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1.
Ann Card Anaesth ; 26(1): 90-93, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36722595

RESUMO

Thrombocytopenia is a common condition that recognizes an infinite number of possible causes, especially in specific settings like the one covered in this case report: the postoperative period of cardiac surgery. We report a case of an old male with multiple comorbidities who underwent a coronary angioplasty procedure and aortic valve replacement. He showed severe thrombocytopenia in the postoperative days. Differential diagnosis required a big effort, also for the experts in the field. Our goal was to aggressively treat the patient with prednisolone, platelets, and intravenous immunoglobulins to maximize the prognosis. Our patient developed no complications and was discharged successfully.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Púrpura Trombocitopênica Idiopática , Trombocitopenia , Masculino , Humanos , Púrpura Trombocitopênica Idiopática/complicações , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Trombocitopenia/etiologia , Diagnóstico Diferencial , Período Pós-Operatório
2.
Lancet Haematol ; 10(2): e107-e116, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36725117

RESUMO

BACKGROUND: Chimeric antigen receptor (CAR) T-cell therapy targeting B-cell maturation antigen (BCMA) has shown activity in treating relapsed or refractory multiple myeloma; however, relapse is still common, and new targets are needed. We aimed to assess the activity and safety profile of G protein-coupled receptor class C group 5 member D (GPRC5D)-targeted CAR T cells (OriCAR-017) in patients with relapsed or refractory multiple myeloma. METHODS: POLARIS was a first-in-human, single-centre, single-arm, phase 1 trial of GPRC5D-targeted CAR T cells (OriCAR-017) done at the First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China. Eligible patients were adults aged 18-75 years with a diagnosis of relapsed or refractory multiple myeloma and an ECOG performance status of 0-2, had GPRC5D expression in bone marrow plasma cells greater than 20% or were positive for GPRC5D by immunohistochemistry, and had received at least three previous lines of treatment including proteasome inhibitors, immunomodulatory drugs, and chemotherapy. Patients were consecutively assigned to receive a single dose of intravenous OriCAR-017 at 1 × 106 CAR T cells per kg, 3 × 106 CAR T cells per kg, or 6 × 106 CAR T cells per kg in the dose-escalation phase. In the expansion phase, patients received the recommended phase 2 dose. Recruitment to the expansion phase terminated early due to the COVID-19 pandemic on May 1, 2022. The primary endpoints were safety, the maximum tolerated dose and the recommended phase 2 dose. Safety and activity analyses included all patients who received OriCAR-017. This trial is registered with ClinicalTrials.gov, NCT05016778. This trial has been completed and is entering long-term follow-up. FINDINGS: Between June 9, 2021, and Feb 28, 2022, we recruited 13 patients for inclusion into the study. One patient was excluded because of GPRC5D negativity and two patients discontinued after apheresis because of rapid progression. Nine patients were assigned to the dose escalation phase (three received 1 × 106 CAR T cells per kg, three received 3 × 106 CAR T cells per kg, and three received 6 × 106 CAR T cells per kg). The maximum tolerated dose was not identified, because no dose-limiting toxic effects were observed. On the basis of safety and preliminary activity, the recommended phase 2 dose was set at 3 × 106 CAR T cells per kg, which was received by one additional patient in the dose expansion phase. Five patients (50%) were female, five (50%) were male, and all were Chinese. Five patients (50%) were previously treated with BCMA-targeted CAR T-cell therapy. Median follow-up was 238 days (IQR 182-307). There were no serious adverse events and no treatment-related deaths. The most common grade 3 or worse adverse events were haematological, including neutropenia (ten [100%] of ten patients), thrombocytopenia (nine [90%]), leukopenia (nine [90%]), and anaemia (seven [70%]). All patients had cytokine release syndrome (nine [90%] grade 1 and one [10%] grade 2). No neurological toxic effects were reported. Ten (100%) of ten patients had an overall response, of whom six (60%) had a stringent complete response and four (40%) had very good partial response. Two patients discontinued due to disease progression (one GPRC5D-positive patient in the middle-dose group and one GPRC5D-negative patient in the low-dose group). INTERPRETATION: The results of this study suggest that GPRC5D is an active target for immunotherapy in multiple myeloma. GPRC5D-targeted CAR T-cell therapy is a promising treatment modality for patients with relapsed or refractory multiple myeloma and deserves further testing. FUNDING: OriCell Therapeutics.


