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1.
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
2.
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
3.
Anesthesiology ; 131(3): 543-554, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31180918

RESUMO

BACKGROUND: The risk of thromboembolic complications with prothrombin complex concentrates (PCCs) appears low when used for reversal of vitamin K antagonists but might be different in other indications (e.g., trauma). A difference in risk could arise from the plasma ratio of pro- versus anticoagulant proteins. This study used a porcine trauma model to investigate combined treatment with PCC and antithrombin. The hypothesis was that antithrombin can modulate prothrombotic effects and prevent adverse events of PCC. METHODS: Nine treatment groups (n = 7 per group) were included: control (placebo), PCC (50 IU/kg), PCC plus antithrombin (three groups, with antithrombin doses of 12.5, 25, or 50 IU/kg), fibrinogen concentrate (100 mg/kg) plus PCC, fibrinogen concentrate plus PCC plus antithrombin dose of 50 IU/kg, tranexamic acid (15 mg/kg) plus fibrinogen concentrate plus PCC, and tranexamic acid plus fibrinogen concentrate plus PCC plus antithrombin dose of 50 IU/kg. In each group, bilateral femur fractures and thorax contusion were followed 60 min later by blunt liver injury. Study treatment was then administered, and animals were subsequently observed for 210 min. RESULTS: Total blood loss (mean ± SD) was statistically significantly lower in all three PCC plus antithrombin groups (PCC plus antithrombin dose of 50 IU/kg, 672 ± 63 ml; PCC plus antithrombin dose of 25 IU/kg, 535 ± 72 ml; and PCC plus antithrombin dose of 12.5 IU/kg, 538 ± 50 ml) than in the PCC group (907 ± 132 ml), which in turn had statistically significantly reduced bleeding versus the control group (1,671 ± 409 ml). Signs of disseminated intravascular coagulation were apparent with PCC monotherapy, and early deaths occurred with fibrinogen concentrate plus PCC, attributable to pulmonary emboli. Antithrombin was protective against both of these effects: signs of disseminated intravascular coagulation were absent from the PCC plus antithrombin groups, and there were no early deaths in the group with fibrinogen concentrate plus PCC plus antithrombin dose of 50 IU/kg. CONCLUSIONS: According to this trauma model, 50 IU/kg PCC increases the risk of disseminated intravascular coagulation and other thromboembolic complications, most notably when coadministered with fibrinogen concentrate. The addition of antithrombin appears to reduce this risk.


Assuntos
Antitrombinas/uso terapêutico , Fatores de Coagulação Sanguínea/efeitos adversos , Coagulação Intravascular Disseminada/prevenção & controle , Animais , Modelos Animais de Doenças , Coagulação Intravascular Disseminada/complicações , Masculino , Suínos , Ferimentos não Penetrantes/complicações
5.
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
6.
Neurol Sci ; 40(4): 813-827, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30689075

RESUMO

BACKGROUND: Prothrombin complex concentrate (PCC) is the treatment of choice in vitamin K antagonist-associated intracranial hemorrhage (VKA-ICH). However, the efficiency and safety associated with their use remain unclear. AIMS: This study aimed to assess the current evidence of the clinical outcomes in patients with VKA-ICH treated with or without PCC. A meta-analysis was conducted. Two randomized controlled trials and 19 observational studies were included. PCC use demonstrated a significant increased likelihood of international normalized ratio (INR) normalization (OR = 3.76; 95% CI 1.74-8.12), shortened time to INR correction (MD = - 1.30; 95% CI - 2.08 to - 0.53) and reduction of hematoma expansion (HE) rate (OR = 0.37; 95% CI 0.23-0.60). Although PCC use revealed a statistical reduction at 30-day mortality (OR = 0.62; 95% CI 0.50-0.78), the result was inconsistent with mortality at discharge (OR = 1.03; 95% CI 0.68-1.57) and 90-day follow-up (OR = 0.50; 95% CI 0.24-1.07), both of which yielded no significant difference. When subgroup analyses were performed focus on PCC only treatment with FFP, no statistically significant difference was observed in 30-day mortality (OR = 0.43; 95% CI 0.11-1.71) as well. Besides, significant difference was not found in neurologic improvement at discharge (OR = 1.85; 95% CI 0.32-10.75), 30-day follow-up (OR = 3.00; 95% CI 0.93-9.70), or 90-day follow-up (OR = 1.55; 95% CI 0.84-2.86). No statistically significant difference was noted in the risk of thromboembolism following PCC administration (OR = 0.61; 95% CI 0.23-1.63). CONCLUSIONS: PCC use for VKA-ICH reversal was associated with a significant reduction in INR and HE rate, without an increased risk of thromboembolic events. However, this reduction was not associated with improvement in neurologic deficits or overall survival. Well-designed randomized trials with special considerations to the aspect are necessary.


