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PubMed1990

Interleukin-1 beta (IL-1 beta) induces thrombocytosis in mice: possible implication of IL-6.

We administered recombinant human interleukin-1 beta (IL-1 beta), the common mediator of inflammation process, to C57B1/6 male mice (0.5 microgram, every 12 hours over five times) intraperitoneally and consequently induced a remarkable thrombocytosis. Day 1 was designated as the following day of the last injection in the morning. A significant thrombocytosis was observed on days 1 through 5 with a peak on day 2 (162 +/- 9 x 10(4)/mm3) compared with the control mice injected with heated IL-1 beta (101 +/- 11 x 10(4)/mm3). A striking increase in mean size of marrow megakaryocytes was noted on days 1 and 2. The incorporation of 75Se-selenomethionine into circulating platelets as a measure of platelet production was about 2.3 times higher in IL-1 beta-treated mice than in control mice. To determine which factor(s) is responsible for elicited thrombocytosis, the in vitro studies and bioassays for several hematopoietic factors were performed. IL-1 beta by itself did not stimulate megakaryocytopoiesis in vitro, suggesting that the thrombocytosis is attributed to other factor(s) via IL-1 beta stimulation. Serum colony-stimulating factor (CSF) activity after a single IL-1 beta (0.5 microgram) injection, monitored by colony assay with 10% tested serum, peaked at 3 hours. Formed colonies were mostly granulocyte (G) and granulocyte-macrophage (GM)-types, and studies using rabbit anti-mouse GM-CSF serum or using human marrow as target cells showed that the CSF activity of the tested serum consisted of, at least, GM-CSF and G-CSF. Addition of IL-3 concomitantly with the tested serum gave rise to a greater number of megakaryocytic colonies. Serum IL-3, monitored by IL-3-dependent cell line 32D clone 5, and erythropoietin activities were not detected at serum level in IL-1 beta-treated mice. Serum IL-6 assay by IL-6-dependent mouse hybridoma cell line MH-60.BSF2 showed high levels of the tested serum with a peak at 2.5 hours with no detection at 10 hours after the injection. Heated IL-1 beta caused an increase of neither IL-6 nor CSF activities. Our data suggest that the thrombocytosis induced by IL-1 beta is mediated by IL-6 or a combination of IL-6 and other cytokine(s), and that IL-6 may play a regulatory role in platelet production in vivo.

Animals↗
PubMed1989

Thrombocytosis and thrombocythemia: qualitative platelet abnormalities.

Thrombocytosis occurs as a primary disease of the bone marrow (primary thrombocytosis or thrombocythemia) or as a reactive phenomenon in pathologic and physiologic conditions (secondary thrombocytosis or thrombocytosis in a narrow sense). As a rule, secondary thrombocytosis is symptomless and shows normal platelet functions, while thrombocythemia is frequently associated with bleeding and/or thrombosis as well as various platelet abnormalities. These platelet abnormalities were reviewed, and our recent studies on functional and biochemical alterations in platelets of thrombocythemia were focused on: 1) abnormal platelet aggregation. 2) deficient epinephrine-induced elevation of the cytoplasmic Ca2+ concentration in platelets with defective aggregation response to epinephrine, 3) altered (subnormal and increased) platelet responses to thromboxane A2 (abnormal thromboxane A2 receptor), and 4) abnormal platelet 12-lipoxygenase enzyme. Although the clinical significance of the in vitro qualitative platelet defects is not always clear, these altered platelets could be useful models to elucidate platelet pathophysiology.

Blood Platelets↗
PubMedDate not supplied

[Thrombocytosis in juvenile rheumatoid arthritis].

To find out the possible relationship between thrombocytosis and JRA, 2 to 11 platelet counts (every 1 to 6 months) were performed in each of 26 patients with active JRA, and were compared with figures for hemoglobin, WBC, sedimentation rate and articular index. Thrombocytosis was found in 88% of the cases. There was positive correlation, with statistical significance, among thrombocytosis, anemia, and sedimentation rate. Significant relationship was also found among thrombocytosis, the presence of articular inflammation and leukocytosis. There was no parallelism between platelets types of the disease. We conclude that in active JRA, thrombocytosis is a frequent finding in relation with anemia and the inflammatory activity of the disease.

