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1.
Clin Med Res ; 22(2): 112-114, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39231624

RESUMO

Platelet counts in reactive thrombocytosis rarely exceed 1000 × 109/L. We present the case of a male patient, aged 80 years, with quiescent rheumatoid arthritis who was found to have a platelet count of 1011 × 109/L on routine laboratory testing. The patient was initially asymptomatic but developed leukocytosis to 23.1 × 109/L on hospital day 2. Diagnostic work-up revealed obstructive nephrolithiasis and pyelonephritis, and the thrombocytosis and leukocytosis gradually resolved with empiric antibiotic treatment and ureteral stent placement. Tests for myeloproliferative disorders, including JAK-2V617F mutation, BCR-ABL for chronic myeloid leukemia and acute lymphocytic leukemia, and myeloproliferative neoplasms (MPL/CALR), were negative. Physicians should be aware that in rare cases reactive thrombocytosis can exceed 1000 × 109/L, and that markedly elevated platelet counts in the setting of urinary tract infections may be an early sign of obstructive uropathy.


Assuntos
Nefrolitíase , Pielonefrite , Trombocitose , Humanos , Pielonefrite/complicações , Pielonefrite/diagnóstico , Masculino , Trombocitose/complicações , Trombocitose/diagnóstico , Trombocitose/sangue , Nefrolitíase/complicações , Nefrolitíase/diagnóstico , Idoso de 80 Anos ou mais , Contagem de Plaquetas , Antibacterianos/uso terapêutico
2.
Sci Rep ; 14(1): 18858, 2024 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-39143127

RESUMO

C-Mannosyl tryptophan (CMW), a unique glycosylated amino acid, is considered to be produced by degradation of C-mannosylated proteins in living organism. Although protein C-mannosylation is involved in the folding and secretion of substrate proteins, the pathophysiological function in the hematological system is still unclear. This study aimed to assess CMW in the human hematological disorders. The serum CMW levels of 94 healthy Japanese workers were quantified using hydrophilic interaction liquid chromatography. Platelet count was positively correlated with serum CMW levels. The clinical significance of CMW in thrombocytosis of myeloproliferative neoplasms (T-MPN) including essential thrombocythemia (ET) were investigated. The serum CMW levels of the 34 patients with T-MPN who presented with thrombocytosis were significantly higher than those of the 52 patients with control who had other hematological disorders. In patients with T-MPN, serum CMW levels were inversely correlated with anemia, which was related to myelofibrosis (MF). Bone marrow biopsy samples were obtained from 18 patients with ET, and serum CMW levels were simultaneously measured. Twelve patients with bone marrow fibrosis had significantly higher CMW levels than 6 patients without bone marrow fibrosis. Collectively, these results suggested that CMW could be a novel biomarker to predict MF progression in T-MPN.


Assuntos
Transtornos Mieloproliferativos , Trombocitose , Triptofano , Humanos , Masculino , Feminino , Triptofano/sangue , Pessoa de Meia-Idade , Idoso , Transtornos Mieloproliferativos/sangue , Trombocitose/sangue , Adulto , Biomarcadores/sangue , Biomarcadores Tumorais/sangue , Mielofibrose Primária/sangue , Trombocitemia Essencial/sangue , Idoso de 80 Anos ou mais , Contagem de Plaquetas , Medula Óssea/patologia , Medula Óssea/metabolismo
3.
Biochem Med (Zagreb) ; 34(2): 021002, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38882587

RESUMO

This case report describes a case of pseudonormokalemia, true hypokalemia. Often, only laboratory values outside the normal range gain attention and false normal results are at risk of not being noticed. However, a disease state may be masked by another pathological process. Here, a 50-year old male was admitted to the Department of Internal Medicine due to sepsis from a dental infection. Initially, serum potassium measurement revealed a normal value of 4 mmol/L (reference interval 3.8-5.1 mmol/L). Thrombocyte number was above 500x109/L. Due to our policy to recommend a repeated measurement of potassium in whole blood or heparin plasma if a patient has thrombocytosis, pseudonormokalemia was identified because the heparin plasma potassium value was only 2.9 mmol/L (reference interval 3.5-4.8 mmol/L). The physiological difference between serum and plasma concentration is no more than 0.3 mmol/L. In this case, potassium concentration were falsely elevated in the serum sample, probably caused by the high number of platelets releasing potassium during clotting. Interpretative comments in patients with thrombocytosis over 500x109/L recommending plasma potassium measurement are helpful. The best way to eliminate pseudohyperkalemia and pseudonormokalemia phenomena caused by thrombocytosis is to completely change towards heparin plasma as the standard material.


