Significant Increase In Platelet Count Research Articles

Fresh Frozen Plasma and Platelet Transfusion Practices in Neonatal Intensive Care Unit of a Tertiary Care Hospital.

Blood transfusion is an indispensable part of modern medical and surgical practices. More than 35% of critically ill patients receive transfusion of blood components during their intensive care unit stay. The aim of study is to obtain an information regarding the relationship of platelet concentrate (PC) and fresh frozen plasma (FFP) transfusion on clinical outcome of neonates admitted in neonatal ICU (NICU). This prospective cohort study was conducted from 1st November 2011 to 30th April 2013. The clinical history, blood component details and laboratory parameters were evaluated with clinical outcome. The neonates requiring PC and FFP transfusion were followed up in blood bank for laboratory parameters. Clinical parameters were noted from case file. During the study period, 291 neonates were admitted in NICU. 2 neonates had congenital malformations and thus, were excluded from the study. Of the remaining 289 neonates, 49 neonates received transfusion of platelets and/or FFP. The combined mean donor exposure for all components was found to be 1.48. The mean volume of PC and FFP transfused was 20ml and 30ml respectively. The mean pre- and post-transfusion platelet count was 34,000µl and 42,000µl respectively. The mean pre- and post-transfusion INR was 2.37 and 1.53 respectively. There was a significant increase in platelet count and decrease in INR in transfused neonates. However, no clinical benefit of PC and FFP transfusion seen on bleeding. Transfusion of PC and FFP has significant effect on laboratory parameters as compared to clinical parameter.

PS1467 EARLY RESULTS OF A PHASE II STUDY OF COMBINED RUXOLITINIB AND THALIDOMIDE IN PATIENTS WITH MYELOFIBROSIS

Background:Among the most frequent and challenging hematologic manifestations of myelofibrosis (MF) are anemia and thrombocytopenia, the presence of which portends an adverse outcome. Few effective modalities to address these cytopenias exist, particularly thrombocytopenia. Further, although Ruxolitinib (RUX) has demonstrated significant clinical efficacy in MF patients, RUX frequently results in anemia and thrombocytopenia. Thalidomide (THAL) is an immunomodulatory agent which has demonstrated demonstrated improvements in anemia and thrombocytopenia in patients with MF.Aims:We sought to examine whether the combination of RUX and THAL could result in improvement in both disease‐ and therapy‐related cytopenias, as well as improve overall disease response in patients with MF.Methods:We conducted a multicenter two stage phase II trial designed to assess the effect of RUX and THAL combination in subjects with myelofibrosis (NCT03069326). Patients taking RUX at the time of enrollment must have had less than PR per IWG‐MRT/ELN 2013 criteria. Patients must have been taking RUX for a minimum of 3 months. Treatment‐naïve patients received single‐agent RUX for 3 months (run‐in phase) per label, and went on to combination therapy if they achieved less then a PR. Each cycle of therapy was 28 days. Response assessment was evaluated according to the IWG‐MRT/ELN 2013 criteria. Platelet response criteria (in patients with baseline thrombocytopenia) included: Major response (≥75% increase in platelet count), Intermediate Response (50–74% increase) and Minor Response (25–49% increase). Adverse events were assessed using the NCI CTCAE v. 4.0. The primary endpoint was the proportion of treated subjects that achieved a response by IWG‐MRT criteria and by platelet response criteria.Results:A total of 25 patients are planned to be accrued. At the time of this writing, 24 have been accrued. The median age was 70 years (43–85). 9 patients had received prior therapies. 11 patients enrolled to the run‐in phase. 16 patients had received red blood cell transfusions prior to study enrollment. A significant increase in platelet count was observed by cycle 3 of therapy compared to baseline (Figure 1A, P < 0.05). An increase in Hgb was observed over successive cycles of combination therapy (Figure 1B). 12 of 21 accrued patients were evaluable for response assessment at the time of abstract submission. The overall response rate in these patients was 58.3% (7/12 patients). Four of 12 (33.3%) evaluable patients had stable disease. 1 patient progressed to accelerated phase. Clinical Improvement (anemia response, spleen response, or symptom response) occurred in 5 patients. Major platelet response was observed in 6 patients with baseline thrombocytopenia (Table 1). Grade 3/4 non‐hematologic adverse events regardless of attribution included; limb edema, diverticulitis, hypertension, syncope, and a thromboembolic event (one patient each).Summary/Conclusion:The combination of THAL and RUX has demonstrated a promising efficacy signal in this initial analysis of an ongoing phase II study, and appears to be well tolerated. Reductions in spleen size, symptom burden, and improvements in hemoglobin and platelet count were observed. Improvement in platelet count is particularly important given the lack of treatment modalities for thrombocytopenia in this patient population. These data indicate a potential role for this regimen in patients with cytopenias and/or persistent disease manifestations while on RUX. Updated data on duration of response and overall response rate in all accrued patients will be presented.image

Platelet number is positively and independently associated with glycated hemoglobin in non-diabetic overweight and obese subjects

