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1.
Curr Opin Hematol ; 31(6): 285-293, 2024 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-39177058

RESUMO

PURPOSE OF REVIEW: Pregnancy for people with sickle cell disease (SCD) is high risk with persistently high rates of severe maternal and fetal mortality and morbidity. Transfusion therapy is the best-studied treatment for SCD in pregnancy; hydroxyurea is not usually used because of teratogenicity concerns. In high-resource settings, red cell transfusions are likely underutilized, while in low-resource settings, they may be altogether unavailable. RECENT FINDINGS: A randomized controlled trial and meta-analysis, two of the strongest forms of clinical research, show transfusion significantly reduces maternal and fetal death, painful crisis, thrombosis, and acute respiratory failure. Downstream benefits of treatment are less well measured and may include improving maternal anemia, reducing opioid exposure, and avoiding hospitalization, which presents risk for additional complications. Alloimmunization is a particular transfusion risk in SCD. However, many strategies can mitigate this risk. Accordingly, the American Society of Hematology classifies chronic transfusion in pregnancy as low risk. SUMMARY: Given the low risk classification, lack of alternative therapies, dismal, stagnant pregnancy outcomes and the potential for profound treatment benefit, wider use of chronic transfusion therapy for SCD pregnancy is likely indicated. This review discusses the benefits and potential risks of prophylactic transfusions for SCD pregnancy. Use of chronic transfusions during pregnancy is indicated to help urgently transform outcomes.


Assuntos
Anemia Falciforme , Transfusão de Eritrócitos , Complicações Hematológicas na Gravidez , Humanos , Anemia Falciforme/terapia , Gravidez , Feminino , Transfusão de Eritrócitos/efeitos adversos , Complicações Hematológicas na Gravidez/terapia , Resultado da Gravidez
2.
Br J Haematol ; 204(4): 1500-1506, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38291731

RESUMO

The thrombotic risk with haemoglobin C trait (HbAC) or haemoglobin C disease (HbCC) is unclear. However, individuals with HbCC have demonstrated chronic haemolysis, higher blood viscosity and altered rheology when compared to individuals with wild-type haemoglobin (HbAA). These physiological alterations may theoretically translate to increased risk of thrombosis; therefore, a systematic literature review was performed to investigate the possible association between HbAC and/or HbCC and thrombosis. Twenty-two studies met inclusion criteria representing 782 individuals with HbAC (n = 694) or HbCC (n = 88). Fifteen studies described the presence/absence of venous thromboembolism (VTE) in patients with HbAC (n = 685) or HbCC (n = 79), while seven studies described patients with HbAC (n = 9) or HbCC (n = 9) and arterial thrombosis. Most (n = 20) studies were case reports or case series; however, two studies suggested a potential increased VTE risk with HbAC compared to HbAA in (i) all patients (OR 2.2, 95% CI: 0.9-5.5) and in (ii) pregnant individuals (RR 3.7, 95% CI 0.9-16). This review is the largest assessment of patients with HbC trait or disease and thrombosis to date; despite its limitations, the findings suggest HbC may be a predisposing risk factor to thrombosis. Prospective cohort studies are warranted to definitively elucidate the risk of thrombosis in this population.


Assuntos
Doença da Hemoglobina C , Hemoglobinopatias , Trombose , Tromboembolia Venosa , Gravidez , Feminino , Humanos , Hemoglobina C , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologia , Estudos Prospectivos , Trombose/etiologia , Fatores de Risco
3.
Transfusion ; 2024 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-39373054

