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PubMed1997

Proposal for revised diagnostic criteria of essential thrombocythemia and polycythemia vera by the Thrombocythemia Vera Study Group.

The present study revises the criteria of the Polycythemia Vera Group (PVSG) for the diagnoses of essential thrombocythemia (ET) and polycythemia vera (PV) in view of accumulating data on in vitro cultures of hematopoietic progenitors and by adding histopathology from bone marrow biopsies. The majority of ET patients show spontaneous megakaryocyte or erythroid growth or both, but in about 35% the growth pattern is normal. So far none of the patients with reactive thrombocytosis have shown either spontaneous megakaryocyte or erythroid colony growth. Virtually all PV patients show spontaneous or endogenous erythroid colony (EEC) formation, whereas patients with secondary erythrocytosis and healthy controls do not show any erythroid colony growth in the absence of erythropoietin (EPO). Some rare patients with a disorder other than a myeloproliferative disease (MPD) may show spontaneous growth of erythroid colonies caused by a mutation in the EPO receptor. Megakaryocytes in bone marrow smears and biopsy material from ET and PV patients are typically increased in number and size. Enlarged megakaryocytes with mature cytoplasm and multilobulated nuclei and the tendency of these megakaryocytes to cluster in a normal or slightly increased cellular bone marrow represent the diagnostic hallmark of ET. Increase and clustering of enlarged, mature, and pleiomorphic megakaryocytes in a moderate to marked hypercellular bone marrow with hyperplasia of dilated sinuses is the diagnostic feature of untreated PV. In reactive thrombocytosis and secondary erythrocytosis the size and morphology of megakaryocytes remain normal and there is no tendency of the megakaryocytes to cluster. Both spontaneous EEC and histopathology of bone marrow biopsies appear to offer specific clues to the diagnosis of overt and latent ET or PV and have the potential to differentiate ET from reactive thrombocytosis and PV from secondary erythrocytosis. Moreover, bone marrow histopathology has the diagnostic power to distinguish and to stage the various MPDs without regard to clinical and laboratory data.

Biopsy↗
PubMed1987

Intracellular growth factors in polycythemia vera and other myeloproliferative disorders.

In polycythemia vera, idiopathic myelofibrosis, and essential thrombocytosis, hematopoietic cell proliferation is increased in the absence of a recognizable stimulus, suggesting the autonomous production of growth factors in these disorders. Sonicates of peripheral blood mononuclear cells (PBMNC) from patients with polycythemia vera, idiopathic myelofibrosis, and essential thrombocytosis contained soluble factors that stimulated the proliferation of quiescent-confluent 3T3 cells. PBMNC sonicates from normal individuals; from patients with secondary erythrocytosis, chronic myelogenous leukemia, B-cell chronic lymphocytic leukemia, and acute myelogenous leukemia; and from K-562 and HL-60 cells did not stimulate proliferation. Polycythemia vera PBMNC sonicates also induced anchorage-independent colony formation in soft agar by normal rat kidney fibroblasts. Both the mitogenic and transforming activities of the polycythemia vera PBMNC sonicates resided in the T-lymphocyte-depleted mononuclear fraction of the PBMNC and were not secreted. By gel filtration, reversed-phase HPLC and NaDodSO4/PAGE, the mitogenic and transforming activities in the polycythemia vera PBMNC were localized to three proteins with molecular masses of 13-, 17-, and 65-kDa. The 13-kDa protein was only mitogenic, and the 17-kDa protein was only transforming, whereas the 65-kDa protein had both mitogenic and transforming activity. These proteins may be involved in the autonomous hematopoiesis that characterizes polycythemia vera, idiopathic myelofibrosis, and essential thrombocytosis.

Animals↗
PubMed1975

Mesenteric thrombosis following splenectomy.