Background and aimsA significant increase in platelet count may be a risk factor for atherosclerotic cardiovascular disease. This study investigates the association between platelet number and glucose metabolism, evaluated by glycated hemoglobin (HbA1c) levels, in a apparently healthy population represented by overweight and obese subjects with normal glucose and HbA1c levels. Methods and resultsAs many as 240 subjects, 177 women and 63 men, aged 18–70 years, were enrolled. Body mass index (BMI), waist circumference (WC), systolic and diastolic blood pressure levels, platelet count and fasting blood glucose, insulin, insulin resistance, HbA1c, uric acid, triglyceride, total cholesterol, high and low density lipoprotein cholesterol concentrations were evaluated. Concerning the univariate correlation analyses between platelets number and all other variables, platelet count was significantly (and positively) correlated only with HbA1c (P < 0.05) and female sex (P < 0.01). HbA1c (P < 0.05), female sex (P < 0.001), and diastolic blood pressure (P < 0.01), positively, and age (P < 0.05) and systolic blood pressure (P < 0.05), negatively, were significantly and independently associated to platelet count in a final multiple regression analysis. ConclusionThis is the first study showing a strong positive and independent relationship between HbA1c and platelet number in non-diabetic overweight and obese subjects.

Evaluating the effect of direct-acting agents on liver fibrosis, by real-time elastography, Fibroscan and FIB4 score in chronic HCV patients

Background One of the most important questions is what happens with liver fibrosis following a sustained virological response (SVR), although the current anti-HCV therapies were not designed to be antifibrotic. Liver biopsy was replaced by multiple noninvasive means, which were validated in chronic HCV patients, such as Fibroscan, seromarkers such as aminotransferase-to-platelet ratio index (APRI) and FIB4 scores, and new nonvalidated means such as real-time elastography (RTE). The aim of the study was to evaluate the early changes of liver fibrosis after direct-acting agents (DAAs) using these noninvasive means. Materials and methods This was a prospective study that included 200 chronic HCV-naive patients during the period spanning from December 2014 to January 2016. All patients received sofosbuvir − based treatment regimen (with or without pegylated interferon). They were evaluated using Fibroscan, RTE, APRI and FIB4 scores at the baseline and SVR24. Results All the studied patients showed a statistically significant decline in ALT, AST, liver stiffness (by Fibroscan), elasticity index (RTE), FIB4 score and APRI score, regardless of the response to DAAs. Moreover, there was a significant increase in platelet count from baseline to SVR24. The average improvement of the liver stiffness in different fibrosis stages was 22%. There was a positive correlation between stiffness score and all other fibrosis markers before and after treatment. Conclusion There was a significant improvement of liver stiffness after 12 weeks of end of treatment, regardless of the DAA regimen used, and regardless of the treatment outcome (response), as evidenced by Fibroscan, RTE, FIB4 and APRI scores.

Diagnostic value of platelet indices, carbohydrate antigen 19-9 and carcinoembryonic antigen in differentiating malignant from benign gastric ulcers

Objective To elucidate the value of platelet indices, carbohydrate antigen 19-9 (CA 19-9) and carcinoembryonic antigen (CEA) in differentiating malignant from benign gastric ulcers. Background Gastric cancer is one of the most common malignant diseases and benign gastric ulcer is a worldwide disease, responsible for substantial premature mortality. Clinical symptoms of early gastric cancer could not be used to distinguish gastric cancer from ulcers. Platelet indices: mean platelet volume (MPV) and platelet distribution width (PDW) are a group of platelet parameters investigated as platelet activation indicators. Patients and methods This prospective study included 150 patients: 30 patients with malignant gastric ulcer, 60 patients with benign gastric ulcer, and 60 healthy control participants. Upper endoscope with tissue biopsy and pathological evaluation, Helicobacter pylori stool antigen, platelet count, PDW, MPV, CEA, CA 19-9, computed tomography scan of the chest, abdomen, and the pelvis were assessed. Results Platelet count, MPV, PDW, CEA, and CA 19-9 were significantly higher in malignant gastric ulcer patients than benign ulcer patients and controls. MPV and PDW showed sensitivity, specificity, and area under the curve (93.3, 70 and 0.934% and 96.7, 86.7 and 0.966%, respectively) in predicting malignancy in gastric ulcer patients with improved diagnostic accuracy when combined with CEA and CA 19-9. Higher platelet count and PDW were significantly associated with advanced clinicopathological parameters of gastric cancer. Conclusion Changes in platelet indices are valuable markers in predicting malignancy in gastric ulcer patients. Significant increase in platelet count and PDW correlate and could be reliable markers, together with other markers of gastric cancer (CEA and CA 19-9), for clinicopathological features of malignant gastric ulcer.

