Baseline Platelet Research Articles

Abstract 4136085: The Prognostic Impact of Thrombocytopenia at 6 months after Transcatheter Aortic Valve Replacement: A Retrospective Multicenter Study

Background: Transient thrombocytopenia after transcatheter aortic valve replacement (TAVR) is a common phenomenon. Thrombocytopenia after TAVR during the perioperative period has been reported to impact prognosis. However, the impact of thrombocytopenia in the mid-term post-TAVR period is currently unknown. Methods: A retrospective observational study was conducted on 1405 patients who underwent TAVR from May 2016 to February 2023 at four institutions. Of these, 850 patients were analyzed. Patients who underwent dialysis (67), converted to an open chest surgery (8), had a Valve-in-Valve procedure (30), underwent a direct aortic approach (16), had a malignant tumor (66), and patients whose platelet levels could not be measured at 6 months after TAVR due to death or dropout were excluded from the analysis. The clinical follow-up occurred at 1, 6, and 12 months after the procedure. Laboratory testing was conducted before TAVR, during the perioperative period, 1 month post-procedure, and 6 months later. The decrease in platelet count (DPC) 6 months after TAVR was calculated by the following formula: [(Baseline platelet – 6 months platelet)/baseline platelet *100]. A receiver operating characteristics curve was plotted for all-cause mortality at 1 year and DPC at 6 months. The calculated cutoff value for the DPC at 6 months (28.68%) was utilized to classify and compare the two groups. Multivariate logistic regression models were also used to examine the association between the DPC at 6 months and all-cause mortality at 1 year. Adjusted for propensity score matching, the DPC was compared at 6 months in self-expandable and balloon-expandable prosthetic valves. Result: Of the 850 eligible patients (age: 85.5 ± 4.9 years), 31 (3.4%) died between 6 months and 1 year after TAVR. The DPC at 6 months after TAVR was 11.9 ± 22.5%. Multivariate logistic regression analysis including the DPC at 6 months, age, gender, and STS score showed that the DPC at 6 months was independently associated with all-cause mortality at 1 year (odds ratio: 1.03, 95% confidence interval: 1.005-1.046, p=0.01). After adjustment for propensity score matching, the balloon-expandable prosthetic valve had a higher rate of thrombocytopenia at 6 months (15.0% vs. 9.6%, p=0.04). Conclusion: The DPC at 6 months after TAVR may predict all-cause mortality at 1 year.

Reduction of thrombus burden by cangrelor in ticagrelor-loaded st-elevation myocardial infarction patients with high residual platelet reactivity: the imaging sub-study of the ERMIT randomized trial

Abstract Background Residual high platelet reactivity (HPR) at the time of primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) is associated with higher residual thrombus burden and the subsequent suboptimal reperfusion. Purpose We sought to determine the impact of intravenous Cangrelor on the residual post-PCI thrombus burden in patients with HPR admitted for primary PCI in a prespecified intracoronary optical coherence tomography (OCT) sub-study of the ERMIT randomized trial. Methods In the ERMIT trial patients pre-treated with ticagrelor and aspirin with residual HPR (baseline platelet reactivity unit >208) were randomly assigned in a 1:1 ratio to receive cangrelor on top of standard therapy or standard therapy alone prior to PCI. The primary endpoint of the sub-study was the relative thrombus volume quantified on OCT. Other OCT quantified parameters were predefined as secondary endpoints. Results After screening of 128 patients, a total of 60 patients with HPR were enrolled and randomized. The OCT sub-study included 53 patients, 29 in the cangrelor and 24 in the control group. As reported in the table, baseline characteristics were similar between the groups. The post-PCI PRU was dramatically lower in the cangrelor as compared to the standard group (p<0.001). The primary endpoint was 4.5% [3.4;7.2] versus 6.9% [5.2;8.5], (p=0.03) in the cangrelor and control groups respectively. All other imaging parameters confirmed the significantly lower thrombus burden in patients receiving cangrelor (Table). Conclusion The imaging sub-study of the randomized ERMIT trial shows that cangrelor use is associated with a more effective platelet inhibition and lower post-PCI residual thrombus burden in ticagrelor-loaded STEMI patients with residual HPR. The clinical implications of such finding warrant larger size trials.Table

Cangrelor use in ticagrelor-loaded ST-elevation myocardial infarction patients with high residual platelet reactivity: a randomized controlled trial

