Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 28.587
Filtrar
1.
Ann Lab Med ; 43(1): 86-91, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36045061

RESUMO

Antibodies against human CD36 are responsible for several immune-mediated disorders. The detection of anti-CD36 antibodies using the standard monoclonal antibody (mAb) immobilization of platelet antigens (MAIPA) assay is hampered by a high frequency of false-negative results, most likely due to competitive inhibition of the mAb used as the capture antibody. We generated a panel of mouse mAbs against CD36 and seven hybridomas (GZ-3, GZ-13, GZ-70, GZ-143, GZ-413, GZ-507, and GZ-608), which were selected for MAIPA assays, as they reacted with mouse and human CD36. Fourteen anti-CD36 sera were assayed; all of which showed a positive reaction in a PakPlus (Immucor GTI Diagnostics, Inc., Waukesha, WI, USA) ELISA-based screening (optical density: 0.257-2.292). When the reference anti-CD36 mAb FA6-152 was used in the MAIPA assay, only 6/14 (42.9%) sera displayed a positive reaction. In contrast, anti-CD36 antibodies were detected in 13/14 (92.9%) sera when GZ-70 and GZ-608 mAbs were used. This significant improvement resulted in the identification of anti-CD36 antibodies by an antigen capture assay. Since patient's platelets possibly carrying rare native antigens are used, this method will facilitate the identification of new platelet antibodies against CD36 that are involved in immune-mediated thrombocytopenia and other diseases, such as transfusion-related acute lung injury.


Assuntos
Antígenos de Plaquetas Humanas , Trombocitopenia , Animais , Anticorpos Monoclonais , Plaquetas , Antígenos CD36 , Humanos , Camundongos , Trombocitopenia/diagnóstico
2.
Vasc Endovascular Surg ; 57(1): 83-87, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36151060

RESUMO

We report a case of an infrarenal abdominal aortic aneurysm that developed acute onset thrombocytopenia and disseminated intravascular coagulation (DIC) after a previous coronary artery bypass grafting. Open surgical intervention was successfully performed for the treatment of aortic aneurysm; however, thrombocytopenia and enhanced-fibrinolytic-type DIC were prolonged even after the surgery, and improved after Helicobacter pylori eradication therapy and medication with warfarin and oral tranexamic acid. Surgical intervention alone was not effective as a treatment for DIC associated with aortic aneurysm, and multidisciplinary management was necessary for the optimization of the coagulation and fibrinolytic systems, even after successful surgery.


Assuntos
Aneurisma da Aorta Abdominal , Aneurisma Aórtico , Coagulação Intravascular Disseminada , Trombocitopenia , Humanos , Coagulação Intravascular Disseminada/diagnóstico , Coagulação Intravascular Disseminada/tratamento farmacológico , Coagulação Intravascular Disseminada/etiologia , Aneurisma da Aorta Abdominal/complicações , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/cirurgia , Resultado do Tratamento , Aneurisma Aórtico/cirurgia , Trombocitopenia/complicações , Trombocitopenia/tratamento farmacológico , Dacarbazina/uso terapêutico
3.
Platelets ; 34(1): 2135694, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36281771

RESUMO

Primary immune thrombocytopenia (ITP) is an acquired autoimmune hemorrhagic disease. Loss of immune tolerance plays a crucial role in the pathogenesis of ITP. Monocytes and macrophages play an indispensable role in the pathophysiology of hematopoietic malignancies and have been implicated as key players in platelet destruction. Approximately 80% of adult patients with ITP exhibit corticosteroid treatment failure or become dependent, requiring novel therapy. Thrombopoietin (TPO) receptor agonists (TPO-RAs) have been used clinically to manage ITP effectively, however, little is known about the effect of TPO-RAs on monocyte and macrophage modulation in adult ITP. In this study, we investigated the phenotypic evolution and potential immunomodulatory roles of monocytes/macrophages in ITP patients receiving eltrombopag therapy. Results showed that the peripheral monocyte count positively correlated with IFN-γ/IL-4 ratio in ITP patients. Moreover, numerous phenotype-associated genes in ITP macrophages exhibited diverse responses, and ITP macrophages exhibited more M1-related characteristics. After eltrombopag therapy, the peripheral monocyte count and IFN-γ/IL-4 ratio significantly decreased in ITP patients. M1-related characteristics of ITP macrophages were partially reversed by eltrombopag. Therefore, this study revealed eltrombopag restored the monocyte dynamics and the associated Th1/Th2 imbalance, and partially reversed the M1-related characteristics of the ITP macrophages, which suggest the potential vital roles of TPO-RAs in regulating the monocyte/macrophage plasticity in ITP.


What is the context? Primary immune thrombocytopenia (ITP) is an acquired autoimmune hemorrhagic disease. Loss of immune tolerance plays a crucial role in the pathogenesis of ITP.Monocytes and macrophages play an indispensable role in the pathophysiology of hematopoietic malignancies and have been implicated as key players in platelet destruction.Approximately 80% of adult patients with ITP exhibit corticosteroid treatment failure or become dependent, requiring novel therapy. Thrombopoietin (TPO) receptor agonists (TPO-RAs) have been used clinically to manage ITP effectively, however, little is known about the effect of TPO-RAs on monocyte and macrophage modulation in ITP.What is new?In this study, we investigated the phenotypic evolution and potential immunomodula-tory roles of monocytes/macrophages in ITP patients receiving eltrombopag therapy.The expansion of peripheral monocytes positively correlated with IFN-γ/IL-4 ratio in ITP patients.ITP macrophages exhibited more M1-related characteristics.After eltrombopag therapy, the peripheral monocyte count and IFN-γ/IL-4 ratio significantly decreased in ITP patients.M1-related characteristics of ITP macrophages were partially reversed by eltrombopag.What is the impact?This study provides evidence that the potential vital roles of TPO-RAs in regulating the monocyte/macrophage plasticity in ITP.