RESUMO

BACKGROUND: Acute chest syndrome (ACS) is the leading cause of mortality, accounting for 25% of all deaths among individuals with sickle cell disease (SCD). There is a lack of evidence-based laboratory and clinical risk stratification guidelines for the diagnosis and management of ACS. STUDY DESIGN AND METHODS: To better understand physician practices for the management of ACS in the United States, we created an ACS Working Group including hematology and transfusion medicine physicians from four different SCD treatment centers in the United States. The working group created a physician survey that included physician demographics and ACS diagnostic criteria that they had to rate. The survey also included three case scenarios to assess physician attitudes about the management of ACS. Management options included supportive and preventive strategies in addition to transfusion therapy options. RESULTS: Out of 455 physicians who received the survey, 195 responded (response rate = 43%). The respondents were primarily hematology/oncology physicians. The responses showed wide variability among physicians in how diagnostic criteria for ACS are used and how physicians risk-stratify ACS patients in their practice. The responses also reflected variability in the use of transfusions for ACS. DISCUSSION: Based on our results, we conclude that ACS is diagnosed and managed inconsistently among expert physicians, especially in their transfusion practices due to a lack of consensus on risk stratification criteria. Our data suggest an urgent need for well-designed prospective studies to provide evidence-based guidelines and minimize management variability among physicians who care for individuals with SCD and ACS.

4.
Am J Hematol ; 2024 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-39324647

RESUMO

The neonatal fragment crystallizable (Fc) receptor (FcRn) transports IgG across mucosal surfaces and the placenta and protects IgG from degradation. Numerous clinical trials are investigating therapeutic FcRn inhibition for various immune-mediated neuromuscular and rheumatologic conditions; however, FcRn inhibition also represents a potential therapy for IgG-mediated hematologic conditions (e.g., immune thrombocytopenia, autoimmune hemolytic anemia, immune thrombotic thrombocytopenic purpura, acquired hemophilia, red blood cell/platelet alloimmunization). Current evidence derived from both in vitro and in vivo studies suggests that FcRn inhibitors effectively reduce total IgG levels without impacting its production or altering the levels of other immunoglobulin isotypes. Moreover, the risk of serious adverse events, including serious infections, appears to be lower than that seen with other commonly used immunomodulatory/immunosuppressive therapies, albeit in the setting of limited clinical trial data. Ultimately, additional clinical trials that include varied patient populations are required prior to incorporating these agents into standard treatment algorithms for most hematologic conditions. However, based on the pathophysiology of IgG-mediated hematologic disorders and the mechanism of action of FcRn inhibitors, these agents may represent a future novel therapeutic strategy for patients with hematologic conditions caused by IgG antibodies.

5.
Br J Haematol ; 198(4): 745-752, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35719004

RESUMO

Blood transfusion is an integral component in the management of children and adults with sickle cell disease (SCD). Concerns about blood safety due to the high risk of bloodborne infections in sub-Saharan Africa limits the application of this cost-effective strategy in the management of individuals with SCD. In a single-centre, retrospective, longitudinal study in southwest Nigeria, we hypothesised that the use of stringent blood donor selection, along with very sensitive enzyme-linked immunosorbent assay (ELISA) screening methods would reduce transfusion-transmitted infections (TTIs). Among 45 002 eligible blood donors at the Lagos University Teaching Hospital in Nigeria, over a 5-year review period (2015-2019), the seroprevalence rate of viral TTIs was 9.83%. The seroprevalence rates for human immunodeficiency, hepatitis B, and hepatitis C viruses were 1.37%, 6.2%, and 2.25% respectively. Among 172 children with SCD, 71% (122/172) on regular blood transfusion and 29% (50/172) who had never been transfused or had less than two transfusions per lifetime, none acquired any TTIs using our enhanced screening approach during the study period. Thus, safe blood transfusion practices can be provided for children with SCD in sub-Saharan Africa with the use of stringent donor selection protocols and fourth-generation ELISA kits for TTI screening.


