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1.
West J Emerg Med ; 20(4): 619-625, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31316701

RESUMO

Introduction: Warfarin is a potent anticoagulant used for the prevention and treatment of venous and arterial thrombosis. Occasionally, patients require emergent warfarin reversal due to active bleeding, supratherapeutic international normalized ratio, or emergent diagnostic or therapeutic interventions. Various agents can be used for emergent warfarin reversal, including fresh frozen plasma (FFP) and 4-factor prothrombin complex concentrate (4F-PCC). Both FFP and 4F-PCC are generally considered safe; however, both agents contain coagulation factors and have the potential to provoke a thromboembolic event. Although clinical trials have compared the efficacy and safety of FFP and 4F-PCC, data are limited comparing the risk of thromboembolism between the two agents. Methods: A retrospective chart review was performed at a single, urban, academic medical center comparing the incidence of thromboembolism with FFP or 4F-PCC for warfarin reversal during a three-year period in the emergency department (ED) at Massachusetts General Hospital. Patients were included in the study if they were at least 18 years of age and were on warfarin per electronic health records. Patients were excluded if they had received both FFP and 4F-PCC during the same visit. The primary outcome was the frequency of thromboembolism within 30 days of 4F-PCC or FFP. Secondary outcomes included time to thromboembolic event and in-hospital mortality. Results: Three hundred and thirty-six patients met the inclusion criteria. Thromboembolic events within 30 days of therapy occurred in seven patients (2.7%) in the FFP group and 14 patients (17.7%) in the 4F-PCC group (p=<0.001). Death occurred in 39 patients (15.2%) who received FFP and 18 patients (22.8%) who received 4F-PCC (p=0.115). Since the 4F-PCC group was treated disproportionately for central nervous system (CNS) bleeding, a subgroup analysis was performed including patients requiring reversal due to CNS bleeds that received vitamin K. The primary outcome remained statistically significant, occurring in four patients (4.1%) in the FFP group and nine patients (14.1%) in the 4F-PCC group (p=0.02). Conclusion: Our study found a significantly higher risk of thromboembolic events in patients receiving 4F-PCC compared to FFP for urgent warfarin reversal. This difference remained statistically significant when controlled for CNS bleeds and administration of vitamin K.


Assuntos
Fatores de Coagulação Sanguínea/efeitos adversos , Plasma , Tromboembolia/induzido quimicamente , Idoso , Anticoagulantes/efeitos adversos , Fatores de Coagulação Sanguínea/administração & dosagem , Serviço Hospitalar de Emergência , Feminino , Humanos , Masculino , Estudos Retrospectivos , Tromboembolia/epidemiologia , Varfarina/efeitos adversos
2.
Transfus Med ; 29(4): 268-274, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31347218

RESUMO

OBJECTIVE: To evaluate the effectiveness and safety of prothrombin complex concentrates (PCCs) in approved and off-label indications. BACKGROUND: PCCs are approved for the urgent reversal of vitamin K antagonists (VKAs). Data concerning the efficacy, safety and dosing for off-label indications are limited, but they are included in massive bleeding protocols. METHODS: This was a retrospective review of cases treated with four-factor PCCs (4F-PCCs) between January 2009 and 2016. Efficacy end-points include: (i) VKA reversal efficacy assessed by international normalised ratio (INR) normalisation (<1·5) and (ii) clinical efficacy as bleeding cessation and/or decreased number of transfused blood components and 24-h mortality in bleeding coagulopathy. The safety end-point is the incidence of thromboembolic events. RESULTS: A total of 328 patients were included (51·8% male, median age 78 years old). Indications were as follows: VKA reversal (66·6%), bleeding coagulopathy (30·5%) and direct anticoagulant (DOAC) reversal due to bleeding (2·5%). VKA reversal was effective in 97·1% of patients, and 76·5% demonstrated complete reversal (INR < 1·5); only 34·3% patients needed hemoderivatives. Prior to emergency procedures, PCCs achieved global responses in 83% of patients, with no bleeding complication during intervention. DOAC reversal was effective in 88·9% of patients. Bleeding cessation was associated with the dose administered (P = 0·002). In coagulopathy bleeding, haemorrhage cessation, established by the International Society of Thrombosis and Haemostais (ISTH) definition, occurred in 56·7% of massive bleeding events and in 42·5% of other coagulopathies; 24-h mortality was 30%, mainly related to active bleeding. Ten thrombotic episodes were observed (3·1%). CONCLUSION: 4F-PCC was effective as adjuvant treatment with an acceptable safety profile, not only for the emergent reversal of VKAs but also for refractory coagulopathy associated with major bleeding.


