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1.
Niger J Clin Pract ; 23(8): 1141-1147, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32788493

RESUMO

Aims: This study was aimed at investigating the prognostic impact of pretreatment thrombocytosis in epithelial ovarian cancer (EOC) patients in Lagos, Nigeria. Methods: This was a retrospective cohort study involving the review of the clinical record of 72 patients with histologically confirmed EOC who were managed at the Lagos University Teaching Hospital, Lagos, Nigeria over a 7-year period from January 2010 to December 2016. Information on the sociodemographic data and platelet counts at diagnosis of EOC were retrieved from the patients' medical records. Descriptive statistics were then computed for all baseline patients' characteristics. Survival analyses were carried out using the Kaplan-Meier estimates. Multivariate analysis of these data was performed with the Cox proportional hazards model. Results: This study revealed that the prevalence of pretreatment thrombocytosis was 41.7% among the women with EOC. Fifty-three (73.6%) of the women had the advanced-stage disease (FIGO stage III-IV) while 52 (72.2%) had high-grade disease (II-III). The majority (66.7%) of the women had a serous histological type of EOC while 76.4% had documented recurrence. Pretreatment thrombocytosis was significantly associated with the women's parity (P = 0.009), serum carbohydrate antigen 125 levels (P = 0.018), median progression-free survival (PFS) (P < 0.001), 3-year median overall survival (OS) (P < 0.001), type of primary treatment (P = 0.002), extent of cytoreduction (P < 0.001), presence of ascites (P = 0.002), International Federation of Gynecology and Obstetrics (FIGO) stage (P = 0.008), and histological type (P = 0.011). Pretreatment thrombocytosis was negatively associated with PFS (hazard ratio [HR] = 0.25; 95% CI 0.83, 0.75; P = 0.014) and 3-year OS (HR = 0.03; 95% CI 0.03, 0.27; P = 0.002). Conclusions: The study suggests that pretreatment thrombocytosis may be a useful predictor of survivals in EOC patients.


Assuntos
Transtornos Plaquetários/etiologia , Carcinoma Epitelial do Ovário/mortalidade , Neoplasias Ovarianas/mortalidade , Trombocitose/epidemiologia , Adulto , Idoso , Antígenos Glicosídicos Associados a Tumores/sangue , Carcinoma Epitelial do Ovário/sangue , Carcinoma Epitelial do Ovário/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Nigéria/epidemiologia , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/patologia , Contagem de Plaquetas , Período Pré-Operatório , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Trombocitose/sangue
2.
Hamostaseologie ; 40(2): 221-225, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32455462

RESUMO

Patients with ventricular assist devices (VADs) and extracorporeal membrane oxygenation (ECMO) suffer from an increased risk for thromboembolic events as well as for hemorrhages. High shear stress in the mechanical device results in acquired von Willebrand syndrome (AVWS), characterized by a loss of high-molecular-weight multimers of von Willebrand factor (VWF) leading to an increased bleeding risk. Onset of AVWS occurs within hours, persists during the whole period of mechanical support, and subsides rapidly after explantation. Patients with the older HeartMate II exhibit more severe AVWS than those with the newer HeartMate III, thanks to lower shear stress in the latter. All ECMO and VAD patients exhibit thrombocytopathia and often thrombocytopenia which further increases the bleeding risk. Etiological models for AVWS are increased cleavage by the metalloproteinase ADAMSTS13, mechanical destruction of VWF, and shear-induced VWF binding to platelets. Platelet secretion defects may be caused by transient platelet activation leading to degranulation. AVWS can be diagnosed by detection of VWF multimers using gel-electrophoresis and functional assays of varying sensitivity (VWF ristocetin cofactor activity, VWF activity, VWF collagen binding). Platelet dysfunction is monitored using light transmission aggregometry and secretion defects are detectable using flow cytometry. Modest use of anticoagulants and a target-controlled therapy based on VWF parameters and other coagulation and platelet parameters are shown to be beneficial in this patient group. Persistent hemorrhages may be controlled with tranexamic acid and platelet concentrates. Prompt weaning from the device, when indicated, is the best therapeutic option to prevent recurrent bleeding.