Three cases of postsplenectomy mesenteric thrombosis, two associated with thrombocytosis, are presented. Experience has shown that persistent thrombocytosis, accompanied by abnormal platelet function, is not a benign condition and may be associated with thrombosis. When encountered, postsplenectomy thrombocytosis of greater than 800,000 per mm-3 must be evaluated by platelet function studies and anticoagulation begun. Post-prandial cramping abdominal pain may be an early symptom of thrombosis, demanding immediate anticoagulation. Low-dose heparin, ASA, and dipyridamole are three of the more commonly used treatment modalities. Small bowel resection is indicated if thrombosis occurs.

Adult↗
PubMed2000

ET gets HIT--thrombocytotic heparin-induced thrombocytopenia (HIT) in a patient with essential thrombocythemia (ET).

Immune-mediated heparin-induced thrombocytopenia (HIT) is a relatively common complication in patients receiving heparin, and represents a strong risk factor for thromboembolic disease associated with high morbidity and mortality. The condition is commonly defined as a platelet count fall of greater than 30-50% to values below 150 x 10(9)/l. Despite this, several cases with platelet count nadirs in the normal range have been reported. This report describes a patient with status post-carotid thrombendarterectomy presenting with neurological symptoms and thrombocytosis (1235 x 10(9)/l), which in due course was diagnosed to be caused by essential thrombocythemia (ET). Heparin therapy was established and symptoms resolved markedly. After 5 days of standard heparin therapy, serologically confirmed HIT with new neurological symptoms occurred. The platelet count nadir attributed to HIT was far above normal (633 x 10(9)/l), which nevertheless represented a substantial relative platelet count fall (49%). This is the first reported case of serologically confirmed HIT in a patient with ET. Furthermore, it represents the first published case of HIT being present in thrombocytosis. Clinicians should be aware that atypical HIT can even be present in thrombocytosis and, because of nomenclature, HIT with normal and elevated platelet count nadirs is likely to be largely underdiagnosed.

Heparin↗
PubMed1992

Possible role of Streptococcus pyogenes in mucocutaneous lymph node syndrome. XV. Potential utility of streptococcal pyrogenic exotoxin toxoid for the prophylaxis and treatment of MCLS.

Mice made tolerant to streptococcal pyrogenic exotoxin (SPE) by neonatal inoculation with SPE emulsified in incomplete Freund's adjuvant demonstrated early thrombocytopenia followed by thrombocytosis. This state is the perfect counterpart of patients with mucocutaneous lymph node syndrome (MCLS). We have hypothesized that by inducing tolerance to SPE, the biological activities of the toxin might play leading roles in the pathogenesis of MCLS. In the present investigations, the efficacy of SPE on the prophylaxis and treatment of diseases caused by Streptococcus pyogenes (including MCLS) were monitored using the murine model system accompanied with a platelet-counting technique. The mice, rendered tolerant due to neonatal SPE inoculation and followed by immunization with SPE toxoid about 1 month prior to the provocative injections with SPE, demonstrated an almost complete lack of response to the provocation, keeping platelet counts within the normal range of values (except for a marginally significant thrombocytosis 7 days postprovocation). Moreover, anti-SPE titers of the sera from the mice sacrificed on day 35, at which point the observation was terminated, were proved to be markedly elevated when compared with controls. These findings seem to suggest that immunization with the toxoid could overcome tolerance, resulting in the production of an antitoxin. In a second experiment that examined the effect of administration with rabbit antiserum raised against the toxoid, the antiserum-treated mice demonstrated a transitory thrombocytosis on 7 days postprovocation with SPE, followed by an abrupt decrease in the number of platelets from day 10 onward.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Acute leukaemia after hydroxyurea therapy in polycythaemia vera and allied disorders: prospective study of efficacy and leukaemogenicity with therapeutic implications.

