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1.
Ann Hematol ; 102(10): 2753-2763, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37422592

RESUMEN

Burkitt lymphoma (BL) is an extremely aggressive but curable subtype of non-Hodgkin lymphoma. While younger patients have excellent outcomes in response to aggressive chemoimmunotherapy, the rarity of this disease in older patients and limitations caused by age, comorbidities, and performance status may negate survival advantages. This analysis assessed outcomes of older adults with BL through data provided by the Texas Cancer Registry (TCR). Patients ≥65 years with BL were assessed. Patients were dichotomized into 1997-2007 and 2008-2018. Median overall survival (OS) and disease-specific survival (DSS) were assessed using Kaplan-Meier methodology, and covariates including age, race, sex, stage, primary site, and poverty index were analyzed using Pearson Chi-squared analysis. Odds ratio (OR) with 95% confidence intervals (CI) was used to assess factors contributing to patients not offered systemic therapy. P value <0.05 was considered statistically significant. Non-BL mortality events were also categorized. There were 325 adults, 167 in 1997-2007 and 158 in 2008-2018; 106 (63.5%) and 121 (76.6%) received systemic therapy, a trend that increased with time (p = 0.010). Median OS for 1997-2007 and 2008-2018 was 5 months (95% CI 2.469, 7.531) and 9 months (95% CI 0.000, 19.154) (p = 0.013), and DSS was 72 months (95% CI 56.397, 87.603) (p = 0.604) and not reached, respectively. For patients that received systemic therapy, median OS was 8 months (95% CI 1.278, 14.722) and 26 months (95% CI 5.824, 46.176) (p = 0.072), respectively, and DSS was 79 months (95% CI: 56.416, 101.584) and not reached, respectively (p = 0.607). Age ≥75 years (HR 1.39 [95% CI 1.078, 1.791], p = 0.011) and non-Hispanic whites (HR 1.407 [95% CI 1.024, 1.935], p = 0.035) had poorer outcomes, and patients at the 20-100% poverty index (OR 0.387 [95% CI 0.163, 0.921], p = 0.032) and increasing age at diagnosis (OR 0.947 [95% CI 0.913, 0.983], p = 0.004) were less likely to receive systemic therapy. Of 259 (79.7%) deaths, 62 (23.9%) were non-BL deaths, and 6 (9.6%) of these were from a second cancer. This two-decade analysis of older Texas patients with BL indicates a significant improvement in OS over time. Although patients were more likely to receive systemic therapy over time, treatment disparities existed in patients residing in poverty-stricken regions of Texas and in advancing age. These statewide findings reflect an unmet national need to find a systemic therapeutic strategy that can be tolerated by and augment outcomes in the growing elderly population.


Asunto(s)
Linfoma de Burkitt , Humanos , Anciano , Linfoma de Burkitt/tratamiento farmacológico , Linfoma de Burkitt/epidemiología , Texas/epidemiología , Sistema de Registros
2.
Am J Transplant ; 19(10): 2900-2909, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31152491

RESUMEN

This study sought to retrospectively investigate the outcomes of patients with light-chain amyloidosis (AL) with advanced cardiac involvement who were treated with a strategy of heart transplantation (HT) followed by delayed autologous stem cell transplantation (ASCT) at 1-year posttransplant. Patients with AL amyloidosis with substantial cardiac involvement have traditionally had very poor survival (eg, several months). A few select centers have reported their outcomes for HT followed by a strategy of early ASCT (ie, 6 months) for CA. The outcomes of patients undergoing a delayed strategy have not been reported. All patients with AL amyloidosis at a single institution undergoing evaluation for HT from 2004-2018 were included. Retrospective analyses were performed. Sixteen patients underwent HT (including two combined heart-kidney transplant) for AL amyloidosis. ASCT was performed in a total of nine patients to date at a median 13.5 months (12.8-32.9 months) post-HT. Survival was 87.5% at 1 year and 76.6% at 5 years, comparable to institutional outcomes for nonamyloid HT recipients. In addition to these 16 patients, two patients underwent combined heart-lung transplantation. A strategy of delayed ASCT 1-year post-HT for patients with AL amyloidosis is feasible, safe, and associated with comparable outcomes to those undergoing an earlier ASCT strategy.


