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1.
Blood Coagul Fibrinolysis ; 30(1S Suppl 1): S14-S18, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31517711

RESUMO

: The development of inhibitors continues to be the most important complication in severe hemophilia A. The management of inhibitor patients revolves around two basic principles: eradication of the inhibitor and management and prevention of bleeding. In this paper, we review the prophylactic treatments carried out in the last two decades with the two available bypassing agents and the results of the clinical trials carried out with the new molecules under investigation or already licensed for the prevention of hemorrhagic episodes in hemophilia, like emicizumab.


Assuntos
Hemofilia A/terapia , Hemorragia/prevenção & controle , Anticorpos Biespecíficos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Fatores de Coagulação Sanguínea/uso terapêutico , Ensaios Clínicos como Assunto , Gerenciamento Clínico , Fator IX/uso terapêutico , Fator VIII/uso terapêutico , Fator VIIa/uso terapêutico , Humanos , Proteínas Recombinantes/uso terapêutico
2.
Haemophilia ; 25(5): 814-820, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31365176

RESUMO

INTRODUCTION: Extended half-life (EHL) clotting factors have been shown to offer people with haemophilia (PwH) protection from bleeding with fewer infusions, which might reduce treatment burden. AIM: The HOw Patients view Extended half-life products (HOPE) study aimed to explore, understand and describe patient expectations around the prophylactic use of EHL products and to establish whether these expectations were met through individual follow-up analysis. METHODS: The HOPE study was a prospective, qualitative cohort study conducted among PwH who had switched to Fc fusion protein EHL products in routine clinical care and who had not been recruited to clinical trials of these products. Semi-structured audio-recorded interviews were undertaken over two time points; transcripts were analysed to systematically generate theory from data that contains both inductive and deductive thinking. RESULTS: Forty-three interviews were conducted with 25 participants. Most participants were positive about EHL treatment and intended to continue using them. Reduced frequency of infusions meant lives were less disrupted or dominated by haemophilia, and there was less perceived stress on overused veins. For those PwH who did not reduce infusion frequency, there were other perceived benefits from EHLs with respect to greater protection with higher trough levels and fewer bleeds. CONCLUSION: Patients switching to EHL treatments believe these products will result in fewer infusions and less disruption of everyday life, leaving them feeling more protected with fewer bleeds and increased activity levels, as well as enhanced well-being and mental health. Understanding patient expectation and experience around using products adds real-world data to clinical trial experience.


Assuntos
Fatores de Coagulação Sanguínea/farmacologia , Meia-Vida , Hemofilia A/tratamento farmacológico , Adolescente , Adulto , Fatores de Coagulação Sanguínea/uso terapêutico , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Pesquisa Qualitativa , Adulto Jovem
3.
Med Klin Intensivmed Notfmed ; 114(7): 613-619, 2019 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-31468107

RESUMO

BACKGROUND: Intracerebral hemorrhage (ICH) represents one of the most severe forms of stroke with high morbidity and mortality; however, effective treatment options to significantly improve patient outcome do not exist so far. OBJECTIVE: This review article evaluates the most recent developments in acute ICH treatment. MATERIAL AND METHODS: Analysis and interpretation of currently available evidence regarding ICH treatment, focusing on the most important studies from the last 3 years. RESULTS: Hematoma enlargement, perhaps the most important prognostic factor, should be counteracted by aggressive blood pressure management (targeted systolic pressure 140 mm Hg). In cases of ICH under oral anticoagulation, inhibition of coagulation must be immediately antagonized: vitamin K antagonists with prothrombin complex concentrates (PCC), idarucizumab for dabigatran and andexanet if available or high-dose PCC for factor Xa inhibitors. Currently, surgical treatment strategies, both open and minimally invasive, to evacuate the hematoma can currently not be routinely recommended. In patients with intraventricular ICH, treatment with intraventricular fibrinolysis with or without additional lumbar drainage represents a promising treatment option. CONCLUSION: In recent years, several randomized controlled and observational studies have generated robust evidence regarding ICH treatment; however, there is still no single breakthrough intervention, which significantly improves patient functional outcome. Nevertheless, the sum of various, possibly interacting treatment concepts may potentially improve outcome after ICH.