Adolescent↗
PubMed1982

[Occurrence and clinical relevance of thrombocytosis].

Automated routine platelet counting in 18,602 patients revealed thrombocytosis (platelet count above 400,000/mm3) in 9% (n = 1602) of cases. In 32% of the patients with thrombocytosis an acute or chronic inflammatory process was found, 9% had a malignant tumor and 9% anemia. 6% were alcoholics and 6% had a myeloproliferative syndrome. Chronic gastrointestinal disease was found in 4% and postoperative thrombocytosis in 3% of cases. 32% of the thrombocytosis cases could not be classified under any of the known causes of this disorder. In 51% of the cases the platelet count ranged from 400,000 to 450,000/mm3. Primary thrombocythemia often produced clinical symptoms, whereas secondary thrombocytosis almost always was asymptomatic.

Adolescent↗
PubMed1993

[Thrombocytosis of celiac disease in adults: a diagnostic and prognostic marker?].

In 14 of 23 patients seen with coeliac disease thrombocytosis was present (range: 420,000 to 789,000 platelets per cubic mm) and was unrelated to iron deficiency or inflammatory syndrome. Among patients with thrombocytosis (group I), 6 had an associated autoimmune disease; this association was absent in patients without thrombocytosis (group II). There was no correlation between thrombocytosis and lymphocyte count, plasma IgA, IgG, IgM and fibrinogen levels, presence of HLA B8 antigen or histological stage. On the other hand, group I patients had a lower plasma level of albumin, phosphorus and folates. We conclude that thrombocytosis is useful in the assessment of patients with coeliac disease and reflects an enhanced activity of the disease. Moreover, the presence of thrombocytes in these patients' blood may indicate a major risk of associated autoimmune disease.

Adolescent↗
PubMed1998

[The O'Brien filter test in the differential diagnosis of disorders with high-grade thrombocytosis].

In the differential diagnosis of primary and secondary thrombocytosis, platelet function test can be used. We have examined the possible role of O'Brien's filter test in the differentiation of primary and secondary thrombocytosis in 53 patients with myeloproliferative diseases with primary thrombocytosis and in 21 patients with other disorders complicated by secondary thrombocytosis. By using heparin as an anticoagulant, the sensitivity of O'Brien's filter test proved to be 75%, and it's specificity was 85.7%. In blood samples anticoagulated with citrate, the sensitivity was 100% and specificity 83.3%. Based on these studies we suggest the use of O'Brien's filterometer as a screening test in the differential diagnosis in patients with elevated (> 400 x 10(9)/L) platelet count. In case of normal results, the causes of reactive thrombocytosis should be cleared first, while with pathologic results, haematological examination of the patients should be performed.

Chronic Disease↗
PubMed1978

Thromboembolic risk of postsplenectomy thrombocytosis.

Although thrombocytosis is a very common finding after splenectomy, the thromboembolic risk of postsplenectomy thrombocytosis has not been clarified. To our knowledge, this retrospective study of 318 patients without myeloproliferative disorders who underwent splenectomy is the largest of its type. Thrombocytosis developed in 75% of the patients. No substantial increase in the incidence of thromboembolism was detected in patients with thrombocytosis.

Aspirin↗
PubMed1993

Combined plateletpheresis and cytotoxic chemotherapy for symptomatic thrombocytosis in myeloproliferative disorders.