Safety and Efficacy of Combined Ruxolitinib and Thalidomide in Patients with Myelofibrosis: Initial Results of a Phase II Study

Background: Among the most frequent and challenging hematologic manifestations of myelofibrosis (MF) are anemia and thrombocytopenia, the presence of which portends an adverse outcome. Few effective modalities to address these cytopenias exist, particularly thrombocytopenia. Further, although the FDA-approved JAK1/2 inhibitor Ruxolitinib (RUX) has demonstrated significant clinical efficacy in MF patients, RUX frequently results in anemia and thrombocytopenia. Thrombocytopenia in particular often results in dose attenuation of RUX. Thalidomide (THAL) is a first-in-class immunomodulatory agent. Studies of THAL in MF patients, alone and with prednisone, have demonstrated improvements in anemia and thrombocytopenia. We therefore sought to examine whether combination of RUX and THAL could result in improvement in both disease-related and therapy-related cytopenias, as well as improve overall disease response in patients with MF. Here we report initial analysis of this study (NCT03069326). Methods: We conducted a multicenter two stage phase II trial designed to assess the effect of RUX and THAL combination in subjects with primary, post-polycythemia vera, or post-essential thrombocythemia myelofibrosis. Patients taking RUX at the time of enrollment must have had less than PR per IWG-MRT/ELN 2013 criteria, or be refractory, to RUX single-agent therapy. Patients must have been taking RUX for a minimum of 3 months, and must have been on a stable dose of RUX for a minimum of 4 weeks immediately prior to enrollment. Treatment-naive patients received single-agent RUX for 3 months (run-in phase) per label, and went on to combination therapy if they achieved less then a PR per IWG-MRT/ELN criteria. Each cycle of therapy was 28 days. Response assessment was evaluated according to the IWG-MRT/ELN 2013 criteria. Platelet response criteria in patients with baseline thrombocytopenia (less than lower limit of normal) included: Major response (≥75% increase in platelet count), Intermediate Response (≥50% increase) and Minor Response (≥25% increase). Adverse events were assessed using the NCI CTCAE v. 4.0. The primary endpoint was the proportion of treated subjects that achieved a response by IWG-MRT criteria and by platelet response criteria. Results: A total of 25 patients are planned to be accrued. At the time of this writing, a total of 18 patients have been accrued. The median age was 70.5 years (47-85). 8 patients had received prior therapies other than RUX, including imetelstat, momelotinib, danazol, pomalidomide, darbepoetin alpha and sotatercept. 7 patients enrolled to the run-in phase. 14 patients received red blood cell transfusions prior to study enrollment. Evaluation of platelet count in patients with baseline thrombocytopenia demonstrated a significant increase in platelet count at cycle 3 of therapy compared to baseline (Figure 1A and B; P Conclusions: The combination of THAL and RUX has demonstrated a promising efficacy signal in this initial analysis of an ongoing phase II study, and appears to be well tolerated. Platelet count increases were observed in all patients who entered study with baseline thrombocytopenia, a response which appears to be maintained in the majority of patients observed 6 months after starting combination therapy. As well, anemia responses were observed in 3 of 5 evaluable patients. Collectively, these data indicate a potential role for this regimen in patients with anemia and/or thrombocytopenia, who otherwise have limited treatment options. Updated data on duration of response and overall response of all accrued patients will be presented. Disclosures Rampal:Constellation: Research Funding; Celgene: Honoraria; Incyte: Honoraria, Research Funding; Jazz: Consultancy, Honoraria; Stemline: Research Funding. Verstovsek:Italfarmaco: Membership on an entity9s Board of Directors or advisory committees; Celgene: Membership on an entity9s Board of Directors or advisory committees; Incyte: Consultancy; Novartis: Membership on an entity9s Board of Directors or advisory committees, Research Funding, Speakers Bureau. Stein:Celgene: Consultancy; Bayer: Consultancy; Agios: Consultancy; Daiichi Sankyo: Consultancy; Novartis: Consultancy; Pfizer: Consultancy. Kadia:Pfizer: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Novartis: Consultancy; Amgen: Consultancy, Research Funding; Takeda: Consultancy; Takeda: Consultancy; Celgene: Research Funding; BMS: Research Funding; Novartis: Consultancy; Abbvie: Consultancy; Amgen: Consultancy, Research Funding; Celgene: Research Funding; BMS: Research Funding; Jazz: Consultancy, Research Funding; Abbvie: Consultancy; Jazz: Consultancy, Research Funding. Mauro:Bristol-Myers Squibb: Consultancy; Novartis: Consultancy, Research Funding; Pfizer: Consultancy; Takeda: Consultancy. Pemmaraju:SagerStrong Foundation: Research Funding; daiichi sankyo: Research Funding; novartis: Research Funding; abbvie: Research Funding; cellectis: Research Funding; samus: Research Funding; Affymetrix: Research Funding; stemline: Consultancy, Honoraria, Research Funding; celgene: Consultancy, Honoraria; plexxikon: Research Funding. Bose:Blueprint Medicines Corporation: Research Funding; Astellas Pharmaceuticals: Research Funding; Incyte Corporation: Honoraria, Research Funding; Constellation Pharmaceuticals: Research Funding; Celgene Corporation: Honoraria, Research Funding; Pfizer, Inc.: Research Funding; CTI BioPharma: Research Funding.