Fifty consecutive patients, 30 of whom had polycythaemia vera (PV), 10 essential thrombocythaemia (ET), and 10 myelofibrosis (MF), entered a long-term prospective study of hydroxyurea (HU) therapy. The indication for treatment was mainly thrombocytosis or symptomatic splenomegaly. Control of erythrocytosis and thrombocytosis was achieved in 70% of the patients. Continuous maintenance treatment was required. In 15% of responding patients with thrombocytosis, unexpected rises of the platelet count occurred during maintenance therapy. Severe thrombo-embolic events occurred in 6 patients. The size of the spleen decreased in all patients who did not develop thrombocytopenia and could absorb adequate HU doses. Acute leukaemia (AL) was diagnosed in 9 patients and a myelodysplastic syndrome in one. Seven of them had been treated with HU alone. Among the patients with PV and ET, 6 developed AL and 4 of them were treated with HU alone (3 PV and 1 ET), giving an incidence of 10.5%. In previously untreated patients with initially normal karyotypes (n = 19), chromosome abnormalities developed during HU therapy in 7 (37%). Our results indicate that HU should be regarded as leukaemogenic, at least when used for treatment of PV and allied diseases. Since myelosuppressive treatment of PV does not prolong survival, the use of HU should be restricted to patients in whom the treatment indication outweights the risk of leukaemia induction.

Acute Disease↗
PubMed2002

Cytogenetic and molecular genetic aspects of essential thrombocythemia.

Essential thrombocythemia (ET) is a chronic myeloid disorder that is characterized by thrombocytosis, thrombohemorrhagic and vasomotor symptoms, a long median survival, and a low risk of transformation to leukemia. ET can be difficult to distinguish from secondary (reactive) thrombocytosis, and the diagnosis of ET can only be made after the exclusion of other marrow disorders with similar features. Although ET has been assumed to be a clonal process, recent studies have suggested that a substantial number of cases classified as ET may actually not be clonal, and nonclonality may be associated with a lower risk of thrombosis. The lack of a characteristic cytogenetic marker for ET confounds analyses of clonality and offers no insight into disease pathogenesis. There is controversy over the proper classification of thrombocytosis associated with the pathological BCR-ABL gene rearrangement; such cases are not clearly distinguishable from chronic myelogenous leukemia (CML) and should be provisionally classified as CML. New insights are emerging into the role of the megakaryocytopoiesis regulator thrombopoietin (TPO) and its receptor, c-Mpl, in ET and related disorders, but TPO-Mpl dynamics appear to be complex. In some familial thrombocythemic syndromes, mutations in the 5' untranslated region of TPO have recently been described, but these have not yet been observed in sporadic ET. In the future, global analysis of gene expression patterns may help overcome diagnostic dilemmas, refine disease classification, and lead to an improved understanding of the pathogenesis of ET.

Chromosome Aberrations↗
PubMed1991

Studies of von Willebrand factor in essential thrombocythemia patients treated with alpha-2b recombinant interferon.

The crucial role of the von Willebrand Factor (vWF) and its interaction with platelets in myeloproliferative disorders (MPD) have emerged in recent years. Recently, many authors have reported the therapeutical efficacy of interferon (IFN) in MPD with thrombocytosis in decreasing platelet number. The purpose of our report is to study the modifications of vWF in a series of 20 patients affected by essential thrombocythemia (ET) or MPD with thrombocytosis, treated with alpha 2b recombinant IFN (alpha 2b-rIFN). Patients were studied before treatment and after complete or partial response: vWF-related properties, bleeding time (BT) and ristocetin-induced platelet aggregation (RIPA) were evaluated. Before treatment, we found prolonged BT in 5 patients (25%), abnormal RIPA in 8 (40%), reduced factor VIII coagulant activity (VIII:C) in 2 (10%), reduced vWF-related antigen (vWF:Ag) in 5 (25%) and low vWF:ristocetin cofactor (vWF:Ricof) in 5 (25%). Twelve subjects were evaluated after hematologic remission: in all patients, BT, VIII:C, vWF:Ag and vWF:Ricof were within normal range or upper normal limits. RIPA was abnormal in 7 subjects. Multimer patterns of vWF were performed in 3 patients before and after treatment: 2 of them showed loss of high-molecular-weight multimers that seemed to recover at remission. IFN seems to induce improvement of platelet number and their functions in MPD with thrombocytosis.

Adult↗
PubMed2004

[Analysis of a series of 55 patients with biopsy proven giant cell temporal arteritis].