Assuntos
Anticoagulantes , Hemorragia Cerebral , Anticoagulantes/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Fatores de Coagulação Sanguínea/uso terapêutico , Hemorragia Cerebral/tratamento farmacológico , Hemorragia Cerebral/cirurgia , Dabigatrana , Inibidores do Fator Xa , Hematoma , Humanos
4.
World Neurosurg ; 131: e570-e578, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31400524

RESUMO

OBJECTIVE: Spine surgeons increasingly encounter acute spinal pathologies in patients treated with direct oral anticoagulants (DOACs), but only limited data on the management of these patients are currently available. METHODS: We retrospectively analyzed patients who presented to our department with acute spinal pathology during treatment with DOAC and who required urgent surgical therapy. Patient characteristics and treatment modalities were studied, with specific focus on the management of hemostasis and surgical therapy. Furthermore, we analyzed 19 cases of spinal emergencies during DOAC treatment reported in the literature. RESULTS: A total of 12 patients were identified and included in the present analysis. Patients suffered from acute spinal cord compression caused by spinal tumor manifestation (n = 5), empyema (n = 4), degenerative spinal stenosis (n = 1), hematoma (n = 1), and vertebral body fracture/dislocation (n = 2). All patients underwent emergency surgical treatment. Prohemostatic substances were administered perioperatively in 10 patients (83%) and included administration of prothrombin complex concentrates (83%), tranexamic acid (17%), and transfusion of platelets (8%). A total of 9 patients (75%) showed postoperative improvement of neurologic symptoms, and the in-hospital mortality in this patient cohort was 17%. CONCLUSIONS: Emergency spine surgery is feasible and should be considered in patients on treatment with DOAC. The (low) risk of intraoperative bleeding complications has to be weighed against the risk of permanent disability if surgical decompression is delayed. Administration of prothrombin complex concentrates and tranexamic acid may improve the coagulation before surgery, especially in cases of unavailable specific antidotes.


Assuntos
Perda Sanguínea Cirúrgica/prevenção & controle , Descompressão Cirúrgica/métodos , Emergências , Inibidores do Fator Xa/efeitos adversos , Hemostáticos/uso terapêutico , Compressão da Medula Espinal/cirurgia , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Antitrombinas/efeitos adversos , Fatores de Coagulação Sanguínea/uso terapêutico , Feminino , Hematoma Subdural Espinal/complicações , Hematoma Subdural Espinal/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Infecções Perimeníngeas/complicações , Infecções Perimeníngeas/cirurgia , Transfusão de Plaquetas , Estudos Retrospectivos , Compressão da Medula Espinal/etiologia , Fraturas da Coluna Vertebral/complicações , Fraturas da Coluna Vertebral/cirurgia , Neoplasias da Coluna Vertebral/complicações , Neoplasias da Coluna Vertebral/cirurgia , Estenose Espinal/complicações , Estenose Espinal/cirurgia , Ácido Tranexâmico/uso terapêutico
5.
Clin Appl Thromb Hemost ; 25: 1076029619862052, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31298044

RESUMO

Hemophilic arthropathy from joint bleeding remains a complication with major morbidity in the increasingly aging patients with hemophilia. Prophylactic clotting factor infusions, based on pharmacokinetic dosing to reduce bleeding rates, are being explored more and more. However, there is little evidence on the benefits of pharmacokinetic dosing in direct association with bleeding events. Here, we prospectively followed a cohort of adult patients with hemophilia A and B (n = 26) and arthropathic joints on various clotting factor products over a period of 2 years with clinical and radiographic joint health assessments, frequent joint ultrasound, and pharmacokinetic studies. Joint bleeds and synovitis with synovial vascularity changes were objectively diagnosed by musculoskeletal ultrasound and power Doppler and analyzed in relation to pharmacokinetic, joint- and patient-specific parameters. Results revealed that, contrary to common beliefs, bleeding episodes were not readily explained by pharmacokinetic features, as they were not associated with more time spent below certain clotting factor thresholds. Joint bleeding was found to be associated with prominent vascularity changes, suggesting that vascular remodeling and leakiness may contribute to joint bleeding that cannot be prevented by clotting factor replacement alone.


