Platelet Function and Activation in Patients with Immune Thrombocytopenia Treated with Eltrombopag: Comparison with Steroid-Treated and Untreated Patients,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3280-3280
Author(s):  
Johanna Haselboeck ◽  
Alexandra Kaider ◽  
Ingrid Pabinger ◽  
Simon Panzer

Abstract Abstract 3280 Background: Eltrombopag has recently been approved for treatment in immune thrombocytopenia (ITP). Studies on platelet function in eltrombopag-treated patients in comparison to steroid-treated or untreated ITP patients are not available. Objectives: To assess the function of eltrombopag-induced platelets, we compared platelets from eltrombopag-treated patients to those from ITP patients treated with steroids and a group of patients without treatment in a prospective study (ClinicalTrials.gov number NCT00888901). Patients/Methods: We compared platelet function in patients treated with eltrombopag after treatment-induced platelet rise (group 1) to those under steroid treatment (group 2) and ITP patients without treatment (group 3) in a non-randomized prospective study. Platelet function was assessed by adhesion under high shear conditions (surface coverage, SC), P-selectin expression, and formation of platelet-monocyte aggregates (PMA) after treatment induced platelet rise or, in group 3, in patients with ITP without treatment and platelet count between 50–100×109/L at the time of inclusion. Data are given as median [quartiles]. Correlations of the outcome measures are described by the Spearman correlation coefficient. In case of normally distributed data, analysis of variance (ANOVA) and of covariance (ANCOVA) models and in case of non-normally distributed parameters the nonparametric Kruskal-Wallis test were used to compare the groups Results: Eleven patients (female=9) were included in the treatment group with eltrombopag (group 1), thirteen (female=5) in the steroid treatment (group 2) and 6 patients as untreated controls (group 3). None of these patients developed severe bleeding during the study period, none received rescue medication. Four/30 patients were not included in the final analysis, three because they had no treatment induced platelet rise (1 on eltrombopag and 2 on steroids) and 1 because of aspirin medication. Thus, ten patients on eltrombopag, ten patients on steroid treatment and 6 untreated patients were evaluated in the comparative analyses of platelet function. Platelet counts [x109/L] were 48.25 [45.00–59.00] in group 1 after eltrombopag-induced platelet rise, 82.75 [78.50–112.00] in group 2 and 69.25 [65.00–73.00] in group 3. SC was highest in steroid-treated patients (11.25% [8.10–14.00%]) compared to eltrombopag-treated (5.80% [1.80–9.00%]) and untreated (5.03% [3.80–6.20%]) patients and correlated significantly with the platelet count (r=0.72, p<0.0001). There were no differences in P-selectin expression [GeoMFI] (1.15 [0.47–2.77] in group 1, 0.27 [0.10–0.99] in group 2 and 0.59 [0.47–1.44] in group 3; p=0.34) and PMA levels (6.19% [3.91–21.39%] in group 1, 9.73% [1.88–13.29%] in group 2, and 6.56% [4.82–8.43%] in group 3; p=0.93) between the groups. Two patients developed venous thromboses during eltrombopag treatment. No characteristic alteration of platelet function and activation was identified in those 2 patients when compared to the other eltrombopag-treated patients. Conclusions: We proofed a good functional competence of eltrombopag-induced platelets. No substantial hyper-reactivity of eltrombopag-induced platelets in comparison to those of steroid-treated and untreated patients was determined. Disclosures: Pabinger: GlaxoSmithKline: Research Funding, Speakers Bureau. Panzer:GlaxoSmithKline: Speakers Bureau.

Perfusion ◽  
2006 ◽  
Vol 21 (1) ◽  
pp. 61-66 ◽  
Author(s):  
Edmundas Sirvinskas ◽  
Audrone Veikutiene ◽  
Pranas Grybauskas ◽  
Jurate Cimbolaityte ◽  
Ausra Mongirdiene ◽  
...  