Abstract Background Despite the use of potent P2Y12 inhibitor, many patients still present with high platelet reactivity (HPR) at the time of primary percutaneous coronary intervention (PCI). HPR is associated with impaired myocardial reperfusion and the subsequent poor outcome. Purpose We sought to determine the impact of Cangrelor -a rapid and potent intravenous P2Y12 inhibitor- on myocardial reperfusion in patients with HPR admitted for primary PCI in a randomized trial. Methods Patients pre-treated with ticagrelor and aspirin with residual HPR (baseline platelet reactivity unit (PRU) > 208) were randomly assigned in a 1:1 ratio to receive cangrelor (experimental group) or not (control group) just before PCI. The primary endpoint was optimal myocardial reperfusion defined as a final myocardial blush grade (MBG) 3 assessed by an independent core laboratory. Results After screening of 128 patients, a total of 60 patients were with HPR were enrolled and randomized. The ticagrelor loading dose to PRU measurement times were 83 ± 32 and 90 ± 47 minutes in the experimental and control groups, respectively. Baseline PRU were 245 ± 30 and 252 ± 35 in the experimental and standard group, respectively. A final MBG 3 was observed in 21/30 (55%) and 17/30 (45%) the experimental and standard groups (p=0.29). A final TIMI flow grade 3 was observed in 30/30 (100%) and 27/30 (90%) the experimental and standard groups (p=0.24). Peak troponin levels after PCI were 51381 ± 50047 and 51078 ± 63960 ng/L (p=0.98) in the experimental and standard group, respectively. At the end of the PCI, control PRU were 36 ± 57 and 198 ± 107 (p<0.0001) in the experimental and standard group, respectively. One patient of the experimental group presented an in-hospital major bleeding (BARC 3). Conclusion In ticagrelor-loaded STEMI patients with residual HPR at the time of PCI, cangrelor use was associated with a more effective platelet inhibition but failed to significantly improve the rates of optimal final myocardial blush grades.

Avatrombopag Elevates Platelet Counts and Reduces Platelet Transfusions in Patients With Chronic Liver Diseases During the Perioperative Period of Liver Transplantation

ABSTRACTBackgroundAvatrombopag has been approved for elevating platelet counts in patients with chronic liver diseases (CLDs) accompanied by thrombocytopenia (TCP). However, limited research focuses on its safety and efficacy in CLD patients during the perioperative period of liver transplantation (LT).MethodsWe retrospectively enrolled CLD patients with severe TCP who received avatrombopag during the perioperative period of LT and analyzed therapeutic efficacy, changes in platelet counts, and related adverse events. Comparisons were conducted between liver transplant recipients who received avatrombopag and those who did not use platelet‐raising drugs, focusing on intraoperative and postoperative bleeding as well as platelet transfusions.ResultsOf 93 patients who received avatrombopag, 67 cases (72%) achieved remission, with their platelet counts increasing to over 50 × 109/L without transfusion. Additionally, 38 cases (40.9%) reached platelet counts above 100 × 109/L, achieving complete remission. The overall remission rate was significantly correlated with the baseline platelet counts, suggesting that individuals with higher baselines (25−50 × 109/L vs. < 25 × 109/L) were more likely to achieve remission (82.1% vs. 57.7%, χ2 = 5.989, p = 0.014). Using propensity score‐overlap weighting to balance the baseline bias, we compared 33 liver transplant recipients who received avatrombopag to those who did not receive any platelet‐raising drugs. Recipients who used avatrombopag achieved significantly higher platelet counts both before and after propensity score‐overlap weighting ([63.76 ± 31.33] × 109/L vs. [45.73 ± 16.44] × 109/L, p = 0.004; [65.37 ± 38.41] × 109/L vs. [42.73 ± 17.27] × 109/L, p = 0.044) and required fewer intraoperative and postoperative platelet transfusions (p < 0.05). No adverse events related to avatrombopag were observed.ConclusionsAvatrombopag is safe and effective for CLD patients with TCP during the perioperative period of LT, resulting in elevated platelet counts and reduced need for platelet transfusions.

Avatrombopag in immune thrombocytopenia: A real-world study of the Spanish ITP Group (GEPTI).

