Significant Improvement In Platelet Count Research Articles

Improvement of Platelet Count after Helicobacter Pylori Screening and Eradication in Immune Thrombocytopenia Patients: A Randomized Open-Label Study

Background:Helicobacter pylori (HP) has been known as a secondary cause of immune thrombocytopenia (ITP). Previous studies have demonstrated platelet count improvement after HP eradication in ITP. However, the impact of HP screening in adults with ITP remains unclear. Methods: We conducted a randomized open-label study to evaluate the benefit of HP screening to improve platelet count in ITP patients. Persistent or chronic ITP patients with ≥ 18 years of age who had platelet count below 150 x109/L were eligible. Patients were excluded if there were HIV or hepatitis C virus infection, active cancer, history of HP eradication within 1 year, or antibiotics/bismuth use within one month before enrollment. Patients were allocated in a 3:1 ratio to the HP screening arm or non-screening arm. Patients in the HP screening arm underwent 2 methods of HP screening: urea breath test (UBT) and HP serology test (Assure® H. pylori Rapid Test). Patients who had positive HP results by either test were received HP eradication with a 14-day course of proton pump inhibitor-based triple therapy. Treated patients were subsequently confirmed HP eradication by stool antigen test at 1 month. Dose modifications of treatments for ITP were allowed according to the treating physician's decision. Platelet count and 3-month cumulative dose of prednisolone were measured at baseline, 3 months, and 6 months. Quality of life using the Thai version of EQ-5D-5L was assessed at baseline and 6 months. The primary outcome was the mean difference in platelet count at 6 months. Key secondary outcomes were the prevalence of HP infection in adult ITP patients and improvement of EQ-5D-5L score at 6 months. Other outcome was the diagnostic accuracy of the HP serology test. Results: A total of 64 patients were enrolled. Forty-nine patients were assigned to the HP screening arm and 15 patients to the non-screening arm. Mean age was 47.2 years (SD 15.7). Fifty patients (78%) were female. Forty patients (62.5%) were using prednisolone with a mean dose of 8.5 mg/day. Mean platelet count at baseline was 73.8 x109/L (SD 29.5). Baseline characteristics were balanced (Table 1). All of the patients, except one, in the HP screening arm completed 2 methods of screening. Twenty-three of 48 patients had HP positive results by UBT, as a result, the prevalence of HP was 47.9%. All HP-positive patients completed an HP eradication course. One patient had a positive result of stool antigen test after HP eradication, which was successfully eradicated with levofloxacin-based treatment. At 6 months follow-up, patients in the HP screening arm had a significant improvement in platelet count as compared to baseline with a mean difference of 21.8 x109/L (95% CI 22.2 - 41.3, p=0.030) (Table 2). In addition, the EQ-5D-5L score revealed a significant improvement at 6 months as compared to baseline in the HP screening arm with a mean difference of 4.2 points (95% CI 0.8 - 7.6, p=0.016) (Table 2). Patients in the non-screening arm had no significant changes in platelet count or EQ-5D-5L score. A 3-month cumulative dose of prednisolone and dose adjustments of concomitant ITP treatments at 6 months in both arms were not significantly changed. Of 23 UBT-positive patients, only 11 patients had positive results with HP serology. All 25 UBT-negative patients also had negative results with HP serology. The sensitivity and specificity of the HP serology test were 47.8% and 100%, respectively. Conclusion: The prevalence of HP infection in adult Thai ITP patients was 47.9%. HP screening is effective in the improvement of platelet count and quality of life at 6 months in adult ITP patients with platelet count below 150 x 109/L. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Factors Associated with Significant Platelet Count Improvement in Thrombocytopenic Chronic Hepatitis C Patients Receiving Direct-Acting Antivirals.