Assuntos
Hipopotassemia , Potássio , Humanos , Masculino , Potássio/sangue , Pessoa de Meia-Idade , Hipopotassemia/sangue , Hipopotassemia/diagnóstico , Trombocitose/sangue , Trombocitose/diagnóstico
4.
Urol Int ; 108(5): 421-428, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38714188

RESUMO

INTRODUCTION: Studies assessing the impact of preoperative and first-day postoperative values of leukocytes, thrombocytes, and platelet/leukocyte ratio (PLR) after radical cystectomy (RC) are sparse. We aimed to assess the impact of these factors on long-term survival after RC. METHODS: An analysis of patients undergoing open RC from 2004 to 2023 at our center was performed. Leukocytosis was defined as ≥8,000 leukocytes/µL and thrombocytosis as ≥400,000 thrombocytes/µL. Similarly, the cutoff for PLR was set at 28. A multivariable Cox regression analysis was performed to assess the role of leukocytosis, thrombocytosis, and PLR on long-term survival after RC. For all analyses, hazard ratios (HRs) with the corresponding 95% confidence intervals (CIs) were estimated. RESULTS: A total of 1,817 patients with a median age of 70 years (interquartile range [IQR]: 62-77) were included. Overall, 804 (44%), 175 (10%), and 1,296 (71%) patients presented with leukocytosis, thrombocytosis, and PLR ≥28 preoperatively. Accordingly, 1,414 (78%), 37 (2%), and 249 (14%) patients presented with leukocytosis, thrombocytosis, and PLR ≥28 on the first day after RC. At a median follow-up of 26 months (IQR: 8-68) after RC, 896 (49%) patients died. In the multivariate Cox regression analysis after adjusting for major perioperative risk factors, only preoperative leukocytosis (HR: 1.3, 95% CI: 1.1-1.6, p = 0.01), as well as both preoperative and first-day thrombocytosis (HR: 2.1, 95% CI: 1.5-2.9, and HR: 2.8, 95% CI: 1.6-5.1, p < 0.001, accordingly) were associated with worse overall survival. CONCLUSION: PLR should not be used as a prognostic marker for survival after RC. On the contrary, preoperative leukocytosis, as well as preoperative and first-day thrombocytosis should raise awareness among clinicians performing RC since they were independently associated with worse survival after RC.


Assuntos
Cistectomia , Neoplasias da Bexiga Urinária , Humanos , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Cistectomia/efeitos adversos , Estudos Prospectivos , Prognóstico , Neoplasias da Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/sangue , Contagem de Plaquetas , Fatores de Tempo , Contagem de Leucócitos , Leucocitose/sangue , Trombocitose/sangue , Período Perioperatório , Estudos de Coortes , Taxa de Sobrevida
5.
Brain Inj ; 38(10): 818-826, 2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-38679938

RESUMO

OBJECTIVE: To determine the role of platelet counts in the context of the decision to treat patients with non-compounded, non-surgically-treated blunt traumatic brain injury (NCNS-bTBI) with anticoagulants/antiaggregants. METHODS: A retrospective analysis of 141 anticoagulants/antiaggregants-naïve patients with NCNS-bTBI. Changes in PT-INR and prolonged aPTT were examined and correlated with Marshall and Rotterdam scores, clinical and neuroradiological outcomes. RESULTS: Three groups of platelet counts were identified. Group 1 (83% of patients) had normal platelet counts (150,000-450,000 platelets/mm3) from admission to discharge. Group 2 (13%) developed transient thrombocytopenia (<150,000 platelets/mm3) 2-3 days post-trauma. Group 3 (4%) developed extreme thrombocytosis > 1,000,000/mm3 platelets 6-9 days post-trauma. Neither acute coagulopathy of trauma nor progressive hemorrhagic insults followed NCNS-bTBI. Moreover, while patients with thrombocytosis/extreme thrombocytosis presented with a worse Glasgow coma score (GCS) on admission (8.8 ± 2.9 vs. 13 ± 2, p < 0.01) and had longer hospitalization (13.5 ± 10.4 vs. 4.5 ± 2.1 days), their improvement at discharge was the highest (delta GCS, 4 ± 2.8 vs. 1.2 ± 2.1, p = 0.05). Traumatic subarachnoid hemorrhage was associated with isolated thrombocytosis and 'best improvement.' No thromboembolic or hemorrhagic complications occurred. CONCLUSION: NCNS-bTBI, thrombocytosis was correlated with better outcomes and was not associated with an increased risk for developing thromboembolism or hemorrhage, precluding the immediate need for any additional antiaggregates.