Assuntos
Anticoagulantes/efeitos adversos , Fatores de Coagulação Sanguínea/administração & dosagem , Coagulação Intravascular Disseminada , Hemorragia , Uso Off-Label , Segurança , Vitamina K/antagonistas & inibidores , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/administração & dosagem , Fatores de Coagulação Sanguínea/efeitos adversos , Coagulação Intravascular Disseminada/sangue , Coagulação Intravascular Disseminada/tratamento farmacológico , Coagulação Intravascular Disseminada/mortalidade , Feminino , Hemorragia/sangue , Hemorragia/induzido quimicamente , Hemorragia/tratamento farmacológico , Hemorragia/mortalidade , Humanos , Incidência , Coeficiente Internacional Normatizado , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tromboembolia/sangue , Tromboembolia/induzido quimicamente , Tromboembolia/mortalidade
3.
BMC Anesthesiol ; 19(1): 97, 2019 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-31185916

RESUMO

BACKGROUND: Most centres use fresh frozen plasma (FFP) based protocols to prevent or treat haemostatic disturbances during liver transplantation. In the present study, we used a rotational thrombelastometry (ROTEM™, TEM, Munich, Germany) guided haemostasis management with fibrinogen concentrates, prothrombin complex concentrates (PCC), platelet concentrates and tranexamic acid without FFP usage and determined the effect on 30 day mortality. METHODS: Retrospective data analysis with 372 consecutive adult liver transplant patients performed between 2007 and 2011. RESULTS: Thrombelastometry guided coagulation management resulted in a transfusion rate for fibrinogen concentrates in 50.2%, PCC in 18.8%, platelet concentrates in 21.2%, tranexamic acid in 4.5%, and red blood cell concentrates in 59.4%. 30 day mortality for the whole cohort was 14.2%. The univariate analyses indicated that nonsurvivors received significantly more fibrinogen concentrates, PCC, red blood cell concentrates, platelet concentrates, and infusion volume, and had a higher MELD score. However, association with mortality was weak as evidenced by receiver operating characteristic curve analyses. Further univariate analyses demonstrated, that up to 8 g of fibrinogen did not increase mortality compared to patients not receiving the coagulation factor. Multivariate analysis demonstrated that platelet concentrates (p = 0.0002, OR 1.87 per unit), infused volume (p = 0.0004, OR = 1.13 per litre), and MELD score (p = 0.024; OR 1.039) are independent predictors for mortality. Fibrinogen concentrates, PCC, and red blood cell concentrates were ruled out as independent risk factors. CONCLUSIONS: ROTEM™ guided substitution with fibrinogen concentrates and PCC does not negatively affect mortality after liver transplantation, while the well-known deleterious effect associated with platelet concentrates was confirmed.


Assuntos
Fatores de Coagulação Sanguínea/metabolismo , Coagulação Sanguínea/fisiologia , Hemostáticos/sangue , Transplante de Fígado/mortalidade , Transplante de Fígado/métodos , Rotação , Adolescente , Adulto , Idoso , Antifibrinolíticos/administração & dosagem , Antifibrinolíticos/sangue , Coagulação Sanguínea/efeitos dos fármacos , Fatores de Coagulação Sanguínea/administração & dosagem , Plaquetas/metabolismo , Criança , Feminino , Fibrinogênio/administração & dosagem , Fibrinogênio/metabolismo , Hemostasia/efeitos dos fármacos , Hemostasia/fisiologia , Hemostáticos/administração & dosagem , Humanos , Transplante de Fígado/efeitos adversos , Transplante de Fígado/tendências , Masculino , Pessoa de Meia-Idade , Mortalidade/tendências , Estudos Retrospectivos , Tromboelastografia/efeitos adversos , Tromboelastografia/métodos , Ácido Tranexâmico/administração & dosagem , Ácido Tranexâmico/sangue , Adulto Jovem
5.
Am J Emerg Med ; 37(8): 1534-1538, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31130370

RESUMO

INTRODUCTION: For reversal of warfarin-induced coagulopathy, FDA labeling of four-factor prothrombin complex concentrate (4F-PCC) endorses a dosing strategy based on body weight and baseline INR. Recent literature suggests lower, fixed doses of 4F-PCC may be equally efficacious. The present evaluation aims to characterize the relationship between 4F-PCC dose and degree of reduction in INR. METHODS: This is a retrospective, single-center review of 4F-PCC administrations for warfarin reversal between May 2014 and August 2017. The primary endpoint evaluates the relationship between doses of 4F-PCC and INR measurement after reversal, represented as a linear regression. Exploratory endpoints characterize the relationships of both body weight and baseline INR, the components determining initial 4F-PCC dose, with INR after reversal. Additionally, for records presenting with an INR of 2-3.9, mean INR after reversal was characterized as a function of two 4F-PCC dose cohorts (< 30 and ≥30 IU fIX/kg). RESULTS: A significant linear relationship between 4F-PCC dose and INR after reversal (INR after 4F-PCC = 1.3651-0.00004(4F-PCC Dose), p = 0.0071, R2 = 0.0630) was observed. Body weight and baseline INR were not correlated with INR after reversal. The subgroup analysis of records with presenting INR of 2-3.9 demonstrated no difference in mean INR after reversal with 4F-PCC for those receiving <30 IU fIX/kg and those receiving ≥30 IU fIX/kg. CONCLUSION: This evaluation found no clinically relevant relationship with 4F-PCC doses and degree of INR reversal. Further prospective study is required to determine optimal dosing schemes of 4F-PCC for warfarin reversal.