To clarify the predictive factors of significant platelet count improvement in thrombocytopenic chronic hepatitis C (CHC) patients. CHC patients with baseline platelet counts of <150 × 103/μL receiving direct-acting antiviral (DAA) therapy with at least 12-weeks post-treatment follow-up (PTW12) were enrolled. Significant platelet count improvement was defined as a ≥10% increase in platelet counts at PTW12 from baseline. Platelet count evolution at treatment week 4, end-of-treatment, PTW12, and PTW48 was evaluated. This study included 4922 patients. Sustained virologic response after 12 weeks post-treatment was achieved in 98.7% of patients. Platelet counts from baseline, treatment week 4, and end-of-treatment to PTW12 were 108.8 ± 30.2, 121.9 ± 41.1, 123.1 ± 43.0, and 121.1 ± 40.8 × 103/μL, respectively. Overall, 2230 patients (45.3%) showed significant platelet count improvement. Multivariable analysis revealed that age (odds ratio (OR) = 0.99, 95% confidence interval (CI): 0.99–1.00, p = 0.01), diabetes mellitus (DM) (OR = 1.20, 95% CI: 1.06–1.38, p = 0.007), cirrhosis (OR = 0.66, 95% CI: 0.58–0.75, p < 0.0001), baseline platelet counts (OR = 0.99, 95% CI: 0.98–0.99, p < 0.0001), and baseline total bilirubin level (OR = 0.80, 95% CI: 0.71–0.91, p = 0.0003) were independent predictive factors of significant platelet count improvement. Subgroup analyses showed that patients with significant platelet count improvement and sustained virologic responses, regardless of advanced fibrosis, had a significant increase in platelet counts from baseline to treatment week 4, end-of-treatment, PTW12, and PTW48. Young age, presence of DM, absence of cirrhosis, reduced baseline platelet counts, and reduced baseline total bilirubin levels were associated with significant platelet count improvement after DAA therapy in thrombocytopenic CHC patients.

A Phase I Study Of The Oral Btk Inhibitor ONO-4059 In Patients With Relapsed/Refractory and High Risk Chronic Lymphocytic Leukaemia (CLL)

