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PubMed1993

Management of Kawasaki disease in the British Isles.

Kawasaki disease in the British Isles was surveyed by an active reporting scheme, based on all cases reported to the British Paediatric Surveillance Unit that were diagnosed between 1 January and 31 December 1990. The study was prompted by the need to investigate the high case fatality rate of Kawasaki disease of 2% observed in 1988. One hundred and sixty three patients were identified of whom six (3.7%) died. Forty five children (28%) suffered cardiac complications of which 39 (24%) were coronary artery abnormalities; five children were diagnosed at postmortem examination, and coronary artery abnormalities were detected by echocardiography in 34. One hundred and forty nine children (93%) had echocardiography. High thrombocytosis, leucocytosis, duration of fever, and younger age were associated with the presence of coronary artery abnormalities. Erythrocyte sedimentation rate, sex, and the number of diagnostic criteria were not. One hundred and thirty three children (87%) received aspirin. Ninety three children (61%) received intravenous gammaglobulin (IVGG). Children were more likely to receive IVGG if they had thrombocytosis or typical Kawasaki disease. The incidence of coronary artery abnormalities was found to be similar in those treated with IVGG (29%) and those untreated (20%), including those treated within 10 days of onset. This may have reflected selection of the more serious cases to receive IVGG or that Kawasaki disease in the British Isles is a different illness to that experienced elsewhere. It amy be, however, that IVGG is less effective in the treatment of British patients with Kawasaki disease than has been the experience in the United States and Japan. These observations emphasise the need for a therapeutic trial of treatment modalities for Kawasaki disease in the UK and the Republic of Ireland.

Adolescent↗

PubMed1983

No evidence for a prethrombotic state in stable chronic inflammatory bowel disease.

Ulcerative colitis and Crohn's disease are associated with a high risk of thromboembolic complications. The questions whether reported risk factors such as low antithrombin III concentrations, thrombocytosis and spontaneous platelet aggregation are merely related to the activity of the inflammatory process remains to be answered. Therefore we investigated 40 patients with an established colitis or Crohn's disease, without signs of active inflammation (normal history, normal ESR and leucocyte count). Of these patients only one patient revealed thrombocytosis, six patients spontaneous platelet aggregation. All patients had normal beta-thromboglobulin and platelet factor 4 plasma levels. No other prethrombotic abnormalities were encountered. There was normal factor VIII C (increased in three patients), normal VIII C/VIII R Ag ratio (1.2), antithrombin III, normal plasminogen and normal alpha 2-antiplasmin. Normal fibrinopeptide A and B beta (15-42) plasma levels (n = 15) in these patients excluded in vivo thrombin or plasmin generation. We conclude that stable chronic inflammatory bowel disease is in general not associated with prethrombotic coagulation abnormalities.

Adolescent↗

PubMed2000

Interleukin-6 induces demargination of intravascular neutrophils and shortens their transit in marrow.

Recombinant human interleukin-6 (IL-6) causes both a thrombocytosis and leukocytosis. The thrombocytosis is caused by an accelerating thrombocytopoiesis, but the mechanism of the leukocytosis is unknown. This study was designed to determine the relative contributions of marrow stimulation and intravascular demargination to the IL-6 induced neutrophilia. IL-6 (2 microgram/kg), administered intravenously to rabbits, caused a biphasic neutrophilia with an initial peak at 3 h and a second peak at 9 h. Using the thymidine analog 5'-bromo-2'-deoxyuridine (BrdU) to label dividing polymorphonuclear leukocytes (PMNs) in the bone marrow, we showed that IL-6 treatment mobilizes PMNs from the marginated pool into the circulating pool at 2-6 h with a decrease in L-selectin expression on PMNs and also accelerates the release of PMNs from the postmitotic pool in the bone marrow at 12-24 h. We have concluded that IL-6 causes a biphasic neutrophilia wherein the first peak results from the mobilization of PMNs into the circulating pool from the marginated pool and the second peak results from an accelerated bone marrow release of PMNs.

Animals↗

PubMedDate not supplied

Platelets and anticoagulant capacity in patients with inflammatory bowel disease.