Assuntos
Lesões Encefálicas Traumáticas , Humanos , Masculino , Feminino , Lesões Encefálicas Traumáticas/sangue , Lesões Encefálicas Traumáticas/complicações , Estudos Retrospectivos , Adulto , Contagem de Plaquetas , Pessoa de Meia-Idade , Escala de Coma de Glasgow , Trombocitopenia/sangue , Trombocitopenia/etiologia , Anticoagulantes/uso terapêutico , Idoso , Trombocitose/sangue , Trombocitose/etiologia , Adulto Jovem , Traumatismos Cranianos Fechados/complicações , Traumatismos Cranianos Fechados/sangue , Resultado do Tratamento
6.
7.
Morphologie ; 108(362): 100777, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38579392

RESUMO

The presence of schistocytes can be responsible for spurious thrombocytosis and spuriously low red blood count (RBC). The hemoglobin concentration will be correct (as the method usually used, destroys the red cells and converts a substantial proportion of the hemoglobin to a stable pigment) but mean corpuscular hemoglobin (MCH) is falsely high. The platelets and RBC histograms of the full blood count analyzers play an important role in the identification of schistocytes and must be carefully analyzed before reporting the previously full blood count parameters. In patients in ECMO, where can be expected the presence of a small number of schistocytes, this evaluation is particularly important to avoid wrong clinical decisions.


Assuntos
Oxigenação por Membrana Extracorpórea , Humanos , Masculino , Trombocitose/sangue , Trombocitose/etiologia , Eritrócitos Anormais/patologia , Índices de Eritrócitos , Plaquetas , Contagem de Eritrócitos
8.
J Appl Lab Med ; 9(4): 833-847, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38549553

RESUMO

BACKGROUND: The most ordered laboratory test worldwide is the complete blood count (CBC). CONTENT: In this primer, an introduction to platelet testing in the context of the CBC is provided with a discussion of the laboratory evaluation of platelet abnormalities including thrombocytopenia and thrombocytosis. SUMMARY: As clinical chemists continue to be tasked to direct laboratories outside of the traditional clinical chemistry sections such as hematology, expertise must be developed. This primer is dedicated to that effort.


Assuntos
Plaquetas , Trombocitopenia , Trombocitose , Humanos , Trombocitose/sangue , Trombocitose/diagnóstico , Trombocitopenia/diagnóstico , Trombocitopenia/sangue , Contagem de Plaquetas/métodos , Contagem de Células Sanguíneas/métodos , Contagem de Células Sanguíneas/instrumentação , Química Clínica/métodos , Química Clínica/normas
10.
Int J Gynecol Cancer ; 31(11): 1437-1442, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34725243

RESUMO

OBJECTIVE: Endometrial cancer prognosis is related to stage, histology, myometrial invasion, and lymphovascular space invasion. Several studies have examined the association between pretreatment thrombocytosis and patient outcomes with contrasting results regarding prognosis. Our aim was to evaluate the association of pretreatment platelet count with outcomes in endometrial cancer patients. METHODS: This is an Israeli Gynecologic Oncology Group multicenter retrospective cohort study of consecutive patients with endometrial cancer, who underwent surgery between January 2002 and December 2014. Patients were grouped as low risk (endometrioid G1-G2 and villoglandular) and high risk (endometrioid G3, uterine serous papillary carcinoma, clear cell carcinoma, and carcinosarcoma). Those with stage I disease were compared with stages II-IV. Disease stages were reviewed and updated to reflect International Federation of Gynecology and Obstetrics (FIGO) 2009 staging. All patients underwent pelvic washings for cytology and total abdominal or laparoscopic hysterectomy with bilateral salpingo-oophorectomy. Pelvic lymph node assessment was performed in patients with tumors of moderate-high risk histology or deep myometrial invasion. Para-aortic sampling was performed at the surgeon's discretion. Patients were categorized by pretreatment platelet count into two groups: ≤400×109/L and >400×109/L (defined as thrombocytosis). Clinical and pathological features were compared using Student t-test, χ2 or Fisher's exact test. Survival measures were plotted with the Kaplan-Meier method and compared using the log-rank test. A Cox proportional hazards model was used for multivariable comparison of associations. RESULTS: Of the 1482 patients included, most had stage I disease (961; 74.8%) and most had endometrioid histology (927; 64.1%). A total of 1392 patients (94%) had pretreatment platelet counts ≤400×109/L and 90 (6%) had pretreatment thrombocytosis. Patients with thrombocytosis had a significantly higher rate of high-grade malignancy, advanced stage, lymphovascular space invasion, low uterine segment involvement, and lymph node metastases. They also had shorter 5 year disease-free survival (65% vs 80%, p=0.003), disease-specific survival (63% vs 83%, p<0.05) and overall survival (59% vs 77%, p<0.05). On multivariate analysis, an elevated pretreatment thrombocyte count remained a significant independent predictor for disease-specific survival and overall survival. CONCLUSIONS: Pretreatment thrombocytosis is an independent prognostic factor for decreased disease-specific survival and overall survival among patients with endometrial cancer, and can serve as a predictor of poor outcome.