Assuntos
Transtornos da Coagulação Sanguínea/tratamento farmacológico , Transtornos da Coagulação Sanguínea/mortalidade , Fatores de Coagulação Sanguínea/administração & dosagem , Varfarina/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Fatores de Coagulação Sanguínea/farmacologia , Peso Corporal , Relação Dose-Resposta a Droga , Feminino , Humanos , Coeficiente Internacional Normatizado , Modelos Lineares , Masculino , Estudos Retrospectivos
6.
Scand J Trauma Resusc Emerg Med ; 27(1): 48, 2019 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-31014373

RESUMO

BACKGROUND: Prothrombin complex concentrate (PCC) is widely used to reverse the action of direct oral anticoagulants (DOACs) in accordance with current guidelines and because of a lack of specific reversal agents. Indications, clinical characteristics and patient outcomes of patients might differ in comparison to reversal of vitamin K antagonists where reversal with PCC is well established. METHODS: Our cohort study explores patient characteristics, indications and clinical outcomes for reversal of all DOAC patients receiving PCC at our university emergency department from 01.06.2012 to 01.07.2017, in comparison with patients on VKA. RESULTS: Out of 199,982 consultations, we studied 346 patients who were given PCC for reversal of either DOAC (n = 74) or VKA (n = 272). The most common reason for treatment was acute bleeding; in 86.7% of both groups. 37.3% of bleeding was traumatic (p = 0.666). The most frequent bleeding location was intracranial (61.6%, p = 0.881). Gastrointestinal bleeding was more often found in the DOAC group (18.9% vs. 8.8%, p = 0.014). More erythrocyte concentrates (ECs) were given to DOAC patients with blood transfusion (p = 0.014). Tranexamic acid was used more often in DOAC patients than in VKA patients (28.4% vs. 7.4%, p < 0.001). No significant group differences were found for the following patient outcomes: in-hospital mortality, ICU stay, and length of stay at the ICU or in hospital. CONCLUSION: In DOAC treated patients, PCC was applied more often because of gastrointestinal bleeding and patients received higher numbers of ECs as well as tranexamic acid. No differences were observed with regard to important clinical outcomes.


Assuntos
Anticoagulantes/administração & dosagem , Fatores de Coagulação Sanguínea/administração & dosagem , Hemorragia/tratamento farmacológico , Vitamina K/antagonistas & inibidores , Doença Aguda , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Feminino , Seguimentos , Hemorragia/mortalidade , Mortalidade Hospitalar/tendências , Humanos , Masculino , Conduta do Tratamento Medicamentoso , Estudos Retrospectivos , Suíça/epidemiologia , Resultado do Tratamento
7.
Int J Hematol ; 109(6): 650-656, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30963470

RESUMO

Patients with severe congenital protein (P)C deficiency require long-term anticoagulant management. Recombinant PC concentrates for prophylactic use are not available in Japan; prothrombin complex concentrates (PCC), containing factors (F)II, VII, IX, X, and PC (PPSB-HT®), have been used 'off-label' in a few patients. We investigated the combined use of prophylactic PCC and Warfarin (VKA; PT-INR 2.0-2.5) in a severely PC-deficient patient in whom VKA alone did not prevent recurrent purpura. Plasma VKA-dependent factor levels and global PC function (Thrombopath®) were assessed. Plasma activity levels of FII/FVII/FIX/FX post-infusion of PCC (6.3 unit/kg) increased 35/27/27/35 (initial level) to 59/60/38/83 IU/dl, respectively. FVII:C and FIX:C rapidly returned to baseline levels 12-24 h post-infusion, but FII:C and FX:C returned more slowly. PC antigen (< 5%) increased to ~ 15%, followed by return to baseline levels 24 h post-infusion. Global PC function was very low (%PiCi 24%), but improved post-PCC infusion. This potential was slightly detectable even at an undetectable PC level. At day 3, high levels of D-dimer and FDP were observed without thrombotic event, but these improved post-infusion. Although PCC restored VKA-dependent coagulation factors, PC contained in PCC significantly improved global anticoagulation, and was clinically beneficial in this severely deficient patient.


Assuntos
Anticoagulantes/administração & dosagem , Fatores de Coagulação Sanguínea/administração & dosagem , Hemostasia , Deficiência de Proteína C/sangue , Deficiência de Proteína C/tratamento farmacológico , Varfarina/administração & dosagem , Adulto , Quimioterapia Combinada , Humanos , Masculino , Índice de Gravidade de Doença , Resultado do Tratamento , Vitamina K Epóxido Redutases/sangue , Adulto Jovem
8.
J Thromb Thrombolysis ; 48(2): 250-255, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30941571