Assuntos
Transtornos Plaquetários/sangue , Oxigenação por Membrana Extracorpórea/métodos , Doenças de von Willebrand/complicações , Doenças de von Willebrand/terapia , Feminino , Humanos , Masculino
3.
Int J Clin Pharmacol Ther ; 58(8): 454-456, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32324131

RESUMO

OBJECTIVE: Piperacillin/tazobactam (TZP ) is commonly used against multi-resistant nosocomial Pseudomonas infections. While TZP-induced thrombocytopenia is a well-known and easily diagnosed complication, we herein present an unusual case of spontaneous TZP-induced bleeding caused by platelet dysfunction. CASE SUMMARY: A 73-year-old-man experienced severe pulmonary hemorrhage and bloody diarrhea during the treatment with TZP for Pseudomonas aeruginosa ventilator-associated pneumonia. While both platelet count and coagulation tests were normal, platelet functional test revealed severely impaired ADP-dependent platelet aggregation. CONCLUSION: Platelet dysfunction is a little-known mechanism of TZP-induced bleeding. This is the second reported case of TZP-related bleeding that has been attributed to platelet dysfunction, and the first case report that has not been associated with surgery. While thrombocytopenia is easily recognized, this form of TZP-induced bleeding can be detected only by platelet functional tests.


Assuntos
Transtornos Plaquetários/etiologia , Piperacilina/efeitos adversos , Idoso , Antibacterianos/efeitos adversos , Infecção Hospitalar/tratamento farmacológico , Humanos , Combinação Piperacilina e Tazobactam , Pneumonia Associada à Ventilação Mecânica/tratamento farmacológico
4.
Int J Mol Sci ; 21(3)2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32041177

RESUMO

RasGRP2 is calcium and diacylglycerol-regulated guanine nucleotide exchange factor I that activates Rap1, which is an essential signaling-knot in "inside-out" αIIbß3 integrin activation in platelets. Inherited platelet function disorder caused by variants of RASGRP2 represents a new congenital bleeding disorder referred to as platelet-type bleeding disorder-18 (BDPLT18). We review here the structure of RasGRP2 and its functions in the pathophysiology of platelets and of the other cellular types that express it. We will also examine the different pathogenic variants reported so far as well as strategies for the diagnosis and management of patients with BDPLT18.


Assuntos
Transtornos Plaquetários/genética , Plaquetas/patologia , Fatores de Troca do Nucleotídeo Guanina/genética , Hemorragia/genética , Transtornos Plaquetários/congênito , Pré-Escolar , Feminino , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Hemorragia/congênito , Humanos , Lactente , Masculino , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/metabolismo , Transdução de Sinais/genética , Proteínas de Ligação a Telômeros/metabolismo
5.
J Small Anim Pract ; 61(1): 3-18, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31919851

RESUMO

Abnormal platelet activity can either lead to bleeding tendencies or inappropriate thrombus formation and can occur secondarily to a wide variety of disease processes, with a range of clinical consequences and severity. This article will discuss the pathophysiology of platelet function abnormalities and consider a logical diagnostic approach applicable to veterinary practice. Recent advances in platelet function testing will then be discussed, with regards to detection of platelet dysfunction and tailoring of pharmacological manipulation. Although many of these tests are still confined to research or academic institutions, techniques for indirectly assessing platelet function are starting to become more widely available. Although we still require further research to develop guidelines for the use of these tests in clinical decision-making, the recent advances in this field are an exciting step forward in being able to detect and manage platelet dysfunction in both primary care and referral practice.