Assuntos
Adenocarcinoma de Células Claras/mortalidade , Carcinoma Endometrioide/mortalidade , Cistadenocarcinoma Seroso/mortalidade , Neoplasias do Endométrio/mortalidade , Trombocitose/epidemiologia , Adenocarcinoma de Células Claras/sangue , Adenocarcinoma de Células Claras/cirurgia , Carcinoma Endometrioide/sangue , Carcinoma Endometrioide/cirurgia , Cistadenocarcinoma Seroso/sangue , Cistadenocarcinoma Seroso/cirurgia , Neoplasias do Endométrio/sangue , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Israel/epidemiologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Trombocitose/sangue
11.
JAMA Netw Open ; 4(8): e2120633, 2021 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-34383058

RESUMO

Importance: Individuals with newly diagnosed cancer often have a high platelet count (thrombocytosis). Whether thrombocytosis is associated with the presence of an undiagnosed cancer remains unknown. Objective: To assess whether a new diagnosis of thrombocytosis is associated with a subsequent risk of cancer among adults. Design, Setting, and Participants: This population-based retrospective cohort study was conducted using linked laboratory data from Ontario, Canada, from January 1, 2007, to December 31, 2017, with follow-up until December 31, 2018. The study cohort included adults aged 40 to 75 years on the date of a routine complete blood count (CBC) test (index test) who had a normal platelet count in the 2 previous years and no history of cancer. Data analysis was performed in December 2020. Exposures: Exposed individuals were those with a platelet count greater than 450 × 109/L. Matched unexposed control individuals had a platelet count within the reference range (150 × 109/L to 450 × 109/L) reported within 30 days of the exposure. Main Outcomes and Measures: Incident cancers within 5 years after diagnosis of thrombocytosis. Absolute and relative risks for cancer associated with thrombocytosis were estimated for all cancers and for cancers at specific sites. Results: Of the 3 386 716 Ontario residents with a recorded routine CBC test result, 53 339 (1.6%) had thrombocytosis and a prior normal platelet count. Among individuals with thrombocytosis, the median age was 59.7 years (interquartile range, 50.2-67.4 years) and 37 349 (70.0%) were women. Among the 51 624 individuals with thrombocytosis included in the matched analysis, 2844 (5.5%) had received a diagnosis of a solid cancer in the 2-year follow-up period and 3869 (7.5%) had received a diagnosis within 5 years. The relative risk (RR) for developing any solid cancer within 2 years was 2.67 (95% CI, 2.56-2.79). Associations were found between thrombocytosis and cancers of the ovary (RR, 7.11; 95% CI, 5.59-9.03), stomach (RR, 5.53; 95% CI, 4.12-7.41), colon (RR, 5.41; 95% CI, 4.80-6.10), lung (RR, 4.41; 95% CI, 4.02-4.85), kidney (RR, 3.64; 95% CI, 2.94-4.51), and esophagus (RR, 3.64; 95% CI, 2.46-5.40). Conclusions and Relevance: In this cohort study, an increased platelet count was associated with an increased risk of cancer for at least 2 years. The results suggest that individuals with unexplained thrombocytosis should be offered screening for several cancers.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias/sangue , Neoplasias/etiologia , Trombocitose/sangue , Trombocitose/complicações , Trombocitose/epidemiologia , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Ontário/epidemiologia , Valor Preditivo dos Testes , Estudos Retrospectivos
12.
Hematology ; 26(1): 301-304, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33663351