Asunto(s)
Amiloidosis/mortalidad , Cardiomiopatías/mortalidad , Trasplante de Corazón/mortalidad , Trasplante de Células Madre/mortalidad , Tiempo de Tratamiento/estadística & datos numéricos , Adulto , Anciano , Amiloidosis/complicaciones , Amiloidosis/patología , Amiloidosis/terapia , Cardiomiopatías/complicaciones , Cardiomiopatías/patología , Cardiomiopatías/terapia , Estudios de Casos y Controles , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Trasplante Autólogo , Resultado del Tratamiento
3.
Blood ; 130(19): 2055-2063, 2017 11 09.
Artículo en Inglés | MEDLINE | ID: mdl-28912376

RESUMEN

Safety, tolerability, and pharmacokinetics of recombinant ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13; BAX 930; SHP655) were investigated in 15 patients diagnosed with severe congenital ADAMTS-13 deficiency (plasma ADAMTS-13 activity <6%) in a prospective phase 1, first-in-human, multicenter dose escalation study. BAX 930 was well tolerated, no serious adverse events occurred, and no anti-ADAMTS-13 antibodies were observed. After single-dose administration of BAX 930 at 5, 20, or 40 U/kg body weight to adolescents and adults, there was approximate dose proportionality with respect to maximum plasma concentration (Cmax [U/mL]) and area under the concentration-time curve (AUC [h∙U/mL]). Dose-related increases of individual ADAMTS-13:Ag and activity were observed and reached a maximum within 1 hour. With escalating BAX 930 doses administered, a dose-dependent persistence of ADAMTS-13-mediated von Willebrand factor (VWF) cleavage products and reduced VWF multimeric size were observed. This study demonstrated that pharmacokinetic parameters of BAX 930 were comparable to those estimated in previous plasma infusion studies and provided evidence of pharmacodynamic activity. This study was registered at www.clinicaltrials.gov as #NCT02216084.


Asunto(s)
Proteína ADAMTS13/administración & dosificación , Proteína ADAMTS13/farmacocinética , Púrpura Trombocitopénica Trombótica/sangre , Púrpura Trombocitopénica Trombótica/tratamiento farmacológico , Adolescente , Adulto , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Proteínas Recombinantes , Factor de von Willebrand/metabolismo
5.
J Card Fail ; 22(7): 501-11, 2016 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-26762651

RESUMEN

BACKGROUND: Thrombotic events in patients with continuous flow left ventricular assist devices (CF-LVADs) are associated with significant morbidity and mortality. The objective of this study was to delineate the frequency, clinical characteristics, and outcomes of patients with hypercoagulable states who undergo CF-LVAD implantation. METHODS: We performed a retrospective review of 168 consecutive patients who underwent CF-LVAD implantation between 2010 and 2013. Chart and laboratory data were reviewed for the presence of a hereditary and/or acquired hypercoagulable state. Adverse outcomes were defined as death, confirmed pump thrombosis, aortic root clot, stroke, deep vein thrombosis, and pulmonary embolism. Fisher's exact test and Kaplan-Meier estimate were used to analyze frequency of adverse outcomes and event free survival, respectively. RESULTS: A hypercoagulable state was identified in 20 patients (11.9%). There were 18 patients with acquired, 1 with a congenital, and 1 with both congenital and acquired hypercoagulable states. The median follow-up was 429 days and 475 days in patients with and without hypercoagulable states, respectively. During the study period, 15% (3/20) of the patients with a hypercoagulable state had a diagnosis of deep vein thrombosis vs 3% (4/148) of the patients without a hypercoagulable state (P = .030). Only patients with a hypercoagulable state had a subarachnoid hemorrhage (3/20 vs 0/148; P < .01). The event-free survival was lower in the patients with hypercoagulable states (P = .005). CONCLUSION: Hypercoagulable states are not uncommon in patients with CF-LVADs and may be associated with increased morbidity. Prospective studies are needed to more accurately identify the incidence, prevalence, and significance of hypercoagulable states in patients being considered for CF-LVAD.


