Patients with thrombocytosis have normal or slightly elevated thrombopoietin levels

BACKGROUND AND OBJECTIVE: The distinction between clonal and reactive thrombocytoses is a frequent problem and implies different therapeutic options. As thrombopoietin (TPO) is the main regulator of megakaryocytopoiesis and thrombopoiesis, we measured TPO levels in patients with thrombocytosis in an attempt to understand the regulation and potential utility of distinguishing thrombocytoses. DESIGN AND METHODS: Serum TPO levels, platelet counts, mean platelet volume, hemoglobin, erythrocyte sedimentation rate and age were evaluated in 25 patients with clonal thrombocytosis (15 with essential thrombocythemia, 6 with polycythemia vera and 4 with chronic myeloid leukemia) and in 50 patients with reactive thrombocytosis distributed in three groups: 1) patients in post-surgical states; 2) patients with solid tumors; and 3) patients with inflammatory diseases. RESULTS: TPO levels were slightly increased in patients with clonal (135+/-50 pg/mL) and reactive (147+/-58 pg/mL) thrombocytosis compared with controls (121+/-58 pg/mL). Analyzing the different groups, patients with essential thrombocythemia had the lowest TPO levels (120+/-28 pg/mL) and patients with solid tumors the highest levels (162+/-59 pg/mL). Patients with clonal thrombocytosis were older, had higher platelet counts, mean platelet volume and hemoglobin, and lower erythrocyte sedimentation rate than patients with reactive thrombocytosis. INTERPRETATION AND CONCLUSIONS: Minor differences were observed in TPO levels between patients with primary and secondary thrombocytoses. Erythrocyte sedimentation rate, but not TPO levels, may be a useful tool for discriminating both types of thrombocytoses.     

Post-therapeutic recovery of serum interleukin-35 level might predict positive response to immunosuppressive therapy in pediatric aplastic anemia

Background: The predictive value of interleukin-35 (IL-35) on efficacy of immunosuppressive therapy (IST) in aplastic anemia (AA) has not been well investigated. The aim of the study was to evaluate the association between serum IL-35 level and response to IST in pediatric AA.

Methods: A total of 154 children with AA and 154 controls were included between January 2012 and December 2013. Blood and bone marrow fluid specimens were collected. Serum level of IL-35 was determined by enzyme-linked immunosorbent assay. Patients were treated with IST, and response to therapy was evaluated during 180-day follow-up period after starting therapy.

Results: Serum levels of IL-35 at admission decreased significantly in patients compared with that in controls (10.9?±?5.5?pg ml^?1 and 45.3?±?8.8?pg ml^?1, p??1 in the first 28 days (p??1 in the first 28 days was associated with effective response to therapy (odds ratio 7.97, 95% confidence interval 3.82–16.79). In addition, Fas/FasL protein expression in bone marrow mononuclear cells dropped significantly in the same group of patients in the first 28 days (p?Conclusion: The study revealed that post-therapeutic recovery of circulating IL-35 concentration might be an independent predictor for effective response to IST in pediatric AA. Moreover, apoptosis might be involved in such a forecasting process.     

Thrombopoietin serum concentration in patients with reactive and myeloproliferative thrombocytosis

 We wished to test whether thrombopoietin (TPO) is entirely regulated by receptor binding or if other factors may play a role in the mechanism of TPO regulation. Therefore, we analyzed the TPO serum levels in 43 patients with reactive (secondary) thrombocytosis and in 37 with myeloproliferative thrombocytosis. Thrombocytosis was defined as a platelet level greater than 440×10⁹/l. Forty-two patients (98%) with reactive thrombocytosis had high concentrations of IL-6 correlating with elevated C-reactive protein levels. Twenty-three patients (53%) in this group had TPO serum concentrations of more than 300 pg/ml (normal: below 300 pg/ml). Only nine patients (24%) with myeloproliferative thrombocytosis had TPO serum levels above normal range, whereas 28 patients (76%) had normal levels of TPO. No correlation between the TPO serum levels and the concentrations of IL-6 or EPO was established. The other investigated thrombopoietic cytokines (IL-3, IL-11, GM-CSF) were unmeasurable; therefore, a correlation could not be assessed. We conclude that TPO concentrations are not strictly inversely related to platelet count. TPO serum levels are elevated especially in a considerable percentage of patients with reactive thrombocytosis, arguing for the existence of additional mechanisms of TPO regulation. Received: February 28, 1998 / Accepted: August 18, 1998     

