Objective, planimetry-based assessment of megakaryocyte histological pictures in Philadelphia-chromosome-negative chronic myeloproliferative disorders: a perspective for a valuable adjunct diagnostic tool

Philadelphia-chromosome-negative chronic myeloproliferative disorders (Ph− CMPDs)—essential thrombocythemia (ET), chronic idiopathic myelofibrosis (CIMF), and polycythemia vera (PV)—may show clinical and morphological similarities, particularly at the early stages. The differential diagnosis of Ph− CMPDs is important due to their different treatment and prognosis. Cytological features of megakaryocytes are considered valuable in this differentiation. To establish an objective measure of megakaryocyte dysplasia in Ph− CMPDs, we performed computer-assisted morphometry of more than 4,000 cells from 20 cases of ET, 10 of CIMF, 10 of PV, and 10 controls. Megakaryocyte sets from three Ph− CMPDs differed significantly in respect to many planimetric parameters, but not a single shape or size parameter could have been used as a discriminative tool between the entities. However, the discriminant function analysis with the simultaneous assessment of 12 planimetric variables allowed for a proper classification of 20 of 20 ET, 10 of 10 PV, and 9 of 10 CIMF cases based solely on the morphometric features of megakaryocytes. Additionally, we identified certain new patterns of megakaryocytes specific for ET, PV, and CIMF, which, although not dominating in one Ph− CMPD, are unlikely to occur in two others. Objective measurements of megakaryocyte sizes and shapes may assist the diagnosis of Ph− CMPDs.     

Budd-chiari syndrome and thrombosis of other abdominal vessels in the chronic myeloproliferative diseases

Summary Of 501 patients with chronic myeloproliferative diseases (c-MPD) 18 developed thrombosis of major abdominal vessels including 6 with hepatic vein thrombosis (Budd-Chiari syndrome). The complication was seen in 14 of 140 (10%) patients with polycythemia vera (PV), 3 of 23 (13%) patients with essential thrombocythemia (ET), 1 of 106 (1%) patients with idiopathic myelofibrosis (IMF), and none of 232 patients with chronic myelogenous leukemia (CML). Leading symptoms and signs were abdominal pain, progressive splenomegaly, widening abdominal girth, ascites, venous collaterals, and nausea and vomiting. The diagnostic modalities with highest specificity were angiography and explorative laparotomy. A causal relationship between the thrombotic event and hematocrit, thrombocyte count, or hemostatic abnormalities at the time of diagnosis could not be established. Detailed laboratory tests of platelet function and coagulation and fibrinolytic parameters of 5 surviving patients did not show any specific defect. Despite medical and surgical intervention, 39% of the patients died within 2 months after diagnosis of the thrombosis. The majority of the survivors developed further complications like liver cirrhosis with portal hypertension and esophageal varices or the short bowel syndrome after extensive bowel resection for mesenterial infarction.Abbreviations CML Chronic myelocytic leukemia - c-MPD Chronic myeloproliferative diseases - ET Essential thrombocythemia - IMF Idiopathic myelofibrosis - PV Polycythemia vera     

Morphologic Characteristics of Blastic Plasmacytoid Dendritic Cell Neoplasm: A Case Report

Abstract

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare aggressive lymphoma derived from plasmacytoid dendritic cells or precursor dendritic cells. Despite some 240 reported cases, its morphology and especially ultrastructure has not been satisfactorily studied. A case is reported of a 13 year old boy, who, despite chemotherapy, died within a 12-month period. The electron microscopy findings – microvillous processes, nuclei with slight irregularities, a moderate amount of heterochromatin, and rough endoplasmic reticulum in the form of long, narrow profiles, often in parallel arrangements – taken together, serve to distinguish BPDCN from other neoplastic cells, such as monocytes, plasma cells and the cells of chronic lymphocyte leukemia.     

