Artrite reumatoide do tipo EORA com trombocitose significativa: relato de caso / Elderly-onset rheumatoid arthritis with significant thrombocytosis: a case report

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.

Screening PCR Versus Sanger Sequencing: Detection of CALR Mutations in Patients With Thrombocytosis

BACKGROUND: Mutations in calreticulin (CALR) have been reported to be key markers in the molecular diagnosis of myeloid proliferative neoplasms. In most previous reports, CALR mutations were analyzed by using Sanger sequencing. Here, we report a new, rapid, and convenient system for screening CALR mutations without sequencing. METHODS: Eighty-three bone marrow samples were obtained from 81 patients with thrombocytosis. PCR primers were designed to detect wild-type CALR (product: 357 bp) and CALR with type 1 (product: 302 bp) and type 2 mutations (product: 272 bp) in one reaction. The results were confirmed by Sanger sequencing and compared with results from fragment analysis. RESULTS: The minimum detection limit of the screening PCR was 10 ng for type 1, 1 ng for type 2, and 0.1 ng for cases with both mutations. CALR type 1 and type 2 mutants were detected with screening PCR with a maximal analytical sensitivity of 3.2% and <0.8%, respectively. The screening PCR detected 94.1% (16/17) of mutation cases and showed concordant results with sequencing in the cases of type 1 and type 2 mutations. Sanger sequencing identified one novel mutation (c.1123_1132delinsTGC). Compared with sequencing, the screening PCR showed 94.1% sensitivity, 100.0% specificity, 100.0% positive predictive value, and 98.5% negative predictive value. Compared with fragment analysis, the screening PCR presented 88.9% sensitivity and 100.0% specificity. CONCLUSIONS: This screening PCR is a rapid, sensitive, and cost-effective method for the detection of major CALR mutations.

Pseudohiperkalemia por trombocitosis esencial: una entidad pobremente reconocida / Pseudohyperkalaemia in essential thrombocytosis: a poorly recognized

INTRODUCCIÓN: La hiperkalemia representa una emergencia médica frecuentemente manejada en servicios de urgencia. Identificar una pseudohiperkalemia en pacientes que presentan recuentos plaquetarios elevados permite evitar terapias innecesarias e iatrogenia que pueden tener consecuencias potencialmente fatales. PRESENTACIÓN DEL CASO: Mujer de 73 años, con enfermedad renal crónica (ERC) etapa-3a (etiología no precisada). En consulta neurológica por crisis isquémica transitoria (abril 2011), se demostró hiperkalemia de 6,0 mEq/L (suero), tasa de filtración glomerular(TFG) de 51 mL/min y trombocitosis de 1.113.000 plaquetas/mm3. Se trata la hiperkalemia con furosemida y dieta pobre en potasio. Inició hidroxiurea indicada por hematología. En control nefrológico (diciembre 2012) presenta hiperkalemia de 7,5 mEq/L (suero), TFG de 37 ml/min y trombocitosis de 1.052.000 plaquetas/mm3. Electrocardiograma (ECG), sin signos de cardiotoxicidad acordes al nivel de kalemia. Se sospechó pseudohiperkalemia secundaria a trombocitosis esencial (PSTE), se suspendió atenolol, furosemida y se continuó hidroxiurea. En febrero de 2013 presentó kalemia de 6,1 mEq/L (suero), trombocitosis de 713.000 plaquetas/mm3 y TFG de 31 mL/min. En mayo de 2014 la kalemia en suero fue de 5,5 mEq/L y en plasma de 5,2 mEq/L; trombocitosis de 503.000plaquetas/mm3 y TFG de 23 ml/min, confirmándose la PSTE. DISCUSIÓN: Hiperkalemia asociada a trombocitosis exige descartar PSTE. La regresión de la kalemia junto con la trombocitosis y ECG sin alteraciones en hiperkalemia, apoyan este diagnóstico. Su confirmación exige demostrar una hiperpotasemia mayor en suero que en plasma (0,36 +/-0,18 meq/L). Tratar una pseudohiperkalemia, puede generar iatrogenia (hipokalemia y/o hemoconcentración que aumenta riesgo de trombosis). Se descarta hiperkalemia secundaria a ERC con TFG>15ml/min