IntroductionThe B-cell receptor (BCR) pathway plays a central role in signal transduction pathways that regulate survival, activation, proliferation and differentiation of B-lineage lymphoid cells. Bruton's tyrosine kinase (Btk) is a critical kinase in BCR signal transduction and recent studies support that targeting Btk is effective in the treatment of B-cell malignancies. ONO-4059 is a highly potent and selective oral Btk inhibitor with an IC50 in the sub-nmol/L range that has demonstrated anti-tumour activity in several pre-clinical models (Yasuhiro T et al, AACR 2013). MethodsThis Phase I study was initiated to determine the safety, tolerability, dose-limiting toxicity (DLT), pharmacokinetics and pharmacodynamics of ONO-4059 given as monotherapy to patients with relapsed/refractory, high risk CLL for whom no therapy of higher priority was available. In this safety-driven, dose-escalating 3+3 design, ONO-4059 was administered as an oral, daily dose (flat dose) given continuously initially for up to 6 months, with the option of additional dosing up to 2 years. We present the safety and efficacy data on 16 evaluable patients, median age 67 yrs (range 40-77), with high risk cytogenetics (17p [38% (6/16)] or 11q [19% (3/16)], 12/16 displaying unmutated IgVH status, 8/16 displaying TP53 mutation), median baseline tumour burden 4,534mm2 [461-14,492 mm2]. Patients had received a median of 3 prior therapies [2-7], including fludarabine (16/16) and rituximab-containing therapy (13/16). Baseline median haematology parameters included hemoglobin 11.3 g/dL [8.5 -15.2], WBC 56.02 x 109/L [2.06-394.74], platelets 95.5 x 109/L [23-173], lymphocytes 50.6 x 109/L [0.5-390], neutrophils 2.46 x 109/L [0.5-11.1]. Patients were treated with ONO-4059 at doses ranging from 20mg-320mg (cohorts 1-5) and the study is currently ongoing with additional dose escalation cohorts to be completed. ResultsONO-4059 was found to be well tolerated, with no dose limiting toxicities (DLTs). A total of 15 ONO-4059-related Grade 1 (n=10) and 2 (n=5) adverse events were reported in 8 out of 16 patients, including one event of diarrhea (G2) and two events of rash (G1, G2). ONO-4059-related G3 or G4 haematological toxicities were infrequent and independent of dose; neutropenia (n=3 [G4 x1, G3 x 2]), febrile neutropenia (n=1 [G3]) occurring in 2 patients at the 20mg dose level only. Only one Grade 3 ONO-4059-related non-haematological event (pyrexia) was reported. Infection rate was low with only one event of bronchitis reported (G2, related). Three ONO-4059-related SAEs were reported in two patients (febrile neutropenia [G3] and pyrexia [G3] in one patient [20 mg]; rash [G2] in another [80 mg]). The pharmacokinetics of ONO-4059 reflects rapid absorption and elimination, a half-life of ∼6 hours, a dose dependent increase in exposure with no accumulation of ONO-4059 exposure and low inter- or intra-patient variability; with Btk occupancy in peripheral blood (as measured by phosphorylated Btk) being maintained for at least 24 hours across all dose levels.Responses have occurred across all dose levels. All patients experienced rapid reductions in lymphadenopathy observed early in treatment, between D1-D28 of the first cycle, accompanied by an increase in absolute lymphocyte count in some, but not all patients. Best overall response rate according to IWCLL criteria (including modified PR with lymphocytosis) was 70% [based on CT-scan and P/E for 7/10 evaluable patients]; with 2 PR, 5 PR with lymphocytosis (For 7 responding patients, median reduction of lymph nodes was 67% [Range 61%-79%]), 2 SD, 1 patient PD (possible Richter's). All patients showed an improvement in haematological parameters after ≥3 months on treatment. Patients (ONO-4059 20mg [1pt] and 40mg [1pt] respectively) who had grade 3 thrombocytopenia at study baseline had a significant improvement in platelet count (>100 x 109/L) with ONO-4059 treatment. To date, 15 of 16 patients remain on treatment with a median progression-free survival of 99 days [Range 8-268].In conclusion, ONO-4059 is a highly potent and selective oral Btk inhibitor with a favourable safety profile along with promising efficacy in this heavily pre-treated population, with responses observed in relapsed, refractory and 17p deleted patients. Disclosures:Salles:Janssen: Honoraria; Gilead: Honoraria; Celgene: Honoraria. Karlin:Janssen: Honoraria; Celgene: Honoraria. Morschhauser:ONO Pharma: Honoraria; Roche: Honoraria; Celgene: Honoraria; Mundipharma: Honoraria. Dyer:ONO Pharma: Honoraria, Research Funding. Hutchinson:ONO Pharma: Research Funding. Fegan:ONO Pharma: Honoraria. Cartron:ONO Pharma: Honoraria. Knurowski:ONO Pharma: Consultancy. Saunders:ONO Pharma: Consultancy; Pharmacyclics: Consultancy. Wright:ONO Pharma: Consultancy. Honda:ONO Pharma: Employment. Mazur:ONO Pharma: Consultancy. Yoshizawa:Ono Pharma: Employment. Kawabata:Ono Pharmaceutical Co., Ltd.: Employment. Birkett:Ono Pharma UK: Employment.

Baseline thrombopoietin level is associated with platelet count improvement in thrombocytopenic chronic hepatitis C patients after successful direct-acting antiviral agent therapy

BackgroundThrombocytopenia can rapidly improve in chronic hepatitis C (CHC) patients receiving direct-acting antiviral agents (DAA). The role of baseline (BL) thrombopoietin (TPO) in this phenomenon is unclear.MethodsFrom June 2016 to February 2019, a total of 104 CHC patients receiving DAA, with a sustained virologic response and BL thrombocytopenia, at Dalin Tzu Chi Hospital, were enrolled in this retrospective study. Significant platelet count improvement and platelet count improvement ratio were analyzed for correlation with BL TPO.ResultsThis cohort included 40 men (38.5%). Seventy-two (69.2%) patients had advanced fibrosis. The platelet count [median (range)] increased from 110.5 (32–149) × 103/µL at BL to 116.5 (40–196) and 118.0 (35–275) × 103/µL at end of treatment (EOT) and 12 weeks after EOT (P12), respectively, (EOT vs. BL, P < 0.001; P12 vs. BL, P < 0.001). BL TPO was positively correlated with significant platelet count improvement (P < 0.001), platelet count improvement ratio at EOT (P = 0.004), and P12 (P < 0.001). The area under the receiver operating characteristic curve and optimal cutoffs (pg/ml) were 0.77 (95% confidence interval, 0.67–0.86) and 120, respectively, for significant platelet count improvement prediction. The sensitivity, specificity, and accuracy were 88.6%, 71.7%, and 78.8%, respectively.ConclusionsBL TPO level might be a useful marker for predicting significant platelet count improvement in thrombocytopenic patients after successful DAA therapy.