RESUMO

BACKGROUND: Acquired von Willebrand syndrome (AVWS) is a rare, frequently underdiagnosed and underestimated bleeding disorder. Careful personal and family history and late-onset mucocutaneous bleeding could help clarify the etiology of bleeding deficiency. CASE PRESENTATION: An 82-year-old male patient was admitted to our clinic with a severe nosebleed on 30.05.2018. Laboratory results revealed thrombocytosis, elevated white blood cell count and high LDH. Basic coagulation parameters were normal. He was referred to our clinic, where a bone marrow biopsy was taken. His personal and family history had no mention of bleeding disorders, nor was he on anticoagulant therapy. We detected elevated VWF antigen and decreased VWF ristocetin cofactor activity. Loss of high molecular weight multimers was detected by using agarose gel electrophoresis. These laboratory results were indicative of AVWS. Hydroxyurea treatment was initiated, leading to a gradual decrease in platelet count. The histological examination revealed essential thrombocytosist while mutation analysis was JAK2/CALR/MPL negative. However, due to severe nosebleeds, the patient was hospitalized and needed blood transfusion. A cardiological check-up revealed the progression of aortic valve stenosis. After, balloon-dilation a transcatheter aortic valve implantation was performed. As a result, VWF activity and activity to antigen ratio returned to normal as did multimeric structure. In July 2019, the follow-up examination showed that the patient was in a satisfactory condition, with normal hematological parameters, and no new nosebleed episode occurred. CONCLUSIONS: The patient complained of recurring nosebleeds, which stopped completely after the resolution of both underlying conditions successful cytoreductive treatment of triple-negative ET and transcatheteric aortic valve replacement.


Assuntos
Doenças de von Willebrand/diagnóstico , Doenças de von Willebrand/terapia , Fator de von Willebrand/análise , Idoso de 80 Anos ou mais , Transfusão de Sangue , Inibidores Enzimáticos/uso terapêutico , Hemorragia/sangue , Hemorragia/complicações , Hemorragia/terapia , Humanos , Hidroxiureia/uso terapêutico , Masculino , Trombocitose/sangue , Trombocitose/complicações , Trombocitose/terapia , Doenças de von Willebrand/sangue , Doenças de von Willebrand/complicações
13.
Laryngoscope ; 131(7): 1542-1547, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33443771

RESUMO

OBJECTIVE/HYPOTHESIS: Early and objective prediction of complications in head and neck reconstructive surgery could decrease morbidity and prolonged hospital stays but unfortunately most complications are not identified until their effect is fully realized. There are limited data regarding the association of platelet levels and post-operative complications. Post-operative thrombocytosis (POTCT) is proposed as a possible indicator for complications following free-flap reconstruction. STUDY DESIGN: Retrospective review. METHODS: A multisite retrospective chart review of patients undergoing free tissue transfer between 2013 and 2018 was undertaken. POTCT was recorded and data normalized between institutions. Data were compared between groups using t-tests and logistic regression (P < .05). A lag-1 difference was used to compare the rate of change in platelet values. RESULTS: A total of 398 patients were included. POTCT and a rate of change of 30 K between POD5 and POD6 was significantly associated with the presence of post-operative complication (P = .007). Additionally, lag-1 difference demonstrated a significant association of change in daily platelet counts and complication rates. CONCLUSIONS: Isolated POTCT may be an early predictor of complications in HNC patients undergoing free-flap reconstruction. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:1542-1547, 2021.


Assuntos
Retalhos de Tecido Biológico/efeitos adversos , Neoplasias de Cabeça e Pescoço/cirurgia , Microcirurgia/efeitos adversos , Infecção da Ferida Cirúrgica/epidemiologia , Trombocitose/epidemiologia , Feminino , Retalhos de Tecido Biológico/transplante , Neoplasias de Cabeça e Pescoço/sangue , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Microcirurgia/métodos , Projetos Piloto , Contagem de Plaquetas , Período Pós-Operatório , Valor Preditivo dos Testes , Curva ROC , Valores de Referência , Reprodutibilidade dos Testes , Estudos Retrospectivos , Medição de Risco/métodos , Fatores de Risco , Infecção da Ferida Cirúrgica/etiologia , Trombocitose/sangue , Trombocitose/diagnóstico
14.
Pediatr Res ; 90(2): 341-346, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33469189