BACKGROUND: Patients with myeloproliferative disorders (MPD) may have symptomatic thrombocytosis develop that requires prompt and sustained lowering of platelet counts to avert serious thrombotic or hemorrhagic sequelae. METHODS: The authors retrospectively studied the short- and long-term effects of plateletpheresis combined with three different chemotherapy regimens (busulfan, hydroxyurea, or busulfan/hydroxyurea) in 30 patients with MPD with symptomatic thrombocytosis. RESULTS: Twenty-nine patients entered first remission (FR) with initial treatment. The average number of plateletphereses to FR was three (standard deviation [SD], +/- 3). Average total dose of busulfan (216 mg) and time to FR (1.6 months) were less than for previously reported patients treated without plateletphereses. Addition of hydroxyurea to busulfan decreased the number of plateletpheresis needed (P = 0.02) but did not additionally reduce the amount of busulfan needed or the time to FR. The shortest time to FR was in the hydroxyurea group (mean, 0.6 +/- 0.3 months), but unmaintained remission could be achieved only in the busulfan-treated groups. With median follow-up of 68 months, median survival was 53 months for the busulfan group, 55 months for the hydroxyurea group, and was undefined with no deaths for the busulfan/hydroxyurea group. Neither fatal complications of recurrent symptomatic thrombocytosis nor development of acute leukemia has occurred, except for progression to blast crisis in two patients with chronic myelogenous leukemia. CONCLUSION: Combined plateletpheresis and chemotherapy is a rapidly effective initial treatment for patients with MPD with symptomatic thrombocytosis. With maintenance therapy or prompt treatment at relapse of disease, prolonged good quality survival can be expected.

Adult↗
PubMed2004

Potential role for platelet apheresis for post-liver transplant thrombocytosis complicating portal vein thrombosis.

Except for patients with underlying myeloproliferative diseases (MPD), thrombocytosis is rarely encountered in cirrhotic patients after liver transplantation. Although the long-term control of primary thrombocytosis is important for the prevention of graft thrombosis in MPD patients, the threshold for intervention and best mode for the control of persistent reactive thrombocytosis after liver transplantation is unclear. We present two patients with extreme reactive thrombocytosis (over 1,000 x 10(9)/l) due to intra-abdominal sepsis after liver transplantation. Furthermore, both patients suffered from bleeding problems as well as ongoing venous thrombosis of the graft. Rapid control of the platelet count was achieved using platelet apheresis. The use of cell separation procedures may be a relatively rapid, reversible, and reasonably safe way to control platelet counts peri-operatively in liver transplant recipients.

Adult↗
PubMed1990

Analysis of megakaryocyte ploidy in patients with thrombocytosis.

The DNA content of bone marrow megakaryocytes was analyzed in 24 patients with myeloproliferative disorders, 23 patients with secondary thrombocytosis and 15 normal volunteers using 2-color flow cytometry. Compared with normal controls, the majority of patients with secondary thrombocytosis, polycythemia vera and essential thrombocytosis exhibited a relative increase in higher ploidy (greater than 16N) cells. In contrast, patients with chronic myelogenous leukemia exhibited an increase in lower ploidy cells (less than 16N), with a modal DNA content of 8N. Patients with myeloproliferative disorders tended to show a decrease in the 16N megakaryocyte population compared with patients with secondary thrombocytosis. No correlation between ploidy distribution and platelet count was observed.

Bone Marrow↗
PubMed1996

Cytokines affecting megakaryocytopoiesis in rheumatoid arthritis with thrombocytosis.

Particular interleukins, namely interleukin (IL)-6, IL-4 and IL-1, with pro-inflammatory mediator activities have also been shown to be involved in the regulation of megakaryocytopoiesis. As rheumatoid arthritis (RA) is not uncommonly associated with reactive thrombocytosis, we investigated serum IL-1 alpha, IL-1 beta, IL-4 and IL-6 concentrations in RA patients with marked thrombocytosis, and compared them to the levels in RA patients with normal platelet counts and healthy volunteers. IL-1 beta. IL-4 and IL-6 concentrations were found to be correlated with the disease activity in both groups of RA patients, with higher serum levels of each cytokine in the thrombocythaemic group. Significant positive correlations of IL-1 beta and IL-4 with the platelet counts were documented only in patients with thrombocytosis. According to our results. IL-6 and IL-1 beta were found to be good indicators of disease activity in RA, while IL-1 beta and IL-4 seemed to be related more with the process of reactive thrombocytosis secondary to rheumatoid inflammation.

Adult↗
PubMed2002

Bloodstream thrombopoietin in rheumatoid arthritis with thrombocytosis.