INTRODUCTION: Our main aim with this study is to establish the epidemiologic and clinical features, treatment response and complications of a group composed of 55 patients with biopsy proven temporal arteritis in a local hospital. MATERIAL AND METHODS: Retrospective study based on clinical records revision of patients diagnosed of giant cell arteritis (GCA) made by temporal artery biopsy between 1989 and 2001. RESULTS: The approximated annual incidence of GCA in our area is 4.1 cases per 100,000 persons over the age of 50. The mean age at diagnostic was 74 years and the 78,2% were women. The most common symptom at diagnostic was headache (81.5%) followed by systemic manifestations (74.1%) and later we found jaw claudication (32,7%), visual impairment (30.2%), isquemic manifestations (17%). Polymyalgia rheumatica was associated to GCA in 49.1% of cases. The temporal artery explorations was abnormal in the 76.9% of patients. The mean initial dose of corticoids was 69 mg prednisone per day, with a half dose reduction time of .5 months. In spite of that, 24,1% of patients relapsed during the first year. The 38% of patients did some complications during the corticosteroid treatment. The ESR was lower 50 mm in 12.7% of patients; it was anaemia in the 37.7% and thrombocytosis in 32,1%. In these last patients we detected a relation between thrombocytosis and specific visual impairment. CONCLUSIONS: The incidence of GCA in our area is low. The results of our series aren't different from others publicated before in clinical manifestations, there is a prevalence of female sex and there is a relation between specific visual impairment and the presence of thrombocytosis.

Biopsy↗
PubMed1991

Compensatory mechanisms in platelet production: the response of Sl/Sld mice to 5-fluorouracil.

Sl/Sld mice are a unique animal model for studying platelet production in that they sustain normal platelet mass despite reduced marrow activity. The aim of this study was to determine if the compensatory mechanisms operating in these mice could be augmented by further reducing bone marrow activity with the drug 5-fluorouracil (5-FU), known to induce a strong stimulatory effect on platelet production. The platelet recovery in Sl/Sld mice after 5-FU administration contrasted that found in their normal littermates. Sl/Sld mice did not display the sustained thrombocytosis that was observed in +/+ mice between days 10 and 14. Platelet number was elevated in Sl/Sld mice at day 20, when the marrow megakaryocyte compartment had normalized. A significant increase in marrow megakaryocyte number and size was observed at days 8 and 11 in both +/+ and Sl/Sld mice after 5-FU administration. The data suggest that the increase in megakaryocyte size and number following 5-FU treatment was not able to significantly contribute to a sustained rebound thrombocytosis at the time of increased marrow megakaryocytopoiesis. It is concluded that the already compromised marrow of Sl/Sld mice is able to respond to the damage invoked by 5-FU to produce larger than normal megakaryocytes. In contrast to normal mice (+/+ littermates), the increase in marrow megakaryocytopoiesis observed does not lead to a thrombocytosis, indicating that platelet production and release in Sl/Sld mice cannot be further amplified by a strong marrow stimulation.

Anemia↗
PubMed1990

Regulation of platelet heterogeneity: effects of thrombocytopenia on platelet volume and density.