RESUMO

Oral factor Xa (fXa) inhibitor-related bleeding is a concerning drug safety problem. There is considerable controversy surrounding available reversal strategies. The recently approved reversal agent andexanet alfa has limited data, an unclear safety profile, and imparts a substantial financial burden. This has led to the off-label use of four-factor prothrombin complex concentrates (4F-PCC) for this indication. This study aimed to assess the safety and efficacy of 4F-PCC for the management of major bleeding related to oral fXa inhibitors. This observational, retrospective study included adult patients admitted from 2014 to 2018 who received 4F-PCC (Kcentra®) for fXa inhibitor-related major bleeding. Efficacy was assessed using criteria described by Sarode et al. Secondary outcomes included the incidence of thromboembolism, mortality, and a cost analysis comparing 4F-PCC to andexanet alfa for reversal of oral fXa inhibitors. Thirty-one patients received 4F-PCC for major bleeding associated with apixaban (55%) or rivaroxaban (45%). Intracranial hemorrhage (58%) and pericardial effusion (16%) accounted for the majority of bleeding events. Most patients received a single weight-based 4F-PCC dose of 25 units/kg (38.7%) or 50 units/kg (51.6%). Effective hemostasis was achieved in 80.6% of patients. Five patients (16%) died due to acute bleeding and no thromboembolic events were observed. Administration of 4F-PCC was effective for most patients requiring emergent reversal of anticoagulation with apixaban or rivaroxaban and was associated with a low risk of thromboembolic events. Considerable cost differences limit the use of andexanet alfa and may warrant further study of 4F-PCC for fXa inhibitor reversal.


Assuntos
Fatores de Coagulação Sanguínea/uso terapêutico , Inibidores do Fator Xa/efeitos adversos , Hemorragia/induzido quimicamente , Adulto , Fatores de Coagulação Sanguínea/administração & dosagem , Fatores de Coagulação Sanguínea/economia , Fatores de Coagulação Sanguínea/farmacologia , Fator Xa/farmacologia , Fator Xa/uso terapêutico , Feminino , Hemorragia/tratamento farmacológico , Hemostasia/efeitos dos fármacos , Humanos , Masculino , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento
9.
J Pediatr Hematol Oncol ; 41(3): e135-e140, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30601403

RESUMO

BACKGROUND: To date, clinical experience with prothrombin complex concentrate (PCC) in the neonatal population has been limited. AIM: The objective of this study was to describe our experience regarding the effectiveness and safety of PCC administration in newborns with severe bleeding or coagulopathy resistant to conventional therapy. METHODOLOGY: We retrospectively analyzed data from 37 neonates with intractable bleeding or severe coagulation disturbances. All patients received intravenous bolus administration of 20 or 30 u/kg of PCC per dose, as a rescue procedure. RESULTS: Hemostasis was achieved in the majority of neonates and we observed statistically significant improvement in prothrombin time, international normalized ratio, and activated partial thromboplastin time (P<0.001, P=0.044, P<0.001, respectively). Thirteen neonates survived, whereas 24 did not survive. In those who survived, PCC had been administered earlier (<24 h) in the disease process compared with those who died (P=0.043). Neither acute adverse events nor thromboembolic complications were observed in all neonates. CONCLUSIONS: In our study, PCC seemed to be a safe and effective intervention for hemostasis and early intervention was more effective as a rescue therapy, without any adverse event. Further prospective controlled trials are required to determine optimal dose and timing of PCC administration in neonates.


Assuntos
Transtornos da Coagulação Sanguínea/tratamento farmacológico , Fatores de Coagulação Sanguínea/administração & dosagem , Hemorragia/tratamento farmacológico , Tempo para o Tratamento , Transtornos da Coagulação Sanguínea/mortalidade , Fatores de Coagulação Sanguínea/efeitos adversos , Testes de Coagulação Sanguínea , Feminino , Hemorragia/mortalidade , Hemostasia/efeitos dos fármacos , Humanos , Recém-Nascido , Coeficiente Internacional Normatizado , Masculino , Estudos Retrospectivos
10.
Thromb Res ; 173: 71-76, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30476716

RESUMO

OBJECTIVE: Management of acute, major or life threatening bleeding in the presence of direct acting oral anticoagulants (DOAC) is unclear. In the absence of a specific antidote, or in situations where there is a need for adjunctive therapy, the ideal prothrombin complex concentrate and dose is unclear. The goal of our study was to evaluate the outcomes of our reduced dosing strategy with FEIBA in patients experiencing a DOAC-related bleeding event. DESIGN: Retrospective analysis of patients treated with FEIBA for a DOAC-related bleeding event. SETTING: Academic medical center PATIENTS: Consecutive patients between May 2011 and April 2017 receiving FEIBA for a DOAC-related bleed INTERVENTIONS: None MEASUREMENTS & MAIN RESULTS: Of the 64 patients included in this analysis, 38 patients received low dose FEIBA (mean 10.0 ±â€¯3.6 units/kg) and 26 received moderate dose (mean 24.3 ±â€¯2.1 units/kg) FEIBA; an additional dose was requested in 6 patients. Six dabigatran patients received idarucizumab. 30 day event rates included 5 thromboembolic events (8%) and 9 (14%) patients expired. Follow-up CT-imaging for ICH, endoscopy/colonoscopy, or interventional radiology exams did not reveal any clinically concerning active bleeding or hematoma expansion except in 2 ICH patients with slight expansion between imaging sessions. CONCLUSIONS: Low (<20 units/kg) to moderate (20-30 units/kg) doses of FEIBA, with the option for a repeat dose, may be an effective management strategy for obtaining hemostasis in DOAC-related major bleeding events.