Asunto(s)
Insuficiencia Cardíaca/cirugía , Corazón Auxiliar/efectos adversos , Trombofilia/etiología , Trombosis/etiología , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Trombofilia/congénito , Trombofilia/diagnóstico
6.
N Engl J Med ; 375(17): 1695-6, 2016 10 27.
Artículo en Inglés | MEDLINE | ID: mdl-28103006
7.
Int J Hematol ; 120(3): 290-296, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38976179

RESUMEN

Heparin-induced thrombocytopenia (HIT) is a prothrombotic disorder mediated by platelet-activating antibodies targeting platelet factor 4 (PF4) and heparin complex. A higher antibody titer is reflected in a higher optical density (OD) by enzyme-linked immunosorbent assay for heparin-PF4 antibodies. This single-institution retrospective study of 116 HIT patients examined the effect of heparin-PF4 OD on time to platelet recovery, vascular thrombosis, and in-hospital mortality. Patients were divided into 3 cohorts based on heparin-PF4 OD: cohort 1 had an OD ≥ 2 and ≤ 2.4, cohort 2 had an OD > 2.4 and ≤ 2.8, and cohort 3 had an OD > 2.8. A higher OD titer was associated with significantly increased time to platelet recovery when compared between cohorts 1 versus 2 (HR = 0.599, p = 0.0221) and 1 versus 3 (HR = 0.515, p = 0.0014), as well as an increased risk of thrombosis (79.4%-cohort 3 vs 53.8%-cohort 2 vs 46.1%-cohort 1, p = 0.04), but had no impact on mortality (2.62-alive vs 2.65-deceased, p = 0.7432). A higher OD titer can inform risk assessment and support decision-making in HIT patients; however, prospective studies are needed to further clarify the impact of heparin-PF4 OD on outcomes.


Asunto(s)
Heparina , Factor Plaquetario 4 , Trombocitopenia , Trombosis , Humanos , Heparina/efectos adversos , Trombocitopenia/inducido químicamente , Trombocitopenia/sangre , Trombosis/etiología , Trombosis/sangre , Masculino , Estudios Retrospectivos , Factor Plaquetario 4/inmunología , Femenino , Persona de Mediana Edad , Anciano , Plaquetas/inmunología , Anciano de 80 o más Años , Adulto , Factores de Riesgo , Autoanticuerpos/sangre , Recuento de Plaquetas , Anticuerpos/sangre , Mortalidad Hospitalaria
8.
Blood Coagul Fibrinolysis ; 35(1): 23-26, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-37994629

RESUMEN

Interpretation of coagulation mixing studies is complicated by interference arising from direct oral anticoagulants (DOACs), which are increasingly prescribed. In this retrospective study, we reviewed 1035 consecutive coagulation mixing studies performed from 2017 to 2021. Three hundred and ninety-nine cases with normal prothrombin time (PT) and activated partial thromboplastin time (aPTT) were excluded. aPTT mixing studies were performed at time 0 and after 60 min of incubation. We confirmed the presence of interfering factors with additional laboratory testing, medication records, and medical history. Mixing corrected most prolonged PT samples (93%), but 32 cases showed incomplete correction. Of these 32 cases, 18 were confounded by DOAC use, and 3 by factor V (FV) inhibitor. We observed an unusual pattern of prolongation of aPTT after incubation, which was previously considered a characteristic of specific factor inhibitors, most commonly FVIII inhibitor. However, we found that lupus anticoagulant (28%) and DOAC (25%) contributed to this pattern similarly as specific factor inhibitors (28%). Coagulation laboratories should be aware of interference arising from DOACs and other factors in PT/aPTT mixing studies, especially in some unusual correction patterns.