Assuntos
Anemia Falciforme , Infecções por HIV , Hepatite B , Hepatite C , Reação Transfusional , Adulto , Anemia Falciforme/diagnóstico , Anemia Falciforme/epidemiologia , Anemia Falciforme/terapia , Doadores de Sangue , Criança , Hepatite B/diagnóstico , Hepatite C/diagnóstico , Hepatite C/epidemiologia , Humanos , Estudos Longitudinais , Nigéria/epidemiologia , Estudos Retrospectivos , Estudos Soroepidemiológicos , Reação Transfusional/epidemiologia
6.
Transfus Apher Sci ; 61(1): 103284, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34865973

RESUMO

INTRODUCTION: Anti-M antibodies are usually inactive at physiologic temperatures (37 °C). Rarely, these antibodies have been reported to react at physiologic temperatures, resulting in clinically significant hemolytic transfusion reactions or hemolytic disease of the fetus and newborn. PATIENT AND METHODS: We describe a case of an acute hemolytic transfusion reaction due to an anti-M alloantibody reacting at physiologic temperatures in a critically ill patient. RESULTS: Proper identification and management of anti-M antibody-mediated acute hemolysis rapidly improved and stabilized her hemoglobin. CONCLUSION: Differentiation between anti-M antibody-mediated acute hemolysis and its differential diagnoses is of critical importance to guide therapeutic decisions in these rare clinical scenarios.


Assuntos
Transplante de Coração/métodos , Isoanticorpos/imunologia , Adulto , Feminino , Humanos , Adulto Jovem
7.
J Thromb Thrombolysis ; 53(1): 213-217, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34240279

RESUMO

Pampiniform venous plexus (PVP) thrombosis is exceedingly rare, with fewer than 25 cases described. Thus, the etiology and pathophysiology remain largely unknown. A 38-year-old male with no known risk factors incidentally noted a 10-day history of right testicular discomfort prompting evaluation. Findings included extensive right PVP thrombus, critically elevated hematocrit, and a JAK2 V617F gene variant. Despite no treatment guidelines, conservative management was initiated with therapeutic apixaban, and therapeutic phlebotomy and hydroxyurea for newly diagnosed primary polycythemia vera (PV), sparing exploratory genitourinary surgery. This represents the first reported case of PVP thrombosis as the initial manifestation of a JAK2 V617F positive PV and the first documented report of PVP thrombosis associated with an acquired hypercoagulable state. Of the 8 previous cases with hypercoagulable testing performed, 2 involved inherited hypercoagulable states, suggesting hereditary and acquired prothrombotic disorders should be considered as predisposing factors. Testing for the JAK2 V617F variant in patients with mesenteric, cerebral, and splanchnic venous thromboses is currently recommended, but testing patients with venous thromboses in other anatomical locations remains controversial. We reviewed all previously described cases to expound upon this diagnosis, potential association with hypercoagulable disorders, treatment options, and observed clinical outcomes. This case adds to the minimal literature and supports genetic testing all patients with spontaneous PVP thrombosis for the JAK2 V617F variant and other hypercoagulable conditions. Additionally, conservative management with therapeutic anticoagulation and treatment of the underlying precipitating disease state may be acceptable in select patients, following exclusion of surgical emergencies.


Assuntos
Transtornos Mieloproliferativos , Policitemia Vera , Trombose , Trombose Venosa , Adulto , Humanos , Janus Quinase 2/genética , Masculino , Mutação , Transtornos Mieloproliferativos/complicações , Transtornos Mieloproliferativos/diagnóstico , Transtornos Mieloproliferativos/genética , Policitemia Vera/complicações , Policitemia Vera/genética , Trombose/tratamento farmacológico , Trombose/genética , Trombose Venosa/complicações , Trombose Venosa/genética
8.
J Thromb Thrombolysis ; 54(2): 367-371, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35763168

RESUMO

Heparin-induced thrombocytopenia (HIT) occurs with the development of IgG antibodies that bind complexes of heparin and platelet factor 4 (PF4), which activate platelets and result in a profoundly prothrombotic condition. In rare instances, this syndrome develops in the absence of proximate heparin administration, referred to as spontaneous HIT, for which less than three dozen cases have been reported. Spontaneous HIT is considered a subtype of "autoimmune HIT" (aHIT), characterized by platelet activation in the serotonin release assay (SRA) without the addition of exogenous heparin. Here, we report spontaneous HIT as the presenting feature in a patient with 2019 coronavirus disease infection (COVID-19).A 66-year-old male presented with progressive leg pain and was found to have a platelet count of 39 × 109/L and multiple lower extremity arterial thromboses requiring fasciotomy and thrombectomy. He had no recent hospitalization, heparin exposure, vaccinations, or known thrombophilia. He had a strongly positive IgG-specific enzyme-linked immunosorbent assay for heparin-PF4 antibodies, and the SRA was strongly positive both with and without the addition of heparin. He was treated successfully with bivalirudin, intravenous immunoglobulin, and apixaban.