Assuntos
Anemia , COVID-19 , Mieloma Múltiplo , Trombocitopenia , Adulto , Humanos , Masculino , Feminino , Mieloma Múltiplo/tratamento farmacológico , Antígeno de Maturação de Linfócitos B , Pandemias , Recidiva Local de Neoplasia , Linfócitos T , Receptores Acoplados a Proteínas G/uso terapêutico
3.
Clin Interv Aging ; 18: 115-130, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36726813

RESUMO

Many epidemiological studies have shown that the incidence of immune thrombocytopenia (ITP) increases after age 60 years and peaks in patients over age 80 years. Therefore, ITP is a concern for physicians taking care of older patients, especially regarding its diagnosis and management. The diagnostic work-up should exclude other causes of thrombocytopenia and secondary ITP, including myelodysplastic syndrome and drug-induced ITP. The treatment decision is influenced by an increased risk of bleeding, infectious diseases and thrombosis in this population and should take into account comorbidities and concomitant medications such as anticoagulant drugs. First-line treatment is based on short corticosteroids courses and intravenous immunoglobulin, which should be reserved for patients with more severe bleeding complications, with their higher risk of toxic effects as compared with younger patients. Second-line treatment should be tailored to the patient's history, comorbidities and preferences. Preferred second-line treatments are thrombopoietin receptor agonists for most groups and guidelines given their good efficacy/tolerance ratio, but the thrombotic risk is increased in older people. Other second-line options that can be good alternatives depending on the clinical context include rituximab, dapsone, fostamatinib or immunosuppressive drugs. Splenectomy is less often performed but remains an option for fit patients with chronic refractory disease. Emerging treatments such as Syk or Bruton tyrosine kinase inhibitors and FcRn antagonists are becoming available for ITP and may modify the treatment algorithm in the near future. The aim of this review is to describe the particularities of the diagnosis and treatment of ITP in older people, including the response and tolerance to the currently available drugs. We also discuss some situations related to co-morbidities that can frequently lead to adapt the management strategy in older patients.


Assuntos
Púrpura Trombocitopênica Idiopática , Trombocitopenia , Humanos , Idoso , Idoso de 80 Anos ou mais , Púrpura Trombocitopênica Idiopática/diagnóstico , Púrpura Trombocitopênica Idiopática/epidemiologia , Púrpura Trombocitopênica Idiopática/terapia , Trombocitopenia/diagnóstico , Trombocitopenia/tratamento farmacológico , Imunoglobulinas Intravenosas/uso terapêutico , Rituximab/efeitos adversos , Glucocorticoides/uso terapêutico
4.
Phytomedicine ; 110: 154637, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36610353

RESUMO

BACKGROUND: Non-peptide thrombopoietin receptor (TPOR) agonists are promising therapies for the mitigation and treatment of thrombocytopenia. However, only few agents are available as safe and effective for stimulating platelet production for thrombocytopenic patients in the clinic. PURPOSE: This study aimed to develop a novel small molecule TPOR agonist and investigate its underlying regulation of function in megakaryocytes (MKs) differentiation and thrombopoiesis. METHODS: A potential active compound that promotes MKs differentiation and thrombopoiesis was obtained by machine learning (ML). Meanwhile, the effect was verified in zebrafish model, HEL and Meg-01 cells. Next, the key regulatory target was identified by Drug Affinity Responsive Target Stabilization Assay (DARTS), Cellular Thermal Shift Assay (CETSA), and molecular simulation experiments. After that, RNA-sequencing (RNA-seq) was used to further confirm the associated pathways and evaluate the gene expression induced during MK differentiation. In vivo, irradiation (IR) mice, C57BL/6N-TPORem1cyagen (Tpor-/-) mice were constructed by CRISPR/Cas9 technology to examine the therapeutic effect of TMEA on thrombocytopenia. RESULTS: A natural chemical-structure small molecule TMEA was predicted to be a potential active compound based on ML. Obvious phenotypes of MKs differentiation were observed by TMEA induction in zebrafish model and TMEA could increase co-expression of CD41/CD42b, DNA content, and promote polyploidization and maturation of MKs in HEL and Meg-01 cells. Mechanically, TMEA could bind with TPOR protein and further regulate the PI3K/AKT/mTOR/P70S6K and MEK/ERK signal pathways. In vivo, TMEA evidently promoted platelet regeneration in mice with radiation-induced thrombocytopenia but had no effect on Tpor-/- and C57BL/6 (WT) mice. CONCLUSION: TMEA could serve as a novel TPOR agonist to promote MKs differentiation and thrombopoiesis via mTOR and ERK signaling and could potentially be created as a promising new drug to treat thrombocytopenia.


