RESUMEN
BACKGROUND: Coagulopathy in cardiac surgery is frequently associated with acquired hypofibrinogenaemia, which can be treated with either purified fibrinogen concentrate (FC) or cryoprecipitate. Because the latter is not purified and therefore contains additional coagulation factors, it is thought to be more effective for treatment of coagulopathy that occurs after prolonged cardiopulmonary bypass (CPB). We examined the impact of CPB duration on the efficacy of the two therapies in cardiac surgery. METHODS: This was a post hoc analysis of the Fibrinogen Replenishment in Surgery (FIBRES) RCT comparing FC (4 g) to cryoprecipitate (10 U) in adult patients undergoing cardiac surgery and experiencing bleeding with acquired hypofibrinogenaemia (n=735). The primary outcome was allogeneic blood products transfused within 24 h after CPB. Subjects were stratified by CPB duration (≤120, 121-180, and >180 min). The interaction of treatment assignment with CPB duration was tested. RESULTS: Subjects with longer CPB duration experienced more bleeding and transfusion. With CPB time ≤120 min (FC, n=134; cryoprecipitate, n=146), the ratio of least-squares means between the FC and cryoprecipitate groups for total allogeneic blood products at 24 h was 0.90 (one-sided 97.5% confidence interval [CI]: 0.00-1.12); P=0.004. For subjects with CPB time 121-180 min, it was 1.00 ([one-sided 97.5% CI: 0.00-1.22]; P=0.03], and for CPB time >180 min it was 0.91 ([one-sided 97.5% CI: 0.00-1.12]; P=0.005). Results were similar for all secondary outcomes, with no interaction between treatment and CPB duration for all outcomes. CONCLUSIONS: The haemostatic efficacy of FC was non-inferior to cryoprecipitate irrespective of CPB duration in cardiac surgery. CLINICAL TRIAL REGISTRATION: NCT03037424.
Asunto(s)
Afibrinogenemia , Trastornos de la Coagulación Sanguínea , Hemostáticos , Adulto , Afibrinogenemia/tratamiento farmacológico , Afibrinogenemia/etiología , Trastornos de la Coagulación Sanguínea/complicaciones , Transfusión Sanguínea , Puente Cardiopulmonar/métodos , Fibrinógeno/análisis , Fibrinógeno/uso terapéutico , Hemorragia/tratamiento farmacológico , Hemostáticos/uso terapéutico , HumanosRESUMEN
Cryoprecipitate has been the gold standard for treating acquired hypofibrinogenemia in cardiac surgery for nearly 50 years. More recently, fibrinogen concentrate has been used off-label in the United States and is the standard in European countries and Canada to treat the acquired hypofibrinogenemia during cardiac surgery. Fibrinogen concentrate has multiple potential advantages including rapid reconstitution, greater dose predictability, viral inactivation during processing, and reduced transfusion-related adverse events. However, because fibrinogen concentrate lacks the other components contained in the cryoprecipitate, it may not be the "ideal" product for replacing fibrinogen in all cardiac surgical patients, particularly those with longer cardiopulmonary bypass duration. In this Pro-Con commentary article, we discuss the advantages and disadvantages of using fibrinogen concentrate and cryoprecipitate to treat acquired hypofibrinogenemia in cardiac surgical patients.
Asunto(s)
Afibrinogenemia/tratamiento farmacológico , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Fibrinógeno/administración & dosificación , Fibronectinas/administración & dosificación , Hemostáticos/administración & dosificación , Complicaciones Posoperatorias/tratamiento farmacológico , Afibrinogenemia/sangre , Afibrinogenemia/etiología , Procedimientos Quirúrgicos Cardíacos/tendencias , Factor VIII/administración & dosificación , Factor VIII/química , Fibrinógeno/química , Fibronectinas/química , Hemostáticos/química , Humanos , Complicaciones Posoperatorias/sangre , Complicaciones Posoperatorias/etiología , Resultado del TratamientoRESUMEN
We report a case of acquired hypofibrinogenemia with multiple myeloma presenting λ-type IgG monoclonal protein. The patient had anemia and renal deficiency, and also developed bleeding tendency due to severe coagulopathy. Her fibrinogen level was under the detectable limits in a functional assay. Enzyme-linked immunosorbent assay (ELISA) and immunoblotting analysis results were consistent with functional assay results, and deficiency patterns observed in cross-mixing tests for PT and aPTT confirmed the diagnosis of hypofibrinogenemia. To determine the cause of hypofibrinogenemia, we purified the patient's immunoglobulin via protein A agarose, and confirmed that fibrinogen was included in the bound fraction, strongly indicating paraprotein interference with fibrinogen. As accelerated removal of fibrinogen was indicated, we incubated the patient's plasma up to 48 h, but did not observe significant loss of fibrinogen. In sharp contrast, fibrinogen returned to below the detection level 12 h after infusion of fresh frozen plasma. These findings support leukocyte-mediated fibrinogen removal, rather than paraprotein-triggered fibrinogen instability. Surprisingly, the patient's paraprotein was IgG2, but we speculate the amount of paraprotein (IgG 5346 mg/dL) compensated for lower affinity to Fcγ receptors.