Assuntos
COVID-19 , Trombocitopenia , Idoso , Anticoagulantes/efeitos adversos , COVID-19/complicações , Heparina/efeitos adversos , Humanos , Imunoglobulina G , Fatores Imunológicos , Isquemia , Masculino , Fator Plaquetário 4 , Trombocitopenia/induzido quimicamente , Trombocitopenia/diagnóstico
9.
Br J Haematol ; 194(6): 970-979, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34231198

RESUMO

There is an immediate need to address long-standing questions about the reproductive health of girls and women with sickle cell disease (SCD). There are many SCD-related reproductive risks and uncertainties across girls' and women's reproductive life span, with particularly outstanding concerns about menstruation, contraception, fertility and pregnancy. Extant literature addressing women's reproductive health topics is mostly descriptive; there are few high-quality interventional studies. In 2020, the Centers for Disease Control and Prevention and the Foundation for Women and Girls with Blood Disorders convened an expert panel to assess the knowledge gaps in women's reproductive health in SCD. The panel identified significant limitations to clinical care due to the need for research. The panel also identified prominent barriers to research and care. In this report, we frame these issues, providing a roadmap for investigators, funding agencies, and policy makers to advance care for girls and women with SCD.


Assuntos
Anemia Falciforme , Saúde Reprodutiva , Saúde Sexual , Anemia Falciforme/epidemiologia , Anemia Falciforme/fisiopatologia , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Saúde da Mulher
10.
Transfus Apher Sci ; 60(1): 102965, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33127310

RESUMO

INTRODUCTION: Isohemagglutinins occur naturally and form in an 'opposite' (antigen-negative) pattern to a patient's ABO blood type. Patients undergoing minor and bidirectional ABO incompatible hematopoietic stem cell transplantation (HSCT) may demonstrate detectable antibodies against their native blood type. In this study, we sought to characterize the rates of such antibody formation and evaluate the clinical significance of our findings. MATERIALS AND METHODS: An internal database of HSCT patients at an academic medical center was queried for ABO incompatible transplant patients from 2009-2019. Serum typing results, clinical histories, and laboratory data were compiled and reviewed. RESULTS: A total of 182 minor and bidirectional ABO incompatible HSCT patients were identified. Anti-recipient isohemagglutinins were found in 9% (16/182) of the HSCT patients. The rate was higher in patients with minor incompatibility (12%: 15/127) versus bidirectional ABO incompatibility (2%: 1/55) (p = 0.04). No anti-recipient isohemagglutinins were identified in umbilical cord HSCT patients (0%: 0/7). Serologic agglutination reactions of recipient isohemagglutinins were overall mostly weak (13/16 weak + to 1+). There was a trend towards a higher rate of acute graft-versus-host-disease in patients with anti-recipient isohemagglutinins compared to those without (75% vs. 53%; p = 0.12), though not statistically significant. Rates of alloimmunization to minor red cell antigens were similar between the two groups. Few patients showed laboratory evidence of hemolysis at 12 months follow up. DISCUSSION AND CONCLUSIONS: Anti-recipient isohemagglutinins occur at low rates in ABO incompatible HSCT and are significantly more common in minor ABO incompatible transplant compared to bidirectional transplants. Larger cohort studies are needed to better understand the relationship between anti-recipient isohemagglutinins and HSCT outcomes.