Thrombopoietin levels in patients with primary and reactive thrombocytosis

Human c-mpl ligand or thrombopoietin (TPO) has been proved to be a critical cytokine in the physiological regulation of thrombopoiesis. Previous evidence suggested that TPO production is constitutive and TPO plasma levels are regulated by the platelet–megakaryocyte mass through c-mpl receptor-mediated uptake and metabolism. To evaluate whether this mechanism of TPO level regulation is also operative in subjects with an elevated platelet count, we evaluated serum TPO in 32 patients with thrombocytosis due to essential thrombocythaemia (ET) or polycythaemia vera (PV) and in 70 subjects with reactive thrombocytosis; 32 healthy subjects were also studied. TPO levels were significantly higher in the ET and PV groups (median 246.2 pg/ml, range 93.5–4596) and reactive thrombocytosis patients (median 287 pg/ml, range 82.7–1960.0) than in normal subjects (median 156.7 pg/ml, range 62.2–352.7). No significant difference was found between the two groups of patients, indicating that serum TPO levels cannot differentiate between primary and reactive thrombocytosis. No significant correlation was found between platelet count and TPO levels in either ET-PV or reactive thrombocytosis, whereas a trend toward a correlation between acute-phase reactants and TPO was observed in patients with reactive thrombocytosis. These results indicate that TPO clearance by platelets–megakaryocytes is not fully operative or is not the only mechanism of TPO level regulation in primitive and reactive thrombocytosis.     

Thrombopoietin measurement in thrombocytosis: dysregulation and lack of feedback inhibition in essential thrombocythaemia

Essential thrombocythaemia (ET), a myeloproliferative disorder (MPD) manifested by excessive platelet production, lacks a specific diagnostic test to facilitate differentiation from other thrombocytoses. We studied thrombopoietin (TPO) levels in 41 patients with thrombocytosis: 25 ET patients, eight with other MPD, and eight with reactive thrombocytosis. Mean age and platelet counts for these groups were comparable. TPO levels for 96 healthy individuals provided a reference range for normal. The majority of ET patients (19/25 or 76%) had normal TPO levels. No patient with ET had a TPO level below 75 pg/ml, compared with 57% of healthy donors and 8/16 (50%) patients with other thrombocytoses ( P  < 0.05). TPO levels in ET are not appropriately down-regulated, as occurs with cytokines relevant to other MPD. In thrombocytosis, a TPO level <75 pg/ml indicates that ET is unlikely.     

Bone Marrow and Peripheral Blood C-kit Ligand Concentrations in Patients with Thrombocytosis and Thrombocytopenia

C-kit ligand (stem cell factor, SCF) is a hematopoietic growth factor with diverse effects. It has stimulatory effects on megakaryocytopoiesis acting in synergism with interleukin-3 (IL-3), thrombopoietin (TPO) and granulocyte-macrophage colony stimulating factor (GM-CSF). The relationship between SCF and megakaryocytopoiesis, especially the correlations between blood and bone marrow SCF levels have been not clearly established in the literature. We therefore, investigated peripheral and bone marrow SCF levels in patients with thrombocytosis and thrombocytopenia. Subjects were divided into three groups: those with (i) thrombocytopenia, (ii) thrombocytosis and (iii) healthy adults as controls. When the three groups were compared, the mean peripheral blood SCF level of the thrombocytosis group (2149±197) was significantly higher than the thrombocytopenia (1586±178) and normal control groups (1371±68; p<0.05) and the bone marrow SCF level was higher (2694±267) than the thrombocytopenia group (1700±182; p<0.05). In the correlation analysis, considering all the groups together the bone marrow and peripheral blood SCF concentrations were positively and significantly correlated (p<0.01; r=0.93). Correlations between platelet number and both bone marrow SCF concentration (p<0.01; r=0.51) and peripheral blood concentrations (p<0.01; r=0.40) were also shown. Our results indicate that SCF is operative in the pathological megakaryopoiesis of clonal origin and reactive thrombocytosis both in the local bone marrow microenvironment and the peripheral circulating blood. We feel that further studies on the platelet-SCF relationship and SCF levels in different disease states are required.     