Assuntos
Fatores de Coagulação Sanguínea/farmacocinética , Vasos Sanguíneos/patologia , Hemartrose/etiologia , Hemartrose/prevenção & controle , Hemofilia A/complicações , Hemofilia B/complicações , Adulto , Fatores de Coagulação Sanguínea/análise , Fatores de Coagulação Sanguínea/uso terapêutico , Vasos Sanguíneos/diagnóstico por imagem , Fragilidade Capilar , Hemartrose/diagnóstico por imagem , Hemartrose/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Ultrassonografia/métodos , Remodelação Vascular
6.
Intern Med ; 58(22): 3251-3253, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31292387

RESUMO

Flutamide, a chemotherapeutic agent for prostate cancer, is known to enhance warfarin anticoagulation. However, not much is known about its pharmaceutical interaction. We herein report the case of a patient with an implanted pacemaker for atrial fibrillation with bradycardia who was on warfarin. This patient presented with deterioration of hematuria, gingival, ear, and subcutaneous bleeding. The prothrombin time-international normalized ratio was extremely elevated after starting flutamide to treat progression of prostate cancer. Fatal bleeding complications were able to be prevented by the immediate administration of prothrombin complex concentrate, but the effect of flutamide on warfarin was prolonged for about two more weeks after the withdrawal of flutamide.


Assuntos
Anticoagulantes/farmacologia , Flutamida/farmacologia , Coeficiente Internacional Normatizado , Tempo de Protrombina , Varfarina/farmacologia , Idoso de 80 Anos ou mais , Fibrilação Atrial/terapia , Coagulação Sanguínea/efeitos dos fármacos , Fatores de Coagulação Sanguínea/uso terapêutico , Sinergismo Farmacológico , Flutamida/uso terapêutico , Hemorragia/induzido quimicamente , Hemorragia/terapia , Humanos , Masculino , Marca-Passo Artificial , Neoplasias da Próstata/tratamento farmacológico , Varfarina/uso terapêutico
7.
Rinsho Ketsueki ; 60(6): 667-679, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31281160

RESUMO

Recently, in Japan, the number of patients with autoimmune acquired coagulation factor deficiency (AiCFD) due to anti-coagulation factor autoantibodies has been on the rise. There are several types of such autoantibodies, which can be generated against any coagulation factor: 1) the neutralizing type binds the functional region (s) of a coagulation factor to inhibit its activity (inhibitor type) ; 2) the non-neutralizing type binds the nonfunctional region (s) of a coagulation factor and enhances its clearance from circulation (hyperclearance type) ; 3) the combination of types 1) and 2). Despite clinical manifestations of AiCFD ranging from asymptomatic laboratory abnormalities to fatal exsanguination or even to thromboembolic events, most patients with AiCFD exhibit certain bleeding symptoms. Owing to the major bleeding symptoms of AiCFD not being specific for any particular disease, laboratory tests are essential for the early diagnosis of AiCFD, selection of proper treatment, and assessment of a therapy's efficacy. Because of severe ongoing hemorrhages and anemia, most patients are administered large amounts of the deficient coagulation factors. Moreover, given the rarity of this disease, there is no standardized therapeutic modality for antibody eradication. Most patients receive corticosteroids as first-line immunosuppressive medicines; however, some patients become treatment-resistant or develop a recurrence despite achieving remission once.


Assuntos
Transtornos da Coagulação Sanguínea/diagnóstico , Transtornos da Coagulação Sanguínea/terapia , Autoanticorpos/sangue , Fatores de Coagulação Sanguínea/uso terapêutico , Hemorragia , Humanos , Japão
8.
West J Emerg Med ; 20(4): 587-600, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31316698

RESUMO

Angioedema is defined by non-dependent, non-pitting edema that affects several different sites and is potentially life-threatening due to laryngeal edema. This narrative review provides emergency physicians with a focused overview of the evaluation and management of angioedema. Two primary forms include histamine-mediated and bradykinin-mediated angioedema. Histamine-mediated forms present similarly to anaphylaxis, while bradykinin-mediated angioedema presents with greater face and oropharyngeal involvement and higher risk of progression. Initial evaluation and management should focus on evaluation of the airway, followed by obtaining relevant historical features, including family history, medications, and prior episodes. Histamine-mediated angioedema should be treated with epinephrine intramuscularly, antihistaminergic medications, and steroids. These medications are not effective for bradykinin-mediated forms. Other medications include C1-INH protein replacement, kallikrein inhibitor, and bradykinin receptor antagonists. Evidence is controversial concerning the efficacy of these medications in an acute episode, and airway management is the most important intervention when indicated. Airway intervention may require fiberoptic or video laryngoscopy, with preparation for cricothyrotomy. Disposition is dependent on patient's airway and respiratory status, as well as the sites involved.