Thrombopoietin (TPO) is the major regulator of growth and differentiation of megakaryocytes. Recent studies have shown that TPO may also act as an acute-phase reactant, and it has been suggested as a component of inflammatory reactions. In this study our objective was to investigate serum TPO levels in patients with rheumatoid arthritis, a complex chronic inflammatory disorder not uncommonly associated with thrombocytosis. Bloodstream TPO concentrations were assessed in 13 RA patients with platelet counts between 450 and 650 x 10(9)/l, 10 RA patients with platelet counts >650 x 10(9)/l, 15 RA patients with normal platelet counts and 12 healthy controls. RA patients with normal platelet counts had TPO levels comparable with healthy controls. TPO concentrations in patients with mild thrombocytosis were significantly elevated, whereas patients with markedly increased thrombocyte counts had prominently decreased TPO levels. These results indicate that TPO seems to be associated with reactive thrombocytosis in RA patients with active disease. In patients with extremely increased thrombocytosis serum TPO levels might be regulated by increased platelet mass via receptor-mediated uptake and metabolism.

Adult↗
PubMed1979

Thrombocytosis, coronary thrombosis and acute myocardial infarction.

Clinical and morphologic findings are described in a 22 year old man with prolonged thromboyctosis, and coronary and splenic arterial thrombi causing myocardial and splenic infarcts. The absence of preexistent extensive coronary atherosclerosis, the presence of thrombus in more than one epicardial artery and in multiple intramural coronary arteries, the presence of arterial thrombosis in a noncoronary artery (splenic) and the absence of another apparent cause of the arterial thromboses are evidences that the intraarterial clotting in this patient was related to the severe thrombocytosis. A reveiw of the reported cases of vascular occlusion associated with thrombocytosis indicates that thrombi have infrequently been confirmed as the mechanism of the vascular occlusion. Although the frequency of vascular thrombi in patients with thrombocytosis has not been established, it is clear that vascular thrombosis can be a consequence of thrombocytosis and, as demonstrated by the present patient, that the coronary artery may be the site of the vascular occlusion, a heretofore unconfirmed event.

Adult↗
PubMed1991

alpha Interferon treatment of essential thrombocythaemia and other myeloproliferative disorders with excessive thrombocytosis.

The effect of recombinant interferon alfa-2b on platelet count, thrombocytosis-associated symptoms and marrow fibrosis was studied in 18 patients with myeloproliferative diseases and associated thrombocytosis (nine with essential thrombocythaemia, three with polycythaemia vera, three with myelofibrosis and three with chronic myelogenous leukaemia). A reduction of the platelet count below 600 x 10(9)/L was achieved in 94%, and below 400 x 10(9)/L in 77% of the patients within 8 to 330 days of treatment. The selective thrombocytosis-reducing effect of alpha interferon was maintained for long periods of time in most patients without serious side effects. Thrombocytosis-associated symptoms were relieved once the number of platelets was reduced to near normal levels. Marrow reticulin content was found to be reduced after treatment in two of the seven patients studied. Side effects of alpha interferon were flu-like symptoms, which usually subsided within 7 days of treatment.

Adult↗
PubMed2004

Thrombocytosis associated with poor prognosis in patients with esophageal carcinoma.

BACKGROUND: Thrombocytosis in patients with cancer has been reported to be associated with increased expression of angiogenic factors and with a poor prognosis in some types of cancer. The aim of this study is to analyze the clinicopathologic significance and prognostic value of platelet counts in patients with esophageal cancer. STUDY DESIGN: Platelet counts were measured before surgery in 374 patients diagnosed between 1987 and 1999 with primary esophageal squamous cell carcinoma. We used the cut-off level of 293 x 10(9)/L (mean of 80 healthy controls +/- standard deviation) to define thrombocytosis. We analyzed the relationship between platelet counts, TNM factors, and white blood cell counts. Among 374 patients, the levels of C-reactive protein were analyzed in 170 patients and serum thymidine phosphorylase concentration was analyzed in 91 patients. The multivariate prognostic value of platelet counts, tumor size, and TNM factors were determined using Cox's proportional hazards model. RESULTS: Platelet counts were significantly increased in patients with large tumors (p < 0.001), deep tumors, nodal involvement, and distant metastasis in univariate analysis. C-reactive protein level, white blood cell count, and serum thymidine phosphorylase concentration were also significantly increased in patients analyzed with thrombocytosis in univariate analysis. Adjusting for tumor size and TNM factors, multivariate analysis indicated that thrombocytosis as defined in this study was an independent prognostic factor (hazard ratio = 1.52, 95% CI = 1.11 to 2.08, p = 0.009). CONCLUSIONS: A high platelet count is associated with tumor progression and poor survival in patients with esophageal carcinoma.