Assuntos
Transtornos Plaquetários/veterinária , Doenças do Gato , Doenças do Cão , Animais , Gatos , Cães , Testes de Função Plaquetária/veterinária , Encaminhamento e Consulta
6.
Pathology ; 52(2): 243-255, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31932033

RESUMO

Inherited disorders of platelet function (IPFD) and/or number (IPND) are heterogeneous conditions that result in variable mucocutaneous bleeding symptoms as a result of deranged primary haemostasis caused by platelet dysfunction or thrombocytopenia. Diagnosis is important to guide post-operative bleeding prophylactic strategies, to avoid treatment with inappropriate medications, and inform prognosis. Achieving an accurate diagnosis has traditionally been hampered by the requirement of multiple, often complex, laboratory tests that are not always available at single centres. To improve the diagnosis of these disorders a research collaborative was established, the Sydney Platelet Group, that explored an integrated approach combining traditional and contemporary platelet phenotypic and genetic diagnostic platforms available at four Sydney tertiary hospitals. Herein we report the outcomes of the first 50 patients evaluated using this approach. The cohort included 22 individuals with suspected IPFD and 28 with thrombocytopenia. Bleeding scores were higher in individuals with IPFD (mean 5.75; SD 4.83) than those with IPNDs (mean 2.14; SD 2.45). In cases with suspected IPFD, diagnosis to the level of the defective pathway was achieved in 71% and four individuals were found not to have a definitive platelet function defect. Dense granule secretion disorders were the most common platelet pathway abnormality detected (n=5). Mean bleeding scores in these individuals were not significantly different to individuals with defects in other commonly detected platelet pathways (dense granules, signal transduction and 'undetermined'). A molecular diagnosis was achieved in 52% of individuals with IPNDs and 5% with IPFD. Likely pathogenic and pathogenic variants detected included variants associated with extra-haematological complications (DIAPH1, MYH9) and potential for malignancy (ANKRD26 and RUNX1). The level of platelet investigation undertaken by this initiative is currently not available elsewhere in Australia and initial results confirm the utility of this integrated phenotypic-genetic approach.


Assuntos
Transtornos Plaquetários/diagnóstico , Testes de Função Plaquetária/métodos , Adolescente , Adulto , Idoso , Austrália , Transtornos Plaquetários/genética , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
8.
Platelets ; 31(2): 276-279, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31389738

RESUMO

Chronic hemorrhagic diathesis in patients showing normal levels of plasmatic clotting factors strongly suggests for congenital platelet disorders. We report on a pediatric patient (male, 3 years, D1) with mild bleeding. A sibling (D2), his mother (D3) and father (D4) were included for laboratory investigation. Platelet counts in D1, D2 and D4 indicated mild thrombocytopenia (100 Gpt/L). D1 and D3 platelets showed significantly diminished aggregation response on arachidonic acid and U46619 stimulation. Immunostaining for platelet proteins on blood smears of D1 and D2 indicated defects in ß1-tubulin. Exon sequencing of TBXA2R and TUBB1 revealed heterozygosity for the novel TBXA2R*c.908T>C (p.L303P) mutation in D1 and D3. TUBB1 was either wild type (D2, D3) or heterozygous (D1, D4) for the common polymorphism TUBB1*c.920G>A (rs6070697; p.R307H). In conclusion, the bleeding phenotype of the index patient can be explained by a diminished platelet function caused by the TBXA2R*c.908T>C mutation inherited from the mother and a mild thrombocytopenia with unknown molecular basis that is inherited from the father.


Assuntos
Transtornos Plaquetários/genética , Hemorragia/genética , Receptores de Tromboxano A2 e Prostaglandina H2/genética , Trombocitopenia/congênito , Trombocitopenia/genética , Ácido 15-Hidroxi-11 alfa,9 alfa-(epoximetano)prosta-5,13-dienoico/farmacologia , Adulto , Ácido Araquidônico/farmacologia , Transtornos Plaquetários/metabolismo , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Pré-Escolar , Feminino , Hemorragia/metabolismo , Transtornos Hemorrágicos/genética , Transtornos Hemorrágicos/metabolismo , Heterozigoto , Humanos , Masculino , Mutação , Fenótipo , Contagem de Plaquetas , Receptores de Tromboxano A2 e Prostaglandina H2/metabolismo , Trombocitopenia/metabolismo , Tubulina (Proteína)/sangue , Tubulina (Proteína)/genética
9.
Platelets ; 31(4): 474-482, 2020 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-31524038