Assuntos
Trombocitopenia , Trombopoese , Animais , Camundongos , Diferenciação Celular , Megacariócitos , Camundongos Endogâmicos C57BL , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais , Trombocitopenia/tratamento farmacológico , Trombocitopenia/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Peixe-Zebra/metabolismo , Sistema de Sinalização das MAP Quinases , Receptores de Trombopoetina/antagonistas & inibidores
6.
Platelets ; 34(1): 2159019, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36636835

RESUMO

Increased platelet destruction is central in the pathogenesis of immune thrombocytopenia. However, impaired platelet production is also relevant and its significance underlies the rationale for treatment with thrombopoietin receptor agonists (TPO-RAs). Previous studies have associated enhanced complement activation with increased disease severity. Additionally, treatment refractoriness has been demonstrated to resolve by the administration of complement-targeted therapeutics in a subset of patients. The association between complement activation and the platelet response to TPO-RA therapy has previously not been investigated. In this study, blood samples from patients with immune thrombocytopenia (n = 15) were prospectively collected before and two, six and 12 weeks after the initiation of TPO-RA therapy. Plasma levels of complement degradation product C4d and soluble terminal complement complexes were assessed. Patients with significantly elevated baseline levels of terminal complement complexes exhibited more often an inadequate platelet response (p = .04), were exclusively subjected to rescue therapy with intravenous immunoglobulin (p = .02), and did not respond with a significant platelet count increase during the study period. C4d showed a significant (p = .01) ability to distinguish samples with significant terminal complement activation, implying engagement of the classical complement pathway. In conclusion, elevated levels of complement biomarkers were associated with a worse TPO-RA treatment response. Larger studies are needed to confirm these results. Biomarkers of complement activation may prove valuable as a prognostic tool to predict which patients that potentially could benefit from complement-inhibiting therapy in the future.


What is the context?Primary immune thrombocytopenia (ITP) is a potentially serious illness associated with an increased risk of bleeds. Manifestations range from confined skin bruising to life-threatening intracranial hemorrhages.It is an acquired immune disorder characterized by increased destruction and impaired production of platelets.Treatments aim at suppressing the destruction and supporting the production of platelets.Thrombopoietin receptor agonists (TPO-RA) are medically approved platelet growth factors that contribute to the generation of new platelets.The complement system is an evolutionary preserved part of innate immunity.Previous studies have indicated that complement activation may be an important contributor to disease and that the administration of complement-inhibiting therapy improves the platelet count in a subset of patients with primary ITP.What is new? The potential association between complement activation and a poor platelet response to TPO-RA therapy in primary ITP has not been previously studied.In fifteen patients with primary ITP starting TPO-RA therapy, we prospectively followed the platelet response and levels of complement biomarkers for 12 weeks.We showed that patients with high levels of complement biomarkers exhibited a worse treatment response during the study period.What is the impact?Our results suggest that levels of complement biomarkers may be valuable to predict which patients with treatment-refractory ITP that potentially could benefit from complement-inhibiting therapy in the futureLarger studies are needed to confirm our results.


Assuntos
Púrpura Trombocitopênica Idiopática , Trombocitopenia , Humanos , Receptores de Trombopoetina/agonistas , Estudos Prospectivos , Biomarcadores , Ativação do Complemento , Trombopoetina/farmacologia , Trombopoetina/uso terapêutico , Proteínas Recombinantes de Fusão
7.
Biomed Res Int ; 2023: 5984361, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36660453

RESUMO

Materials and Methods: Compounds of HQHG were scanned by LC-MS/MS, and the target profiles of compounds were identified based on SwissTarget Prediction. ITP target proteins were collected from various databases. Then, KEGG pathway and GO enrichment analyses were performed to explore the signaling pathways related to HQHG for ITP. The PPI and drug-herbs-compounds-targets-pathways network were constructed using Cytoscape 3.7.2. Finally, Discovery studio software was used to confirm the key targets and active compounds from HQHG. Results: A total of 187 interacting targets of 19 potentially active compounds in HQHG and 3837 ITP-related targets were collected. Then, 187 intersection targets were obtained. A total of 20 key targets including EGFR, CASP3, TNF, STAT3, and ERBB2 were identified through PPI network analysis. These targets were mainly focused on the biological processes of positive regulation of protein phosphorylation, cellular response to organonitrogen compound, and cellular response to nitrogen compound. 20 possible pathways of HQHG in the treatment of ITP were identified through KEGG enrichment. EGFR, CASP3, TNF, and STAT3 are the four most important target proteins, while adenosine, caffeic acid, ferulic acid, quercetin-3ß-D-glucoside, rutin, scopoletin, and tianshic acid are the most important active compounds, which were validated by molecular docking simulation. Conclusion: This study demonstrated that HQHG produced relief effects against ITP by regulating multitargets and multipathways with multicompounds. And the combined data provide novel insight of drug developing for ITP.