Eltrombopag Plus Pulsed Dexamethasone As First Line Therapy for Subjects with Immune Thrombocytopenic Purpura (ITP)

▪Background: Eltrombopag is an oral thrombopoietin receptor agonist that has been licensed for use as second line therapy in ITP patients. For most subjects, platelet counts usually return to baseline within 2 weeks of eltrombopag discontinuation, however, up to 15% of subjects may maintain a prolonged response after discontinuation (BJH Volume 165(6) 2014 865-869). Therefore, we conducted a pilot study to evaluate whether a 12-week course of eltrombopag plus pulsed dexamethasone as first line therapy can increase the proportion of patients with prolonged response.Methods: This multicenter, single arm, open-label pilot study was performed on subjects with newly diagnosed ITP. Eligible subjects had confirmed ITP and platelet counts <30×109/L or platelet counts < 50×109/L and significant bleeding symptoms (WHO bleeding scale 2 or above). Patients must have no prior ITP treatment except platelet transfusions. All patients provided written informed consent before enrolment. This study was conducted in accordance with the Declaration of Helsinki.Eligibility criteria included isolated thrombocytopenia with exclusions of secondary immune or drug-induced thrombocytopenia, cancer and pregnancy related thrombocytopenia and virus induced thrombocytopenia. Bone marrow examination is not mandatory but must be consistent with peripheral platelet consumptions with no features of dysplasia, extensive fibrosis, aplasia, marrow infiltration if performed.Treatment consisted of eltrombopag 25-75mg daily according to platelet response for 12 weeks plus pulsed dexamethasone, 40mg daily for 4 consecutive days every 4 weeks for 1-3 courses. The primary endpoint was prolonged response defined as platelet counts > 50×109/L for more than 6 months without any ITP therapy after completion of 12-week therapy.The reported prolonged response rate of dexamethasone alone is around 25%, a sample size of 60 subjects will be required to detect a doubling of the prolonged response rate at a significant level of 0.05 with power of 0.9. Differences between prolonged responder and relapsed subject groups were analyzed by the Student's t-test. P values <0.05 were considered significant.Results:46 subjects were enrolled from February 2015 to July 2018. The median age was 40 years, range 18 to 81; 29 were female and 17 were male. Median platelet counts at baseline were 18×109/L, range 1 to 44×109/L. One subject withdrew consent before starting treatment. One was withdrawn because of protocol violations. Three subjects did not have significant increase in platelet counts during the entire 12 weeks treatment despite a maximum of eltrombopag 75mg daily and 3 courses of pulsed dexamethasone. One of them subsequently turned out to be amegakaryocytic thrombocytopenia. These 5 subjects were still included in the final analysis.Twenty-nine subjects had good initial response to treatment and completed at least 6 months follow-up (Fig 1), 19 of them had achieved the primary end point of platelet counts count> 50×109/L for more than 6 months after discontinuation of eltrombopag. The median platelet counts at 6 months were 150×109/L (range 53 to 371×109/L), Average eltrombopag dose was 36.8mg daily and average pulsed dexamethasone was 2.2 courses. Eleven subjects maintained prolonged response for 12 months or more.Four subjects are still receiving treatment and 8 subjects are still on the 6 months off-therapy observation period (median follow up is 12 weeks, range 4 to 21 weeks).Ten subjects relapsed after discontinuation of eltrombopag(Table 1). The median time to relapse was 47.8 days, range 15 to 148 days. Average daily eltrombopag was 45mg and average pulsed dexamethasone was 2.5 courses.So far, the prolonged response rate of 56 % (19/34) among 34 evaluable subjects is very encouraging. According to statistical analysis, seven more prolonged responders among the remaining 26 subjects (14 yet enrolled and 12 pending final evaluation) would suggest that 12-week of eltrombopag plus pulsed dexamethasone as first line therapy may significantly improve prolonged response rate in ITP patients. All subjects tolerated the treatment well and no Grade 3 or above adverse effects were reported.Conclusions: Eltrombopag plus pulsed dexamethasone is an effective and safe treatment for ITP as a first line therapy that can provide sustained prolonged response in adults. This therapy could be a new treatment option for ITP subjects. DisclosuresCheng:Novartis: Research Funding; BMS: Honoraria, Speakers Bureau; Astrazeneca: Honoraria, Speakers Bureau.

Splenectomy for hypersplenism with or without preoperative splenic artery embolisation

BackgroundAlthough splenectomy is considered the preferred treatment for hypersplenism, intraoperative blood loss remains a common occurrence. We prospectively compared the perioperative and clinical outcome of splenic artery embolisation (SAE) before open splenectomy (OS) versus OS alone in two concurrent patient groups.MethodsFrom January 2016 to January 2018, 50 patients with hypersplenism underwent combined SAE and OS (study group). For comparison, we considered 50 age- and gender-matched case controls undergoing OS without prior SAE during the same period (control group). Perioperative and clinical outcomes were compared between the two groups. Mann–Whitney U test, Student’s t-test, χ2 or Fisher’s exact test were used as appropriate.ResultsNo significant differences were found between the two groups for age, gender and laboratory investigations (p ≥ 0.250). Mortality rate was zero in both groups. No patients of the study group needed perioperative blood transfusion in comparison with patients of the control group (p = 0.003). A significant increase in platelet count was noted in the study group after SAE compared to the control group (p = 0.024). No significant differences between the two groups were observed for operating time, postoperative complications and postoperative stay (p ≥ 0.237).ConclusionWe confirm that preoperative SAE in patients who undergo splenectomy for hypersplenism significantly reduces the need for blood transfusion in comparison to splenectomy without prior embolisation. Preoperative SAE is a safe procedure with neither morbidity nor mortality.