The aim of the study was to assess the effect of aspirin or heparin pretreatment on platelet function and bleeding in the early postoperative period after coronary artery bypass grafting (CABG) surgery. Seventy-five male patients with coronary artery disease who underwent CABG with cardiopulmonary bypass (CPB) were studied. The patients were divided into three groups: Group 1 ( n = 25) included patients receiving aspirin pretreatment, Group 2 ( n = 22) received heparin pretreatment, and Group 3 ( n = 28) included patients who received no antiplatelet or anticoagulant pretreatment. Twenty-four hours after surgery, all patients were administered aspirin therapy that was continued throughout their hospitalization period. We assessed the following preoperative blood coagulation indices: activated partial thromboplastin time (aPTT), international normalized ratio (INR), and fibrinogen. We compared platelet count and platelet aggregation induced by adenosinediphosphate (ADP) before surgery, 1 h after surgery, 20 h after surgery and on the seventh postoperative day. We assessed drained blood loss within 20 postoperative hours. Preoperative blood coagulation indices did not differ among the groups. Platelet count was also similar. One hour after surgery, platelet count significantly decreased in all groups ( p <0.001), after 20 postoperative hours it did not undergo any marked changes, and on the seventh postoperative day, it significantly increased in all groups ( p <0.001). Before surgery, the lowest index of ADP-induced platelet aggregation was found in Group 1 ( p <0.05). One hour after surgery, platelet aggregation significantly decreased in all groups, most markedly in Group 3 ( p <0.001), yet after 20 h, its restitution tendency and a significant increase in all groups was noted. On the seventh day, a further increase in the statistical mean platelet aggregation value was noted in Groups 2 and 3. Comparison of platelet aggregation after 20 postoperative hours and on the seventh day after surgery revealed a significantly higher than 10% increase of the index in 32% of patients in Group 1 ( p <0.05), 27.3% of patients in Group 2 ( p <0.05) and in 35.7% of patients in Group 3 ( p <0.001). The lowest statistically significant value of postoperative blood loss was noted in Group 2 ( p <0.01). Our study has shown that aspirin or heparin pretreatment had no impact on the dynamics of platelet function in the early postoperative period after CABG. The lowest postoperative blood loss was noted in patients pretreated with heparin.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Yukako Yoshikane ◽  
Ryuji Fukazawa ◽  
Kyoko Imanaka-yoshida ◽  
Naho Kobayashi ◽  
Yasuhiro Katsube

Introduction: Kawasaki disease (KD), which is the most common multisystem vasculitis with unknown causes in childhood, causes coronary artery lesions (CALs). Treatment with a high dose of intravenous immunoglobulin (IVIG), plus steroids if needed, is the most effective therapy for the acute phase of KD. However, there are some very severe cases who need several times additional treatments and are at risk for CALs. In Japan, there are some scoring systems that initially predict IVIG-resistant patients. However, the problem is that these scoring systems fail in multiethnic populations. The aim of this study is to find universal biomarkers that predict treatment-resistant cases of KD. Methods: The subject was 276 KD patients, including Group 1 (n=214) who needed only 1 st line treatment, Group 2 (n=48) who needed 2 nd line treatment, Group 3 (n=14) who needed 3 rd line treatment or more. Tenascin C (TN-C), Pentraxin 3 (PTX3) and Procalcitonin (PCT) values, which were selected by systematic review, were measured before initial treatment in each group. Results: TN-C; 99.8±41.05 ng/ml in Group 1, 118.0±71.4 ng/ml in Group 2 and 183.0±25.0 ng/ml in Group 3. The TN-C level of Group 3 was significantly higher than that of all the others (p<0.01). The cutoff value for distinguishing Group 3 was 142.0 ng/ml (Area under the Curve (AUC)=0.81). PTX3; 16.2±9.0 ng/ml in Group 1, 31.4±19.7 ng/ml in Group 2 and 58.0±33.0 ng/ml in Group 3. The PTX3 level of Group 3 was significantly higher than that of all the others (p<0.01). The cutoff value for distinguishing Group 3 was 35.1 ng/ml (AUC=0.86). PCT; 0.79±0.77 ng/ml in Group 1, 2.55±3.01 ng/ml in Group 2 and 4.15±4.49 ng/ml in Group 3. The PCT level of Group 3 was significantly higher than that of all the others (p<0.01). The cutoff value for distinguishing Group 3 was 2.55 ng/ml (AUC=0.88). When those three biomarkers combined, Group 3 can be predicted with the sensitivity 79%, the specificity 96%, the positive predictive value 50% and the negative predictive value 99%. Conclusions: It may be possible to predict treatment-resistant KD cases with high sensitivity and specificity by combining the measurement from the universal biomarkers, TN-C, PTX3 and PCT, before initial treatment.