Assuntos
Medicamentos de Ervas Chinesas , Púrpura Trombocitopênica Idiopática , Trombocitopenia , Humanos , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Simulação de Acoplamento Molecular , Caspase 3 , Farmacologia em Rede , Cromatografia Líquida , Espectrometria de Massas em Tandem , Receptores ErbB , Medicamentos de Ervas Chinesas/farmacologia
8.
Medicina (Kaunas) ; 59(1)2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36676770

RESUMO

Background and Objectives: To find low-cost markers that can identify the hepatitis C virus cirrhotic patients that are at risk for long-term severe adverse liver effects (ascites, ascites or upper gastrointestinal bleeding, hepatocellular carcinoma), after treatment. There is established evidence for the benefits of treating hepatitis C virus cirrhotic patients, but there is still some need for clarification concerning the real impact on the long-term evolution after achieving sustained virological response; there is no general consensus in the literature about identifying the patients that do not improve post-treatment. Materials and Methods: Our retrospective analysis investigated the long-term (2 years) evolution of 46 patients with cirrhosis with thrombocytopenia, previously infected with VHC, treated and who obtained an SVR after DAA treatment. Results: Despite the overall improvement, 8.7% patients developed hepatocellular carcinoma and 6.5% patients ascites/upper GI bleeding. We found that FIB-4, MELD and AFP changes at 1 year were the most significant predictors for these outcomes. Additionally, a drop in leukocyte count after 1 year seemed to indicate a risk for hepatocellular carcinoma, but this was not consistent. Conclusions: It might be beneficial to intensify the surveillance for post-treatment adverse liver effects for the patients with these marker changes at 1 year.


Assuntos
Carcinoma Hepatocelular , Hepatite C Crônica , Hepatite C , Neoplasias Hepáticas , Trombocitopenia , Humanos , Antivirais/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Hepacivirus , Estudos Retrospectivos , Ascite/induzido quimicamente , Ascite/tratamento farmacológico , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Hepatite C/tratamento farmacológico , Cirrose Hepática/complicações , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/epidemiologia , Neoplasias Hepáticas/tratamento farmacológico , Trombocitopenia/complicações , Trombocitopenia/tratamento farmacológico
9.
Platelets ; 34(1): 2157383, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36683325

RESUMO

Circulating platelets maintain low cytosolic Ca2+ concentrations. At sites of vascular injury, agonist-induced Ca2+ release from platelet intracellular stores triggers influx of extracellular Ca2+, a process known as store-operated Ca2+ entry (SOCE). Stromal interaction molecule 1 (Stim1) senses reduced Ca2+ stores and triggers SOCE. Gain-of-function (GOF) mutations in Stim1, such as described for Stormorken syndrome patients or mutant mice (Stim1Sax), are associated with marked thrombocytopenia and increased platelet turnover. We hypothesized that reduced platelet survival in Stim1Sax/+ mice is due to increased Rap1/integrin signaling and platelet clearance in the spleen, similar to what we recently described for mice expressing a mutant version of the Rap1-GAP, Rasa3 (Rasa3hlb/hlb). Stim1Sax/+ mice were crossed with mice deficient in CalDAG-GEFI, a critical calcium-regulated Rap1-GEF in platelets. In contrast to Rasa3hlb/hlb x Caldaggef1-/- mice, only a small increase in the peripheral platelet count, but not platelet lifespan, was observed in Stim1Sax/+ x Caldaggef1-/- mice. Similarly, inhibition of αIIbß3 integrin in vivo only minimally raised the peripheral platelet count in Stim1Sax/+ mice. Compared to controls, Stim1Sax/+ mice exhibited increased platelet accumulation in the lung, but not the spleen or liver. These results suggest that CalDAG-GEFI/Rap1/integrin signaling contributes only minimally to accelerated platelet turnover caused by constitutive SOCE.