RESUMO

Platelets are small, anucleated effector cells that play an important role in linking the hemostatic and inflammatory processes in the body. Platelet function is known to be altered under various inflammatory conditions including aging. A gain in platelet function during aging can increase the risk of thrombotic events, such as stroke and acute myocardial infarction. Anti-platelet therapy is designed to reduce risk of serious cerebrovascular and cardiovascular events, but the adverse consequences of therapy, such as risk for bleeding increases with aging as well. Age-associated comorbidities such as obesity, diabetes, and hyperlipidemia also contribute to increased platelet activity and thus can enhance the risk of thrombosis. Therefore, identification of unique mechanisms of platelet dysfunction in aging and in age-associated comorbidities is warranted to design novel antiplatelet drugs. This review outlines some of the current areas of research on aging-related mechanisms of platelet hyperactivity and addresses the clinical urgency for designing anti-platelet therapies toward novel molecular targets in the aging population.


Assuntos
Envelhecimento/efeitos dos fármacos , Transtornos Plaquetários/tratamento farmacológico , Plaquetas/efeitos dos fármacos , Ativação Plaquetária/efeitos dos fármacos , Trombose/complicações , Idoso , Envelhecimento/imunologia , Envelhecimento/metabolismo , Animais , Plaquetas/imunologia , Plaquetas/metabolismo , Comorbidade , Humanos , Inflamação/imunologia , Estresse Oxidativo , Ativação Plaquetária/imunologia , Fatores de Risco , Transdução de Sinais/genética , Trombose/fisiopatologia
11.
J Trauma Acute Care Surg ; 88(1): 80-86, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31688782

RESUMO

BACKGROUND: Platelet dysfunction (PD) is an independent predictor of mortality in patients with severe traumatic brain injury (sTBI). Platelet transfusions (PLTs) have been shown to be an effective treatment strategy to reverse platelet inhibition. Their use is contingent on availability and may be associated with increased cost and transfusion-related complications, making desmopressin (DDAVP) attractive. We hypothesized that DDAVP would correct PD similarly to PLTs in patients with sTBI. METHODS: This retrospective study evaluated all blunt trauma patients admitted to an urban, level 1 trauma center from July 2015 to October 2016 with sTBI (defined as head abbreviated injury scale [AIS] ≥3) and PD (defined as adenosine diphosphate [ADP] inhibition ≥60% on thromboelastography) and subsequently received treatment. Per our institutional practice, patients with sTBI and PD are transfused one unit of apheresis platelets to reverse inhibition. During a platelet shortage, we interchanged DDAVP for the initial treatment. Patients were classified as receiving DDAVP or PLT based on the initial treatment. RESULTS: A total of 57 patients were included (DDAVP, n = 23; PLT, n = 34). Patients who received DDAVP were more severely injured (injury severity score, 29 vs. 23; p = 0.045), but there was no difference in head AIS (4 vs. 4, p = 0.16). There was no difference between the two groups in admission platelet count (244 ± 68 × 10/µL vs. 265 ± 66 × 10/µL, p = 0.24) or other coagulation parameters such as prothrombin time, partial thromboplastin time, or international normalized ratio. Before treatment, both groups had similar ADP inhibition as measured by thromboelastography (ADP, 86% vs. 89%, p = 0.34). After treatment, both the DDAVP and PLT groups had similar correction of platelet ADP inhibition (p = 0.28). CONCLUSION: In patients with severe traumatic brain injury and PD, DDAVP may be an alternative to PLTs to correct PD. LEVEL OF EVIDENCE: Therapeutic, level IV.


