Review of Prothrombin Complex Concentrates Use in Apixaban and Rivaroxaban Associated Intracranial Hemorrhages

2021 ◽  
pp. 089719002110150
Author(s):  
Francisco Ibarra
Keyword(s):  
Thromboembolic Event ◽  
Prothrombin Complex Concentrate ◽  
Factor Xa ◽  
Mortality Rates ◽  
Intracranial Hemorrhages ◽  
Prothrombin Complex Concentrates ◽  
Title 1 ◽  
Study Objective ◽  
Scale Scores ◽  
Event Rates

Study Objective: Summarize the studies evaluating the use of 4-factor prothrombin complex concentrates in the management of apixaban and rivaroxaban associated intracranial hemorrhages. Methods: A PubMed literature search was conducted for articles published between 2013 and 2020 which contained the following terms in their title: (1) apixaban, rivaroxaban, or factor Xa inhibitor*, and (2) prothrombin complex concentrate*. Results: Eighteen observational studies were included. When a ∼25 units/kg (range: 25-26.9 units/kg) non-activated 4 factor prothrombin complex concentrate dose was administered, the hemostatic effectiveness rates were ≥ 79% in 2/4 studies that utilized the Sarode et al criteria, in comparison to 4/5 studies that administered a 50 units/kg dose. The mortality rates were < 20% in 7/9 studies with hemostatic effectiveness rates ≥ 79%. Mortality rates were lower in the studies demonstrating higher hemostatic effectiveness rates and including patients with higher Glasgow coma scale scores and lower intracerebral hemorrhage volumes. Overall, the thromboembolic event rates were 0-18%, with 16/18 studies demonstrating rates ≤ 10%. The thromboembolic event rates were not dose or agent dependent. Conclusion: Rates of hemostatic effectiveness were influenced by the definition of hemostatic effectiveness, dose administered, and patient severity. Studies suggest that higher doses may result in higher hemostatic effectiveness rates without increasing the risk of experiencing a thromboembolic event. This review may be used by providers to modify or validate their reversal strategy approach until well designed studies are available.

Abstract TP328: Ischemic Stroke Following Prothrombin Complex Concentrates Administration for Intracerebral Hemorrhage

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Andrew Blake Buletko ◽  
Tapan Thacker ◽  
Ken Uchino ◽  
Jennifer Frontera
Keyword(s):  
Intracerebral Hemorrhage ◽  
Prothrombin Complex Concentrate ◽  
Case Reports ◽  
Factor Xa ◽  
Thrombin Inhibitor ◽  
Acute Ischemia ◽  
Hematoma Volume ◽  
Prothrombin Complex Concentrates ◽  
Chi Square ◽  
Apparent Diffusion

Intro: There have been case reports of ischemic infarcts after treatment with prothrombotics for anticoagulation reversal following spontaneous intracerebral hemorrhage (ICH), though there have been no systematic studies evaluating MRI infarction following prothrombin complex concentrate (PCC) or factor eight inhibitor bypassing activity (FEIBA) administration. We evaluated the prevalence of ischemic infarcts on diffusion-weighted imaging (DWI) in ICH patients who received prothrombotics compared to those who did not. Methods: We performed a retrospective review of patients admitted with ICH between January 2013 and April 2016 in whom MRI brain with DWI imaging was performed within 2 weeks of admission and prior to digital subtraction angiography. PCC (4-factor Kcentra, weight, and INR based dosing) was administered to patients on warfarin at the time of ictus with a INR≥1.4 and FEIBA (50 u/kg) was given to patients exposed to an oral Factor Xa inhibitor or direct thrombin inhibitor if ICH occurred within 3-5 half lives of the last dose. Acute ischemia was defined as DWI hyperintensity with corresponding apparent diffusion coefficient hypointensity. Perihematoma lesions, and procedure-related infarctions were excluded from analysis. Groups were compared using chi-square and Wilcoxon Rank Sum tests. Results: A total of 254 patients were enrolled. Of these, 41 (16%) received either 4-factor PCC (n=33) or FEIBA (n=8). Comparing those who received prothrombotics to those who did not, there was no difference in age (median 68 with prothrombotics and without; p=0.724), sex (44% female in both groups; p=0.977), initial NIH Stroke Scale (median 6 versus 8, p=0.838), or hematoma volume (median 15ml versus 10ml; p=0.207). Patients who received prothrombotics were more likely to have lobar ICH than deep ICH (71% versus 47%; p=0.005). DWI infarctions were found in 16% of patients who receive PCC or FEIBA compared with 22% who did not (p=0.404). Conclusions: Our data suggests prothrombotics do not increase the risk of acute ischemic infarcts within two weeks of administration.