What do we know? Platelets are small blood cells which act to prevent blood loss, which circulate in a resting state but are rapidly activated upon exposure to ligands at the site of vascular injuryCalcium (Ca2+) is critical for platelet activation, especially for activation of integrins which support platelet­platelet interactionsIf platelet activation occurs in circulation, platelets can be prematurely cleared from blood and unable to function in hemostasisDisorders of Ca2+ dysregulation such as Stormorken syndrome are associated with reduced platelet counts (thrombocytopenia) and bleedingWhat did we discover? We used a mouse model expressing a mutation causing higher Ca2+ levels in cells including platelets (Stim1Sax), and investigated whether thrombocytopenia is due to stimulation of a specific pathway for integrin activation, mediated by a protein called Rap1 GTPaseWe crossed Stim1Sax mice with mice lacking an important activator of Rap1, the Ca2+-regulated protein CalDAG-GEFI, and saw no major improvement in thrombocytopeniaWe also observed more Stim1Sax platelets in the lung but not the liver or spleen, in contrast to mice with activation of platelet integrins in circulationWhat is the impact? Our results rule out activation of the CalDAG-GEFI/Rap1/integrin pathway as a major cause of thrombocytopenia in Stim1Sax miceOur findings help to narrow down potential causes of thrombocytopenia in disorders such as Stormorken syndrome.


Assuntos
Cálcio , Trombocitopenia , Camundongos , Animais , Fatores de Troca do Nucleotídeo Guanina/genética , Plaquetas , Complexo Glicoproteico GPIIb-IIIa de Plaquetas , Transdução de Sinais , Trombocitopenia/genética , Proteínas Ativadoras de GTPase
12.
Am J Case Rep ; 24: e938358, 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36600572

RESUMO

BACKGROUND Many drugs have been reported to cause immune-mediated adverse drug reactions (IM-ADRs) in human immunodeficiency virus (HIV) patients; the most common is cutaneous adverse drug reaction (CADR). Immune thrombocytopenia purpura (ITP) is frequent in HIV patients, and it can be caused HIV, opportunistic infections, or drugs. Although drugs can cause immune thrombocytopenia, termed drug-induced immune thrombocytopenia (DIIT), there has been no study on DIIT in HIV patients. CASE REPORT A 33-year-old male patient was admitted to our hospital with pruritic skin lesion over the entire body, which started 7 days before. He was diagnosed with HIV infection, brain toxoplasmosis, and pulmonary tuberculosis 2 weeks before admission, and was given trimethoprim sulphamethoxazole, isoniazid, rifampicin, pyrazinamide, and ethambutol. Clindamycin was added 10 days before admission. Skin examination revealed generalized erythematous macules with palpable petechiae and purpura. The platelet count was 141 000/µL when he was diagnosed with HIV, and it was 2000/µL at the time of admission. Clindamycin was discontinued and he was given steroids and platelet transfusion. The skin lesions improved along with an increased platelet count. He was discharged on the 10th day of admission, with platelet count of 42 000/µL. When he returned to the outpatient clinic on the 15th day, his platelet was 54 000/µL. The skin lesions had resolved completely and become hyperpigmented, and no purpura or petechiae were seen. CONCLUSIONS We present a case of an HIV patient with IM-ADR in the form of DIIT in conjunction with CADR that might have been caused by clindamycin.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Infecções por HIV , Púrpura Trombocitopênica Idiopática , Púrpura , Trombocitopenia , Masculino , Humanos , Adulto , Clindamicina/efeitos adversos , Infecções por HIV/tratamento farmacológico , Púrpura Trombocitopênica Idiopática/induzido quimicamente , Trombocitopenia/induzido quimicamente , Púrpura/induzido quimicamente
13.
Dtsch Med Wochenschr ; 148(3): 112-115, 2023 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-36690007

RESUMO

HISTORY: The 37 year old patient was admitted to hospital with persisting fever for 4 weeks. He had a history of weight loss, night sweat and cough. Antipyretic treatment with Paracetamol and up to ineffectiveness therapy with Ibuprofen was taken by the patient. FINDINGS AND DIAGNOSIS: Fever and poor general condition were obvious on time of admission. The ECG showed tachycardia. Liver values were increased. X-ray of the chest showed a central mass on the right site. On computed tomography there was a finding of a possibly necrotic tumour close to central vessels. The patient developed a prolonged thrombocytopenia and bleeding on several sites. Further diagnostic approaches were difficult to perform. After puncture of the central mediastinal mass and bone marrow we diagnosed an extensive extrapulmonary tuberculosis. Toxic hepatitis was getting worse under medical treatment of tuberculosis. In addition, with thrombocytopenia patient condition reached a critical state. THERAPY AND COURSE: After initiation of prednisolone-treatment up to suspicion of drug- induced thrombocytopenia (D-ITP) and switch of the anti- Tb-regimen the general condition improved. There was repetitive need for transfusion of thrombocytes. CONCLUSIONS: Toxic hepatitis is a possible severe complication of anti-Tb-treatment. A critical evaluation of patients' medication and soon initiation of anti -Tb-treatment is necessary. Especially in patients coming from high tb-incidence regions with history of poor general condition and persisting fever the diagnosis of extrapulmonary tuberculosis and bone marrow infiltration should be taken into account.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Febre , Trombocitopenia , Adulto , Humanos , Masculino , Doença Hepática Induzida por Substâncias e Drogas/complicações , Febre/etiologia , Prednisolona , Trombocitopenia/complicações , /diagnóstico
14.
J Pediatr Hematol Oncol ; 45(1): e4-e8, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36598962