Asunto(s)
Anticoagulantes , Coagulación Sanguínea , Humanos , Anticoagulantes/farmacología , Anticoagulantes/uso terapéutico , Pruebas de Coagulación Sanguínea/métodos , Tiempo de Tromboplastina Parcial , Tiempo de Protrombina , Estudios Retrospectivos
9.
Arch Environ Contam Toxicol ; 63(1): 86-94, 2012 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-22402781

RESUMEN

Metal contamination is a common problem in aquatic environments and may result in metal bioaccumulation and toxicity in aquatic biota. Recent studies have reported the significance of dietary metal accumulation in aquatic food chains, particularly in species of lower trophic levels. This research investigated the accumulation and effects of dietary metals in a macroinvertebrate. The seaweed species Ulva lactuca and Enteromorpha prolifera were concurrently exposed to five metals (copper, nickel, lead, cadmium, and zinc) and then individually fed to the green sea urchin Strongylocentrotus droebachiensis for a period of 2 weeks. Body mass, test length, total length, and coelomic fluid ion concentration and osmolality were measured. The sea urchins were also dissected and their organs (esophagus, stomach, intestine, gonads, and rectum) digested and analyzed for metals. The results demonstrated that metal accumulation and distribution varied between seaweed species and among metals. In general, there were greater concentrations of metals within the sea urchins fed E. prolifera compared with those fed U. lactuca. All of the metals accumulated within at least one organ of S. droebachiensis, with Cu being most significant. These results indicate that E. prolifera may accumulate metals in a more bioavailable form than within U. lactuca, which could impact the grazer. In this study, no significant differences in body length, growth, or coelomic fluid ion concentration and osmolality were detected between the control and metal-exposed sea urchins after the 2-week testing period. This research presents new data concerning metal accumulation in a marine herbivore after dietary metal exposure.


Asunto(s)
Exposición a Riesgos Ambientales/análisis , Metales Pesados/farmacocinética , Strongylocentrotus/metabolismo , Contaminantes Químicos del Agua/farmacocinética , Animales , Dieta , Cadena Alimentaria , Herbivoria/efectos de los fármacos , Metales Pesados/toxicidad , Algas Marinas/química , Strongylocentrotus/efectos de los fármacos , Contaminantes Químicos del Agua/toxicidad
10.
Lab Med ; 53(4): e91-e94, 2022 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-34940854

RESUMEN

Acquired von Willebrand disease (avWD) arises because of mechanisms that destroy, decrease, absorb, or clear von Willebrand factor (vWF). A 59-year-old man presented with a 3-year history of recurrent gastrointestinal bleeding. Laboratory workup revealed a prolonged platelet function assay-100. The vWF antigen was decreased, and a low vWF immunofunctional activity/antigen ratio, low collagen binding/antigen ratio, and decreased intermediate and high molecular weight multimers were noted. The patient had no high-shear stress conditions, and an antibody-mediated process was suspected. A vWF mixing study showed complete correction of vWF activity, suggesting no direct functional inhibitor. The patient was given a bolus of vWF concentrate with serial measurements of vWF; the vWF half-life was 2.5 hours. The vWF propeptide/antigen ratio was 4:1, supporting a diagnosis of aVWD resulting from increased antibody-mediated vWF clearance. This case study emphasizes the laboratory's role in the diagnosis and treatment of rare, overlooked acquired bleeding disorders.