Patients with inflammatory bowel disease (IBD) are susceptible to thromboembolic complications. Several mechanisms can be responsible, including abnormal regulation of coagulation activity, disturbances of fibrinolysis, inflammatory reactions and thrombocytosis. The aim of this study was to assess hemostatic alterations in these parameters during exacerbation of disease. We studied disease activity in 99 IBD patients receiving anti-inflammatory therapy, in relation to: procoagulant markers, i.e. prothrombin fragment F1 + 2 (F1 + 2), D-dimer and platelet count, anticoagulant markers, i.e. protein C, protein S and antithrombin, and a mediator of inflammation (IL-6). Coagulation activity and platelet count were increased during active disease in IBD patients compared with those in a state of remission. The IL-6 concentrations were positively correlated with disease activity and thrombocytosis in patients with ulcerative colitis, but no association with the anticoagulant capacity could be demonstrated except for a decrease in protein C during high disease activity.

Adolescent↗

PubMed2005

Usefulness of measurement of reticulated platelets for diagnosis of idiopathic thrombocytopenic purpura.

Reticulated platelets (RP) and large platelets (LP) were measured by an automated hematology analyzer (modified R-2000) in 287 healthy volunteers and 131 patients with thrombocytopenia or thrombocytosis. RP was significantly higher in patients with idiopathic thrombocytopenic purpura (ITP), especially in active phase, while RP was markedly lower in patients with essential thrombocytosis (ET) or chronic myelocytic leukemia (CML). LP was significantly higher in patients with ITP, especially in active phase, while LP was markedly lower in patients with aplastic anemia (AA), ET, or CML. In ITP, RP and LP were significantly higher in patients positive for anti-glycoprotein (Gp) IIb/IIIa antibody. RP and LP were poorly correlated with platelet-associated IgG (PAIgG). RP and LP were poorly correlated with plasma thrombopoietin levels, and negatively correlated with platelet count. These results show that RP reflects the pathology of thrombocytopenic disorders, and that measurement of RP is useful for the differential diagnosis and analysis of platelet kinetics.

Adult↗

PubMed2005

POEMS Syndrome.

POEMS syndrome is defined by the presence of a peripheral neuropathy (P), a monoclonal plasma cell disorder (M), and other paraneoplastic features, the most common of which include organomegaly (O), endocrinopathy (E), skin changes (S), papilledema, edema, effusions, ascites, and thrombocytosis. Virtually all patients will have either sclerotic bone lesion(s) or co-existent Castleman's disease. Not all features of the disease are required to make the diagnosis, and early recognition is important to reduce morbidity. Other names for the syndrome include osteosclerotic myeloma, Crow-Fukase syndrome, or Takatsuki syndrome. Because the peripheral neuropathy is frequently the overriding symptom and because the characteristics of the neuropathy are similar to that chronic inflammatory demyelinating polyneuropathy (CIDP), patients are frequently misdiagnosed with CIDP or monoclonal gammopathy of underdetermined significance (MGUS)-associated peripheral neuropathy. Not until additional features of the POEMS syndrome are recognized is the correct diagnosis made and effective therapies initiated. Clues to an early diagnosis include thrombocytosis and sclerotic bone lesions on plain skeletal radiographs. Therapies that may be effective in patients with CIDP and MGUS-associated peripheral neuropathy (intravenous gammaglobulin and plasmapheresis) are not effective in patients with POEMS. Instead, the mainstays of therapy for patients with POEMS include irradiation, corticosteroids, and alkylator-based therapy, including high-dose chemotherapy with peripheral blood stem cell transplantation.

Adolescent↗

PubMed2002

The expression pattern of c-mpl in megakaryocytes correlates with thrombotic risk in essential thrombocythemia.

Using immunohistochemistry, we investigated the expression of c-mpl in bone marrow megakaryocytes of 88 patients with essential thrombocythemia (ET), 6 patients with secondary thrombocytosis (ST), and 20 patients with lymphoma (controls). Considering both the pattern of expression and the staining intensity, we identified a uniform and a heterogeneous pattern of c-mpl expression. The uniform pattern was found in all the controls, all the patients with ST, and 28 of the patients with ET, with a strong staining intensity observed in most megakaryocytes (> 80%). In contrast, c-mpl expression was heterogeneous in 60 patients with ET, 18 of whom (30%) presented with thrombosis at diagnosis, a significant difference from patients with a uniform c-mpl pattern (2 of 28; 7%; P =.026). In particular, the overrepresentation of thrombotic complications in patients with a heterogeneous c-mpl expression pattern was found mainly among patients with a significant percentage (10% to 40%) of weakly stained or c-mpl-negative megakaryocytes (heterogeneous-weak pattern; 13 of 30; 43%; P =.002). Accordingly, this pattern was associated with a 6.1-fold increased risk of thrombosis compared with that of patients with a uniform c-mpl pattern. In conclusion, the presence of a heterogeneous pattern of c-mpl distribution in bone marrow megakaryocytes could be a useful diagnostic criterion in the differential diagnosis of thrombocytosis. Furthermore, detection of a significant percentage of weakly stained or c-mpl-negative megakaryocytes can identify patients with a higher risk of thrombosis.