Asunto(s)
Afibrinogenemia/diagnóstico , Afibrinogenemia/etiología , Mieloma Múltiple/complicaciones , Afibrinogenemia/sangre , Afibrinogenemia/terapia , Coagulación Sanguínea , Pruebas de Coagulación Sanguínea , Susceptibilidad a Enfermedades , Femenino , Fibrinógeno/metabolismo , Humanos , Inmunoglobulina G , Cadenas lambda de Inmunoglobulina , Persona de Mediana Edad , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/terapiaRESUMEN
B-cell maturation antigen (BCMA)-specific chimeric antigen receptor (CAR) T-cell therapies have shown efficacy in relapsed/refractory multiple myeloma (RRMM). Because the non-human originated antigen-targeting domain may limit clinical efficacy, we developed a fully human BCMA-specific CAR, CT103A, and report its safety and efficacy in a phase 1 trial. Eighteen consecutive patients with RRMM, including 4 with prior murine BCMA CAR exposures, were enrolled. CT103A was administered at 1, 3, and 6 × 106 CAR-positive T cells/kg in the dose-escalation phase, and 1 × 106 CAR-positive T cells/kg in the expansion cohort. The overall response rate was 100%, with 72.2% of the patients achieving complete response or stringent complete response. For the 4 murine BCMA CAR-exposed patients, 3 achieved stringent complete response, and 1 achieved a very good partial response. At 1 year, the progression-free survival rate was 58.3% for all cohorts and 79.1% for the patients without extramedullary myeloma. Hematologic toxicities were the most common adverse events; 70.6% of the patients experienced grade 1 or 2 cytokine release syndromes. No immune effector cell-associated neurotoxicity syndrome was observed. To the cutoff date, CAR transgenes were detectable in 77.8% of the patients. The median CAR transgene persistence was 307.5 days. Only 1 patient was positive for the anti-drug antibody. Altogether, CT103A is safe and highly active in patients with RRMM and can be developed as a promising therapy for RRMM. Patients who relapsed from prior murine BCMA CAR T-cell therapy may still benefit from CT103A. This trial was registered at http://www.chictr.org.cn as #ChiCTR1800018137.
Asunto(s)
Antígeno de Maduración de Linfocitos B/antagonistas & inhibidores , Inmunoterapia Adoptiva , Mieloma Múltiple/terapia , Receptores Quiméricos de Antígenos/uso terapéutico , Anticuerpos de Cadena Única/uso terapéutico , Adulto , Afibrinogenemia/etiología , Anciano , Animales , Anticuerpos Antiidiotipos/biosíntesis , Antineoplásicos/uso terapéutico , Antígeno de Maduración de Linfocitos B/inmunología , Terapia Combinada , Resistencia a Antineoplásicos , Femenino , Enfermedades Hematológicas/etiología , Humanos , Inmunidad Humoral , Inmunoterapia Adoptiva/efectos adversos , Leucemia de Células Plasmáticas/etiología , Leucemia de Células Plasmáticas/terapia , Masculino , Ratones , Persona de Mediana Edad , Mieloma Múltiple/tratamiento farmacológico , Receptores Quiméricos de Antígenos/administración & dosificación , Receptores Quiméricos de Antígenos/inmunología , Inducción de Remisión , Anticuerpos de Cadena Única/inmunología , TransgenesRESUMEN
Fibrinogen is a complex protein playing a major role in coagulation. Congenital afibrinogenemia, characterized by the complete absence of fibrinogen, is associated with major hemostatic defects. Even though the clinical course is unpredictable and can be completely different among patients, severe bleeding is the prominent symptom. Patients are also at increased risk of thrombosis and sometimes suffer from spontaneous spleen rupture, bone cysts and defective wound healing. Due to the relative rarity of afibrinogenemia, there are no evidence-based strategies for helping physicians in care of these patients. Fibrinogen supplementation is the keystone to prevent or treat bleeding events. In addition, fibrinogen, a pleiotropic protein with numerous physiological roles in immunity, angiogenesis and tissue repair, is involved in many diseases. Indeed, depletion of fibrinogen in animal models of infections, tumors and neurological diseases has an effect on the clinical course. The consequences for patients with afibrinogenemia still need to be investigated.
