Abstract W MP110: INR reversal of Oral Anticoagulant-Associated Intracerebral Hemorrhage

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Fernando Testai ◽  
Faisal Mukarram ◽  
Andrew Culpepper ◽  
Maureen Hillmann ◽  
Padmini Sekar ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Oral Anticoagulants ◽  
Case Fatality ◽  
Fresh Frozen Plasma ◽  
Factor Vii ◽  
Hematoma Expansion ◽  
Racial Variations ◽  
Fresh Frozen ◽  
Time And Being ◽  
Admission Variables

Background: The use of oral anticoagulants (OAC) is associated with poor outcome in intracerebral hemorrhage (ICH). In this study we investigated the effect of delayed INR reversal and the factors influencing it in patients with OAC-associated ICH (OAC-ICH). Methods: Data were obtained from the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study which is a prospective, multi-ethnic multicenter study of ICH. Exclusion criteria included missing initial hematoma volume, INR or ED arrival time and being on heparin. Baseline characteristics, INR at baseline and 12h, hematoma location and volume, treatment received, hematoma expansion at 24h, and mortality at 3 months were recorded. INR reversal was defined as INR<1.4 at 12h post admission. Variables associated with INR reversal and case fatality at 3 months in non-OAC users and OAC users with and without INR <1.4 were compared. Results: A total of 1,746 of 2,276 subjects were included in the analysis. A higher proportion of OAC users (n=185) were white and had hypertension, diabetes, hypercholesterolemia, and lobar ICH than non-users (P<0.05). Baseline INRs for the OAC group were 3.1 (28.7%). Subjects on OAC received fresh frozen plasma (FFP, 44%) monotherapy, either recombinant factor VII or prothrombin complex (FVII/PCC, 7%), or a combination of FFP/FVII/PCC (11%). Increasing age (OR=0.96, 95% CI 0.94-0.98), elevated baseline INR (OR=0.34, 95% CI 0.26-0.43), and use of FFP only (OR=0.07, 95% CI 0.04-0.13) was associated with lack of INR reversal at 12h. Median INR at 12h (IQR) were 1.4 (1.3-1.6), 1.1 (0.9-1.1), and 1.0 (1.0-1.3) for the FFP, PCC/FVII, and FFP/FVII/PCC groups, respectively (p1.4 did not influence the rate of hematoma expansion at 24h. Case fatality at 3 months was 22% for non-OAC-ICH, 34% for OAC-ICH with INR<1.4, and 44% for OAC-ICH with INR>1.4 (p=.0005). Conclusion: In the ERICH study, patients treated with FFP monotherapy were less likely to have a normalized INR at 12h and this was associated with increased case fatality at 3 months. The use of FVII/PCC may shorten time to INR correction and improve outcome in OAC-ICH.

scholarly journals Hemostatic Therapy in Experimental Intracerebral Hemorrhage Associated With the Direct Thrombin Inhibitor Dabigatran

Stroke ◽  
2011 ◽  
Vol 42 (12) ◽  
pp. 3594-3599 ◽  
Author(s):  
Wei Zhou ◽  
Sönke Schwarting ◽  
Sergio Illanes ◽  
Arthur Liesz ◽  
Moritz Middelhoff ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Human Factor ◽  
Bleeding Time ◽  
Factor Viia ◽  
Fresh Frozen Plasma ◽  
Hematoma Expansion ◽  
Intracerebral Hematoma ◽  
Fresh Frozen ◽  
Hematoma Growth ◽  
Frozen Plasma