Adolescent↗

PubMed2001

Thrombocytopenic c-mpl(-/-) mice can produce a normal level of platelets after administration of 5-fluorouracil: the effect of age on the response.

Administration of 5-fluorouracil (5-FU) to mice results in a marked increase in the level of circulating platelets in 10 days. Mice lacking Mpl, the receptor for thrombopoietin (TPO), are thrombocytopenic. To gain insight into the mechanism by which 5-FU produces such a substantial stimulation of platelet production, this study investigated whether 5-FU (150 mg/kg) produced thrombocytosis in c-mpl(-/-) mice, thus establishing whether TPO was required for this response. A 5- to 6-fold increase in platelet levels in c-mpl(-/-) mice (to approximately 1000 x 10(9)/L) was observed on days 20 and 25 after 5-FU injection. Thus, at the peak of the response, c-mpl(-/-) mice had platelet levels comparable to those in normal mice. Administration of 5-FU also produced thrombocytosis in previously splenectomized c-mpl(-/-) mice. Comparison of the platelet response to 5-FU in young (6-12 weeks) and old (33-46 weeks) c-mpl(-/-) mice found that older mice produced a much more marked response than younger mice, with a mean maximum platelet level of approximately 1700 x 10(9)/L. To determine whether this increase in circulating platelets was preceded by an increase in hematopoietic progenitors, serial cultures of bone marrow and spleen were evaluated. A considerable increase in all colony types studied was observed on days 15 and 20 in spleens of c-mpl(-/-) mice, but no similar elevations were detected in bone marrow. These results indicate that c-mpl(-/-) mice can achieve a normal level of platelets after 5-FU injection, by means of a TPO-independent mechanism, and that they respond to 5-FU myelosuppression by producing large numbers of megakaryocytic, myeloid, and erythroid progenitors. (Blood. 2001;98:1019-1027)

Age Factors↗

PubMed1984

Follicular large cell lymphoma: analysis and prognostic factors in 62 patients.

Sixty-two patients with follicular large cell lymphoma were treated between 1973 and 1981. The overall median survival was 78 months with a five-year survival of 62%. The complete remission rate was 76%, with a median relapse-free interval of 72 months for responders. Complete remission produced a significantly longer survival than partial response and failure. Patients who tolerated therapy with an intensive doxorubicin-containing regimen had a significantly longer relapse-free interval and survival. Patients with stage I-II disease treated with radiation therapy alone had a higher relapse rate than those treated with radiation and combination chemotherapy. The addition of radiation therapy to combination chemotherapy in stage III-IV disease decreased the incidence of relapse at irradiated sites, but did not translate into improved survival. Pretreatment prognostic factors associated with poor response were thrombocytosis and stage III-IV disease; those associated with shortened survival were thrombocytosis, elevated lactic dehydrogenase level, stage III-IV disease, and bulky abdominal disease. Follicular large cell lymphoma is an aggressive lymphoma. Treatment should be curative in intent, and should include intensive combination chemotherapy even in stage I-II disease. Knowledge of important prognostic factors can be useful for analysis of future trials and planning therapeutic strategies.

Adult↗

PubMed2006

Essential thrombocythemia in a dog.

A two-year old male Welsh Corgi was referred for persistent thrombocytosis and occasional seizure. Hematological findings indicated marked thrombocytosis, eosinophilia, basophilia and moderate anemia. Bone marrow examination revealed marked megakaryocytic hyperplasia with morphologic abnormality. A diagnosis of essential thrombocythemia was made and the treatment was initiated with combination chemotherapy and maintained by prednisolone and busulfan. The dog successfully achieved complete remission on 100 days after initial presentation and has been good in health without chemotherapy since then.

Animals↗

PubMed2005

Patient with double cancer--successfully treated.