Assuntos
Púrpura Trombocitopênica Idiopática , Trombocitopenia , Humanos , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Monócitos , Receptores de Trombopoetina/agonistas , Interleucina-4 , Hidrazinas/farmacologia , Hidrazinas/uso terapêutico , Benzoatos/farmacologia , Benzoatos/uso terapêutico , Trombopoetina , Trombocitopenia/induzido quimicamente , Fenótipo , Macrófagos , Proteínas Recombinantes de Fusão
4.
Eur J Med Res ; 27(1): 244, 2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36369088

RESUMO

BACKGROUND: Immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by the destruction of the platelets resulting from autoimmune recognition and subsequent attack. Heat shock proteins (HSPs) are directly associated with progression and pathogenesis in some specific autoimmune diseases. The aim of this study was to investigate the serum expression of HSP-70 in ITP children and healthy controls. MATERIALS AND METHODS: A total of 86 children aged 1-6 years were enrolled in the study. The participants were divided into 20 newly diagnosed ITP (ndITP), 34 chronic ITP (cITP) patients and 32 healthy children. The white blood cells and platelet counts were determined and compared between the groups. HSP-70 serum levels were analyzed by sandwich ELISA. Data analysis was done using SPSS and the data variables assessment was done through histogram, probability plots and Shapiro-Wilk tests to determine normal distribution. RESULTS: The white blood cell counts were 8.9 (4.2-10.4) for new diagnosis ITP, 7.1(3.9-11.9) for the chronic ITP group and 7.0 (4.3-9.5) for the healthy controls. The platelet counts were significantly increased in the chronic ITP group, 83.5(31.7-297) compared to the ndITP group 27.4 (3.7-63.7), but significantly lower compared to the healthy controls 271(172-462) (P = 0.0009). There were significantly increased HSP-70 serum levels in cITP patients compared to the ndITP and the healthy group. In addition, there was a positive correlation between the serum HSP-70 level and the thrombocyte counts among the ITP children. CONCLUSIONS: HSP-70 has a role in the progression of childhood ITP. Increased HSP-70 level is associated with the severity of childhood primary ITP.


Assuntos
Púrpura Trombocitopênica Idiopática , Trombocitopenia , Criança , Humanos , Púrpura Trombocitopênica Idiopática/diagnóstico , Proteínas de Choque Térmico HSP70 , Contagem de Plaquetas , Plaquetas/patologia
5.
Medicine (Baltimore) ; 101(45): e31385, 2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36397400

RESUMO

At its onset, the coronavirus disease 2019 (COVID-19) pandemic brought significant challenges to healthcare systems, changing the focus of medical care on acute illness. Disruptions in medical service provision have impacted the field of viral hepatitis, with screening programs paused throughout much of 2020 and 2021. We performed a retrospective study on consecutive outpatients with COVID-19 during the second and third wave of COVID-19 in Romania, from November 2020 to April 2021, aiming to characterize the prevalence of undiagnosed hepatitis B virus (HBV) infection among patients presenting with acute illness. Overall, 522 patients had available records during the study timespan. Their mean ±â€…standard deviation age was 51 ±â€…13 years; 274 (52.5%) were male. We identified 16 (3.1%) cases of active HBV infection; only six of these patients were aware of their HBV status, and 3 of the newly diagnosed cases were identified as candidates for HBV treatment. A total of 96 patients (18.4%) had serological markers suggestive for prior HBV vaccination. A large proportion of patients (n = 120, 23.0%) had positive HBV core antibodies; among these, 90 (17.2%) had cleared a previous HBV infection (being positive for HBV surface antibodies and HBV core antibodies). We identified the following parameters that were significantly more frequent in patients with a history of HBV infection: older age (P < .001), hypoalbuminemia (P = .015), thrombocytopenia (P < .001), thrombocytopenia followed by thrombocytosis (P = .041), increased blood urea nitrogen (P < .001) and increased creatinine (P = .011). In conclusion, the COVID-19 pandemic has taught us essential lessons about the importance of maintaining access to screening programs and of ensuring active monitoring of patients with chronic infections such as hepatitis B, even during a medical crisis.