1980 ◽  
Vol 93 (1) ◽  
pp. 13-19 ◽  
Author(s):  
Reiko Demura ◽  
Hajime Yamaguchi ◽  
Ichiji Wakabayashi ◽  
Hiroshi Demura ◽  
Kazuo Shizume

Abstract. The effect of growth hormone (hGH) on the hypothalamic-pituitary-thyroid function was studied in patients with pituitary dwarfism. Twenty-six patients were given KABI hGH, 0.5 U/kg/week, for a period of 4—18 months. Three groups of patients were identified according to their T4 levels before and during the treatment. Group 1: T4 levels were initially normal and stayed in the normal range throughout a course of treatment. Group 2: T4 levels were initially normal but dropped to the subnormal range after hGH. Group 3: T4 levels were initially subnormal and decreased further after hGH. Changes in T4 levels after hGH in groups 2 and 3 were accompanied by a decrease in plasma T3RSU without concomitant decrease in plasma T3. Clinically, most of them lacked symptoms and signs of hypothyroidism and exhibited a good growth response to hGH. Plasma TSH response to TRH in these patients revealed a sustained delayed pattern, which was suggestive of hypothalamic hypothyroidism. This pattern of TSH response to TRH became further exaggerated after hGH therapy. In contrast, TSH response to TRH among patients in group 1 was normal and was not influenced by hGH. Administration of 4.0 U of KABI hGH daily for 21 consecutive days to 3 patients resulted in a shortened half-life of T4 and inversely prolonged that of T3. These results suggest that various degrees of TRH deficiency exist among patients with idiopathic pituitary dwarfism. Therapy with hGH discloses a mild TRH deficiency by accelerating the half-life of T4. This also causes a further drop in the T4 levels in those with marked TRH deficiency. The development of clinical hypothyroidism is not so obvious in these patients because of inverse delay in half-life of T3 by hGH.


2012 ◽  
Vol 7 ◽  
Author(s):  
Füsun Şahin ◽  
Esra Yazar ◽  
Pınar Yıldız

Background: We aimed to investigate the relation of platelet count (PLT) and plateletcrit (PCT), mean platelet volume (MPV) and platelet distribution width (PDW) with other acute phase reactants and radiological extent in pulmonary tuberculosis (PTB). Methods: One hundred patients with PTB (Group 1), 50 patients with community-acquired pneumonia (Group 2) and 28 healthy control individuals (Group 3) were included in this analytic study. Results: WBC (White Blood Cell), ESR (Eritrocyte Sedimentation Rate), CRP (C-Reactive Protein), PLT and PCT values were both in Group 1 and Group 2 than in Group 3. PDW values were significantly higher in Group 1 than Group 3. WBC, ESR and CRP values were lower, while PLT and PCT values were higher in the Group 1 compared to Group 2 (p < 0.001). PLT was positively correlated with CRP and ESR values in the tuberculosis group (p < 0.001), while it was not correlated with CRP and ESR in the pneumonia group (p > 0.05). ESR, CRP, PLT and PCT values were found higher in radiological advanced stage (Stage 3) patients with PTB, while hemoglobin (Hb) was found lower (p < 0.05). Higher WBC, ESR, CRP and PCT values as well as radiological advanced stage were more common in PTB patients with thrombocytosis compared to the patients with normal platelet count, whereas Hb was found lower in these patients. Conclusions: This study indicates that reactive thrombocytosis and higher PCT and PDW develop frequently in PTB and there is a relation between thrombocytosis and acute phase reactants, that is the inflammatory response. In addition, tuberculosis with radiological advanced stage is seen more frequently in the patients with thrombocytosis and higher PCT, drawing attention to the possible role of platelets in the cell-based immune process of tuberculosis.


2019 ◽  
Vol 76 (6) ◽  
pp. 628-634
Author(s):  
Ana Antic ◽  
Zoran Stanojkovic ◽  
Miodrag Vucic ◽  
Milan Lazarevic ◽  
Nebojsa Vacic

Background/Aim. The platelet aggregation, as a laboratory test for assessment of platelet function, is very efficient for optimal antiplatelet treatment and also to identify individuals who have suboptimal response to antiplatelet drugs, such as aspirin and clopidogrel. The aim of this study was to determine the level of inhibition of platelet aggregation using impedance aggregometry in the patients receiving different preparations of acetylsalicylic acid (ASA) in a dose of 100 mg per day. Methods. The examination included 215 patients (110 men and 105 women), treated with one of three different ASA preparations after acute myocardial infarction, as a single therapy or with clopidogrel. Among them, 89 patients were on Aspirin protect? (Bayer, Germany) ? Group 1 and 66 patients were on Cardiopirin? (GL Pharma GMBH, Austria) ? Group 2, while 60 patients were taking Andol? (Pliva, Croatia) ? Group 3. The groups were equal in the presence of factors that can influence platelet aggregation (age, gender, smoking, diabetes, taking other drugs). The platelet function was measured using the impedance aggregometer Multiplate (Multiplate Platelet Function Analyzer, Roche) in the blood samples with heparin for the platelet aggregation activated by the arachidonic acid (ASPI) and by thrombin (TRAP) tests [the area under the aggregation curve (AUC) was used to express the aggregation response over the measured time (AU*min)]. Results. Efficacy of ASA preparations showed statistically significant differences among the three investigated groups (?KW2 = 46.279; p < 0.001), and it was also observed separately in the patients undergoing single therapy (?KW2 = 26.344; p < 0.001) and dual therapy (?KW2 = 23.498; p < 0.001). It was found that the patients who were taking Aspirin protect? obtained significantly better antiplatelet efficiency compared to the patients receiving Cardiopirin? (Z = 5.472; p < 0.001) and Andol? (Z = 5.387; p = 0.022). There is reduced efficiency of all ASA preparations in smokers, while patients receiving Aspirin protect? were 10.5 times more likely to be responders. Conclusion. Different ASA preparations observed in this study showed different efficiency on the platelet function as measured by the method of impedance aggregometry.