Asparagus racemosus Root Extract and Isoprinosine Exhibits Radio-mitigating Activity against Ionizing Radiation-induced Detrimental Effects in Swiss Albino Mice

Objectives: To evaluate the radio – mitigating property of Asparagus racemosus root ethanolic extract and Isoprinosine against ionizing radiationinduced harmful effects in Swiss albino mice. Methods: The experimental animals were exposed to sublethal dose (6 Gy) of whole-body electron beam radiation and administered orally with Asparagus racemosus root ethanolic extract (ARE – 200mg/kg bd. wt) and Isoprinosine (IPR – 400 mg/ kg bd. wt) for 15 consecutive days. After the experimental period, the animals were sacrificed. Blood and liver tissue were collected. Blood sample was used for assessment of hematological parameters, serum was used for biochemical analysis (lipid peroxidation, total antioxidant capacity) and the level of pro-inflammatory cytokines was determined in the liver homogenate. Results: The radiation control group showed a statistically significant reduction in the hematological parameters. IPR post-treatment group showed a substantial increase in the percentage of lymphocytes and monocytes. ARE and IPR post-treatment caused a statistically significant improvement in platelet count. Irradiation of mice resulted in a significant elevation in lipid peroxidation. Post-treatment of mice with ARE and IPR caused significant depletion in lipid peroxidation. The serum total antioxidant capacity (TAC) in the irradiated group decreased significantly. Administration of ARE to the animals after irradiation caused a significant elevation in TAC level. IPR post-treatment did not show any substantial change in the reduced level of TAC. The cytokines level in the liver homogenate of irradiated mice showed that Interleukin -2 (IL-2), Tumor Necrosis Factor alpha (TNF-α) and Interferon gamma (IFN-γ) significantly increased after radiation exposure. Administration of ARE and IPR after irradiation significantly reduced the levels of IL-2 and TNF-α in the posttreatment groups. An elevated level of IFN-γ was reduced considerably in the IPR post-treatment animals. Conclusion: Asparagus racemosus root ethanolic extract and Isoprinosine exhibit radio-mitigating effects against electron beam radiation - induced detrimental effects. This occurs through several mechanisms, such as free radical scavenging, anti-inflammation, facilitation of repair activity, regeneration of hematopoietic cells and affecting to molecular levels. Key words: Asparagus racemosus, Isoprinosine, Radio-mitigation, Ionizing radiation.

Effect of sofosbuvir plus daclatasvir on virological response and liver function tests as a line of treatment for HCV related cirrhosis (a prospective cohort study)

BackgroundPatients with chronic HCV infection are the most in need for antiviral treatment. However, patients with cirrhosis exhibit difficulty with direct antiviral agents (DAA) treatment. We intended to evaluate the virological response of DAA in HCV-related cirrhosis treatment as well as its effect on liver function tests and other laboratory tests. Our study was a prospective cohort study of 240 patients with HCV-related liver cirrhosis. Those patients were consecutively selected from Gastroenterology and Hepatology out-patient clinic at Aswan University Hospital. They were subjected to the DAA regimen (sofosbuvir 400 mg plus daclatasvir 60 mg).ResultsThe study showed a rapid decrease in HCV viral load; HCV RNA was undetectable in 65% of patients on 4th week of treatment and in 88.3% of patients on 8th week of treatment. It was undetectable in 100% of patients on 12th week of treatment and remained unchanged until therapy was completed (24 weeks). The SVR (sustained virological response) was 96.3%. Other laboratory tests demonstrated that serum level of alanine aminotransferase (ALT) decreased rapidly to normal limits on 4th week of treatment and remained within normal range until 12th week post-treatment. Significant improvements in serum albumin, total bilirubin, INR, and alpha-fetoprotein (AFP) levels were observed during and after treatment. Child-Pugh score showed a significant improvement post-treatment. We also observed a significant improvement in platelet count during and after treatment.ConclusionThe DAA regimen (sofosbuvir 400 mg plus daclatasvir 60 mg) for treatment of HCV-related liver cirrhosis can achieve satisfactory virological response (SVR more than 96%). It can lead to improvement of serum ALT, serum albumin, total bilirubin, INR, AFP, and Child-Pugh score and also increase in platelet count after treatment.