Assuntos
COVID-19 , Hepatite B , Trombocitopenia , Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Feminino , Vírus da Hepatite B , Estudos Retrospectivos , Prevalência , COVID-19/diagnóstico , COVID-19/epidemiologia , Pandemias , Doença Aguda , Hepatite B/diagnóstico , Hepatite B/epidemiologia , Hepatite B/prevenção & controle , Anticorpos Anti-Hepatite B , Trombocitopenia/epidemiologia
6.
Vector Borne Zoonotic Dis ; 22(11): 559-567, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36318815

RESUMO

Background: Severe fever with thrombocytopenia syndrome (SFTS), an emerging viral infectious disease, is mainly transmitted by ticks in the surrounding environment. Clinical progress and risk factors for prognosis in SFTS patients were not yet fully understood. Thus, the objective of this study was to analyze clinical progression and laboratory data related to the prognosis of South Korean SFTS patients in a single institution from 2014 to 2021. Materials and Methods: Fifty-three confirmed SFTS patients from August 2014 to September 2021 at Gyeongsang National University Hospital (GNUH) in Jinju, South Korea were enrolled. Electronic medical records of SFTS patients' demographic features, clinical data, and laboratory data were retrospectively reviewed. Risk factors for fatality were statistically analyzed by classifying enrolled patients into fatal and non-fatal groups. Results: The mean age of patients in the fatal group was significantly higher than that in the non-fatal group (p = 0.036). Hemorrhagic manifestations (p = 0.001) and multiple organ dysfunction (MOD) (p < 0.001) were significantly common in the fatal group. Age, hemorrhagic manifestations, and MOD were also associated with death (p = 0.001, p = 0.008, and p = 0.041, respectively), with adjusted hazard ratios (aHRs) of 1.14, 18.25, and 2.36, respectively. Onset of illness to admission was also significantly associated with death (p = 0.005), with aHR of 0.48. Age, interval from onset of illness to admission, hemorrhagic manifestations, and MOD were found to be variables related to the fatality of SFTS patients. Conclusion: Laboratory test results showed a significant difference between the fatal group and the non-fatal group, but they did not have a statistically significant effect on the prognosis of SFTS patients.


Assuntos
Febre Grave com Síndrome de Trombocitopenia , Trombocitopenia , Animais , Phlebovirus , Prognóstico , Estudos Retrospectivos , Febre Grave com Síndrome de Trombocitopenia/diagnóstico , Febre Grave com Síndrome de Trombocitopenia/patologia , Trombocitopenia/diagnóstico , Trombocitopenia/patologia , República da Coreia
7.
Ann Med ; 54(1): 2951-2965, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36382675

RESUMO

BACKGROUND: Cytopenia is one of the most common adverse events following the CAR-T cell infusion, affecting the quality of life and potentially leading to life-threatening bleeding and infection. This study aimed to systematically review the cytopenias following anti-CD19 CAR-T therapy and further analyse the contributing factors. METHODS: Databases including PubMed, MEDLINE, Embase and Cochrane were systematically searched on 8 May 2022. A random-effect meta-analysis was used to estimate the incidence of cytopenia, and subgroup analyses were applied to explore heterogeneity. RESULTS: A total of 68 studies involving 2950 patients were included in this study. The overall incidence of all grade anaemia, thrombocytopenia, neutropenia, leukopoenia, lymphocytopenia and febrile neutropenia was 65%, 55%, 78%, 62%, 70% and 27%, respectively, and the corresponding cytopenias of grade 3 or worse were 33%, 31%, 61%, 45%, 46%, and 21%, respectively. Subgroup analysis showed increased incidence of cytopenias in subgroups with lower median age, proportion of males (<65%) and proportion of bridging therapy (<80%) and in the subgroup with a median line of prior therapy ≥3. In terms of disease and therapeutic target, cytopenias were more frequent in ALL patients and in dual-target CAR-T therapies (targeting CD19 in combination with other targets). Furthermore, CAR-T products manufactured by lentiviral vectors and those with the costimulatory domain of CD28 were more likely to cause haematological toxicity. No significant differences were observed in cytopenia between patients treated with CAR-T products with murine and humanized scFv. CONCLUSION: In conclusion, neutropenia is the most frequent cytopenia after CAR-T therapy, both in all grades or grade ≥3. The incidence of cytopenias following CAR-T therapy is influenced by the age, sex, disease and number of prior therapy lines of the patients, as well as the target and costimulatory domain of CAR-T cells, and viral vectors used for manufacturing.KEY MESSAGESNeutropenia is the most frequent cytopenia after CAR-T therapy.The clinical characteristics of the patients, the design of CAR-T cells and the protocol of CAR-T treatment can influence the occurrence of cytopenias following the CAR-T therapy.


Assuntos
Anemia , Neutropenia , Receptores de Antígenos Quiméricos , Trombocitopenia , Masculino , Humanos , Camundongos , Animais , Qualidade de Vida , Antígenos CD19/uso terapêutico , Trombocitopenia/epidemiologia , Trombocitopenia/etiologia , Trombocitopenia/terapia , Neutropenia/epidemiologia , Neutropenia/etiologia , Neutropenia/tratamento farmacológico , Terapia Baseada em Transplante de Células e Tecidos
8.
Proc Natl Acad Sci U S A ; 119(48): e2212659119, 2022 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-36409883

RESUMO

Platelets play a role not only in hemostasis and thrombosis, but also in inflammation and innate immunity. We previously reported that an activated form of tyrosyl-tRNA synthetase (YRSACT) has an extratranslational activity that enhances megakaryopoiesis and platelet production in mice. Here, we report that YRSACT mimics inflammatory stress inducing a unique megakaryocyte (MK) population with stem cell (Sca1) and myeloid (F4/80) markers through a mechanism dependent on Toll-like receptor (TLR) activation and type I interferon (IFN-I) signaling. This mimicry of inflammatory stress by YRSACT was studied in mice infected by lymphocytic choriomeningitis virus (LCMV). Using Sca1/EGFP transgenic mice, we demonstrated that IFN-I induced by YRSACT or LCMV infection suppressed normal hematopoiesis while activating an alternative pathway of thrombopoiesis. Platelets of inflammatory origin (Sca1/EGFP+) were a relevant proportion of those circulating during recovery from thrombocytopenia. Analysis of these "inflammatory" MKs and platelets suggested their origin in myeloid/MK-biased hematopoietic stem cells (HSCs) that bypassed the classical MK-erythroid progenitor (MEP) pathway to replenish platelets and promote recovery from thrombocytopenia. Notably, inflammatory platelets displayed enhanced agonist-induced activation and procoagulant activities. Moreover, myeloid/MK-biased progenitors and MKs were mobilized from the bone marrow, as evidenced by their presence in the lung microvasculature within fibrin-containing microthrombi. Our results define the function of YRSACT in platelet generation and contribute to elucidate platelet alterations in number and function during viral infection.


