Changes In Platelet Count Research Articles

Determination of Platelet Count and Platelet Indices among Sudanese Patients with Chronic Kidney Disease

Background: Patients with chronic kidney disease (CKD) are at a considerably higher risk of thrombotic and hemorrhagic challenges. Platelet function studies in CKD are contradictory, ranging from decreased platelet function to normal or even increased platelet reaction. Our study aims to evaluate the change in platelet count (PC) and platelet indices (platelet distribution width [PDW], platelet large cell ratio [PLCR], and mean platelet volume [MPV]) among Sudanese patients with CKD.Methods and Results: This case-control study was conducted from February to August 2014 at East Nile Hospital, Khartoum, Sudan. The study involved 75 patients diagnosed with CKD (mean age 52.43±18.4 years) and 75 healthy individuals (mean age 50.3±14 years) as a control group. PC, PDW, PLCR, and MPV tests were conducted using a Sysmex KX-21N Automated Hematology Analyzer (Sysmex Corporation, Japan), and creatinine level was measured by Roche/Hitachi Cobas C311 analyzer (Basel Switzerland). The creatinine level was significantly higher in CKD patients than in the control group: 7.91±4.8 mg/dL and 1.4±1.3mg/dL, respectively (P=0.000). We found an insignificant difference between CKD patients and the control group in terms of PC, MPV, PDW, and PLCR; an insignificant difference in PC and all PI between CKD patients with creatinine levels <6 mg/dL and >6mg/dL; and an insignificant difference in PC and all PI between the group with CKD duration <2 years and >2 years and between CKD patients on hemodialysis and without hemodialysis. Conclusion: This study found no difference in PC and studied platelet indices in CKD patients, compared to the control group and no difference in PC and PI (MPV, PDW, and PLCR) in patients on hemodialysis versus patients not on hemodialysis.

Association between alteration of neutrophil to lymphocyte ratio, platelet to lymphocyte ratio, cancer antigen-125 and surgical outcomes in advanced stage ovarian cancer patient who received neoadjuvant chemotherapy

IntroductionOptimal resection significantly influences the prognosis of advanced-stage epithelial ovarian cancer (EOC) patients undergoing debulking surgery. In patients who received neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS), the determination of the ideal timing for surgery remains a challenge. Inflammatory markers, including the neutrophil-to-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and CA-125 levels, have been recognized as potential predictive markers. ObjectiveThis study aims to evaluate the predictive value of changes in NLR, PLR, and CA-125 levels following NACT, specifically assessing their impact on surgical outcomes during IDS for advanced-stage EOC. MethodsA retrospective cohort study enrolled advanced-stage EOC patients who underwent NACT followed by IDS at Vajira Hospital in Thailand from January 2009 to June 2023. Data on clinical, surgical, and inflammatory markers were collected, and the predictive value of these markers for suboptimal resection outcomes was assessed. ResultsAmong the 65 patients, 98.5 % exhibited radiologic responses post-NACT, while 29.2 % experienced suboptimal resections. Univariate analysis did not reveal significant associations between suboptimal resection and NLR changes after the first NACT cycle or alterations in NLR, PLR, and CA-125 levels at the end of NACT. Subsequent analysis suggested that an NLR decrease exceeding 70 % after the first cycle and NACT completion might predict suboptimal resection, yet statistical analyses showed limited prognostic efficacy (AuROC = 0.608 and 0.597). ConclusionOur study does not support that changes in NLR, PLR, platelet count, and CA-125 levels after NACT reliably predict IDS outcomes. Additional prospective investigations using larger cohorts or a combination of evaluation methods, rather than relying solely on NLR, are recommended.

Platelet Count Doubling after One Course of Demethylated Drug Therapeutic Predicts the Treatment Response and Efficacy of Patients with Myelodysplastic Syndrome

To investigate the predictive value of platelet doubling (platelet count doubling) after one course of hypomethylating agents (HMA) on the treatment response and efficacy of myelodysplastic syndrome (MDS). Clinical and pathological data of 75 patients who received HMA in our hospital from January 2017 to March 2022 were collected and analyzed. All patients were divided into two groups according to whether their platelet count doubled after one course of treatment, including platelet doubling group and non-doubling group, and statistical analysis was performed to compare the treatment response and efficacy between the two groups. In addition, platelet count changes were compared between azacitidine and decitabine therapy. Compared with the non-doubling platelet count group, the ORR of the doubling platelet group was significantly better after 3 courses of treatment (P =0.002), and there was a statistically significant difference in the number of HI between the two groups (P =0.005). In addition, the median survival time (MST) was 26 months in the platelet doubling group and 11 months in the non-doubling group (P =0.001). The overall survival (OS) and 1- and 2-year survival rates of the platelet doubling group were also significantly better than those of the non-doubing group. Multivariate COX analysis showed that platelet count doubling was an independent predictor of OS in MDS patients after 1 course of treatment (P =0.013). There was no significant difference in the response rate of platelet count doubling between MDS patients treated with azacitidine and decitabine (33.3% vs 23.8%, P >0.05). Platelet count doubling after one course of treatment can be used as a predictor of response rate and survival of demethylated drug therapy in MDS patients. In addition, there was no significant difference in the response rate of platelets in MDS patients treated with azacitidine or dicetabine.