Assuntos
Angioedema/etiologia , Angioedema/terapia , Serviço Hospitalar de Emergência , Manuseio das Vias Aéreas , Algoritmos , Anti-Inflamatórios não Esteroides/uso terapêutico , Fatores de Coagulação Sanguínea/uso terapêutico , Bradicinina/análogos & derivados , Bradicinina/metabolismo , Bradicinina/uso terapêutico , Antagonistas de Receptor B2 da Bradicinina/uso terapêutico , Broncodilatadores/uso terapêutico , Epinefrina/uso terapêutico , Glucocorticoides/uso terapêutico , Histamina/metabolismo , Antagonistas dos Receptores Histamínicos/uso terapêutico , Humanos , Peptídeos/uso terapêutico , Plasma , Urticária/etiologia
9.
No Shinkei Geka ; 47(6): 629-636, 2019 Jun.
Artigo em Japonês | MEDLINE | ID: mdl-31235665

RESUMO

BACKGROUND AND PURPOSE: Warfarin-associated intracranial hemorrhage(w-ICH)usually increases and results in unfavorable outcomes. Administration of prothrombin complex concentrate(PCC)can reverse anticoagulation and correct prothrombin time-international normalized ratio(PT-INR)immediately; it is recommended by some guidelines for cases of w-ICH. We assessed the effect of PCC on blood coagulation. METHODS: We administered PCC and vitamin K to 11 patients with w-ICH who were admitted to our hospital between October 2016 and November 2017. We measured the PT-INR at baseline and immediately, 1 hour, 6 hours, and on the day after PCC administration. RESULTS: Patients' mean(range)PT-INR normalized from 1.92(1.64-3.26)to 1.08(1.03-1.29)immediately after receiving PCC. Patients' PT-INR was 1.17(1.08-1.29)1 hour after receiving PCC, 1.22(1.16-1.52)6 hours after receiving PCC, and 1.17(1.05-1.29)on the day after receiving PCC. In all the cases, no side effects emerged. Five patients had a safe operation. All the patients' modified Rankin Scale scores at discharge were stable or within a permissive limit in comparison with the symptoms on admission. CONCLUSION: In our cases, administration of PCC corrected the PT-INR immediately and contributed to a better outcome of w-ICH.


Assuntos
Anticoagulantes , Hemorragias Intracranianas , Varfarina , Anticoagulantes/efeitos adversos , Fatores de Coagulação Sanguínea/uso terapêutico , Humanos , Hemorragias Intracranianas/induzido quimicamente , Hemorragias Intracranianas/tratamento farmacológico , Estudos Retrospectivos , Varfarina/efeitos adversos
10.
Curr Drug Saf ; 14(3): 230-232, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31124425

RESUMO

BACKGROUND: Hemocoagulase agkistrodon has been widely used for visceral bleeding, however, its adverse reaction has not been fully recognized. CASE REPORT: A 65-year-old female with upper gastrointestinal hemorrhage occurred severe coagulation disorder during her hospitalization. Transfusion of blood products can not improve coagulation function. Coagulation parameters returned to normal two days after discontinuation of hemocoagulase agkistrodon. CONCLUSION: So intravenous administration of hemocoagulase should be cautiously used for the treatment of gastrointestinal bleeding.


Assuntos
Batroxobina/uso terapêutico , Fatores de Coagulação Sanguínea/uso terapêutico , Hemorragia Gastrointestinal/tratamento farmacológico , Idoso , Hemorragia Gastrointestinal/induzido quimicamente , Humanos
12.
Turk J Haematol ; 36(3): 141-154, 2019 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-31088040

RESUMO

Despite effective factor replacement and various treatment schedules, there remain several challenges and unmet needs in the prophylactic treatment of hemophilia limiting its adoption and thereby posing an increased risk of spontaneous bleeding. In this regard, extended half-life (EHL) recombinant factor VIII (rFVIII) and factor IX (rFIX) products promise optimal prophylaxis by decreasing the dose frequency, increasing the compliance, and improving the quality of life without compromising safety and efficacy. EHL products might lead to higher trough levels without increasing infusion frequency, or could facilitate the ability to maintain trough levels while reducing infusion frequency. This paper aims to provide a comprehensive review of the rationale for developing EHL coagulation factors and their utility in the management of hemophilia, with special emphasis on optimal techniques for half-life extension and criteria for defining EHL coagulation factors, as well as indications, efficacy, and safety issues of the currently available EHL-rFVIII and EHL-rFIX products. Potential impacts of these factors on quality of life, health economics, and immune tolerance treatment will also be discussed alongside the challenges in pharmacokinetic-driven prophylaxis and difficulties in monitoring the EHL products with laboratory assays.