Asunto(s)
Afibrinogenemia/epidemiología , Afibrinogenemia/etiología , Enfermedades Genéticas Congénitas/epidemiología , Heterogeneidad Genética , Afibrinogenemia/diagnóstico , Afibrinogenemia/terapia , Animales , Manejo de la Enfermedad , Susceptibilidad a Enfermedades , Enfermedades Genéticas Congénitas/diagnóstico , Enfermedades Genéticas Congénitas/terapia , Hemorragia/diagnóstico , Hemorragia/epidemiología , Hemorragia/etiología , Hemorragia/terapia , Humanos , Vigilancia en Salud Pública , Trombosis/diagnóstico , Trombosis/epidemiología , Trombosis/etiologíaRESUMEN
Fibrinogen is a 340-kDa plasma glycoprotein constituted by two sets of symmetrical trimers, each formed by the Aα, Bß, and γ chains (respectively coded by the FGA, FGB, and FGG genes). Quantitative fibrinogen deficiencies (hypofibrinogenemia, afibrinogenemia) are rare congenital disorders characterized by low or unmeasurable plasma fibrinogen antigen levels. Their genetic basis is represented by mutations within the fibrinogen genes. To date, only eight mutations, all affecting a small region of the fibrinogen γ chain, have been reported to cause hereditary hypofibrinogenemia with hepatic storage (HHHS), a disorder characterized by protein aggregation in the endoplasmic reticulum, hypofibrinogenemia, and liver disease of variable severity. Here, we will briefly review the clinic characteristics of HHHS patients and the histological feature of their hepatic inclusions, and we will focus on the molecular genetic basis of this peculiar type of coagulopathy.
Asunto(s)
Afibrinogenemia/etiología , Afibrinogenemia/patología , Hígado/patología , Afibrinogenemia/epidemiología , Fibrinógeno/genética , Fibrinógeno/metabolismo , Humanos , Hígado/metabolismo , Mutación , PrevalenciaRESUMEN
Massive obstetric haemorrhage (MOH) is a leading cause of maternal morbidity and mortality world-wide. Using the Australian and New Zealand Massive Transfusion Registry, we performed a bi-national cohort study of MOH defined as bleeding at ≥20 weeks' gestation or postpartum requiring ≥5 red blood cells (RBC) units within 4 h. Between 2008 and 2015, we identified 249 cases of MOH cases from 19 sites. Predominant causes of MOH were uterine atony (22%), placenta praevia (20%) and obstetric trauma (19%). Intensive care unit admission and/or hysterectomy occurred in 44% and 29% of cases, respectively. There were three deaths. Hypofibrinogenaemia (<2 g/l) occurred in 52% of cases in the first 24 h after massive transfusion commenced; of these cases, 74% received cryoprecipitate. Median values of other haemostatic tests were within accepted limits. Plasma, platelets or cryoprecipitate were transfused in 88%, 66% and 57% of cases, respectively. By multivariate regression, transfusion of ≥6 RBC units before the first cryoprecipitate (odds ratio [OR] 3·5, 95% CI: 1·7-7·2), placenta praevia (OR 7·2, 95% CI: 2·0-26·4) and emergency caesarean section (OR 4·9, 95% CI: 2·0-11·7) were independently associated with increased risk of hysterectomy. These findings confirm MOH as a major cause of maternal morbidity and mortality and indicate areas for practice improvement.