Assuntos
Anticoagulantes/efeitos adversos , Fatores de Coagulação Sanguínea/farmacologia , Hemorragias Intracranianas/induzido quimicamente , Hemorragias Intracranianas/tratamento farmacológico , Vitamina K/antagonistas & inibidores , Fatores de Coagulação Sanguínea/efeitos adversos , Humanos
7.
J Thromb Thrombolysis ; 47(1): 129-133, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30267246

RESUMO

Antifibrinolytics combined with aPCC are not routinely administered to patients with acquired hemophilia A due to increased thrombotic risk. This association normalizes clot stability, and improves the efficacy of therapy, but can increase the risk of severe side effects. Due to these premises it has always raised doubts and perplexities in the clinics. We now report the data of the "FEIBA® on acquired haemophilia A Italian Registry (FAIR Registry)", a retrospective-prospective study that included 56 patients. This is the first study that assessed the clinical response of the combination of aPCC and antifibrinolytic agents in patients with acquired haemophilia A. A total of 101 acute bleeds were treated with aPCC. Antifibrinolytic agents were used in the treatment of 39.6% of total bleeds, based on both, a clinical assessment and an evaluation of bleeding. Twenty-five of the 30 patients (57.1%) treated with antifibrinolytic drugs showed serious co-morbidity. Among them, 40% presented severe cardiovascular diseases. All bleeds treated with combined therapy had a shorter duration of treatment (mean reduction 16.3%). All the treated patients presented a good tolerability and no arterial or venous thromboembolic events were reported. In our retrospective registry the combination of antifibrinolytics and aPCC appears safe and effective in the treatment of patients with AHA, especially in the case of severe and life-threatening bleeding, but this hypothesis needs to be confirmed in adequate, larger clinical trials.


Assuntos
Antifibrinolíticos/uso terapêutico , Fatores de Coagulação Sanguínea/uso terapêutico , Hemofilia A/complicações , Tromboembolia/etiologia , Antifibrinolíticos/efeitos adversos , Fatores de Coagulação Sanguínea/efeitos adversos , Doenças Cardiovasculares/induzido quimicamente , Quimioterapia Combinada/métodos , Hemorragia/tratamento farmacológico , Humanos , Sistema de Registros
9.
Am J Emerg Med ; 37(2): 214-219, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-29802004

RESUMO

BACKGROUND: The incidence of patients who present with life-threatening bleeding complications has been increasing as the use of direct oral anticoagulation (DOAC) has increased. Therefore, effective reversal agents are urgently needed. Current guidelines recommend the use of prothrombin complex concentrates (PCCs) and activated PCCs (aPCC) for reversal of DOAC anticoagulant activity in the setting of traumatic and non-traumatic intracranial hemorrhage (ICH). However, little data is available. OBJECTIVE: Herein, we investigated the safety and effectiveness of Factor Eight Inhibitor Bypassing Activity [FEIBA (an aPCC)] in a population of patients who required emergent reversal of DOAC for hemorrhage or urgent surgical interventions. METHODS: This is a case series study. Medical records from patients who required emergent reversal of DOAC for life threatening hemorrhage or urgent surgical interventions were collected from February 1, 2014, to April 1, 2017 and reviewed. Data, including demographics as well as safety, outcomes, and dosing of FEIBA for reversal of DOAC effects were collected and descriptive statistics were obtained. RESULTS: Forty-two patients who received FEIBA were included in the study. The rates of thrombotic events (10%), hemorrhage progression (10%), and observed mortality (29%) were similar to rates previously published in the limited literature evaluating aPCC use in this population. CONCLUSION: This case series suggests that FEIBA administration is relatively safe and effective to reverse DOACs in the setting of hemorrhage or need for urgent surgical procedures. Until target-specific reversal agents are available, future studies are warranted to evaluate the effectiveness of aPCC administration for DOAC-associated hemorrhagic complications.