Avatrombopag is the newest thrombopoietin receptor agonist (TPO-RA) approved to treat immune thrombocytopenia (ITP). Real-world evidence regarding effectiveness/safety is limited. The Spanish ITP Group (GEPTI) performed a retrospective study with patients starting avatrombopag for the first time. A total of 268 ITP patients were recruited. The median (interquartile range [IQR]) follow-up time was 47.5 (30.4-58.9) weeks. Among the 193 patients with baseline platelet counts <50 × 109/L, 174 (90.1%) of them achieved response (PC ≥50 × 109/L), and 113 (87.6%) of the 129 who persisted on avatrombopag at last visit had platelet levels above such threshold. Results were similar when only those patients switching to avatrombopag due to previous treatment failure were considered (n = 104). Patients reached response in 13 (7-21) days. Among patients with baseline levels ≥50 × 109/L, 73/75 (97.3%) reported response, which was maintained by 53 (94.6%) of the 56 who continued on avatrombopag at the end of the study. Loss-of-response was always <10%. ITP duration did not influence response. Approximately 79% (34/43) of heavily pretreated (≥4 lines) patients with baseline platelet counts <50 × 109/L switching after previous failure achieved PC ≥50 × 109/L. Previous use of eltrombopag and/or romiplostim did not influence response, regardless of whether previous TPO-RA(s) succeeded or failed. Avatrombopag allowed dose-reduction/suspension of corticosteroids in 40/50 (80.0%) patients with baseline platelet counts <50 × 109/L. Overall, 40/268 (14.9%) thrombocytosis and 12/268 (4.5%) thromboembolic events were reported. Our real-world cohort supports the use of avatrombopag to manage ITP, regardless of disease severity and treatment history.

Exploring the impact of baseline platelet count on linezolid-induced thrombocytopenia: a retrospective single-center observation study.

Patients treated with linezolid (LZD) frequently develop thrombocytopenia, and previous studies have identified the risk factors for this condition. However, the relationship between the development of LZD-induced thrombocytopenia and baseline platelet count has varied according to different reports. To explore the relationship between platelet count and the development of LZD-induced thrombocytopenia. Patients who underwent LZD at Hokkaido University Hospital in Japan from September 2008 to March 2023 were included. We collected data on patient characteristics and platelet counts at baseline and during LZD therapy from the electronic medical records. Thrombocytopenia was defined as a decrease in platelet count by 30% or more from baseline, or a platelet level < 100,000/µL. Two hundred and ninety-five patients who received LZD were included in this study, of whom 34.9% developed thrombocytopenia. In the early days of LZD treatment, the thrombocytopenia group showed a nearly 5% decrease in platelet count, while the non-thrombocytopenia group exhibited an increase of over 5%. Additionally, focusing on early onset thrombocytopenia (within 5 days), a baseline platelet count of < 150,000/µL was identified as a risk factor for early thrombocytopenia. Conversely, it was also observed that 24.7% of patients with a baseline platelet count ≥ 150,000/µL still developed early thrombocytopenia. Our findings suggest that while a baseline platelet count of < 150,000/µL is a risk factor for the early onset of thrombocytopenia, vigilant monitoring of platelet counts by clinical pharmacists in the early stages of LZD treatment is essential, regardless of baseline platelet levels.

Baseline Platelet Count Predicts Infarct Size and Mortality after Acute Myocardial Infarction.

Platelets greatly contribute to cardiovascular diseases. We sought to explore the association of platelet counts with infarct size and outcome in patients presenting with acute ST-segment elevation MI (STEMI) treated with primary percutaneous coronary intervention (PPCI). In this retrospective study, we grouped 1,198 STEMI patients into tertiles (T) based on platelet count on admission: T1 = 102-206 [109 platelets/L] (n = 402), T2 = 207-259 [109 platelets/L] (n = 396), and T3 = 260-921 [109 platelets/L] (n = 400). Primary endpoint was 1-year all-cause mortality. Patients with highest platelet counts on admission showed the greatest area at risk and infarct size: area at risk (median) was 22.0% (interquartile range [IQR]: 12.0-39.8%) in T1, 21.0% (IQR: 11.0-37.1%) in T2, and 26.0% (IQR: 14.9-45.0%) of the left ventricle in T3 (p = 0.003); final infarct sizes after 7 to 14 days were as follows: 10.0% (IQR: 2.0-21.0%) in T1, 9.0% (IQR: 2.0-20.7%) in T2, and 12.0% (IQR: 3.0-27.3%) of the left ventricle in T3 (p = 0.015) as serial imaging revealed. At 1 year, 16 all-cause deaths occurred in T1, 5 in T2, and 22 in T3 (log-rank test, p = 0.006). After adjustment, T1 and T3 were associated with all-cause 1-year mortality (T1: hazard ratio [HR] = 3.40, 95% confidence interval [CI] = 1.23-9.54, p = 0.02; T3: HR = 3.55, 95% CI = 1.23-9.78, p = 0.01) compared with T2. At 5 years, all-cause mortality remained numerically higher in the T1 and T3. In patients with STEMI undergoing PPCI, low and high blood platelet levels on admission were associated with increased long-term mortality (Fig. 1).