Plasma levels of thrombin-activatable fibrinolysis inhibitor in primary and secondary thrombocytosis.

An elevated platelet count is a common finding in both hospitalized and ambulatory patients. Thrombosis and bleeding complications are more frequently observed in patients with clonal thrombocytosis than secondary thrombocytosis. The aim of this study was to investigate the behaviors of thrombin-activatable fibrinolysis inhibitor (TAFI) activity, the inhibitor of fibrinolysis, and also prothrombin time (PT), active partial thromboplastin time, and D-dimer and fibrinogen levels in 21 patients affected with clonal thrombocytemia as compared with 21 patients with reactive thrombocytosis and 21 healthy controls. In the clonal thrombocytemia group, plasma levels of TAFI activity were significantly higher than in both the reactive thrombocytosis and the control group. Plasma levels of leukocyte and platelet counts were significantly higher in the clonal thrombocytemia group than in the other two groups and also higher in the reactive thrombocytosis group than in the control group, which was also significant. Fibrinogen and D-dimer levels were higher in patients than in the control group but showed no significant difference between the clonal and secondary thrombocytosis groups. Plasma levels of PT and aPTT were higher in secondary thrombocytosis group than the clonal thrombocytosis group. The results of this study showed for the first time that TAFI activity is increased in patients with clonal thrombocytosis. These increased levels in clonal thrombocytosis can be considered a factor to explain the thrombotic tendency in myeloproliferative disorders.     

Impact of preeclampsia on megakaryocytopoesis and platelet homeostasis of preterm infants

The aim of this article is to investigate the megakaryopoyesis and thrombopoiesis in preterm infants born to mothers with preeclampsia and the potential effects mediated by soluble fms-like tyrosine kinase 1 (sFlt1) and thrombopoietin (TPO). A perspective case–control study was performed on 26 cord blood of preterm newborns born to mothers with preeclampsia (PE group) and 26 of preterms born to mothers without preeclampsia (control group). Circulating megakaryocyte count and megakaryocyte colony forming units (CFU-MK) were quantified by whole blood infiltration method and plasma clot culture system, respectively. Platelet activation markers, CD62P and CD63, were estimated by flow cytometry. Immunosorbent assays (ELISA) were employed to estimate plasma levels of sFlt1 and TPO of the two groups. When compared to the controls, infants born to mothers with PE had significantly lower peripheral platelet count (PE vs. controls: 157.9 [44.6] vs. 239.6 [57.5]?×?10⁹/l, p?p?5 cell, p?p?p?p?p?相似文献   

Thrombocytosis and thrombocythemia

Thrombocytosis is caused by three major pathophysiological mechanisms: (1) reactive or secondary thrombocytosis; (2) familial thrombocytosis; and (3) clonal thrombocytosis, including essential thrombocythemia and related myeloproliferative disorders. Recent work has begun to elucidate the abnormal megakaryocytopoiesis of essential thrombocythemia, which is associated with paradoxically elevated plasma levels of thrombopoietin. The clonal nature of all cases of essential thrombocythemia has been challenged. Thrombotic complications are the major causes of morbidity and mortality in this disease. Indications for platelet cytoreduction and antiplatelet therapy, as well as complications of treatment, are being clarified.     

Serum thrombopoietin levels in patients with reactive thrombocytosis due to lung cancer and in patients with essential thrombocythemia

In patients with thrombocytosis normal to increased serum thrombopoietin (TPO) levels have been reported. The aim of this study was to investigate the relationship between serum TPO concentration, platelet number and plasma levels of fibrinogen in patients with reactive thrombocytosis (RT) due to lung cancer and in patients with essential (primary) thrombocythemia (ET). A total of 70 newly diagnosed patients with RT or ET (platelet counts >600 G/l) were studied: 45 with RT due to lung cancer (25 with non-small cell lung cancer, NSCLC and 20 with small cell lung cancer, SCLC), and 25 with ET. Twenty normal volunteers were used as controls. TPO was measured by immunoassay technique (ELISA). Mean serum TPO values in patients with RT due to lung cancer were statistically significantly higher than those in patients with ET or in controls. The highest platelet count was seen in patients with ET, and mean plasma fibrinogen levels were the highest in RT patients. In NSCLC patients mean serum TPO concentrations were higher (not statistically significant) than in SCLC, and a statistically significant relationship between TPO serum concentration and fibrinogen level was observed. No correlations between platelet counts and TPO serum concentrations were found. Our results indicate increased serum TPO levels in patients with thrombocytosis in lung cancer which may be related to the activity of neoplasms. In addition, it is postulated that the relatively low TPO values in patients with ET may result from a dysregulation of the feedback loop involved in platelet production.     

