Estudio de mutaciones en neoplasias mieloproliferativas Philadelphia negativas en un hospital público chileno / Search for mutations in patients with Philadelphia negative myeloproliferative neoplasms in a public hospital in Chile

BACKGROUND: Philadelphia negative myeloproliferative neoplasms (Ph-MPN) are clonal disorders whose pathogenesis has been elucidated in recent years, creating diagnostic and prognostic algorithms. AIM: To study JAK2, CALR y MPL gene mutations in patients with Ph-MPN. MATERIALS AND METHODS: Descriptive cross-sectional observational study of patients with MPN (2015-2019), reviewing clinical, demographic and laboratory data. JAK2, CALR and MPL gene mutations were analyzed by RT-PCR. Results: We studied 72 patients. Fifty percent had essential thrombocythemia (ET), 26.4% had polycythemia vera (PV) and 23.6% had primary myelofibrosis (PM). Bone marrow biopsy was available in 76.5%. At diagnosis, the mean age was 65.5 years and 61% were symptomatic. A thrombotic event was the most frequent problem in 20% and 25% had splenomegaly. There were statistically significant differences in hematological parameters between the different MPNs. JAK2 V617F mutation was detected in 61.1%. Only 19 JAK2 V617F negative patients were available for CALR and MPL mutation studies, identifying 10 triple negative cases. Kaplan Meier curves showed a median survival of 88 months, being similar in the three MPNs. Causes of death in 20 patients were thrombotic complications in 30%, disease progression in 25%, infection in 20%, other neoplasms in 15% and other causes in 10%. CONCLUSIONS: The presentation and frequency of JAK2 V617F, CALR and MPL mutations in our cohort was similar to those reported in other studies for ET and PM. JAK2 V617F mutation was lower for PV. No significant differences between the three MPNs were observed for overall survival. We could not assess the prognostic value of the mutations.

Differences in Hematological and Clinical Features Between Essential Thrombocythemia Cases With JAK2- or CALR-Mutations

No abstract available.

Incidence, Clinical Features, and Prognostic Impact of CALR Exon 9 Mutations in Essential Thrombocythemia and Primary Myelofibrosis: An Experience of a Single Tertiary Hospital in Korea

We evaluated the incidence, clinical characteristics, and prognostic impact of calreticulin (CALR) mutations in essential thrombocythemia (ET) and primary myelofibrosis (PMF) patients. In all, 48 ET and 14 PMF patients were enrolled, and the presence of CALR mutations was analyzed by direct sequencing. Patients were classified into three subgroups according to Janus kinase 2 (JAK2) V617F and CALR mutation status, and their clinical features and prognosis were compared. CALR mutations were detected in 15 (24.2%) patients, and the incidence increased to 50.0% in 30 JAK2 V617F mutation-negative cases. These included 11 patients with three known mutations (c.1092_1143del [seven cases], c.1154_1155insTTGTC [three cases], and c.1102_1135del [one case]) and 4 patients with novel mutations. ET patients carrying CALR mutation were younger, had lower white blood cell counts, and experienced less thrombosis during follow-up than those carrying JAK2 V617F mutation, while both patient groups showed similar clinical features and prognosis. In ET patients without JAK2 V617F mutation, CALR mutation did not significantly affect clinical manifestation and prognosis. In conclusion, CALR mutation analysis could be a useful diagnostic tool for ET and PMF in 50% of the cases without JAK2 V617F mutations. The prognostic impact of CALR mutations needs further investigation.

Straightforward Identification of Masked Polycythemia Vera Based on Proposed Revision of World Health Organization Diagnostic Criteria for BCR-ABL1-Negative Myeloproliferative Neoplasms

No abstract available.

Place of Bone Marrow Biopsy as Compared to Bone Marrow Aspiration in Different Haematological Disorders.

Bone marrow aspiration (BMA) is much more frequently used than bone marrow biopsy (BMB) in the diagnosis of different haematological disorders. BMB is performed primarily in cases where bone marrow aspiration either fails or gives insufficient information. It is the sole modality of diagnosis in some situations and may give useful information of prognostic importance. The present study was done to find comparative usefulness of each of these procedures in various hematological disorders. Methods: Study subjects included all 45 patients attending the hematology section of pathology department of College of Medicine & Jawaharlal Nehru Memorial Hospital, Kalyani for bone marrow aspiration and who also consented for bone marrow biopsy during the period from 1st July 2011 to 30th June 2012. BMA smears and BMB specimens were obtained from posterior superior iliac spine in the same sitting and stained with Leishman’s stain and Haematoxylin & Eosin stain respectively. Findings of BMA and BMB were compared. Results: BMA was diagnostic in all cases of iron deficiency anemia (IDA), acute myeloid leukemia (AML), chronic myeloid leukemia (CML), chronic lymphocytic leukemia (CLL), idiopathic thrombocytopenic purpura (ITP) and essential thrombocythemia (ET). On the whole, BMA was diagnostic in 82.2% of cases and could accurately reveal hypercellularity in all cases. BMB was the only diagnostic method in myelofibrosis (MF) and provided additional information like fibrosis in cases of AML, CML and MF & pattern of involvement in CLL and multiple myeloma (MM). BMB, however, was poor in assessing iron stores due to leaching of iron during decalcification. Conclusions: BMA alone is sufficient for IDA and ITP. BMB is mandatory for diagnosis of MF and provides additional prognostic information in other cases.