Assuntos
Fatores de Coagulação Sanguínea/uso terapêutico , Hemofilia A/terapia , Fatores de Coagulação Sanguínea/farmacologia , Meia-Vida , Qualidade de Vida
13.
Ann Vasc Surg ; 59: 314.e5-314.e7, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31009721

RESUMO

Splenic infarction is a rare clinical condition seen in the emergency department and can mimic acute abdomen. Hematologic, vascular, and thromboembolic events are considered in the etiology. Treatment options vary between symptomatic treatment and splenectomy. Warfarin is a vitamin K antagonist used for the prevention and treatment of thromboembolic disorders. In overdose situations, there is a possibility of bleeding in every part of the body. Prothrombin complex concentrates, vitamin K, and fresh-frozen plasma are used in the treatment of warfarin overdose. We describe a case of splenic infarction coexistent with warfarin overdose treatment, which has never been published in literature. Prothrombin complex concentrate was administered to the patient because of warfarin overdose. A spleen infarction was detected in computerized tomography of the patient after the occurrence of abdominal pain, and there was no infarction three days before hospitalization. The patient was monitored with symptomatic treatment in the general surgery clinic and discharged without the need for operation. In the pathogenesis, it was thought that prothrombin complex concentrates might be caused by early thrombosis or by warfarin not affecting the existing clot. Emergency physicians should not forget spleen infarction in the differential diagnosis of abdominal pain.


Assuntos
Anticoagulantes/efeitos adversos , Infarto do Baço/induzido quimicamente , Varfarina/efeitos adversos , Dor Abdominal/etiologia , Idoso , Fatores de Coagulação Sanguínea/uso terapêutico , Coagulantes/uso terapêutico , Tratamento Conservador , Diagnóstico Diferencial , Overdose de Drogas , Feminino , Humanos , Coeficiente Internacional Normatizado , Valor Preditivo dos Testes , Infarto do Baço/diagnóstico por imagem , Infarto do Baço/terapia , Tomografia Computadorizada por Raios X , Resultado do Tratamento
14.
Orthop Surg ; 11(2): 236-240, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30932356

RESUMO

OBJECTIVE: To establish the prevalence of clinically significant venous thromboembolic events (VTE) in hemophilia patients undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA) without chemoprophylaxis and a modified coagulation factor substitution. METHODS: A cohort of patients who underwent THA and TKA from June 2002 to April 2017 were included. Based on World Federation of Hemophilia (WFH) guidelines, a modified coagulation factor substitution regimen was adopted. All patients were under a standardized postoperative protocol with routine mechanical prophylaxis against VTE. None of the patients received prophylactic anticoagulation. Only symptomatic patients were referred for radiological examination to exclude VTE. We evaluated the patient demographics and calculated the prevalence of VTE in our cohort. RESULTS: A total of 98 patients were reviewed. The patients were all men. Thirty-one patients underwent primary THA with 39 hip arthroplasties (only 1 case with hemophilia B) and 67 patients underwent primary TKA with 101 knee arthroplasties (5 cases with hemophilia B). The mean age was 34.2 ± 7.8 years. The mean body mass index was 21.2 ± 5.7 kg/m2 . There was 100% compliance to mechanical prophylaxis. The mean time to ambulation was 6.8 days (±2.5 days), and the mean hospital stay was 32.4 days (±7.1 days). There was only 1 hemophilia B patient with clinically significant VTE. None of the other 97 surgical cases had symptomatic VTE within 6 months after the procedure. This translates to a prevalence of 1.02%. CONCLUSION: Given the low incidence (1.02%) of clinically significant VTE in our cohort, routine chemoprophylaxis in hemophilia patients undergoing THA and TKA may not be needed.


Assuntos
Artroplastia de Quadril/efeitos adversos , Artroplastia do Joelho/efeitos adversos , Hemofilia A/complicações , Tromboembolia Venosa/etiologia , Adulto , Fatores de Coagulação Sanguínea/uso terapêutico , Humanos , Incidência , Masculino , Estudos Retrospectivos , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/prevenção & controle
15.
Gastroenterology ; 157(1): 34-43.e1, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30986390