Dexamethasone in HELLP syndrome: experience in Bolivia

Objective: To demonstrate the utility of dexamethasone, used according to the criteria of the attending physician, in patients with HELLP syndrome.Methods: This cross-sectional study was conducted in patients with HELLP syndrome and was based on the daily, real-life management of HELLP syndrome. Patients who received dexamethasone had it administered immediately after giving birth at a dosage of 8 mg every 8 hours for 72 hours, for a total of 72 mg. The analysis was conducted between patients who received corticosteroids and those who did not, with complete or partial HELLP.Results: There were 97 women who suffered complications from HELLP syndrome, there were 43 (44.3%) received dexamethasone. The groups were comparable except for the initial platelet count because this was the criterion used to divide the groups. In addition, the group without corticosteroids comprised more patients with partial HELLP. The platelet count shows that on the third day was similar in both groups, following a difference of more than 40,000 at the beginning of the study. The average platelet increase was 27,448 in the group without corticosteroids and 88,408 in the corticosteroid group; p = .001.Conclusions: This study demonstrates that the administration of postpartum dexamethasone at a dosage of 8 mg every 8 hours for 72 hours in HELLP syndrome is associated with a significant increase in platelet count.

Assessment of hepato-renal damage and genotoxicity induced by long-term exposure to five permitted food additives in rats.

The present study assessed the long-term daily administration of benzoic acid (BA), potassium sorbate (PS), chlorophyll (CPL), tartrazine (TAZ), and butylated hydroxyanisole (BHA) on hepato-renal changes and DNA damage in rats. Animals were orally administered with the 10 times of the acceptable daily intake (ADI) from each tested substance daily for 60 consecutive days. Blood, liver, and kidney samples were collected to evaluate hematological, biochemical, histopathological, and genotoxic alterations. The extent of liver and kidney damage was evaluated by comet assay and histopathologically. Significant reduction of leukocyte numbers and lymphocytes % in CPL- and TAZ-treated rats. However, significant increases in platelet count in all treated groups after 60days were detected. The levels of serum transaminases enzymes (ALT, AST), alkaline phosphatase (ALP), and creatinine were significantly increased in all treatments except with BHA group, but no substantial differences were found in urea after 60days. Aside from BHA, results of DNA damage revealed significant increases in tailed nuclei, tail moment, DNA% in the tail, and tail length in liver and kidney at different degrees. Moreover, the histopathological figures of liver and kidneys affirmed destructive and degenerative changes. The study indicates that most of the tested food additives may provoke genotoxicity and hepato-nephropathy, which could be serious for human health. Therefore, it is necessary to be informed about the hazardous effects of food additives and more attention should be focused towards using natural substitutes.

The Effects of Sample Transport by Pneumatic Tube System on Routine Hematology and Coagulation Tests.

Background Automation helps improve laboratory operational efficiency and reduce the turnaround time. Pneumatic tube systems (PTS) automate specimen transport between the lab and other areas of the hospital. Its effect on complete blood count (CBC) and coagulation is still controversial. Aim To study the effects of pneumatic tube system sample transport on complete blood count and coagulation parameters to compare them with hand delivered samples. Methods 75 paired samples for complete blood count and 25 paired samples for coagulation analysis were compared between samples sent via pneumatic tube system and hand delivered system. Results PTS showed significant decrease in red cell indices such as MCV and RDW and increase in MCHC. Other red cell parameters and WBC parameters showed no statistical significant difference. Statistically significant increase in platelet count was observed with PTS samples. However, these differences were clinically insignificant. No significant effect of PTS was found in PT and APTT samples compared to the hand delivered samples. Conclusion Despite statistically significant changes in RBC parameters such as MCV, RDW, and MCHC and platelet count, these changes were clinically insignificant. Hence, blood samples for CBC and coagulation assay can safely be transported via our hospital's PTS. However, further studies on platelet count are warranted to ensure safe transport and accuracy of the results.