Hematopoietic cell transplantation for chronic myeloproliferative disorders

Myeloproliferative disorders, including chronic idiopathic myelofibrosis (CIMF), polycythemia vera (PV), essential thrombocythemia (ET), and chronic myelomonocytic leukemia (CMML), are clonal diseases of hematopoietic stem or precursor cells. They often show a protracted or chronic course; however, all have the potential of progressing to severe marrow failure, associated with myelofibrosis, or of transforming into acute leukemia. At that point, hematopoietic cell transplantation (HCT) is the only current treatment strategy with curative potential. If transplantation is being considered and a suitable donor is available, HCT should be carried out before leukemic transformation has occurred, as the success rate of HCT declines steeply in patients who have evolved to leukemia. As many as 75–80% of patients with the original diagnoses of PV or ET, about 65–70% with CIMF, and 45% of patients with CMML are surviving long term after allogeneic HCT using conventional transplant regimens, with follow-up now extending to 15 years. Results with HLA-identical related and unrelated donors are comparable. Major risk factors for the outcome after HCT are the disease stage, the presence of comorbid conditions, and patient age. The development of reduced-intensity conditioning regimens has allowed for successful HCT even for older patients and patients with comorbid conditions. Studies on disease mechanisms, including the recent characterization of an activating mutation in JAK2, may provide additional prognostic guidance and are likely to lead to the development of novel treatment strategies, which will require continuous reassessment as to the optimum timing of HCT.     

Silver-stained nucleolar organizer regions in the normal,hyperplastic and neoplastic endometrium

Summary A morphometric evaluation of number and grouping of megakaryocytes (MK) in five different groups of chronic myeloproliferative disorders (CMPD) was performed by counting 60 high power fields equaling approximately 14.28 mm² of haematopoiesis in each case. Twenty-one up to 29 cases were evaluated for each of five categories of CMPD and one control group; a total of 132 cases of CMPD and 33 control cases were used. The mean number of MK per square millimetre was 15.54±1.53 in chronic myeloid leukaemia of common or granulocytic type (CML.CT), 69.91±5.85 in CML with megakaryocytic increase (CML.MI), 59.59 ±3.27 in polycythaemia vera (P. vera), 59.85±4.59 in primary thrombocythaemia (PTH), 67.58±4.11 in chronic megakaryocytic granulocytic myelosis (CMGM), and 19.7±3.07 in controls. The distinction between free or isolated MK, and between clustered or grouped MK corresponds to the total cell counts of MK in the various groups of CMPD. Clustering of MK was significantly higher in CMGM and PTH compared to other groups, but the difference between them was not statistically significant. Significant differences in the mean number of MK were obtained between controls and CML.CT on the one hand and all other groups of CMPD on the other. The results further support the histological sub-classification of CMPD according to the primary disorders of the Hannover classification (not advanced by sclerosis, fibrosis or excess of blasts, respectively).     

Immunohistochemical evaluation of bone marrow lymphoid nodules in chronic myeloproliferative disorders

Summary One hundred and seventy bone marrow biopsies from patients with chronic myeloproliferative disorders (CMPDs) were evaluated for the presence of lymphoid nodules (LNs) and were immunostained using a panel of monoclonal antibodies (UCHL1, 4KB5 and L26) recognizing different lymphocyte antigens. LNs were found in 35% of cases of idiopathic thrombocythaemia, 24.6% of myelofibrosis/osteomyelosclerosis, 18.2% of polycythaemia vera, 12.1% of chronic myeloid leukaemia and 19.2% of borderline cases. Varying degrees of immunohistochemical positivity for the three antibodies tested were found. LNs were always made up of variable proportions of both T-and B-lymphocytes with a prevalence of T-cells. This latter observation suggests that bone marrow LNs in CMPDs could be an expression of reactivity.     