RESUMO

DESCRIPTION: This expert review was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership. The intent is to evaluate the current data on mechanism of altered coagulation in patients with cirrhosis, provide guidance on the use of currently available testing of the coagulation cascade, and help practitioners use anticoagulation and pro-coagulants appropriately in patients with cirrhosis. METHODS: This review is framed around the best practice points, which were derived from the most impactful publications in the area of coagulation in cirrhosis and agreed to by all authors. BEST PRACTICE ADVICE 1: Global tests of clot formation, such as rotational thromboelastometry, thromboelastography, sonorheometry, and thrombin generation, may eventually have a role in the evaluation of clotting in patients with cirrhosis, but currently lack validated target levels. BEST PRACTICE ADVICE 2: In general, clinicians should not routinely correct thrombocytopenia and coagulopathy before low-risk therapeutic paracentesis, thoracentesis, and routine upper endoscopy for variceal ligation in patients with hepatic synthetic dysfunction-induced coagulation abnormalities. BEST PRACTICE ADVICE 3: Blood products should be used sparingly because they increase portal pressure and carry a risk of transfusion-associated circulatory overload, transfusion-related acute lung injury, infection transmission, alloimmunization, and/or transfusion reactions. BEST PRACTICE ADVICE 4: The following transfusion thresholds for management of active bleeding or high-risk procedures may optimize clot formation in advanced liver disease: hematocrit ≥25%, platelet count >50,000, and fibrinogen >120 mg/dL. Commonly utilized thresholds for international normalized ratio correction are not supported by evidence. BEST PRACTICE ADVICE 5: Thrombopoietin agonists are a good alternative to platelet transfusion, but require time (about 10 days) to elevate platelet levels. BEST PRACTICE ADVICE 6: The large volume of fresh frozen plasma required to reach an arbitrary international normalized ratio target, limitations of the usual target, minimal effect on thrombin generation, and adverse effects on portal pressure limit the utility of this agent significantly. BEST PRACTICE ADVICE 7: The 4-factor prothrombin complex concentrate contains both pro- and anticoagulant factors that offer an attractive low-volume therapeutic to rebalance a disturbed hemostatic system. However, dosage is, in part, based on international normalized ratio, which is problematic in cirrhosis, and published experience in liver disease is limited. BEST PRACTICE ADVICE 8: Anti-fibrinolytic therapy may be considered in patients with persistent bleeding from mucosal oozing or puncture wound bleeding consistent with impaired clot integrity. Both ε-aminocaproic acid and tranexamic acid inhibit clot dissolution. Neither is believed to generate a hypercoagulable state, although both may exacerbate pre-existing thrombi. BEST PRACTICE ADVICE 9: Desmopressin releases von Willebrand factor as its primary hemostatic mechanism. As this factor is usually elevated in cirrhosis, the agent lacks a sound evidence-based foundation, but may be useful in patients with concomitant renal failure. BEST PRACTICE ADVICE 10: Systemic heparin infusion is recommended for symptomatic deep vein thrombosis and portal and mesenteric vein thrombosis, but there are unresolved issues regarding monitoring with both the anti-Xa assay and the partial thromboplastin time due to cirrhosis-related antithrombin deficiency (heparin cofactor). BEST PRACTICE ADVICE 11: Treatment of incidental portal and mesenteric vein thrombosis depends on estimated impact on transplantation surgical complexity vs risks of bleeding and falls. Therapy with low-molecular-weight heparin, vitamin K antagonists, and direct-acting anticoagulants improve portal vein repermeation vs observation alone. BEST PRACTICE ADVICE 12: Direct-acting anticoagulants, such as the factor Xa and thrombin inhibitors, are relatively safe and effective in stable cirrhotic patients, but are in need of further study in patients with more advanced liver disease.


Assuntos
Transtornos da Coagulação Sanguínea/terapia , Transfusão de Sangue/métodos , Cirrose Hepática/sangue , Trombofilia/terapia , Trombose Venosa/terapia , Anticoagulantes/uso terapêutico , Antifibrinolíticos/uso terapêutico , Antitrombinas/uso terapêutico , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/complicações , Fatores de Coagulação Sanguínea/uso terapêutico , Inibidores do Fator Xa/uso terapêutico , Fibrinogênio/metabolismo , Hematócrito , Heparina/uso terapêutico , Humanos , Coeficiente Internacional Normatizado , Cirrose Hepática/complicações , Plasma , Contagem de Plaquetas , Veia Porta , Tromboelastografia , Trombocitopenia , Trombofilia/sangue , Trombofilia/complicações , Trombopoetina/agonistas , Reação Transfusional , Trombose Venosa/sangue , Trombose Venosa/complicações
16.
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
17.
Med J Aust ; 210(7): 326-332, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30924538