Asunto(s)
Complicaciones Hematológicas del Embarazo/epidemiología , Hemorragia Uterina/epidemiología , Adulto , Afibrinogenemia/etiología , Australia/epidemiología , Transfusión de Componentes Sanguíneos/estadística & datos numéricos , Cesárea , Cuidados Críticos/estadística & datos numéricos , Parto Obstétrico/efectos adversos , Factor VIII/uso terapéutico , Femenino , Fibrinógeno/análisis , Fibrinógeno/uso terapéutico , Mortalidad Hospitalaria , Humanos , Histerectomía/estadística & datos numéricos , Tiempo de Internación/estadística & datos numéricos , Insuficiencia Multiorgánica/etiología , Nueva Zelanda/epidemiología , Placenta Previa/epidemiología , Placenta Previa/cirugía , Hemorragia Posparto/sangre , Hemorragia Posparto/epidemiología , Hemorragia Posparto/terapia , Embarazo , Complicaciones Hematológicas del Embarazo/sangre , Complicaciones Hematológicas del Embarazo/terapia , Utilización de Procedimientos y Técnicas , Respiración Artificial/estadística & datos numéricos , Hemorragia Uterina/sangre , Hemorragia Uterina/terapia , Inercia Uterina/epidemiologíaAsunto(s)
Hemangioma/diagnóstico por imagen , Síndrome de Kasabach-Merritt/diagnóstico , Neoplasias Hepáticas/diagnóstico por imagen , Afibrinogenemia/etiología , Afibrinogenemia/metabolismo , Anciano , Anemia/etiología , Anemia/metabolismo , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Hemangioma/complicaciones , Hemangioma/patología , Humanos , Síndrome de Kasabach-Merritt/etiología , Síndrome de Kasabach-Merritt/metabolismo , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/patología , Trombocitopenia/etiología , Trombocitopenia/metabolismo , Tomografía Computarizada por Rayos X , Carga TumoralRESUMEN
OBJECTIVE: Cardiovascular surgery often causes massive bleeding due to coagulopathy, with hypofibrinogenemia being a major causative factor. We assessed the intraoperative incidence of hypofibrinogenemia and explored predictors of hypofibrinogenemia. METHODS: The intraoperative serum fibrinogen level (SFL) was routinely measured in 872 consecutive patients [mean age: 66.9 ± 13.3 years; 598 men (68.6%)] undergoing cardiovascular surgery from July 2013 to November 2016 at Nagoya University Hospital. There were 275 aortic surgeries, 200 cases of coronary artery bypass grafting (CABG), 334 valvular surgeries and 63 other surgeries. We estimated hypofibrinogenemia incidence (intraoperative lowest SFL ≤ 150 mg/dL) and identified its predictors by a logistic regression analysis. RESULTS: The average intraoperative lowest SFL of all cases, aortic surgery, CABG and valvular surgery was 185 ± 71, 156 ± 65, 198 ± 69 and 198 ± 68 mg/dL, respectively. Aortic surgery had a significantly lower intraoperative lowest SFL than CABG (p < 0.001) and valvular surgery (p < 0.001). The incidence of hypofibrinogenemia was 32.8%, 50.2%, 26.5% and 22.8% in all cases, aortic surgery, CABG and valvular surgery, respectively. The predictors of hypofibrinogenemia were the preoperative SFL, re-do surgery and perfusion time. A receiver operating characteristics curve analysis showed that the best preoperative SFL cutoff value for predicting hypofibrinogenemia was 308.5 mg/dL. Assuming preoperative SFL 300 mg/dL as the cutoff, the odds ratio for hypofibrinogenemia was 7.22 (95% confidence interval 5.26-9.92, p < 0.001). CONCLUSIONS: The incidence of hypofibrinogenemia in aortic surgery was high. The preoperative SFL, re-do surgery and perfusion time were identified as predictors for hypofibrinogenemia. Intraoperative measurement of SFL is important for detecting hypofibrinogenemia and applying appropriate and prompt transfusion treatment.
Asunto(s)
Afibrinogenemia/sangre , Afibrinogenemia/etiología , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Fibrinógeno/biosíntesis , Procedimientos Quirúrgicos Vasculares/efectos adversos , Anciano , Anciano de 80 o más Años , Aorta/cirugía , Puente de Arteria Coronaria/efectos adversos , Femenino , Válvulas Cardíacas/cirugía , Hemorragia , Humanos , Incidencia , Periodo Intraoperatorio , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Complicaciones Posoperatorias , Curva ROC , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: Infants undergoing cardiac surgery are at risk for bleeding and massive transfusion due to an immature coagulation system, complex surgeries, and cardiopulmonary bypass (CPB) effects. Hemodilution from CPB promotes an acquired hypofibrinogenemia that results in impaired fibrin formation, inadequate clot formation, and increased bleeding. In North America, the current standard of care to supplement fibrinogen is cryoprecipitate. An alternative option is the off-label use of fibrinogen concentrate (FC; RiaSTAP; CSL Behring, Marburg, Germany), a purified fibrinogen. Because perioperative allogenic transfusions are associated with increased morbidity and mortality, we sought to determine whether FC would be an acceptable alternative to cryoprecipitate in a post-CPB transfusion algorithm in infants undergoing open-heart surgery. METHODS: We randomized 60 infants (<12 months) undergoing nonemergent cardiac surgery with CPB at 2 tertiary care children's hospitals to receive either cryoprecipitate or FC in a post-CPB transfusion algorithm. Infants underwent