Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 3.552
Filtrar
1.
Anticancer Res ; 41(11): 5729-5737, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34732446

RESUMO

BACKGROUND/AIM: This study aimed to identify the predictive markers for carboplatin-induced severe thrombocytopenia. PATIENTS AND METHODS: We conducted a retrospective cohort analysis of inpatients who received carboplatin and pemetrexed. RESULTS: Among the 106 eligible patients, the incidence rate of grade ≥3 thrombocytopenia was 29.2% (31/106). Multivariate analysis revealed that grade ≥3 thrombocytopenia was associated with platelet count ≤26.6×104/mm3 [odds ratio (OR)=24.70, 95% confidence interval (CI)=5.75-106.00; p<0.001], neutrophil/lymphocyte ratio (NLR) >2.856 (OR=15.10, 95%CI=2.89-78.60; p=0.0013) and prognostic nutritional index ≤42.511 (OR=6.25, 95%CI=1.53-25.60; p=0.011). In particular, patients with both platelet counts ≤26.6×104/mm3 and NLR >2.856 presented with significantly higher frequencies of thrombocytopenia compared to those without these two factors [23/34 patients (67.6%) vs. 8/72 patients (11.1%), OR=16.1, 95%CI=5.40-53.6; p<0.001]. CONCLUSION: Platelet counts ≤26.6×104/mm3 and NLR >2.856 are predictive markers for carboplatin-induced thrombocytopenia.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Plaquetas/efeitos dos fármacos , Carboplatina/efeitos adversos , Linfócitos , Neoplasias/tratamento farmacológico , Neutrófilos , Pemetrexede/efeitos adversos , Trombocitopenia/induzido quimicamente , Idoso , Feminino , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Neoplasias/sangue , Contagem de Plaquetas , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Trombocitopenia/sangue , Trombocitopenia/diagnóstico , Fatores de Tempo
2.
Clin Appl Thromb Hemost ; 27: 10760296211040110, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34541935

RESUMO

Since the outbreak of Covid-19 in December, 2019, scientists worldwide have been committed to developing COVID-19 vaccines. Only when most people have immunity to SARS-CoV-2, COVID-19 can reduce even wholly overcome. So far, nine kinds of COVID-19 vaccines have passed the phase III clinical trials and have approved for use. At the same time, adverse reactions after COVID-19 vaccination have also reported. This paper focuses on the adverse effects of thrombosis and thrombocytopenia caused by the COVID-19 vaccine, especially the adenovirus-vector vaccine from AstraZeneca and Pfizer, and discusses its mechanism and possible countermeasures.


Assuntos
Adenoviridae/genética , Vacinas contra COVID-19/efeitos adversos , Vetores Genéticos , Trombocitopenia/induzido quimicamente , Trombose/induzido quimicamente , Vacinação/efeitos adversos , Anticorpos/sangue , Vacinas contra COVID-19/genética , Vacinas contra COVID-19/imunologia , Humanos , Fator Plaquetário 4/imunologia , Medição de Risco , Fatores de Risco , Trombocitopenia/sangue , Trombocitopenia/imunologia , Trombose/sangue , Trombose/imunologia
3.
Ann Hematol ; 100(11): 2677-2682, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34519886

RESUMO

Immune thrombocytopenia (ITP) is an acquired bleeding disorder, for which no specific diagnostic test exists. Inherited thrombocytopenia (IT) can mimic ITP and lead to unappropriated management with significant morbidity. Here, in small cohorts of these two disorders, we explored whether platelet sialylation and platelet activation could allow to discriminate the two conditions. We also aimed to confirm the value of immature platelet counts in this discrimination. Platelet sialylation and the expression level of P-selectin were assessed by multiparameter flow cytometry. Immature platelets were estimated on a Sysmex XN 9000 analyzer. No significant difference in platelet sialylation was observed between ITP and IT. Contrarily, platelet activation was significantly higher in ITP patients (p = 0.008). The immature platelet fraction, as previously demonstrated, was significantly lower in the ITP group compared to the IT group (p = 0.014). That statistical significance was achieved in this small pilot study suggests that the two easily available assays of immature platelet count and P-selectin expression could help physicians to reach the proper diagnosis in complex cases of thrombocytopenia.


Assuntos
Plaquetas/química , Ativação Plaquetária , Ácidos Siálicos/sangue , Trombocitopenia/sangue , Adulto , Idoso , Área Sob a Curva , Síndrome de Bernard-Soulier/sangue , Síndrome de Bernard-Soulier/diagnóstico , Síndrome de Bernard-Soulier/genética , Senescência Celular , Diagnóstico Diferencial , Feminino , Citometria de Fluxo/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Selectina-P/sangue , Projetos Piloto , Contagem de Plaquetas , Púrpura Trombocitopênica Idiopática/sangue , Púrpura Trombocitopênica Idiopática/diagnóstico , Curva ROC , Sensibilidade e Especificidade , Trombocitopenia/diagnóstico , Trombocitopenia/genética
4.
Int J Mol Sci ; 22(17)2021 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-34502272