Background and Purpose— Dabigatran-etexilate (DE) recently has been approved for stroke prevention in atrial fibrillation. However, lack of effective antagonists represents a major concern in the event of intracerebral hemorrhage (ICH). The aims of the present study were to establish a murine model of ICH associated with dabigatran, and to test the efficacy of different hemostatic factors in preventing hematoma growth. Methods— In C57BL/6 mice receiving DE (4.5 or 9.0 mg/kg), in vivo and in vitro coagulation assays and dabigatran plasma levels were measured repeatedly. Thirty minutes after inducing ICH by striatal collagenase injection, mice received an intravenous injection of saline, prothrombin complex concentrate (PCC; 100 U/kg), murine fresh-frozen plasma (200 μL), or recombinant human factor VIIa (8.0 mg/kg). ICH volume was quantified on brain cryosections 24 hours later. Results— DE substantially prolonged tail vein bleeding time and ecarin clotting time for 4 hours corresponding to dabigatran plasma levels. Intracerebral hematoma expansion was observed mainly during the first 3 hours on serial T2* MRI. Anticoagulation with high doses of DE increased the hematoma volume significantly. PCC and, less consistently, fresh-frozen plasma prevented excess hematoma expansion caused by DE, whereas recombinant human factor VIIa was ineffective. Prevention of hematoma growth and reversal of tail vein bleeding time by PCC were dose-dependent. Conclusions— The study provides strong evidence that PCC and, less consistently, fresh-frozen plasma prevent excess intracerebral hematoma expansion in a murine ICH model associated with dabigatran. The efficacy and safety of this strategy must be further evaluated in clinical studies.

scholarly journals Contribution of Various Types of Transfusion to Acute and Delayed Intracerebral Hemorrhage Injury

2021 ◽  
Vol 12 ◽  
Author(s):  
Siddharth Kumar ◽  
Matthew Andoniadis ◽  
Ali Solhpour ◽  
Salman Asghar ◽  
Madison Fangman ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Tranexamic Acid ◽  
Brain Edema ◽  
Treatment Options ◽  
Fresh Frozen Plasma ◽  
Hematoma Expansion ◽  
High Morbidity ◽  
Severe Thrombocytopenia ◽  
Acid Infusion ◽  
Fresh Frozen

Intracerebral hemorrhage (ICH) is the second most prevalent type of stroke, after ischemic stroke, and has exceptionally high morbidity and mortality rates. After spontaneous ICH, one primary goal is to restrict hematoma expansion, and the second is to limit brain edema and secondary injury. Various types of transfusion therapies have been studied as treatment options to alleviate the adverse effects of ICH etiopathology. The objective of this work is to review transfusions with platelets, fresh frozen plasma (FFP), prothrombin complex concentrate (PCC), and red blood cells (RBCs) in patients with ICH. Furthermore, tranexamic acid infusion studies have been included due to its connection to ICH and hematoma expansion. As stated, the first line of therapy is limiting bleeding in the brain and hematoma expansion. Platelet transfusion is used to promote recovery and mitigate brain damage, notably in patients with severe thrombocytopenia. Additionally, tranexamic acid infusion, FFP, and PCC transfusion have been shown to affect hematoma expansion rate and volume. Although there is limited available research, RBC transfusions have been shown to cause higher tissue oxygenation and lower mortality, notably after brain edema, increases in intracranial pressure, and hypoxia. However, these types of transfusion have varied results depending on the patient, hemostasis status/blood thinner, hemolysis, anemia, and complications, among other variables. Inconsistencies in published results on various transfusion therapies led us to review the data and discuss issues that need to be considered when establishing future guidelines for patients with ICH.

Direct (new) oral anticoagulants (DOACs): Drawbacks, bleeding and reversal

2021 ◽  
Vol 19 ◽  
Author(s):  
Ozgur Karcioglu ◽  
Sehmus Zengin ◽  
Bilgen Ozkaya ◽  
Eylem Ersan ◽  
Sarper Yilmaz ◽  
...  
Keyword(s):  
Oral Anticoagulants ◽  
Fresh Frozen Plasma ◽  
New Oral Anticoagulants ◽  
Coagulation Cascade ◽  
Thrombin Inhibitor ◽  
Severe Bleeding ◽  
Prothrombin Complex Concentrates ◽  
Clinical Scenarios ◽  
Fresh Frozen ◽  
Frozen Plasma