Assuntos
Transtornos Plaquetários/terapia , Lesões Encefálicas Traumáticas/terapia , Desamino Arginina Vasopressina/administração & dosagem , Traumatismos Cranianos Fechados/terapia , Hemostáticos/administração & dosagem , Transfusão de Plaquetas/estatística & dados numéricos , Escala Resumida de Ferimentos , Adulto , Transtornos Plaquetários/sangue , Transtornos Plaquetários/diagnóstico , Transtornos Plaquetários/etiologia , Plaquetas/efeitos dos fármacos , Lesões Encefálicas Traumáticas/sangue , Lesões Encefálicas Traumáticas/diagnóstico , Lesões Encefálicas Traumáticas/etiologia , Feminino , Traumatismos Cranianos Fechados/sangue , Traumatismos Cranianos Fechados/complicações , Traumatismos Cranianos Fechados/diagnóstico , Humanos , Coeficiente Internacional Normatizado , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tromboelastografia , Resultado do Tratamento , Adulto Jovem
12.
J Surg Res ; 246: 605-613, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31668435

RESUMO

BACKGROUND: Platelet function tests such as thrombelastography platelet mapping and impedance aggregometry have demonstrated universal platelet dysfunction in trauma patients. In this study, we introduce the measurement of platelet contraction force as a test of platelet function. We hypothesize that force will correlate with established coagulation tests such as thrombelastography, demonstrate significant differences between healthy subjects and trauma patients, and identify critically ill trauma patients. METHODS: Blood samples were prospectively collected from level 1 trauma patients at initial presentation, assayed for force of and time to contraction and compared with thrombelastography. Blood from healthy subjects was assayed to establish a reference range. Results from trauma patients were compared with healthy controls and trauma patients that died. RESULTS: The study includes one hundred trauma patients with mean age 45 y, 74% were male, and median injury severity score of 14 ± 12. Patients that survived (n = 90) demonstrated significantly elevated platelet contraction force compared with healthy controls (n = 12) (6390 ± 2340 versus 4790 ± 470 µN, P = 0.043) and trauma patients that died (n = 10) (6390 ± 2340 versus 2860 ± 1830 µN, P = 0.0001). Elapsed time to start of platelet contraction was faster in trauma patients that survived compared with healthy controls (660 ± 467 versus 1130 ± 140 s, P = 0.0022) and those that died (660 ± 470 versus 1460 ± 1340 s, P < 0.0001). CONCLUSIONS: In contrast with all existing platelet function tests reported in the literature, which report platelet dysfunction in trauma patients, contractile force demonstrates hyperfunction in surviving trauma patients and dysfunction in nonsurvivors. Platelet contraction reflects platelet metabolic reserve and thus may be a potential biomarker for survival after trauma. Contractile force warrants further investigation to predict mortality in severely injured trauma patients.


Assuntos
Transtornos Plaquetários/diagnóstico , Plaquetas/fisiologia , Ferimentos e Lesões/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Coagulação Sanguínea/fisiologia , Transtornos Plaquetários/sangue , Transtornos Plaquetários/etiologia , Transtornos Plaquetários/fisiopatologia , Feminino , Humanos , Escala de Gravidade do Ferimento , Masculino , Pessoa de Meia-Idade , Testes de Função Plaquetária/métodos , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Curva ROC , Tromboelastografia , Ferimentos e Lesões/sangue , Ferimentos e Lesões/diagnóstico , Ferimentos e Lesões/mortalidade , Adulto Jovem
14.
Pediatr Blood Cancer ; 67(2): e28078, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31724816

RESUMO

Defects of platelet intracellular signaling can result in severe platelet dysfunction. Several mutations in each of the linked genes FERMT3 and RASGRP2 on chromosome 11 causing a Glanzmann-like bleeding phenotype have been identified so far. We report on novel variants in two unrelated pediatric patients with severe bleeding diathesis-one with leukocyte adhesion deficiency type III due to a homozygous frameshift in FERMT3 and the other with homozygous variants in both, FERMT3 and RASGRP2. We focus on the challenging genetic and functional variant assessment and aim to accentuate the risk of obtaining misleading results due to the phenomenon of genetic linkage.