High dose, short course prednisolone for acute idiopathic thrombocytopenic purpura (ITP) in children

Background: Immune thrombocytopenia (ITP) is a relatively benign and self-limiting condition. Though its dramatic presentation with skin or mucosal bleeds could be worrisome, the incidence of serious bleeding like intracranial hemorrhage (ICH) is relatively low (&lt;1%) occurs at a very low count of &lt;20,000 /mm3. The aim of the study was to compare a high dose, short course prednisolone with conventional Prednisolone therapy in the treatment of acute ITP of childhood.Methods: 20 cases and 18 retrospective controls with acute ITP were enrolled. The study group received 5mg/kg/day of oral prednisolone for four days. All the controls had received 2mg/kg/day of oral prednisolone for 14 days, tapered and stopped over the third week.Results: The study group was found to have significant decrease in clinical bleeding, (p=0.02), and significant increase in platelet count by day 3 of treatment (p=0.03) but no significant difference in platelet counts on day 7 of treatment (p=0.07) when compared with the control group.Conclusions: We conclude that the high dose short course oral prednisolone is significantly better than the conventional regimen in reducing clinically significant bleeding and raising the platelet count to safe levels within first 72 hours of therapy.

A randomized, double-blind, placebo-controlled, proof of concept study to assess the safety and efficacy of Carica papaya and Tinospora cordifolia leaf extract (Thrombobliss) in subjects undergoing chemotherapy treatment and subjects with systemic microbial infection and subsequent reduction in platelet count

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; &lt;span lang="EN-IN"&gt;Thrombocytopenia is defined as persistent decrease in the number of blood platelets. Thrombocytopenia usually serves as symptom for identifying hematologic malignancies, infectious diseases, auto-immune disorders and as common side effect of about 200 different disease types. There was neither a specific treatment available for thrombocytopenia, nor to increase the platelet count leading to mortality. Current methods are less effective and have their limitations. This study was conducted to prove that &lt;em&gt;Carica papaya &lt;/em&gt;and &lt;em&gt;Tinospora cordifolia &lt;/em&gt;leaf extract can increase the platelet count in study subjects with dengue, other microbial infections. &lt;/span&gt;&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; &lt;span lang="EN-IN"&gt;Totally 250 patients were randomized, subjects within inclusion criteria and exclusion criteria were randomly assigned, in a 1:1 ratio, to receive orally thrombobliss in a dose of 5 ml syrup twice daily or placebo for five consecutive days. Platelet count was monitored every day.&lt;/span&gt;&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; &lt;span lang="EN-IN"&gt;The result showed that there is increase in the platelet count from day 2 in median platelet data and more evident after 72 hours seen in both mean and median platelet count. Even in the cancer patients undergoing chemotherapy, there has been significant increase in platelet count. The statistical analysis of the data showed that there is a significant increase in platelet count and is statistical significant p&amp;lt;0.05. &lt;/span&gt;&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; &lt;span lang="EN-IN"&gt;This study showed that novel combination of &lt;em&gt;Carica papaya&lt;/em&gt; and &lt;em&gt;Tinospora cordifolia&lt;/em&gt; &lt;/span&gt;&lt;span lang="EN-IN"&gt;leaf extract&lt;/span&gt;&lt;span lang="EN-IN"&gt; effectively increases platelet count and can be used to treat thrombocytopenia. It is also evident that this combination is safe and effective in treating thrombocytopenia patients due to dengue and other microbial infection&lt;/span&gt;.&lt;/p&gt;

Platelet count and indoor cold exposure among elderly people: Across-sectional analysis of the HEIJO-KYO study.

BackgroundExcess mortality from cardiovascular disease during cold seasons is a worldwide issue. Although some physiologic studies suggests that platelet activation via cold exposure may cause an increased incidence of cardiovascular disease in winter, the influence of indoor cold exposure in real-life situations on platelet (PLT) count remains unclear.MethodsA cross-sectional study was conducted among 1095 elderly individuals. After obtaining a venous sample in the morning, indoor temperature of participants' home was measured every 10 min for 48 h. The mean indoor temperature while the participants stayed at home was calculated. All measurement was conducted during cold seasons (October to April) from 2010 to 2014.ResultsThe mean age of the 1095 participants was 71.9 years. They spent 87.3% of the day at home (20 h 27 min). A 1 °C lower daytime indoor temperature was associated with a significant increase in PLT count of 1.47 × 109/L (95% confidence interval, 0.39–2.56 × 109/L). Compared with the warmest tertile group (20.1 [standard deviation {SD}, 0.09] °C), the coldest group (11.7 [SD, 0.12] °C) showed a 5.2% higher PLT count (238.84 [SD, 3.30] vs. 226.48 [SD, 3.32] × 109/L; P = 0.01), even after adjusting for basic characteristics (age, gender, body weight, and smoking), antihypertensive medication, comorbidities (diabetes, estimated glomerular filtration rate), socioeconomic status (household income and education), day length, and outdoor temperature.ConclusionsWe found a significant and independent association between lower indoor temperature and higher PLT count among elderly in winter.