Antiphospholipid Antibodies Modify the Prognostic Value of Baseline Platelet Count for Clinical Outcomes After Ischemic Stroke.

Antiphospholipid antibodies (aPLs) have been reported to be involved in platelet-mediated thrombosis and inflammation, but the impact on the prognosis of ischemic stroke remains unclear. We aimed to examine whether the association between baseline platelet count (PLT) and long-term clinical outcomes within 2 years after ischemic stroke onset is modulated by aPLs. A total of 2938 patients with ischemic stroke were included in this prospective cohort study. Cox proportional hazards regression models were used to assess the association between the baseline PLT stratified by aPLs status and 2-year clinical outcomes after stroke onset, and an interaction effect between PLT and aPLs on clinical outcomes was tested by likelihood ratio test. There was a significant interaction effect of aPLs and PLT on recurrent stroke (Pinteraction=0.002) and cardiovascular events (Pinteraction=0.001) within 2 years after stroke onset. After multivariate adjustment, high PLT was associated with increased risks of recurrent stroke (hazard ratio [HR], 2.78 [95% CI, 1.03-7.45]; Ptrend=0.039) and cardiovascular events (HR, 2.58 [95% CI, 1.12-5.90]; Ptrend=0.024) when 2 extreme tertiles were compared among patients with aPL positive, but not among those with aPL negative. The aPLs had a modifying effect on the association between PLT and clinical outcomes within 2 years after ischemic stroke onset. Increased PLT was associated with recurrent stroke and cardiovascular events after ischemic stroke onset among patients with aPL positive, but not in those with aPL negative.

Platelet count has a nonlinear association with 30-day in-hospital mortality in ICU end-stage kidney disease patients: a multicenter retrospective cohort study

This study addresses the relationship between platelet count and 30-day in-hospital mortality in End-Stage Kidney Disease (ESRD) patients in the intensive care unit (ICU), a topic with limited existing evidence. Utilizing data from the US eICU-CRD v2.0 database (2014–2015), a retrospective cohort study was conducted involving 3700 ICU ESRD patients. We employed binary logistic regression, smooth curve fitting, and subgroup analyses to explore the association between platelet count and 30-day in-hospital mortality. The 30-day in-hospital mortality rate was 13.27% (491/3700), with a median platelet count of 188 × 109/L. After adjusting for covariates, we observed a relationship between platelet count and 30-day in-hospital mortality (OR = 0.98, 95% CI 0.97, 0.99). Subgroup analyses supported these findings. More importantly, a nonlinear association was detected, with an inflection point at 222 × 109/L. The effect sizes (OR) on the left and right sides of the inflection point were 0.94 (0.92, 0.96) and 1.03 (1.00, 1.05), respectively. The most significant finding of this study is the revelation of a nonlinear relationship between baseline platelet count and 30-day in-hospital mortality in ICU patients with ESRD. This discovery explicitly suggests that when ESRD patients are admitted to the ICU, a platelet level closer to 222 × 10⁹/L may predict a lower 30-day in-hospital mortality risk.

Distinct characteristics of various autoimmune liver diseases: A 22‐year hospital‐based study in Taiwan

AbstractBackground and AimThe characteristics of autoimmune liver diseases (AILDs), including primary biliary cholangitis (PBC), autoimmune hepatitis (AIH), and PBC‐AIH overlap syndrome (OS), have rarely been investigated and compared in Asia.MethodsAt the Taiwan tertiary referral center, 330 PBC patients (87% treated with ursodeoxycholic acid [UDCA]), 143 AIH patients (94.4% treated with immunosuppressive therapy [IST]) and 21 PBC‐AIH OS patients (85.7% treated with UDCA and IST) were enrolled.ResultsCompared with AIH patients, PBC patients were older at baseline and had greater female‐to‐male sex ratios, alkaline phosphatase (ALP) and γ‐glutamyl transferase (γ‐GT) levels, and liver cirrhosis (LC), dyslipidemia, and hepatic and cardiometabolic complication rates. PBC patients had the lowest transaminase levels, whereas AIH patients had the highest transaminase levels. PBC patients had greater 22‐year all‐cause mortality and liver transplantation (ACMaLT) (43.5 vs 25.4%, P = 0.004), LC (75 vs 58.5%, P &lt; 0.01), dyslipidemia (54.4 vs 45.9%, P = 0.001), and cerebrovascular accident (11.3 vs 0.8%, P = 0.019) cumulative incidences (CIs) than did AIH patients; PBC‐AIH OS patients had greater systemic lupus erythematosus (28.9 vs 8.9%, P = 0.009) CI than did PBC patients. Baseline ALP (hazard ratio: 1.001), albumin (0.514), platelet count (0.997), and LC (3.438) were associated with ACMaLT; age (1.110), albumin (0.350), cirrhosis (46.219), and hepatitis C virus antibody positivity (5.068) were associated with hepatocellular carcinoma (HCC); and female sex (2.183) and body mass index (1.054) were associated with autoimmune diseases.ConclusionsCompared with AIH patients, PBC patients had greater cardiometabolic CI, and ACMaLT CI, which was associated with cholestasis, liver functional reserve and LC. Older AILD patients with LC and females with obesity demand special caution for the development of HCC and extrahepatic autoimmune diseases, respectively.

