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.

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 Timing of Fresh Frozen Plasma Administration and Rapid Correction of Coagulopathy in Warfarin-Related Intracerebral Hemorrhage

Stroke ◽  
2006 ◽  
Vol 37 (1) ◽  
pp. 151-155 ◽  
Author(s):  
Joshua N. Goldstein ◽  
Stephen H. Thomas ◽  
Virginia Frontiero ◽  
Annelise Joseph ◽  
Chana Engel ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Fresh Frozen Plasma ◽  
Fresh Frozen ◽  
Frozen Plasma ◽  
Rapid Correction

scholarly journals An Institutional Survey of Warfarin Reversal in the Setting of Life-Threatening Bleeds

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4981-4981
Author(s):  
Ian Garrahy ◽  
Tushar Pawar ◽  
Anthony Donato ◽  
Amber Stevenson ◽  
Daniel Forman
Keyword(s):  
Conflicts Of Interest ◽  
Factor Viia ◽  
Fresh Frozen Plasma ◽  
P Value ◽  
Anticoagulation Management ◽  
Clinical Scenarios ◽  
Fresh Frozen ◽  
Life Threatening ◽  
Warfarin Reversal ◽  
Frozen Plasma

Introduction: The bleeding risk of warfarin is well known. Therapeutic options for warfarin reversal in life-threatening bleeds include fresh frozen plasma (FFP), recombinant factor VIIa (rFVIIa), and prothrombin complex concentrate (PCC). Despite the theoretical advantage and clinical evidence supporting PCC, it is not widely used in the US. Methods: An online anonymous questionnaire was sent to all providers in the Tower Health System asking them about their practice, specialty, degree, years in practice, and basic questions regarding their comfort and frequency of prescribing anticoagulants. The questionnaire also asked the providers how they would manage ten various clinical scenarios related to anticoagulation management. One question specifically addressed the management of warfarin reversal in an 85-year-old presenting with hemorrhagic shock. Analysis of variance was used to compare the scoring means between groups while linear regression and Pearson's correlation coefficient measured the relationship between years of practice and test scores. Results: Out of 404 responders, 232 (57.4%) selected an incorrect answer and 212 (52.5%) incorrectly selected fresh frozen plasma as the answer to the question (see uploaded image) that addressed warfarin reversal in the setting of major bleeding. Those providers who answered this question correctly and those who answered it incorrectly had mean scores of 68.26% and 52.16% respectively on the overall survey (p value 0.000). Conclusion: As compared to FFP, the use of PCC for warfarin reversal is associated with a significant reduction in all-cause mortality. This project demonstrates a professional practice gap and serves to highlight an area in medicine where many providers are not practicing in accordance with evidence-based practice. Furthermore, this particular question from the survey discovered that providers who performed better on the survey were more likely to answer questions regarding anticoagulation reversal correctly. Figure Disclosures No relevant conflicts of interest to declare.

Liver Cirrhosis Manifested by Dysfibrinogenemia

1997 ◽  
Vol 3 (2) ◽  
pp. 102-103 ◽  
Author(s):  
Takeshi Wajima
Keyword(s):  
Liver Cirrhosis ◽  
Gastrointestinal Bleeding ◽  
Bleeding Time ◽  
Degradation Products ◽  
Liver Function Tests ◽  
Fresh Frozen Plasma ◽  
Activated Partial Thromboplastin Time ◽  
Thrombin Time ◽  
Fresh Frozen ◽  
Frozen Plasma

We report a case in which liver cirrhosis was manifested by dysfibrinogenemia before the diagnosis of liver cirrhosis was made. A patient developed gastrointestinal bleeding and hepatic encephalopathy although liver function tests, prothrombin time (PT), activated partial thromboplastin time (aPTT), bleeding time, fibrin (ogen) degradation products (FDP), and platelet counts were normal. However, thrombin time (TT) was prolonged. The gastrointestinal bleeding (GI bleeding) was successfully treated with cryoprecipitate and fresh frozen plasma (FFP). Key Words: Dysfibrinogenemia—Liver disease—Thrombin time.

Successful Control of Massive Gastrointestinal Bleeding Following Umbilical Cord Blood Transplantation (UCBT) by Use of Recombinant Activated Factor VII (rFVIIa) and Octreotide Infusion

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4336-4336
Author(s):  
Satya Prakash Yadav ◽  
Anupam Sachdeva ◽  
Madasu Anjan ◽  
Nita Radhakrishnan ◽  
Sunil Bhat ◽  
...  
Keyword(s):  
Gastrointestinal Bleeding ◽  
Factor Viia ◽  
Fresh Frozen Plasma ◽  
Gi Bleeding ◽  
Blood Products ◽  
Fresh Frozen ◽  
Life Threatening ◽  
Lower Gi Bleeding ◽  
Gi Bleed ◽  
Frozen Plasma

