scholarly journals How Do I Reverse Oral and Parenteral Anticoagulants?

2020 ◽  
Vol 40 (02) ◽  
pp. 201-213
Author(s):  
Jürgen Koscielny ◽  
Edita Rutkauskaite ◽  
Christoph Sucker ◽  
Christian von Heymann
Keyword(s):  
Vitamin K ◽  
Prothrombin Complex Concentrate ◽  
Vitamin K Antagonists ◽  
Factor Xa ◽  
International Normalized Ratio ◽  
Low Molecular Weight ◽  
Limited Data ◽  
Additional Risk ◽  
Treatment Volume ◽  
Adequate Management

AbstractAn understanding of reversal strategies alone is important to safely and effectively care for patients in cases of bleeding or invasive procedures. The recent diversification in the number of licensed anticoagulants makes an understanding of drug-specific reversal strategies essential. Intravenous or oral vitamin K can reverse the effect of vitamin K antagonists (VKAs) within 12 to 48 hours and is indicated for any bleeding or an international normalized ratio >10 or 4.5 to 10 in patients with additional risk factors for bleeding. Furthermore, an additional administration of prothrombin complex concentrate (PCC) may be necessary in cases of major bleeding related to VKA. Protamine (chloride or sulfate) fully reverses the effect of unfractionated heparin and partially in low-molecular-weight heparin. Idarucizumab has been approved for dabigatran reversal, whereas andexanet alfa is approved for the reversal of some oral factor Xa inhibitors (apixaban, rivaroxaban). PCC seems to enhance the haemostatic potential for the reversal of the effect of FXa-inhibitors. So far, there are promising but only limited data on the efficacy of this approach available. Each reversal strategy needs an adequate management beyond the hemostatic treatment (volume replacement, stabilization of homeostasis, e.g., pH and temperature, resumption of anticoagulation after successful treatment of bleeding, etc.) that is crucial for the successful management of acute bleedings, urgent high-risk surgery, thrombolytic therapies or thrombectomies as well as overdosing of anticoagulants.

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.

How I treat target-specific oral anticoagulant–associated bleeding

Blood ◽  
2014 ◽  
Vol 123 (8) ◽  
pp. 1152-1158 ◽  
Author(s):  
Deborah M. Siegal ◽  
David A. Garcia ◽  
Mark A. Crowther
Keyword(s):  
Prothrombin Complex Concentrate ◽  
Clinical Evidence ◽  
Recombinant Factor Viia ◽  
Factor Viia ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Supportive Therapy ◽  
Factor Xa ◽  
Low Molecular Weight ◽  
Life Threatening

Abstract Target-specific oral anticoagulants (TSOACs) that directly inhibit thrombin (dabigatran) or factor Xa (rivaroxaban, apixaban) are effective and safe alternatives to vitamin K antagonists (VKAs) and low-molecular-weight heparin (LMWH). Although these agents have practical advantages compared with VKAs and LMWH, there are no antidotes that reverse their anticoagulant effect. Clinical evidence for the efficacy of nonspecific therapies that promote formation of fibrin (prothrombin complex concentrate [PCC], activated PCC [aPCC], and recombinant factor VIIa) in the setting of TSOAC-associated bleeding is lacking, and these prohemostatic products are associated with a risk of thrombosis. In the absence of specific antidotes, addition of PCC or aPCC to maximum supportive therapy may be reasonable for patients with severe or life-threatening TSOAC-associated bleeding. Targeted antidotes for these agents are in development.

Decreased Levels Of Procoagulant Phospholipids In Bleeding Patients With Overcoagulation By Vitamin K Antagonists

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4768-4768
Author(s):  
Patrick Van Dreden ◽  
Dominique François ◽  
Emmanuel Mathieu ◽  
Matthieu Grusse ◽  
Marc Vasse
Keyword(s):  
Vitamin K ◽  
Conflicts Of Interest ◽  
Vitamin K Antagonists ◽  
Factor Xa ◽  
International Normalized Ratio ◽  
Bleeding Complications ◽  
Functional Assay ◽  
Minor Bleeding ◽  
Asymptomatic Patients ◽  
Increased Risk