Assuntos
Sistema ABO de Grupos Sanguíneos/imunologia , Incompatibilidade de Grupos Sanguíneos/imunologia , Doença Enxerto-Hospedeiro/etiologia , Hemaglutininas/metabolismo , Transplante de Células-Tronco Hematopoéticas/métodos , Adulto , Feminino , Doença Enxerto-Hospedeiro/patologia , Humanos , Estudos Retrospectivos
11.
Transfus Apher Sci ; 59(2): 102681, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31831326

RESUMO

Delayed hemolytic transfusion reactions (DHTR) occurring in individuals with sickle cell disease (SCD) are usually indolent but may rarely progress to life-threatening hemolysis known as hyperhemolysis syndrome (HHS), which can be difficult to diagnose and manage. We evaluate a predictive model for DHTR proposed by Drs. Pirenne and Yazdanbakhsh. A scoring system and nomogram were utilized in three individuals with SCD and delayed hemolysis, with one likely having HHS. The scoring system is based on identified risk factors for developing hemolysis from patient transfusion history, while the nomogram utilizes persistence of hemoglobin A (HbA) which is not innate to SCD patients. We propose a novel method for HbA estimation to facilitate application of the nomogram. Application of the recently published predictive scoring system revealed a low risk of developing DHTR in one patient and an intermediate risk in two patients. As serial HbA values are not routinely assessed, HbA measurements were only available in one of the three patients, though use of the nomogram predicted a high likelihood of DHTR. The recently published predictive score and nomogram yielded mixed results and should be interpreted with caution when predicting the risk of developing DHTR in individuals with SCD. Management of DHTR/HHS continues to be a challenge for transfusion medicine and hematology services standardized methods to facilitate their early diagnosis and treatment are warranted to improve the safety of blood transfusions in individuals with SCD.


Assuntos
Anemia Falciforme/complicações , Transfusão de Sangue/métodos , Reação Transfusional/etiologia , Adolescente , Adulto , Feminino , Hemólise , Humanos , Masculino , Fatores de Risco
13.
South Med J ; 112(3): 174-179, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30830232

RESUMO

OBJECTIVES: Women with sickle cell disease (SCD) are living longer as a result of advances in the care of their underlying disease. With the population growing of women living with SCD, reproductive health issues in this population have become an emphasized area of medical care. We sought to describe current patterns of contraception use, menstruation, and quality-of-life (QOL) measures in women with SCD. METHODS: Using a cross-sectional study design, we administered paper surveys at two academic medical centers to women aged 10 to 55 years with SCD to capture current contraceptive use, characteristics of menstrual cycles, and QOL metrics. RESULTS: Of the 103 women who participated, 12.7% (13/102) experienced a duration of menses >7 days (defined here as prolonged menstrual bleeding). Approximately half of women (51.5%, 53/103) used some form of contraception, with depot medroxyprogesterone acetate injections and condoms being the most common. During their last menstrual periods, women with both dysmenorrhea and prolonged menstrual bleeding (6.9%, 7/102) were more likely to experience more days of poor QOL, with more nights with sleep disturbance (P = 0.001) and more days with trouble taking care of themselves (P = 0.003), as well as being unable to do things they previously enjoyed (P = 0.001), compared with those with neither phenomenon (28.2%, 29/103). CONCLUSIONS: Dysmenorrhea and prolonged menstrual bleeding negatively affect the QOL of women with SCD. Menstrual histories and preventive measures for menstruation-related morbidity should be incorporated into routine evaluations of women with SCD.


Assuntos
Anemia Falciforme/epidemiologia , Anticoncepção/estatística & dados numéricos , Dismenorreia/epidemiologia , Distúrbios Menstruais/epidemiologia , Menstruação , Qualidade de Vida , Adolescente , Adulto , Criança , Preservativos/estatística & dados numéricos , Anticoncepcionais Femininos , Anticoncepcionais Orais/uso terapêutico , Estudos Transversais , Preparações de Ação Retardada , Dismenorreia/fisiopatologia , Dismenorreia/psicologia , Feminino , Humanos , Dispositivos Intrauterinos/estatística & dados numéricos , Acetato de Medroxiprogesterona/uso terapêutico , Distúrbios Menstruais/fisiopatologia , Distúrbios Menstruais/psicologia , Pessoa de Meia-Idade , Inquéritos e Questionários , Adulto Jovem
14.
Pediatr Blood Cancer ; 65(1)2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28834316