The investigation of thrombocytopenia after transcatheter occlusion of patent ductus arteriosus

ObjectiveTo investigate the risk factors for thrombocytopenia after transcatheter occlusion operation of patent ductus arteriosus (PDA).MethodRetrospective analyses were conducted using clinical data from 106 patients with PDA who underwent transcatheter closure operations at Henan Provincial Chest Hospital, Zhengzhou University, from January 2018 to June 2022. The study compared the changes in platelet counts before and after the operation, and investigated the risk factors for thrombocytopenia following PDA closure in different groups and layers.ResultsThe platelet count of patients with PDA significantly decreased after undergoing transcatheter PDA occlusion. Logistic regression analysis revealed that factors such as PDA diameter, occluder diameter, pressure difference on the two sides of the occluder, and residual shunt were associated with an increased risk of thrombocytopenia following PDA occlusion. Specifically, the size of the occluder and the pressure difference between the two sides of the occluder were found to have a negative correlation with the postoperative platelet count. Further subgroup analysis demonstrated that the incidence of total thrombocytopenia was significantly higher in the large PDA group compared to the small-medium PDA groups.ConclusionOur findings suggest that occluder diameter, the pressure difference between the two sides of the occluder, and the residual shunt are major risk factors correlated with the incidence of postoperative thrombocytopenia. However, a multicenter and long-term prospective study is required to further evaluate the prognosis of PDA patients with thrombocytopenia after transcatheter occlusion.

Examining the Changes in Coagulation Parameters in Patients Infected with SARS-CoV-2 Variants (Alpha, Beta, Delta, and Omicron)

Background: It is known that the change in coagulation parameters has an effect on mortality and prognosis in COVID-19 patients. The SARS-CoV-2 virus has changed with mutations in the genome of the virus since the beginning of the pandemic, and the resulting variants have been recorded by the World Health Organization. With these variations, the clinical severity of the disease and laboratory parameters have also changed. Objectives: In this study, we examined the changes in D-dimer levels, fibrinogen levels, platelet count (PLT), and mean platelet volume (MPV) between SARS-CoV-2 Alpha (B.1.1.7), Beta (B.1.351) Delta (B.1.617.2), and Omicron (B.1.1.529) variants. Methods: The study was conducted retrospectively on 28 195 adult patients with SARS-CoV-2 infection. At the time of application, data on age, gender, SARS-CoV-2 variant status, D-dimer levels (n = 7090), fibrinogen (n = 5709), PLT (n = 7066), and MPV (n = 8330) were collected. Patients were divided according to alpha, beta, delta, and omicron variants. The changes in variants were examined statistically. Results: The incidence of the delta variant in women was higher than the other variants, followed by alpha and omicron (P = 0.001). The Beta variant was detected at a higher rate in males. The ages of the cases with the Omicron variant were higher than the cases with Alpha, Beta, and Delta variants (P = 0.001, P = 0.001, P = 0.001, and P < 0.01, respectively). In laboratory parameters, D-dimer and fibrinogen levels were detected to be significantly higher in Delta and Omicron variants. PLT and MPV were determined to be lower in delta and omicron than in alpha and beta variants. Conclusions: Examination of the changes in laboratory coagulation parameters according to variants shows that the tendency to clot increases from alpha to omicron.

Platelet to lymphocyte ratio: can it be an early economical mortality predictor of AKI patients?

Abstract Background Acute kidney injury (AKI) affects over 13 million individuals annually worldwide, resulting in 1.7 million deaths. The potential long-term progression to chronic kidney disease (CKD) and renal failure, as well as the acute use of health care resources associated with acute kidney injury (AKI), impose enormous costs on society. The platelet-to-lymphocyte ratio (PLR) has emerged as a useful economical marker for detecting changes in platelet and lymphocyte counts owing to acute inflammatory and prothrombotic states. This study aimed to determine the PLR in patients with AKI and evaluate the in-hospital mortality. Results The median PLR was compared between the non-survivor and survivor groups, and it was determined that the non-survivor group had a significantly higher PLR. ( p < 0.001) For further subgroup analysis, the PLR was stratified into three groups: ≤ 100, 101–200, and > 200. Significantly more patients were demised in the PLR group 101–200 than in the PLR group ≤ 100, while all of the patients died in the PLR group greater than 200. The group with a PLR > 200 had a higher SOFA score > 10 (p = 0.006), a lower eGFR (p = 0.001), and higher platelet counts (p = 0.001), higher serum creatinine (p = 0.001), BUN (p < 0.001), and procalcitonin levels (p = 0.007). In multivariate Logistic regression analysis to predict the mortality outcome, PLR (OR 1.051; 95% CI, 1.016–1.087; p = 0.004) was identified as one of the significant indicators predicting AKI mortality. Other statistically significant indicators included SOFA scores (OR 2.789; 95% CI, 1.478–5.260; p = 0.002), procalcitonin levels (OR 0.898; 95% CI, 0.818–0.987; p = 0.025), and duration of hospital stay (OR 0.494; 95% CI, 0.276–0.886; p = 0.017). The ROC curve for the PLR yielded a value of 0.803 [95% CI, 0.720–0.886; p < 0.001] with the optimal cutoff value for the PLR to determine prognosis being 107.905, with a sensitivity of 82.5% and a specificity of 51.2%. Conclusion PLR plays a significant role in the early prediction of prognosis (survival or death) for patients with AKI in ICU on a short-term basis.