scholarly journals Four-factor Prothrombin Complex Concentrate for the Management of Patients Receiving Direct Oral Activated Factor X Inhibitors

2019 ◽  
Vol 131 (5) ◽  
pp. 1153-1165 ◽  
Author(s):  
Oliver Grottke ◽  
Sam Schulman
Keyword(s):  
Prothrombin Complex Concentrate ◽  
Factor Xa ◽  
Factor Xa Inhibitors ◽  
Factor X ◽  
Prothrombin Complex Concentrates ◽  
Life Threatening

Factor Xa inhibitors prevent thrombosis but are associated with severe or life-threatening bleeding. Here, the authors present data on four-factor prothrombin complex concentrates in management of anticoagulation-associated bleeding and restoring hemostasis, including recent results from the UPRATE study.

The Factor VIII Bypassing Activity of Prothrombin Complex Concentrates: The Roles of Factor VIla and of Endothelial Cell Tissue Factor

1991 ◽  
Vol 66 (05) ◽  
pp. 559-564 ◽  
Author(s):  
Jerome M Teitel
Keyword(s):  
Factor Viii ◽  
Tissue Factor ◽  
Factor Viia ◽  
Factor Xa ◽  
Procoagulant Activity ◽  
Tissue Factor Expression ◽  
Prothrombin Complex Concentrates ◽  
Cell Tissue ◽  
Factor Expression ◽  
Necrosis Factor

SummaryAn experimental model incorporating cultured endothelial cells (EC) was used to study the "factor VIII bypassing" activity of prothrombin complex concentrates (PCC), a property exploited in the treatment of hemophiliacs with alloantibodies to factor VIII. Two PCC preparations were ineffective as stimuli of tissue factor expression by EC. However, incubation with a combination of PCC plus endotoxin (lipopolysaccharide, LPS) or tumor necrosis factor (TNF) induced much greater tissue factor expression than was seen in response to either substance alone. PCC expressed an additional direct procoagulant activity at the EC surface, which could not be attributed to either thrombin or factor Xa, and which was diminished by an anti-tissue factor antibody. Therefore factor VIIa, which was detectable in both PCC preparations, likely provided this additional direct procoagulant activity at the EC surface. We also excluded the possibility that coagulation proteases contained in or generated in the presence of PCC are protected from inactivation by AT III. Therefore, PCC can indirectly bypass factor VIII by enhancing induced endothelial tissue factor expression, and also possess direct procoagulant activity, probably mediated by factor VIIa.

High-dose versus low-dose 4-factor prothrombin complex concentrate for factor Xa inhibitor reversal in intracranial hemorrhage

2021 ◽  
Author(s):  
Spencer Davis ◽  
Stephanie Chauv ◽  
Abby W. Hickman ◽  
Dave S. Collingridge ◽  
Sara Kjerengtroen ◽  
...  
Keyword(s):  
Intracranial Hemorrhage ◽  
Prothrombin Complex Concentrate ◽  
Low Dose ◽  
Factor Xa ◽  
High Dose ◽  
Factor Xa Inhibitor

Evaluation of the Use of Low-Dose 4-Factor Prothrombin Complex Concentrate in the Reversal of Direct Oral Anticoagulants in Bleeding Patients