RESUMO

The actin cytoskeleton plays a central role in platelet formation and function. Alpha-actinins (actinins) are actin filament crosslinking proteins that are prominently expressed in platelets and have been studied in relation to their role in platelet activation since the 1970s. However, within the past decade, several groups have described mutations in ACTN1/actinin-1 that cause congenital macrothrombocytopenia (CMTP)-accounting for approximately 5% of all cases of this condition. These findings are suggestive of potentially novel functions for actinins in platelet formation from megakaryocytes in the bone marrow and/or platelet maturation in circulation. Here, we review some recent insights into the well-known functions of actinins in platelet activation before considering possible roles for actinins in platelet formation that could explain their association with CMTP. We describe what is known about the consequences of CMTP-linked mutations on actinin-1 function at a molecular and cellular level and speculate how these changes might lead to the alterations in platelet count and morphology observed in CMTP patients. Finally, we outline some unanswered questions in this area and how they might be addressed in future studies.


Assuntos
Actinina/metabolismo , Plaquetas/fisiologia , Trombocitopenia/etiologia , Actinina/genética , Humanos , Integrinas , Megacariócitos/patologia , Megacariócitos/fisiologia , Mutação , Adesividade Plaquetária , Trombocitopenia/sangue
6.
Andes Pediatr ; 92(3): 382-388, 2021 Jun.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-34479244

RESUMO

INTRODUCTION: The multisystem inflammatory syndrome in children associated with SARS-CoV-2 (MIS-C) is cha racterized by a hyperinflammatory state resulting from a cytokine storm, evidenced by alterations in laboratory blood testing and acute-phase proteins. OBJECTIVE: to describe the clinical and labora tory characteristics of patients hospitalized due to MIS-C and identify predictive markers of severity. PATIENTS AND METHOD: Retrospective study of 32 patients. The group was divided into critical and non-critical according to clinical presentation and therapy used. Clinical and laboratory aspects were studied, including complete blood count, coagulation tests, and biomarkers. RESULTS: 18/32 were males, with a median age of 6.8 years. The most frequent manifestations were cardiovascular (84.3%), digestive (84%), and mucocutaneous (59%). The group of critical patients included 15 patients, 12 were males with a median age of 8.9 years, and the non-critical group included 17 patients, 6 were males with a median age of 5.4 years. The laboratory parameters at the admission in the global group showed increased C-reactive protein, D-dimer, leukocytes, neutrophils, ferritin, and fibrinogen. In contrast, albumin and blood sodium levels were decreased. At admission, the critical group was cha racterized by presenting thrombocytopenia, hypoalbuminemia, prolonged prothrombin time, and elevated ferritin. At the time of deterioration, there was an intensification of thrombocytopenia, in creased C-reactive protein together with increased neutrophils level. CONCLUSION: The blood count, C-reactive protein, and albuminemia at admission proved to be significantly important in the identi fication of patients at risk of clinical deterioration.


Assuntos
COVID-19/complicações , SARS-CoV-2 , Índice de Gravidade de Doença , Síndrome de Resposta Inflamatória Sistêmica/complicações , Biomarcadores/sangue , Proteína C-Reativa/análise , COVID-19/classificação , Criança , Deterioração Clínica , Estado Terminal , Feminino , Ferritinas/sangue , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Fibrinogênio/análise , Humanos , Leucócitos , Masculino , Neutrófilos , Estudos Retrospectivos , Síndrome de Resposta Inflamatória Sistêmica/classificação , Trombocitopenia/sangue
7.
Blood Coagul Fibrinolysis ; 32(7): 480-490, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34475331

RESUMO

Inherited thrombocytopenia is a heterogeneous group of hereditary disorders with varying bleeding tendencies, not simply related to platelet count. Platelets transform into different subpopulations upon stimulation, including procoagulant platelets and platelet microparticles (PMPs), which are considered critical for haemostasis. We aimed to investigate whether abnormalities in PMP and procoagulant platelet function were associated with the bleeding phenotype of inherited thrombocytopenia patients. We enrolled 53 inherited thrombocytopenia patients. High-throughput sequencing of 36 inherited thrombocytopenia related genes was performed in all patients and enabled a molecular diagnosis in 57%. Bleeding phenotype was evaluated using the ISTH bleeding assessment tool, dividing patients into bleeding (n = 27) vs. nonbleeding (n = 26). Unstimulated and ADP, TRAP or collagen-stimulated PMP and procoagulant platelet functions were analysed by flow cytometry using antibodies against granulophysin (CD63), P-selectin (CD62P), activated GPIIb/IIIa (PAC-1) and a marker for phosphatidylserine expression (lactadherin). Procoagulant platelets were measured in response to collagen stimulation. An in-house healthy reference level was available. Overall, higher levels of activated platelets, PMPs and procoagulant platelets were found in nonbleeding patients compared with the reference level. Nonbleeding patients had higher proportions of phosphatidylserine and PMPs compared with bleeding patients and the reference level, in response to different stimulations. Interestingly, this finding of high proportions of phosphatidylserine and PMPs was limited to PMPs, and not present in procoagulant platelets or platelets. Our findings indicate that nonbleeding inherited thrombocytopenia patients have compensatory mechanisms for improved platelet subpopulation activation and function, and that generation of phosphatidylserine expressing PMPs could be a factor determining bleeding phenotype in inherited thrombocytopenia.