RESUMO

BACKGROUND: The relationship between silent cerebral infarcts (SCIs) and history of parvovirus B19 (B19V) has not been systematically evaluated. As an ancillary study from the Silent Cerebral Infarct Trial (SIT) (NCT00072761), we tested the hypothesis that a history of B19V infection is associated with an increased prevalence of SCIs in children with sickle cell anemia. PROCEDURE: We used a retrospective cross-sectional cohort study design; each participant underwent a brain magnetic resonance imaging (MRI) scan and medical record review for prior B19V infection (n = 958). RESULTS: SCI was present in 30% (287 of 958) of participants and 17% (165 of 958) had a history of B19V infection. Based on prior evidence that low baseline hemoglobin (Hgb) levels are associated with increased odds of SCI, Hgb levels were divided into tertiles (<7.6 g/dl, ≥7.6-≤8.5 g/dl, ≥8.6 g/dl) and multivariable analysis was used to determine the relationship between the joint effect of prior B19V infection, Hgb levels, and SCI. Prior B19V infection and the lowest Hgb tertile were associated with increased risk of SCI (odds ratio [OR] 2.12; 95% CI, 1.17-3.84; P = 0.013); no prior B19V infection and the highest Hgb tertile were associated with a decreased risk (OR 0.56; 95% CI, 0.38-0.84; P = 0.004). CONCLUSIONS: Efforts to decrease the incidence of B19V infection, such as the development of a B19V vaccine, may decrease SCI prevalence.


Assuntos
Infarto Cerebral , Eritema Infeccioso , Imageamento por Ressonância Magnética , Parvovirus B19 Humano , Infarto Cerebral/diagnóstico por imagem , Infarto Cerebral/epidemiologia , Infarto Cerebral/etiologia , Infarto Cerebral/virologia , Criança , Pré-Escolar , Eritema Infeccioso/complicações , Eritema Infeccioso/diagnóstico por imagem , Eritema Infeccioso/epidemiologia , Feminino , Humanos , Incidência , Masculino , Estudos Retrospectivos , Fatores de Risco
15.
BMC Neurol ; 16: 72, 2016 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-27206499

RESUMO

BACKGROUND: Primary central nervous system lymphoma (PCNSL) may rarely be preceded by "sentinel demyelination," a pathologic entity characterized by histologically confirmed demyelinating inflammatory brain lesions that mimic multiple sclerosis (MS) or acute disseminated encephalomyelitis (ADEM). Interpreting the overlapping radiologic and clinical characteristics associated with each of these conditions-contrast-enhancing demyelination of white matter and relapsing and remitting steroid-responsive symptoms respectively-can be a significant diagnostic challenge. CASE PRESENTATION: We describe a 57-year-old woman with an unusual clinical course who presented with multi-focal enhancing white matter lesions demonstrated to be inflammatory demyelination by brain biopsy. Despite a good initial response to steroids and rituximab for treatment of presumed tumefactive multiple sclerosis, the patient's condition rapidly deteriorated, and a repeat brain biopsy six months later was consistent with a diagnosis of diffuse large B-cell lymphoma. CONCLUSIONS: Early clinical suspicion for PCNSL and awareness that biopsied lesions may initially show sentinel demyelination suggestive of alternate diagnoses may be essential for early initiation of appropriate therapies and mitigation of disease progression. Clinical, pathophysiological, and diagnostic aspects of sentinel demyelination and PCNSL are discussed.