Baseline platelet count and long-term clinical outcomes in patients with acute venous thromboembolism: a prospective cohort study.

An abnormal platelet count (PC) is common in acute venous thromboembolism (VTE) but its relationship with clinical outcomes remains ill-defined. We aimed to explore the association between baseline PC and the long-term risk of clinically relevant outcomes in a prospective cohort of 991 patients with acute VTE. We classified patients into four PC groups: very low (< 100 G/l), low (≥ 100 to < 150 G/l), normal (≥ 150 G/l to ≤ 450 G/l), and high (> 450 G/l). The primary outcome was major bleeding (MB), secondary outcomes were recurrent VTE and overall mortality. We examined the association between PC and clinical outcomes, adjusting for confounders, competing risk for mortality, and periods of anticoagulation. After a median follow-up of 30 months, 132 (13%) of patients experienced MB, 122 (12%) had recurrent VTE, and 206 (21%) died. Compared to patients with a normal PC, patients with a very low PC had a sub-distribution hazard ratio (SHR) for MB of 1.23 (95% confidence interval [CI] 0.52-2.91) and those with a high PC a SHR of 1.87 (95%CI 0.82-4.29). Patients with a low PC had a twofold increased VTE recurrence risk (SHR 2.05, 95%CI 1.28-3.28). Patients with low and very low PC had a hazard ratio for mortality of 1.43 (95%CI 0.99-2.08) and of 1.55 (95%CI 0.80-2.99), respectively. Our findings do not suggest a consistent relationship between baseline PC and long-term clinical outcomes in patients with VTE.

Thrombocytopenia after transcatheter aortic valve implantation

Introduction and objectivesThrombocytopenia frequently occurs after transcatheter aortic valve implantation (TAVI) but its impact is poorly understood. We aimed to analyze the incidence, clinical impact, and predictors of acquired thrombocytopenia after TAVI. MethodsThis retrospective multicenter registry included 3913 patients undergoing TAVI with a baseline platelet count of ≥ 100 *109/L. Acquired thrombocytopenia was defined as a decrease in baseline platelet count of ≥ 50% (early nadir ≤ 3 days and late nadir ≥ 4 days) post-TAVI. The primary endpoint was 30-day all-cause mortality and secondary endpoints were procedural safety and 2-year all-cause mortality. ResultsThe incidence of acquired thrombocytopenia was 14.8% (early nadir: 61.5%, late nadir: 38.5%). Thirty-day mortality occurred in 112 (3.0%) patients and was significantly higher in those with thrombocytopenia (8.5% vs 2.0%, adjusted OR, 2.3; 95%CI, 1.3-4.2). Procedural safety was lower and 2-year mortality was higher in patients with thrombocytopenia vs those without (52.1 vs 77.0%; P <.001, and 30.2% vs 16.8%; HR, 2.2, 95%IC, 1.3-2.7) and especially in those with late nadir thrombocytopenia (45.8% vs 54.5%; P=.056, and 38.6% vs 23.8%, HR, 2.1; 95%CI, 1.5-2.9). Independent predictors of thrombocytopenia comprised baseline and procedural factors such as body surface area, absence of diabetes, poorer renal function, peripheral vascular disease, nontransfemoral access, vascular complications, type of transcatheter heart valve, and earlier TAVI procedures. ConclusionsAcquired thrombocytopenia was common (15%) after TAVI and was associated with increased short- and mid-term mortality and decreased procedural safety. Moreover, late thrombocytopenia compared with early thrombocytopenia was associated with significantly worse clinical outcomes. Further investigations are needed to elucidate the etiologic mechanisms behind these findings.

Evaluation of pharmacokinetic target attainment and hematological toxicity of linezolid in pediatric patients.