Effects of quercetin and extracts from Phyllanthus emblica, Morus alba, and Ginkgo biloba on platelet recovery in a rat model of chemotherapy-induced thrombocytopenia

BackgroundChemotherapy-induced thrombocytopenia (CIT) is a major reason for chemotherapy delays, dose reduction, or even treatment discontinuation, which may impact oncologic outcomes. We investigated the effects of quercetin and extracts of Phyllanthus emblica fruit (PEE), Morus alba leaf (MAE), and Ginkgo biloba leaf (GBE) on platelet recovery in a rat model of chemotherapy-induced thrombocytopenia. MethodsThe total phenolic content (TPC), total flavonoid content (TFC), quercetin content, and antioxidant activities of all the extracts were determined. Sixty male Sprague Dawley rats were categorized into healthy controls and CIT groups. The CIT groups was administered a cyclophosphamide solution, while the control group received a saline solution. Each group was then subdivided into five subgroups of six animals which were administered with PEE, MAE, GBE, quercetin, or a vehicle for 15 days. ResultsThe highest quercetin content was found in PEE, followed by MAE and GBE, which correlated with their antioxidant properties. Administration of these extracts and quercetin did not significantly change the platelet counts in healthy rats. Thrombocytopenic rats treated with PEE, MAE, and GBE also were not associated with significant changes in platelet counts. However, more rapid platelet count recovery was observed in all groups receiving extracts. On day 11, platelet counts in the PEE, MAE, and GBE groups returned to near baseline levels with a mean of 4.29 %, −40.77 %, and −14.24 %, respectively, compared to −71 % in the CIT group. In thrombocytopenic rats treated with quercetin, there was a significant increase in platelet counts on days 9 and 11, with a mean decrease of 5.41 % from baseline on day 11. ConclusionQuercetin improved platelet recovery in the animal model of CIT. This finding merits for further investigation to better elucidate the health benefits of quercetin and quercetin-rich plants and potential pharmacokinetics underpinning their activity in thrombocytopenia.

Тромбоцитарные индексы и их прогностическая значимость у больных хроническим гепатитом С

The purpose — to determine the role of platelet count (Tr) and platelet indices — average platelet volume (MPV), platelet distribution width (PDW) in the prognostic significance of the activity of the infectious process in patients with chronic hepatitis C (CHC). Material and methods. 310 CHC patients were under observation. The patients were divided into groups, depending on the number Tr in the phases of disseminated intravascular coagulation (DIC). The first group corresponded to the hypercoagulation phase (Tr > 330 x 109/l, n = 22); the second to the intermediate phase (Tr 330–200 x 109/l, n = 132), the third to hypocoagulation (Tr < 200 x 109/l, n = 91). A group of patients with liver cirrhosis (n = 65), class A (n = 54), class B (n = 11) by Child — Turcotte — Pugh was studied separately. The Tr number and platelet indices PDW and MPV were determined as part of a routine blood test using an automatic analyzer XN-20 (SYSMEX, Japan). Results. The most significant changes in platelet counts were in patients in the phase of hypocoagulation and with liver cirrhosis in comparison with other groups of patients – intermediate phase and hypercoagulation in the form of their growth. In all groups, according to the phases of DIC syndrome, the fibrosis level was lower (p=0.00) compared with patients with liver cirrhosis. Against this background, there was a parallel increase in platelet counts. This confirmed the presence of an inverse correlation between the number of blood plates and the level of liver tissue fibrosis, as well as a direct correlation between the values of platelet parameters: PDW and fibrosis; MPV and fibrosis. An inverse correlation was found between blood platelets and platelet indices PDW and MPV, as well as a direct correlation between PDW and MPV indices. Conclusion. Platelet counts (RDW, MPV) in patients with CHC had an inverse correlation with the number of blood plates and a direct correlation with fibrosis and with each other. The Tr number and platelet indices (RDW, MPV) reflect the activity of the infectious process, which allows using them to predict the course of the disease under the long-term infection with hepatitis C virus.

The development and validation of a liquid chromatography tandem mass spectrometry method for the quantification of selinexor and its application in Chinese multiple myeloma patients.