Abstract No. 396 Partial splenic artery embolization: a nonsurgical approach to hypersplenism

Partial splenic embolization (PSE) is a novel percutaneous interventional method and an alternative to open and laparoscopic splenectomy because of its minimally invasive nature and fewer complications. PSE can be particularly useful in high-risk surgical patients allowing preservation normal splenic function and thus avoiding the risk of infections. Retrospective study of 14 patients (8 males and 6 females) in the age group of 10 to 49 years with hypersplenism (massive splenomegaly and Platelet count 10000-60000) referred to IR department for partial splenic artery embolization between October 2013 and October 2018. Baseline data was documented. PSE was performed though transfemoral approach using PVA Particles (355 to 500 microns) sparing one or two sectors to retain 20- 30% of the blood supply and to achieve ∼70% splenic infarction. Intra-arterial gentamycin was given to all patients after splenic artery catheterization. Follow-up for splenic size and complete blood counts were done at one month and six months post procedure and were analyzed. All patients achieved a splenic infarction rate of more than 50% with a significant improvement in platelet count. All patients had a well-maintained splenic function. Post-embolization syndrome was noted in 8 patients which was managed conservatively. There were no major complications identified in any of the patients PSE is a safe and minimally invasive technique having a good long-term effect on the hematological parameters, minimal complications and preservation of normal splenic function.

A Randomized Open Label Parallel Group Clinical Study to Evaluate the Efficacy and Safety of Clevira in Fever of Viral Origin

Objective: To evaluate the efficacy and safety of Clevira, an ayurvedic formulation in fever of viral origin. Methods: This was a prospective, randomised, multicentre, open label, parallel group interventional clinical end point study. Patients attending general outpatient department, were screened for viral fever including Dengue by using the haematological, Biochemical and microbiological anti body assay for Dengue and NS1 (Non-structural protein) antigen testing. Forty eight patients who satisfied the selection criteria were enrolled in the study. Participants were randomized into 4 groups with 12 patients in each group. Patients were given standard treatment. In addition, Tab. Clevira of Apex laboratories Pvt. Ltd., was administered to test groups. Results: There is highly significant improvement (P&lt;0.001) in the subjects Temperature, fever score, arthralgia score, Myalgia score, Headache and loss of appetite, suggesting a good Analgesic and anti pyretic activity of Clevira. There is a significant improvement in platelet count in the Clevira treated group (P&lt;0.01) when compared to the control group, proving its efficacy in treating thrombocytopenia. The improvement (P&lt;0.01) in the WBC count in the Clevira treated group depicts the anti viral property of Clevira. The overall quality of life was better in Clevira treated group compared to the control group. There were no serious adverse events reported. Conclusion: Clevira is safe and efficacious in reversing thrombocytopenia and thus normalizing the platelet counts and relieving the clinical signs and symptoms (fever, myalgia, arthralgia, headache) of Viral fever associated with thrombocytopenia and other cases of viral fever without thrombocytopenia. Clevira is having good anti-viral, antipyretic, analgesic and immunomodulatory property. Hence, Clevira should be used as an add on drug in patients with viral fever with or without thrombocytopenia for a rapid recovery without any adverse effects.

Impact of Helicobacter pylori Eradication Therapy on Platelet Counts in Patients With Chronic Idiopathic Thrombocytopenic Purpura.