Linezolid is commonly used to treat severe and/or resistant Gram-positive infections. Few studies have assessed its pharmacokinetic (PK) target attainment in pediatrics. To evaluate the percentage of pediatrics achieving the PK targets of linezolid with standard dosing regimens and to assess the incidence and risk factors associated with its hematologic toxicity. This prospective observational study included pediatric patients aged 0-14 who received linezolid for suspected or proven Gram-positive infections. Linezolid trough concentrations and the 24-h area under the curve (AUC24) were estimated, and hematologic toxicity was assessed. Seventeen pediatric patients (5 neonates and 12 older pediatrics) were included. A wide variability was observed in linezolid's trough and AUC24 (ranging from 0.5 to 14.4mg/L and from 86 to 700mg.h/L, respectively). The median AUC24 was significantly higher in neonates than older pediatrics (436 [350-574] vs. 200 [134-272] mg,h/L, P = 0.01). Out of all patients, only 41% achieved adequate drug exposure (AUC24 160-300mg.h/L and trough 2-7mg/L), with 24% having subtherapeutic, and 35% having higher-than-optimal exposures. Hematological toxicity was observed in 53% of cases. Identified risk factors include treatment duration over 7days, baseline platelet counts below 150 × 109/L, sepsis/septic shock, and concomitant use of meropenem. Linezolid's standard dosing failed to achieve its PK targets in approximately half of our pediatric cohort. Our findings highlight the complex interplay between the risk factors of linezolid-associated hematological toxicity and underscore the importance of its vigilant use and monitoring, particularly in pediatrics with concomitant multiple risk factors.

Relative value of novel systemic immune-inflammatory indices and classical hematological parameters in predicting depression, suicide attempts and treatment response

This study compared the power of the novel inflammatory markers systemic immune inflammation index (SII) and the system inflammation response index (SIRI) versus the classical hematological indices neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and platelet counts in distinguishing between major depressive disorder (MDD) with and without suicide attempts and distinguishing the non-response to selective serotonin reuptake inhibitor (SSRI) treatment. A total of 139 young adult MDD patients and 54 healthy controls (HC) were included. We found that, in comparison to HC, baseline NLR, PLR, SII, and SIRI were significantly higher in MDD patients, but only NLR and SII had area under the ROC curve (AUC) values greater than 0.7. MDD patients with suicide attempts (SA) showed significantly higher baseline MLR and SIRI, and a tendency to increase NLR compared to those without SA. In terms of AUC, sensitivity, and specificity, NLR was better than MLR, SIRI, SII, and PLR in distinguishing SA. Non-responders to SSRI treatment showed a significant increase in baseline platelet count and PLR compared to responders with an AUC greater than 0.7. These findings highlight the potential benefit of combining novel and classical hematological indices in predicting depression, suicide attempts and treatment response.

Psychological and physical side effects during G-CSF mobilization in related donors of allo-HCT.

The psychological side effects of granulocyte colony-stimulating factor mobilization in related donors of allogeneic hematopoietic cell transplantation (allo-HCT) and impacts of psychological/physical side effects on harvest outcomes remain largely unknown. We prospectively analyzed 349 consecutive related peripheral blood stem cell (PBSC) donors for allo-HCT at the First Affiliated Hospital, Zhejiang University, School of Medicine from March 2021 to August 2023. Higher baseline peripheral blood white blood cell counts (p = 0.046), monocyte counts (p < 0.001), platelet counts (p = 0.001), and hemoglobin (p < 0.001) had a positive correlation to CD34+ cell counts in the first leukapheresis, while female donors (male vs. female, p < 0.001) and older age (> 40 vs. < = 40, p = 0.003) were negatively related to CD34+ cell counts. Bone pain was the most observed physical side effect and was more frequent in female donors (p = 0.032). The incidence of fatigue was higher in female donors and older donors (female vs. male, p = 0.016; > 40 vs. < = 40, p = 0.015). Donor depression (pre vs. during mobilization, p < 0.001), anxiety (pre vs. during mobilization, p = 0.043) and insomnia (pre vs. during mobilization, p = 0.011) scores increased during the mobilization period. Donors with higher depression, anxiety and stress scores at admission were more likely to experience nausea. At 1 month after the last leukapheresis, the counts of white blood cell, neutrophil, monocyte and hemoglobin were significant lower than baseline counts, while the platelet counts recovered to baseline. The mobilization and harvest process can increase the depression, anxiety and insomnia scores. Poor psychological status of the donor can aggravate the occurrence of physical side effects.