Assuntos
Ataxias Espinocerebelares , Trombocitopenia , Trombose , Tirosina-tRNA Ligase , Viroses , Camundongos , Animais , Trombopoese , Camundongos Transgênicos
9.
Lupus Sci Med ; 9(1)2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36376015

RESUMO

OBJECTIVE: SLE is more prevalent in populations of African (AA) than European ancestry (EA) and leucopenia is common. A homozygous variant in ACKR1 (rs2814778-CC) is associated with lower white cell counts; the variant is common in AA but not EA populations. We hypothesised that in SLE: (1) leucopenia is more frequent in patients of AA than EA, and (2) the ACKR1-CC genotype accounts for the higher frequency of leucopenia in AA patients. METHODS: We performed a retrospective cohort study in patients with SLE at a tertiary care system. Ancestry was defined by genetic principal components. We compared the rate of leucopenia, thrombocytopenia and anaemia between (a) EA and AA patients, and (b) ACKR1-CT/TT and CC genotype in AA patients. RESULTS: The cohort included 574 patients of EA and 190 of AA; ACKR1-CC genotype was common in AA (70%) but not EA (0%) patients. Rates of leucopenia for ancestry and genotype were AA 60.0% vs EA 36.8 % (p=1.9E-08); CC 67.7% vs CT/TT 42.1% (p=9.8E-04). The rate of leucopenia did not differ by ancestry comparing EA patients versus AA with CT/TT genotype (p=0.59). Thrombocytopenia (22.2% vs 13.2%, p=0.004) and anaemia (88.4% vs 66.2%, p=3.7E-09) were more frequent in AA patients but were not associated with ACKR1 genotype (p=0.82 and p=0.84, respectively). CONCLUSIONS: SLE of AA had higher rates of anaemia, leucopenia, and thrombocytopenia than those of EA; only the difference in leucopenia was explained by ACKR1-CC genotype. This genotype could affect clinical practice.


Assuntos
Anemia , Lúpus Eritematoso Sistêmico , Trombocitopenia , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/epidemiologia , Lúpus Eritematoso Sistêmico/genética , Predisposição Genética para Doença , Estudos Retrospectivos , Trombocitopenia/complicações , Trombocitopenia/epidemiologia
10.
Sci Rep ; 12(1): 19975, 2022 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-36404341

RESUMO

Mutations in the MYH9 gene result in macrothrombocytopenia often associated with hemorrhages. Here, we studied the function and structure of platelets in three family members with a heterozygous mutation R1933X in the MYH9 gene, characteristic of closely related disorders known as the May-Hegglin anomaly and Sebastian syndrome. The examination included complete blood count, blood smear microscopy, platelet flow cytometry (expression of P-selectin and active integrin αIIbß3 before and after activation), the kinetics of platelet-driven contraction (retraction) of blood clots, as well as scanning/transmission electron microscopy of platelets. Despite severe thrombocytopenia ranging (36-86) × 109/l, none of the patients had hemorrhages at the time of examination, although they had a history of heavy menstruation, spontaneous ecchymosis, and postpartum hemorrhage. Flow cytometry showed background platelet activation, revealed by overexpression of P-selectin and active αIIbß3 integrin above normal levels. After TRAP-induced stimulation, the fractions of platelets expressing P-selectin in the proband and her sister were below normal response, indicating partial platelet refractoriness. The initiation of clot contraction was delayed. Electron microscopy revealed giant platelets with multiple filopodia and fusion of α-granules with dilated open canalicular system, containing filamentous and vesicular inclusions. The novel concept implies that the R1933X mutation in the MYH9 gene is associated not only with thrombocytopenia, but also with qualitative structural and functional defects in platelets. Platelet dysfunction includes impaired contractility, which can disrupt the compaction of hemostatic clots, making the clots weak and permeable, therefore predisposing patients with MYH9 gene mutations to the hemorrhagic phenotype.


Assuntos
Cadeias Pesadas de Miosina , Trombocitopenia , Feminino , Humanos , Cadeias Pesadas de Miosina/genética , Proteínas Motores Moleculares/genética , Selectina-P/genética , Mutação
11.
Rev Med Liege ; 77(11): 637-643, 2022 Nov.
Artigo em Francês | MEDLINE | ID: mdl-36354224

RESUMO

Platelet transfusion is commonly used for the prevention of bleeding in central thrombocytopenia. It is estimated that 7-34 % of chronically transfused patients become progressively refractory until they no longer have an increase in post-transfusion platelet count. In this case, and in the presence of bleeding, a therapeutic option is continuous transfusion (CT) of platelet concentrates (PC). We performed a retrospective study of patients at the University Hospital of Liege who received a CT between 01/01/2019 and 31/12/2020. We explored the etiology, immune or non-immune, of the refractory state and analyzed the clinical and biological evolution after TC. In our cohort, 13 patients received CT during the study period; for 8 of them, the refractory state was explained by non-immune causes. The mean platelet count increased during CT and in 61 % of cases, an improvement in bleeding symptomatology was obtained.