This study was a before and after clinical evaluation of Helicobacter pylori eradication on platelet counts in a group of 23 patients with chronic Idiopathic (Autoimmune) thrombocytopenic purpura (CITP). H. pylori infection was identified in patients by a 13C-urea breath test and confirmed by an H. pylori stool antigen test. Eradication was conducted in patients testing positive. Infected (n = 10) and uninfected (n = 13) patient groups did not differ with respect to age, gender, history of previous splenectomy, treatment with anti-D, current treatment with corticosteroids, or initial platelet counts. H. pylori eradication was successful in eight infected CITP patients, with two patients not responsive to treatment. Compared to the uninfected group, patients in the infected group who responded to eradication therapy had significantly increased platelet counts after six months (56.2 ± 22.2 vs. 233 ± 85.6 ×103 million cells/L; P < 0.01), whereas platelet counts in the non-responding patients and uninfected group did not differ after this period of time. H. pylori eradication promotes significant platelet count improvement in patients with CITP. Thus, all patients with CITP should be tested and treated for H. pylori infections.

Frequency of Helicobactor pylori infection among adult patients with chronic immune thrombocytopenia: A Pakistani Perspective

Objective: Many studies have reported an association between chronic immune thrombocytopenia and Helicobactor pylori infection. Significant improvement in platelet count is seen after eradication therapy. We looked for the frequency of H. pylori infection in immune thrombocytopenia and clinico-hematological features. Material and Method: A prospective case-control study was conducted from January 2009 to December 2011. One hundred and ten chronic immune thrombocytopenic patients and 40 control subjects were enrolled. H. pylori infection was documented by H. pylori stool antigen enzyme immunoassay method. Results: H. pylori infection in immune thrombocytopenic patients was seen in 45 cases (40.9%) and in 24 (60%) controls; not significant statistically. No significant differences were seen in H. pylori positive and negative patients with respect to maternal characteristics and clinical features except for mean platelet count, which was lower in H. pylori negative group (P = 0.035). Conclusion: Unlike many related studies, we found no significant difference between the frequencies of cases versus controls. Degree of thrombocytopenia appears more marked in H pylori negative patients.

Eculizumab (ECU) in Atypical Hemolytic Uremic Syndrome (aHUS) Patients with Progressing Thrombotic Microangiopathy (TMA): 2-Year Data.