Asunto(s)
Enfermedades de von Willebrand , Factor de von Willebrand , Pruebas de Coagulación Sanguínea , Hemorragia Gastrointestinal/complicaciones , Hemorragia Gastrointestinal/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Pruebas de Función Plaquetaria , Enfermedades de von Willebrand/diagnóstico , Enfermedades de von Willebrand/terapia
13.
Am J Ther ; 18(1): 14-22, 2011 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21079512

RESUMEN

Because of an extreme risk for thromboemboli, patients with suspected heparin-induced thrombocytopenia (HIT) require immediate initiation of an alternative anticoagulant. The only therapies approved by the Food and Drug Administration require intravenous infusion of expensive direct thrombin inhibitors. This prospective, randomized, open-label, exploratory study compared the clinical and economic utility of subcutaneous desirudin vs argatroban, the most frequently used agent for suspected or immunologically confirmed HIT, with or without thrombosis. Sixteen patients were randomized to treatment with fixed-dose desirudin (15 or 30 mg) every 12 hours or activated partial thromboplastin time-adjusted argatroban by intravenous infusion. Arm A included 8 patients naive to direct thrombin inhibitor therapy, whereas Arm B included 8 patients on argatroban for at least 24 hours before randomization. The primary efficacy measure was the composite of new or worsening thrombosis (objectively documented), amputation, or death. Other end points included major and minor bleeding while on drug therapy, time to platelet count recovery, and pharmacoeconomics. No amputations or deaths occurred. One patient randomized to argatroban had worsening of an existing thrombosis. Major bleeding occurred in 2 patients on argatroban and in none during desirudin treatment. There was 1 minor bleed in each treatment group. The average medication cost per course of treatment was $1688 for desirudin and $8250 for argatroban. Desirudin warrants further study as a potentially cost-effective alternative to argatroban in patients with suspected HIT.


Asunto(s)
Anticoagulantes/efectos adversos , Anticoagulantes/uso terapéutico , Heparina/efectos adversos , Ácidos Pipecólicos/uso terapéutico , Trombocitopenia/tratamiento farmacológico , Trombosis/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anticoagulantes/economía , Arginina/análogos & derivados , Progresión de la Enfermedad , Femenino , Hemorragia/etiología , Hirudinas/efectos adversos , Hirudinas/economía , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Ácidos Pipecólicos/efectos adversos , Ácidos Pipecólicos/economía , Recuento de Plaquetas , Complicaciones Posoperatorias/prevención & control , Periodo Posoperatorio , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/economía , Proteínas Recombinantes/uso terapéutico , Sulfonamidas , Trombina/antagonistas & inhibidores , Trombocitopenia/sangre , Trombocitopenia/inducido químicamente , Trombosis/complicaciones , Trombosis/etiología , Resultado del Tratamiento , Adulto Joven
14.
Clin Lymphoma Myeloma Leuk ; 20(1): 18-23, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31699655

RESUMEN

BACKGROUND: Ruxolitinib is a selective Janus kinase inhibitor (JAKI) 1/2 approved for the treatment of myelofibrosis (MF) and polycythemia vera (PV). These patients may be at risk for developing opportunistic infections. We assessed the number of patients that developed typical (Mycobacterium tuberculosis [MTB]) and atypical mycobacterial infections (AMI) while on treatment with ruxolitinib by utilizing the United States Food and Drug Administration (FDA) adverse events reporting system (FAERS). MATERIALS AND METHODS: This is a retrospective study utilizing FAERS, a pharmacovigilance database. We queried FAERS for cases of MTB and AMI secondary to ruxolitinib between January 1, 2011 and December 31, 2018. Disproportionality signal analysis was done by calculating the reporting odds ratio (ROR). ROR was considered significant when the lower limit of 95% confidence interval (CI) was > 1. RESULTS: There were 91 reported cases of MTB associated with ruxolitinib compared with 4575 cases from all other drugs. The ROR was significant at 9.2 (95% CI, 7.5-11.4). There were 23 reports of AMI with ruxolitinib compared with 1287 reported with all other drugs. The ROR was significant at 8.3 (95% CI, 5.5-12.6). Twelve (13.2%) patients with MTB and 8 (34.8%) with AMI died. CONCLUSION: Patients on ruxolitinib are at increased risk of developing MTB and AMI. Clinicians should be aware of this risk and consider screening patients for latent MTB prior to initiating ruxolitinib.