Assuntos
Anticoagulantes/efeitos adversos , Fatores de Coagulação Sanguínea/uso terapêutico , Coagulantes/uso terapêutico , Hemorragia/induzido quimicamente , Hemorragia/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Fatores de Coagulação Sanguínea/administração & dosagem , Coagulantes/administração & dosagem , Dabigatrana/efeitos adversos , Relação Dose-Resposta a Droga , Inibidores do Fator Xa/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pirazóis/efeitos adversos , Piridonas/efeitos adversos , Estudos Retrospectivos , Rivaroxabana/efeitos adversos , Resultado do Tratamento , Adulto Jovem
11.
Br J Haematol ; 184(5): 808-816, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30515764

RESUMO

This retrospective study investigated the efficacy and safety of prothrombin complex concentrates (PCCs) for management of major bleeding events (MBE) in 344 patients receiving the anticoagulants rivaroxaban, apixaban or warfarin during the period January 2016 to April 2018. Median (range) PCC dose was 2000 units (1000-4500). Intracranial haemorrhage (ICH) was the most common indication (137/344, 39·8%) for PCC use followed by gastrointestinal bleeding (93/344, 27%). ICH patients more frequently received rivaroxaban (62·5%) or apixaban (52·5%) compared to warfarin (34·5%), P = 0·002; and visceral bleeding patients received warfarin more frequently (24·2%) than rivaroxaban (5%) or apixaban (10%), P = 0·003. Median rivaroxaban and apixaban levels were 230 ng/ml (47-759) and 159 ng/ml (45-255). Median International Normalised Ratio pre- and post-PCC in patients on warfarin were 3·4 (1·9-15·4) and 1·2 (1·0-1·9). Blood products use was the same between groups. Thirty-day mortality and re-bleeding rates in patients with ICH were 35% (P = 0·50) and 18% (P = 0·90) with no differences between the groups. Thrombosis occurred in 4·1% patients within 30 days with no difference between groups. Two of 91 (2·2%) patients with ICH only (both on warfarin) had ischaemic strokes within 30 days post-PCC. In conclusion, there was no difference in the safety (thrombosis) or efficacy (30-day mortality, re-bleeding) in use of PCC for MBE in patients on warfarin, rivaroxaban or apixaban.


Assuntos
Fatores de Coagulação Sanguínea/administração & dosagem , Hemorragia Gastrointestinal , Hemorragias Intracranianas , Pirazóis/administração & dosagem , Piridonas/administração & dosagem , Rivaroxabana/administração & dosagem , Varfarina/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Fatores de Coagulação Sanguínea/efeitos adversos , Intervalo Livre de Doença , Feminino , Hemorragia Gastrointestinal/tratamento farmacológico , Hemorragia Gastrointestinal/mortalidade , Humanos , Hemorragias Intracranianas/tratamento farmacológico , Hemorragias Intracranianas/mortalidade , Masculino , Pessoa de Meia-Idade , Pirazóis/efeitos adversos , Piridonas/efeitos adversos , Rivaroxabana/efeitos adversos , Taxa de Sobrevida , Varfarina/efeitos adversos
12.
J Thromb Thrombolysis ; 47(2): 263-271, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30443817

RESUMO

BACKGROUND: Four-factor PCC is the recommended standard of care for acute warfarin reversal but optimal dosing is unknown. We aim to show that a low-dose strategy is often adequate and may reduce the risk of thromboembolic events when compared to manufacturer-recommended dosing. METHODS: A weight-based dosing strategy of 15-25 units/kg was established as the institutional standard of care in May 2015. This retrospective, before-and-after cohort analysis included patients receiving 4F-PCC according to a manufacturer-recommended (n = 122) or a low-dose (n = 83) strategy. The primary efficacy outcome was a combination of INR reversal on first check and hemostatic efficacy at 24 h. RESULTS: Demographics, indications for warfarin, and presenting INR values were similar between the two groups. Patients in the manufacturer-recommended dose group received significantly more 4F-PCC than the low dose group (2110 units vs. 1530 units). More patients in the manufacturer-recommended dose group achieved the primary endpoint (75.4% vs. 61.4%), with more patients achieving the target INR on recheck in the manufacturer-recommended dose group (95.9% vs. 84.3%) and no difference in hemostatic efficacy between groups (79.5% vs. 74.7%). There was no difference in thromboembolic events at 72 h (4.1% vs. 1.2%) or at 30 days (8.2% vs. 4.8%). Significantly more patients in the manufacturer-recommended dose group died or were transferred to hospice care during hospitalization (21.3% vs. 9.6%). CONCLUSION: Utilization of a low-dose 4F-PCC strategy resulted in fewer patients achieving target INR reversal, but no difference in hemostatic efficacy, thromboembolic events, or survival.