a stratified randomization based on institution and surgical complexity. The primary outcome was the difference in number of intraoperative allogenic blood product transfusions. Secondary outcomes included 24-hour chest tube output (CTO), mechanical ventilation time, adverse events (AEs), intensive care unit (ICU) length of stay (LOS), hospital LOS, postoperative thrombosis, and death within 30 days of surgery. The primary analysis followed the intent-to-treat (ITT) principle and was performed using linear regression adjusted for institution and complexity of surgery. A per-protocol (PP) analysis was also performed. RESULTS: Between June 2016 and January 2018, we enrolled 60 patients with complete data available for 25 patients who received cryoprecipitate and 29 patients who received FC. Patients in the cryoprecipitate group (median age: 4 months [2-6 months]) received 5.5 (4.0-7.0) allogeneic blood units in the ITT analysis and 6.0 units (5.0-7.0 units) in the PP analysis. Patients in the FC group (median age: 4 months [2-5]) received 4 units (3.0-5.0 units) in the ITT analysis and 4.0 units (3.0-5.0 units) in the PP analysis. In the adjusted ITT analysis, the FC group received 1.79 units (95% confidence interval [CI], 0.64-2.93; P = .003) less than the cryoprecipitate group. In the adjusted PP analysis, the FC group received 2.67 units (95% CI, 1.75-3.59; P < .001) less than the cryoprecipitate group. There were no significant differences in secondary outcomes or AEs. CONCLUSIONS: Our findings suggest that FC may be considered as an alternative to cryoprecipitate for the treatment of hypofibrinogenemia in infants with bleeding after CPB. Although we found no significant differences between secondary outcomes or AEs, further studies are needed to assess safety.
Asunto(s)
Afibrinogenemia/tratamiento farmacológico , Algoritmos , Pérdida de Sangre Quirúrgica/prevención & control , Transfusión Sanguínea , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Protocolos Clínicos , Coagulantes/administración & dosificación , Factor VIII/administración & dosificación , Fibrinógeno/administración & dosificación , Hemorragia Posoperatoria/terapia , Afibrinogenemia/sangre , Afibrinogenemia/etiología , Factores de Edad , Coagulación Sanguínea/efectos de los fármacos , Coagulantes/efectos adversos , Factor VIII/efectos adversos , Femenino , Fibrinógeno/efectos adversos , Humanos , Lactante , Masculino , Hemorragia Posoperatoria/sangre , Hemorragia Posoperatoria/etiología , Estudios Prospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Estados UnidosRESUMEN
BACKGROUND: Congenital afibrinogenemia is characterized by the absence of fibrinogen. Congenital fibrinogen disorders result from several mutations in FGA, FGB, or FGG. Their epidemiology is not well known. OBSERVATION: The present study reports on 2 children with congenital afibrinogenemia. The first child, a male who is now 9 years old, was diagnosed with afibrinogenemia after spontaneous intracranial bleeding at the age of 3 years. The second child is a 2-year-old female cousin of the first patient, who was diagnosed with afibrinogenemia after coagulation tests were carried out due to frequent epistaxis and mucocutaneous bleeding. At follow-up, blood samples of the patients and their parents were sent to the Department of Genetic Medicine and Development, University Medical Center, Switzerland, for polymerase chain reaction analysis. In both patients, the novel homozygous frameshift mutation in the FGA exon 3: c.196 delT was detected. The parents of the patients were both heterozygous for the same mutation. CONCLUSIONS: Congenital afibrinogenemia is a rare coagulation disease. The molecular epidemiology of congenital fibrinogen disorders is complex, and the identification of new mutations will help shed light on this complex molecular structure. Therefore, a genetic analysis that includes more centers is needed.
Asunto(s)
Afibrinogenemia/etiología , Fibrinógeno/genética , Mutación del Sistema de Lectura , Afibrinogenemia/patología , Niño , Preescolar , Femenino , Pruebas Genéticas , Humanos , Masculino , PronósticoAsunto(s)
Afibrinogenemia/tratamiento farmacológico , Afibrinogenemia/etiología , Anticoagulantes/uso terapéutico , Arteria Braquial/fisiopatología , Tromboembolia/complicaciones , Tromboembolia/tratamiento farmacológico , Afibrinogenemia/diagnóstico , Afibrinogenemia/fisiopatología , Femenino , Humanos , Persona de Mediana Edad , Polonia , Recurrencia , Resultado del TratamientoRESUMEN
INTRODUCTION: Thromboelastometry evaluates viscoelastic changes in the coagulation process. It offers a graphic representation of the formation of the coagulum, its stability and the presence of lysis. OBJECTIVE: This first case of transfusion management guided by thromboelastography in Mexico and we conducted a review of the literature. METHOD: A metasearch search was performed (PubMed, Scielo, Medigraphic) with the words thromboelastometry, coagulopathy, transfusion medicine and the most influential works were included. CONCLUSIONS: The rotational thromboelastometry is a diagnostic tool that graphs the functionality of the clot, for a directed and individualized management of the coagulopathy associated with bleeding.