Assuntos
Transtornos Plaquetários/patologia , Fatores de Troca do Nucleotídeo Guanina/genética , Transtornos Hemorrágicos/patologia , Proteínas de Membrana/genética , Mutação , Proteínas de Neoplasias/genética , Adolescente , Transtornos Plaquetários/genética , Criança , Feminino , Ligação Genética , Transtornos Hemorrágicos/genética , Homozigoto , Humanos , Masculino , Linhagem , Fenótipo , Prognóstico
15.
Med. lab ; 24(2): 162-164, 2020.
Artigo em Espanhol | LILACS, COLNAL | ID: biblio-1097278

RESUMO

Las pruebas de función plaquetaria realizadas con el analizador PFA-200 (del inglés, Platelet Function Analyzer) han venido reemplazando el tiempo de sangría, una prueba ya obsoleta, de acuerdo con el College of American Pathologists (CAP) y la American Society for Clinical Pathology (ASCP). Este analizador, mediante un sistema que utiliza cartuchos, posee la capacidad de simular in vitro las condiciones hemodinámicas del paciente para el tamizaje rápido, sencillo y automatizado de la disfunción plaquetaria. Las pruebas son de utilidad para evaluar la función plaquetaria en pacientes con alteraciones como enfermedad de von Willebrand y otras trombocitopatías congénitas o adquiridas, y evalúa la disfunción plaquetaria causada por inhibidores de la agregación plaquetaria, como la aspirina. Además, son de gran utilidad para el tamizaje prequirúrgico y en los embarazos de alto riego. Este sistema ofrece con su más reciente prueba, la INNOVANCE® PFA-200 P2Y, la posibilidad de evaluar la respuesta de pacientes que están siendo tratados con antagonistas del receptor plaquetario P2Y12, como son clopidogrel, prasugrel y ticagrelor, determinando el porcentaje de adhesión y agregación plaquetaria, logrando discriminar entre un paciente antiagregado y un paciente resistente al tratamiento


Assuntos
Humanos , Testes de Função Plaquetária , Tempo de Sangramento , Transtornos Plaquetários
16.
Sci Transl Med ; 11(522)2019 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-31826978

RESUMO

Platelet transfusions can fail to prevent bleeding in patients with inherited platelet function disorders (IPDs), such as Glanzmann's thrombasthenia (GT; integrin αIIbß3 dysfunction), Bernard-Soulier syndrome [BSS; glycoprotein (GP) Ib/V/IX dysfunction], and the more recently identified nonsyndromic RASGRP2 variants. Here, we used IPD mouse models and real-time imaging of hemostatic plug formation to investigate whether dysfunctional platelets impair the hemostatic function of healthy donor [wild-type (WT)] platelets. In Rasgrp2-/- mice or mice with platelet-specific deficiency in the integrin adaptor protein TALIN1 ("GT-like"), WT platelet transfusion was ineffective unless the ratio between mutant and WT platelets was ~2:1. In contrast, thrombocytopenic mice or mice lacking the extracellular domain of GPIbα ("BSS-like") required very few transfused WT platelets to normalize hemostasis. Both Rasgrp2-/- and GT-like, but not BSS-like, platelets effectively localized to the injury site. Mechanistic studies identified at least two mechanisms of interference by dysfunctional platelets in IPDs: (i) delayed adhesion of WT donor platelets due to reduced access to GPIbα ligands exposed at sites of vascular injury and (ii) impaired consolidation of the hemostatic plug. We also investigated the hemostatic activity of transfused platelets in the setting of dual antiplatelet therapy (DAPT), an acquired platelet function disorder (APD). "DAPT" platelets did not prolong the time to initial hemostasis, but plugs were unstable and frequent rebleeding was observed. Thus, we propose that the endogenous platelet count and the ratio of transfused versus endogenous platelets should be considered when treating select IPD and APD patients with platelet transfusions.