INTRODUCTION: Hyperkalemia is a medical emergency often managed in emergency services. Identifying a pseudohiperkalemia in patients with high platelet counts will avoid unnecessary iatrogenic therapies, which can have potentially fatal consequences. CASE REPORT: 73 year old woman, with chronic kidney disease (CKD) stage-3a (unknown etiology). In neurological consultation by transient ischemic attack (april 2011) it was evidenced a hyperkalemia of 6.0 mEq/L (serum), glomerular filtration rate (GFR) of 51 mL/min and thrombocytosis of 1,113,000 platelets/mm3. Hyperkalemia is treated with furosemide and potassium poor diet. Started on hydroxyurea indicated by hematology. Nephrology consultant (december 2012) realized hyperkalemia of 7.5 mEq/L (serum), GFR of 37mL/min and thrombocytosis of 1,052,000 platelets/mm3. EKG with no sign of cardiotoxicity was found in relation to potassium serum level. A pseudohyperkalemia secondary to essential thrombocytosis (PSET) was suspected. Atenolol and furosemide were discontinued and hidroxiurea was continued. In February 2013 potassium serum level was 6.1 mEq/L, platelet count: 713,000/ mm3 and GFR: 31 mL/min. In may 2014 serum potassium was 5.5 mEq/L and plasma potassium was 5.2 mEq/L; platelet count: 503,000//mm3 and GFR: 23 mL/min, confirming PSET. DISCUSSION: Hiperkalemia associated with thrombocytosis requires to rule out PSET. Regression of serum potassium with platelet count and the abscense of EKG changes with simultaneous hyperkalemia, support this diagnosis. Confirmation of PSTE diagnosis needs to demonstrate a potassium serum level greater than in plasma (0.36 +/- 0.18 mEq/L). Treating a pseudohiperkalemia can generate iatrogenia (hypokalemia and/or hemoconcentration, increasing the risk of thrombosis). A hyperkalemia secondary to CKD is ruled out with GFR >15mL/min

Prognostic Significance of Initial Platelet Counts and Fibrinogen Level in Advanced Non-Small Cell Lung Cancer

Thrombocytosis and coagulation systems activation are commonly associated with disease progression and are suggested poor prognostic factors in patients with malignancies. This study aimed to investigate the prevalence and prognostic significance of thrombocytosis and elevated fibrinogen levels in patients with advanced non-small cell lung cancer (NSCLC). Initial platelet counts and fibrinogen levels were reviewed in 854 patients with histologically proven NSCLC. Thrombocytosis was defined as platelet counts > 450 x 10(9)/L. A serum fibrinogen level > 4.5 g/L was considered high. At the time of diagnosis, initial platelet counts and serum fibrinogen levels were evaluated before treatment. Clinicopathologic data including histological type, tumor, node, metastasis (TNM) stage, performance status, treatment method, and survival time were evaluated. Initial thrombocytosis was found in 6.9% of patients, and elevated fibrinogen levels were found in 55.1% of patients. Patients with thrombocytosis had a significantly poorer prognosis than patients with normal platelet counts (P < 0.001). In multivariate survival analysis, thrombocytosis was an independent prognostic factor (P < 0.001). An elevated serum fibrinogen level was associated with poor prognosis (P < 0.001). In conclusion, initial thrombocytosis and a high fibrinogen level are independent factors for predicting poor prognosis in patients with advanced NSCLC.

Trombocitosis esencial: comunicación de dos casos / Essential thormbocytosis: report of two cases

La trombocitosis esencial (TE) es una panmielopatía clonal de escasa frecuencia, que está incluida dentro de los síndromes mieloproliferativos crónicos. Se caracteriza por la proliferación anormal de los megacariocitos, y las manifestaciones clínicas principales son: hemorragia y/o diátesis tromboembólica, en cuyo caso se presentan fenómenos necróticos y ulcerosos. Se presentan dos pacientes de sexo masculino de 54 y 80 años, cuyas primeras manifestaciones fueron lesiones úlcero-necróticas cutáneas. Con recuentos plaquetarios mayores a 1.000.000 mm3 y la punción biopsia de médula ósea que reveló hiperplasia megacariocítica, se arriba al diagnóstico de TE.