RESUMO

BACKGROUND: Vitamin D deficiency is ubiquitous within the population of children. A similar problem is recognized among pediatric patients with acute lymphoblastic leukemia. The purpose of this study was to analyze the prevalence of vitamin D deficiency and to investigate the connection between vitamin D status and the course of induction treatment of ALL. MATERIALS AND METHODS: A cross-sectional study including 59 patients with newly diagnosed ALL from May 2017 until November 2020. RESULTS: Vitamin D deficiency was found in 39% of the patients. There were no seasonal differences in vitamin D status. Patients with optimal 25(OH)D concentration presented more profound thrombocytopenia ( P =0.015) and required more frequent platelet transfusions ( P =0.018). Good prognosis factors such as B phenotype and hyperdiploidy were also more frequent among children with higher 25(OH)D concentration ( P =0.01 and 0.014, respectively). CONCLUSIONS: The study showed that patients with a higher serum concentration of 25(OH)D presented deeper thrombocytopenia and needed more frequent transfusions. Moreover, those patients showed higher rates of B-cell leukemia and hyperdiploid karyotype. We did not find any influence of the possible exposure to sunlight (defined as the season of the year on admission) on serum 25(OH)D concentration, which supports the argument for supplementing vitamin D all year round. Moreover, the supplementing of vitamin D seems to be safe and does not cause any renal complications connected to calcium and phosphorus imbalance as no correlation between their levels and 25(OH)D concentration was found.


Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras , Trombocitopenia , Deficiência de Vitamina D , Criança , Humanos , Vitamina D , Estudos Transversais , Vitaminas , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Trombocitopenia/complicações , Estações do Ano , Prevalência
16.
J Investig Med High Impact Case Rep ; 11: 23247096221145104, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36594290

RESUMO

Multisystem inflammatory syndrome in children (MIS-C) has been extensively described in patients following severe acute respiratory syndrome coronavirus 2 infection. There are now questions about what MIS-C may look like in vaccinated children. Multisystem inflammatory syndrome in children has many clinical and laboratory features in common with other inflammatory disorders including Kawasaki disease and toxic shock syndrome. Rheumatologic conditions can present with similar musculoskeletal complaints and elevated inflammatory markers. Laboratory markers and clinical symptoms of MIS-C usually improve once therapy is begun. We describe a child with persistent thrombocytopenia as an example of variable presentation of MIS-C in vaccinated children. This case report discusses an atypical progression of MIS-C in a vaccinated child with a known prior positive COVID-19 polymerase chain reaction (PCR) test. She presented with nonspecific abdominal pain and fever and was found to have elevated inflammatory markers, lymphopenia, and thrombocytopenia. Intravenous immunoglobulin and steroid treatment failed to induce rapid recovery in her clinical condition or thrombocytopenia. Rheumatologic, hematologic, oncologic, and infectious causes were considered and worked up due to the uncertainty of her case and persistence of pancytopenia but ultimately were ruled out with extensive testing and monitoring. It was key to include a broad differential including viral-induced bone marrow suppression, idiopathic thrombocytopenic purpura, secondary hemophagocytic lymphohistiocytosis, systemic juvenile idiopathic arthritis, and malignancy. The spectrum of MIS-C and response to treatment continues to evolve, and prior vaccination in this child's case complicated the clinical picture further. Additional evaluation of MIS-C in vaccinated cases will permit characterization of the range of MIS-C presentation and response to standard therapy.