Selinexor is a nuclear exportin-1 (XPO1) inhibitor that has been approved for the treatment of multiple myeloma patients. However, sustained use of selinexor may result in some undesirable consequences. Furthermore, selinexor has moderate inter-patient variability. Herein, we developed an ultrahigh-performance liquid chromatography tandem mass spectrometry method for measuring selinexor levels in human plasma ranging from 1 to 1000 ng mL-1. Furthermore, the developed approach was validated in accordance with FDA criteria. The established approach demonstrated inter-day and intra-day precision, expressed as the relative standard deviation, of less than 8%, with accuracies of less than 6%, expressed as relative error. The results showed that the protein depletion was quite complete for selinexor extraction, with recoveries ranging from 85.89 to 108.38%. The validated method facilitates the quantitation of selinexor in multiple myeloma patients. The selinexor plasma concentration exhibits obvious inter-patient' variability after administration. Thus, it is necessary to make a personalized prescription through therapeutic drug monitoring. Furthermore, the change in platelet counts before and after selinexor treatment was shown to be related to the plasma concentration at 3 h after administration, which provides the basis for therapeutic drug monitoring sampling time points and a method for predicting the occurrence of thrombocytopenia. In conclusion, the developed method can be used for the quantification of the plasma concentration of selinexor, and it is of great significance to conduct therapeutic drug monitoring for patients taking selinexor in order to enhance therapeutic effects and prevent the occurrence of adverse reactions.

Role of thrombopoietin receptor agonists in chemotherapy-induced thrombocytopenia: A meta-analysis.

Chemotherapy-induced thrombocytopenia (CIT) is a significant challenge in cancer treatment, often leading to dose reductions and reduced number of cycles. The limited effectiveness of platelet transfusions in managing CIT highlights the need for alternative treatments. Thrombopoietin receptor agonists (TPO-RA), including romiplostim, eltrombopag and avatrombopag, have shown potential in increasing platelet counts in CIT patients, necessitating a comprehensive analysis of their efficacy. This meta-analysis followed the Preferred Reporting Items for Systemic Reviews and Meta-analysis guidelines, searching Ovid databases up to 5 October 2023. The primary metric of interest was platelet count changes post-TPO-RA administration in CIT patients. From the initial 867 studies obtained, 7 studies were selected based on the inclusion criteria. The analysis included 348 patients. A significant association was found between TPO-RA administration and platelet count increase, with a combined-effect increase of 69.52 ± 2.24 × 109/l. Subgroup analysis based on Romiplostim use suggested an increase of approximately 70.11 ± 39.07 × 109/l, while non-Romiplostim TPO-RAs showcased an increase of about 68.09 ± 82.58 × 109/l. The meta-analysis demonstrates the effectiveness of TPO-RAs in managing CIT. Further research comparing platelet increases across standardised TPO-RA regimens is recommended to refine treatment strategies. This analysis provides valuable insights for clinicians in tailoring CIT treatment using TPO-RAs.

The Mechanism Underlying Lenalidomide-Induced Thrombosis Susceptibility

Introduction: Lenalidomide, a well-established drug for the treatment of multiple myeloma, significantly enhances patients' survival. Previous clinical studies have demonstrated that its main side effect is an increased risk of thrombotic events. However, the underlying mechanism remains unexplored. Therefore, this study aims to elucidate the mechanism and offer insights into the selection of clinical thrombotic prophylaxis drugs. Methods: Firstly, we conducted a retrospective analysis of clinical data from 169 newly diagnosed multiple myeloma patients who received lenalidomide. To confirm the impact of lenalidomide on thrombosis formation, FeCl3-induced thrombosis and deep venous thrombosis models in mice were established. To investigate the effects of lenalidomide on platelet function, both in vivo and in vitro experiments were designed. Results From January 2013 to June 2021, 169 NDMM patients with VRD as the first-line treatment were included in this study. During our follow-up, 8 patients had TEs . TEs included 8 VTE and 1 ATE. There were 7 DVT and 1 PE including in 8 VTE. Among the 8 patients suffering from thrombus, 2 patients did not receive thromboprophylaxis because of low platelet count, and the other 6 patients took aspirin, warfarin and rivaroxaban. Lenalidomide (25 mg/kg, 50 mg/kg, per day) or vehicle (DMSO) for 14 days were administrated for 2 weeks to healthy male mice. Compared with DMSO group, lenalidomide 25 mg/kg group and lenalidomide 50 mg/kg group significantly affected the formation of venous thrombosis , and there were significant statistical differences in both the length ( p=0.002; p=0.0005) and weight ( p<0.0001; p<0.0001) of thrombosis. In contrast, the formation of arterial thrombosis was not affected by lenalidomide administration in vivo, occlusion time of experiment group had control group did not have difference, which is consistent with the low incidence of ATE in clinical practice. To further explore the mechanism, we firstly focused on whether lenalidomide affects platelet function. Compared to baseline data, after taking one cycle of lenalidomide, the mean platelet volume (MPV, p<0.0001), platelet distribution width (PDW, p<0.0001), large platelet ratio ( p<0.0001), platelet hematocrit ( p=0.0005), and fibrinogen ( p=0.0008) of patients increased significantly. To evaluate the effect of lenalidomide on NDMM patient's platelet activation in vitro, we pretreated the washed platelets from NDMM with lenalidomide (5 or 10 um) or DMSO for platelet function assays . There was no difference between the three groups. To clarify the effect of lenalidomide on platelet function and parameters in vivo, lenalidomide (25 mg/kg, once per day), (50 mg/kg, once per day) or DMSO were administrated for 2 weeks to mice . The last dose was taken the night before narcotism, and platelet function was measured the next morning. We found that different from the changes in platelet related parameters in patients, in vivo data of mice showed no significant changes in platelet count , MPV , PDW , large platelet ratio , and platelet hematocrit after taking lenalidomide.Then we prepared washed platelets from mice for functional experiments. There was no difference between the three groups. In order to further explore the impact of lenalidomide on coagulation function in NDMM patients, we compared the coagulation parameters of NDMM patients who were enrolled at the time of diagnosis and after one cycle of taking lenalidomide. We found significant differences in prothrombin time, thrombin time, and prothrombin time ratio ( PTR, p<0.0001), while there was no statistical difference in some changes in activated partial thrombin time ( APTT, p=0.0881). These results may suggest that lenalidomide promotes the formation of venous thrombosis in vivo by influencing the coagulation pathway. Conclusions: The administration of lenalidomide had no significant impact on platelet function, which may affect venous thrombus formation by affecting coagulation. Therefore, anticoagulant drugs may be superior to antiplatelet drugs in the selection of clinical thrombus prophylaxis.