INTRODUCCIÓN: La tromboelastometría evalúa los cambios viscoelásticos en el proceso de coagulación. Ofrece una representación gráfica de la formación del coágulo, su estabilidad y la presencia de lisis. OBJETIVO: Se notifica el primer caso de manejo transfusional guiado por tromboelastografía en México con revisión de la bibliografía. MÉTODO: Se realizó una búsqueda en metabuscadores (PubMed, Scielo, Medigraphic) con las palabras tromboelastometría, coagulopatía y medicina transfusional y se incluyeron los trabajos más influyentes. CONCLUSIONES: La tromboelastometría rotacional es una herramienta diagnóstica que grafica la funcionalidad del coágulo para un manejo dirigido e individualizado de la coagulopatía relacionada con hemorragia.
Asunto(s)
Transfusión de Componentes Sanguíneos/métodos , Choque/terapia , Tromboelastografía/métodos , Tiempo de Coagulación de la Sangre Total/métodos , Adolescente , Afibrinogenemia/tratamiento farmacológico , Afibrinogenemia/etiología , Plaquetas/fisiología , Traumatismos Craneocerebrales/complicaciones , Traumatismos Craneocerebrales/cirugía , Soluciones Cristaloides/administración & dosificación , Urgencias Médicas , Transfusión de Eritrocitos/métodos , Resultado Fatal , Femenino , Fibrinógeno/uso terapéutico , Humanos , México , Plasma , Choque/etiología , Heridas por Arma de Fuego/complicaciones , Heridas por Arma de Fuego/cirugíaRESUMEN
Patients with multiple myeloma (MM) are at risk for acquired dysfibrinogenemia resulting in laboratory abnormalities and/or bleeding complications. We describe a 63-year-old man who presented with bleeding diathesis in the presence of a low fibrinogen activity level with a normal fibrinogen antigen level. Further studies revealed elevated levels of lambda free light chains, and he was diagnosed with MM. Despite initiating treatment with bortezomib/dexamethasone, he continued to have recurrent bleeds along with hypofibrinogenaemia, prompting a switch to carfilzomib/dexamethasone. The patient responded with improvement in bleeding symptoms, normalisation of fibrinogen activity and a decrease in serum free light chains.
Asunto(s)
Afibrinogenemia/diagnóstico , Hemorragia/diagnóstico , Mieloma Múltiple/diagnóstico , Afibrinogenemia/etiología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bortezomib/administración & dosificación , Dexametasona/administración & dosificación , Sustitución de Medicamentos , Hemorragia/etiología , Humanos , Cadenas lambda de Inmunoglobulina/sangre , Masculino , Persona de Mediana Edad , Mieloma Múltiple/sangre , Mieloma Múltiple/complicaciones , Mieloma Múltiple/tratamiento farmacológico , Oligopéptidos/administración & dosificaciónRESUMEN
: We aim to present a case of chronic myeloid leukemia (CML) in chronic phase, in major molecular response for 5 years of treatment with imatinib 400âmg OD. He presented with recurrent melena for one and a half years, requiring 11âU of packed red cell transfusion since then. Various causes of bleeding in CML, such as thrombocytopenia, disease progression related to accelerated phase/blast crisis or imatinib-induced cytopenia were ruled out. His investigations revealed reduced plasma fibrinogen (150âmg/ml; range 200-450âmg/ml). The platelet count, prothrombin time, activated partial thromboplastin time and thrombin time were 314â×â10/l, 13âs (control 13âs), 31âs (control 30âs) and 16âs (control 16âs), respectively. Platelet aggregometry revealed normal platelet aggregation with adenine-di-phosphate, epinephrine and ristocetin, and reduced response with arachidonic acid (30%). Bleeding subsided with transfusion of fresh frozen plasma. Moreover, his medication was changed to nilotinib 300âmg BD. Thereafter, his subsequent repeat investigations were normal. Platelet function defects in CML both pretherapy and on tyrosine kinase inhibitors has been described in the literature. However, concomitant hypofibrinogenemia has rarely been reported.