Assuntos
Anticoagulantes/efeitos adversos , Fatores de Coagulação Sanguínea/efeitos adversos , Fatores de Coagulação Sanguínea/uso terapêutico , Coagulantes/efeitos adversos , Coagulantes/uso terapêutico , Hemorragia/induzido quimicamente , Hemorragia/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Perda Sanguínea Cirúrgica/prevenção & controle , Feminino , Hemorragia/prevenção & controle , Humanos , Hemorragias Intracranianas/induzido quimicamente , Hemorragias Intracranianas/tratamento farmacológico , Hemorragias Intracranianas/prevenção & controle , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios
10.
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
11.
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
12.
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
13.
BioDrugs ; 32(6): 561-570, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30430367

RESUMO

Current unmet needs in haemophilia A patients with inhibitors include the need for intravenous infusion of replacement therapy and the high burden of treatment associated with prophylaxis. Emicizumab is a humanised bispecific monoclonal antibody designed to address these unmet needs and has completed phase III clinical trials in adolescents/adults (HAVEN 1) and paediatric (HAVEN 2) inhibitor populations. In HAVEN 1, there was an 80% bleed reduction across all bleeds, 89% reduction in treated joint bleeds, 92% reduction in treated spontaneous bleeds, and 95% reduction in treated target joint bleeds on emicizumab compared with no prophylaxis. In HAVEN 2, there was a 63% reduction in all bleeds, 94.7% reduction in treated bleeds, 94.7% reduction in treated spontaneous bleeds, 100% reduction in treated joint bleeds, and 100% reduction in treated target joint bleeds on emicizumab prophylaxis when compared with no prophylaxis. For patients on bypassing agent prophylaxis, emicizumab resulted in a 68% reduction in bleeds in HAVEN 1 and a 100% reduction in bleed rates in HAVEN 2. In HAVEN 1, three patients developed thrombotic microangiopathy (TMA) and two developed thrombosis when emicizumab was used together with an activated prothrombin complex concentrate (aPCC) at high or frequent doses. When the combination was avoided in HAVEN 2, no patient developed TMA or thrombosis. In both studies, no anti-emicizumab antibodies developed and the pharmacokinetic profile of emicizumab was similar. Emicizumab use is currently being explored in haemophilia A patients without inhibitors as well as in combination with other haemophilia A replacement therapies. The role of emicizumab in combination with current factor VIII replacement therapies and evolving non-replacement therapies remains to be established.


Assuntos
Anticorpos Biespecíficos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Fatores de Coagulação Sanguínea/efeitos adversos , Coagulantes/uso terapêutico , Hemofilia A/tratamento farmacológico , Hemorragia/prevenção & controle , Ensaios Clínicos Fase III como Assunto , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Fator VIII/genética , Necessidades e Demandas de Serviços de Saúde , Hemofilia A/complicações , Hemofilia A/genética , Hemorragia/epidemiologia , Hemorragia/etiologia , Humanos , Expectativa de Vida , Qualidade de Vida , Microangiopatias Trombóticas/induzido quimicamente , Microangiopatias Trombóticas/prevenção & controle , Resultado do Tratamento
14.
Blood Transfus ; 16(6): 525-534, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30201084

RESUMO

Selecting therapeutic products for the treatment of haemophilia follows the process of obtaining market approval of products submitted to the scrutiny of a regulatory agency. In well-resourced countries, key decisions on whether a product is sufficiently safe and of high quality are made by highly expert and well-resourced agencies, such as the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA). In countries lacking such agencies, well-informed decisions can still be made through an appreciation of the key issues affecting the quality, safety and efficacy of haemophilia products. A number of well-established principles may then be applied in order to make a choice. In this review, reflecting principles outlined by the World Federation of Hemophilia, we outline the key features in determining the acceptability of therapeutic products for haemophilia in order to ensure an optimal choice in all the environments providing haemophilia care.


Assuntos
Fatores de Coagulação Sanguínea/uso terapêutico , Fator VIII/uso terapêutico , Fibrinogênio/uso terapêutico , Hemofilia A/dietoterapia , Fatores de Coagulação Sanguínea/efeitos adversos , Fator VIII/efeitos adversos , Fibrinogênio/efeitos adversos , Hemofilia A/sangue , Humanos , Estados Unidos , United States Food and Drug Administration
15.
J Crit Care ; 48: 183-190, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30218958