La transfusion plaquettaire est couramment utilisée pour la prévention des saignements en cas de thrombopénie centrale. On estime que 7 à 34 % des patients transfusés chroniquement deviennent progressivement réfractaires jusqu'à ne plus présenter d'augmentation de la numération plaquettaire post-transfusionnelle. Dans ce cas, et en présence de saignements, une option thérapeutique correspond à la transfusion continue (TC) de concentrés plaquettaires (CP). Nous avons réalisé une étude rétrospective sur les patients du CHU de Liège ayant reçu une TC entre le 01/01/2019 et le 31/12/2020. Nous avons exploré l'étiologie, immune ou non immune, de l'état réfractaire et analysé l'évolution clinique et biologique après TC. Dans notre cohorte, 13 patients ont bénéficié de TC durant la période étudiée; pour 8 d'entre eux, l'état réfractaire s'expliquait par des causes non immunes. La numération plaquettaire moyenne a augmenté durant la TC et, dans 61 % des cas, une amélioration de la symptomatologie hémorragique a été obtenue.


Assuntos
Transfusão de Plaquetas , Trombocitopenia , Humanos , Transfusão de Plaquetas/efeitos adversos , Estudos Retrospectivos , Plaquetas , Trombocitopenia/terapia , Contagem de Plaquetas , Hemorragia/etiologia , Hemorragia/terapia
12.
Medicine (Baltimore) ; 101(44): e31429, 2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36343065

RESUMO

RATIONALE: Lusutrombopag is a thrombopoietin receptor agonist which reduces the need for platelet transfusions before planned invasive procedures. A post hoc analysis of data from the registration trials observed that lusutrombopag-treated patients who achieved a platelet count > 50 × 109/L (responder patients) did so in a median of 6 days and the effect on platelet count lasted for nearly 3 weeks in total. Since patients with cirrhosis often require repeat invasive procedures, this kind of response-time trend sheds light on the possibility of placing more than one invasive procedure within a single course of lusutrombopag treatment. PATIENT CONCERNS: Platelet transfusion represents the gold standard in this setting, but is limited by the risk of adverse events and limited availability. DIAGNOSES: We describe our experience with lusutrombopag in three patients with severe cirrhosis-associated thrombocytopenia who underwent multiple invasive procedures after a single course of treatment. INTERVENTIONS: The treatment schedule is lusutrombopag orally 3 mg/daily for 7 days and then a time window of 6 days (day 9-14) for the elective invasive procedure. OUTCOMES: All three patients achieved good response to lusutrombopag treatment and were able to undergone more invasive procedures in the same course of treatment without need of platelet transfusion. LESSONS: our preliminary experience supports the safety and the effectiveness of lusutrombopag in patients with severe cirrhosis-associated thrombocytopenia who underwent multiple invasive elective procedures after a single course.


Assuntos
Trombocitopenia , Humanos , Trombocitopenia/complicações , Trombocitopenia/tratamento farmacológico , Cinamatos/uso terapêutico , Cirrose Hepática/complicações , Tiazóis/uso terapêutico
13.
Cells ; 11(21)2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36359896

RESUMO

BACKGROUND: Platelets are major players of thrombosis and inflammation after acute myocardial infarction (AMI). The impact of thrombocytopenia on platelet-induced cellular processes post AMI is not well defined. METHODS: The left anterior descending artery was ligated in C57/Bl6 mice and in two thrombocytopenic mouse models to induce AMI. RESULTS: Platelets from STEMI patients and from C57/Bl6 mice displayed enhanced platelet activation after AMI. This allows platelets to migrate into the infarct but not into the remote zone of the left ventricle. Acute thrombocytopenia by antibody-induced platelet depletion resulted in reduced infarct size and improved cardiac function 24 h and 21 days post AMI. This was due to reduced platelet-mediated inflammation after 24 h and reduced scar formation after 21 days post AMI. The collagen composition and interstitial collagen content in the left ventricle were altered due to platelet interaction with cardiac fibroblasts. Acute inflammation was also significantly reduced in Mpl-/- mice with chronic thrombocytopenia, but cardiac remodeling was unaltered. Consequently, left ventricular function, infarct size and scar formation in Mpl-/- mice were comparable to controls. CONCLUSION: This study discovers a novel role for platelets in cardiac remodeling and reveals that acute but not chronic thrombocytopenia protects left ventricular function post AMI.