We have examined the effects of variable degrees of acute thrombocytopenia on platelet levels, mean platelet volume (MPV), and buoyant density after induction of thrombocytopenia by platelet antiserum (PAS) in mice with or without spleens. Mice were studied serially 10-16, 36, 48, 60-64, 84, 108, 144, 180, 228, 276, 348-360, 372, and 516 h after PAS treatment. MPV and platelet count (PC) x 10(6)/microliters for normal intact mice (n = 136) were 4.7 +/- 0.3 fl (SD) and 1.69 +/- 0.52 (SD), respectively. Twelve hours after PAS-induced severe thrombocytopenia (PC less than 0.05 x 10(6)/microliters), MPV increased significantly (p less than 0.01) to 6.4 fl, was maximal at 36 h (8.2 fl), remained elevated until 144 h following PAS treatment, and then returned to normal. Platelet density decreased significantly (p less than 0.05) 64 h after PAS treatment and returned to normal at 144 h. Hematocrits of repeatedly bled intact control mice decreased from 45% to 30%, accompanied by thrombocytosis (maximal PC 2.24 x 10(6)/microliters) without significant changes in either MPV or platelet density. Moderate thrombocytopenia (PC 0.1-0.2 x 10(6)/microliters) in intact mice produced significantly (p less than 0.05) increased MPV, at 5.7 fl 12 h after PAS treatment, with a peak MPV of 7.6 fl (p less than 0.001) at 36 h; MPV returned to normal at 84 h. Platelet density decreased (p less than 0.001) 12 h after PAS treatment and returned to baseline at 228 h. Control splenectomized mice (n = 185) had an MPV of 5.0 fl +/- 0.7 fl and a PC of 2.14 +/- 0.6 x 10(6)/microliters. Comparably severe and moderate thrombocytopenia in splenectomized mice produced alterations in platelet count, MPV, and density similar to those in intact mice, although maximal MPV and the degree of rebound thrombocytosis after severe thrombocytopenia were more marked in splenectomized mice. In response to reduction of the platelet mass in both intact and splenectomized mice, MPV increased in proportion to the severity of thrombocytopenia, occurred as early as 4 h after induction, and persisted during early rebound thrombocytosis. Previous observations that megakaryocyte ploidy did not shift until 48 h after onset of thrombocytopenia confirm that both initial and maximal changes in MPV in response to this stimulus are regulated by processes other than alterations of megakaryocyte DNA levels.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMedDate not supplied

Platelet abnormalities in patients with cystic fibrosis and obligate heterozygotes.

Following our previous report that thrombocytosis and platelet hyperaggregability (as tested in platelet rich plasma) occur in patients with cystic fibrosis (CF), we have now examined whether this thrombocytosis is related to leukocytosis, and whether platelet hyperaggregability can be documented in whole blood using impedance aggregometry. Our observations show that platelet counts are related to white cell counts (r = 0.34; p = 0.001) and that therefore thrombocytosis may be part of a secondary response to bronchopulmonary infection, which is characteristic of these patients. Platelet counts were, however, not related to serum iron concentration despite the finding of varying degrees of iron deficiency in approximately 50% of patients with cystic fibrosis. Whole blood aggregometry demonstrated platelet hyperaggregability in patients with cystic fibrosis independently of platelet counts. Platelet aggregation (in platelet rich plasma and in whole blood) was normal in obligate heterozygotes, thus suggesting that platelet hyperaggregability in CF is not a consequence of abnormal genetic information.

Adult↗
PubMed1985

Platelet factor 4 release induced by intravenous administration of heparin.

When heparin is injected intravenously, it can induce an immediate release of platelet factor 4 PF4), probably from the non-platelet pool of endothelial cells. We evaluated this release in a group of normal subjects and patients with cardiovascular disorders or thrombocytosis after an intravenous injection of a bolus of 5,000 I.U. of a commercial mucous heparin. The mean level in normals was 102 +/- 32 (range 50-160) ng/ml and no correlation was found before and after heparin injection between PF4 and heparin level, body weight or platelet count. Only three cardiovascular patients had an elevated level of PF4 released by heparin (HR-PF4) that could be the expression of an increased platelet turnover, whereas all the patients with thrombocytosis had an extremely elevated level of HR-PF4. These patients have much more PF4 available for the binding sites of endothelial cells since only a small percentage of potential binding sites are normally occupied "in vivo". Although no correlation could be found between platelet count and HR-PF4 in subjects with a normal platelet count or in patients with thrombocytosis there was a positive correlation, however, when all the cases were considered together. The other proteins with heparin affinity, B-thromboglobulin, antithrombin III and fibronectin were not influenced by a bolus of heparin and did not correlate in normals as well in patients with HR-PF4.

Adolescent↗
PubMed1995

Platelet consumption in thrombocythemia complicated by erythromelalgia: reversal by aspirin.