INTRODUCTION: Etiology of thrombosis in malignant diseases is multifactorial, and mechanisms that lead to thrombosis include release of the procoagulants from tumor cells (PC), factor related to bed rest, infections, as well as oncological therapy --chemotherapy, hormones, radiotherapy and surgical treatment. Thrombocytosis has frequently been found to be associated with various malignancies. CASE REPORT: 53 years old female patient hospitalised because of hypopharingeal cancer with metastasis in the left neck. Her state was complicated with deep leg vein trombosis and pseudomonas infection. Persistent thrombocitosis in laboratory monitoring indicated more adequate diagnostic procedures, which led to discovering of Chorioidal Malignant Mellanoma as a second cancer. She was treated: surgically, with antibiotics, with anticoagulants and radiotherapy. Patient was discharged from the hospital in good health condition, free of any other symptom of the malignant disease. CONCLUSION: Presense of thrombocytosis and idiopatic thrombosis can suggest occult malignancy. It would be prudent to further evaluate the relationship of trombotic events, trombocitosis and head and neck tumors. We suggest anticoagulants to prevent thromboembolic complications, affect the angiogenesis and prevent development of metastatic disease. It may lead to lower mortality rate.

Carcinoma, Squamous Cell↗

PubMed1990

Familial essential thrombocythemia.

We report three siblings (2 F, 1 M) aged 9, 12, and 15 years with a thrombocytosis, above 650 X 10(9)/l for at least 18 months and a leukocyte alkaline phosphatase score below 37. The diagnosis of essential thrombocythemia was based upon the exclusion of a reactive thrombocytosis or another myeloproliferative disease. Cytogenetic examination of marrow cells was normal.

Adolescent↗

PubMedDate not supplied

Analysis of thrombopoietin and c-mpl expression in a child with essential thrombocythemia.

The pathogenesis of the increased number of megakaryocytes and thrombocytosis in essential thrombocythemia (ET) is still unknown. We examined the expression of c-mpl, a receptor of thrombopoietin (TPO), and its signaling molecules in a patient with ET. An 8-year-old girl showed a high platelet count and an increased number of bone marrow megakaryocytes. Neither chromosomal abnormalities nor myelofibrosis was observed. Following the diagnosis of ET, aspirin therapy was begun for the patient, with only modest improvement of symptoms. Her platelet count ranged from 1,200,000/microL to 2,200,000/microL for more than 2 years. In the analyses, the serum TPO level in the patient was 420 attomoles/mL (normal, 760 +/- 320). The level of c-mpl expression in bone marrow mononuclear cells was higher in the patient than in healthy children, while there was no difference in the level of c-mpl expression in CD34+ cells, indicating an expanded pool of megakaryocytic lineage cells. The level of Janus kinase 2 (Jak2) expression was lower in the patient than in a healthy child. These findings indicate that the signal pathway mediated by c-Mpl after binding to TPO may be impaired in ET. Further analysis is needed to clarify the mechanism underlying the development of thrombocytosis in ET patients.

Child↗

PubMed2000

Non-Hodgkin's lymphoma following untreated essential thrombocythemia.

The coexistence of essential thrombocythemia (ET) and non-Hodgkin's lymphoma (NHL) is an extremely rare event, with only two such cases having been reported in the medical literature. We describe here a 25-year old woman who developed high-grade B-cell NHL of the stomach three years after the diagnosis of ET, for which she had received no treatment, due to her young age and the lack of thrombotic risk factors other than thrombocytosis. The lymphoma showed a favorable response to CHOP chemotherapy, whereas the thrombocytosis remained unchanged throughout the patient's clinical course. The possible etiologic and pathogenetic mechanisms leading to the association of these two disorders are discussed. Given the relative frequency of ET and the fact that the present case represents only the third reported instance of NHL developing in such patients, the coincidental ocurrence of both diseases is a possibility that cannot be excluded.

Adult↗

PubMed1998

Clonality analysis of hematopoiesis and thrombopoietin levels in patients with essential thrombocythemia.