Janus kinase 2 V617F mutation is detectable in spleen of patients with chronic myeloproliferative diseases suggesting a malignant nature of splenic extramedullary hematopoiesis

Extramedullary hematopoiesis occurs in patients with a variety of hematologic diseases, and the spleen is a common site. Extramedullary hematopoiesis is very common in chronic myeloproliferative diseases and myeloproliferative/myelodysplastic diseases. The pathogenesis of extramedullary hematopoiesis is unknown. Using JAK2 V617F mutation as a molecular marker, we assessed paired spleen and bone marrow samples of 15 patients with various types of chronic myeloproliferative diseases and myeloproliferative/myelodysplastic diseases. The diagnosis was chronic idiopathic myelofibrosis (n=8), polycythemia vera (n=3), and chronic myelomonocytic leukemia (n=4). DNA was extracted from fixed, paraffin-embedded tissue and assessed for JAK2 V617F by real-time polymerase chain reaction assay followed by melting curve analysis. Concordant JAK2 mutation was detected in the paired samples in 7 patients. A discordant result with JAK2 V617F found in the spleen but not bone marrow was noted in 1 patient. These results indicate that extramedullary hematopoiesis in patients with chronic myeloproliferative diseases and myeloproliferative/myelodysplastic diseases is a clonal process and lend support to the theory that the cells of extramedullary hematopoiesis are carried from the bone marrow.     

Untersuchungen zur Thrombozytenfunktion bei essentieller Thrombozythämie und reaktiver Thrombozytose

Summary Blood of 16 patients with essential thrombocythemia (ET), 9 patients with reactive thrombocytosis (RT) and 13 healthy persons was used for platelet aggregation studies. When the aggregation was induced with adenosine diphosphate (0.01 µM), collagen (0.1 µg/ml) or platelet activating factor (PAF 0.5 µM) the plasma of the patients with ET showed significantly decreased aggregation (35%–44% of the value for the control groups). Independent of inhibitors of platelet aggregation, thrombin (0.05 U/ml) caused similar aggregation in healthy controls and patients with ET; patients with RT showed an increased aggregation. Adrenalin-induced aggregation discriminated best between patients with ET and controls. Adrenalin in concentrations ranging from 0.01 µg/ml to 100 µg/ml caused comparable dose-related amounts of aggregation in healthy controls and patients with RT. Over the whole concentration range, patients with ET showed significantly decreased aggregation (28%–34% of the value for the control groups). This difference proved to be independent of the influence of inhibitors of platelet aggregation. Though concentrations of alpha₁-acid glycoprotein never reached inhibitory levels in the plasma of patients with ET (n=12) they were significantly higher compared with those in normal plasma (n=12). Fibrinogen concentrations in plasma of ET-patients (n=12) were in the normal range. Cellular adenosine 3–5-cyclic monophosphate concentrations in ET (n=10) are comparable with normal values (n=5). The significance of the results for diagnosis and better pathophysiological understanding of ET is discussed.

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Abkürzungen ADP Adenosindiphosphat - cAMP zyklisches Adenosin-3,5-monophosphat - ET essentielle Thrombozythämie - IBMX Isobutyl-methyl-xanthin - PAF Plättchen aktivierender Faktor - PFP Plättchenfreies Plasma - PRP Plättchenreiches Plasma - RT Reaktive Thrombozytose Herrn Prof. Dr. N. Zöllner zum 65. Geburtstag gewidmet     

Chronic myeloproliferative disorders (CMPD)