Adult↗
PubMed2004

A retrospective analysis of myelodysplastic syndromes with thrombocytosis: reclassification of the cases by WHO proposals.

Myelodysplastic syndromes (MDS) show occasionally thrombocytosis, common feature of myeloproliferative diseases (MPD), with the overlapping of both disorders. Classically, thrombocytosis has been associated with some MDS subtypes: refractory anaemia with ringed sideroblasts (RARS), 5q- syndrome and those MDS with 3q chromosome rearrangements. The recent WHO classification recognises an unclassifiable MDS/MPD category including some of these disorders. Our aim is to determine the frequency of presentation, subtype classification and chromosome abnormalities of MDS with thrombocytosis diagnosed in our institution. Between 1990 and 2003 we studied 317 SMD patients according to FAB and WHO revised classifications and identified 22 cases presenting thrombocytosis associated with dysplasia, that are analysed in this article.

Age Distribution↗
PubMed2006

Association of pretreatment thrombocytosis with disease progression and survival in oral squamous cell carcinoma.

The objective of this study was to review the prevalence and prognostic impact of pretreatment thrombocytosis in patients with oral squamous cell carcinoma (OSCC). Medical records of 253 patients with OSCC were retrospectively reviewed. The relationship between the platelet count, TNM stage, histologic differentiation, recurrence rate, metastasis, and survival were analyzed. Pretreatment thrombocytosis was found in 61 (24.1%) of 253 patients and was associated with aggressive tumour growth (p=0.015), lymph node metastasis (p=0.009), and distant metastasis (p=0.001). Association with tumour recurrence fell just short of statistical significance (p=0.058). Patients with preoperative thrombocytosis had a poorer survival than those with normal platelet counts (p=0.004). Multivariate analysis using Cox's proportional hazards model indicated that thrombocytosis was an independent predictor of shorter survival (RR 2.48, 95% CI 1.30- 4.73, p=0.006).

Adult↗
PubMed1999

Circulating levels of thrombopoietic and inflammatory cytokines in patients with clonal and reactive thrombocytosis.

The regulation of megakaryocytopoiesis and thrombopoiesis appears to be under the control of an array of hematopoietic growth factors. To determine the relationship between endogenous cytokine levels and circulating platelet counts, we measured the serum levels of both thrombopoietic and inflammatory cytokines in the peripheral blood and bone marrow samples from 70 patients with clonal thrombocytosis (CT) caused by myeloproliferative disorders, 28 patients with reactive thrombocytosis (RT), and 35 normal control subjects. The levels of thrombopoietin (TPO), interleukin-6 (IL-6), soluble IL-6 (sIL-6) receptor, IL-11, stem cell factor (SCF), IL-3, and IL-8 were determined by enzyme-linked immunosorbent assay (ELISA). Platelet counts were significantly higher in both CT and patients with RT (699+/-399x10(9)/L, P<.001; 642+/-200 x 10(9)/L, P<.001; respectively) as compared with the normal control subjects (240+/-47x10(9)/L). The concentrations of cytokines in the bone marrow correlated well with those in the peripheral blood. The endogenous levels of TPO, IL-6, and sIL-6 receptor were significantly higher in both CT and patients with RT than those in normal control subjects. The median level of IL-6 was significantly higher in patients with RT than in patients with CT (40 pg/mL vs. 5 pg/mL; P<.001); however, there was no detectable difference in TPO and sIL-6 receptor levels between the two groups. Significantly higher levels of SCF and IL-8 were also found in patients with CT as compared with those found in normal control subjects (median 2460 pg/mL vs 1995 pg/mL, P<.05; 20 ng/mL vs. 5 ng/mL, P = .001; respectively). Finally, IL-11 and IL-3 levels were undetectable in most patients with thrombocytosis. Our results reveal that the endogenous levels of TPO, IL-6, sIL-6 receptor, IL-8, and SCF are elevated in patients with CT or RT. These cytokines appear to be active mediators involved in the regulation of thrombopoiesis during clonal and reactive thrombocytosis.

Adult↗