The Role of Platelets and Aneurysm Thrombus in the EVAR Post Implantation Syndrome

ObjectivePost implantation syndrome (PIS) is a well-defined entity with unclear etiology, complicating a number of patients with AAAs treated with EVAR. The aim of this study was to assess the platelets’ role and the influence of aneurysmal sac thrombus volumes in the development of PIS. DesignA retrospective analysis of prospectively collected data was performed and 76 patients that were treated by EVAR (2011-2013) were studied. Aneurysms with endoleak were not included in the study. Based on the criteria for SIRS (Systemic Inflammatory Response Syndrome), 17 patients (22%) developed PIS (which is considered a SIRS analogue), while 59 (78%) did not. MethodsThe two groups were compared in relation to the following parameters: baseline platelet count (PLT), decrease of platelet count (PLT drop), volume of the arterial flow before the procedure (V Flow), volume of thrombus of the aneurysm (V thromb), ratio of thrombus volume to aneurysm sac volume (V ratio) and the volume of new formed thrombus (V new). Volume flow measurements were calculated by Osirix ™ software preoperatively and in the 1st month postoperatively. Parametric and non-parametric techniques (unpaired t-test, Mann-Whitney U test) were used accordingly. ResultsBaseline platelets absolute count was greater in the PIS group (239000 ± 17000) vs. the non-PIS group (194000 ± 6900, p=0.004), and the PLT drop was larger in the PIS group (74000 ± 15600 vs. 45000 ± 5300, p=0.019). No difference was found regarding the aneurysm volumes (Vflow, Vthromb, Vratio, Vnew) between the two groups. ConclusionPlatelets, in terms of their absolute baseline count and their decrease after the procedure, seem to be an important factor in developing PIS after EVAR. Further, more tailored studies are needed to elucidate the role of platelets and flow/thrombus volumes in the development of PIS.

Development and Validation of a Prediction Model for Thyroid Dysfunction in Patients During Immunotherapy

ObjectiveThis study was designed to develop and validate a predictive model for assessing the risk of thyroid toxicity following treatment with immune checkpoint inhibitors. MethodsA retrospective analysis was conducted on a cohort of 586 patients diagnosed with malignant tumors who received programmed cell death 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors. The patients were randomly divided into training and validation cohorts in a 7:3 ratio. Logistic regression analyses were performed on the training set to identify risk factors of thyroid dysfunction, and a nomogram was developed based on these findings. Internal validation was performed using K-fold cross-validation on the validation set. The performance of the nomogram was assessed in terms of discrimination and calibration. Additionally, decision curve analysis was utilized to demonstrate the decision efficiency of the model. ResultsOur clinical prediction model consisted of 4 independent predictors of thyroid immune-related adverse events, namely baseline thyrotropin (TSH, OR = 1.427, 95%CI:1.163-1.876), baseline thyroglobulin antibody (TgAb, OR = 1.105, 95%CI:1.035-1.180), baseline thyroid peroxidase antibody (TPOAb, OR = 1.172, 95%CI:1.110-1.237), and baseline platelet count (platelet, OR = 1.004, 95%CI:1.000-1.007). The developed nomogram achieved excellent discrimination with an area under the curve of 0.863 (95%CI: 0.817-0.909) and 0.885 (95%CI: 0.827-0.944) in the training and internal validation cohorts respectively. Calibration curves exhibited a good fit, and the decision curve indicated favorable clinical benefits. ConclusionThe proposed nomogram serves as an effective and intuitive tool for predicting the risk of thyroid immune-related adverse events, facilitating clinicians making individualized decisions based on patient-specific information.

Eltrombopag plus diacerein vs eltrombopag in patients with ITP: a multicenter, randomized, open-label phase 2 trial

AbstractThis study aimed to compare the efficacy and safety of eltrombopag plus diacerein vs eltrombopag alone in patients with primary immune thrombocytopenia (ITP) who were previously unresponsive to 14 days of eltrombopag treatment at the full dose. Recruited patients were randomly assigned 1:1 to receive either eltrombopag plus diacerein (n = 50) or eltrombopag monotherapy (n = 52). Overall response rate, defined as a platelet count of ≥30 × 109/L, at least doubling of the baseline platelet count, and no bleeding, was reached in 44% of patients in the eltrombopag plus diacerein group compared with 13% in the eltrombopag group at day 15 (P = .0009), and reached in 42% of patients in the combination group compared with 12% in the monotherapy group at day 28 (P = .0006). The addition of diacerein to eltrombopag also led to a longer duration of response (P = .0004). The 2 most common treatment-emergent adverse events were respiratory infection and gastrointestinal reactions in the combination group, and fatigue and respiratory infection in the eltrombopag group. In conclusion, eltrombopag plus diacerein was well tolerated, and induced higher overall response rates and longer duration of response than eltrombopag alone, offering a rejuvenating salvage therapy for patients with ITP unresponsive to 14 days of full dosage eltrombopag. Our work has the potential to enhance the care of patients treated with thrombopoietin receptor agonists, reducing the need for rapid transitions to less-preferable therapies. This study is registered at ClinicalTrials.gov as #NCT04917679.