AbstractAbstract 2084 Introduction:aHUS is a rare, life-threatening genetic disease marked by chronic, uncontrolled complement activation leading to TMA and subsequent kidney and vital organ damage. 33%–40% patients (pts) die or progress to end-stage renal disease after the first clinical manifestation. In a phase 2 extension trial (64-week [wk] median ECU duration), pts receiving the terminal complement inhibitor ECU had a highly significant increase in platelet count (98×109/L; P=0.0001)—a measure of TMA improvement—and 4 pts (80%) discontinued prior dialysis by data cutoff. Here we report 2-year (y) results. Methods:Pts ≥12 y with aHUS and progressing TMA enrolled in an open-label, phase 2 trial with long-term extension. Pts had ≥4 plasma exchange/infusion (PE/PI) sessions in the wk before screening. ECU was administered at 900 mg/wk × 4 wk, 1200 mg at wk 5 and 1200 mg q2 wk thereafter. Results:The 26-wk study enrolled 17 pts, and 13 entered the extension phase. Data analysis was on the intention-to-treat population (n=17). Median time from diagnosis to screening was 10 months (range 0.3–236). Four pts (24%) had no identified complement regulatory factor mutation. Seven pts (41%) had prior renal transplant. All pts had estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 prior to ECU. Median ECU duration was 100 wk (range 2–145).Suppression of terminal complement activity was sustained at data cutoff. Significant platelet count improvement from baseline was seen at the 2-y data cutoff (P<0.0001; Table), with 15 pts (88%) achieving and maintaining a platelet count ≥150×109/L. Hematologic normalizationa was achieved by 88% of pts for an average duration of 629 days (d). Fifteen pts (88%) achieved TMA event-free status,b and TMA intervention ratec decreased from a median 0.88 (range 0.04–1.59) prior to ECU to 0 (range 0–0.31) during ECU treatment. Significant improvements in eGFR were observed throughout the study period (P=0.0008; Table). Earlier intervention with ECU was associated with greater eGFR improvement (P<0.01). Results of a 3-piece linear model demonstrated a flat slope for eGFR change from d −42 to 0, followed by a steep positive slope from d 0 to 28 (P<0.0001), then a continuous increase from d 28 to 860 (P=0.03). Improvements in other renal endpoints, including serum creatinine, proteinuria, and chronic kidney disease (CKD) stage, were observed with ongoing ECU. Significant improvements in quality of life (QOL) were observed. Pts received benefit regardless of the presence or absence of an identified complement mutation. Treatment with ECU was generally well tolerated, with 1 report of a serious adverse event (SAE; hypertension) deemed possibly drug related, which resolved with no change in ECU dosing. Two pts discontinued treatment due to worsening renal function unrelated to ECU. Conclusions:Long-term ECU therapy inhibited complement-mediated TMA and resulted in significant and continuous time-dependent improvements in renal function. At a median duration of almost 2 y, all pts entering the extension phase remain alive and report better QOL. The low rate of SAEs is consistent with the known safety profile of ECU. These results highlight the ongoing benefit of earlier intervention and long-term treatment with ECU in aHUS.TableChange from baseline in key outcomes from 26 wk and 100 wk of ECU treatment (N=17)Key OutcomesWk 26Median 100 WkMean platelet count change (primary), ×109/L (95% CI)73 (40–105)88 (63–112)P=0.0001P<0.0001 (wk 96)Hematologic normalization (primary),a n (%)13 (76)15 (88)TMA event-free status,b n (%)15 (88)15 (88)eGFR increase of ≥15 mL/min/1.73 m2, n (%)8 (47)10 (59)CKD improvement ≥1 stage, n (%)10 (59)12 (71)Serum creatinine decrease ≥25%, n (%)11 (65)13 (76)Mean eGFR change, mL/min/1.73 m2 (95% CI)31 (17, 45)32 (15, 49)dP=0.0001P<0.0008 (wk 96)Proteinuria decrease ≥1 grade,e n/N12/157/9 (wk 96)Mean health-related QOL change,f0.32 (0.27, 0.38)0.33 (0.30, 0.36)EuroQOL 5D score (95% CI)P<0.0001P=0.0001 (wk 96)CI=confidence interval.cPE/PI or new dialysis events/pt/d.aNormal platelet and lactate dehydrogenase levels, ≥2 consecutive measurements, ≥4 wk apart.b≥12 wk of stable platelet count, no PE/PI and no new dialysis.dECU eliminated need for dialysis in 4/5 pts receiving dialysis at baseline. An additional pt initiated dialysis at wk 64 (eGFR, 19 mL/min/1.73 m2 at screening).eEvaluable pts.fClinically meaningful threshold ≥0.6. Disclosures:Greenbaum:Alexion Pharmaceuticals: Consultancy, Honoraria, Research Funding, Speakers Bureau. Legendre:Alexion Pharmaceuticals: Speakers Bureau. Babu:Alexion Pharmaceuticals: Honoraria, Research Funding. Cohen:Alexion Pharmaceuticals Inc.: Research Funding. Bedrosian:Alexion Pharmaceuticals: Employment. Loirat:Alexion Pharmaceuticals: Coordinator of Alexion trials of eculizumab in atypical HUS for France. Honoraria for conferences. Other.