The wide clinical range of CMPD can be understood as leukaemia of pluripotent stem cells according to the pathogenic concepts reviewed above. Blastic metamorphoses of CMPD are regressions to a more primitive level of cellular differentiation. The predominant proliferative cell line characterizes the classical entities of PV, PT and CML, and their different prognoses. Pure erythrocytic and megakaryocytic proliferations are more compatible with sustained physiologic bone marrow functions than granulocytic proliferations. The combinations of granulocytic and megakaryocytic growth are especially prone to develop MF/OMS, in which participation of immune reactions, of granulocytic and of platelet factors is probable. An etiologic role for ineffective thrombocytopoiesis is supported by experimental as well as by histologic evidence. Myelofibrosis and osteomyelosclerosis may have similar causes, but develop independently. The prevalence of the female sex among thrombocythaemic patients was proven statistically also for the increase of giant type megakaryocytes in the form of clusters in the bone marrow, and for longer median survival of females in CMPD, especially when there is megakaryocytosis in the bone marrow. It is assumed that females may be better protected against the detrimentous effects of abnormal platelet production. An arbitrary classification according to haematologic and histologic criteria was applied to PV, PT and CML, and groups with typical and atypical haematologic and histologic signs were distinguished. The latter cannot be separated from each other by their various haematologic manifestations, but by histology and their different propensity to progress into more immature and/or fibrotic stages. Three major groups are characterized by histology: mixed granulocytic-megakaryocytic myelosis with giant megakaryocytic clusters, a similar variant with diffuse distribution of giant megakaryocytes, and immature and/or pleomorphic megakaryocytic myelosis. Transitions from each of these groups have been observed as well as transitions from each of the typical CMPD-entities into these less typical forms. CML, frequently accompanied by dwarf-megakaryocytes, often develops into pleomorphic megakaryocytic or blastic myelosis. Blastic dedifferentiation and myelofibrosis manifest themselves as closely related end stages, to which principally all groups proceed after a longer or shorter period of time, modified by the proliferating cell lines in each group. Clinical, experimental and histologic evidence of this natural history has been reviewed, with special emphasis on the re-evaluation of technically optimal bone marrow biopsies of untreated patients.(ABSTRACT TRUNCATED AT 400 WORDS)     

Impact of JAK2V617F Mutation Burden on Disease Phenotype in Chinese Patients with JAK2V617F-positive Polycythemia Vera (PV) and Essential thrombocythemia (ET)

Most patients with polycythemia vera (PV) and half of essential thrombocythemia (ET) possess an activating JAK2V617F mutation. The objective of this study was to better define the effect of JAK2V617F mutant allele burden on clinical phenotypes in Chinese patients, especially thrombosis. By real-time polymerase chain reaction (RT-PCR), the JAK2V617F mutation burden was detected in 170 JAK2V617F-positive patients, including 54 PV and 116 ET. The results showed that JAK2V617F allele burden was higher in PV than in ET (P< 0.001). Higher percentage of patients had JAK2V617F allele burden over 20% in PV than in ET (68.5% VS 26.7%) (P< 0.001). In PV patients, higher JAK2V617F allele burden was observed in female (P< 0.05) and leukocytosis patients (WBC above 10×10⁹/L) (P< 0.001). Meanwhile, ET patients showed increased JAK2V617F allele burden in the group with higher hemoglobin (HGB above 150g/L) (P< 0.05), leukocytosis (WBC above 10×10⁹/L) (P< 0.001), splenomegaly (P< 0.05) and thrombosis (P< 0.05). In conclusion, the JAK2V617F mutation allele burden is higher in Chinese patients with PV than ET. In PV patients, JAK2V617F mutation burden had influence on WBC counts. And the clinical characteristics of ET patients, such as WBC counts, hemoglobin level, splenomegaly and thrombosis, were influenced by JAK2V617F mutation burden. Male, high hemoglobin (HGB above 150g/L), and increased JAK2V617F mutation burden (JAK2V617F allele burden ≥16.5%) were risks of thrombosis (P< 0.05) for ET patients by Logistic Regression.     

The role of beta-catenin in chronic myeloproliferative disorders

The goal of the current study is to evaluate the role of beta-catenin in chronic myeloproliferative disorders. Expression of beta-catenin was analyzed by immunohistochemistry in formalin-fixed decalcified bone marrow biopsy specimens from 52 chronic myeloproliferative disorder cases and 6 nonchronic myeloproliferative disorder bone marrows as controls. The frequency of moderate to strong beta-catenin staining of megakaryocytes was significantly higher in polycythemia vera cases and in essential thrombocythemia cases than in chronic myelogenous leukemia cases (polycythemia vera versus chronic myelogenous leukemia, P = .002345, Fisher exact; and essential thrombocythemia versus chronic myelogenous leukemia, P = .002288), chronic idiopathic myelofibrosis cases (polycythemia vera versus chronic idiopathic myelofibrosis, P = .006707 and essential thrombocythemia versus chronic idiopathic myelofibrosis, P = .006932) or control cases (polycythemia vera versus control, P = .010489 and essential thrombocythemia versus control, P = .0113120). The erythroid and myeloid lineages showed absent to weak beta-catenin staining in most cases. In conclusion, these results indicate that the Wnt/beta-catenin signaling pathway may have a role in megakaryocytopoiesis in polycythemia vera and essential thrombocythemia. In addition, beta-catenin may be a useful marker for differentiating polycythemia vera and essential thrombocythemia from other types of chronic myeloproliferative disorders.     