The pretreatment platelet and plasma fibrinogen level correlate with tumor progression and metastasis in patients with pancreatic cancer

Abstract

Cancer patients frequently present with activated coagulation pathways and thrombocytosis, which are potentially associated with tumor progression and prognosis. However, the prognostic value of abnormal plasma fibrinogen and platelet levels for the treatment of pancreatic cancer is unclear. The purpose of our study was to evaluate the prognostic value of plasma fibrinogen and platelet levels in pancreatic cancer, and to devise a prognostic model to identify the patients with greatest risk for a poor overall survival. One hundred and twenty-five patients diagnosed with pancreatic ductal adenocarcinoma in our hospital between May 2000 and June 2005 were included in this study. The plasma fibrinogen and platelet levels were examined before treatment and analyzed along with patient clinicopathological parameters and overall survival. The foundation of prognostic model was based on the risk factors according to the Cox proportional hazard model. The incidence of hyperfibrinogenemia and thrombocytosis was 24.8% (31/125) and 15.2% (19/125), respectively. The mean fibrinogen concentration differed significantly between the early (I/II) and late (III/IV) stage patients (3.19?±?0.70 vs. 3.65?±?0.90?g/l, p?=?0.008). Patients with a higher concentration of plasma fibrinogen and platelets had a worse prognosis (p?<?0.05). There also existed a significant correlation between higher fibrinogen/platelet levels and distant organ metastasis (p?<?0.05, respectively). Bivariate correlation analysis showed that plasma fibrinogen levels correlated significantly with platelet levels (p?=?0.000). Multivariate analysis revealed that pretreatment plasma fibrinogen levels (p?=?0.027), tumor stage (p?=?0.026) and distant metastasis (p?=?0.027) were independent prognostic factors. The median survival time for the low-, intermediate-, and high-risk groups was 9.6 months (95% CI 6.2–13.0), 3.8 months (95% CI 2.3–5.3), and 2.3 months (95% CI 0.9–3.7), respectively (p?=?0.000). Pretreatment plasma fibrinogen and platelet levels closely correlated with tumor progression, metastasis and overall survival in pancreatic cancer. The foundation of prognostic model may help us identify the greatest risk populations with pancreatic cancer.     

The plasma levels of prostanoids and plasminogen activator inhibitor-1 in primary and secondary thrombocytosis.

An elevated platelet count is a common finding in both hospitalized and ambulatory patients. Thrombosis and bleeding complications are more frequently observed in patients with clonal thrombocytosis than secondary thrombocytosis. The aim of this study was to investigate the behaviors of plasminogen activator inhibitor type 1 (PAI-1), the inhibitor of fibrinolysis; and thromboxane A2 and 6-keto-PGF1 alpha, the products of endoperoxides, in 16 patients affected with clonal thrombocytemia as compared with 16 patients with reactive thrombocytosis and 15 normal controls. In the clonal thrombocytemia group, plasma levels of PAI-1 antigen and activity were significantly higher than both reactive thrombocytosis and control group. Plasma levels of 6-keto-PGF1alpha were significantly higher in the clonal thrombocytemia group than the other two groups and also higher in the reactive thrombocytosis group than the control group, which was also significant. This study confirms that arachidonate metabolism is frequently deranged in patients with thrombocytosis and hypofibrinolysis due to increased PAI-1 plasma levels as shown in the clonal thrombocytosis group. This may explain the thrombotic tendency in myeloproliferative disorders.     