RESUMO

INTRODUCTION: There have been significant advances in the understanding of the management of inherited bleeding disorders in pregnancy since the last Australian Haemophilia Centre Directors' Organisation (AHCDO) consensus statement was published in 2009. This updated consensus statement provides practical information for clinicians managing pregnant women who have, or carry a gene for, inherited bleeding disorders, and their potentially affected infants. It represents the consensus opinion of all AHCDO members; where evidence was lacking, recommendations have been based on clinical experience and consensus opinion. MAIN RECOMMENDATIONS: During pregnancy and delivery, women with inherited bleeding disorders may be exposed to haemostatic challenges. Women with inherited bleeding disorders, and their potentially affected infants, need specialised care during pregnancy, delivery, and postpartum, and should be managed by a multidisciplinary team that includes at a minimum an obstetrician, anaesthetist, paediatrician or neonatologist, and haematologist. Recommendations on management of pregnancy, labour, delivery, obstetric anaesthesia and postpartum care, including reducing and treating postpartum haemorrhage, are included. The management of infants known to have or be at risk of an inherited bleeding disorder is also covered. CHANGES IN MANAGEMENT AS A RESULT OF THIS STATEMENT: Key changes in this update include the addition of a summary of the expected physiological changes in coagulation factors and phenotypic severity of bleeding disorders in pregnancy; a flow chart for the recommended clinical management during pregnancy and delivery; guidance for the use of regional anaesthetic; and prophylactic treatment recommendations including concomitant tranexamic acid.


Assuntos
Transtornos Herdados da Coagulação Sanguínea/terapia , Fatores de Coagulação Sanguínea/uso terapêutico , Hemostáticos/uso terapêutico , Hemorragia Pós-Parto/prevenção & controle , Complicações Hematológicas na Gravidez/terapia , Anestesia Obstétrica/normas , Austrália , Transtornos Herdados da Coagulação Sanguínea/complicações , Consenso , Feminino , Humanos , Recém-Nascido , Equipe de Assistência ao Paciente , Gravidez , Sociedades Médicas
18.
Ther Drug Monit ; 41(2): 192-212, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30883513

RESUMO

Hemophilia A and hemophilia B are hereditary bleeding disorders, caused by a deficiency of clotting factor VIII or clotting factor IX, respectively. To treat and prevent bleedings, patients can administer clotting factor concentrates (hemophilia A and B) or desmopressin (hemophilia A). Both clotting factor concentrates and desmopressin are currently dosed according to the patients' body weight. However, clotting factor concentrates exhibit considerable pharmacokinetic (PK) variability. Therefore, several alternative dosing strategies to individualize dosing of clotting factor concentrates and desmopressin in hemophilia A and B have been proposed. In this study, a review of the existing literature on the individualization of dosing based on PK guidance was performed. In total, 79 articles were included. The methods to individualize dosing were divided into 3 categories: (1) methods using clinical parameters, (2) empirical individual PK-guided methods, and (3) maximum a posteriori (MAP) Bayesian estimation methods. The clinical parameter mainly used to individualize dosing is bleeding phenotype. Dosing based on bleeding phenotype may decrease clotting factor consumption. However, with this method, it is not possible to individualize on-demand dosing during bleeding events or in the perioperative setting. Empirical individual PK-guided methods can be used both for prevention and treatment of bleedings. These methods include dose individualization using a nomogram and individualized in vivo recovery. In the perioperative setting, adjustment of the rate of continuous infusion can be applied to obtain a specific target level. The final category, MAP Bayesian estimation methods, relies on the availability of a population PK model. In total, 22 population PK models describing clotting factor concentrate or desmopressin dosing are currently available in literature. MAP Bayesian estimates can be used to calculate the individualized doses required to achieve or maintain a target level in every setting. The application of PK-guided and pharmacodynamic-guided dosing of clotting factor concentrates and desmopressin seems promising, although further investigation is warranted. Prospective studies analyzing its potential benefit are on the way.


Assuntos
Fatores de Coagulação Sanguínea/uso terapêutico , Desamino Arginina Vasopressina/uso terapêutico , Hemofilia A/tratamento farmacológico , Hemofilia B/tratamento farmacológico , Medicina de Precisão/métodos , Humanos
19.
J Trauma Acute Care Surg ; 87(2): 274-281, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30889141