Background and Objective: Direct (new) Oral Anticoagulants (DOACs) have emerged as a contemporary and promising option in the treatment of thromboses and VTE, while protecting the coagulation cascade against untoward bleeding events. They are used in the management and prophylaxis of Venous Thromboembolism (VTE) and other thrombotic diseases. The most prominent complication of these agents is bleeding. These agents have similar or lower rates of major intracranial hemorrhages, while they had a higher risk of major gastrointestinal bleeding when compared to warfarin. This manuscript is aimed to revise and update the literature findings to outline the side effects of DOACs in various clinical scenarios. Methods: A narrative review of currently published studies was performed. Online database searches were performed for clinical trials published before July 2021, on the efficacy and adverse effects attributed to the anticoagulant treatment, especially DOACs. A literature search via electronic databases was carried out, beginning with the usage of the agents in the Western Languages papers. The search terms initially included direct (new) oral anticoagulants, dabigatran, rivaroxaban, apixaban, edoxaban, idarucizumab, andexanet, prothrombin complex concentrates, and fresh frozen plasma. Papers were examined for methodological soundness before being included. Results: Severe bleeding episodes require aggressive interventions for successful management. Therefore, bleeding should be evaluated in special regard to the location and rate of hemorrhage, and total volume of blood loss. Patient's age, weight and organ dysfunctions (e.g., kidney/liver failure or chronic respiratory diseases) directly affect the clinical course of overdose. Conclusion: Management recommendations for hemorrhage associated with DOAC use vary, depending on the class of the culprit agent (direct thrombin inhibitor vs. FXa inhibitor), the clinical status of the patient (mild/ moderate vs. severe/life-threatening), and capabilities of the institution. Specific reversal agents (i.e., idarucizumab and andexanet alfa) can be used if available, while prothrombin complex concentrates, fresh frozen plasma and/ or tranexamic acid can also be employed as nonspecific replacement agents in the management of DOAC-related bleeding diathesis.

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.

scholarly journals Congenital Deficiency in Factor VII Revealed by Menorrhagia: Case Report

2020 ◽  
pp. 1-5
Author(s):  
Nadia Mebrouk ◽  
Abdelilah Radi ◽  
Mohamed Selouti ◽  
Amal Hassani ◽  
Abdelhakim Ourrai ◽  
...  
Keyword(s):  
Treatment Options ◽  
Specific Treatment ◽  
Fresh Frozen Plasma ◽  
Factor Vii ◽  
Activity Measurement ◽  
Recombinant Activated Factor Vii ◽  
Congenital Deficiency ◽  
Activated Factor Vii ◽  
Fresh Frozen ◽  
Fvii Deficiency

Factor VII (FVII) deficiency is the most common among rare inherited autosomal recessive bleeding disorders. It is a multifaceted disease because of the lack of a direct correlation between plasma levels of coagulation FVII and bleeding manifestations. Clinical phenotypes range from asymptomatic condition—even in homozygous subjects—to severe, life-threatening bleedings (e.g., central nervous system and gastrointestinal bleeding). Menorrhagia is a frequent type of bleeding in FVII deficiency, with a prevalence rate of two in three women aged 10 to 50 years and with a peak prevalence in teenagers. When menorrhagia is observed and once the gynecological causes are excluded, it is important to carry out a hemostasis assessment because, if an anomaly is found, specific treatment can be administered and preventive measures taken. Basic diagnostic work-up includes routine assays, prothrombin level, activated partial thromboplastin time and platelet count, followed by FVII coagulant activity measurement for isolated decreased prothrombin level. To confirm the diagnosis, FVII assay should be repeated at least once. Several treatment options are currently available for FVII deficiency: Recombinant activated Factor VII (rFVIIa), plasma-derived Factor VII, fresh frozen plasma and prothrombin complex concentrates. rFVIIa is the most used replacement therapy. Other medical therapies of menorrhagia includes hemostatic agents and hormonal treatments (combined oral contraceptives, levonorgestrel intrauterine devices), in combination or not with rFVIIa. We report the case of a fourteen-and-a-half-year-old girl who presented menorrhagia of great abundance at the age of thirteen, the exploration of which revealed a congenital deficit in FVII.

scholarly journals Case Report: Large ileal intramural hematoma presenting as an intestinal obstruction in a patient on Warfarin with incidental breast cancer

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 724
Author(s):  
Maryam Alizadeh Forutan ◽  
Fereshteh Araghian Mojarad ◽  
Nasrin Rahmani
Keyword(s):  
Abdominal Pain ◽  
Case Report ◽  
Rare Complication ◽  
Oral Anticoagulants ◽  
Previous History ◽  
Oral Intake ◽  
Intramural Hematoma ◽  
Left Breast ◽  
Fresh Frozen Plasma ◽  
Fresh Frozen