JAK2 V617F,MPL, and CALR Mutations in Korean Patients with Essential Thrombocythemia and Primary Myelofibrosis

Mutations in the calreticulin gene, CALR, have recently been discovered in subsets of patients with essential thrombocythemia (ET) or primary myelofibrosis (PMF). We investigated Korean patients with ET and PMF to determine the prevalence, and clinical and laboratory correlations of CALR/JAK2/MPL mutations. Among 84 ET patients, CALR mutations were detected in 23 (27.4%) and were associated with higher platelet counts (P=0.006) and lower leukocyte counts (P=0.035) than the JAK2 V617F mutation. Among 50 PMF patients, CALR mutations were detected in 11 (22.0%) and were also associated with higher platelet counts (P=0.035) and trended to a lower rate of cytogenetic abnormalities (P=0.059) than the JAK2 V617F mutation. By multivariate analysis, triple-negative status was associated with shorter overall survival (HR, 7.0; 95% CI, 1.6-31.1, P=0.01) and leukemia-free survival (HR, 6.3; 95% CI, 1.8-22.0, P=0.004) in patients with PMF. The type 1 mutation was the most common (61.1%) type among all patients with CALR mutations, and tended toward statistical predominance in PMF patients. All 3 mutations were mutually exclusive and were never detected in patients with other myeloid neoplasms showing thrombocytosis. CALR mutations characterize a distinct group of Korean ET and PMF patients. Triple-negative PMF patients in particular have an unfavorable prognosis, which supports the idea that triple-negative PMF is a molecularly high-risk disease.

Graphical Abstract

相似文献   

JAK2-V617F mutation in Moroccan patients with myeloproliferative disorders: Contribution, diagnosis and therapeutic prospects

Aims

The JAK2 V617F is a recent discovery. The implication of this mutation in the pathogenesis of the myeloproliferative disorders (MPDs) is currently confirmed. Our study is the first to be interested in the status of the JAK2 V617F mutation among myeloproliferative disorders patients in Morocco.

Patients and methods

Our study focused on 70 non-CML MPD patients, attending several departments of hematology and internal medicine across Morocco. The mutation was detected by allele-specific PCR (AS-PCR).

Results

The V617F JAK2 mutation incidence in polycythemia vera, essential thrombocythemia and idiopathic myelofibrosis are respectively 89.47%, 62.5% and 33.33%. The V617F JAK2 mutation was absent within the patients with secondary erythrocytosis or thrombocytosis. We also found that the patients carrying the mutation displayed a leucocytosis and higher levels of haemoglobin and hematocrit than mutation-negative patients.

Conclusion

Our study is the first to assess the status of the JAK2 V617F mutation in patients with MPDs in Morocco. However, our data seem to confirm that the JAK2 V617F mutation is rather uncommon in myeloid malignancies other than the classical BCR/ABL MPD negative.     

Stare i nowe czynniki ryzyka zakrzepicy u chorych z nadpłytkowością samoistną

Essential Thrombocythemia (ET) is one of the classical Philadelphia negative myeloproliferative neoplasms. Despite the chronic course of the disease, the ET patients had an inferior survival compared to the general population, because of higher mortality, mainly due to thrombotic complications. Besides well known old risk factors, such as old age (>60 year) and previous history of thrombosis, still some new ones appeared. In 2005 the JAK2V617F point mutation was found in 50-60% of ET patients. An increased risk of thrombosis in patients with this mutation has been reported. In this study there is a summary of old and new risk factors which may contribute to thrombotic complications in ET patients.     