Pharmacologic Reduction of Platelet Count Attenuates Whole Blood Hypofibrinolysis in a Mouse Model of Sickle Cell Disease

Increased risk of venous thrombosis is a hallmark of sickle cell disease (SCD). We previously reported that SCD dramatically alters the properties of venous clots, including resistance to tissue plasminogen activator (tPA)-mediated fibrinolysis. Using an internal fibrinolysis assay (tPA added to whole blood before clot formation), clot lysis time (CLT) was significantly (p<0.01) prolonged in clots formed ex vivo from whole blood of SCD patients (SS) (651±34 min) compared to race-matched controls (AA) (370±75). We then investigated how therapeutic RBC exchange affects CLT in SCD patients. Interestingly, despite hemoglobin A levels of approximately 50%, CLT for the pre-exchange SS clots (639±81 min) was similar to CLT recorded for blood clots from SS patients who did not undergo RBC exchange (see above). However, CLT for post-exchange SS clots was significantly shortened (240±34; p<0.05 vs pre-exchange) to the level observed for clots from AA controls. We noticed that the RBC exchange procedure not only changes the proportion of AA and SS RBCs, but also reduces both platelet counts and serum plasminogen activator inhibitor-1 (PAI-1) levels by approximately 50-60%. Importantly, exvivo restoration of the platelet number in post-exchange samples to the level observed in pre-exchange blood resulted in restoration of the hypofibrinolytic phenotype and a partial restoration of serum PAI-1 levels. Changes in platelet count after RBC exchange are quickly normalized. Therefore, in the current study, we investigated the effect of sustained reduction of platelet count on whole blood hypofibrinolysis in SCD mice. Using an external fibrinolysis assay (2.5 nM tPA added after clot formation) as described by Bonnard et al. (Sci Rep, 2017) we determined if hypofibrinolysis is also observed in Townes sickle cell mice (SS). Consistent with human SCD, the CLT was profoundly increased in ex vivo clots formed from whole blood of SS mice (n=13) compared to non-sickle (AA) control mice (n=12) (Figure 1A; first two bars). Next, we demonstrated that the cellular fraction of SS blood was responsible for resistance of the clots to tPA-mediated fibrinolysis, regardless of whether the plasma was from SS or AA mice (Figure 1A; last four bars). We then used a pharmacologic strategy to reduce platelet counts. Thrombopoietin (TPO) is a growth factor that promotes maturation of hematopoietic stem cells into megakaryocytes and thereby increases platelet production. We previously showed that silencing liver TPO expression using a liver-specific antisense oligonucleotide (TPO-ASO) resulted in a sustained 50% reduction in both plasma TPO levels and platelet counts without affecting hemostasis in both baboons and mice. In the present study, TPO-ASO (20 mg/kg subcutaneous) or vehicle control were administered to 3-month old AA and SS mice (n=3-6) on days 0, 3, 5 and 7, followed by weekly maintenance injections for the next 3 weeks. 4 weeks after initiation of treatment, mice were euthanized, and blood was collected to evaluate plasma levels of TPO and external whole blood fibrinolysis. Platelet, but no other cell count was significantly reduced in both AA (by 62%, p<0.05) and SS (by 47%, P<0.05) mice treated with TPO-ASO. Baseline plasma levels of TPO were reduced in SS mice (101±20 pg/ml) compared to AA controls (182±10; p<0.05). TPO-ASO treatment resulted in significant reduction of TPO plasma levels in both AA (21±16; p<0.01) and SS (17±9; p<0.05) mice. Interestingly, TPO-ASO-mediated reduction of platelet count did not affect CLT of ex vivo clots formed from whole blood of AA mice (Figure 1B). In contrast, TPO-ASO treatment dramatically reduced CLT in SS clots (p<0.05) (Figure 1B). In conclusion, we demonstrated that: (i) the resistance of ex vivo formed clots to tPA-mediated fibrinolysis observed in SCD patients can be reproduced in a mouse model of the disease; (i) the external fibrinolysis assay provides a robust and reliable model for studying whole blood hypofibrinolysis in SCD; (iii) hypofibrinolysis in SCD appears to be predominantly driven by the cellular fraction of blood; and (iv) platelets play an important role in the hypofibrinolytic phenotype in SCD, demonstrated by mitigation of the hypofibrinolytic phenotype in SS mice subjected to long-term reduction of platelet count. Further studies investigating the effect of platelet count reduction on venous thrombosis and vascular stasis in SS mice are currently ongoing.