Intramural hematoma of the gastrointestinal (GI) tract, which can present as abdominal pain or obstruction, can be a rare complication of oral anticoagulants, in particular Warfarin. In this case report, we describe an 81-year-old female patient presenting with abdominal pain, nausea, and vomiting with a previous history of rectorrhagia. The patient was receiving Warfarin therapy due to cardiac valve replacement for the past 8 years. Laboratory workup revealed elevated INR and anemia. Diagnosis of ileal intramural hematoma was based on ultrasound and CT scan findings. The patient was treated by conservative approaches including administration of fresh frozen plasma, cessation of oral intake, and fluid resuscitation. In CT images, a mass on the left breast and lymphadenopathy on the left axilla were also noticed. Given that most GI intramural hematomas caused by over-anticoagulation are treated non-surgically, considering a patient's drug history, especially in older patients with abdominal pain and obstruction symptoms, is of particular importance.

Preparation of a Factor VII Concentrate

1979 ◽  
Author(s):  
A.J. MacLeod ◽  
I. Dickson
Keyword(s):  
Specific Activity ◽  
Fresh Frozen Plasma ◽  
Factor Vii ◽  
Batch Adsorption ◽  
Citrate Buffer ◽  
Linear Gradient ◽  
Fresh Frozen ◽  
Frozen Plasma ◽  
Phosphate Citrate Buffer

A factor VII concentrate has been prepared from pooled citrated fresh frozen plasma following removal of cryoprecipitate and factors II, IX and X. The method involved batch adsorption on DEAE-Sephadex A-50, fractionation of the subsequent batch eluate by PEG precipitation and passage through a column of DEAE-Sepharose CL-.6B. A phosphate-citrate buffer pH 6.9 was used throughout, this was made 0.2M with NaCl for the batch elution and a 0 - 0.2H NaCl linear gradient was used to elute the components from the column. Factor VII activity was clearly resolved from the bulk of the protein, including caeruloplasmin, and could be recovered as a concentrate at about 20 U FVII/ml with a specific activity of in excess of 1 U FVII/mg of protein and an overall recovery of 40% to 50%

Anticoagulants and antithrombotics in critical illness

2016 ◽  
Author(s):  
Vickie McDonald ◽  
Marie Scully
Keyword(s):  
Platelet Count ◽  
Critical Illness ◽  
Prothrombin Complex Concentrate ◽  
Oral Anticoagulants ◽  
Fresh Frozen Plasma ◽  
Heparin Therapy ◽  
Heparin Induced Thrombocytopenia ◽  
Routine Monitoring ◽  
Fresh Frozen ◽  
Frozen Plasma

Coagulation is best thought of using the cell-based model of coagulation. Patients commenced on heparin therapy should have their platelet count monitored early because of the risk of heparin-induced thrombocytopenia, which can occur on any type or dose of heparin. Emergency reversal of warfarin should be with prothrombin complex concentrate (containing factors II, VII, IX, and X) and not fresh frozen plasma. New oral anticoagulants have the advantage of predictable pharmacokinetics and do not require routine monitoring, but optimal reversal strategies for these agents are not clear. Thrombolytic agents lead to variable degrees of systemic lysis, which may cause haemorrhage, including intracerebral haemorrhage

IVH in VLBW Preterm Babies – Therapy with Recombinant Activated F VII?

2017 ◽  
Vol 229 (06) ◽  
pp. 335-341 ◽  
Author(s):  
Matthias Knüpfer ◽  
Jenny Ritter ◽  
Ferdinand Pulzer ◽  
Corinna Gebauer ◽  
Nadine Wolf ◽  
...  
Keyword(s):  
Very Low Birth Weight ◽  
Demographic Data ◽  
Fresh Frozen Plasma ◽  
Coagulation Cascade ◽  
Factor Vii ◽  
Control Group ◽  
Posthemorrhagic Hydrocephalus ◽  
Activated Factor Vii ◽  
Fresh Frozen ◽  
Group A