RESUMO

BACKGROUND: Iron deficiency anemia (IDA)-induced reactive thrombocytosis can occur in children and adults. The underlying mechanism for this phenomenon is indeterminate. Traditional cytokines such as thrombopoietin (TPO), interleukin-6 (IL-6), and IL-11 involved in megakaryopoiesis have not been shown to be the cause. Recent studies suggest that growth factors and signaling molecules involved with angiogenesis influence the proliferation and differentiation of megakaryocytes. METHODS: We investigated the possible association between angiogenic cytokines with reactive thrombocytosis due to IDA in an iron-deficient (ID) rat model. Complete blood count, iron panels, and TPO levels were measured at baseline and 5 weeks later in both control (C) and ID rats. Angiogenic cytokines were evaluated in the bone marrow in all rats. RESULTS: We successfully induced IDA in our rats by phlebotomy and reduced iron diet. We did not find an increase of TPO in ID rats. A review of the bone marrow showed an increase in the number of megakaryocytes, vascular structures, as well as increased intensity of stain for vascular endothelial growth factor (VEGF), and CXC chemokine receptor 4 (CXCR4) in rats with IDA compared to controls. CONCLUSIONS: Our results of histological bone marrow data suggest an important role for angiogenesis in the development of IDA-induced thrombocytosis. IMPACT: Thrombocytosis is common with IDA in both children and adults, but the mechanism is unclear. We confirmed that TPO is not the major driver of iron deficiency-associated thrombocytosis. We confirmed the increase in the number of megakaryocytes in the bone marrow despite stable TPO levels. We provided evidence supporting an important role of angiogenesis in megakaryocytopoiesis/thrombopoiesis with increased vascular structures and angiogenic cytokines in the bone marrow of iron-deficient rats. The demonstration that angiogenesis may play an important role in secondary thrombocytosis could lead to a new approach in treating symptomatic reactive thrombocytosis by targeting angiogenesis.


Assuntos
Anemia Ferropriva/complicações , Medula Óssea/irrigação sanguínea , Megacariócitos/metabolismo , Neovascularização Patológica , Receptores CXCR4/metabolismo , Trombocitose/etiologia , Trombopoese , Fator A de Crescimento do Endotélio Vascular/metabolismo , Anemia Ferropriva/sangue , Anemia Ferropriva/patologia , Animais , Modelos Animais de Doenças , Masculino , Megacariócitos/patologia , Ratos Sprague-Dawley , Transdução de Sinais , Trombocitose/sangue , Trombocitose/patologia , Trombopoetina/metabolismo
15.
Cells ; 11(1)2021 12 24.
Artigo em Inglês | MEDLINE | ID: mdl-35011611

RESUMO

Over 95% of Polycythemia Vera (PV) patients carry the V617F mutation in the tyrosine kinase Janus kinase 2 (JAK2), resulting in uncontrolled erythroid proliferation and a high risk of thrombosis. Using mass spectrometry, we analyzed the RBC membrane proteome and showed elevated levels of multiple Ca2+ binding proteins as well as endoplasmic-reticulum-residing proteins in PV RBC membranes compared with RBC membranes from healthy individuals. In this study, we investigated the impact of JAK2V617F on (1) calcium homeostasis and RBC ion channel activity and (2) protein expression and sorting during terminal erythroid differentiation. Our data from automated patch-clamp show modified calcium homeostasis in PV RBCs and cell lines expressing JAK2V617F, with a functional impact on the activity of the Gárdos channel that could contribute to cellular dehydration. We show that JAK2V617F could play a role in organelle retention during the enucleation step of erythroid differentiation, resulting in modified whole cell proteome in reticulocytes and RBCs in PV patients. Given the central role that calcium plays in the regulation of signaling pathways, our study opens new perspectives to exploring the relationship between JAK2V617F, calcium homeostasis, and cellular abnormalities in myeloproliferative neoplasms, including cellular interactions in the bloodstream in relation to thrombotic events.


Assuntos
Cálcio/metabolismo , Eritrócitos/metabolismo , Eritropoese , Homeostase , Organelas/metabolismo , Policitemia Vera/sangue , Policitemia Vera/metabolismo , Animais , Tamanho Celular , Eritroblastos/metabolismo , Células Eritroides/metabolismo , Células Eritroides/patologia , Humanos , Canais de Potássio Ativados por Cálcio de Condutância Intermediária/metabolismo , Espaço Intracelular/metabolismo , Janus Quinase 2/genética , Camundongos Endogâmicos C57BL , Mutação/genética , Proteoma/metabolismo , Reticulócitos/metabolismo , Ribossomos/metabolismo , Trombocitose/sangue
16.
Int J Mol Sci ; 21(21)2020 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-33142915

RESUMO

Platelets are critical components of a number of physiologic processes, including tissue remodeling after injury, wound healing, and maintenance of vascular integrity. Increasing evidence suggests that platelets may also play important roles in cancer. In ovarian cancer, thrombocytosis, both at the time of initial diagnosis and at recurrence, has been associated with poorer prognosis. This review describes current evidence for associations between thrombocytosis and ovarian cancer prognosis and discusses the clinical relevance of platelet count thresholds and timing of assessment. In addition, we discuss several mechanisms from in vitro, in vivo, and clinical studies that may underlie these associations and recommend potential approaches for novel therapeutic targets for this lethal disease.