Assuntos
Infarto do Miocárdio , Trombocitopenia , Disfunção Ventricular Esquerda , Camundongos , Animais , Remodelação Ventricular , Cicatriz/patologia , Infarto do Miocárdio/complicações , Colágeno , Trombocitopenia/complicações , Inflamação
14.
Proc Natl Acad Sci U S A ; 119(47): e2213361119, 2022 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-36322776

RESUMO

Severe COVID-19 is characterized by a prothrombotic state associated with thrombocytopenia, with microvascular thrombosis being almost invariably present in the lung and other organs at postmortem examination. We evaluated the presence of antibodies to platelet factor 4 (PF4)-polyanion complexes using a clinically validated immunoassay in 100 hospitalized patients with COVID-19 with moderate or severe disease (World Health Organization score, 4 to 10), 25 patients with acute COVID-19 visiting the emergency department, and 65 convalescent individuals. Anti-PF4 antibodies were detected in 95 of 100 hospitalized patients with COVID-19 (95.0%) irrespective of prior heparin treatment, with a mean optical density value of 0.871 ± 0.405 SD (range, 0.177 to 2.706). In contrast, patients hospitalized for severe acute respiratory disease unrelated to COVID-19 had markedly lower levels of the antibodies. In a high proportion of patients with COVID-19, levels of all three immunoglobulin (Ig) isotypes tested (IgG, IgM, and IgA) were simultaneously elevated. Antibody levels were higher in male than in female patients and higher in African Americans and Hispanics than in White patients. Anti-PF4 antibody levels were correlated with the maximum disease severity score and with significant reductions in circulating platelet counts during hospitalization. In individuals convalescent from COVID-19, the antibody levels returned to near-normal values. Sera from patients with COVID-19 induced higher levels of platelet activation than did sera from healthy blood donors, but the results were not correlated with the levels of anti-PF4 antibodies. These results demonstrate that the vast majority of patients with severe COVID-19 develop anti-PF4 antibodies, which may play a role in the clinical complications of COVID-19.


Assuntos
COVID-19 , Trombocitopenia , Humanos , Masculino , Feminino , Fator Plaquetário 4 , Heparina , Anticorpos , Fatores Imunológicos , Índice de Gravidade de Doença
15.
Pediatr Infect Dis J ; 41(12): 1012-1016, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36375101

RESUMO

BACKGROUND: Carbapenem-resistant Acinetobacter baumannii (CRAB) sepsis is becoming an extreme threat caused by high-case fatality rates and poor prevention and control in ICUs worldwide. However, the risk of mortality among neonatal CRAB sepsis is still unclear. METHODS: A retrospective medical records review study, which aimed to identify the risk factors of mortality in neonates with CRAB sepsis (including both bacteremia and/or meningitis) in Thailand from 1996 to 2019. All cases featuring positive blood and cerebrospinal fluid cultures for CRAB were reviewed. A multivariable logistic regression model was analyzed for nonsurvivors and survivors of neonatal CRAB sepsis. RESULTS: In a 24-year period, 47 of these were identified with CRAB sepsis. The median (interquartile range) gestational age and birth weight were 30 (28-35) weeks and 1500 (933-2482) g, respectively. The 30-day case fatality rate was 55% (26/47). In multivariable analysis, nonsurvivors of neonatal CRAB sepsis were associated with congenital heart disease (adjusted odds ratio [OR] = 1.33; 95% CI 1.06-1.66, P = 0.02), CRIB II score ≥9 (adjusted OR = 1.65; 95% CI: 1.20-2.27, P = 0.004), severe thrombocytopenia (adjusted OR = 1.45; 95% CI: 1.09-1.94, P = 0.02), and septic shock (adjusted OR = 1.62; 95% CI: 1.33-1.99, P <0.001). CONCLUSION: The risk factors of mortality in neonates with CRAB sepsis are associated with congenital heart disease, CRIB II score ≥9, shock, and severe thrombocytopenia.


Assuntos
Infecções por Acinetobacter , Acinetobacter baumannii , Sepse , Trombocitopenia , Recém-Nascido , Humanos , Carbapenêmicos/farmacologia , Carbapenêmicos/uso terapêutico , Infecções por Acinetobacter/tratamento farmacológico , Estudos Retrospectivos , Sepse/tratamento farmacológico , Fatores de Risco , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Testes de Sensibilidade Microbiana
16.
Zhonghua Yu Fang Yi Xue Za Zhi ; 56(11): 1642-1647, 2022 Nov 06.
Artigo em Chinês | MEDLINE | ID: mdl-36372757

RESUMO

To investigate the correlation between serum cytomegalovirus (CMV) IgM antibody/viral load and infection-related clinical symptoms in neonates infected with CMV, and provide basis for clinical assessment and monitoring of neonatal CMV infection. A total of 70 neonates with CMV infection admitted to neonatology in Women's Hospital, School of Medicine Zhejiang University, from January 2014 to December 2020 were included in this study. Using real-time quantitative PCR as the diagnostic criteria, congenital cytomegalovirus-infected neonates (n=29) was diagnosed within the first 3 weeks of life, otherwise, it was postnatally acquired cytomegalovirus infection (n=41). The differences in general information and clinical indicators between IgM antibody positive and negative patients were analyzed, combined with the PCR result, the correlation between the IgM/viral load and the occurrence of symptoms were analyzed. T-test and non-parametric test were used to compare the differences of indicators between groups, logistic regression was used for multivariate analysis, and ROC curve was used to evaluate the auxiliary diagnostic value of relevant indicators. In the congenital CMV infection group and the postnatally acquired CMV infection group, viral load and the proportion of symptomatic patients in IgM positive group were significantly higher than IgM negative group (Z=-2.616, P=0.008; 80% vs. 21%, P=0.005) (Z=-2.405, P=0.016; 56% vs. 19%, P=0.025). Logistic regression analysis of the included population showed the risk factors of CMV infection-related symptoms were IgM positive (OR 4.562, 95%CI:1.461-14.246,P=0.009) and viral load (OR 1.728, 95%CI:1.068-2.798,P=0.026). Regressive analysis for single symptom with correction showed IgM antibody positive was associated with hearing dysfunction(OR 3.954, 95%CI:1.066-14.677,P=0.040),the CMV viral load was associated with thrombocytopenia (OR 2.228, 95%CI:1.124-4.413,P=0.022), and brain imaging abnormalities (OR 3.956, 95%CI:1.421-11.011, P=0.008). Receiver operating characteristic (ROC) analysis showed the area under ROC curve of CMV viral load for brain imaging abnormalities was 0.883 (P<0.001), with a sensitivity of 75.0% and specificity of 90.3%. For neonates infected with CMV, the risk of infection-related clinical symptoms and hearing dysfunction may be increased when IgM antibody was positive. Meanwhile, the higher the CMV viral load at diagnosis, the higher the risk of thrombocytopenia and abnormal brain imaging.