2018 ◽  
Vol 35 (9) ◽  
pp. 903-908 ◽  
Author(s):  
Teresa A. Allison ◽  
Pei Jen Lin ◽  
Jennifer A. Gass ◽  
Kenneth Chong ◽  
Samuel J. Prater ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Prothrombin Complex Concentrate ◽  
Low Dose ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Final Analysis ◽  
Factor Xa Inhibitor ◽  
Direct Factor

Objective: This study investigated the percentage of patients who achieved hemostasis with 4-factor prothrombin complex concentrate (4-factor PCC) 35 U/kg. The primary end point was to determine the effect of 4-factor PCC 35 U/kg on bleeding progression, assessed using computed tomography. Methods: This was a retrospective, observational, single-center study conducted in patients with a major bleed admitted to a level 1 trauma center from May 1, 2013, to June 15, 2015, who received 4-factor PCC 35 U/kg for reversal of a direct factor Xa inhibitor taken prior to admission. Results: Thirty-three patients were included in the study, with 31 patients in the final analysis. The mean (standard deviation) age was 73 (14.8) years; 54.5% of patients were female. Of the 33 patients, 13 presented with a traumatic brain injury, 9 with an aneurysmal subarachnoid hemorrhage, 8 with an intracerebral hemorrhage, 1 with a gastrointestinal bleed, 1 with a hematoma with active extravasation, and 1 with an intra-abdominal bleed. The most frequently used direct factor Xa inhibitor was rivaroxaban (81.8%). Overall, 83.8% of patients achieved hemostasis with 4-factor PCC 35 U/kg. Progression of hemorrhage was observed in 4 patients on repeat computed tomography scan and 1 patient had continued surgical bleeding. No thromboembolic events were reported. Conclusions: Low-dose, 4-factor PCC 35 U/kg appeared to produce hemostasis in a majority of the patients. This may be an effective dosing regimen for anticoagulant reversal of factor Xa inhibitors in clinically bleeding patients.

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.

scholarly journals The efficacy of remdesivir in coronavirus disease 2019 (COVID-19): a systematic review

2020 ◽  
Author(s):  
Amirhossein Roshanshad ◽  
Alireza Kamalipour ◽  
Mohammad Ali Ashraf ◽  
Romina Roshanshad ◽  
Sirous Jafari ◽  
...  
Keyword(s):  
Systematic Review ◽  
Adverse Event ◽  
Cohort Studies ◽  
Clinical Improvement ◽  
Day Treatment ◽  
Mortality Rates ◽  
Severe Adverse Event ◽  
Adverse Event Rate ◽  
Significant Difference ◽  
Event Rates

Background and Objectives: Researchers all around the world are working hard to find an effective treatment for the new coronavirus 2019. We performed a comprehensive systematic review to investigate the latest clinical evidence on the efficacy and safety of treatment with Remdesivir in hospitalized patients with COVID-19. Materials and Methods: We performed a systematic search in Pubmed, Embase, Web of Science, Google scholar and MedRxiv for relevant observational and interventional studies. The outcomes measures were mortality rates, improvement rates, time to clinical improvement, all adverse event rates and severe adverse event rates. Results: Three randomized controlled trials and 2 cohort studies were included in our study. In the 2 cohort studies, patients received Remdesivir for 10 days. 2 RCTs evaluated 10-day efficacy of treatment with Remdesivir versus placebo group and the other RCT compared its 5-day regimen versus 10-day regimen. Visual inspection of the forest plots revealed that the efficacy of Remdesivir was not much different in reducing 28-day mortality versus 14-day mortality rates. Besides, 10-day treatment regimen overpowered 5-day treatment and placebo in decreasing time to clinical improvement. All adverse event rates did not have a significant difference; however, severe adverse event rate was lower in the 5-day Remdesivir group compared to the 10-day and placebo groups. Conclusion: 5-day course of Remdesivir therapy in COVID-19 patients is probably efficacious and safe, and patients without invasive mechanical ventilation benefit the most. Treatment can be extended to 10 days if satisfactory improvement is not seen by day 5. Most benefits from Remdesivir therapy take place in the first 14 days of the start of the treatment.

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