Assuntos
Plaquetas/patologia , Neoplasias Ovarianas/patologia , Trombocitose/patologia , Feminino , Humanos , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/etiologia , Prognóstico , Trombocitose/sangue
17.
Toxicol Lett ; 335: 71-81, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33122006

RESUMO

Destruction of liver sinusoidal endothelial cells (LSECs) is an initial event in sinusoidal obstruction syndrome (SOS) that leads to accumulation of platelets in the liver. Herein, we explored the role of platelets during progression of experimental SOS induced by monocrotaline (MCT) in mice. Depletion of platelets using an anti-CD41 antibody or anti-thrombocyte serum exacerbated MCT-induced liver injury in C57BL/6 mice, as indicated by an increase in the alanine transaminase (ALT) level, which was associated with hemorrhagic necrosis. Thrombocytosis induced by thrombopoietin (TPO) or the TPO receptor agonist romiplostim (ROM) attenuated MCT-induced liver injury, as evidenced by lower levels of ALT and mRNA encoding matrix metalloproteinase (MMP) 9, and higher levels of mRNA encoding vascular endothelial growth factor receptor (VEGFR) 2 and VEGFR3. The level of activated hepatic platelets was higher in TPO- and ROM-treated mice than in saline-treated mice. Co-culture with a high number of platelets increased the viability of LSECs and their mRNA levels of CD31, VEGFR2, and VEGFR3, and decreased their mRNA level of MMP9. The level of VEGF-A was increased in the culture medium of LSECs co-cultured with platelets. These results indicate that platelets attenuate MCT-induced liver injury by minimizing damage to LSECs.


Assuntos
Plaquetas/efeitos dos fármacos , Doença Hepática Crônica Induzida por Substâncias e Drogas/sangue , Hepatopatia Veno-Oclusiva/sangue , Hepatopatia Veno-Oclusiva/induzido quimicamente , Monocrotalina/toxicidade , Trombocitose/sangue , Animais , Plaquetas/citologia , Sobrevivência Celular/efeitos dos fármacos , Doença Hepática Crônica Induzida por Substâncias e Drogas/prevenção & controle , Técnicas de Cocultura , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/patologia , Hepatopatia Veno-Oclusiva/prevenção & controle , Testes de Função Hepática , Masculino , Camundongos Endogâmicos C57BL , Contagem de Plaquetas , Receptores Fc , Receptores de Trombopoetina/agonistas , Proteínas Recombinantes de Fusão/farmacologia , Trombocitose/induzido quimicamente , Trombopoetina/farmacologia
18.
Bull Exp Biol Med ; 169(6): 795-797, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33098506

RESUMO

The effects of TLR4 blocker on blood cell morphology, concentrations proinflammatory cytokines, and functional state of the liver and kidneys were studied in outbred male rats (n=60) after intravenous injection of 20 mg/kg LPS isolated from opportunistic Proteus mirabilis strain ATCC 51393. TLR4 blocker TLR4-IN-C34 was injected intravenously in a dose of 1 mg/kg/day over 3 days. Systemic inflammatory reaction induced by LPS was characterized by elevation of serum TNFα, IL-1ß, IL-6, erythrocyte sedimentation rate, leukocytosis, and thrombocytosis. Increased activity of hepatocyte enzymes (ALT, alkaline phosphatase, and lactate dehydrogenase), retention of nitrogen metabolites (urea and creatinine), elevated content of protein oxidation products, and enhanced protein catabolism were also observed. Administration of TLR4 blocker reduced parameters of inflammatory reaction and prevented the development of hypercatabolic syndrome; endotoxicosis and kidney function indicators approached the normal levels.


Assuntos
Anti-Inflamatórios/farmacologia , Leucocitose/tratamento farmacológico , Lipopolissacarídeos/antagonistas & inibidores , Piranos/farmacologia , Sepse/tratamento farmacológico , Trombocitose/tratamento farmacológico , Receptor 4 Toll-Like/antagonistas & inibidores , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Animais , Animais não Endogâmicos , Creatinina/sangue , Modelos Animais de Doenças , Regulação da Expressão Gênica , Injeções Intravenosas , Interleucina-1beta/sangue , Interleucina-1beta/genética , Interleucina-6/sangue , Interleucina-6/genética , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , L-Lactato Desidrogenase/sangue , Leucocitose/sangue , Leucocitose/patologia , Lipopolissacarídeos/toxicidade , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Proteus mirabilis/química , Ratos , Sepse/sangue , Sepse/patologia , Transdução de Sinais , Trombocitose/sangue , Trombocitose/patologia , Receptor 4 Toll-Like/sangue , Receptor 4 Toll-Like/genética , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/genética , Ureia/sangue
19.
Int J Mol Sci ; 21(17)2020 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-32867390