Asunto(s)
Quinasas Janus/efectos adversos , Infecciones por Mycobacterium no Tuberculosas/inducido químicamente , Pirazoles/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Quinasas Janus/farmacología , Masculino , Persona de Mediana Edad , Nitrilos , Farmacovigilancia , Pirazoles/farmacología , Pirimidinas , Estudios Retrospectivos
15.
Br J Haematol ; 144(3): 409-15, 2009 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-19016720

RESUMEN

Health-related quality of life (HRQoL) is a major concern for adults with chronic immune thrombocytopenic purpura (ITP) due to the symptoms associated with the disease and its treatment. This study utilized the ITP-patient assessment questionnaire (ITP-PAQ), a specialized HRQoL questionnaire for ITP, to investigate the humanistic burden of ITP and the impact of romiplostim therapy on HRQoL in two, placebo-controlled, phase 3 clinical trials of splenectomized and non-splenectomized patients. ITP-PAQ was self-administered to ITP patients at baseline, and weeks 4, 12 and 24 of treatment. Splenectomized patients had lower baseline HRQoL scores than non-splenectomized patients in seven of 10 scales (P < 0.05). After 24 weeks of romiplostim therapy, splenectomized patients showed significant improvements over placebo in four of 10 ITP-PAQ Scales (Symptoms, P = 0.0337; Bother, P = 0.0126; Social Activity, P = 0.0145; and Women's Reproductive Health, P = 0.0184). Non-splenectomized patients demonstrated significant improvement over placebo in the Activity Scale (P = 0.0458). Data pooled from the two trials, adjusted for splenectomy status, showed significant improvement for romiplostim-treated patients in six scales; Symptoms, Bother, Activity, Fear, Social Activity and Women's Reproductive Health. These results suggest that adult patients with chronic ITP have improved HRQoL following romiplostim therapy.


Asunto(s)
Proteínas Portadoras/uso terapéutico , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Púrpura Trombocitopénica Idiopática/psicología , Calidad de Vida , Receptores Fc/uso terapéutico , Adulto , Anciano , Enfermedad Crónica , Terapia Combinada , Método Doble Ciego , Femenino , Indicadores de Salud , Humanos , Masculino , Persona de Mediana Edad , Psicometría , Púrpura Trombocitopénica Idiopática/cirugía , Proteínas Recombinantes de Fusión , Esplenectomía , Trombopoyetina , Resultado del Tratamiento
16.
Lancet ; 371(9610): 395-403, 2008 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-18242413

RESUMEN

BACKGROUND: Chronic immune thrombocytopenic purpura (ITP) is characterised by accelerated platelet destruction and decreased platelet production. Short-term administration of the thrombopoiesis-stimulating protein, romiplostim, has been shown to increase platelet counts in most patients with chronic ITP. We assessed the long-term administration of romiplostim in splenectomised and non-splenectomised patients with ITP. METHODS: In two parallel trials, 63 splenectomised and 62 non-splenectomised patients with ITP and a mean of three platelet counts 30x10(9)/L or less were randomly assigned 2:1 to subcutaneous injections of romiplostim (n=42 in splenectomised study and n=41 in non-splenectomised study) or placebo (n=21 in both studies) every week for 24 weeks. Doses of study drug were adjusted to maintain platelet counts of 50x10(9)/L to 200x10(9)/L. The primary objectives were to assess the efficacy of romiplostim as measured by a durable platelet response (platelet count > or =50x10(9)/L during 6 or more of the last 8 weeks of treatment) and treatment safety. Analysis was per protocol. These studies are registered with ClinicalTrials.gov, numbers NCT00102323 and NCT00102336. FINDINGS: A durable platelet response was achieved by 16 of 42 splenectomised patients given romplostim versus none of 21 given placebo (difference in proportion of patients responding 38% [95% CI 23.4-52.8], p=0.0013), and by 25 of 41 non-splenectomised patients given romplostim versus one of 21 given placebo (56% [38.7-73.7], p<0.0001). The overall platelet response rate (either durable or transient platelet response) was noted in 88% (36/41) of non-splenectomised and 79% (33/42) of splenectomised patients given romiplostim compared with 14% (three of 21) of non-splenectomised and no splenectomised patients given placebo (p<0.0001). Patients given romiplostim achieved platelet counts of 50x10(9)/L or more on a mean of 13.8 (SE 0.9) weeks (mean 12.3 [1.2] weeks in splenectomised group vs 15.2 [1.2] weeks in non-splenectomised group) compared with 0.8 (0.4) weeks for those given placebo (0.2 [0.1] weeks vs 1.3 [0.8] weeks). 87% (20/23) of patients given romiplostim (12/12 splenectomised and eight of 11 non-splenectomised patients) reduced or discontinued concurrent therapy compared with 38% (six of 16) of those given placebo (one of six splenectomised and five of ten non-splenectomised patients). Adverse events were much the same in patients given romiplostim and placebo. No antibodies against romiplostim or thrombopoietin were detected. INTERPRETATION: Romiplostim was well tolerated, and increased and maintained platelet counts in splenectomised and non-splenectomised patients with ITP. Many patients were able to reduce or discontinue other ITP medications. Stimulation of platelet production by romiplostim may provide a new therapeutic option for patients with ITP.