Background The major adverse effect of vitamin K antagonists (VKA) is the increased risk for bleeding complications. In addition to well-identified risk factors such as age, prior gastrointestinal tract bleeding, or hypertension, the intensity of anticoagulation evaluated by the International Normalized Ratio (INR) measurement is a major determinant of VKA-induced bleeding. However, for the same degree of VKA overcoagulation and comorbidities, some patient will bleed, whereas others remain asymptomatic. Therefore, identifying specific biological markers that identify patients at high risk of bleeding would have great clinical impact. Microparticles, derived from different cellular origins (endothelium, red blood cells, leukocytes, platelets or apoptotic tissues), can be detected in plasma and express procoagulant phospholipids (PPL). The presence of PPL has been associated with various diseases complicated by an hypercoagulable state. Therefore, we hypothesize that the procoagulant activity of PPL could protect against haemorrhage in patients with VKA overcoagulation. Patients and methods 53 consecutive patients who were referred to the emergency department of our institution and with an INR > 5 were enrolled in the study: 22 (10 females; 12 males, median age 82 years) were symptomatic (20 cases of minor bleeding, 2 cases of non-fatal major bleeding), whereas 31 (18 females, 13 males, median age 78 years) were asymptomatic. Median INR was 7.36 (range: 5 – 22.6) and 6.3 (range: 5 – 10.7) in symptomatic and asymptomatic patients, respectively (p = 0.17, not significant). PPL were evaluated using a factor Xa-based coagulation assay (STA-Procoag-PPL, Diagnostica Stago) in which shortened clotting times are associated with increased levels of PPL. We also quantified thrombomodulin (TM) by an ELISA assay (Asserachrom Thrombomodulin, Diagnostica Stago) and by a functional assay based on the ability of TM to activate Protein C in the presence of thrombin, since high plasma levels of TM were previously identified as a predictor of bleeding complications. Results Clotting times were significantly lower in asymptomatic patients than in bleeding patients [respective median values 36.5 seconds (range: 27.1 – 72.2) and 47.2 seconds (range : 30.5 – 72.8); p = 0.03. In contrast, there were no significant differences for TM levels, whatever the assay used (functional or immunological). Conclusion Increased PPL could contribute to decrease the haemorrhagic risk of patients treated by VKA. It is not clear if the decrease of PPL is directly responsible of the hemorrhagic syndrom, or if PPL are decreased because of a consumption during the hemorrhagic episode. In order to answer this question, it could be of interest to analyse if a prospective follow-up of this parameter could help to identify patients with an increased hemorrhagic risk when treated by VKA. Disclosures: No relevant conflicts of interest to declare.

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.

scholarly journals Comparison of international normalized ratio audit parameters in patients enrolled in GARFIELD-AF and treated with vitamin K antagonists

2016 ◽  
Vol 174 (4) ◽  
pp. 610-623 ◽  
Author(s):  
David A. Fitzmaurice ◽  
Gabriele Accetta ◽  
Sylvia Haas ◽  
Gloria Kayani ◽  
Hector Lucas Luciardi ◽  
...  
Keyword(s):  
Vitamin K ◽  
Vitamin K Antagonists ◽  
International Normalized Ratio

Abstract WP304: Prothrombin Complex Concentrate Rapidly Reverses Coagulopathy but does not Alter Mortality in Warfarin Intracerebral Hemorrhage

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Xuemei Cai ◽  
Susannah Orzell ◽  
Sarah Suh ◽  
Linda Bresette ◽  
Farzaneh Sorond ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Vitamin K ◽  
Conventional Therapy ◽  
Prothrombin Complex Concentrate ◽  
International Normalized Ratio ◽  
Fresh Frozen Plasma ◽  
Thromboembolic Complication ◽  
Complication Rates ◽  
Significant Difference ◽  
Fresh Frozen

INTRODUCTION: Warfarin-associated intracerebral hemorrhage (wICH) remains the most lethal form of iatrogenic stroke. Conventional therapy with fresh frozen plasma (FFP) and intravenous vitamin K takes up to 30 hrs to normalize the international normalized ratio (INR). Prothrombin complex concentrate (PCC) does not require cross-match and is fast acting. We hypothesized that PCC can rapidly reverse coagulopathy and reduce mortality in wICH. Methods: We identified 130 consecutive adult wICH patients over five years from a prospectively collected database. 33 patients were excluded for death or withdrawal of care within 48 hours of admission and 8 patients were excluded for antecedent head trauma, leaving 89 patients for analysis. Forty patients received FFP and vitamin K (conventional therapy) and 49 received PCC in addition to conventional therapy. We compared 6-month mortality, time to INR normalization, quantity of FFP transfused, and thromboembolic complication rates between the two groups. We used logistic regression to adjust for important confounders. Results: PCC-treated and conventional therapy patients had similar distributions of age, sex, co-morbidities, ICH location, initial blood pressure and INR. PCC-treated patients had a higher incidence of intraventicular hemorrhage (IVH) (67% vs 33%). PCC-treated patients required less FFP (mean 6.8 units vs 3.3 units, p<0.0001) and had faster time to INR normalization (mean 3.8 hrs vs 9.8 hrs, p<0.0001). Incidence of ICH expansion was low in both groups. There was no difference in the incidence of deep venous thrombosis and pulmonary embolism (p=0.236) or troponin elevation (p=0.573). There was no significant difference in 6-month mortality (p=0.437) after adjusting for age, ICH location, ICH volume, and presence of IVH. Conclusions: PCC use in wICH was associated with shorter time to INR normalization and reduced FFP transfusion but was not associated with 6-month mortality in this cohort. There was no difference in thromboembolic complication rates between PCC-treated and FFP and vitamin K treated patients. Prospective trials of PCC are necessary to determine if its use can improve morbidity and mortality in wICH and to identify potential subgroups of wICH patients who may benefit from PCC.

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