Phospho-STAT5 expression pattern with the MPL W515L mutation is similar to that seen in chronic myeloproliferative disorders with JAK2 V617F

Abnormal nuclear megakaryocytic staining for phospho-STAT5 (pSTAT5) correlates with JAK2 V617F mutational status in non-chronic myelogenous leukemia chronic myeloproliferative disorders. However, a proportion of wild-type JAK2 non-chronic myelogenous leukemia chronic myeloproliferative disorders cases also demonstrate this abnormal pSTAT5 expression pattern. We report a patient with a JAK2 V617F-negative myeloproliferative/myelodysplastic syndrome who had abnormal megakaryocytic pSTAT5 expression and a MPL W515L mutation. The patient was a 71-year-old man with anemia and thrombocythemia on laboratory examination. His peripheral blood smear demonstrated occasional dysplastic neutrophils. Bone marrow biopsy revealed hypercellular marrow with features consistent with myeloproliferative/myelodysplastic syndrome. Immunohistochemistry for pSTAT5 showed abnormal nuclear megakaryocyte positivity. Cytogenetic analysis revealed a normal karyotype, fluorescence in situ hybridization for BCR-ABL was negative, and JAK2 genotyping demonstrated wild-type JAK2. However, MPL genotyping showed a MPL W515L mutation. Abnormal nuclear megakaryocytic staining for pSTAT5 expression, previously associated with the JAK2 V617F mutation, is also associated with MPL W515L, likely reflecting activation of the JAK-STAT signaling pathway.     

Productin of Basic Fetoprotein in Human Peripheral Lymphocytes during Blastic Transformation

To clarify the significance of basic fetoprotein (BFP) in lymphocytes, we investigated whether BFP is produced in lymphocytes during blastic transformation. Peripheral blood lymphocytes obtained from 14 adults were cultured under the stimulation of lectins. The concentration of BFP in the culture medium (extracellular BFP) was estimated serially. The incorporation of [6-³ H] thymidine was assayed simultaneously. The intracellular BFP was measured by dual flow cytometry for DNA and BFP. A lymph node was studies immunohistochemically. Serum BFP was measured in four cases of lumphocytic leukaemia. In two cases, dual staining was performed. The intracellular BFP of the mitogen-stimulated lymphocytes was increased within 24 h. The extracellular BFP was increased exponentially from 72 h. The extracellular BFP at 96 h did not correlate with the [³H]-thymidine incorporation. The intracellular BFP increase began in G₁ phase. Immunostaining showed that the B cells also produced BFP. The
serum BFP level in leukaemia was high in 1 of 4 cases and the leukaemic cells in two cases showed high intracellular BFP content. These observations indicate that BFP is produced in activated human lymphocytes and in lymphocytic leukaemic cells. The production of BFP during blastic transformation will be a useful new in vitro model for studying the biological role of BFP, and BFP labelling may offer some new possibilities for study of lymphocytes.     

Bone marrow histomorphology and JAK2 mutation status in essential thrombocythemia

A retrospective study of 38 essential thrombocythemia (ET) patients was conducted, reviewing bone marrow biopsies according to WHO criteria using a semiquantitative scoring system. Four patients did not fulfil the WHO criteria for a myeloproliferative disorder and one biopsy was insufficient for evaluation. 14 patients were reclassified as having prefibrotic idiopathic myelofibrosis (IMF), whilst the ET diagnosis was sustained in 19 patients. The individual bone marrow parameters of the reviewed diagnosis showed no correlation with JAK2 V617F mutation status, which was determined by a highly sensitive quantitative real-time PCR (qPCR) method. However, we could confirm previous findings of higher haemoglobin and lower platelet levels in the JAK2 V617F positive patients. Thus, the well-established phenotypic relationship of JAK2-positive ET and PV at the biochemical and molecular level was not recorded as regards bone marrow morphology according to the WHO criteria. Accordingly, the WHO concept of two distinct entities, ET and prefibrotic IMF, does not seem to fit the model of JAK2-positive ET as part of a biological continuum of JAK2 V617F-positive chronic myeloproliferative disorders.     