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.

JAK2 V617F and MPL W515L/K Mutations in Korean Patients with Essential Thrombocythemia / 대한진단검사의학회지

JAK2 V617F and MPL W515L/K mutations have been reported in approximately 50% and 5% of the patients with essential thrombocythemia (ET), respectively. We investigated the frequency of MPL W515L/K mutations in a series of consecutive patients with ET and post-essential thrombocythemia myelofibrosis (post-ET MF). The study subjects were 63 patients diagnosed either with ET (N=59) or post-ET MF (N=4) at our institution between June 2006 and February 2010. Among them, 35 (55.6%) had the JAK2 V617F mutation. MPL W515L/K mutations were detected by direct sequencing analyses of exon 10, and 2 patients were found to harbor the following MPL mutations: W515L in 1 patient with ET and W515K in 1 patient with post-ET MF. Neither of the patients had the JAK2 V617F mutation. The frequencies of the MPL W515L/K and JAK2 V617F-negative mutations in our subjects with ET/post-ET MF were 3.2% (2/63) and 7.1% (2/28), respectively. This is the first study to report the frequency of JAK2 V617F and MPL W515L/K mutations in Korean patients with ET/post-ET MF.

Evaluation of Platelet Indices for Differential Diagnosis of Thrombocytosis by ADVIA 120 / 대한진단검사의학회지

BACKGROUND: For the diagnosis of essential thrombocythemia (ET), no single clinical or laboratory finding of diagnostic value is available and a differential diagnosis of other myeloproliferative neoplasms or reactive thrombocytosis (RT) is needed. Following recent developments in automated blood cell analyzers, various platelet indices can now be measured. In this study, we analyzed whether platelet counts and 6 platelet indices can be used for the differentiation of ET from RT in patients with a platelet count of 600x10(3)/microliter or more. METHODS: The subjects studied were 31 patients with ET and 224 patients with RT. The platelet counts, mean platelet volume (MPV), plateletcrit (PCT), platelet distribution width (PDW), mean platelet mass (MPM), mean platelet component concentration (MPC) and large platelets (LPLT) were measured by ADVIA 120 (Bayer Diagnostics, USA). The mean values of each item were compared between the two patient groups and the sensitivity and specificity of each item in the diagnosis of ET were determined by ROC curve analysis. RESULTS: In essential thrombocythemia, all parameters except MPC were significantly higher than in reactive thrombocytosis. For the diagnosis of ET, the sensitivity and specificity were: 74.2% and 84.4%, when the platelet count was > or = 820x10(3)/microliter; 80.6% and 80.0%, when the plateletcrit was > or =0.63%; and 64.5% and 99.1%, respectively, when LPLT was > or = 23x10(3)/microliter. CONCLUSIONS: The platelet counts and platelet indices are useful for the differential diagnosis of thrombocytosis. The plateletcrit and LPLT are particularly useful for the diagnosis of ET when the platelet count is markedly increased.

JAK2 mutation and myeloproliferative disorders in Pakis

To study the haematological features and JAK2 mutation in Pakistani patients of myeloproliferative disorders. Descriptive cross sectional. Department of Heamatology, Armed Forces Institute of Pathology, Rawalpindi from Jan 2004 to Jan 2007. Forty seven consecutive patients of myeloproliferative disorders [MPD] diagnosed by the conventional haematological criteria were included in the study. The patients on treatment were excluded. Age, sex, splenic enlargement, blood complete counts and bone marrow examination findings were recorded. All patients were screened for G-T Point mutation [V617F] in the JAK2 gene on chromosome 9 by an allele specific PCR Out of the 47 MPD patients, 17 [36%] had polycythaemia rubra vera [PRV], 7 [15%] had essential thrombocythaemia [ET] and 18 [38%] had idiopathic myelofibrosis [MF]. JAK2 positive was seen in 37/47 [79%] patients including 17/17 [100%] in PRV, 4/7 [57%] in ET and 13/18 [72%] in IMF. MPDs are an important group of haematology disorders in Pakistan. Vast majority of these disorders [79%] showed mutation in the JAK2 gene. JAK2 mutation analysis is especially useful in the diagnosis of polycythaemia vera where it was found in 100% of the cases

Essential thrombocythaemia.