Assuntos
Infecções por Citomegalovirus , Trombocitopenia , Recém-Nascido , Humanos , Feminino , Citomegalovirus/genética , Imunoglobulina M , Carga Viral , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/diagnóstico , Anticorpos Antivirais , Reação em Cadeia da Polimerase em Tempo Real , Trombocitopenia/complicações , DNA Viral
17.
Rinsho Ketsueki ; 63(10): 1430-1439, 2022.
Artigo em Japonês | MEDLINE | ID: mdl-36351652

RESUMO

The COVID-19 pandemic has cast a shadow over transfusion medicine based on the blood donation system. However, managing alloimmune platelet transfusion refractoriness (allo-PTR) has already been difficult. As a first step toward resolving this issue using induced pluripotent stem cell-derived platelet products (iPSC-PLTs), a clinical trial of autologous products (iPLAT1) was conducted in a patient with allo-PTR caused by anti-HPA-1a antibodies who had no compatible donor, and safety was confirmed. To produce iPSC-PLTs, a master cell bank (MCB) of expandable megakaryocyte lines (imMKCLs) is established from iPSCs. From this MCB, iPSC-PLTs are manufactured using a newly developed turbulent-type bioreactor and various compounds. Their quality, safety, and efficacy are confirmed by extensive preclinical studies. Based on the findings of the iPLAT1 study, a clinical trial of allo-transfusion of HLA homozygous iPSC-PLTs is currently ongoing and HLA class I-deficient O-type universal iPSC-PLTs are also being developed. iPSC-PLTs are expected to solve various problems, including allo-PTR in platelet transfusion, and greatly contribute to the advancement of transfusion medicine.


Assuntos
COVID-19 , Células-Tronco Pluripotentes Induzidas , Trombocitopenia , Humanos , Plaquetas/metabolismo , Pandemias , Transfusão de Plaquetas
18.
Nat Commun ; 13(1): 7169, 2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36418321

RESUMO

Population-based studies can provide important evidence on the safety of COVID-19 vaccines. Here we compare rates of thrombosis and thrombocytopenia following vaccination against SARS-CoV-2 with the background (expected) rates in the general population. In addition, we compare the rates of the same adverse events among persons infected with SARS-CoV-2 with background rates. Primary care and linked hospital data from Catalonia, Spain informed the study, with participants vaccinated with BNT162b2 or ChAdOx1 (27/12/2020-23/06/2021), COVID-19 cases (01/09/2020-23/06/2021) or present in the database as of 01/01/2017. We included 2,021,366 BNT162b2 (1,327,031 with 2 doses), 592,408 ChAdOx1, 174,556 COVID-19 cases, and 4,573,494 background participants. Standardised incidence ratios for venous thromboembolism were 1.18 (95% CI 1.06-1.32) and 0.92 (0.81-1.05) after first- and second dose BNT162b2, and 0.92 (0.71-1.18) after first dose ChAdOx1. The standardised incidence ratio for venous thromboembolism in COVID-19 was 10.19 (9.43-11.02). Standardised incidence ratios for arterial thromboembolism were 1.02 (0.95-1.09) and 1.04 (0.97-1.12) after first- and second dose BNT162b2, 1.06 (0.91-1.23) after first-dose ChAdOx1 and 4.13 (3.83-4.45) for COVID-19. Standardised incidence ratios for thrombocytopenia were 1.49 (1.43-1.54) and 1.40 (1.35-1.45) after first- and second dose BNT162b2, 1.28 (1.19-1.38) after first-dose ChAdOx1 and 4.59 (4.41- 4.77) for COVID-19. While rates of thrombosis with thrombocytopenia were generally similar to background rates, the standardised incidence ratio for pulmonary embolism with thrombocytopenia after first-dose BNT162b2 was 1.70 (1.11-2.61). These findings suggest that the safety profiles of BNT162b2 and ChAdOx1 are similar, with rates of adverse events seen after vaccination typically similar to background rates. Meanwhile, rates of adverse events are much increased for COVID-19 cases further underlining the importance of vaccination.