Assuntos
Micropartículas Derivadas de Células/metabolismo , Hemorragia/metabolismo , Fosfatidilserinas/metabolismo , Trombocitopenia/metabolismo , Adulto , Idoso , Coagulação Sanguínea , Plaquetas/citologia , Plaquetas/metabolismo , Feminino , Hemorragia/sangue , Hemorragia/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Fosfatidilserinas/sangue , Ativação Plaquetária , Trombocitopenia/sangue , Trombocitopenia/complicações , Adulto Jovem
8.
JAMA Neurol ; 78(11): 1314-1323, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34581763

RESUMO

Importance: Thrombosis with thrombocytopenia syndrome (TTS) has been reported after vaccination with the SARS-CoV-2 vaccines ChAdOx1 nCov-19 (Oxford-AstraZeneca) and Ad26.COV2.S (Janssen/Johnson & Johnson). Objective: To describe the clinical characteristics and outcome of patients with cerebral venous sinus thrombosis (CVST) after SARS-CoV-2 vaccination with and without TTS. Design, Setting, and Participants: This cohort study used data from an international registry of consecutive patients with CVST within 28 days of SARS-CoV-2 vaccination included between March 29 and June 18, 2021, from 81 hospitals in 19 countries. For reference, data from patients with CVST between 2015 and 2018 were derived from an existing international registry. Clinical characteristics and mortality rate were described for adults with (1) CVST in the setting of SARS-CoV-2 vaccine-induced immune thrombotic thrombocytopenia, (2) CVST after SARS-CoV-2 vaccination not fulling criteria for TTS, and (3) CVST unrelated to SARS-CoV-2 vaccination. Exposures: Patients were classified as having TTS if they had new-onset thrombocytopenia without recent exposure to heparin, in accordance with the Brighton Collaboration interim criteria. Main Outcomes and Measures: Clinical characteristics and mortality rate. Results: Of 116 patients with postvaccination CVST, 78 (67.2%) had TTS, of whom 76 had been vaccinated with ChAdOx1 nCov-19; 38 (32.8%) had no indication of TTS. The control group included 207 patients with CVST before the COVID-19 pandemic. A total of 63 of 78 (81%), 30 of 38 (79%), and 145 of 207 (70.0%) patients, respectively, were female, and the mean (SD) age was 45 (14), 55 (20), and 42 (16) years, respectively. Concomitant thromboembolism occurred in 25 of 70 patients (36%) in the TTS group, 2 of 35 (6%) in the no TTS group, and 10 of 206 (4.9%) in the control group, and in-hospital mortality rates were 47% (36 of 76; 95% CI, 37-58), 5% (2 of 37; 95% CI, 1-18), and 3.9% (8 of 207; 95% CI, 2.0-7.4), respectively. The mortality rate was 61% (14 of 23) among patients in the TTS group diagnosed before the condition garnered attention in the scientific community and 42% (22 of 53) among patients diagnosed later. Conclusions and Relevance: In this cohort study of patients with CVST, a distinct clinical profile and high mortality rate was observed in patients meeting criteria for TTS after SARS-CoV-2 vaccination.


Assuntos
Vacinas contra COVID-19/uso terapêutico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/mortalidade , Sistema de Registros , Trombose dos Seios Intracranianos/mortalidade , Trombocitopenia/mortalidade , Tromboembolia Venosa/mortalidade , Adulto , Idoso , Vacinas contra COVID-19/efeitos adversos , Estudos de Coortes , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Fatores Sexuais , Trombose dos Seios Intracranianos/sangue , Trombose dos Seios Intracranianos/induzido quimicamente , Síndrome , Trombocitopenia/sangue , Trombocitopenia/induzido quimicamente , Tromboembolia Venosa/sangue , Tromboembolia Venosa/induzido quimicamente , Adulto Jovem
9.
Am J Cardiol ; 157: 85-92, 2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-34404506

RESUMO

The pathophysiology of thrombocytopenia after transcatheter aortic valve implantation (TAVI) thrombocytopenia is still poorly understood. We assessed the association of spleen size with acquired thrombocytopenia in patients undergoing TAVI. We included 732 patients who underwent TAVI with new generation transcatheter heart valves (THVs) at our center from February 2016 to July 2019. We measured splenic volume index in consecutive patients derived from multidetector row computed tomographic datasets. Patients were stratified according to post-TAVI thrombocytopenia, which was defined as a decline in platelet count (DPC) ≥50% at nadir, and evaluated regarding baseline characteristics and outcome parameters. After the procedure, platelet counts declined from 212.9 ± 67.4 × 109/L at baseline to 138.8 ± 49.8 × 109/L at nadir after a median of 2 days (interquartile range [IQR] 2 to 3). Of all patients, 10.1% showed a DPC ≥50%. Compared with patients with DPC <50%, patients with DPC ≥50% had significantly lower splenic volume index (95.5 ml/m2 [IQR 78.0 to 123.7] vs 85.8 ml/m2 [IQR 71.4 to 102.6], p = 0.008). A multivariable analysis revealed that the splenic volume index was negatively associated with a DPC ≥50% (OR 0.89, 95% CI 0.82 to 0.97, p = 0.005), independent of the type of THV (balloon-expandable THV: OR 2.06, 95% CI 1.13 to 3.76, p = 0.02), major bleeding (OR 13.40, 95% CI 3.58 to 50.40, p <0.001), blood transfusion (OR 3.63, 95% CI 1.54 to 8.56, p = 0.003), or postprocedural paravalvular leakage ≥moderate (OR 5.48, 95% CI 1.23 to 24.40, p = 0.03). Furthermore, DPC ≥50% was independently associated with 1-year mortality (HR 3.36, 95% CI 1.66 to 6.81, p <0.001). In conclusion, acquired thrombocytopenia remains prevalent in modern TAVI patients. Spleen size appears to be associated with the occurrence of thrombocytopenia after TAVI, which is independently correlated with 1-year mortality.