Asunto(s)
Afibrinogenemia/etiología , Trastornos de las Plaquetas Sanguíneas/inducido químicamente , Mesilato de Imatinib/efectos adversos , Leucemia Mielógena Crónica BCR-ABL Positiva/complicaciones , Hemorragia , Humanos , Mesilato de Imatinib/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Masculino , Inhibidores de Proteínas Quinasas/efectos adversos , Pirimidinas/uso terapéuticoRESUMEN
Liver transplant is a life-saving procedure in patients with end-stage liver disease. However, this procedure may be associated with transmission of various deficiencies of proteins synthesized by the liver. Factor I (fibrinogen) deficiency is one of the rare inherited coagulation disorders with an extremely low risk of transmission by liver transplant. We report a case of a patient with no inherited coagulation disorders but who demonstrated disturbance of fibrinogen after liver transplant. This case highlights the ever-present risk of donor-to-recipient disease transmission during transplant and emphasizes the difficulty in procuring organs from donors in which standard blood tests are insufficient to determine the likelihood of this event.
Asunto(s)
Afibrinogenemia/etiología , Trasplante de Hígado/efectos adversos , Complicaciones Posoperatorias/etiología , Humanos , Masculino , Persona de Mediana EdadAsunto(s)
Afibrinogenemia/sangre , Afibrinogenemia/diagnóstico , Factor XIII/metabolismo , Afibrinogenemia/etiología , Afibrinogenemia/terapia , Biomarcadores , Coagulación Sanguínea , Pruebas de Coagulación Sanguínea , Activación Enzimática , Terapia de Reemplazo Enzimático , Factor XIII/inmunología , Fibrinógeno/administración & dosificación , Fibrinógeno/efectos adversos , Fibrinógeno/uso terapéutico , Humanos , Resultado del TratamientoRESUMEN
BACKGROUND: Viscoelastic near-patient assays of global hemostasis have been found useful and cost-effective in perioperative settings. Shortcomings of current systems include substantial laboratory intensity, user-dependent reproducibility, relatively large sample volumes, sensitivity to ambient vibration and limited comparability between techniques and devices. The aim of this study was to assess feasibility of a new, resonance-based viscoelastic whole blood methodology (TEG6s) in cardiac surgery with cardiopulmonary bypass (CPB) and to compare the parameters this system produces with the ROTEM delta system and standard coagulation tests. METHODS: In a prospective evaluation study, twenty-three consecutive cardiac surgery patients underwent hemostasis management according to current guidelines, using the ROTEM delta system and standard coagulation tests. Blood samples were collected prior to CPB before anesthetic induction (pre-CPB), during CPB on rewarming (CPB), and 10 minutes after heparin reversal with protamine (post-CPB). ROTEM and standard coagulation test results were compared with TEG6s parameters, which were concurrently determined using its multi-channel microfluidic cartridge system. RESULTS: TEG6s provided quantifiable results pre-CPB and post-CPB, but only R (clotting time) of CKH (kaolin with heparinase) was measurable during CPB (full heparinization). Spearman's correlation coefficient (rs) was 0.78 for fibrinogen levels and MA CFF (functional fibrinogen). Correlation of several TEG6s parameters was good (0.77 to 0.91) with MCF FIBTEM, and poor (<0.56) with prothrombin time and activated partial thromboplastin time (<0.44). Rs with platelet count was moderate (0.70, MA CK; 0.73, MA CRT). Accuracy of MA CFF for detection of fibrinogen deficiency < 1.5 g/L was high (ROC-AUC 0.93). CONCLUSIONS: The TEG6s system, which is based on resonance viscoelastic methodology, appears to be feasible for POC hemostasis assessment in cardiac surgery. Its correlations with standard coagulation parameters are quite similar to those of ROTEM and there is good diagnostic accuracy for fibrinogen levels lower than 1.5 g/L. During full heparinization, TEG6s testing is limited to R measurement. Larger studies are needed to assess superiority over other POC systems.