Efficacy and Safety of Avatrombopag in the Treatment of Chemotherapy-Induced Thrombocytopenia in Children with Acute Lymphoblastic Leukemia: A Retrospective Study

Introduction: Chemotherapy-induced thrombocytopenia (CIT) is one of the most common complications during cancer treatment, increasing the risk of bleeding, medical costs, and potentially affecting treatment outcomes by necessitating chemotherapy dose reductions or delays. Avatrombopag, a thrombopoietin receptor agonist, has been approved as the first-line drug for the treatment of thrombocytopenia in chronic liver diseases. Its efficacy and safety was demonstrated in disorders like aplastic anemia and primary immune thrombocytopenia. However, the research regarding its use in children with CIT is lack. Objective: This retrospective study aimed to analyze the efficacy and safety of avatrombopag in the treatment of chemotherapy-induced thrombocytopenia in children with acute lymphoblastic leukemia, providing a potential new therapeutic option for managing CIT in pediatric cancer patients. Methods: The data of experimental group were collected from 30 pediatric patients with acute lymphoblastic leukemia and CIT who received avatrombopag treatment in the pediatric ward of Southern Hospital from August 2022 to July 2023. Additional data from 250 pediatric patients with acute lymphoblastic leukemia and CIT who did not receive avatrombopag treatment at Southern Hospital from January 2020 to July 2023 were collected as the control group. A propensity score matching method was employed to analyze the two patient groups, resulting in a successful matching of 30 pairs (CAT 21 pairs, CAT+9 pairs). The collected clinical data included age, gender, height, weight, risk stratification, infection status, platelet count changes during each chemotherapy cycle, platelet transfusion frequency, clinical manifestations of bleeding, avatrombopag usage, and complications. All patients were treated with the 2020-CCCG-ALL chemotherapy regimen,diagnosed with CIT,under 18 years of age, and excluded if they had concomitant hematological disorders, chronic liver disease, cardiovascular diseases, severe arterial or venous thrombosis, or splenomegaly. The initial avatrombopag dose was 10mg daily for patients weighing less than 30kg and 20mg daily for patients weighing 30kg or more. Avatrombopag was stopped when PLT≥100×10 9/L or an increase in PLT by ≥50×10 9/L compared to pre-treatment levels. Results: Comparison between the experimental and control groups revealed that the experimental group had a shorter duration of grade 3 or higher thrombocytopenia (3.36±1.77 days vs. 4.7±2.46 days, P=0.019) and a shorter time to platelet recovery (7.9±2.63 days vs. 9.76±2.77 days, P=0.01). Subgroup analysis within the CAT and CAT+ chemotherapy phases indicated that significant platelet value differences (P<0.05) were observed between the two groups at the start of platelet decline (day 10±2) [PLT: (268.13±216.52) ×10 9/L vs. (152.13±89.58) ×10 9/L] and during platelet nadir (day 14±2) [PLT: (435.97±285.83) ×10 9/L vs. (285.07±148.67) ×10 9/L]. Additionally, a statistically significant difference (P<0.05) in PLT change from baseline to day 5 and day 7 was observed in the experimental group [46.5 (20.5, 93) ×10 9/L and 67 (15.5, 180) ×10 9/L, respectively]. During the chemotherapy cycles, only 4 patients (8.3%) experienced bleeding events, and after avatrombopag treatment, 11 patients (22.9%) did not require platelet transfusions. Four adverse events of secondary platelet increase were recorded, and no other adverse events were reported. Conclusion: Avatrombopag, as an alternative treatment for chemotherapy-induced thrombocytopenia in children with acute lymphoblastic leukemia, demonstrated the potential to promote platelet recovery and exhibited good safety. keywords:avatrombopag,Chemotherapy-induced thrombocytopenia,acute lymphoblastic leukemia

Management of Immune Thrombotic Thrombocytopenic Purpura without Therapeutic Plasma Exchange: Analysis of Efficacy and Safety Data