The involvement of platelets in the pathogenesis of erythromelalgia, a frequent and characteristic microvascular thrombotic manifestation in patients with primary thrombocythemia and polycythemia rubra vera, was investigated by measuring the survival and turnover of 51Cr labeled autologous platelets in 10 patients with thrombocythemia complicated by erythromelalgia, in 10 asymptomatic thrombocythemia patients and in 6 subjects with reactive thrombocytosis. The mean platelet survival time of the erythromelalgia patients was 4.2 +/- 0.2 days, which is significantly decreased as compared with asymptomatic thrombocythemia patients (6.6 +/- 0.3 days, p < 0.001) and patients with reactive thrombocytosis (8.0 +/- 0.4 days, p < 0.001). The mean platelet survival time of asymptomatic thrombocythemia patients was significantly decreased (p < 0.01) as compared with reactive thrombocytosis patients. Treatment of erythromelalgia with aspirin increased the mean platelet survival time from 4.0 +/- 0.3 days to 6.9 +/- 0.4 days (p < 0.001) and was associated with an elevation of the platelet count of 216 +/- 30 x 10(9) platelets per liter (p < 0.001). Coumadin failed to improve platelet survival or symptoms caused by erythromelalgia. The increased platelet consumption in erythromelalgia is attributed to the formation of platelet thrombi in the arterial microvasculature. This conclusion is supported by the ability of aspirin to interrupt platelet consumption and clinical features of erythromelalgia.

Adult↗
PubMed1993

[Interferon therapy in essential thrombocythemia].

Interferon-alpha (IFN-alpha) exhibits a clear platelet reductive effect in patients with essential thrombocythemia as well as in other chronic myeloproliferative disorders with thrombocytosis. In a total of 51 patients with chronic myeloproliferative disorders with thrombocytosis we analyzed the effect of IFN-alpha in respect to platelet reduction, remission rates, induction- and maintenance dosage, long term tolerance and side effects. According to our classification CML 6, chronic mega-karyocytic granulocytic myelosis 5, essential thrombocythemia 26 and polycythemia vera 15 patients were treated. Treatment consisted of induction with 3 or 5 MU IFN-alpha daily followed by a maintenance therapy with 3 or 5 MU thrice weekly. Platelet reduction was found in all patients, CR (platelets < 450 G/l) in 78%. Within 2 months of induction therapy, CR in patients treated with 5 MU IFN daily was found in 75% compared to 52% in patients treated with 3 MU IFN daily. Dosage reduction in maintenance periode caused an increase of platelets to more than 450 G/l in 39% of patients. Out of 40 Philadelphia-negative chronic myeloproliferative disorders treated for more than 3 months in 10 patients treatment was disrupted after 5 to 18 months because of the following side effects: nausea, fatigue, vertigo, fever, headache, diarrhea, anorexia, heartburn, hairloss, myalgia, and thrombocytopenia. Due to the mutagenic effect of alkylating cytostatics and Radiophosphorus, IFN-alpha treatment represents a first line strategy for chronic myeloproliferative disorders with thrombocytosis especially in younger patients who are symptomatic and in those who suffered from episodes of bleeding or thrombosis.

Dose-Response Relationship, Drug↗
PubMed1998

[Adenovirus long-term expression of thrombopoietin in vivo: a new model for myeloproliferative syndrome and osteomyelofibrosis].