Assuntos
Artrite Reumatoide , COVID-19 , Trombocitopenia , Feminino , Humanos , Criança , COVID-19/complicações , Síndrome de Resposta Inflamatória Sistêmica , Trombocitopenia/etiologia
17.
BMC Cancer ; 23(1): 27, 2023 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-36611025

RESUMO

BACKGROUND: Early death remains a major factor in survival in APL. We aimed to analyze the risk factors for differentiation syndrome and early death in acute promyelocytic leukemia (APL). METHODS: The clinical data of APL patients who were newly diagnosed at Mianyang Central Hospital from January 2013 to January 2022 were retrospectively analyzed. RESULTS: Eighty-six newly diagnosed APL patients (37 males and 49 females) were included in this study. The median age was 46 (17-75) years. Sixty-one patients (70.9%) had low/intermediate-risk APL, and 25 patients (29.1%) had high-risk APL. The incidence of differentiation syndrome (DS) was 62.4%. The multivariate analysis showed that a peak white blood cell (WBC) count ≥16 × 10^9/L was an independent risk factor (OR = 11.000, 95% CI: 2.830-42.756, P = 0.001) for DS in all APL patients, while a WBC count ≥10 × 10^9/L on Day 5 was an independent risk factor for DS in low-intermediate risk APL patients (OR = 9.114, 95% CI: 2.384-34.849, P = 0.001). There were 31 patients (36.5%) with mild DS and 22 patients (25.9%) with severe DS. The multivariate analysis showed that WBC count ≥23 × 10^9/L at chemotherapy was an independent risk factor for severe DS (OR = 10.500, 95% CI: 2.344-47.034, P = 0.002). The rate of early death (ED) was 24.4% (21/86). The multivariate analysis showed that male gender (OR = 7.578,95% CI:1.136-50.551, P = 0.036), HGB < 65 g/L (OR = 16.271,95% CI:2.012-131.594, P = 0.009) and WBC count ≥7 × 10^9/L on Day 3(OR = 23.359,95% CI:1.825-298.959, P = 0.015) were independent risk factors for ED. The WBC count at diagnosis, WBC count on Day 3 and WBC count on Day 5 had moderate positive correlations with tumor necrosis factor-α (TNF-α) at diagnosis, and the correlation coefficients were 0.648 (P = 0.012), 0.615 (P = 0.033), and 0.609 (P = 0.035), respectively. The WBC count had no correlation with IL-6. CONCLUSION: During induction treatment, cytotoxic chemotherapy may need to be initiated to reduce the risk of DS for APL patients with a low-intermediate risk WBC count ≥10 × 10^9/L on Day 5 or for all patients with a peak WBC count ≥16 × 10^9/L. Patients with WBC > 7 × 10^9/L on Day 3 have a higher risk of ED. Leukocyte proliferation is associated with TNF-α rather than IL-6, and TNF-α may be a potential biomarker for predicting ED.


Assuntos
Leucemia Mieloide Aguda , Leucemia Promielocítica Aguda , Leucopenia , Trombocitopenia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Interleucina-6 , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Promielocítica Aguda/diagnóstico , Contagem de Leucócitos , Leucócitos/patologia , Leucopenia/induzido quimicamente , Estudos Retrospectivos , Síndrome , Trombocitopenia/induzido quimicamente , Tretinoína , Fator de Necrose Tumoral alfa , Adolescente , Adulto Jovem , Adulto , Idoso
18.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 54(1): 161-164, 2023 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-36647660

RESUMO

Objective: To investigate the efficacy and safety of treating refractory chemotherapy-induced thrombocytopenia (RCIT) with San Wei Sheng Huo Decoction (SWSHD) as the main formula. Methods: A retrospective study was conducted and the data of RCIT patients treated with SWSHD as the main formula were collected. Changes in peripheral blood platelet (PLT) levels at different time points of treatment were examined and the significant effective rate (SER) and effective rate (ER) were analyzed. We measured the increase in peripheral blood PLT count before and after treatment, analyzed the differences in PLT count increase for different degrees of RCIT treatment, and evaluated the safety of the treatment. Results: A total of 35 cases of RCIT were included in the study. With SWSHD as the main treatment formula, the 2-week ER and SER were 74.29% and 14.29%, respectively, the 2-month ER and SER were 84.38% and 60.50, respectively, and the 1-year ER and SER were 92.31% and 80.77%, respectively. PLT count increased at all time points after treatment compared with that before treatment ( P<0.01). Subgroup analysis showed that, 2 months after treatment started, peripheral blood PLT counts increased by as much as 51.02×10 9L -1 in the severe RCIT group, higher than that of the moderate RCIT group at 36.58×10 9L -1 ( P<0.05), and the difference persisted until 1 year after the treatment. No obvious traditional Chinese medicine-related adverse reaction was observed during the treatment. Conclusion: SWSHD takes effect rapidly and its effect is long-lasting and stable. Furthermore, SWSHD has a more significant effect on severe RCIT.