Assuntos
Neoplasias do Sistema Nervoso Central/patologia , Doenças Desmielinizantes/patologia , Linfoma de Células B/patologia , Corticosteroides/uso terapêutico , Neoplasias do Sistema Nervoso Central/complicações , Doenças Desmielinizantes/complicações , Doenças Desmielinizantes/diagnóstico por imagem , Doenças Desmielinizantes/tratamento farmacológico , Progressão da Doença , Feminino , Humanos , Linfoma de Células B/complicações , Linfoma de Células B/diagnóstico por imagem , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Rituximab/uso terapêutico , Substância Branca/patologia
16.
Platelets ; 27(7): 703-711, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27135253

RESUMO

Platelets and their granular contents influence both angiogenesis and breast cancer progression. This study was performed to assess the effect of breast cancer and its treatment on platelet biology and the response to inhibition of the platelet P2Y12 receptor. Receptor-specific platelet activation and inhibition was studied for three platelet-associated proteins important in cancer angiogenesis and progression, vascular endothelial growth factor (VEGF), thrombospondin1 (TSP1), and transforming growth factor beta 1 (TGF-ß1). Twenty-four women with active breast cancer and 10 healthy controls not receiving antiplatelet therapy participated in the study. Ex vivo activation of platelets in whole blood was accomplished using PAR1AP, PAR4AP, convulxin, and ADP. Platelet inhibition was accomplished using the P2Y12 receptor antagonist cangrelor (the in vitro equivalent of clopidogrel). VEGF, TSP1, and TGF-ß1 were measured using standard ELISA. Platelet activation by ADP, PAR1, PAR4, and collagen receptors increased VEGF, TSP1, and TGF-ß1 secretion in patients with breast cancer. Agonist-induced release of VEGF was greater in cancer patients as compared to healthy controls (p = 0.02 for ADP, p < 0.001 for PAR1AP, PAR4AP, and convulxin) despite a decrease in the efficiency of VEGF secretion in patients with breast cancer. These differences were not observed for TSP1 and TGF-ß1 secretion. P2Y12 receptor inhibition decreased VEGF, TSP1, and TGF-ß1 secretion. In patients with cancer, cangrelor inhibited TSP1 release to a greater extent than VEGF and TGF-ß1 release. In patients with breast cancer, the magnitude of platelet inhibition achieved by cangrelor was greater than that achieved with healthy controls for all agonists and platelet proteins studied. While platelets are known to influence progression of breast cancer, our results show that breast cancer and its treatment influence the platelet phenotype by increasing the secretion of pro-angiogenic proteins following platelet activation, modulating the efficiency of platelet protein release as well as increasing the response to antiplatelet therapy.


Assuntos
Plaquetas/metabolismo , Neoplasias da Mama/sangue , Neoplasias da Mama/terapia , Fenótipo , Biomarcadores , Plaquetas/efeitos dos fármacos , Estudos de Casos e Controles , Feminino , Citometria de Fluxo , Humanos , Ativação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/farmacologia , Antagonistas do Receptor Purinérgico P2Y/farmacologia , Receptores Purinérgicos P2Y12/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
18.
J Cell Physiol ; 229(8): 1005-15, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24374897

RESUMO

While platelets are well known to play a central role in hemostasis and thrombosis, there is emerging experimental evidence to suggest that they also mediate tumor cell growth, dissemination, and angiogenesis. An increase in platelet number (thrombocytosis) and activity is seen in patients with a wide spectrum of malignancies, and the former is correlated with a decrease in overall survival and poorer prognosis. Preclinical data suggest that circulating tumor cell partnerships with platelets in the blood facilitate tumor metastases through direct interactions and secreted bioactive proteins. Platelets form aggregates with tumor cells, thereby protecting them from host immune surveillance through physical shielding and induction of "platelet mimicry." There is also laboratory evidence to suggest that activated platelets interact with cancer cells within the tumor microenvironment through paracrine signaling and direct contact, thereby promoting tumor cell growth and survival. For example, platelets release mediators of both tumor angiogenesis and osteoclast resorption. The interplay between platelets and tumor cells is complex and bidirectional with involvement of multiple other components within the tumor microenvironment, including immune cells, endothelial cells, and the extracellular matrix. We review the role of platelets in tumor progression, emphasizing the opportunity these interactions afford to target platelets and platelet function to improve patient outcomes in the cancer prevention and treatment setting.