RESUMO

PURPOSE: Current guidelines favor 4F-PCC over plasma for warfarin reversal. Uncertainty remains on its thrombotic risk and hemostatic effectiveness when used for direct-acting oral anticoagulants (DOACs), transplants, massive transfusion protocols (MTP), and non-anticoagulated patients. This study sought to evaluate the tolerability and effectiveness of 4F-PCC in a real-world setting. MATERIALS AND METHODS: This was a retrospective study of adults who received 4F-PCC from March 2014 to December 2015. The primary outcome was thromboembolic events within 14 days. The secondary outcome was hemostatic effectiveness within 24 h. RESULTS: The final analysis included 212 patients. Primary reversal indication was major bleed in 165 patients (77.8%) and emergent surgery in 47 patients (22.2%). Thromboembolism occurred in 22 patients (10.4%), more in emergent surgery than major bleed reversals (17% and 8.5%, respectively). MTP and heart transplant patients had the highest thromboembolic event rates (44.4% and 28.6%, respectively). Hemostatic effectiveness was 65.8% (68% in major bleed and 58.1% in emergent surgery). DOAC patients achieved hemostasis most often (78.9%). Administration of any reversal agent, major surgery within 14 days, and MTP activation were significant predictors of thromboembolism. CONCLUSIONS: Use of 4F-PCC in this real-world setting was associated with variable thromboembolic and hemostatic effectiveness rates based on the indication for reversal.


Assuntos
Anticoagulantes/efeitos adversos , Fatores de Coagulação Sanguínea/uso terapêutico , Hemorragia/tratamento farmacológico , Varfarina/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Fatores de Coagulação Sanguínea/administração & dosagem , Fatores de Coagulação Sanguínea/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Hemorragia/etiologia , Hemostasia , Humanos , Coeficiente Internacional Normatizado , Registros Médicos , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
16.
J Clin Pharm Ther ; 43(6): 903-905, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29885249

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Prothrombin complex concentrate (PCC) is a plasma-derived concentrate used to replenish clotting factors. There are limited recommendations for treating coagulopathy induced by direct oral anticoagulants (DOAC). Data are limited regarding both total dose and repeated dosing with this population. CASE SUMMARY: We describe a case of an adult patient anticoagulated with apixaban who received two 35 unit/kg doses of PCC resulting in suspected pulmonary embolism. WHAT IS NEW AND CONCLUSION: Treatment of DOAC-induced bleeding remains an "off-label" indication for PCC. Additional doses should be given with caution if given at all and patients monitored closely.


Assuntos
Fatores de Coagulação Sanguínea/administração & dosagem , Inibidores do Fator Xa/efeitos adversos , Embolia Pulmonar/etiologia , Pirazóis/efeitos adversos , Piridonas/efeitos adversos , Idoso , Fatores de Coagulação Sanguínea/efeitos adversos , Inibidores do Fator Xa/administração & dosagem , Hemorragia/induzido quimicamente , Hemorragia/terapia , Humanos , Masculino , Uso Off-Label , Embolia Pulmonar/patologia , Pirazóis/administração & dosagem , Piridonas/administração & dosagem
17.
Eur J Haematol ; 101(3): 349-353, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29862565

RESUMO

BACKGROUND/OBJECTIVE: While four-factor prothrombin complex concentrate (4F-PCC) is FDA-approved for reversal of warfarin-induced major bleeding, its use in real-world settings is unclear. This study's objective was to identify indications leading to 4F-PCC use and associated outcomes at a single university hospital. METHODS: This was a retrospective cohort study of patients receiving 4F-PCC over a 22-month period. A dose was "on-label" if given for reversal of warfarin-induced coagulopathy in patients with major bleeding or requiring urgent surgeries/procedures; other doses were "off-label". RESULTS: A total of 165 doses of 4F-PCC in 154 patients were given. Sixty-one percent of doses were on-label, while 39% were off-label. Intracranial hemorrhage was the most common indication (55% of doses). On-label patients had significantly higher rate of INR normalization and survival to hospital discharge than off-label patients. There was no difference in time to INR normalization, time to hemostasis, or incidence of thromboembolic complications. CONCLUSIONS: Off-label use of 4F-PCC is likely common, occurring in nearly 40% of drug administrations at our center. Larger-scale prospective trials studying specific indications are needed for validation in off-label settings. Until such evidence is available, given potential harms historically displayed by off-label use of other hemostatic agents, limiting off-label 4F-PCC use is recommended.