Mice Lacking the Inhibitory Collagen Receptor LAIR-1 Exhibit a Mild Thrombocytosis and Hyperactive Platelets

Leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is a collagen receptor that belongs to the inhibitory immunoreceptor tyrosine-based inhibition motif-containing receptor family. It is an inhibitor of signaling via the immunoreceptor tyrosine-based activation motif-containing collagen receptor complex, glycoprotein VI-FcRγ-chain. It is expressed on hematopoietic cells, including immature megakaryocytes, but is not detectable on platelets. Although the inhibitory function of LAIR-1 has been described in leukocytes, its physiological role in megakaryocytes and in particular in platelet formation has not been explored. In this study, we investigate the role of LAIR-1 in megakaryocyte development and platelet production by generating LAIR-1-deficient mice. Mice lacking LAIR-1 exhibit a significant increase in platelet counts, a prolonged platelet half-life in vivo, and increased proplatelet formation in vitro. Interestingly, platelets from LAIR-1-deficient mice exhibit an enhanced reactivity to collagen and the glycoprotein VI-specific agonist collagen-related peptide despite not expressing LAIR-1, and mice showed enhanced thrombus formation in the carotid artery after ferric chloride injury. Targeted deletion of LAIR-1 in mice results in an increase in signaling downstream of the glycoprotein VI-FcRγ-chain and integrin αIIbβ3 in megakaryocytes because of enhanced Src family kinase activity. Findings from this study demonstrate that ablation of LAIR-1 in megakaryocytes leads to increased Src family kinase activity and downstream signaling in response to collagen that is transmitted to platelets, rendering them hyper-reactive specifically to agonists that signal through Syk tyrosine kinases, but not to G-protein-coupled receptors.

Value of DNA content in comet tail in predicting changes in blood cell counts in workers exposed to benzene

Objective: To investigate the value of DNA content in comet tail (TailDNA) in predicting the changes in peripheral blood cell counts in workers exposed to benzene. Methods: In 2011, cluster sampling was used to select 150 male workers exposed to benzene in a petrochemical factory. Cubital venous blood and urine samples were collected for routine blood rest, comet assay, and measurement of s-phenylmercapturic acid (SPMA) and urine creatinine. The population was divided into groups according to urinary SPMA or TailDNA, and routine blood test results within 3 years were collected to analyze the changes in blood cell counts. Results: The low-SPMA group had significantly higher white blood cell and neutrophilcounts in all years than the high-SPMA group (P<0.05) . The low-Tail DNA group had a significant increase in platelet count from 2012 to 2014 (P<0.05) , while the high-Tail DNA group had no significant change (P>0.05) . During the 4-year period, the high-TailDNA group had a significantly lower red blood cell count than the low-TailDNA group (P<0.05) . The high-TailDNA group showed a gradual reduction in white blood cell count over time (β=-0.113, P<0.05) , and the low-TailDNA group showed no trend of the reduction in white blood cell count (P>0.05) . Conclusion: TailDNA can be used to predict the changes in blood cell counts in workers exposed to benzene.

Juglans regia Seeds have Effects on Platelets and Peripheral Fat Deposition in the Aorta and Heart of C57BL/6J Mice Fed with Normal and High Fat Simple Carbohydrate Diet

Background: Consumption of nuts particularly walnuts has been widely recommended for lowering the risk of coronary heart disease; however, very few studies have evaluated the potential unfavourable effects that Walnut seeds might have in vivo. Objective: To investigate the long-term effects of Juglans regia seed supplementation in specially formulated feed when fed to developed mice model. Method: C57BL/6J male mice were divided into four groups, labelled, C (control), T (High Fat Simple Carbohydrate- HFSC), Cw (control + walnut) and Tw (HFSC+ walnut) based on diet. Four mice from each group were sacrificed at the end of the first and fifth month respectively. Blood samples were collected every month. Bleeding time, blood platelet number and morphology were studied. Histopathological analysis of heart and aorta were also performed. Results: Groups Cw and Tw showed a significant increase in platelet count; however, platelet activation was not detected. There was a trend to an increase in bleeding time in group Cw. Expanded lumen diameter of the aorta was observed in Cw and Tw mice initially, however, it was found to constrict by the end of the study. A large amount of peripheral fat deposition in the aortas of Cw and Tw was observed, which increased through the course of the experiment. Conclusion: Kashmiri walnut seed supplementation was found to reduce the signs in shape change of platelets as well as increase platelet number with a trend to an increased bleeding time. This observation could be of medical interest. Histopathological analysis of heart and aorta showed lipid sequestration which merits further investigations. Keywords: Kashmiri walnut seed, platelet number, platelet activation, histopathology, heart, aorta.

Effect of prewarming EDTA blood samples to 37°C on platelet count measured by Sysmex XT-2000iV in dogs, cats, and horses.