Final Results from the First European Real-World Experience on Lusutrombopag Treatment in Cirrhotic Patients with Severe Thrombocytopenia: Insights from the REAl-World Lusutrombopag Treatment in ITalY Study.

Background and aims: Management of severe thrombocytopenia poses significant challenges in patients with chronic liver disease. Here, we aimed to evaluate the first real-world European post-marketing cohort of cirrhotic patients treated with lusutrombopag, a thrombopoietin receptor agonist, verifying the efficacy and safety of the drug. Methods: In the REAl-world Lusutrombopag treatment in ITalY (REALITY) study, we collected data from consecutive cirrhotic patients treated with lusutrombopag in 19 Italian hepatology centers, mostly joined to the "Club Epatologi Ospedalieri" (CLEO). Primary and secondary efficacy endpoints were the ability of lusutrombopag to avoid platelet transfusions and to raise the platelet count to ≥50,000/μL, respectively. Treatment-associated adverse events were also collected. Results: A total of 66 patients and 73 cycles of treatment were included in the study, since 5 patients received multiple doses of lusutrombopag over time for different invasive procedures. Fourteen patients (19%) had a history of portal vein thrombosis (PVT). Lusutrombopag determined a significant increase in platelet count [from 37,000 (33,000-44,000/μL) to 58,000 (49,000-82,000), p < 0.001]. The primary endpoint was met in 84% of patients and the secondary endpoint in 74% of patients. Baseline platelet count was the only independent factor associated with response in multivariate logistic regression analysis (OR for any 1000 uL of 1.13, CI95% 1.04-1.26, p 0.01), with a good discrimination power (AUROC: 0.78). Notably, a baseline platelet count ≤ 29,000/μL was identified as the threshold for identifying patients unlikely to respond to the drug (sensitivity of 91%). Finally, de novo PVT was observed in four patients (5%), none of whom had undergone repeated treatment, and no other safety or hemorrhagic events were recorded in the entire population analyzed. Conclusions: In this first European real-world series, lusutrombopag demonstrated efficacy and safety consistent with the results of registrational studies. According to our results, patients with baseline platelet counts ≤29,000/μL are unlikely to respond to the drug.

A novel scoring model for predicting efficacy and guiding individualised treatment in immune thrombocytopaenia.

Despite diverse therapeutic options for immune thrombocytopaenia (ITP), drug efficacy and selection challenges persist. This study systematically identified potential indicators in ITP patients and followed up on subsequent treatment. We initially analysed 61 variables and identified 12, 14, and 10 candidates for discriminating responders from non-responders in glucocorticoid (N = 215), thrombopoietin receptor agonists (TPO-RAs) (N = 224), and rituximab (N = 67) treatments, respectively. Patients were randomly assigned to training or testing datasets and employing five machine learning (ML) models, with eXtreme Gradient Boosting (XGBoost) area under the curve (AUC = 0.89), Decision Tree (DT) (AUC = 0.80) and Artificial Neural Network (ANN) (AUC = 0.79) selected. Cross-validated with logistic regression and ML finalised five variables (baseline platelet, IP-10, TNF-α, Treg, B cell) for glucocorticoid, eight variables (baseline platelet, TGF-β1, MCP-1, IL-21, Th1, Treg, MK number, TPO) for TPO-RAs, and three variables (IL-12, Breg, MAIPA-) for rituximab to establish the predictive model. Spearman correlation and receiver operating characteristic curve analysis in validation datasets demonstrated strong correlations between response fractions and scores in all treatments. Scoring thresholds SGlu ≥ 3 (AUC = 0.911, 95% CI, 0.865-0.956), STPO-RAs ≥ 5 (AUC = 0.964, 95% CI 0.934-0.994), and SRitu = 3 (AUC = 0.964, 95% CI 0.915-1.000) indicated ineffectiveness in glucocorticoid, TPO-RAs, and rituximab therapy, respectively. Regression analysis and ML established a tentative and preliminary predictive scoring model for advancing individualised treatment.