhibits thrombin, and rivaroxaban, apixaban, and edoxaban, which inhibit factor Xa. In phase III randomized clinical trials that included over 100,000 patients these agents have proven to be at least as effective as vitamin K antagonists for prevention of stroke in patients with non-valvular atrial fibrillation and for treatment of venous thromboembolism, and to produce less bleeding, particularly less intracranial bleeding.

scholarly journals Reversal of Oral Anticoagulants for Intracerebral Hemorrhage Patients: Best Strategies

2017 ◽  
Vol 38 (06) ◽  
pp. 726-736 ◽  
Author(s):  
Lanting Fuh ◽  
Jonathan Sin ◽  
Joshua Goldstein ◽  
Bryan Hayes
Keyword(s):  
Intracerebral Hemorrhage ◽  
Vitamin K ◽  
Prothrombin Complex Concentrate ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Factor Xa ◽  
Quality Data ◽  
Reversal Agent ◽  
Intravenous Vitamin ◽  
Time Of Presentation

AbstractIn patients with acute intracerebral hemorrhage (ICH), one of the major concerns is ongoing bleeding or ICH expansion. Anticoagulated patients are at higher risk of ongoing expansion and worse outcome. It may be that rapid anticoagulation reversal can reduce the risk of expansion and improve clinical outcome. For those taking coumarins, the best available evidence suggests that intravenous vitamin K combined with four-factor prothrombin complex concentrate (4F-PCC) is the most rapid and effective regimen to restore hemostasis. For those on dabigatran, the highest quality data available for reversal are for idarucizumab, although it is not yet clear whether patients derive clinical benefit from this reversal. In the absence or failure of idarucizumab, activated prothrombin complex concentrate (aPCC) is recommended. For those on factor Xa inhibitors, the ideal reversal agent is not clear. Many providers use 4F-PCC or aPCC, but more specific agents are in clinical trials and may soon be available. In addition, the half-lives of the non–vitamin K antagonists are relatively short compared with warfarin, and so some patients may not have a clinically relevant coagulopathy at the time of presentation. Overall, the optimal reversal agent, when one is required, is a function of which anticoagulant the patient is taking.

scholarly journals Vitamin K in COVID-19—Potential Anti-COVID-19 Properties of Fermented Milk Fortified with Bee Honey as a Natural Source of Vitamin K and Probiotics

Fermentation ◽  
2021 ◽  
Vol 7 (4) ◽  
pp. 202
Author(s):  
Amira Mohammed Ali ◽  
Hiroshi Kunugi ◽  
Hend A. Abdelmageed ◽  
Ahmed S. Mandour ◽  
Mostafa Elsayed Ahmed ◽  
...  
Keyword(s):  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Empirical Studies ◽  
Fermented Milk ◽  
Organ Damage ◽  
Natural Source ◽  
Vitamin K Deficiency ◽  
K Deficiency

Vitamin K deficiency is evident in severe and fatal COVID-19 patients. It is associated with the cytokine storm, thrombotic complications, multiple organ damage, and high mortality, suggesting a key role of vitamin K in the pathology of COVID-19. To support this view, we summarized findings reported from machine learning studies, molecular simulation, and human studies on the association between vitamin K and SARS-CoV-2. We also investigated the literature for the association between vitamin K antagonists (VKA) and the prognosis of COVID-19. In addition, we speculated that fermented milk fortified with bee honey as a natural source of vitamin K and probiotics may protect against COVID-19 and its severity. The results reported by several studies emphasize vitamin K deficiency in COVID-19 and related complications. However, the literature on the role of VKA and other oral anticoagulants in COVID-19 is controversial: some studies report reductions in (intensive care unit admission, mechanical ventilation, and mortality), others report no effect on mortality, while some studies report higher mortality among patients on chronic oral anticoagulants, including VKA. Supplementing fermented milk with honey increases milk peptides, bacterial vitamin K production, and compounds that act as potent antioxidants: phenols, sulforaphane, and metabolites of lactobacilli. Lactobacilli are probiotic bacteria that are suggested to interfere with various aspects of COVID-19 infection ranging from receptor binding to metabolic pathways involved in disease prognosis. Thus, fermented milk that contains natural honey may be a dietary manipulation capable of correcting nutritional and immune deficiencies that predispose to and aggravate COVID-19. Empirical studies are warranted to investigate the benefits of these compounds.

Prediction of Vitamin K Response Using the Echis Time and Echis-Prothrombin Time Ratio

1990 ◽  
Vol 64 (03) ◽  
pp. 353-357 ◽  
Author(s):  
C Solano ◽  
R G Cobcroft ◽  
D C Scott
Keyword(s):  
Prothrombin Time ◽  
Vitamin K ◽  
Factor X ◽  
Time Ratio ◽  
Factor Ii ◽  
Before And After ◽  
K Deficiency ◽  
Echis Carinatus ◽  
Factor X Activation ◽  
K Response

Summary Echis carinatus venom contains proteases capable of activating both normal and descarboxy prothrombin. We showed this venom (Sigma) principally activates prothrombin with almost no factor X activation. Echis time in combination with prothrombin time can predict vitamin K responsiveness since the Echis time is usually normal in the presence of descarboxy prothrombin associated with vitamin K deficiency.38 patients with abnormal routine prothrombin times (PT) had both coagulant and immunogenic factor II assays along with Echis times done before and after vitamin K. Of 22 patients responding to vitamin K, based on correction of PT, 21 had normal initial Echis times and of 16 not responding, 11 had abnormal Echis times, giving a sensitivity of 95.4% and specificity of 68.8% for vitamin K responsiveness. 90% of patients with a PT/Echis time ratio <1.3 and a prolonged Echis time did not correct their PTs with vitamin K therapy.The 5 non-responders with normal Echis times all showed normal initial coagulant and antigenic prothrombin, but 3 had low F V and/or F VII.