Assuntos
Anticoagulantes , Fatores de Coagulação Sanguínea/administração & dosagem , Hemorragia/tratamento farmacológico , Hemostasia/efeitos dos fármacos , Antagonistas de Heparina/administração & dosagem , Varfarina/antagonistas & inibidores , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Fatores de Coagulação Sanguínea/efeitos adversos , Peso Corporal , Cálculos da Dosagem de Medicamento , Monitoramento de Medicamentos/métodos , Feminino , Hemorragia/induzido quimicamente , Hemorragia/diagnóstico , Antagonistas de Heparina/efeitos adversos , Humanos , Coeficiente Internacional Normatizado , Masculino , Modelos Biológicos , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Resultado do Tratamento , Varfarina/administração & dosagem , Varfarina/efeitos adversos
13.
Exp Clin Transplant ; 17(2): 222-230, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30295585

RESUMO

OBJECTIVES: Increased transfusion requirements in liver transplantation have been reported to be associated with worsened outcomes, more frequent reinterventions, and higher expenses. Anesthesiologists might counteract this through improved coagulation management. We evaluated the effects of rotational thromboelastometry on transfusion and coagulation product requirements and on outcome measurements. MATERIALS AND METHODS: Patients who were 14 years or older and who were undergoing liver transplant at Hannover Medical School between January 2005 and December 2009 were included in this retrospective analysis. Demographic, clinical, and laboratory data, use of rotational thromboelastometry, intraoperative need for blood or coagulation products and antifibrinolytic substances, and clinical course were recorded. Correlations were examined using appropriate statistical tests. RESULTS: Our study included 413 patients. Use of rotational thromboelastometry was associated with less frequent intraoperative administration of red blood cell concentrates, fresh frozen plasma, platelet concentrates, prothrombin complex concentrates, and antithrombin concentrates (all P < .05). In addition, univariate and multivariate tests showed that rotational thromboelastometry was correlated with decreased need for red blood cell concentrates and fresh frozen plasma (all P < .05). Intraoperative administration rates of antifibrinolytic substances and fibrinogen concentrate were significantly increased in patients who received rotational thromboelastometry monitoring (both P < .05). However, use of rotational thromboelastometry was not associated with massive transfusion rates (> 10 units vs less), clinical outcome, or length of stay in the intensive care unit (all P > .05). CONCLUSIONS: Use of rotational thromboelastometry during liver transplant may reduce the need for intraoperative transfusion and coagulation products. Relevant effects of rotational thromboelastometry on patient outcomes or lengths of stay in the intensive care unit could not be ascertained. However, readjustment of therapeutic thresholds may improve the clinical impact.


Assuntos
Anticoagulantes/administração & dosagem , Coagulação Sanguínea/efeitos dos fármacos , Transfusão de Eritrócitos , Transplante de Fígado/métodos , Monitorização Intraoperatória/métodos , Plasma , Transfusão de Plaquetas , Tromboelastografia , Adulto , Anticoagulantes/efeitos adversos , Antitrombinas/administração & dosagem , Fatores de Coagulação Sanguínea/administração & dosagem , Transfusão de Eritrócitos/efeitos adversos , Feminino , Alemanha , Humanos , Unidades de Terapia Intensiva , Tempo de Internação , Transplante de Fígado/efeitos adversos , Masculino , Pessoa de Meia-Idade , Transfusão de Plaquetas/efeitos adversos , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
14.
J Thromb Thrombolysis ; 47(3): 369-374, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30460443

RESUMO

The package insert of 4-factor prothrombin complex concentrate (4F-PCC) contains specific dosing recommendations stating to determine the patients dose based on their INR and weight, capping the weight at 100 kg. However, the mean body mass index (BMI) in the 4F-PCC U.S. approval study was 27 kg/m2, and there is a lack of literature identifying the ideal dosing strategy in obesity. We conducted a retrospective analysis of obese patients (BMI ≥ 30 kg/m2) who received 4F-PCC for warfarin associated emergent bleeding reversal. Treatment groups were those that received 4F-PCC on adjusted body weight (AdjBW) and those on actual body weight (ActBW). The primary outcome was the percent of patients achieving coagulopathy reversal, defined as a post-treatment INR < 1.4 for neurologic indications and < 1.5 for all others. A total of 78 obese patients were included (28 AdjBW and 50 ActBW). Baseline INR (3.1 vs. 2.8; p = 0.052) and BMI (33.6 vs. 33.6 kg/m2) were similar between groups. Achievement of goal INR was significantly lower in the AdjBW group (36% vs. 68%; p = 0.006). A majority of patients had intracranial hemorrhage (32% vs. 54%; p = 0.06), and the median dose of 4F-PCC was lower in the AdjBW group (2120 vs. 2500 units; p = 0.02). Dosing 4F-PCC using adjusted body weight in obese patients resulted in a significantly lower rate of coagulopathy reversal. ActBW should be used to dose 4F-PCC in obese patients when the 100 kg dose cap is utilized per the package insert recommendations.


Assuntos
Fatores de Coagulação Sanguínea/administração & dosagem , Cálculos da Dosagem de Medicamento , Hemorragia/tratamento farmacológico , Obesidade , Varfarina/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Peso Corporal , Feminino , Hemorragia/induzido quimicamente , Humanos , Coeficiente Internacional Normatizado , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
15.
Can J Surg ; 62(1): 14-19, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30265643