Nucleolar organizer regions of megakaryocytes in chronic myeloproliferative disorders

Summary To study megakaryocyte activation, the argyrophilic staining method of nucleolar organizer regions (AgNOR) has been applied to decalcified bone marrow biopsies of 16 individuals with no haematopoietic disorders and 59 patients with chronic myeloproliferative disease. Of the 59 patients, 18 had chronic myeloid leukaemia (CML), 21 chronic megakaryocytic granulocytic myelosis (CMGM), 13 polycythaemia vera (PV) and 7 essential thrombocythaemia (ET). The AgNOR number of megakaryocytes in CML was significantly lower, and in CMGM, PV and ET significantly higher than in healthy individuals. The high number and the clusters of fine-grained AgNORs of megakaryocytes in CMGM, PV and ET are suggestive of active, proliferating cells. The AgNOR number of megakaryocytes and the platelet counts of the patients did not show a convincing correlation. In CMGM, PV and ET the pyknotic, heterochromatinized megakaryocytes with narrow rims of cytoplasm called bare (nude) nuclei, possessed few, large AgNOR granules. The AgNOR staining of bare nuclei and the roughly identical number of granules found in CMGM, PV and ET indicate a common, active mechanism of apoptosis.     

Klinische Charakterisierung der essentiellen Thrombozythämie im Vergleich zu anderen myeloproliferativen Erkrankungen und reaktiven Thrombozytosen

Summary 60 patients with essential thrombocythemia (ET) have been retrospectively and prospectively followed from 1974 through 1987. The presenting signs and symptoms and the course of the disease were analyzed and compared to 10 patients with persisting reactive thrombocytosis selected from 6000 patients with reactive thrombocytosis and to 50 patients with other myeloproliferative diseases. 54 ET-patients presented with complications, 46 with thrombembolic, 3 with hemorrhagic problems and 5 with thrombembolic and hemorrhagic problems. In 6 patients ET was detected accidentally. Disturbances of the microcirculation, mainly of the fingers and the toes, were the most frequent symptom. The average maximal platelet count was 1 207 000/µl. The average platelet count at diagnosis was 880 000/µl. 16 patients had an elevation of the serum creatinin at diagnosis, which deteriorated during the course of the disease. Bone marrow examinations were performed in 56 patients, histology in 48 patients, cytology in 29 patienst. In contrast to the clinical diagnosis the histological diagnosis was in 4 cases each polycythemia vera and myeloproliferative syndrome without further specifiction. 12 patients died thus far. The causes of death were thrombembolic complications in 9, acute leukemia in 2 patients, in 1 patient the cause of death is not known. 10 years after diagnosis 61% of the patients are still alive. It appears that ET is a more important risk factor for the disturbances of the micro- and marcrocirculation than has been recognized until now. ET is, if thrombembolic complications are avoided, a disease with a relatively benign course.

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Abkürzungsverzeichnis ET essentielle Thromobozythämie - PRT persistierende reaktive Thombozytose - PV Polyzythämia vera - CML chronisch myeloische Leukämie - MF Myelofibrose - CMPE chronische myeloproliferative Erkrankung unklarer Zuordnung - MM megakaryozytäre Myelose - ALP alkalische Leukozytenphosphatase - Hb Hämoglobin Herrn Prof. Dr. N. Zöllner zum 65. Geburtstag gewidmet     

Łagodna hiperhomocysteinemia u chorych z nadpłytkowością samoistną (NS), związek z mutacją genu MTHFR i poziomem kwasu foliowego

In this study we assessed homocysteine level in 106 patients with ET – 80 females and 26 males, mean age 54 (23–82) and in 20 healthy persons – 6 males and 14 females, mean age 41 (31–54). We also searched for a relation between homocysteine level and MTHFR gene mutation as well as vitamin B12 and folic acid concentration. Median homocysteine serum level was higher in ET patients than in control group. Elevated homocysteine level primarily stems from folic acid deficiency rather than from the presence of MTHFR gene mutation. Median folic acid level was lower in ET patients presenting thrombotic and bleeding complications than in ET patient without vascular episodes. We concluded that folic acid substitution may not only prevent hyperhomocysteinemia but also the development of vascular complications in ET patients.