Assuntos
Estenose da Valva Aórtica/cirurgia , Sistema de Registros , Baço/diagnóstico por imagem , Trombocitopenia/etiologia , Substituição da Valva Aórtica Transcateter/efeitos adversos , Idoso de 80 Anos ou mais , Valva Aórtica/cirurgia , Estudos Transversais , Feminino , Seguimentos , Alemanha/epidemiologia , Humanos , Incidência , Masculino , Tomografia Computadorizada Multidetectores , Contagem de Plaquetas , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Trombocitopenia/sangue , Trombocitopenia/epidemiologia
10.
Blood Coagul Fibrinolysis ; 32(5): 305-311, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34231501

RESUMO

Treatment of venous thromboembolism with concomitant thrombocytopenia is challenging. The platelet threshold for safe administration of anticoagulants is under debate, with minimum platelet count of 50 × 109/l being recommended as the safe cutoff. However, some evidence suggests administration of anticoagulants may still be safe at platelet levels of 30 × 109/l. Therefore, we developed an in-vitro thromboelastography (TEG) study to examine the effect of therapeutic or prophylactic levels of unfractionated heparin (UFH) and low molecular weight heparin (LMWH) on the clotting profile of platelet-reduced whole blood. Using magnetic bead-based antibody chromatography, platelets were removed to achieve platelet-depleted blood (<10 × 109/l of platelets). Platelet-depleted blood was then mixed with whole blood to produce blood samples with platelet counts of 30 × 109, 50 × 109 and 150 × 109/l. These blood samples were incubated with therapeutic or prophylactic levels of UFH or LMWH in disposable TEG cups. Clotting was initiated with 10 mmol/l calcium and optimized tissue factor levels for each anticoagulant used (2.25 pmol/l for UFH and 2.05 pmol/l for LMWH). Clotting was monitored by TEG at 37 °C for 180 min. The following TEG parameters were evaluated: R (time to clot), maximum amplitude (strength of clot) and area under the curve in 15 min (overall speed and strength of the clot at 15 min of clotting). No statistically significant differences were observed between platelet counts of 30 × 109 and 50 × 109/l for R, maximum amplitude or area under the curve in 15 min for most of the therapeutic and prophylactic doses of UFH and LMWH tested in this study. Use of anticoagulants compromised all of the TEG parameters relative to a normal platelet count of 150 × 109/l, in a dose dependent manner. The current study demonstrates that in-vitro clotting is impaired with use and increasing doses of anticoagulants. Despite this observation, we did not observe a significant difference in clotting between platelet levels of 30 × 109 and 50 × 109/l. Overall, this work provides further insight in the debated use of anticoagulants in patients with venous thromboembolism and concomitant thrombocytopenia, and provides support for possible use of anticoagulants at lower platelet thresholds.


Assuntos
Anticoagulantes/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Plaquetas , Heparina de Baixo Peso Molecular/farmacologia , Heparina/farmacologia , Plaquetas/efeitos dos fármacos , Humanos , Contagem de Plaquetas , Tromboelastografia , Trombocitopenia/sangue , Tromboembolia Venosa/sangue
11.
PLoS One ; 16(7): e0255413, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34329360

RESUMO

BACKGROUND: During hematopoietic stem cell transplantation (HSCT) the patients perform activities of low and moderate intensity because have reduced hematological lineages, leaving them susceptible to hemorrhagic events. The objective of this study was to describe the frequency of bleeding events, severity, and possible association with physical exercise in thrombocytopenic patients. METHODS: A retrospective study with seventy-seven HSCT patients hospitalised, that had a platelet count ≤ 50,000 /µL and received physical exercise during physiotherapy intervention. RESULTS: Regarding bleeding events, only six were related to physical exercise, and bleeding events occurred more frequently at platelet levels ≤ 10,000 /µL. The most frequent bleeding event was epistaxis, considered of low severity, and with the moderate possibility of being related to physical exercise; followed by extremity hematoma, considered of medium severity and highly related to physical exercise. In this study, there was no occurrence of bleeding events considered of high severity. CONCLUSION: Bleeding frequency in supervised physical exercise during physiotherapy in adults with thrombocytopenia undergoing HSCT is minor and relatively rare but occurs more frequently in patients with platelet count ≤10,000 /µL. These results encourage the maintenance of physical activity in this population who is at high risk of developing immobility-related complications.