RESUMO

BACKGROUND: Patients with hip fracture who present anticoagulated with warfarin often require reversal of anticoagulation for safe hip fracture surgery. Vitamin K is typically administered for this, but requires 24-48 hours for maximal effect. These patients have an increased delay to surgery and increased mortality. Octaplex is a prothrombin complex concentrate (PCC) that reverses warfarin anticoagulation in less than an hour. This study assesses the effectiveness and safety of Octaplex for reversal of warfarin anticoagulation for hip fracture surgery. METHODS: We reviewed the medical records of all patients with hip fracture in Calgary who received Octaplex between 2009 and 2015. Timing of admission, Octaplex administration and hip fracture surgery were recorded. Mortality and cardiac, thrombotic and orthopedic complications were assessed. RESULTS: Median time from Octaplex administration to an international normalized ratio of 1.4 or lower was 1.1 hours. The median time from admission to surgery was 22 hours. Thirty-day mortality was 15.2%, with 4 cases of cardiac arrest and 1 respiratory arrest. Patients who received both Octaplex and fresh frozen plasma (FFP) had a lower rate of 30-day survival than those who received only Octaplex (95.7% v. 60.0%, p = 0.002). CONCLUSION: There were significant rates of cardiac events and 30-day mortality among patients who received Octaplex, but this is unsurprising in this population with multiple medical comorbidities. We caution against administrering both FFP and a PCC in patients for warfarin reversal. Octaplex is effective for rapidly reversing warfarin anticoagulation and reducing delays to hip fracture surgery. Further study comparing Octaplex to reversal using only vitamin K is required.


Assuntos
Anticoagulantes , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Fatores de Coagulação Sanguínea/administração & dosagem , Fraturas do Quadril/cirurgia , Varfarina/antagonistas & inibidores , Idoso , Idoso de 80 Anos ou mais , Coagulação Sanguínea/efeitos dos fármacos , Transtornos da Coagulação Sanguínea/induzido quimicamente , Fatores de Coagulação Sanguínea/efeitos adversos , Feminino , Humanos , Coeficiente Internacional Normatizado , Masculino , Estudos Retrospectivos , Fatores de Tempo , Tempo para o Tratamento , Resultado do Tratamento
16.
Neurocrit Care ; 30(2): 322-333, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30382531

RESUMO

BACKGROUND: Anticoagulation therapy is a major risk factor for unfavorable patient outcomes following (traumatic) intracranial hemorrhage. Direct oral anticoagulants (DOAC) are increasingly used for the prevention and treatment of thromboembolic diseases. Data on patients treated for acute subdural hemorrhage (SDH) during anticoagulation therapy with DOAC are limited. METHODS: We analyzed the medical records of consecutive patients treated at our institution for acute SDH during anticoagulation therapy with DOAC or vitamin K antagonists (VKA) during a period of 30 months. Patient characteristics such as results of imaging and laboratory studies, treatment modalities and short-term patient outcomes were included. RESULTS: A total of 128 patients with preadmission DOAC (n = 65) or VKA (n = 63) intake were compared. The overall 30-day mortality rate of this patient cohort was 27%, and it did not differ between patients with DOAC or VKA intake (26% vs. 27%; p = 1.000). Similarly, the rates of neurosurgical intervention (65%) and intracranial re-hemorrhage (18%) were comparable. Prothrombin complex concentrates were administered more frequently in patients with VKA intake than in patients with DOAC intake (90% vs. 58%; p < 0.0001). DOAC treatment in patients with acute SDH did not increase in-hospital and 30-day mortality rates compared to VKA treatment. CONCLUSIONS: These findings support the favorable safety profile of DOAC in patients, even in the setting of intracranial hemorrhage. However, the availability of specific antidotes to DOAC may further improve the management of these patients.


Assuntos
Anticoagulantes/efeitos adversos , Fatores de Coagulação Sanguínea/administração & dosagem , Hematoma Subdural Agudo/induzido quimicamente , Hematoma Subdural Agudo/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Feminino , Hematoma Subdural Agudo/mortalidade , Humanos , Masculino , Vitamina K/antagonistas & inibidores
18.
J Cardiothorac Vasc Anesth ; 33(2): 321-327, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30057251

RESUMO

OBJECTIVES: To investigate whether administering fibrinogen concentrate or cryoprecipitate is associated with increased postoperative thromboembolic events and improved mortality in patients undergoing thoracic aortic surgery. DESIGN: Multicenter retrospective cohort study using propensity-score analyses and multivariate logistic regression analysis to control for confounders. SETTING: Four hospitals (1 national cardiovascular center and 3 university hospitals). PARTICIPANTS: Patients undergoing thoracic aortic surgery with cardiopulmonary bypass between January 2010 and October 2012 (n = 1,047). INTERVENTIONS: Outcomes in patients treated with fibrinogen concentrate or cryoprecipitate (fibrinogen group) were compared with those who did not receive these products (no fibrinogen group) based on propensity-score matching. Multivariate logistic regression analysis then was performed to confirm the results. MEASUREMENTS AND MAIN RESULTS: Among 1,047 patients enrolled in this study, 247 patients received fibrinogen concentrate or cryoprecipitate. The median amount of administered fibrinogen was 3 g (interquartile range 2-4 g). Eighty-seven patients were excluded from the propensity-score matching because of missing data. Propensity-score-matched analysis showed no significant difference in the incidence of thromboembolic events or 30-day mortality rate between the groups. Multivariate analysis revealed that the fibrinogen group showed no significant difference in thromboembolic events (odds ratio 1.22; 95% confidence interval 0.76-1.95; p = 0.408) or mortality rate (odds ratio 0.44; 95% confidence interval 0.18-1.12; p = 0.081) compared with those in the no fibrinogen group. CONCLUSIONS: Administering fibrinogen concentrate or cryoprecipitate was associated with neither thromboembolic events nor 30-day mortality in patients undergoing thoracic aortic surgery. Administering fibrinogen concentrate or cryoprecipitate is safe and does not appear to increase thromboembolic events and mortality in thoracic aortic surgery patients.