Assuntos
COVID-19 , Trombocitopenia , Trombose , Tromboembolia Venosa , Humanos , SARS-CoV-2 , Espanha/epidemiologia , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologia , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Vacina BNT162 , Trombocitopenia/epidemiologia , Trombocitopenia/etiologia , Trombose/epidemiologia , Trombose/etiologia , Vacinação/efeitos adversos
19.
Klin Padiatr ; 234(6): 388-390, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36379227

RESUMO

Congenital amegakaryocytic thrombocytopenia (CAMT) is an autosomal recessive disorder characterized by severe thrombocytopenia that presents soon after birth and is usually not accompanied by specific somatic malformations [Germeshausen M, Ballmaier M. Best Pract Res Clin Haematol 2021; 34: 101286]. CAMT is more prevalent in females than males [Ballmaier M, Germeshausen M. Semin Thromb Hemost 2011; 37: 673-681; Germeshausen M, Ballmaier M. Haematologica 2021; 106: 2439-2448], in contrast to other congenital bone marrow failure syndromes. Patients with CAMT also exhibit cardiac malformations, cerebellar hypoplasia, growth retardation, and a distinctive facial appearance [Yldrm A T, Günes B T, Oymak Y, et al. Blood Coagul Fibrinolysis 2015; 26: 337-341], although it remains unknown whether these are related to CAMT. Mutations in the MPL gene, which encodes the thrombopoietin receptor, are the pathogenetic cause of CAMT [Germeshausen M, Ballmaier M. Haematologica 2021; 106: 2439-2448]. Since thrombopoietin is involved in the maintenance of hematopoietic stem cells and megakaryocyte development [Germeshausen M, Ballmaier M. Best Pract Res Clin Haematol 2021; 34: 101286], CAMT may eventually manifest as a hematopoietic failure. Currently, allogeneic hematopoietic stem cell transplantation (HSCT) is the only cure for CAMT. Human leukocyte antigen (HLA)-matched siblings are the first-choice donors for HSCT because transplantations from matched unrelated donors have a low success rate [King S, Germeshausen M, Strauss G, et al. Br J Haematol 2005; 131: 636-644]. Cancio et al. [Cancio M, Hebert K, Kim S, et al. Transplant Cell Ther 2022; 28: 101 e101-101 e106] reviewed 86 patients treated over 18 years and reported that although HLA-mismatched donors can extend the survival of CAMT patients, HLA-matched donors are preferred. The present report describes the successful treatment of a 3-year-old girl with CAMT using haploidentical allogeneic HSCT from the father, even though he harbored a mutant MPL gene.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Trombocitopenia , Masculino , Feminino , Humanos , Pré-Escolar , Síndrome Congênita de Insuficiência da Medula Óssea , Megacariócitos/patologia , Trombocitopenia/diagnóstico , Trombocitopenia/genética , Trombocitopenia/terapia
20.
Orphanet J Rare Dis ; 17(1): 401, 2022 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-36329499

RESUMO

BACKGROUND: Gaucher disease (GD) is an autosomal recessive disease caused by GBA1 mutations resulting in glucosylceramide accumulation in macrophages. GD is characterized by hepatosplenomegaly, anemia, thrombocytopenia, bone complications, and neurological complications. Glucosylsphingosine (lyso-Gb1), a deacylated form of glucosylceramide, has been identified as a promising biomarker for the diagnosis and treatment response in GD. The aim of this study was to examine the relationship between plasma lyso-Gb1 and therapeutic goals for GD (improvements in hepatomegaly, splenomegaly, anemia, thrombocytopenia, bone pain, and bone crisis), as well as disease type and GBA1 mutation type, in Japanese patients with GD receiving velaglucerase alfa, an enzyme replacement therapy (ERT). Furthermore, this study compared the plasma lyso-Gb1 concentration observed in Japanese patients included in this study with that observed in a previous non-Japanese clinical study. RESULTS: This non-interventional, open-label, multicenter observational cohort study (October 2020 to March 2021) included a total of 20 patients (of any age) with GD (type 1: n = 8; type 2: n = 9; type 3: n = 3) treated with velaglucerase alfa for ≥ 3 months. Median (minimum-maximum) duration of velaglucerase alfa treatment was 49.5 (3-107) months. A total of 14 (70.0%) patients achieved all therapeutic goals (i.e., 100% achievement; improvements in hepatomegaly, splenomegaly, anemia, thrombocytopenia, bone pain, and bone crisis). Overall, median (minimum-maximum) lyso-Gb1 concentration was 24.3 (2.1-150) ng/mL. Although not statistically significant, numerically lower plasma lyso-Gb1 concentrations were observed in patients with 100% achievement compared with those without; no statistically significant difference in plasma lyso-Gb1 concentration was observed between patients with different disease type or mutation type. Furthermore, lyso-Gb1 concentrations observed in Japanese patients were numerically lower than that observed in a previous study of non-Japanese patients with GD receiving ERT. CONCLUSIONS: In this study, high achievement rates of therapeutic goals with low lyso-Gb1 concentration were observed, demonstrating a correlation between therapeutic goals and lower plasma lyso-Gb1 concentration in Japanese patients with GD treated with velaglucerase alfa. This study further suggests that plasma lyso-Gb1 concentration may be a useful biomarker for treatment response in patients with GD.


Assuntos
Doença de Gaucher , Trombocitopenia , Humanos , Doença de Gaucher/diagnóstico , Glucosilceramidas/uso terapêutico , Esplenomegalia/induzido quimicamente , Esplenomegalia/tratamento farmacológico , Hepatomegalia/induzido quimicamente , Hepatomegalia/tratamento farmacológico , Glucosilceramidase/genética , Terapia de Reposição de Enzimas/métodos , Resultado do Tratamento , Biomarcadores , Trombocitopenia/induzido quimicamente , Trombocitopenia/tratamento farmacológico , Dor/tratamento farmacológico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...