Granulocyte-macrophage colony-stimulating factor as a cause of paraneoplastic leukaemoid reaction in advanced transitional cell carcinoma

Abstract. Increasing evidence suggests that paraneoplastic syndromes may be mediated by tumour-related cytokine release, although the specific factor(s) involved remain poorly defined. Colony-stimulating factors (CSF) and interleukins (IL) promote colony growth in semi-solid media and, when administered in recombinant form, increase blood counts in patients. However, normal serum CSF levels in individuals with physiologic blood counts and the relationship between specific serum CSF levels and paraneoplastic leukaemoid reaction are not well established. In this study, we found that normal serum levels of granulocyte-macrophage CSF (GM-CSF), as measured by ELISA, were generally < 55 pg ml^?1; IL-3, < 30 pg ml^?1; and granulocyte CSF (G-CSF), < 50 pg ml^?1. In contrast, high levels of GM-CSF (132 pg ml^?1), but not G-CSF or IL-3, were found in a patient with a transitional cell carcinoma of the renal pelvis and increased leukocytosis correlating with the tumour burden. The GM-CSF was biologically active, as demonstrated by its ability to stimulate colony growth in vitro. Based on these results it appears that autonomous production of GM-CSF is one possible pathophysiologic mechanism underlying leukaemoid reaction in cancer patients.     

The Effects of Diet and Insulin Therapy on Coagulation Factor VII,Blood Viscosity,and Platelet Release Proteins in Diabetic Patients with Secondary Sulphonylurea Failure

The effect of intensified dietary measures and subsequently insulin therapy upon haemorheological measures were studied in Type 2 diabetic patients with secondary sulphonylurea failure. Coagulation factors VIIc and VIIIc, fibrinogen, plasma viscosity, whole blood viscosity, β-thromboglobulin, platelet factor 4, von Willebrand factor, and euglobulin clot lysis time were measured at baseline, after 3 months intensified dietary therapy and after 4 months insulin therapy. During intensified dietary therapy there was a significant fall in serum cholesterol (p < 0.05) and a small decrease in weight, but no significant change in blood glucose control. Factor VIIc levels fell significantly (1.22 (SE 0.07) vs 1.42 (0.08) u ml^?1, p < 0.01), and plasma viscosity and whole blood viscosity (23 s^?1) also improved (both p < 0.05). Insulin therapy was instituted with either continuous subcutaneous insulin therapy or twice daily injections of soluble and isophane (NPH) insulin. During this period glycosylated haemoglobin improved (mean (SE) 49.5 (1.4) vs 65.0 (2.1) mmol-HMF mol-Hb^?1 p < 0.001; normal range 29–39 mmol-HMF mol-Hb^?1) as did serum triglyceride (p < 0.01), but weight increased (p < 0.001). The only haemorheological changes with insulin were increased levels of the platelet release proteins β-thromboglobulin (37 (3) vs 28 (2) μg l^?1 p < 0.01) and platelet factor 4 (median 7.5 (range 3.0–18.0) vs 4.5 (2.0–10.5) μg l^?1, p < 0.01).     

High IL-6 levels in ascitic fluid correlate with reactive thrombocytosis in patients with epithelial ovarian cancer

Summary. Non-haematopoietic malignancies are commonly associated with thrombocytosis. The aetiology of tumour-associated thrombocytosis is still unclear but may be related to tumour-derived thrombopoietin-like factors. Epithelial ovarian tumour cells have been shown to release IL-6 in vitro and high IL-6 levels have been identified in ascites of patients with ovarian cancer. Since IL-6 is a potent stimulator of megakaryocytopoiesis we examined IL-6 production at the tumour site and its relationship to serum IL-6 levels and circulating platelet counts in patients with ovarian cancer. Forty patients undergoing exploratory laparotomy for epithelial ovarian cancer [stage I + II: 6 (15%); stage III: 25 (62.5%); stage IV: 9 (22.5%)] and 24 women with benign ovarian conditions were evaluated. Sera were available from 39 cases with ovarian cancer and from 19 cases with benign ovarian tumours. Ascites was obtained from 35 patients with ovarian cancer. IL-6 activity in serum and ascitic fluid was determined by the standard B9 proliferation assay (detection level: 1 pg/ml). IL-6 bioactivity was detectable in 22 (56%) sera from patients with ovarian cancer, but in only five (26%) of the serum samples obtained from benign cases (P < 0.001). Serum IL-6 levels in patients with ovarian cancer were significantly higher (median 3 pg/ml; range < 1 to 1221 pg/ml) than in patients with benign ovarian conditions (median 0 pg/ml; range < 1 to 4 pg/ml) (P < 0.001). However, much higher concentrations of IL-6 were measured in malignant ascites specimens (median 22 100 pg/ml; range < 1 to 182 600 pg/ml). IL-6 bioactivity in serum and ascites samples was completely inhibited by a neutralizing goat antihuman IL-6 antiserum. Thrombocytosis (platelet counts > 400 × 10⁹/l) occurred in 25 (62.5%) of the 40 patients with ovarian cancer, but in only two (8%) of the 24 cases with benign ovarian tumours. In eight (20%) cases with malignant disease platelet counts ranged between 600 × 10⁹/l and 1060 × 10⁹/l. IL-6 bioactivity in ascitic fluid correlated significantly with circulating platelet counts (r = 0.5916; P < 0.001). Maximum IL-6 bioactivity in ascites and highest platelet counts occurred in patients with undifferentiated ovarian adenocarcinoma or advanced disease. In conclusion, these observations strongly suggest a role for IL-6 in the development of tumour-associated thrombocytosis.     

