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INTRODUCTION:Thrombocytopenia (TP) is commonly encountered in cirrhotic patients, likely secondary to splenic congestion from portal hypertension. The few available studies showed inconsistent effect of Transjugular Intrahepatic Portosystemic Shunt (TIPS) on thrombocytopenia and were limited mostly by short term (≤3 months) follow up after TIPS which can underestimate the effect. Moreover, the majority of studies did not examine the predictors of improved thrombocytopenia, so it is not clear which patients would benefit from the procedure. In this study, we assess the effect of TIPS on TP up to 6 months after TIPS.METHODS:We conducted a retrospective study including adults with cirrhosis who underwent TIPS at Tertiary referral center between January 2016 and June 2018. Only patients with average platelet count <150 k/ul in the 3 months before TIPS were included. Charts were manually reviewed to collect baseline and outcome variables. The shunt patency was ensured using Doppler ultrasound in 3-6 months after TIPS. Primary outcome was the percentage of patients with improved TP after TIPS. This was defined based on the difference between average count in the 3 months before TIPS and the average count in the 3-6 months after. Secondary outcome was to determine the predictors of improved TP on a multivariate logistic regression model.RESULTS:Forty-one patients were included. Table 1 shows the demographic and clinical characteristics of the patients. 22 patients (54%) had an improved TP after TIPS (median absolute rise 15.04 [0.25, 133.67], median percent increase 14.59% [0.40, 122.26] (Figure 1). The majority of patients (13/22) had mild improvement by <20 k/ul. The improved TP group had more variceal bleed as an indication for TIPS, lower pre-TIPS average platelet count, and a lower pre-TIPS portosystemic pressure gradient (PSPG). The predictors of improved TP were TIPS for variceal bleeding rather than refractory ascites; OR 31 [2.3-432], lower mean platelets count before TIPS, OR 0.96 [0.93-0.99] and lower change in PSPG; OR 0.55 [0.32-0.95].CONCLUSION:Our result is in agreement with previous studies that showed improvement in TP in a subset of patients following TIPS. However, the improvement was modest in most patients. Predictors of improvement in our cohort were lower pre-TIPS average platelet count, lower pre-TIPS PSPG, and variceal bleeding as an indication for TIPS placement. More studies are demanded to validate the role of TIPS in the management of TP.

Background: Germline mutations in the TP53 gene are primarily associated with Li-Fraumeni syndrome (LFS), a hereditary cancer predisposition disorder. While the predominant manifestations are various malignancies, there is limited information regarding non-malignant clinical features, particularly affecting the skin and musculoskeletal systems, in TP53 mutation carriers. We report a rare case of LFS presenting with immune thrombocytopenia (ITP) and changes of early aging and discuss the possible underlying pathophysiological mechanisms for these. Case presentation: A 16-year-old female presented with complaints of spontaneous ecchymotic patches over both upper limbs, lower limbs, and chest along with menorrhagia. Comprehensive evaluation with bone marrow examination confirmed diagnosis of ITP which was treated with steroids, intravenous immunoglobulin, and thrombopoietin receptor agonists, and the patient responded completely with normalization of platelet count. Given the positive family history of thrombocytopenia in the sister and early malignancy in the maternal family, a whole exome sequencing was done which showed a heterozygous pathogenic variant in the TP53 gene confirming the background of LFS. Conclusion: A case of LFS with a positive family history presenting as primary ITP successfully managed with ITP-like treatment is a rare immunological complication and has not been reported in the literature to date.

The rate of death or major bleeding was significantly higher among preterm infants with severe thrombocytopenia assigned to transfusions at higher platelet-count thresholds (50,000 per cubic millimeter) than among those assigned to lower thresholds (25,000 per cubic millimeter).

Severe fever with thrombocytopenia syndrome (SFTS) is an acute febrile illness characterized by fever, leukopenia, thrombocytopenia, and gastrointestinal symptoms such as diarrhea, nausea, and vomiting resulting from infection with the SFTS virus (SFTSV). The SFTSV is transmitted to humans by tick bites, primarily from Haemaphysalis longicornis, Amblyomma testudinarium, Ixodes nipponensis, and Rhipicephalus microplus. Human-to-human transmission has also been reported. Since the first report of an SFTS patient in China, the number of patients has also been increasing. The mortality rate of patients with SFTS remains high because the disease can quickly lead to death through multiple organ failure. In particular, an average fatality rate of approximately 20% has been reported for SFTS patients, and no treatment strategy has been established. Therefore, effective antiviral agents and vaccines are required. Here, we aim to review the epidemiology, clinical manifestations, laboratory diagnosis, and various specific treatments (i.e., antiviral agents, steroids, intravenous immunoglobulin, and plasma exchange) that have been tested to help to cope with the disease.

Severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV) is an emerging tick-borne virus with high fatality and an expanding endemic. Currently, effective anti-SFTSV intervention remains unavailable. Favipiravir (T-705) was recently reported to show in vitro and in animal model antiviral efficacy against SFTSV. Here, we conducted a single-blind, randomized controlled trial to assess the efficacy and safety of T-705 in treating SFTS (Chinese Clinical Trial Registry website, number ChiCTR1900023350). From May to August 2018, laboratory-confirmed SFTS patients were recruited from a designated hospital and randomly assigned to receive oral T-705 in combination with supportive care or supportive care only. Fatal outcome occurred in 9.5% (7/74) of T-705 treated patients and 18.3% (13/71) of controls (odds ratio, 0.466, 95% CI, 0.174–1.247). Cox regression showed a significant reduction in case fatality rate (CFR) with an adjusted hazard ratio of 0.366 (95% CI, 0.142–0.944). Among the low-viral load subgroup (RT-PCR cycle threshold ≥26), T-705 treatment significantly reduced CFR from 11.5 to 1.6% ( P  = 0.029), while no between-arm difference was observed in the high-viral load subgroup (RT-PCR cycle threshold <26). The T-705-treated group showed shorter viral clearance, lower incidence of hemorrhagic signs, and faster recovery of laboratory abnormities compared with the controls. The in vitro and animal experiments demonstrated that the antiviral efficacies of T-705 were proportionally induced by SFTSV mutation rates, particularly from two transition mutation types. The mutation analyses on T-705-treated serum samples disclosed a partially consistent mutagenesis pattern as those of the in vitro or animal experiments in reducing the SFTSV viral loads, further supporting the anti-SFTSV effect of T-705, especially for the low-viral loads.

Background Severe neonatal thrombocytopenia, as a rare but life-threatening disease with multiple etiologies, has limited relevant reports in China. The single-center study was performed in a severe thrombocytopenic cohort to improve the prognosis of this disease. Methods We included all the patients diagnosed with severe thrombocytopenia (platelet counts ≤ 50 × 10 3 /µL) in our institution between October 2016 and February 2021, and retrospectively reviewed their electronic records. Comparisons were made according to etiology and outcome. Results Among the 5819 inpatients, 194 with severe thrombocytopenia were included in this study, with 64.4% of the cases manifesting thrombocytopenia within 72 h of life. The highest incidence was recorded among extremely low birth weight neonates (6.5%). The main etiologies included sepsis (22.2%), genetic syndromes (14.4%), perinatal asphyxia (9.8%), necrotizing enterocolitis (NEC; 8.8%), and cytomegalovirus infection (6.7%). The median platelet nadir was 5.0 × 10 3 /µL [IQR:2.0 × 10 3 /µL-16.0 × 10 3 /µL], and 112 patients developed very severe thrombocytopenia (platelet counts ≤ 30 × 10 3 /µL), of which 21.4% were associated with late-onset sepsis. In 45 culture-positive cases, the gram-negative group had a lower level of platelets (mean [SD]: 28 [11]×10 3 /µL) as compared to the gram-positive group (mean [SD]: 39 [12]×10 3 /µL). A total of 120 cases (61.9%) exhibited evidence of hemorrhage, with patients diagnosed with NEC demonstrating the highest incidence of hemorrhage at 58.8%. The platelet counts took a median of 10 days to recover: 11 and 7 days for early and late-onset cases; 15 days without and 21 days with platelet transfusions, respectively. The overall mortality rate was 26.8%. The causes of severe thrombocytopenia in 32.7%, 19.2%, and 17.3% of patients who died were identified as sepsis, birth asphyxia, and NEC, respectively. The levels of PT ( P  = 0.025), APTT ( P  = 0.046), and lactate ( P  = 0.028) were lower among surviving patients. Conclusions Sepsis, genetic syndromes, and perinatal asphyxia are the predominant etiologies of severe neonatal thrombocytopenia in China. The overall prognosis of severe neonatal thrombocytopenia is poor, but its severity and outcome were related to laboratory results (PT, APTT, and lactate) and the underlying etiology.

Severe thrombocytopenia in dengue often prompts platelet transfusion primarily to reduce bleeding risk. In India, about 11-43% of dengue patients report receiving platelet transfusions which is considered scarce and expensive especially in resource limited settings. Herein, we evaluated the efficacy and safety of Carica papaya leaf extract (CPLE) in the management of severe thrombocytopenia (≤30,000/μL) in dengue infection. 51 laboratory confirmed adult dengue patients with platelet counts ≤30,000/μL were randomly assigned to either treatment (n = 26) or placebo (n = 24) group. By day 3, CPLE treated patients reported significantly (p = 0.007) increased platelet counts (482%± 284) compared to placebo (331%±370) group. In the treatment group, fewer patients received platelet transfusions (1/26 v/s 2/24) and their median time for platelets to recover to ≥ 50,000/μL was 2 days (IQR 2-3) compared to 3 days (IQR 2-4) in placebo. Overall, CPLE was safe and well tolerated with no significant decrease in mean hospitalization days. Plasma cytokine profiling revealed that by day 3, mean percent increase in TNFα and IFNγ levels in treatment group was less compared to that observed in placebos; (TNFα: 58.6% v/s 127.5%; p = 0.25 and IFNγ: 1.93% v/s 62.6% for; p = 0.12). While a mean percent increase in IL-6 levels occurred in placebos (15.92%±29.93%) by day 3, a decrease was noted in CPLE group (12.95%±21.75%; p = 0.0232). Inversely, CPLE treated patients reported a mean percent increase compared to placebo by day 3 (143% ±115.7% v/s 12.03%± 48.4%; p = 0.006). Further, by day 3, a faster clearance kinetics of viral NS1 antigenemia occurred-mean NS1 titers in treatment group decreased to 97.3% compared to 88% in placebos (p = 0.023). This study demonstrates safety and efficacy of CPLE in increasing platelet counts in severe thrombocytopenia in dengue infections. A possible immunomodulatory and antiviral activity may be attributed to CPLE treatment. These findings merit validation in larger prospective studies. Trial registration Name of the registry: Clinical Trials Registry-India (CTRI) Registration No.: CTRI-REF/2017/02/013314.