Essential thrombocythemia (ET) is a myeloproliferative disorder, characterized by sustained thrombocytosis. Diagnosis requires the elimination of all known causes of thrombocytosis. ET is believed to be a clonal disorder, and we investigated the frequency of a clonal hematopoiesis in this disease with the aim of using this as a positive diagnostic criterion. However, a non-random inactivation pattern can be encountered in normal females which mimics clonal hematopoiesis. In addition, the percentage of normal females with skewed lyonization seems higher using techniques based on the difference in DNA methylation, compared to G6PD enzyme polymorphism. Recently, new techniques based on transcript analysis have been developed. We report here the results of clonality studies of hematopoiesis in 53 ET patients using two different techniques based on DNA and RNA polymorphisms, and T-lymphocytes as a control tissue of lyonization. The majority of ET patients showed monoclonal hematopoiesis in the presence of polyclonality of T-lymphocytes. Because all ET patients did not show the same clonal pattern of hematopoiesis, we searched for inappropriate secretion of thrombopoietin (TPO) in patients with polyclonal disease. This assay was performed in 48 patients, of whom 9 showed polyclonal hematopoiesis and 27 monoclonal hematopoiesis. We found no difference in TPO levels between ET patients and normal controls, nor between patients with polyclonal hematopoiesis and those with monoclonal hematopoiesis. Our results confirm the high frequency of monoclonal hematopoiesis in ET, the usefulness of RNA markers, and the possibility of using T-lymphocytes as a control tissue for X-chromosome inactivation patterns. On the other hand, TPO levels are not decreased even in ET patients with high platelet counts, suggesting an increased production or decreased clearance of TPO in this disease.

Adolescent↗

PubMed1998

The Philadelphia chromosome negative chronic myeloproliferative disorders: a practical overview.

The chronic myeloid disorders are collectively characterized by a stem cell origin of the clonal process and a variable tendency to undergo indigenous disease transformation and leukemic conversion. Classification of the chronic myeloid processes is based primarily on the presence or absence of the Philadelphia chromosome (bcr-abl translocation) and secondarily on the morphologic picture of the bone marrow in conjunction with the clinical manifestation. Essential thrombocythemia (ET), polycythemia vera (PV), and agnogenic myeloid metaplasia (AMM) constitute the classical group of bcr-abl negative chronic myeloproliferative disorders. PV is characterized by a clonal increase in red blood cell mass, AMM by bone marrow fibrosis, and ET by thrombocytosis. Most of these features, however, are not diagnostically specific, and secondary causes of erythrocytosis, thrombocytosis, and bone marrow fibrosis must be excluded. Treatment may be deferred or limited to phlebotomy alone in some patients with ET or PV, respectively. In contrast, thrombosisprone patients with PV or ET require drug therapy, and new platelet-lowering agents are increasingly being used. In this article, current diagnostic and therapeutic issues of ET, PV, and AMM are discussed.

Chronic Disease↗

PubMed2005

[Extranodal T/NK-cell lymphoma, nasal type: a case report and review of the literature].

Extranodal T/NK-cell lymphoma, nasal type: a case report and review of the literature. Extranodal NK/T-cell lymphoma, nasal type, is an extranodal lymphoma, usually with an NK-cell phenotype and EBV positive, with a broad morphologic spectrum, frequent necrosis and angioinvasion, and most commonly presenting in the midfacial region, but also in other extranodal sites. We present the case of a 42-years old-man with a intranasal mass, left cervical adenopathies and indolent thrombocytosis. The biopsy of the nasal mass showed a diffuse infiltrate of medium-sized lymphoid cells, with slightly irregular nuclei and moderate polymorphous. The immunophenotype of tumor cells was CD45+, cCD3+, Granzyme B+, CD56+, CD20-,CD4-,CD8-, LMP1(EBV)-. The diagnosis of the case was Extranodal T/NK-cell lymphoma, nasal type. There was not disseminated disease in the extent studies. With the diagnosis of localized extranodal T/NK-cell lymphoma and reactive thrombocytosis, the patient was treated with chemotherapy and sequential radiotherapy, followed by bone marrow transplantation.

Adult↗

PubMed1975

Sideroblastic anemia with splenic abscess and fatal thromboemboli after splenectomy.

A man with sideroblastic anemia had a splenectomy because of a salmonella abscess of the spleen that had ruptured into the colon. Two months later he developed recurrent thrombophiebitis and fatal thromboembolism associated with thrombocytosis. A review of the literature showed multiple additional cases of sideroblastic anemia with thrombocytosis and thromboembolism after splenectomy. In many of these cases the patient died. Splenectomy for treatment of a sideroblastic anemia probable is contraindicated. If splenectomy is done, long-term therapy to avoid thromboembolic complications probably should be maintained for many months or even years.

Abscess↗