Spontaneous and cytokine-induced thrombocytopenia in myelodysplastic syndromes: serum thrombopoietin levels and bone marrow morphology

Thrombocytopenia is a substantial clinical problem for patients with myelodysplastic syndromes (MDS). Cytokine treatment for granulocytopenia and anaemia may further reduce the platelet counts. We studied serum thrombopoietin levels (S-TPO) in 52 patients with MDS and 96 healthy controls and related the results to clinical and morphological variables. S-TPO was also assessed after treatment with granulocyte-CSF (G-CSF) and erythropoietin (EPO) in 30 of these patients. S-TPO in MDS was not a normally distributed variable; mean value was 394 pg/ml, SD +/-831 and median value 123 (12-5000 pg/ml). The controls showed lower S-TPO levels than the patients (median 78 pg/ml, P = 0.003) whereas no differences between the MDS subgroups were observed (P = 0.86). Patients with ringed sideroblastic anaemia (RARS) showed the highest platelet counts and higher S-TPO levels than the controls (P = 0.005). No association between platelet counts and S-TPO levels was found in the patients (P = 0.67). TPO levels were generally low in patients with refractory anaemia with an excess of blasts (RAEB), but very high levels were found in five patients. Patients with a high transfusion need had higher S-TPO levels, whereas bone marrow blast counts, cellularity or megakaryocytes showed no correlation with S-TPO. Patients with 5q- showed lower TPO levels than the other patients, indicating that thrombopoietin is not a mediator of thrombocytosis in these cases. Treatment with G-CSF + EPO significantly reduced the platelet counts (P = 0.0002), but this change was not related to significant changes in S-TPO levels or morphology. Patients with RARS and thrombocytosis who normalized their platelet counts showed a concomitant reduction in S-TPO. This may suggest that the increased platelet counts observed in RARS may be caused by increased S-TPO levels. In conclusion, our study shows that platelet, megakaryocyte and thrombopoietin regulation is rather complex in myelodysplastic syndromes and that spontaneous or induced thrombocytopenia are not usually mirrored by increased S-TPO levels.     

Preliminary investigation about the expression of tubulin in platelets from patients with iron deficiency anemia and thrombocytosis

Objective: In order to inquire into the pathogenesis of increased platelet counts in peripheral blood of patients with iron deficiency anemia (IDA), the phenomenon of thrombocytosis was confirmed, and then the expression of tubulin within platelets from IDA patients was investigated.

Methods: Peripheral blood samples were collected from 79 patients with IDA and were divided into 2 groups, group of IDA with normal platelet counts (34 cases), and group of IDA with increased platelet counts (thrombocytosis) (45 cases). Additionally, 45 peripheral blood samples from healthy volunteers were enrolled as a group of healthy controls. Count of platelets in peripheral blood was detected by means of LH-780 hematology analyzer and hemocytometer under a microscope respectively, and analyzed statistically.

Results: There was no statistical difference between platelet counts detected by LH-780 hematology analyzer and hemocytometer under a microscope (P?>?.05). The mean fluorescence intensity (MFI) of both α-tubulin and β-tubulin within platelets from IDA patients with thrombocytosis was significantly less than that from healthy volunteers and IDA patients with normal platelet counts (P?P?>?.05).

Conclusion: Some patients with IDA are accompanied by thrombocytosis, from which the expression of α-tubulin and β-tubulin within platelets reduced obviously compared with those with normal platelet counts and healthy controls respectively. It is implied that downregulation of tubulin probably is a part of the pathogenesis leading to increased platelet counts in IDA.     