Abstract Post stem cell transplantation (SCT) bleeding is a dreaded complication especially gastrointestinal (GI). Platelet refractoriness is another but rare cause of bleeding post SCT. Use of rFVIIa for bleeding in setting of SCT was tested by Pihusch et al in 100 patients. Despite no overall effect of rFVIIa treatment on primary endpoint, post hoc analysis showed an improvement in the control of bleeding for 80 ug kg rFVIIa vs. standard haemostatic treatment. There were 38 patients with GI bleeding but none with massive bleeding. There are only 8 other case reports of use of rFVIIa for massive lower GI bleeding post allogeneic SCT with only one patient showing partial response and none of the patients surviving. The role of octreotide is less clear in gastrointestinal bleeding unrelated to portal hypertension. Y. Eroglu reported that, the response rate of gastrointestinal bleeding to octreotide in patients without portal hypertension was 50%. We present a 10 month-old female child, who had three episodes of life threatening lower GI bleeding post unrelated UCBT controlled successfully each time by use of rFVIIa and octerotide infusion. Patient underwent an unrelated UCBT for Thalassemia Major with a 4/6 matched cord unit and was conditioned with Busulfan 14 mg/kg, Cyclophosphamide120 mg/kg and Anti- Thymocyte Globulin. Cyclosporine and Methotrexate was given for Graft vs. host Disease prophylaxis. Cell dose infused was 7 × 107 nucleated cell/kg. She failed to engraft and also developed refractory thrombocytopenia. On Day + 48 post UCBT she developed massive lower GI bleed (passing big clots per rectum) with hypotension. Her platelets were 8,000/mm3, Hb of 4.5 gm/dl. Her coagulation parameters were normal. She was given packed cells, platelets (random donor and apheresis), Fresh Frozen Plasma (FFP) and tranexamic acid (250 mg IV 8 hrly). She was also started on injection octreotide infusion (1μg/kg bolus followed by 1μg/kg/hr infusion). Patient continued to have life threatening lower GI bleed (bleeding score-4) with no rise in platelets so a decision was made to administer rFVIIa (once she was repleted with packed cells, platelets and fresh frozen plasma) using the bolus dose of 90 μg/kg IV 3 doses 2 hrly. Autologous marrow was infused with CD34 cell dose 7 million/kg in view of non-engraftment. The bleeding subsided completely (within 6 hrs) after three doses of rFVIIa and the blood pressure normalized. Octreotide infusion was stopped after 12 hrs of bleeding free interval. After a 24 hr bleeding free period on Day +50 post UCBT, patient again bled with hypotension and again required factor VIIa (two doses) along with blood products and octreotide infusion and again showed excellent response. Again on Day+59 post UCBT she had another episode of massive lower GI bleed with hypotension and again required activated factor VIIa (two doses only) along with blood products and octreotide infusion) and bleeding stopped in next 8 hr. There was no further episode of lower GI bleed. No adverse effects due to rFVIIa were observed. She was discharged after 2 weeks with recovery of neutrophills and platelets and continues to be well Day +100 post transplant. Following this case we suggest that rVIIa with octerotide be considered as a mode of additional therapy for life-threatening GI bleeding in the face of severe thrombocytopenia and platelet refractoriness, where platelet transfusions and other haemostatic agents have failed.

Homozygous 2bp Deletion in the Human Factor VII Gene: A Non-Lethal Mutation that Is Associated with a Complete Absence of Circulating Factor VII

2000 ◽  
Vol 84 (10) ◽  
pp. 635-637 ◽  
Author(s):  
Pier Mannucci ◽  
P. Jenkins ◽  
Anselm Lee ◽  
Raffaella Coppola ◽  
David Perry ◽  
...  
Keyword(s):  
Human Factor ◽  
Fresh Frozen Plasma ◽  
Factor Vii ◽  
Causative Mutation ◽  
Direct Sequence ◽  
Factor Vii Deficiency ◽  
Plasma Factor ◽  
Fresh Frozen ◽  
Direct Sequence Analysis ◽  
Frozen Plasma

SummaryWe report the case of a 5-year-old boy with severe factor VII deficiency. The affected child presented at the age of 8 months and again at 18 months with bleeding from the gastrointestinal tract but the diagnosis of factor VII deficiency was not made until the age of 3 years. He was treated with fresh frozen plasma and subsequently factor VII concentrates and to date remains well. To identify the causative mutation, the factor VII gene was screened by SSCP and direct sequence analysis. A single homozygous 2bp deletion (-CT) mutation was identified in exon 1a removing nucleotides 27/28 (codons 52/53). Both parents, who were first cousins, were heterozygous for the mutation. The mutation located in the prepropeptide of factor VII, results in a complete absence of factor VII in plasma. This case indicates that a complete absence of plasma factor VII is not necessarily a lethal condition.

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