2014 ◽  
Vol 10 (2) ◽  
Author(s):  
Febiola Rama Sari ◽  
Yudha Fahrimal ◽  
Ummu Balqis ◽  
Didik T Subekti ◽  
Aprilia Wardana

This study aimed to find out the parasitemia of DDY white mice infected with T. evansi of Pidie and Pemalang isolates obtained from Bbalitvet Bogor. A total of 12 mice were divided into 3 treatment groups. Group 1 (K1) without any treatment, group 2 (K2) was inoculated with 104 T. evansi Pidie isolate, and group 3 (K3) was inoculated with 104 T. evansi Pemalang isolate. Parasitemia examination was carried out every two days and the level of parasitemia was observed as well. Parasitemia examination was conducted until all mice died. Parasitemia of mice infected with Pidie isolate was characterized by rapid rise of parasitemia in blood (107-108/mL of blood) in a short time (2-4 days) since first parasitemia was detected and followed by death at day 4. The parasitemia of mice infected with Pemalang isolate increased in the blood (108-109/mL of blood) on day 4 and maintained for a few more days and then fluctuated for a few more days before the animal was dead. In conclusion, there was the difference in parasitemia level between Pidie and Pemalang isolates. Key words: Trypanosoma evansi, parasitemia, Pidie isolate, Pemalang isolate


Author(s):  
Rajanna Ajumeera ◽  
Vijayalakshmi Venkatesan

Aims: To study the effects of pyridoxal phosphate (PLP) on oxidative stress in isolated pancreatic acinar cells. We have previously shown that PLP has cytoprotective and insulinotropic effects on mice islet cells in vivo and in vitro studies. Main methods: Acinar cells were isolated from three months old WNIN male rats and were cultured in vitro for a period of 24 h in CO2 incubator. Later the cells were divided into four groups as untreated (group 1), H2O2 treatment (group 2), PLP treatment (group 3) and PLP followed by H2O2 treatment (group 4). Cell viability was confirmed using MTT assays, oxidative stress levels were measured with ROS assay, change in different protein levels were recorded by flow cytometry. The acinar cells insulin secretion assay was performed with ELISA. The amylase protein expression was assessed using confocal microscopy. Key findings: The cell viability of acinar cell in group 1 was considered as 100%, while in group 2 it was reduced to 82% due to H2O2 effect, and in group 3 (99.8%) and group 4 (99.5%) were near to group 1 due to the cytoprotective effect of PLP. The ROS levels were increased by 1.47 folds in group 2, while PLP decreased to 1.02 fold in group 4, which was comparable with the changes in group 1. Beneficial effects of PLP were also observed from the increased expression levels of acinar cells are amylase -2.01, neurogenin-3-9.51, PDX-1- 23.6 and insulin-13.5 in group 3 compared to group 1. The specificity of PLP&rsquo;s response was confirmed by amino oxy acetic acid (AOAA), a specific PLP inhibitor. The increased amylase protein localization with PLP was confirmed by confocal microscopy. Insulin secretion efficiency of acinar cells was observed to be 6.13 folds higher at basal and 24.63 fold higher at stimulated levels in group3 compared to group1. Significance: Our results advocate the antioxidant and cytoprotective effects of PLP on the pancreatic acinar cell along with increased pancreatic marker expressions of amylase,PDX-1, neurogenin-3 and insulin proteins.