A case of essential thrombocythaemia which responded to aspirin and hydroxyurea is presented.

Trombocitosis en la edad pediátrica / Thrombocytosis in paedriatric patients

El valor normal de plaquetas varía entre 150,000 y 450,000 x mm al cubo. Se define trombocitosis como un recuento mayor de 600,000. Pueden ser primarias, por un trastorno mieloproliferativo o secundarias a un gran número de patologías. Objetivos: conocer en nuestro medio la frecuencia de ambos tipos de trombocitosis, describir las patologías asociadas y relacionar la magnitud de la trombocitosis con los diferentes diagnósticos. Material y métodos: se analizaron 18,000 hemogramas realizados entre enero y diciembre de 1998, en el Hospital Roberto del Río. Se evaluó sexo, recuento de plaquetas y leucocitos, hematocrito, hemoglobina, VCM, CHCM y diagnósticos. Resultados: se encontró trombocitosis en 584 exámenes (3,24 por ciento). Se evaluaron 334 fichas, el 62 por ciento eran de sexo masculino. El 0,9 por ciento presentó cifras de plaquetas > 1,000,000 x mm al cubo (dos casos fueron trombocitosis primarias: trombocitemia esencial y leucemia mieloide crónica y un caso de meningitis bacteriana). Las trombocitosis secundarias se asociaron a: infecciones (48,8 por ciento), principalmente respiratorias, deficiencia de hierro (18,6 por ciento) y daño tisular (12,6 por ciento). Conclusiones: la frecuencia de trombocitosis en niños es baja. Cuando la trombocitosis es menor de 1,000,000 x mm al cubo debe sospecharse una etiología secundaria

Hipertrigliceridemia posterior a terapia con interferon alfa en trombocitemia esencial / Hypertriglyceridemia after therapy with alpha interferon in essential thrombocythemia

Se describe un caso de trombocitemia esencial, en una mujer mestiza de 19 años de edad tratada con hidroxiurea hasta lograr remisión y luego como mantenimiento se utilizó como única terapia interferon alfa, observando resultado en el control del número de plaquetas. Seis meses después del uso continuo de este medicamento, la paciente presenta hipertrigliceridemia con cifras de colesterol normal, y cuatro semanas después de la interrupción de éste las cifras de triglicéridos se normalizaron. Este es el primer caso reportado en Venezuela de trombocitemia esencial tratado con hidroxiurea e Interferon alfa que logra remisión hematológica total, pero luego de seis meses de uso del Interferon alfa, desarrolla hipertrigliceridemia, que remite con la interrupción del mismo. Se llama la atención sobre el desarrollo de la hipertrigliceridemia como efecto secundario del uso del Interferon alfa

Tromboastenia de Glanzmann: déficit parcial del complejo glicoproteico IIb/IIIa de la membrana plaquetaria / Glanzmann's thromboasthenia

La tromboastenia de Glanzmann es un trastorno hemorrágico de herencia autosómica recesiva, caracterizado por la ausencia o déficit de complejo glicoproteico IIb/IIIa de la membrana de las plaquetas, que se traduce en alteración de la agregación plaquetaria y sangramientos. Se describre el caso clínico de una niña de tres años de edad con síndrome purpúrico-equimótico y antecedente de hemorragias desde el año de vida, con recuento y morfología plaquetaria normales, tiempo de sangría prolongado, modificación en la retracción del coágulo, ausencia de agregación plaquetaria frente a ADP, colágeno, araquinodato de Na, epinefrina, ionóforo A23187 y agregación subnormal con ristocetina. Mediante técnicas de inmunofluorescencia y anticuerpos monoclonales se confirmó disminución del complejo GP IIb/IIIa de la membrana plaquetaria y reducción en el número de sitios de fijación de este complejo por plaqueta, lo que permite catalogar a la paciente como una variante de tromboastenia de Glanzmann

Essential thrombocythemia: a hypercoagulable state

Essential thrombocythemia is an entity characterized by clonal proliferation of megakaryocytes and thromboccytosis. We have analyzed the presenting manifestation of 13 patients with Essential Thrombocythemia diagnosed in the last three years. The major findings include the frequent presence of symptomatology of a hypercoagulable state with pro,pt improvement of these symptoms once the thrombocytosis is controlled. Constitutional symptoms, organomegaly, modest Leukocytosis and eosinophillia were also often seen. No catastrophic events were detected with a mean follow up period of 17.5 months