Essential thrombocytosis (ET) is a rare, clonal panmyelopathy and one of a group of disordersknown as chronic myeloproliferative diseases.ET is associated with sustained megakaryocyte proliferation, and clinically presents hemorrhage orthrombosis with ulcerative or necrotic lesions.We report two male patients aged 54 and 80-years-old, respectively, with ulcerative and necroticlesions on the skin as the first manifestation of this disease. The platelet count was higher than1.000.000 mm3 and the bone marrow aspirate biopsy showed megakaryocytic hyperplasiadiagnostic of ET.

Stroke in the young: relationship with iron deficiency anemia and thrombocytosis.

The recognition and treatment of stroke in children is challenging as there are fundamental developmental differences in children compared to adults. A young boy presented with sudden weakness of right side of body followed by unconsciousness and convulsion that was not preceded by any history of fever or trauma. Neurological examination revealed upper motor neuron lesion in the right extremities. CT scan showed diffuse hypodense area in fronto-parietal regions. Complete blood count and iron profile evaluated iron deficiency anemia with thrombocytosis. Thrombosis resulting from thrombocytosis secondary to iron deficiency anemia was considered as etiological explanation of stroke in this young child.

Non-ST-elevation myocardial infarction in a patient with essential thrombocytosis: Successful treatment with GP-IIbIIIa inhibitor

We treated a 37 years old female who has essential thrombocytosis and developed NSTEMI with GPIIb IIIa inhibitors in addition to standard treatment with dual anti platelet therapy, low molecular heparin, beta blocker and ACE inhibitor and had good recovery of left ventricular function without any bleeding complication. Since these patients have both bleeding and thrombotic complications, it is prudent to carefully follow these patients during treatment and on follow up

Thrombocytosis in advanced epithelial ovarian cancer.

OBJECTIVE: Thrombocytosis (platelet count greater than 400,000/mm3) has been identified as a poor prognostic factor in many cancers. The objectives of the present study were to determine the incidence of thrombocytosis in advanced epithelial ovarian cancer and the cut off point level of platelet count in Thai patients determining thrombocytosis condition and association between survival time in both thrombocytosis condition (platelet count greater than 400,000/mm3 and 305,000/mm3). DESIGN: Descriptive study. MATERIAL AND METHOD: One hundred and twenty epithelial ovarian cancer patients were included between January 2004 and December 2005. Their medical records were retrospectively reviewed and data was analyzed using chi2, Fisher's exact test, and Student t- test. The level of platelet counts determining thrombocytosis condition in Thai patients were record and analyzed by ROC curve. Survival was analyzed by the method of Kaplan and Meier. RESULTS: When using the standard criteria of thrombocytosis (platelet counts greater than 400,000/mm3), the incidence was 35% (42/120 cases). Among advanced-stage patients, such incidence was 56.7% (42/74 cases). The criteria for diagnosis of thrombocytosis in the present study was platelet counts greater than 305,000/ mm3. When using such criteria, the overall incidence of thrombocytosis was 49.1% (59/120 cases) and was 72.97% (54/74 cases) in advanced stage. Patients with preoperative thrombocytosis were found to have higher CA - 125 level, greater prevalence of ascites, and worse prognosis. CONCLUSION: The incidence of thrombocytosis in Thai patients with advanced epithelial ovarian cancer was 56.7% and 72.9% when using platelet count level greater than 400,000/mm3 and 305,000/mm3 respectively, which was higher than that of the early stage. This implies that thrombocytosis is probably a marker of cancer aggressiveness.