Assuntos
Aneurisma da Aorta Torácica/cirurgia , Procedimentos Cirúrgicos Cardiovasculares/efeitos adversos , Fibrinogênio/administração & dosagem , Hemorragia Pós-Operatória/prevenção & controle , Tromboembolia/epidemiologia , Idoso , Aneurisma da Aorta Torácica/sangue , Fatores de Coagulação Sanguínea/administração & dosagem , Bases de Dados Factuais , Feminino , Hemostáticos/administração & dosagem , Humanos , Incidência , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Hemorragia Pós-Operatória/sangue , Hemorragia Pós-Operatória/mortalidade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Tromboembolia/sangue , Tromboembolia/etiologia
19.
BMC Anesthesiol ; 18(1): 198, 2018 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-30579327

RESUMO

BACKGROUND: Perioperative bleeding and transfusion are important causes of morbidity and mortality in patients undergoing liver transplantation. The aim of this study is to assess whether viscoelastic tests-guided therapy with the use of synthetic factor concentrates impact transfusion rates of hemocomponents in adult patients undergoing liver transplantation. METHODS: This is an interventional before-after comparative study. Patients undergoing liver transplantation before the implementation of a protocol using thromboelastometry and synthetic factor concentrates were compared to patients after the implementation. Primary outcome was transfusion of any hemocomponents. Secondary outcomes included: transfusion of red blood cells (RBC), fresh frozen plasma (FFP), cryoprecipitate or platelets, clinical complications, length of stay and in-hospital mortality. RESULTS: A total of 183 patients were included in the control and 54 in the intervention phase. After propensity score matching, the proportion of patients receiving any transfusion of hemocomponents was lower in the intervention phase (37.0 vs 58.4%; OR, 0.42; 95% CI, 0.20-0.87; p = 0.019). Patients in the intervention phase received less RBC (30.2 vs 52.5%; OR, 0.21; 95% CI, 0.08-0.56; p = 0.002) and FFP (5.7 vs 27.3%; OR, 0.11; 95% CI, 0.03-0.43; p = 0.002). There was no difference regarding transfusion of cryoprecipitate and platelets, complications related to the procedure, hospital length of stay and mortality. CONCLUSIONS: Use of a viscoelastic test-guided transfusion algorithm with the use of synthetic factor concentrates reduces the transfusion rates of allogenic blood in patients submitted to liver transplantation. TRIAL REGISTRATION: This trial was registered retrospectively on November 15th, 2018 - clinicaltrials.gov - Identifier: NCT03756948.


Assuntos
Fatores de Coagulação Sanguínea/administração & dosagem , Transfusão de Sangue/métodos , Transplante de Fígado/métodos , Tromboelastografia/métodos , Adulto , Algoritmos , Perda Sanguínea Cirúrgica/prevenção & controle , Estudos Controlados Antes e Depois , Feminino , Mortalidade Hospitalar , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Plasma , Transfusão de Plaquetas/métodos , Estudos Prospectivos , Estudos Retrospectivos
20.
Expert Opin Drug Saf ; 17(12): 1233-1237, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30462521

RESUMO

INTRODUCTION: Patients affected by hemophilia A often require frequent prophylactic and therapeutic self-infusion. For those who develop inhibitors, treatment options are limited and mortality is increased. Emicizumab, a bispecific antibody to Factors IXa and X that carries out the function of Factor VIII (FVIII), represents a novel therapeutic approach. Areas covered: We review the clinical trials and key laboratory assay research for emicizumab. Emicizumab reduced the annualized bleeding rate by 87% compared to placebo in patients with inhibitors. For patients without inhibitors, emicizumab reduced the annualized bleeding rate 96-97% compared to no prophylaxis and 68% compared to prior FVIII prophylaxis. Three patients developed a thrombotic microangiopathy (TMA) and two patients had thrombotic events while on emicizumab in combination with activated prothrombin complex concentration (aPCC) alone or concurrent with activated recombinant factor FVII (rFVIIa). Expert opinion: Emicizumab represents a much-needed alternative approach to managing Factor VIII deficiency, especially for those with inhibitors or limited ability to self-infuse. For patients with inhibitors, thrombotic complications including TMA, not seen with other bypassing agents, raises concern about the use of emicizumab in combination with aPCC and how patients who have breakthrough bleeding can be safely managed.


Assuntos
Anticorpos Biespecíficos/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Hemofilia A/tratamento farmacológico , Trombose/induzido quimicamente , Anticorpos Biespecíficos/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Fatores de Coagulação Sanguínea/administração & dosagem , Hemofilia A/fisiopatologia , Hemorragia/prevenção & controle , Humanos
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