Asunto(s)
Proteínas Portadoras/uso terapéutico , Púrpura Trombocitopénica Trombótica/tratamiento farmacológico , Receptores Fc/uso terapéutico , Adulto , Anciano , Proteínas Portadoras/administración & dosificación , Proteínas Portadoras/efectos adversos , Enfermedad Crónica/tratamiento farmacológico , Método Doble Ciego , Esquema de Medicación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recuento de Plaquetas , Púrpura Trombocitopénica Trombótica/sangre , Púrpura Trombocitopénica Trombótica/inmunología , Receptores Fc/administración & dosificación , Proteínas Recombinantes de Fusión , Esplenectomía , Trombopoyetina , Resultado del Tratamiento
17.
Am Heart J ; 157(4): 651-7, 2009 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-19332191

RESUMEN

BACKGROUND: Thrombocytopenia and heparin-induced thrombocytopenia (HIT) are potentially devastating paradoxical side effects of heparin therapy. We explored the evaluation, management, and clinical consequences of thrombocytopenia occurring during heparin therapy in diverse clinical settings. METHODS: CATCH was a prospective observational study that enrolled 3,536 patients in 48 US hospitals. Data were collected on 3 strata: patients receiving any form of heparin for > or =96 hours (n = 2,420); cardiac care unit (CCU) patients treated with heparin who developed thrombocytopenia (n = 1,090); patients who had an HIT assay performed (n = 449). RESULTS: Thrombocytopenia occurred in 36.4% of patients in the prolonged heparin stratum and was associated with an increased risk of death or thromboembolic complication (OR 1.5, 95% CI 1.2-1.9). Among a subset of patients whose clinical presentation suggested they were at high risk for HIT, suspicion for HIT was uncommon (prolonged heparin stratum 19.8%, CCU stratum 37.6%) and often did not arise until > or =1 day after patients developed thrombocytopenia. Often patients were not evaluated for HIT until after they had had a thromboembolic complication (prolonged heparin stratum 43.8%, CCU stratum 61%). Even after HIT was suspected, patients often continued to receive heparin. Direct thrombin inhibitor use was infrequent (prolonged heparin stratum 29.4%, CCU stratum 35.6%). Among the few patients who underwent evaluation, HIT was confirmed in 46.7% of the prolonged heparin stratum and 31.4% of the CCU stratum. CONCLUSIONS: Thrombocytopenia is common among patients receiving heparin, and it is associated with substantial risk for catastrophic complications. Despite the high risk for HIT in this population, recognition, evaluation, and appropriate treatment are infrequent and delayed.