Assuntos
Terapia por Exercício , Transplante de Células-Tronco Hematopoéticas , Hemorragia , Adulto , Idoso , Aloenxertos , Feminino , Hemorragia/sangue , Hemorragia/etiologia , Hemorragia/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Estudos Retrospectivos , Trombocitopenia/sangue , Trombocitopenia/terapia
12.
N Engl J Med ; 385(8): 720-728, 2021 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-34107198

RESUMO

The use of high-dose intravenous immune globulin (IVIG) plus anticoagulation is recommended for the treatment of vaccine-induced immune thrombotic thrombocytopenia (VITT), a rare side effect of adenoviral vector vaccines against coronavirus disease 2019 (Covid-19). We describe the response to IVIG therapy in three of the first patients in whom VITT was identified in Canada after the receipt of the ChAdOx1 nCoV-19 vaccine. The patients were between the ages of 63 and 72 years; one was female. At the time of this report, Canada had restricted the use of the ChAdOx1 nCoV-19 vaccine to persons who were 55 years of age or older on the basis of reports that VITT had occurred primarily in younger persons. Two of the patients in our study presented with limb-artery thrombosis; the third had cerebral venous and arterial thrombosis. Variable patterns of serum-induced platelet activation were observed in response to heparin and platelet factor 4 (PF4), indicating the heterogeneity of the manifestations of VITT in serum. After the initiation of IVIG, reduced antibody-induced platelet activation in serum was seen in all three patients. (Funded by the Canadian Institutes of Health Research.).


Assuntos
Vacinas contra COVID-19/efeitos adversos , Imunoglobulinas Intravenosas , Trombocitopenia/terapia , Trombose/terapia , Idoso , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Fibrinogênio/análise , Heparina/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Fator Plaquetário 4/farmacologia , Serotonina/sangue , Trombocitopenia/sangue , Trombocitopenia/etiologia , Trombose/etiologia , Trombose/imunologia
13.
PLoS One ; 16(6): e0252939, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34153056

RESUMO

BACKGROUND: Coagulopathy and thromboembolic events are among the complications of Corona Virus disease 2019 (COVID-19). Abnormal coagulation parameters in COVID-19 patients are important prognostic factors of disease severity. The aim of this study was to analyze coagulation profiles of hospitalized COVID-19 patients in Addis Ababa, Ethiopia. METHODS: This prospective cross-sectional study was conducted among 455 Covid-19 patients admitted at Millennium COVID-19 care and treatment center, Addis Ababa, Ethiopia from July 1- October 23, 2020. Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT) and International normalized ratio (INR) were determined on HUMACLOT DUE PLUS® coagulation analyzer (Wiesbaden, Germany). In all statistical analysis of results, p<0.05 was defined as statistically significant. RESULT: A prolonged prothrombin time was found in 46.8% of study participants with COVID-19 and a prolonged prothrombin time and elevated INR in 53.3% of study subjects with severe and 51% of critically COVID patients. Thrombocytopenia was detected in 22.1% of COVID-19 patients. 50.5% and 51.3% of COVID-19 patients older than 55 years had thrombocytopenia and prolonged APTT respectively. CONCLUSION: In this study, prolonged prothrombin time and elevated INR were detected in more than 50% of severe and critical COVID-19 patients. Thrombocytopenia and prolonged APTT were dominant in COVID-19 patients older than 55 years. Thus, we recommend emphasis to be given for monitoring of platelet count, PT, APTT and INR in hospitalized and admitted COVID-19 patients.


Assuntos
COVID-19/diagnóstico , Índice de Gravidade de Doença , Trombocitopenia/epidemiologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , COVID-19/sangue , COVID-19/complicações , COVID-19/mortalidade , Criança , Pré-Escolar , Estado Terminal , Estudos Transversais , Etiópia/epidemiologia , Hospitalização , Humanos , Coeficiente Internacional Normatizado , Pessoa de Meia-Idade , Tempo de Tromboplastina Parcial , Contagem de Plaquetas , Prognóstico , Estudos Prospectivos , Tempo de Protrombina , Fatores de Risco , SARS-CoV-2/isolamento & purificação , Fatores Sexuais , Trombocitopenia/sangue , Trombocitopenia/diagnóstico , Trombocitopenia/etiologia , Adulto Jovem
15.
Elife ; 102021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34059198

RESUMO

Thrombocytopenic disorders have been treated with the Thrombopoietin-receptor agonist Eltrombopag. Patients with the same apparent form of thrombocytopenia may respond differently to the treatment. We describe a miniaturized bone marrow tissue model that provides a screening bioreactor for personalized, pre-treatment response prediction to Eltrombopag for individual patients. Using silk fibroin, a 3D bone marrow niche was developed that reproduces platelet biogenesis. Hematopoietic progenitors were isolated from a small amount of peripheral blood of patients with mutations in ANKRD26 and MYH9 genes, who had previously received Eltrombopag. The ex vivo response was strongly correlated with the in vivo platelet response. Induced Pluripotent Stem Cells (iPSCs) from one patient with mutated MYH9 differentiated into functional megakaryocytes that responded to Eltrombopag. Combining patient-derived cells and iPSCs with the 3D bone marrow model technology allows having a reproducible system for studying drug mechanisms and for individualized, pre-treatment selection of effective therapy in Inherited Thrombocytopenias.