New oral anticoagulants in development

2010 ◽  
Vol 103 (01) ◽  
pp. 62-70 ◽  
Author(s):  
Jeffrey Weitz
Keyword(s):  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Factor Xa ◽  
New Oral Anticoagulants ◽  
Dietary Vitamin ◽  
Multiple Drug ◽  
Coagulation Monitoring ◽  
Advanced Stages

SummaryAlthough currently available anticoagulants are effective for the prevention and treatment of thromboembolic disorders, they have several drawbacks. Low-molecular-weight heparins and fondaparinux produce a predictable level of anticoagulation that obviates the need for coagulation monitoring, but they must be given parenterally, which renders them inconvenient for long-term use. Vitamin K antagonists, such as warfarin, are administered orally, but produce a variable anticoagulant response because genetic polymorphisms, dietary vitamin K intake and multiple drug-drug interactions affect their metabolism. Consequently, coagulation monitoring and frequent dose adjustments are needed to ensure that a therapeutic level of anticoagulation is achieved. This is burdensome for patients and physicians, and costly for the healthcare system. These limitations have prompted the development of new oral anticoagulants that target thrombin or factor Xa and can be given in fixed doses without coagulation monitoring. This paper focuses on the new oral anticoagulants in the most advanced stages of development.

scholarly journals Should we Test the Prothrombin Time in Anticoagulated Epistaxis Patients?

2013 ◽  
Vol 4 (1) ◽  
pp. ar.2013.4.0049 ◽  
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.

scholarly journals Treatment with new oral anticoagulants in the family medicine practice

2015 ◽  
Vol 10 (4) ◽  
pp. 329-332
Author(s):  
Camelia DIACONU ◽  
◽  
Giorgiana DEDIU ◽  
Mădălina ILIE ◽  
Mihaela Adela IANCU ◽  
...  
Keyword(s):  
Drug Interactions ◽  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Rapid Onset ◽  
New Oral Anticoagulants ◽  
Anticoagulant Treatment ◽  
Oral Anticoagulant Treatment ◽  
Rapid Clearance ◽  
Concomitant Medications

Vitamin K antagonists represented for more than 50 years the only oral anticoagulant treatment option, though encumbered by numerous food and drug interactions, with direct impact on the safety and efficacy of this treatment. The frequent complications of anticoagulant treatment with vitamin K antagonists led to the need for the emergence of new oral anticoagulants (NOAC). The main NOACs used today are dabigatran, rivaroxaban and apixaban. NOAC have a number of advantages over antivitamin K anticoagulants: fewer drug interactions, no food interactions, rapid onset of the anticoagulant action, rapid clearance, no need for INR monitoring. NOAC therapy must be individualized according to patient age, comorbidities and medical history, renal function, concomitant medications. Given that clinical experience with NOAC is still limited in practice, physicians (including family physicians) must monitor these patients and need to pay attention and report any side effects.

Anticoagulants

2006 ◽  
Author(s):  
Richard C. Becker ◽  
Frederick A. Spencer
Keyword(s):  
Clinical Practice ◽  
Prothrombin Time ◽  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Plasma Concentrations ◽  
Therapeutic Index ◽  
Dose Titration ◽  
Direct Thrombin Inhibitors ◽  
Factor V ◽  
High Concentrations

Because of the narrow therapeutic index of warfarin and unfractionated heparin (UFH), monitoring their anticoagulant effects is required. On the other hand, lowmolecular- weight heparin (LMWH) and fibrinolytic agents need to be monitored only under certain circumstances. Although newer anticoagulants will not require routine monitoring for dose titration, a means to determine their systemic effects and individual (patient-specific) response to administration will likely have roles in clinical practice. The prothrombin time is used to monitor vitamin K antagonist therapy. This test is sensitive to the plasma concentrations (activity) of clotting factors II (prothrombin), V, VII, and X. Vitamin K antagonists affect the vitamin K–dependent factors II, VII, IX, and X, as well as proteins C, S, and Z. Thus, the prothrombin time does not reflect the effect of vitamin K antagonists on some factors (IX and proteins C, S, and Z) and is sensitive to others (factor V) (not directly influenced by treatment). The prothrombin time is not an ideal test for monitoring vitamin K antagonists; however, its simplicity and widespread availability have established its place in clinical practice. By convention, prothrombin times are now reported as international normalized ratios (INRs). This is the ratio of the patient’s prothrombin time to a control prothrombin time, raised to a power—the international sensitivity index (ISI). The latter reflects the calibration of the thromboplastin used for the prothrombin time testing to an internationally agreed upon standard. In many laboratories the reagent currently used is a recombinant thromboplastin, which has an ISI of 1.0 There are several cautions related to interpreting the results of prothrombin time tests that are worth monitoring. Since the test is sensitive to the level of factor V in the plasma, improper sample storage or delayed testing may cause loss of factor V (activity) and yield prothrombin time values above the expected range. High concentrations of heparin may also prolong the prothrombin time; this usually occurs when the sample is obtained within a few minutes of administering a bolus dose. Direct thrombin inhibitors, such as hirudin, bivalirudin, argatroban, and ximelagatran, may also prolong the prothrombin time to a variable degree.

Sign in / Sign up

Export Citation Format

Share Document