Pseudothrombocytopenia secondary to platelet clumping is a common cause of preanalytic error for platelet counts in dogs, cats, and horses. In human beings, it is suggested that prewarming blood samples to 37°C prior to hematology analysis will reduce platelet clumping. The purpose of the study was to evaluate the effect of prewarming EDTA blood samples to 37°C on measured platelet counts and other hematologic variables. The EDTA blood samples from dogs, cats and horses submitted to the clinical pathology laboratory at the University of Cambridge were included. Complete blood cell counts performed using a Sysmex XT-2000iV hematology analyzer were done on samples at room temperature (approximately 22°C) and following warming of the samples to 37°C in a water bath. The Wilcoxon signed rank test was used to compare hematologic variables, including platelet count, before and after sample warming to 37°C. Data are presented as median (25(th) , 75(th) percentile) increase. Blood samples from 39 dogs, 19 cats, and 10 horses were included. Sample warming to 37°C resulted in a statistically significant increase in platelet counts in dogs (11 [-2, 30] ×10(9) /L), cats (36 [14, 84] ×10(9) /L), and horses (42 [31, 79] ×10(9) /L). Sample warming did not significantly affect other hematologic variables. Prewarming EDTA blood samples to 37°C prior to hematologic analysis increased platelet counts overall in canine, feline, and equine blood, but did not abrogate platelet clumping and pseudothrombocytopenia fully in some cases. Furthermore, true pseudothrombocytopenia was not confirmed in these animals.

Cryopreserved platelet concentrate transfusions in 43 dogs: a retrospective study (2007-2013).

To clinically characterize a group of thrombocytopenic dogs that received cryopreserved platelet concentrate (cPC) transfusion, assess efficacy of cPC treatment in improving patient outcome, and compare treated dogs to a control population of thrombocytopenic dogs that did not receive cPC transfusions. Retrospective study. University teaching hospital. Eighty-six client-owned dogs (43 in treatment group, 43 in control group). None. Medical records of thrombocytopenic dogs that received cPC transfusions and those of thrombocytopenic dogs that did not receive cPC (control population) from January 2007 through March 2013 were reviewed. Dogs receiving cPC were statistically more likely than controls to have a platelet trigger for cPC transfusion (P = 0.01), lower platelet count (P = 0.009) and hematocrit at presentation (P = 0.001), and lower hematocrit after cPC (P = 0.02). Although there was a statistically significant increase in platelet count from pre- to post-cPC transfusion (P = 0.002), cPC was not found to be effective in improving clinical bleeding or increasing survival compared to the control group. No other characteristics were statistically different between groups. No dogs receiving cPC had an acute transfusion reaction during hospitalization. In the population described in this study, cPC was not found to increase survival, but was well tolerated. Controlled, prospective studies are necessary to determine indications for and efficacy of cPC transfusions.

Steroid-refractory immune thrombocytopenia in the era of the new thrombomimetic drugs: is there still a role for rituximab?

TO THE EDITOR: Although corticosteroids and splenectomy represents the main therapeutic strategies [1,2] for immune thrombocytopenia (ITP), some steroid-refractory patients may be unsuitable for the surgical procedure and therefore require alternative treatment options currently available, such as rituximab [2,3] and thrombomimetic drugs [4,5]. Although rituximab is usually used in refractory ITP patients who have failed multiple previous treatments [3], its role in the era of thrombomimetic drugs represents an open question. Herein, we would like to provide our perspective on this topic in the light of our clinical experience, reporting indications to rituximab in a small series of consecutive steroid–refractory/relapsed ITP patients treated with rituximab. There were seven patients (4 male) with a median age of 38 (19-43) years. Rituximab (4 wk infusions of 375 mg/m2) was given after 50 (6–84) months from the date of ITP diagnosis. One patient suffered from active bleeding requiring platelet transfusions and was refractory to all measures, including thrombomimetic agents (eltrombopag and then romiplostim); he achieved a complete response (CR) with rituximab and was soon after splenectomized, having taken into account the high risk of recurrence and his severe bleeding tendency. Splenectomy was offered to four other patients who refused; in the remaining two patients, splenectomy as well as thrombomimetic agents were not indicated given suspected underlying autoimmune disorders and thrombophilic states. All patients who received rituximab achieved a fast response; indeed, a significant increase in platelet count was recorded early during the course of treatment: one week after the first rituximab infusion in five and after two weeks in the remaining two patients respectively. All patients maintained a sustained CR; six did not necessitate further therapy whereas one was splenectomized soon after the response to rituximab. In all patients, CR was durable and persisted after a median follow-up of 19 months (range, 6-64). No patients relapsed. Based on these findings, rituximab therapy allowed, in our experience, for long-lasting remission in patients with relapsed or refractory ITP, with a good safety profile. All patients but one, who successfully received rituximab as a bridge to splenectomy, refused or presented contraindications for the surgical procedure. Although thrombopoietin agonists, such as eltrombopag or romiplostim, in light of their high efficacy, have substantially changed the clinical scenario and the management of steroid refractory ITP [4,5], this treatment option requires prolonged administration, namely for the remainder of one's life and without a predictable suspension of therapy. Indeed, the option of a potentially life-long treatment with thrombopoietin agonists was offered to patients who refused splenectomy after a thorough explanation of the expected benefits and possible disadvantages from the therapy. The long-lasting and dependent therapy, virtually to be administered for life, was the main reason patients sought out an alternative treatment; they wanted to induce a prolonged remission of their disease without needing to depend on the therapy for life. This concern, in the setting of patients who refuse or are unsuitable for splenectomy, can allow them to find a therapy the administration of which can be predictable and carried out in limited time. This includes rituximab, the role of which is yet to be defined for selected indications even in the era of the new thrombomimetic medications.