Assuntos
Benzoatos/farmacologia , Plaquetas/efeitos dos fármacos , Células-Tronco Hematopoéticas/efeitos dos fármacos , Hidrazinas/farmacologia , Células-Tronco Pluripotentes Induzidas/efeitos dos fármacos , Megacariócitos/efeitos dos fármacos , Pirazóis/farmacologia , Receptores de Trombopoetina/agonistas , Nicho de Células-Tronco , Trombocitopenia/tratamento farmacológico , Trombopoese/efeitos dos fármacos , Adulto , Idoso , Reatores Biológicos , Plaquetas/metabolismo , Técnicas de Cultura de Células , Células Cultivadas , Feminino , Fibroínas/metabolismo , Células-Tronco Hematopoéticas/metabolismo , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/genética , Masculino , Megacariócitos/metabolismo , Pessoa de Meia-Idade , Miniaturização , Mutação , Cadeias Pesadas de Miosina/genética , Receptores de Trombopoetina/metabolismo , Trombocitopenia/sangue , Trombocitopenia/genética , Adulto Jovem
16.
BMC Infect Dis ; 21(1): 507, 2021 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-34059017

RESUMO

BACKGROUND: Hematological abnormalities are common features in falciparum malaria but vary among different populations across countries. Therefore, we compared hematological indices and abnormalities between Plasmodium falciparum-infected patients and malaria-negative subjects in Kosti city of the White Nile State, Sudan. METHODS: A comparative, cross-sectional study was conducted at the Clinical Laboratory Unit of Kosti Teaching Hospital from June to December 2018. A total of 392 participants (192 P. falciparum-infected patients and 200 malaria-negative subjects) were recruited in the study. Hematological indices of hemoglobin (Hb), red blood cells (RBCs), white blood cells (WBCs) and platelets were measured, and their median values were statistically compared. RESULTS: The majority of P. falciparum-infected patients (67.6%) showed a low-level parasitemia. The median values of Hb concentration, RBC count, mean corpuscular volume (MCV), mean corpuscular Hb (MCH) and mean corpuscular Hb concentration (MCHC) were significantly lower in P. falciparum-infected patients, while the median red cell distribution width (RDW) was significantly higher in the patients compared to malaria-negative subjects. Anemia, low MCV, low MCH, low MCHC and high RDW were significantly associated with falciparum malaria, but parasitemia level was not significantly associated with anemia severity. The median total WBC count was non-significantly higher in P. falciparum-infected patients, with neutropenia being significantly associated with falciparum malaria. The median platelet count was significantly lower in P. falciparum-infected patients, with thrombocytopenia being significantly associated with falciparum malaria. CONCLUSIONS: Falciparum malaria among patients in Kosti city of the White Nile State, Sudan is predominantly of low-level parasitemia. It is significantly associated with anemia, low MCV, low MCH, low MCHC, high RDW, thrombocytopenia and neutropenia. However, parasitemia level is not a significant predictor of anemia severity. On the other hand, leucopenia is not useful to predict falciparum malaria. Further large-scale studies in community and healthcare settings and inclusion of patients with complicated or severe malaria and those with high parasite densities are recommended.


Assuntos
Malária Falciparum/sangue , Adolescente , Adulto , Anemia/sangue , Anemia/parasitologia , Criança , Pré-Escolar , Estudos Transversais , Feminino , Testes Hematológicos , Humanos , Lactente , Leucopenia/sangue , Leucopenia/parasitologia , Malária Falciparum/parasitologia , Masculino , Pessoa de Meia-Idade , Parasitemia/sangue , Parasitemia/parasitologia , Plasmodium falciparum , Trombocitopenia/sangue , Trombocitopenia/parasitologia , Adulto Jovem
17.
Front Immunol ; 12: 616394, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33995345

RESUMO

In tropical and subtropical regions, mosquito-borne dengue virus (DENV) infections can lead to severe dengue, also known as dengue hemorrhage fever, which causes bleeding, thrombocytopenia, and blood plasma leakage and increases mortality. Although DENV-induced platelet cell death was linked to disease severity, the role of responsible viral factors and the elicitation mechanism of abnormal platelet activation and cell death remain unclear. DENV and virion-surface envelope protein domain III (EIII), a cellular binding moiety of the virus particle, highly increase during the viremia stage. Our previous report suggested that exposure to such viremia EIII levels can lead to cell death of endothelial cells, neutrophils, and megakaryocytes. Here we found that both DENV and EIII could induce abnormal platelet activation and predominantly necrotic cell death pyroptosis. Blockages of EIII-induced platelet signaling using the competitive inhibitor chondroitin sulfate B or selective Nlrp3 inflammasome inhibitors OLT1177 and Z-WHED-FMK markedly ameliorated DENV- and EIII-induced thrombocytopenia, platelet activation, and cell death. These results suggest that EIII could be considered as a virulence factor of DENV, and that Nlrp3 inflammasome is a feasible target for developing therapeutic approaches against dengue-induced platelet defects.


