Clinical Implications of Elevated Antiphospholipid Antibodies in Adult Patients with Primary Immune Thrombocytopenia

BACKGROUND/AIMS: Antiphospholipid antibodies (aPL) have been detected in various proportions of patients with primary immune thrombocytopenia (ITP), but the clinical significance of this is debatable. The present study aimed to determine the frequency and clinical implications of elevated aPL in adult patients with ITP. METHODS: We prospectively studied newly diagnosed adult patients with ITP who were enrolled between January 2003 and December 2008 at Chungnam National University Hospital. They were evaluated for the presence of lupus anticoagulant (LA) and anticardiolipin antibodies (aCL) at diagnosis and were followed for the development of thrombosis. RESULTS: Seventy consecutive patients with ITP (median age, 48 years; range, 18 to 79) were enrolled. Twenty patients (28.5%) were positive for aPL at the time of diagnosis: aCL alone in 15 (75%), aCL and LA in two (10%), and LA alone in three (15%). Patients who had platelet counts < 50,000/microL were administered oral prednisolone with or without intravenous immune globulin. No difference was found between the aPL-positive and -negative groups regarding gender, initial platelet count, and response to the therapy. After a median follow-up of 20 months (range, 2 to 68), two of 20 patients who were aPL-positive (10%) developed thrombosis, whereas no thrombotic event was found among those who were aPL-negative. CONCLUSIONS: Our data suggest that aPL levels should be determined at the initial presentation of ITP and that patients found to be aPL-positive should receive closer follow-up for thrombotic events.

Niveles de citoquinas megacariocitopoyéticas en pacientes con trombocitemia esencial y su relación con características clínicas y bioquímicas / Megakaryopoietic cytokine levels in patients with essential thrombocythemia and their relationship with clinical and biochemical features

La megacariocitopoyesis y la producción de plaquetas están regidas por factores de transcripción y citoquinas presentes en el microambiente medular. La trombocitemia esencial (TE) es una enfermedad mieloproliferativa crónica caracterizada por aumento del recuento de plaquetas e hiperplasia megacariocítica. En el presente trabajo se evaluaron los niveles de las citoquinas que participan en el desarrollo megacariocítico en plasma de pacientes con TE que se encontraban sin tratamiento y los de trombopoyetina (TPO) antes y durante el tratamiento con anagrelide. Las determinaciones se realizaron por técnica de ELISA. Dentro de las citoquinas involucradas en la etapa de proliferación, los niveles de interleuquina 3 (IL-3) se encontraron aumentados en los pacientes (p=0.0383) respecto al grupo control. Los niveles de factor estimulante de colonias granulocito-macrofágico y stem cell factor fueron normales. Dentro de las citoquinas con acción sobre la maduración megacariocítica, tanto la interleuquina 6 como la interleuquina 11 y la eritropoyetina estuvieron normales. Los niveles de TPO antes del tratamiento no difirieron del grupo control y durante el tratamiento aumentaron de manera no significativa. Los pacientes que presentaron agregación espontánea tuvieron niveles más altos de TPO que los que no lo hicieron (p=0.049). Los niveles de las citoquinas no tuvieron relación con ninguno de los parámetros clínicos ni de laboratorio evaluados. El aumento de los niveles de IL-3 podría contribuir al incremento en la proliferación megacariocítica en este grupo. La presencia simultánea de niveles más altos de TPO y trombocitosis sería un factor predisponente para la ocurrencia de agregación espontánea en los pacientes con TE

Megakaryopoiesis and platelet production are driven by transcription factors and cytokines present in bone marrow environment. Essential thrombocythemia (ET) is a chronic myeloproliferative disorder characterized by high platelet count and megakaryocytic hyperplasia. In the present work we evaluated plasmatic levels of cytokines involved in megakaryocytic development in a group of patients with ET that were not on treatment, as well as thrombopoietin (TPO) levels before and during anagrelide treatment. The assays were carried out using ELISA techniques. Among the cytokines mainly involved in proliferation of megakaryocytic progenitors, interleukin 3 (IL-3) levels were found increased in patients compared to normal controls (p=0.0383). Granulocyte-macrophage colony stimulating factor and stem cell factor levels were normal. Interleukin 6, as well as interleukin 11 and erythropoietin (EPO), cytokines mainly related to megakaryocytic maturation, were normal. Plasma TPO levels before treatment were within the normal range and increased during treatment but the difference was not statistically significant. Patients who displayed spontaneous platelet aggregation had higher plasma TPO levels compared to those who did not (p=0.049). We did not find any relationship between cytokine levels and clinical or laboratory parameters. The high IL-3 levels seen in some patients with ET could contribute to megakaryocytic proliferation. The simultaneous occurrence of higher TPO levels and elevated platelet count could be a predisposing factor for the development of spontaneous platelet aggregation in ET patients

Asymptomatic essential thrombocythemia: a case report.

Essential thrombocythemia (ET) is a clonal disorder of unknown etiology involving multipotent hematopoietic progenitor cell and belongs to the spectrum of chronic myeloproliferative disorders (CMPD). It is rarest of the CMPD with no case reported from India. The case being presented was detected incidentally during routine investigations in an adult female who presented with mild abdominal discomfort.

Tromboxano B2 y factor de crecimiento derivado de las plaquetas en la trombocitemia esencial tratada con anagrelide / Thromboxane B2 and platelet derived growth factor in essential thrombocythemia treated with anagrelide

Presentamos los resultados obtenidos en 17 pacientes con trombocitemia esencial antes del tratamiento con anagrelide y durante la remisión hematológica y clínica inducida por esta droga. Diez pacientes tenían manifestaciones clínicas relacionadas con la trombocitemia, en 8 de ellos al momento de iniciar el tratamiento. Se midieron los niveles plasmáticos del TXB2 y del PDGF por técnica de ELISA. Antes del tratamiento los valores plasmáticos del PDGF corregidos por el recuento de plaquetas eran significativamente menores que en los controles (p = 0.02), y no difirieron de los resultados obtenidos durante la remisión. En cambio, los valores plasmáticos del TXB2, corregidos de acuerdo al recuento de plaquetas, estaban más elevados que en los controles (p = 0.04), y disminuyeron significativamente durante la remisión (p = 0.04), aunque todavía estaban por sobre los valores normales (p = 0.008). Los síntomas desaparecieron en todos los pacientes cuando el recuento de plaquetas se normalizó. Estos resultados muestran que los pacientes con trombocitemia esencial tratados con anagrelide y en remisión hematológica y clínica tienen tendencia a normalizar los niveles del TXB2.

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

Megakaryoblastic transformation of a myeloproliferative disorder.

A case of megakaryoblastic transformation of a myeloproliferative disorder presenting initially as chronic granulocytic leukaemia with an intermediate phase of essential thrombocythaemia in a Chinese woman of 65 years is reported. The diagnosis of megakaryoblastic crisis was based on morphological, cytochemical and immunocytochemical features present in blast cells in the blood, together with cytochemical and ultrastructural features of micromegakaryocytes and megakaryoblasts which were predominant in the marrow. A literature review showed newer refinements in diagnosis such as ultrastructural platelet peroxidase and additional immunologic techniques employing antisera against further platelet products. The response to treatment remains uniformly poor.