RESUMO

INTRODUCTION: Post-traumatic hemorrhage is the most common preventable cause of death in trauma. Numerous small single-center studies have shown the superiority of four-factor prothrombin complex concentrate (4-PCC) along with fresh frozen plasma (FFP) over FFP alone in resuscitation of trauma patients. The aim of our study was to evaluate outcomes of severely injured trauma patients who received 4-PCC + FFP compared to FPP alone. METHODS: Two-year (2015-2016) analysis of the American College of Surgeons-Trauma Quality Improvement Program database. All adult (age ≥18 years) trauma patients who received 4-PCC + FFP or FFP alone were included. We excluded patients who were on preinjury anticoagulants. Patients were stratified into two groups: 4-PCC + FFP versus FFP alone and were matched in a 1:1 ratio using propensity score matching for demographics, vitals, injury parameters, comorbidities, and level of trauma centers. Outcome measures were packed red blood cells, plasma and platelets transfused, complications, and mortality. RESULTS: A total of 468 patients (4-PCC + FFP, 234; FFP alone, 234) were matched. Mean age was 50 ± 21 years; 70% were males; median injury severity score was 27 [20-36], and 86% had blunt injuries. Four-PCC + FFP was associated with a decreased requirement for packed red blood cells (6 units vs. 10 units; p = 0.02) and FFP (3 units vs. 6 units; p = 0.01) transfusion compared to FFP alone. Patients who received 4-PCC + FFP had a lower mortality (17.5% vs. 27.7%, p = 0.01) and lower rates of acute respiratory distress syndrome (1.3% vs. 4.7%, p = 0.04) and acute kidney injury (2.1% vs. 7.3%, p = 0.01). There was no difference in the rates of deep venous thrombosis (p = 0.11) and pulmonary embolism (p = 0.33), adverse discharge disposition (p = 0.21), and platelets transfusion (p = 0.72) between the two groups. CONCLUSIONS: Our study demonstrates that the use of 4-PCC as an adjunct to FFP is associated with improved survival and reduction in transfusion requirements compared to FFP alone in resuscitation of severely injured trauma patients. Further studies are required to evaluate the role of addition of PCC to the massive transfusion protocol. LEVEL OF EVIDENCE: Therapeutic studies, level III.


Assuntos
Fatores de Coagulação Sanguínea/uso terapêutico , Hemorragia/tratamento farmacológico , Ressuscitação/métodos , Ferimentos e Lesões/complicações , Transfusão de Sangue/métodos , Feminino , Hemorragia/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Plasma , Pontuação de Propensão , Ressuscitação/mortalidade , Estudos Retrospectivos , Ferimentos e Lesões/tratamento farmacológico , Ferimentos e Lesões/mortalidade
20.
Curr Opin Anaesthesiol ; 32(2): 200-205, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30817396

RESUMO

PURPOSE OF REVIEW: Uncontrolled bleeding in trauma secondary to a combination of surgical bleeding and trauma-induced complex coagulopathy is a leading cause of death. Prothrombin complex concentrates (PCCs), recombinant activated factor seven (rFVIIa) and recombinant human prothrombin act as procoagulants by increasing thrombin generation and fibrinogen concentrate aids stable clot formation. This review summarizes the current evidence for procoagulant use in the management of bleeding in trauma, and data and evidence gaps for routine clinical use. RECENT FINDINGS: Retrospective and prospective studies of PCCs (±fibrinogen concentrate) have demonstrated a decreased time to correction of trauma coagulopathy and decreased red cell transfusion with no obvious effect on mortality or thromboembolic outcomes. PCCs in a porcine model of dilutional coagulopathy demonstrated a sustained increase in thrombin generation, unlike recombinant human prothrombin which showed a transient increase and has been studied only in animals. In other retrospective studies, there is a suggestion that lower doses of PCCs may be effective in the setting of acquired coagulopathy. SUMMARY: There is increasing evidence that early correction of coagulopathy has survival benefits, and the use of procoagulants as first-line therapy has the potential benefit of rapid access and timely treatment. This requires confirmation in prospective studies.


Assuntos
Coagulantes/uso terapêutico , Hemorragia/tratamento farmacológico , Ferimentos não Penetrantes/complicações , Ferimentos Penetrantes/complicações , Coagulação Sanguínea/efeitos dos fármacos , Fatores de Coagulação Sanguínea/farmacologia , Fatores de Coagulação Sanguínea/uso terapêutico , Coagulantes/farmacologia , Relação Dose-Resposta a Droga , Fator VIIa/farmacologia , Fator VIIa/uso terapêutico , Hemorragia/etiologia , Hemorragia/mortalidade , Humanos , Protrombina/farmacologia , Protrombina/uso terapêutico , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/uso terapêutico , Fatores de Tempo , Resultado do Tratamento , Ferimentos não Penetrantes/tratamento farmacológico , Ferimentos não Penetrantes/mortalidade , Ferimentos Penetrantes/tratamento farmacológico , Ferimentos Penetrantes/mortalidade
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