Assuntos
Plaquetas/metabolismo , Vírus da Dengue/fisiologia , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Dengue Grave/complicações , Trombocitopenia/etiologia , Trombocitopenia/metabolismo , Animais , Biomarcadores , Coagulação Sanguínea , Testes de Coagulação Sanguínea , Plaquetas/imunologia , Morte Celular , Modelos Animais de Doenças , Suscetibilidade a Doenças , Metabolismo Energético , Imunofenotipagem , Camundongos , Camundongos Knockout , Mitocôndrias/metabolismo , Ativação Plaquetária , Domínios e Motivos de Interação entre Proteínas/imunologia , Dengue Grave/virologia , Trombocitopenia/sangue , Trombocitopenia/diagnóstico , Proteínas do Envelope Viral/química , Proteínas do Envelope Viral/metabolismo
18.
J Med Virol ; 93(9): 5474-5480, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33963559

RESUMO

In this study, laboratorial parameters of hospitalized novel coronavirus (COVID-19) patients, who were complicated with severe pneumonia, were compared with the findings of cytokine storm developing in macrophage activation syndrome (MAS)/secondary hemophagocytic lymphohistiocytosis (sHLH). Severe pneumonia occurred as a result of cytokine storm in some patients who needed intensive care unit (ICU), and it is aimed to determine the precursive parameters in this situation. Also in this study, the aim is to identify laboratory criteria that predict worsening disease and ICU intensification, as well as the development of cytokine storm. This article comprises a retrospective cohort study of patients admitted to a single institution with COVID-19 pneumonia. This study includes 150 confirmed COVID-19 patients with severe pneumonia. When they were considered as severe pneumonia patients, the clinic and laboratory parameters of this group are compared with H-score criteria. Patients are divided into two subgroups; patients with worsened symptoms who were transferred into tertiary ICU, and patients with stable symptoms followed in the clinic. For the patients with confirmed COVID-19 infection, after they become complicated with severe pneumonia, lymphocytopenia (55.3%), anemia (12.0%), thrombocytopenia (19.3%), hyperferritinemia (72.5%), hyperfibrinogenemia (63.7%) and elevated lactate dehydrogenase (LDH) (90.8%), aspartate aminotransaminase (AST) (31.3%), alanine aminotransaminase (ALT) (20.7%) are detected. There were no significant changes in other parameters. Blood parameters between the pre-ICU period and the ICU period (in which their situation had been worsened and acute respiratory distress syndrome [ARDS] was developed) were also compared. In the latter group lymphocyte levels were found significantly reduced (p = 0.01), and LDH, highly sensitive troponin (hs-troponin), procalcitonin, and triglyceride levels were significantly increased (p < 0.05). In addition, there was no change in hemoglobin, leukocyte, platelet, ferritin, and liver function test levels, including patients who developed ARDS, similar to the cytokine storm developed in MAS/sHLH. COVID-19 pneumonia has similar findings as hyperinflammatory syndromes but does not seem to have typical features as in cytokine storm developed in MAS/sHLH. In the severe patient group who has started to develop ARDS signs, a decrease in lymphocyte level in addition to the elevated LDH, hs-troponin, procalcitonin, and triglyceride levels can be a predictor in progression to ICU admission and could help in the planning of anti-cytokine therapy.


Assuntos
COVID-19/patologia , Síndrome da Liberação de Citocina/patologia , Linfo-Histiocitose Hemofagocítica/patologia , Síndrome de Ativação Macrofágica/patologia , SARS-CoV-2/patogenicidade , Idoso , Alanina Transaminase/sangue , Anemia/sangue , Anemia/diagnóstico , Anemia/imunologia , Anemia/patologia , Aspartato Aminotransferases/sangue , Biomarcadores/sangue , COVID-19/sangue , COVID-19/diagnóstico , COVID-19/imunologia , Síndrome da Liberação de Citocina/sangue , Síndrome da Liberação de Citocina/diagnóstico , Síndrome da Liberação de Citocina/imunologia , Diagnóstico Diferencial , Progressão da Doença , Feminino , Fibrinogênio/metabolismo , Humanos , Hiperferritinemia/sangue , Hiperferritinemia/diagnóstico , Hiperferritinemia/imunologia , Hiperferritinemia/patologia , Unidades de Terapia Intensiva , L-Lactato Desidrogenase/sangue , Linfo-Histiocitose Hemofagocítica/sangue , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/imunologia , Linfopenia/sangue , Linfopenia/diagnóstico , Linfopenia/imunologia , Linfopenia/patologia , Síndrome de Ativação Macrofágica/sangue , Síndrome de Ativação Macrofágica/diagnóstico , Síndrome de Ativação Macrofágica/imunologia , Masculino , Pessoa de Meia-Idade , Pró-Calcitonina/sangue , Estudos Retrospectivos , Trombocitopenia/sangue , Trombocitopenia/diagnóstico , Trombocitopenia/imunologia , Trombocitopenia/patologia , Triglicerídeos/sangue , Troponina/sangue
19.
Front Immunol ; 12: 649465, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33968041