Assuntos
Fatores de Coagulação Sanguínea/uso terapêutico , Hemorragia/tratamento farmacológico , Uso Off-Label , Idoso , Idoso de 80 Anos ou mais , Fatores de Coagulação Sanguínea/administração & dosagem , Fatores de Coagulação Sanguínea/efeitos adversos , Feminino , Hemorragia/diagnóstico , Hemorragia/etiologia , Hemorragia/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Varfarina/efeitos adversos
18.
J Trauma Acute Care Surg ; 85(1): 18-24, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29664892

RESUMO

BACKGROUND: Coagulopathy is a common complication after severe trauma. The efficacy of 4-factor prothrombin complex concentrate (4-PCC) as an adjunct to fresh frozen plasma (FFP) in reversal of coagulopathy of trauma (COT) has not been studied. The aim of our study is to compare 4-PCC + FFP versus FFP alone for the treatment of COT. METHODS: We reviewed all trauma patients older than 18 years who received PCC + FFP or FFP alone at our Level I trauma center from 2015 to 2016. We excluded patients on preinjury oral anticoagulants. Patients were divided into two groups (4-PCC + FFP: FFP alone) and were matched in a 1:2 ratio using propensity score matching for demographics, vital and injury parameters, and initial international normalized ratio (INR). COT was defined as admission INR > 1.5. Corrected INR was defined as an INR of 1.5 or less. Outcome measures were time to correction of INR, packed red blood cells units transfused, thromboembolic complications, and mortality. RESULTS: We analyzed 516 trauma patients, of which 120 patients (4-PCC + FFP: 40, FFP: 80) were matched. Mean age was 58 ± 20 years; 60% were male, median Injury Severity Score was 29 (14-38). Mechanism of injury was blunt in 87% patients. 4-PCC + FFP was associated with an accelerated correction of INR (373 minutes vs. 955 minutes; p = 0.001), a decrease in packed red blood cells units (7 units vs. 9 units; p = 0.04), and FFP units (5 units vs. 7 units; p = 0.03) transfused compared to FFP alone. 4-PCC + FFP was associated with a lower mortality (25% vs. 33% p = 0.04) compared with FFP alone; however, there was no difference in the thromboembolic complications (2.5% vs. 1.2%, p = 0.5) between the two groups. Administration of PCC + FFP led to an earlier correction of the INR compared with FFP alone. CONCLUSION: Results of our study demonstrated that the use of 4-PCC in conjunction with FFP is associated with the rapid reversal of INR and reduction in transfusion requirements as compared with FFP alone. Four-factor PCC as a component therapy along with FFP is superior to FFP alone for the reversal of COT. LEVEL OF EVIDENCE: Therapeutic studies, level IV.


Assuntos
Transtornos da Coagulação Sanguínea/terapia , Fatores de Coagulação Sanguínea/uso terapêutico , Ferimentos e Lesões/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Transtornos da Coagulação Sanguínea/etiologia , Fatores de Coagulação Sanguínea/efeitos adversos , Feminino , Humanos , Coeficiente Internacional Normatizado , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Plasma , Pontuação de Propensão , Estudos Retrospectivos , Resultado do Tratamento
19.
Drug Discov Ther ; 12(2): 104-107, 2018 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-29681563

RESUMO

Thromboembolic events such as deep vein thrombosis and pulmonary embolism are well-known complications that can occur after prothrombin complex concentrate therapy. However, acute myocardial infarction is a very rare but potentially life-threatening complication that was exclusively described in patients with bleeding disorders who received chronic and recurrent concentrate infusions. We report the case of a 70 year-old male patient with cholangiocarcinoma who was admitted to our hospital with worsening fatigue and weakness. His stay was complicated by uncontrolled bleeding secondary to rivaroxaban use and advanced liver disease. By the end of the prothrombin complex concentrate infusion used to reverse his coagulopathy, patient developed ST-segment elevation myocardial infarction with cardiogenic shock and passed away. This is the first reported case of acute myocardial infarction that occurs in a patient without hemophilia and after the first prothrombin complex concentrate infusion.


Assuntos
Fatores de Coagulação Sanguínea/efeitos adversos , Infarto do Miocárdio com Supradesnível do Segmento ST/mortalidade , Choque Cardiogênico/mortalidade , Idoso , Neoplasias dos Ductos Biliares/tratamento farmacológico , Fatores de Coagulação Sanguínea/uso terapêutico , Colangiocarcinoma/tratamento farmacológico , Evolução Fatal , Hemorragia/induzido quimicamente , Hemorragia/tratamento farmacológico , Humanos , Masculino , Rivaroxabana/efeitos adversos , Infarto do Miocárdio com Supradesnível do Segmento ST/induzido quimicamente , Choque Cardiogênico/induzido quimicamente
20.
Praxis (Bern 1994) ; 107(9-10): 485-493, 2018 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-29690851
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