Does prematurity affect thrombocytopoiesis?

Data concerning thrombocytopoiesis in newborns are poorly recognized. Platelets have a crucial role in hemostatic physiology, which is deficient in newborns, especially in preterm newborns. A total of 51 preterm newborns (PTN), 25 girls and 26 boys, were recruited for the study. The control group consisted of 25 female and 30 male healthy term newborns (HTN). Plasma thrombopoietin (TPO) was measured using Quantikine human TPO system. Reticulated platelets (PLRET) was estimated by means of Retic-Count Kit. Platelet count (PLT) was determined using Advia^TU 120 Hematology System. TPO was evidently higher in PTN (110.9?pg/ml) than in HTN (71.5?pg/ml), (p?<?0.001). The percentage of reticulated platelets (PLRET) was also twice as high in PTN (3.49%) in comparison to HTN (1.7%), (p?<?0.001). The PLT count was lower in PTN (246.7?×?10³?µL) than in HTN (287.2?×?10³?µL), (p?<?0.01). Increased TPO levels and the percentage of PLRET indicate that thrombocytopoiesis is more active in prematurity. Our finding may be useful in therapeutic strategies.     

Platelet-monocyte cross talk and tissue factor expression in stable angina vs. unstable angina/non ST-elevation myocardial infarction

Tissue factor (TF), the major procoagulant in vivo, is usually absent from blood cells. However, since both monocyte TF (MoTF) expression and platelet activation are present in acute coronary syndrome we hypothesized that MoTF expression may in part depend on monocyte platelet aggregate (MPA) formation in coronary artery disease (CAD). Patients with unstable angina/non-ST-elevation myocardial infarction (UA/NSTEMI, n?=?20) had significantly higher levels of MoTF (17.4?±?3.1MFI) and MPAs (CD42b:273?±?183MFI; CD62P:256.3?±?48.5MFI) than patients with stable angina (SA, n?=?40; MoTF:13.2?±?2.2MFI, p?=?0.001; CD42b:160?±?113MFI, p?=?0.025; CD62P:118.7?±?24.5MFI, p?=?0.018) as measured by whole blood flow cytometry on CD14⁺-cells. TF-activity of isolated mononuclear cells (MNC) was elevated in UA/NSTEMI (75?±?27?pg/mL) in comparison to SA (47?±?17?pg/mL, p?=?0.001) as determined by chromogenic assay, and TF mRNA expression in isolated MNC was more frequent in UA/NSTEMI than in SA (50% vs. 18.2%; p?=?0.017). MoTF expression significantly correlated with the constitutive platelet marker CD42b (r?=?0.69, p?<?0.001) and the platelet activation marker CD62P (r?=?0.47, p?=?0.001) on CD14⁺-cells suggesting its association with MPAs in UA/NSTEMI. In addition, MoTF expression correlated with MoTF activity of isolated MNC (r?=?0.41, p?=?0.01) and plasma levels of the F1.2 prothrombin fragment (r?=?0.35, p?=?0.02). In conclusion, MoTF and MPAs are elevated in UA/NSTEMI compared with SA. MoTF expression correlates with platelet mass and activity attached to monocytes.     

Thrombopoietin and its receptor expression in pediatric patients with chronic immune thrombocytopenia

Objectives: Chronic immune thrombocytopenia (cITP) is common in children. However, the pathogenesis has not been fully elucidated. This study aimed to determine whether thrombopoietin (TPO) and its receptor c-mannosylation of the TPO receptor (c-Mpl) have an impact on childhood cITP.

Methods: Sixty-four patients with newly diagnosed ITP (nITP), 64 patients with persistent ITP, 80 patients with cITP, and 64 healthy children (control) were enrolled in this study. Plasma TPO was measured with an ELISA, and c-Mpl was determined by flow cytometry.

Results: Plasma TPO levels showed differences among the four groups (p?=?0.001). TPO levels in the cITP group were significantly decreased compared to those in the nITP group (p?p?=?0.0275). c-Mpl MFI was lower in the cITP group than in the nITP group(p?p?p?=?0.023). The control group, compared with the other groups, had lower levels of c-Mpl mRNA.

Conclusions: The expression of TPO and c-Mpl was significantly decreased in the cITP group compared to the nITP group, suggesting that TPO and its receptor may play important roles in childhood cITP pathogenesis.