Asunto(s)
Enfermedad Coronaria/tratamiento farmacológico , Heparina/efectos adversos , Pacientes Internos , Sistema de Registros , Trombocitopenia/inducido químicamente , Anciano , Anticoagulantes/efectos adversos , Anticoagulantes/uso terapéutico , Femenino , Heparina/uso terapéutico , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Factores de Riesgo , Trombocitopenia/epidemiología
19.
Blood Cells Mol Dis ; 42(1): 1-4, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-18823803

RESUMEN

A 55 year old man with a history of chronic hepatitis C infection was found to have severe hemochromatosis: hepatic cirrhosis, cardiomyopathy, arrhythmia, hypogonadism, diabetes and bronzed skin color. After 50 phlebotomies, he underwent a combined heart and liver transplant. Genetic analyses identified a novel mutation in the iron responsive element of the ALAS2 gene. No mutations were found in other genes associated with adult or juvenile hemochromatosis including HFE, transferrin receptor-2 (TFR2), ferroportin (SLC40A1), hepcidin (HAMP) and hemojuvelin (HJV). We suggest that the ALAS2 mutation together with chronic hepatitis C infection may have caused the severe iron overload phenotype.


Asunto(s)
5-Aminolevulinato Sintetasa/genética , Hepatitis C Crónica/complicaciones , Sobrecarga de Hierro/etiología , Sobrecarga de Hierro/genética , 5-Aminolevulinato Sintetasa/metabolismo , Trasplante de Corazón , Hemocromatosis/etiología , Hemocromatosis/genética , Hemocromatosis/cirugía , Hemocromatosis/terapia , Hepatitis C Crónica/virología , Humanos , Hierro/metabolismo , Sobrecarga de Hierro/cirugía , Sobrecarga de Hierro/terapia , Trasplante de Hígado , Masculino , Persona de Mediana Edad , Mutación/genética , Elementos de Respuesta/genética
20.
J Investig Med ; 57(5): 650-4, 2009 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-19491629

RESUMEN

BACKGROUND: Neocytolysis, the selective hemolysis of young circulating red blood cells (RBCs), contributes to the physiologic control of red cell mass and to pathophysiologic phenomena such as anemia of renal disease, anemia after spaceflight, and blood doping by athletes. Progress in understanding the process is hampered by the lack of established markers to distinguish young from older RBC. METHODS: Twelve potentially informative RBC surface markers were assayed by flow cytometry in normal blood samples, and 4 were preferentially expressed in young RBC. To create a model of neocytolysis, 3 normal volunteers had recombinant human erythropoietin (rhEpo) administered until mild erythrocytosis occurred, then were studied upon rhEpo withdrawal. RESULTS: Neocytolysis ensued that most evident from a rapid rise in serum ferritin as the iron from young RBC was transferred back to stores. Five additional volunteers had surface markers monitored during and after rhEpo administration. Three subjects with marginal baseline iron stores had blunted response to rhEpo, no significant neocytolysis, and no change in RBC surface marker expression. Two subjects with adequate baseline iron stores developed erythrocytosis followed by neocytolysis. Decreased expression of CD44 (homing-associated cell adhesion molecule) and CD71 (transferrin receptor) seemed to correlate best with neocytolysis; CD35 (complement receptor) less so. Of note, further studies are needed to determine if these changes are causative of red cell destruction. CONCLUSION: This study begins to establish a human model of neocytolysis, to establish markers differentiating young and old RBC, and to establish a basis for better definition of the process. Although our study is preliminary, the results support the possibility that flow could be useful to detect blood doping because neocytolysis should predictably occur in athletes who surreptitiously blood dope.


Asunto(s)
Doping en los Deportes , Membrana Eritrocítica/metabolismo , Adulto , Antígenos CD/sangre , Biomarcadores/sangre , Eritropoyetina/administración & dosificación , Femenino , Humanos , Masculino , Modelos Biológicos , Proteínas Recombinantes
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