RESUMO

There is an increasing number of studies showing that thrombocytosis-accompanying a variety of solid tumors including colorectal cancer (CRC)-is associated with shorter survival and earlier development of metastases. The mechanisms of cancer-associated thrombocytosis are not completely understood yet. The aim of our study was to evaluate the role of IL-6 in tumor development and thrombocytosis in mice with inflammation-induced CRC, using a CRISPR/cas9 IL-6 knockout (KO) strain. Adult male FB/Ant mice (n = 39) were divided into four groups: (1) IL-6 KO controls (n = 5); (2) IL-6 KO CRC model group (n = 18); (3) Wild-type (WT) controls (n = 6); and (4) WT CRC model group (n = 10). CRC model animals in (2) and (4) received azoxymethane (AOM)/dextran sodium sulfate (DSS) treatment to induce inflammation-related CRC. Plasma and liver tissues were obtained to determine platelet counts, IL-6 and thrombopoietin-1 (TPO) levels. In 1 WT and 2 IL-6 KO mice in vivo confocal endomicroscopy and 18F-fluorodeoxyglucose (FDG) PET/MRI examinations were performed to evaluate the inflammatory burden and neoplastic transformation. At the end of the study, tumorous foci could be observed macroscopically in both CRC model groups. Platelet counts were significantly elevated in the WT CRC group compared to the IL-6 KO CRC group. TPO levels moved parallelly with platelet counts. In vivo fluorescent microscopy showed signs of disordered and multi-nuclear crypt morphology with increased mucus production in a WT animal, while regular mucosal structure was prominent in the IL-6 KO animals. The WT animal presented more intense and larger colonic FDG uptake than IL-6 KO animals. Our study confirmed thrombocytosis accompanying inflammation-related CRC and the crucial role of IL-6 in this process. Significantly higher platelet counts were found in the WT CRC group compared to both the control group and the IL-6 KO group. Concomitantly, the tumor burden of WT mice was also greater than that of IL-6 KO mice. Our findings are in line with earlier paraneoplastic IL-6 effect suggestions.


Assuntos
Neoplasias Associadas a Colite/genética , Interleucina-6/genética , Trombocitose/genética , Animais , Azoximetano/efeitos adversos , Neoplasias Associadas a Colite/induzido quimicamente , Neoplasias Associadas a Colite/complicações , Neoplasias Associadas a Colite/diagnóstico por imagem , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Técnicas de Inativação de Genes , Imageamento por Ressonância Magnética , Masculino , Camundongos , Contagem de Plaquetas , Tomografia por Emissão de Pósitrons , Trombocitose/sangue , Trombocitose/etiologia , Trombocitose/metabolismo , Trombopoetina/metabolismo
20.
Rev. Soc. Bras. Clín. Méd ; 18(3): 171-173, mar 2020.
Artigo em Português | LILACS | ID: biblio-1361517

RESUMO

Este relato teve como objetivo apresentar um caso de elderly onset rheumatoid arthritis associada à trombocitose reacional significativa. À admissão, o paciente apresentava quadro de poliartrite de pequenas e grandes articulações associado à rigidez matinal. Após exames solicitados, evidenciaram-se trombocitose de 1.697.000 cel./mm³ e anticorpos antipeptídeos citrulinados positivos, sendo diagnosticado com artrite reumatoide do tipo elderly onset rheumatoid arthritis.


This report aimed at presenting a case of elderly-onset rheumatoid arthritis associated with significant reactive thrombocytosis. On admission, the patient presented polyarthritis of small and large joints associated with morning stiffness. After the performance of the requested tests, thrombocytosis of 1,697,000 cells/mm3 and positive anti-CCP were evidenced, and the patient was diagnosed with elderly-onset rheumatoid arthritis.


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Artrite Reumatoide/diagnóstico , Trombocitose/diagnóstico , Artrite Reumatoide/complicações , Artrite Reumatoide/sangue , Fator Reumatoide/análise , Trombocitose/complicações , Trombocitose/sangue , Contagem de Células Sanguíneas , Sedimentação Sanguínea , Proteína C-Reativa/análise , Edema/etiologia , Anticorpos Antiproteína Citrulinada/isolamento & purificação
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