Background: Immune thrombotic thrombocytopenic purpura (iTTP) is a rare, life-threatening autoimmune disorder caused by ADAMTS13 deficiency. Caplacizumab, an anti-VWF nanobody, is approved for iTTP treatment, reducing the need for therapeutic plasma exchange (TPE) and improving platelet recovery and survival. Methods: We conducted a retrospective study on 42 acute iTTP cases in Austria and Germany, treated with a modified regimen aimed at avoiding TPE if platelet count increased post-first caplacizumab dose. An extensive efficacy and safety analysis of this approach was performed, in comparison with a control group of 59 patients with iTTP, receiving frontline caplacizumab treatment with TPE and immunosuppression (standard of care, SOC). The main outcome was time to platelet count normalization. Secondary outcomes included clinical response, exacerbation, refractory iTTP, and iTTP-related deaths. Retrospective safety assessments with evaluation of treatment emergent adverse events (TEAE) were performed in both cohorts. Results: The median time to platelet count normalization was similar between the two cohorts (3 and 4 days; P = 0.31, see Figure 1). There were no significant differences in clinical response, exacerbations, refractoriness, or iTTP-related deaths (see Table 1). Four patients did not respond to the first dose of caplacizumab, and TPE was initiated. Cytomegalovirus infection, HIV/hepatitis B co-infection, and ovarian teratoma may have hindered immediate treatment response. Platelet count doubling and median platelet count change after first caplacizumab dose were unaffected by TPE. The median time to LDH normalization was 11 days in the TPE-free cohort. During overall follow-up at least one adverse event (TEAE) was observed in 11 patients (26.2%) in the TPE-free group and 15 patients (25.4%) in the SOC group (excluding adverse events of iTTP that were evaluated as outcome parameters) (see Table 1). There was one TTP-related death reported in the SOC group (1.7%). The cause of death in this patient was cerebral ischemia due to multiple strokes. Serious adverse events associated with therapeutic plasma exchange were observed in 3 patients (5.1%) exclusively in the SOC cohort. These included (1) in-hospital cardiac arrest (IHCA), (2) generalized seizure and supraventricular tachycardia and (3) a transfusion reaction with hypotension, rigors, pruritus and exanthema. Bleeding complications were reported without a significant difference and mainly comprised gingival bleeding and epistaxis. Two patients in the TPE-free cohort (4.8%) experienced major bleeding events, namely subdural hematoma requiring surgical intervention and gastrointestinal bleeding with mass transfusion. Spontaneous subdural hematoma occurred in one patient after 20 days of caplacizumab treatment. Gastrointestinal bleeding from a colon diverticulum occurred in another patient after a clinical response and resulted in a significant drop in hemoglobin and thrombocytes. Gastrointestinal bleeding worsened with concomitant factor XIII deficiency, which was reconstituted intravenously in addition to mass transfusion. Conclusion: Caplacizumab and immunosuppression, without TPE, rapidly controlled microvascular thrombosis and achieved a sustained clinical response in iTTP. The efficacy was similar to the control group, which received SOC. Standard iTTP treatment with TPE may lead to a prolonged hospital stay, including admission to the ICU, multiple sessions of daily TPE with associated risks, and the associated costs of plasma, equipment, nursing care, and medical supervision. The number of patients experiencing critical adverse events was comparable between groups. Bearing all restrictions of a retrospective cohort in mind, we did not identify a critical safety signal for TPE-free iTTP-treatment. However, TPE itself resulted in three life-threatening adverse events in the SOC cohort, including an in-hospital cardiac arrest. In conclusion, omitting TPE appears to be a viable choice for acute iTTP management that may reduce treatment burden without compromising patient outcomes or safety.

384. Factors Potentiating the Risk of Linezolid-induced Thrombocytopenia in Patients without Haemato-oncologic Diseases: A Case-control Study

Abstract Background Thrombocytopenia is a major adverse effect of linezolid due to myelosuppression. Many studies assessed factors associated with this effect, but most included patients with haemato-oncologic diseases, which may confound the assessment of thrombocytopenia. Therefore, this study aimed to investigate risk factors for linezolid-induced thrombocytopenia in patients without haemato-oncologic diseases. Methods This was a multicenter retrospective case-control study of adults treated with linezolid 600 mg twice daily for ≥ 3 days. Cases were the patients who developed thrombocytopenia while controls are those who didn't develop it. Exclusion criteria were haemato-oncologic diseases, active COVID-19, active dengue fever, baseline platelet count < 100 × 103/mm3, concurrent therapy with trimethoprim/sulfamethoxazole or valproic acid, platelet transfusion within 7 days before linezolid therapy, and insufficient platelets data. Various factors were assessed for potential association with linezolid-induced thrombocytopenia (defined as drop in platelet count below 100 × 103/mm3). Results 142 patients were included, 31 cases and 111 controls. Patients in both groups had a median age of 62 years and received linezolid for a median of 8 days. Platelet counts significantly dropped in the cases (Figure 1). Figure 2 shows the trend of change in platelet count (the white square indicates the median duration to thrombocytopenia, 8 days). In the univariate analysis, serum creatinine, creatinine clearance, baseline hemoglobin, baseline platelet count, and bacteremia were significantly associated with thrombocytopenia. However, after adjusting for confounders in the multivariate analysis, only low baseline hemoglobin and bacteremia were associated with thrombocytopenia (adjOR = 0.71; 95% CI 0.53-0.95; P = 0.022 and adjOR = 17.02; 95% CI 1.15-251-71; P = 0.039, respectively). Among the cases, those who had a baseline platelet count of < 200 × 103/mm3 developed thrombocytopenia faster as early as 3 days (log-rank P = 0.002; figure 3). Figure 1 Rate of change in platelet count between the cases (thrombocytopenia) and controls (no thrombocytopenia) Figure 2 Trend of platelet counts over 14 days in the cases (thrombocytopenia) and controls (no thrombocytopenia) Figure 3 Kaplan-Meier curve for the development of thrombocytopenia depending on baseline platelet count Conclusion Patients without haemato-oncologic diseases are at risk of linezolid-induced thrombocytopenia. especially those with bacteremia and low hemoglobin level. Patients with low baseline platelet count should be monitored closely early in therapy. Disclosures All Authors: No reported disclosures