Perda visual bilateral grave como sinal de apresentação de trombose de seio venoso cerebral: relato de caso / Severe bilateral visual loss as the presenting sign of cerebral venous sinus thrombosis: case report

O objetivo é relatar um caso de trombose de seio venoso cerebral causando síndrome de pseudotumor, onde a principal manifestação clínica foi uma perda visual bilateral grave. Homem de 24 anos apresentando perda visual bilateral grave, obscurecimentos transitórios da visão, cefaléia, papiledema bilateral e campos visuais constrictos. Tomografia computadorizada, bem como exame neurológico, apresentavam-se normais. Punção lombar mostrou um aumento da pressão liquórica inicial e o hemograma mostrou aumento do número de plaquetas. A ressonância magnética de crânio apresentava sinais característicos de papiledema crônico e sinais sugestivos de trombose de seio sagital superior. A venorressonância magnética de crânio mostrou trombose de seios sagital superior, transversos e sigmóides. Paciente foi tratado com descompressão de bainha de nervo óptico do olho esquerdo, acetazolamida e anticoagulação. O exame oftalmológico após o tratamento mostrou redução do papiledema, mas com persistência de perda visual acentuada. O pseudotumor cerebral com perda visual severa pode ser um sinal de apresentação de trombose venosa cerebral secundária a doença hematológica grave.

Trombocitose essencial e infarto agudo do miocárdio tratado com angioplastia coronariana de resgate / Essential thrombocythemia and acute myocardial infarction treated with rescue coronary angioplasty

Homens de 48 anos, portador de trombocitose essencial, apresentou infarto agudo do miocárdio anterior extenso, associação raramente observada. Submetido a trombólise química sem êxito, foi levado a angioplastia coronariana de resgate, com sucesso. Até onde se pôde pesquisar, não há, na literatura, outra publicação relacionando a tríade trombocitose essencial, infarto agudo do miocárdio e angioplastia coronariana de resgate.

Essential thrombocythemia: an uncommon cause of digital gangrene.

We describe a case of essential thrombocythemia (ET), presenting as digital gangrene. ET is a rare myeloproliferative disorder characterised by a persistently elevated platelet count which commonly presents with haemorrhagic manifestations. Thrombosis occurs less frequently and digital gangrene is an uncommon presentation.

Trombosis de la vena porta asociada a trombocitosis esencial: casos clínicos y revisión de la literatura / Thrombosis of the portal vein associated to primary thrombocytosis: clinical cases and literature rewiew

Lately, myeloprolipherative disorders are frequently reported as causes of portal vein thrombosis, probably due to the early detection of latent cases of this condition. We report 2 patients with portal vein thrombosis that presented with abdominal pain, nausea, vomiting and clinical consequences of portal hypertension such as variceal hemorrhage, splenomegaly and ascitis. Diagnosis was made by a CAT scan in one patient and doppler ultrasound in the other. Both patients had a higher platelet counts and an essential thrombocytosis in the bone marrow

Síndrome de 5q- anemia refractaria, trombocitosis e hipolobulación de megacariocitos / 5q- syndrome: refractory anemia, thrombocytosis and hypolubulation of megakaryocytes

Se describe el caso de una mujer de raza blanca, de 30 años de edad, con anemia crónica de 3 años de evolución, refractaria a tratamiento médico y a esplenectomía. Los estudios citogenéticos demostraron una anomalía única, la delección parcial del brazo largo del cromosoma No. 5, defecto denominado "Síndrome del 5q-" descrito en aproximadamente 15 pacientes en la literatura mundial. Este síndrome aparentemente adquirido se caracteriza por anemia refractaria, moderada leucopenia, trombosistosis e hipolobulación de los megacariocitos. La anemia es resistente a los tratamientos conocidos y no evoluciona a leucemia aguda. La mayor parte de los pacientes fallecen por las complicaciones de la hemosiderosis producida por la gran cantidad de transfusiones que requieren para mantener una hemoglobina adecuada. La terapia quelante de hierro con desferroxamina, utilizando minibombas de infusión continua, es, hasta el momento, la única forma de prevenir la muerte por falla cardíaca en los pacientes dependientes de transfusiones. Este es el primer caso del "Síndrome del 5q-" informado en la literatura médica colombiana

Increased circulating platelet aggregates in thalassaemia.

Examination for circulating platelet aggregates according to Wu and Hoak revealed increased circulating platelet aggregates in 71% of splenectomized and 35% of nonsplenectomized patients with beta (0)-thalassaemia/Hb E disease. This may be causally related to the newly observed high incidences of pulmonary artery thrombosis and hypoxaemia in splenectomized thalassaemic patients. It is recommended that anti-platelet aggregation drugs such as aspirin and/or dipyridamole are given to thalassaemic patients after splenectomy.