Abstract Backround Intraventricular hemorrhage (IVH) remains a dangerous and frequent complication in very low birth weight (VLBW) infants. Activated factor VII (aFVII) activates the coagulation cascade and is a potential tool for stopping active bleeding, including limiting the extent of an IVH. This retrospective treatment observation compared data for infants with IVH progression treated with fresh frozen plasma (FFP) alone or with a combination of FFP and aFVII. Methods/Intervention All infants were subject to cranial ultrasonography at least twice daily. When an IVH was detected, treatment with FFP (5–20 ml/kg every 4–6 h) was commenced and the parents were informed. If the parents endorsed aFVII treatment and the IVH showed progress, aFVII (30–50 µg/kg body weight 4–6 times within 16–24 h) was given. Otherwise, infants were treated with FFP only. We compared the course of IVH between the aFVII+FFP treated infants and a control group (FFP only). Results 35 patients throughout were included in the analysis (17 control and 18 aFVII group). Demographic data was not different between groups. The progress of IVH was significantly less in the aFVII group (p<0.01). During the hospital stay, 2 of the infants in the aFVII group died compared to 4 in the control group. A posthemorrhagic hydrocephalus developed in 3 aFVII and 6 control infants. All other outcome parameters and follow-up-results 2 years after treatment did not differ significantly. Conclusion These data show that in the case of a progressing IVH, aFVII may be a candidate for limiting its extent. A prospective randomized trial is warranted.

The Risk of Thrombotic Events in Neonates Treated with Recombinant Factor VIIa.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3193-3193
Author(s):  
John Puetz ◽  
Ginger Darling ◽  
Petr Brabec ◽  
Jan Blatny ◽  
Prasad Mathew
Keyword(s):  
Recombinant Factor Viia ◽  
Factor Viia ◽  
Accurate Determination ◽  
Thrombotic Event ◽  
Fresh Frozen Plasma ◽  
Factor Vii ◽  
Control Group ◽  
Fresh Frozen ◽  
Surgical Bleeding ◽  
A Prospective Study

Abstract Background: In recent years, recombinant factor VIIa (rFVIIa) has been used in non-hemophilia bleeding situations (factor VII deficiency, trauma, liver disease, uremia, surgical bleeding, platelet disorders, and intracranial hemorrhage) for achievement of hemostasis. Although, the risk of thrombosis in hemophilia patients with inhibitors receiving rFVIIa is quite low, its use in other clinical situations has been complicated by some reports of thrombotic events. Recently, rFVIIa has been used to treat coagulopathic and/or bleeding neonates with good success. However, the prevalence of thrombotic events in these neonates is completely unknown. This study was initiated to determine the risk of thrombotic events associated with rFVIIa use in neonates. Methods: We reviewed all published literature in neonates receiving rFVIIa. In addition, we reviewed all data submitted to the SeveN Bleep Registry, a database developed by the scientific standardization subcommittee on pediatric and neonatal hemostasis of the International Society on Thrombosis and Haemostasis (ISTH) to record all uses of rFVIIa in pediatric non-hemophilic patients. As the baseline prevalence of thrombosis for bleeding and/or coagulopathic neonates is also unknown, we also reviewed the records of 100 consecutive neonates from a single institution who received fresh frozen plasma (FFP) alone to treat their coagulopathy and/or bleeding. Results: A total of 98 non-hemophilic neonates received rFVIIa. The majority of these neonates received rFVIIa only after failing to achieve hemostasis with standard care (FFP, cryoprecipitate, platelet transfusions). Of those receiving rFVIIa, 7 had a thrombotic event reported. In the control group that received FFP alone, 7 neonates also suffered a thrombotic event. Although the risk of thrombosis in these two groups is similar, neonates receiving rFVIIa tended to have indwelling line related thrombosis, while those receiving FFP tended to have strokes or myocardial insults. Overall the prevalence of thrombotic events in bleeding and/or coagulopathic neonates appears to be 7%, whether or not they received rFVIIa. Conclusions: In this study, the overall prevalence of thrombotic events was similar in the rFVIIa and FFP group. As data for this study was collected in a retrospective manor, and thereby subject to publication and submission bias, a more accurate determination of the prevalence of thrombosis in neonates will require a prospective study.

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