RESUMO

The immune and inflammatory responses of platelets to human immunodeficiency virus 1 (HIV-1) and its envelope proteins are of great significance to both the treatment of the infection, and to the comorbidities related to systemic inflammation. Platelets can interact with the HIV-1 virus itself, or with viral membrane proteins, or with dysregulated inflammatory molecules in circulation, ensuing from HIV-1 infection. Platelets can facilitate the inhibition of HIV-1 infection via endogenously-produced inhibitors of HIV-1 replication, or the virus can temporarily hide from the immune system inside platelets, whereby platelets act as HIV-1 reservoirs. Platelets are therefore both guardians of the host defence system, and transient reservoirs of the virus. Such reservoirs may be of particular significance during combination antiretroviral therapy (cART) interruption, as it may drive viral persistence, and result in significant implications for treatment. Both HIV-1 envelope proteins and circulating inflammatory molecules can also initiate platelet complex formation with immune cells and erythrocytes. Complex formation cause platelet hypercoagulation and may lead to an increased thrombotic risk. Ultimately, HIV-1 infection can initiate platelet depletion and thrombocytopenia. Because of their relatively short lifespan, platelets are important signalling entities, and could be targeted more directly during HIV-1 infection and cART.


Assuntos
Plaquetas/imunologia , Infecções por HIV/imunologia , HIV-1/imunologia , Trombocitopenia/imunologia , Trombose/imunologia , Antirretrovirais/farmacologia , Antirretrovirais/uso terapêutico , Plaquetas/efeitos dos fármacos , Plaquetas/virologia , Linfócitos T CD4-Positivos/imunologia , Comunicação Celular/efeitos dos fármacos , Comunicação Celular/imunologia , Quimioterapia Combinada , Eritrócitos/imunologia , Infecções por HIV/sangue , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , HIV-1/metabolismo , Humanos , Agregação Plaquetária/imunologia , Trombocitopenia/sangue , Trombocitopenia/virologia , Trombose/sangue , Trombose/virologia , Carga Viral , Replicação Viral/imunologia , Produtos do Gene env do Vírus da Imunodeficiência Humana/metabolismo
20.
Medicine (Baltimore) ; 100(21): e25985, 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34032713

RESUMO

ABSTRACT: Cytopenias in systemic lupus erythematosus (SLE) require clinical and laboratory workup and bone marrow (BM) examination to determine the cause and for appropriate patient management. Common causes include an increase in SLE activity, immune-mediated hemolysis, iron deficiency, antiphospholipid antibody syndrome, infection, or the effect of medications. We retrospectively evaluated the clinical and laboratory findings of patients with SLE and cytopenias who had undergone BM studies to determine the indicators of malignancy.We retrospectively reviewed medical records of patients with SLE who presented with cytopenias for their disease course, medications, laboratory parameters and documented the spectrum of morphological changes in BM including CD34 expression.Twenty patients with SLE had undergone BM biopsy for evaluation of cytopenias. 14/20 (70%) of the patients had reactive BM, and the rest had hematologic malignancies involving the BM. Of these 14 patients, 8 had hypocellular marrow with loss of precursor cells (low CD34), 4 had left shift in myeloid lineage, 3 had serous atrophy, and 1had multilineage dysplasia. The 6 patients with hematologic malignancies included 2 with diffuse large B cell lymphoma, and one each of natural killer/T cell lymphoma, post-transplant lymphoproliferative disorder, Hodgkin lymphoma, and myelodysplastic syndrome evolving to acute myelogenous leukemia. The presence of autoantibodies, SLE activity, and lupus nephritis were comparable in patients with and without neoplasia. However, the duration of the use of multiple immunosuppressants, years since renal transplant (22 vs 10), multiple transplants, and the presence of other autoimmune diseases were greater in those with neoplasia. Two of the 14 patients with non-neoplastic BM and 1 with the neoplastic BM had nonhematological malignancy.Clinical and laboratory findings, the number of transplants, and the use of immunosuppressive agents can guide physicians to identify patients with a higher risk of developing hematologic malignancy. BM findings of cytopenia in SLE are often due to increased disease activity causing global cell death and dysmaturation. SLE patients presenting with cytopenias, with a history of long-term exposure to immunosuppressive drugs, should be regularly screened for hematologic and nonhematologic malignancies.


Assuntos
Neoplasias Hematológicas/epidemiologia , Imunossupressores/efeitos adversos , Transplante de Rim/efeitos adversos , Leucopenia/diagnóstico , Lúpus Eritematoso Sistêmico/complicações , Trombocitopenia/diagnóstico , Adulto , Idoso , Biópsia/estatística & dados numéricos , Medula Óssea/patologia , Exame de Medula Óssea/estatística & dados numéricos , Suscetibilidade a Doenças , Feminino , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/imunologia , Neoplasias Hematológicas/patologia , Humanos , Transplante de Rim/estatística & dados numéricos , Leucopenia/sangue , Leucopenia/imunologia , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/terapia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Trombocitopenia/sangue , Trombocitopenia/imunologia , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...