Assuntos
Transtornos Plaquetários/patologia , Plaquetas/patologia , Hemostasia , Transfusão de Plaquetas , Animais , Sítios de Ligação , Terapia Antiplaquetária Dupla , Fatores de Troca do Nucleotídeo Guanina/deficiência , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Humanos , Integrinas/metabolismo , Ligantes , Camundongos Endogâmicos C57BL , Complexo Glicoproteico GPIb-IX de Plaquetas/metabolismo , Trombastenia/patologia , Doadores de Tecidos
18.
Rev Med Liege ; 74(12): 655-661, 2019 Dec.
Artigo em Francês | MEDLINE | ID: mdl-31833276

RESUMO

The diagnosis of inherited platelet disorders (IPD) is a complex task. Indeed, due to their rarity, their wide clinical spectrum (intensity of hemorrhagic symptoms) and the need for specialized biological assays (only performed in reference centers) IPDs can be diagnosed very late. However, it is important to remember the crucial need for early diagnosis in order to avoid the use of unnecessary and potentially harmful treatments for the patient. A thorough personal and family history, a complete physical examination and a simple biological work up (blood count, blood smear and platelet occlusion time) will lead to the suspicion of an IPD. It will then be up to the physician to refer the patient to a specialist in order to complete the diagnostic work up and therefore establishing a definitive diagnosis. Here is a description of the most well-known IPDs and their diagnostic algorithms.


Assuntos
Transtornos Plaquetários , Algoritmos , Transtornos Plaquetários/diagnóstico , Plaquetas , Hemorragia , Humanos , Anamnese
19.
Stem Cell Res ; 41: 101603, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31698193

RESUMO

Familial Platelet Disorder with associated Myeloid Malignancy (FPDMM) is a rare platelet disorder caused by mutations in RUNX1. We generated an iPSC line (GENYOi005-A) from a FPDMM patient with a non-previously reported variant p.Thr196Ala. Non-integrative Sendai viruses expressing the Yamanaka reprogramming factors were used to reprogram peripheral blood mononuclear cells from this FPDMM patient. Characterization of GENYOi005-A included genetic analysis of RUNX1 locus, Short Tandem Repeats profiling, alkaline phosphatase enzymatic activity, expression of pluripotency-associated factors and differentiation studies in vitro and in vivo. This iPSC line will provide a powerful tool to study developmental alterations of FPDMM patients.


Assuntos
Transtornos Herdados da Coagulação Sanguínea/genética , Transtornos Herdados da Coagulação Sanguínea/patologia , Transtornos Plaquetários/genética , Transtornos Plaquetários/patologia , Diferenciação Celular , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Células-Tronco Pluripotentes Induzidas/patologia , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Leucócitos Mononucleares/patologia , Mutação , Células Cultivadas , Reprogramação Celular , Feminino , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Leucócitos Mononucleares/metabolismo , Pessoa de Meia-Idade
20.
BMC Bioinformatics ; 20(Suppl 18): 572, 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31760951

RESUMO

BACKGROUND: The Gene Ontology (GO) knowledgebase is the world's largest source of information on the functions of genes. Since the beginning of GO project, various tools have been developed to perform GO enrichment analysis experiments. GO enrichment analysis has become a commonly used method of gene function analysis. Existing GO enrichment analysis tools do not consider tissue-specific information, although this information is very important to current research. RESULTS: In this paper, we built an easy-to-use web tool called TS-GOEA that allows users to easily perform experiments based on tissue-specific GO enrichment analysis. TS-GOEA uses strict threshold statistical method for GO enrichment analysis, and provides statistical tests to improve the reliability of the analysis results. Meanwhile, TS-GOEA provides tools to compare different experimental results, which is convenient for users to compare the experimental results. To evaluate its performance, we tested the genes associated with platelet disease with TS-GOEA. CONCLUSIONS: TS-GOEA is an effective GO analysis tool with unique features. The experimental results show that our method has better performance and provides a useful supplement for the existing GO enrichment analysis tools. TS-GOEA is available at http://120.77.47.2:5678.


Assuntos
Transtornos Plaquetários/genética , Biologia Computacional/métodos , Ontologia Genética , Humanos , Internet , Probabilidade , Software
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