Using a new adenoviral vector (Ad) construct, we expressed human thrombopoietin (TPO) cDNA (AdTPO) in mice with various inherited immune deficiency syndromes such as nude, SCID and NOD-SCID mice. Immune normal Balb/c mice and a vector construct without TPOcDNA (AdNull), respectively, were used for controls. All animals (3 per group) were treated with a single application of 10(9) PFU (plaque forming unit) of Ad (AdTPO or AdNull) intraperitoneally on day 0. Four to 5 weeks following AdTPO administration, SCID and NOD-SCID mice demonstrated peak concentration of PLT of 12- to 14-fold normal value simultaneously with maximum concentration of PMNs (10- to 12-fold normal value). Later on these animals had a chronic thrombocytosis. In contrast, Balb/c mice and nude mice experienced PLT peak concentration of 4- to 6-fold normal value without granulocytosis 1 to 2 weeks following AdTPO treatment. Only nude mice had chronically elevated PLTs. In contrast, Balb/c mice developed thrombocytopenia due to cross-reacting anti-TPO antibodies. Animals with chronic thrombocytosis revealed increased content of CFU-G/GM, CFU-GEMM and CFU-Meg in bone marrow compared with controls. In contrast, Balb/c mice showed decreased content of CFUs if anti-TPO-antibodies were present. Histologically, only SCID mice developed severe osteomyelofibrosis and osteomyelosclerosis, hepato-splenomegaly, extramedullary hematopoiesis in liver and lung and ultimately suffered of progressive pancytopenia, anisocytosis, fragmentocytosis and a lethal wasting syndrome. In contrast, NOD-SCID mice which demonstrated similar extent of TPO overexpression and in addition to the B- and T-cellular immune deficiency harbour defective monocytes and macrophages, did not develop fibrotic changes of the bone marrow. From these results, we conclude (1) chronic TPO overexpression in vivo may lead to thrombocytosis and granulocytosis with expansion of CFU-GM, -GEMM and -Meg; (2) in vivo expression of adenovirally mediated TPOcDNA depends on immune competency of the host; (3) functionally normal monocytes and macrophages are indispensable for development of secondary osteomyelofibrosis and (4) adenovirally mediated expression of xenogeneic transgenes may brake immune tolerance for the respective self protein leading to autoimmune phenomena. Our in vivo model might provide further insights into the pathophysiology of secondary osteomyelofibrosis and may prove useful in designing new strategies for immune therapies of cancer.

Animals↗
PubMed1991

An atypical myeloproliferative disorder with high thrombotic risk and slow disease progression.

Among 761 consecutive patients with chronic myeloproliferative disorders (CMD), it was found that 18 (nine men and nine women) did not fulfill at presentation the established diagnostic criteria for the typical forms. In seven patients, the diagnosis of CMD was made on the basis of an intense and persistent thrombocytosis that complicated splenectomy. The other 11 patients had various combinations of the following signs suggesting CMD: splenomegaly, bone marrow myeloid hyperplasia and/or slight myelofibrosis, mild thrombocytosis and/or leukocytosis, and rare immature myeloid cells in the peripheral blood. All patients were younger than 46 years of age (median age, 31.5 years; range, 20 to 45 years). A major thrombotic event was the most frequent presenting feature (eight of 18 cases), and thrombotic complications supervened in seven of the eight splenectomized patients (six in the portal system), raising the overall rate of patients with thrombotic events in their history to 11 of 18. At a median follow-up of 50 months (range, 24 to 241 months), three patients had died of thrombotic complications (two after splenectomy). The 15 surviving patients had stable disease, and 12 of them were not receiving cytoreductive therapy. Spontaneous growth of circulating burst-forming units erythroid was demonstrated in one patient, and erythroid responsiveness to erythropoietin appeared higher than in the normal controls in four. Spontaneous in vitro platelet aggregation in whole blood and/or platelet-rich plasma was seen in five of seven patients. It was concluded that a difficult to identify, slowly progressive form of CMD occurs in young people, that it carries a high risk of thrombosis, and that splenectomy is a high risk procedure in these cases.

Adult↗
PubMed1991

Absent neutrophil alkaline phosphatase in the eosinophilia myalgia syndrome associated with L-tryptophan use.

The clinical constellation of leukocytosis, thrombocytosis, and low or absent stainable neutrophil alkaline phosphatase (NAP) is considered characteristic of chronic myelogenous leukemia (CML). CML with eosinophilic differentiation (eosinophilic leukemia) is well described, and leukemia and other clonal hematologic malignancies are associated with the syndrome of eosinophilic fasciitis. We describe leukocytosis, thrombocytosis, eosinophilia, mild basophilia, and absent stainable NAP, initially suggesting the diagnosis of CML in a patient with the eosinophilia myalgia syndrome associated with L-tryptophan use, a condition resembling eosinophilic fasciitis. Cytogenetic and molecular genetic studies failed to demonstrate a clonal proliferation of eosinophils.

Adult↗