Severe Fever with Thrombocytopenia Syndrome (SFTS) is an emerging infectious disease caused by a novel bunyavirus, SFTS virus (SFTSV), with fatal outcome developed in approximately 17% of the cases. Thrombocytopenia is a hallmark feature of SFTS, and associated with a higher risk of fatal outcome, however, the pathophysiological involvement of platelet in the clinical outcome of SFTS remained under-investigated. In the current study, by retrospectively analyzing 1538 confirmed SFTS patients, we observed that thrombocytopenia was associated with enhanced activation of the cytokine network and the vascular endothelium, also with a disturbed coagulation response. The platelet phenotypes were also extensively altered in the process of thrombocytopenia development of SFTS patients. More importantly, all these disturbed host responses were related to the severity of thrombocytopenia, thus were considered to play in a synergistic way to influence the disease outcome. Moreover, the clinical effect of platelet transfusion was assessed by comparing two groups of patients with or without receiving this therapy. As a result, we observed no therapy effect in altering frequencies of fatal outcome, clinical bleeding development, or dynamic change of platelet count during the hospitalization. It's suggested that platelet supplementation alone acted a minor role in improving disease outcome, therefore new therapeutic intervention to regulate host response should be proposed. The current results revealed some evidence of interrelationship between platelet count and clinical outcome of SFTS disease from the perspective of activation of the cytokine network, the vascular endothelium, and the coagulation/fibrinolysis system. These evaluations might help to attain a better understanding of the pathogenesis and therapy choice in SFTS.

Background Sepsis is still a common critical disease with high morbidity and mortality in intensive care unit. Despite published guidelines for sepsis, development of antibiotic therapy and advanced organ support technologies, the mortality of sepsis patients is still 25% or more. It is necessary to distinguish the subtypes of sepsis, and the targeted therapy for the patients need to be explored. Platelets have various biological functions in hemostasis and thrombosis, host defense, inflammatory/immune responses and tissue repair/regeneration. Moreover, severe thrombocytopenia or sustained thrombocytopenia was closely associated with multiply organ dysfunction and higher mortality in sepsis patients. The clinical therapies for thrombocytopenia are platelet transfusion and platelet-elevating drugs. However, platelet transfusion has many defects in clinical practice in sepsis patients, and the impact of platelet-elevating drugs for sepsis patients is still unclear. RESCUE trial is aim to explore the effect of a platelet-elevating drug, recombinant human thrombopoietin (rhTPO), as an effective rescue therapy on sepsis patients with acute severe thrombocytopenia. Methods It is a randomized, open-label, multi-center, controlled trial in 5 tertiary academic hospitals including medical, surgical or general ICUs. In this study, a total of 200 sepsis patients with severe thrombocytopenia will be randomly assigned in a 1:1 ratio to the control and rhTPO group. The patients will be followed up to 28 days after randomization. All patients in two groups receive the same treatment based on the guideline of Surviving Sepsis Campaign. Primary outcome is 28-day mortality. Secondary outcomes are the changes of PCs, blood transfusion, biomarkers of infection and organ function, days free from advanced organ support, drug-related adverse events, the length of ICU and hospital stay. Discussion RESCUE trial is the first randomized controlled trial to explore the impact of rhTPO for severe thrombocytopenia in sepsis patients diagnosed by sepsis-3.0 standard. Furthermore, RESCUE trial results will be of significant clinical value on the targeted therapy and add clinical evidence that rhTPO is an effective rescue therapy for these sepsis patients. Trial registration ClinicalTrials.gov : NCT02707497. Registered Date: March 3rd, 2016. Protocol Version 3. Protocol Date: January 25th, 2019.

Infection with severe fever with thrombocytopenia syndrome (SFTS) virus, which can cause hemorrhagic febrile illness, is often transmitted by ticks. We identified 3 patients with SFTS in or near Bangkok, Thailand. Our results underscore a need for heightened awareness by clinicians of possible SFTS virus, even in urban centers.