Assuntos
Antineoplásicos , Trombocitopenia , Humanos , Estudos Retrospectivos , Trombocitopenia/induzido quimicamente , Trombocitopenia/tratamento farmacológico , Contagem de Plaquetas , Plaquetas , Antineoplásicos/efeitos adversos
19.
J Paediatr Child Health ; 59(1): 199, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36630277
20.
BMC Pharmacol Toxicol ; 24(1): 2, 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36639796

RESUMO

INTRODUCTION: The literature recommends against the use of fondaparinux in patients with kidney failure and dialysis as it may, with repeated dosing, accumulate and put patients at risk of bleeding. The management of patients with thrombosis in the presence of heparin-induced thrombocytopenia HIT requires the introduction of an alternative anticoagulant like bivalirudin or argatroban. When these drugs are not available, fondaparinux, remains the only alternative. In similar scenarios, there are few studies addressing how to administer it.  METHODS: We developed a protocol for fondaparinux in patients with renal failure where pharmacokinetic parameters are altered, and levels changed only after hemodialysis or in cases of residual renal activity. Patients received a full first dose except for high risk of bleeding. We targeted a peak anti-factor Xa activity level of 0.6-1.3 units/ml and changed the subsequent dose accordingly. Furthermore, we monitored the patients for signs of bleeding, a drop in hemoglobin level, or clinical signs of thrombosis.  DISCUSSION: We described 10 patients with kidney failure and suspected HIT taking fondaparinux. All the patients achieved therapeutic anti-factor Xa activity levels. However, one developed new-onset venous thromboembolism (VTE) despite therapeutic anti-factor Xa levels. Another patient experienced a bleeding episode. We believe that these two patients developed complications due to their medical conditions rather than the use of fondaparinux. CONCLUSION: Fondaparinux can be safely used in kidney failure using our protocol. However, despite its safety profile and relative success, this case series was small. More robust studies need to be conducted prior to drawing conclusions.


New Fondaparinux Protocol to Reduce the Risk of Blood Thickening and Blood Clots Formation in Adults with Kidney Disease and Heparin-induced Thrombocytopenia (drop in platelets after the use of heparin): A Test Study.Fondaparinux is a drug used to treat patients suffering from thrombosis (clot in blood) and prevent vessels occlusions. When patients have kidney disease, the ideal treatment for thrombosis would be heparin; and, in case of Heparin Induced Thrombocytopenia (HIT), an unexpected drop in platelets after the use of heparin, the ideal treatment would be argatroban or bivalirudin. Fondaparinux can be used for HIT. However, studies recommend against its use in kidney disease as it might accumulate and cause bleeding.We were put in a challenging situation where we had patients with life-threatening thrombosis, kidney disease, HIT and unavailability of both argatroban and bivalirudin. Our only option was fondaparinux. We had to devise a safe and efficient protocol. The starting dose was the one used had the patient had a normal kidney function. Then, anti-Factor Xa activity was regularly measured with the target level 0.6-1.3units/ml 4 h after a dose. The dose was individualized, changed based on the Factor Xa activity result, the risk of bleeding or thrombosis, the overall kidney function and the need for dialysis.Our protocol was tested on 10 patients. All our patients could reach the target and safe Factor Xa activity. We had 2 exceptions. The first had a clotting event despite having therapeutic Factor Xa activity and the second was a very sick cancer patient who was bleeding despite skipping many doses of fondaparinux. We consider that these 2 cases developed complications due to their medical conditions rather than the use of fondaparinux.We concluded that fondaparinux can be safely used in patients with kidney disease, granted that Factor Xa activity is measured, the risk of bleeding is weighed to the risk of thrombosis and the dose is individualized. However, our sample size is small and further studies with a larger number of patients are needed to draw a conclusion.


Assuntos
Anticoagulantes , Fondaparinux , Insuficiência Renal , Trombocitopenia , Trombose , Adulto , Humanos , Anticoagulantes/uso terapêutico , Fondaparinux/uso terapêutico , Hemorragia/induzido quimicamente , Heparina/efeitos adversos , Insuficiência Renal/tratamento farmacológico , Estudos Retrospectivos , Trombocitopenia/induzido quimicamente , Trombocitopenia/tratamento farmacológico , Trombose/tratamento farmacológico
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