Assuntos
Plaquetas/fisiologia , Neoplasias/metabolismo , Humanos , Metástase Neoplásica/patologia , Osteoclastos , Comunicação Parácrina/fisiologia
19.
Blood Adv ; 8(4): 1018-1029, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38206762

RESUMO

ABSTRACT: Data to guide evidence-based management of pregnant people with sickle cell disease (SCD) are limited. This international Delphi panel aimed to identify consensus among multidisciplinary experts for SCD management during pregnancy. The 2-round Delphi process used questionnaires exploring 7 topics (antenatal care, hydroxyurea use, transfusion, prevention of complications, treatment of complications, delivery and follow-up, and bottlenecks and knowledge gaps) developed by a steering committee. Thirteen panelists (hematologists, physiologists, obstetricians, maternal fetal medicine, and transfusion medicine physicians) from the United States, the United Kingdom, Turkey, and France completed the first survey; 12 panelists completed the second round. Anonymized responses were collected and summarized by a contract research organization (Akkodis Belgium). Consensus and strong consensus were predefined as 75% to 90% (9-10 of 12) and >90% (≥11 of 12) of panelists, respectively, agreeing or disagreeing on a response to a predefined clinical scenario or statement. In several areas of SCD management, consensus was achieved: experts recommended performing at least monthly multidisciplinary antenatal follow-up, administering prophylactic aspirin for preeclampsia prevention between gestational weeks 12 and 36, initiating prophylactic transfusion therapy in certain cases, or choosing automated red blood cell exchange over other transfusion methods for patients with iron overload or severe acute chest syndrome. No consensus was reached on several topics including the prophylactic aspirin dose, indications for starting infection prophylaxis, routine use of prophylactic transfusions, or use of prophylactic transfusions for preventing fetal complications. These recommendations could inform clinical care for patients with SCD who are pregnant in the absence of large clinical trials involving this population; the identified knowledge gaps can orient future research.


Assuntos
Síndrome Torácica Aguda , Anemia Falciforme , Humanos , Feminino , Gravidez , Anemia Falciforme/complicações , Anemia Falciforme/terapia , Transfusão de Sangue/métodos , Hidroxiureia/uso terapêutico , Síndrome Torácica Aguda/terapia , Síndrome Torácica Aguda/complicações , Aspirina
20.
Environ Sci Pollut Res Int ; 30(44): 98787-98795, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36849684

RESUMO

Since the electroplating and alloy industries continuously pollute water resources, this paper presents a novel adsorbent to adsorb nickel ions from aqueous solutions prepared in the lab. Chhotidudhi, a creeping weed that is commonly called Euphorbia thymifolia, was used as an adsorbent in its pristine and activated forms. In order to characterize the structure, morphology, and thermal properties of ground Euphorbia thymifolia (ETR) and activated Euphorbia thymifolia (ETA), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscope (SEM), and thermal gravimetric analysis (TGA) were used. It was observed that the FTIR spectrum showed different functional groups, such as OH, CH, CO, CN, and CF, which indicated a strong bond with metals. XRD and SEM revealed that the adsorbent is amorphous with a porous structure. Additionally, different adsorbent doses, contact times, pH, concentrations, and temperatures were investigated. Approximately 2 h was required for effective adsorption with an initial concentration of 20 mg/L, pH 7, adsorption dose of 20 mg, and temperature of 303 K. At optimized conditions, the adsorption capacity for ETR and ETA was 52.4 mg/g and 109.05 mg/g, respectively, and the removal efficiency was 81.6% and 93.8%. Both Langmuir and pseudo-second-order reactions matched the experimental results perfectly.


Assuntos
Euphorbia , Poluentes Químicos da Água , Cinética , Temperatura , Níquel/química , Água/química , Adsorção , Espectroscopia de Infravermelho com Transformada de Fourier , Íons , Concentração de Íons de Hidrogênio , Poluentes Químicos da Água/química , Termodinâmica
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