Asunto(s)
Afibrinogenemia/diagnóstico , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Puente Cardiopulmonar/efectos adversos , Complicaciones Intraoperatorias/diagnóstico , Monitoreo Intraoperatorio/instrumentación , Adulto , Afibrinogenemia/sangre , Afibrinogenemia/etiología , Afibrinogenemia/prevención & control , Anciano , Coagulación Sanguínea , Pruebas de Coagulación Sanguínea/instrumentación , Pruebas de Coagulación Sanguínea/métodos , Pruebas de Coagulación Sanguínea/normas , Procedimientos Quirúrgicos Cardíacos/métodos , Puente Cardiopulmonar/métodos , Estudios de Factibilidad , Femenino , Humanos , Complicaciones Intraoperatorias/sangre , Complicaciones Intraoperatorias/etiología , Masculino , Persona de Mediana Edad , Monitoreo Intraoperatorio/métodos , Monitoreo Intraoperatorio/normas , Guías de Práctica Clínica como Asunto , Estudios Prospectivos , Reproducibilidad de los ResultadosRESUMEN
Low plasma fibrinogen level is common after cardiopulmonary bypass (CPB). Current substitution practice with fibrinogen concentrate generally follows a single measurement and cut-off values from the literature, whereas early postoperative endogenous fibrinogen kinetics is incompletely described and widely disregarded. The aim of this study was to determine the short-term recovery pattern of plasma fibrinogen after CPB weaning. Our hypothesis was that in the absence of surgical bleeding, CPB-induced hypofibrinogenemia would resolve spontaneously and predictably within a few hours. In a prospective, observational study of 26 patients undergoing conventional CPB (cCPB) or minimally invasive extracorporeal circulation (MiECC), Clauss fibrinogen level (C-FIB) was determined at 10 closely spaced time points after protamine administration. Primary endpoint was the time to recovery of post-CPB fibrinogen levels to ≥1.5 g/L. C-FIB reached its nadir after protamine administration corresponding to 62 ± 5% (mean ± SD) of the baseline level after cCPB and 68 ± 7% after MiECC (p = 0.027 vs. cCPB). C-FIB recovered spontaneously at a nearly constant rate of approximately 0.08 g/L per hour. In all patients, C-FIB was ≥1.5 g/L at 4 hours and ≥2.0 g/L at 13 hours after CPB weaning. Following cardiac surgery with CPB and in the absence of surgical bleeding, spontaneous recovery of normal endogenous fibrinogen levels can be expected at a rate of 0.08 g/L per hour. Administration of fibrinogen concentrate triggered solely by a single-point measurement of low plasma fibrinogen some time after CPB is not justified.
Asunto(s)
Afibrinogenemia/tratamiento farmacológico , Puente Cardiopulmonar/efectos adversos , Circulación Extracorporea/efectos adversos , Fibrinógeno/análisis , Protaminas/administración & dosificación , Afibrinogenemia/sangre , Afibrinogenemia/etiología , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Periodo Posoperatorio , Estudios Prospectivos , Protaminas/uso terapéutico , Remisión Espontánea , Resultado del TratamientoRESUMEN
BACKGROUND: Thrombocytopenia and hypofibrinogenemia during neonatal cardiopulmonary bypass (CPB) contribute to bleeding and morbidity. Rotational thromboelastometry (ROTEM) is a viscoelastic assay with a rapid turnaround time. Data validating ROTEM during neonatal cardiac surgery remain limited. This study examined perioperative hemostatic trends in neonates treated with standardized platelet and cryoprecipitate transfusion during CPB. We hypothesized that ROTEM would predict thrombocytopenia, hypofibrinogenemia, and the correction thereof. METHODS: Forty-four neonates undergoing CPB were included in this prospective observational study. Blood samples were obtained at Baseline, On CPB, Post-CPB, and Postoperative. The ROTEM analysis included extrinsically activated (Extem) and fibrinogen-specific (Fibtem) assays. Platelet-specific thromboelastometry (Pltem) values were calculated. Platelet and cryoprecipitate transfusion was initiated prior to termination of CPB. RESULTS: Platelet count and Extem amplitude decreased significantly On CPB ( P < .0001), increased significantly Post-CPB ( P < .0001), and Postoperative values were not significantly different from Baseline. Extem amplitude at 10 minutes (A10) > 46.5 mm (AUC = 0.941) and Pltem A10 > 37.5 mm [area under curve (AUC) = 0.960] predicted platelet count > 100 × 103/µL, and they highly correlated with platelet count ( R = 0.89 and R = 0.90, respectively). Fibrinogen concentration and Fibtem amplitude decreased significantly On CPB ( P ≤ .0001) and normalized after cryoprecipitate transfusion. Fibtem A10 > 9.5 mm predicted fibrinogen >200 mg/dL (AUC = 0.817), but it correlated less well with fibrinogen concentration ( R = 0.65). CONCLUSIONS: ROTEM analysis during neonatal cardiac surgery is sensitive and specific for thrombocytopenia and hypofibrinogenemia, identifying deficits within 10 minutes. Platelet and cryoprecipitate transfusion during neonatal CPB normalizes platelet count, fibrinogen level, and ROTEM amplitudes.