Platelet transfusion in dengue fever: a randomized controlled trial

Background: Immune mediated destruction of platelets can possibly lead to poor response to platelet transfusion in dengue fever.Weconducted this trial to study effects of platelet transfusion in dengue-related thrombocytopenia. Methods: A single center, randomized, non blind trial was conducted at Jinnah Hospital Lahore between August and October 2011. Adults of the age ≥14 years with dengue fever or dengue hemorrhagic fever and platelet counts <30,000/mm3 were eligible.Patients were randomized to treatment and control group. Treatment group received single donor platelets. Responsiveness to platelet transfusion was assessed by 1 hr post-transfusion platelet increments (PPI) and corrected count increments (CCI). Patients with PPI ≥10,000/mm3 and/or CCI≥5,000/mm3 1 hr post-transfusion were considered responders. Primary outcome measurewas platelet count increments at 24 and 72hrs. Secondary outcome measure was duration of bleeding. Results: Eighty seven (87) patientswere enrolled and43 (48.2%) received platelet transfusion. Mean PPI and CCI at 1 hr posttransfusion in treatment group were 18,800/mm3 (range -7,000 to 77,000) and 7,000/mm3 (range -1,050 to 27,260) respectively. 22 (53.6%) patients in treatment groupwere non-responders.Mean platelet incrementswere higher in treatment group as compared to control group at 24hrs (34,780/mm3 vs 4,280/mm3, p<0.001) and 72hrs (75,430/mm3 vs 32,840/mm3, p=0.001). At 24hrs, responders showed significantly higher increments (mean 53,310/mm3) than non-responders (mean 18,770/mm3) and controls (mean 4,280/mm3) (p=0.004, p <0.001 respectively). Significant difference was also found between non-responders and controls (p <0.001). Similarly, 72hrs post-transfusion platelet increments were significantly higher in responders (mean 103,440/mm3) as compared to non-responders (mean 51,430/mm3) and control group (mean 32,840/mm3) (p=0.001, p <0.001 respectively). However, no significant differences were found between nonresponders andcontrol group (p=0.104). Three severeanaphylactic reactions including two deaths occurred in treatment group. Both deathswere innon-responders.No significantdifferencewas found in duration of bleeding between treatment and control group. Conclusion: Although half of the patients show significant improvement in platelet count following platelet transfusion, no beneficial effect occurs on duration of bleeding. Platelet transfusion in dengue fever is associated with high incidence of severe complications including death and should not be routinely done. The risk of complications is higher in non-responders.

Resolution of Dialyzer Membrane-Associated Thrombocytopenia with Use of Cellulose Triacetate Membrane: A Case Report

Blood and dialyzer membrane interaction can cause significant thrombocytopenia through the activation of complement system. The extent of this interaction determines the biocompatibility of the membrane. Although the newer synthetic membranes have been shown to have better biocompatibility profile than the cellulose-based membranes, little is known about the difference in biocompatibility between synthetic membrane and modified cellulose membrane. Herein, we report a case of a patient on hemodialysis who developed dialyzer-membrane-related thrombocytopenia with use of synthetic membrane (F200NR polysulfone). The diagnosis of dialyzer membrane-associated thrombocytopenia was suspected by the trend of platelet count before and after dialysis, and the absence of other possible causes of thrombocytopenia. We observed significant improvement in platelet count when the membrane was changed to modified cellulose membrane (cellulose triacetate). In patients at high risk for thrombocytopenia, the modified cellulose membrane could be a better alternative to the standard synthetic membranes during hemodialysis.

Hemostatic consequences of a non‐fresh or reconstituted whole blood small volume cardiopulmonary bypass prime in neonates and infants

Despite aggressive measures to miniaturize the cardiopulmonary bypass (CPB) circuit in neonates and infants, the CPB prime volume is often at least as large as the patients' blood volume. We conducted an observational study to characterize the hemostatic consequences of a CPB prime consisting of either non-fresh or reconstituted whole blood. Hematocrit, fibrinogen, platelet count, plasminogen, anti-thrombin III (AT-III), and factors (F) II, V, VII, IX, and X of 30 neonates and infants undergoing cardiac surgery with CPB utilizing either a non-fresh or reconstituted whole blood prime were prospectively evaluated at eight time points. Following protamine administration, microvascular bleeding was treated by protocol. The hemostatic composition of the CPB prime was the same following the use of either non-fresh or reconstituted whole blood. The CPB prime platelet count (mean +/- SD) was 5.87 +/- 2.84 x 10(3) microl(-1) when compared to a preoperative platelet count of 298 +/- 142 x 10(3) microl(-1) (P < 0.0001). Twenty patients received 17.3 +/- 9.2 ml x kg(-1) (0.86 +/- 0.46 units x kg(-1)) of platelets with significant improvement in platelet count. Nine patients received 16.7 +/- 13.4 ml x kg(-1) (0.84 +/- 0.67 units x kg(-1)) of cryoprecipitate with significant improvements in FVIII and fibrinogen. Non-fresh or reconstituted whole blood as a component of a small volume CPB prime in neonates and infants induces clinically significant dilutional thrombocytopenia in conjunction with less significant reductions in fibrinogen, FII, FV, FVII, FVIII, FIX, FX, plasminogen, and AT-III.