PEDIATRICS ◽  
1987 ◽  
Vol 79 (5) ◽  
pp. 778-785
Author(s):  
S. Jean Emans ◽  
Elizabeth R. Woods ◽  
Nancy T. Flagg ◽  
Amanda Freeman

Although evaluation of the vulva of sexually abused girls using magnification with a colposcope or pediatric otoscope has become increasingly popular, the incidence of various genital findings in sexually abused and asymptomatic children has not been reported. A prospective study was carried out in which 20 genital findings from three groups of girls (mean age 4.8 ± 2.6 years) were analyzed. The three groups were (1) sexually abused girls (n = 119), (2) normal girls with no genital complaints (n = 127), and (3) girls with other genital complaints (n = 59). Group 1 was more likely than group 2 to have scars on the hymen or posterior forchette (9% v 1%, P = .002), increased friability of the posterior forchette (10% v 1%, P = .001), attenuated hymen (18% v 4%, P = .0003), and synechiae from the hymenal ring to the vagina (8% v 0%, P = .0009). Groups 1 and 3 were remarkably similar with the exception of erythema which was more common in group 3 (34% v 68%, P = .0001). Hymenal diameter was slightly greater in group 1 than 2 but not 3. Although genital findings distinguish some sexually abused girls from asymptomatic girls, many findings also occur in girls with other genital complaints, which suggests that many of these girls have also been molested or that vulvar inflammation may lead to some of these findings.


2003 ◽  
Vol 17 (3) ◽  
pp. 212-216 ◽  
Author(s):  
Adriene Mara Souza Lopes-Silva ◽  
José Luiz Lage-Marques

The purpose of this study was to evaluate in vitro the dentin permeability of the deciduous pulp chamber floor after employing 2-octyl cyanoacrylate and Er:YAG laser. Twenty four deciduous molars were used, divided into four groups. After chemical-surgical preparation each group received a different treatment: Group 1 - control, without treatment; Group 2 - the floor of the pulp chamber was covered with a fine layer of 2-octyl cyanoacrylate; Group 3 - the floor of the pulp chamber was irradiated with Er:YAG laser (250 mJ, 10 Hz for 30 seconds, 80 J of energy and 320 pulses), and covered with a fine layer of 2-octyl cyanoacrylate; and Group 4 - the floor of the pulp chamber was irradiated with Er:YAG laser set at the parameters already described. After that the specimens received application of 0.5% methylene blue, for 15 minutes. The teeth were cut, photographed, and the digitalized images were analyzed using the ImageLab program. The results obtained were submitted to statistical analysis. Group 4 (Er:YAG) presented the largest averages in percentage of dye penetration area (19.5%), followed by Group 1 (11.1%), Group 3 (1.4%) and Group 2 (0.2%). The experimental model allowed to conclude that the specimens conditioned with 2-octyl cyanoacrylate (Group 2) and Er:YAG laser associated to 2-octyl cyanoacrylate (Group 3) presented a decrease in permeability, and the specimens treated with Er:YAG laser (Group 4) presented an increase in permeability of the analyzed area.


Biomedicines ◽  
2019 ◽  
Vol 7 (1) ◽  
pp. 7 ◽  
Author(s):  
Sara Mohamed ◽  
Shahinaz Shalaby ◽  
Soumia Brakta ◽  
Lelyand Elam ◽  
Amro Elsharoud ◽  
...  

Background: Premature ovarian insufficiency (POI) is a challenging disease, with limited treatment options at the moment. Umbilical cord blood mesenchymal stem cells (UCMSCs) have demonstrated promising regenerative abilities in several diseases including POI. Materials and Method: A pre-clinical murine case versus vehicle control randomized study. Two experiments ran in parallel in each of the three groups. The first was to prove the ability of UCMSCs in restoring ovarian functions. The second was to prove improved fertility. A total of 36 mice were randomly assigned; 6 mice into each of 3 groups for two experiments. Group 1 (control), group 2 (sham chemotherapy), group 3 (stem cells). Results: In the first experiment, post-UCMSCs treatment (group 3) showed signs of restored ovarian function in the form of increased ovarian weight and estrogen-dependent organs (liver, uterus), increased follicular number, and a significant decrease in FSH serum levels (p < 0.05) compared to group 2, and anti-Mullerian hormone (AMH) serum levels increased (p < 0.05) in group 3 versus group 2. Immuno-histochemistry analysis demonstrated a higher expression of AMH, follicle stimulating hormone receptor (FSHR) and Inhibin A in the growing follicles of group 3 versus group 2. In the second experiment, post-UCMSCs treatment (group 3) pregnancy rates were higher than group 2, however, they were still lower than group 1. Conclusion: We demonstrated the ability of UCMSCs to restore fertility in female cancer survivors with POI and as another source of stem cells with therapeutic potentials.


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