Effects of CYP3A5 Genotypes on Thrombocytopenia in Liver Transplantation Patients Treated with Tacrolimus.

Thrombocytopenia is a complication after liver transplantation. This study's aims were to evaluate the role of CYP3A5 genotypes on tacrolimus-induced thrombocytopenia after orthotopic liver transplantation. In this retrospective case-control study, data from 100 patients who underwent deceased-donor liver transplantation (DDLT) were divided into CYP3A5*3 genotype (donor/recipient) tacrolimus fast- (A*/A*, n = 22), intermediate- (A*/GG, n = 20; GG/A*, n = 31) and slow-metabolizer (GG/GG, n = 27) groups. Platelet count changes and prognosis for 180 days after surgery were compared. Platelet counts declined significantly after DDLT, especially on postoperative day (POD) 3, and continued at low levels for a week thereafter in all groups. In the GG/GG group, platelet counts on POD3 (50.29 ± 5.44 × 109/L) were the lowest among the groups (A*/A*, 71.00 ± 6.22 × 109/L; A*/GG, 57.95 ± 6.21 × 109/L; GG/A*, 75.90 ± 5.56 × 109/L) (p = 0.006). Compared with the A*/A* genotype, tacrolimus nadir levels were significantly higher in GG/GG genotype patients, who also exhibited a higher incidence of hemorrhage (22.2%, p = 0.011). A combination of a nadir blood concentration of tacrolimus ≥ 4.74 ng/mL and spleen size ≥ 165.5 mm was a risk factor for increased thrombocytopenia after DDLT on POD3, with an AUC of 0.735 (sensitivity, 77.2%; specificity, 41.7%). A high blood concentration of tacrolimus after the early stage of DDLT is a major risk factor for hemorrhage. For the CYP3A5 genotype (GG/GG), controlling the blood concentration of tacrolimus below the target concentration until POD3 can avoid thrombocytopenia-related complications.

Thrombogenesis-related characteristics of platelets and platelet indices in pregnant COVID-19 women

Introduction. Thrombosis emerging in COVID-19 represents one of its most common complications. The period of pregnancy is accompanied by elevated susceptibility to infectious diseases and increased risk of thrombosis.Aim: to assess time-dependent change in platelet count and platelet indices in general clinical blood test in pregnant COVID-19 women related to illness onset and developed thrombosis.Materials and Methods. A retrospective analysis of 230 case histories from pregnant COVID-19 women at the third trimester was carried out. Of these, 99 women were selected who met the inclusion criteria: COVID-19 infection laboratory-verified by polymerase chain reaction (PCR); third trimester of pregnancy; presence/absence of thrombotic complications. All patients were divided into 2 groups: the control group consisted of 94 pregnant women aged 31.5 [28.0; 35.0] years without thrombotic complications and the average gestational age at illness onset was 34.1 [30.2; 37.6] weeks; the main group included 5 patients aged 33.0 [28.5; 37.5] years and the average gestational age at illness onset was 33.2 [30.2; 37.8] weeks, with thrombotic complications emerged during the disease course: thrombosis of upper and lower extremity veins; massive pulmonary embolism; thrombosis of the splenic vein at the spleen hilum; left atrial thrombus. The following parameters were evaluated dynamically (on day 6–8, 9–11, 12–15, 16–23 and 24–72 of the disease): total platelet count, thrombocrit, mean platelet volume, platelet distribution width (PDW), large platelet count. A comparative analysis of the study data and a correlation analysis with the time from disease onset and detected thrombosis were carried out.Results. Over the entire observation period, there were noted increased RDW (16.30 [15.80; 16.50]%), average platelet volume (10.70 [9.70; 11.80] fl), and large platelet count (73.00 [59.00; 96.00]×109/L) along with platelet count (182.50 [155.00; 184.50]×109/L) tended to elevate in main vs. control group. A correlation was established between the above parameters and illness onset as well as thrombogenesis time point (p < 0.05). The beginning of developing thrombosis in main group was mainly recorded on day 12–15 after the onset. РDW increased in both groups by day 16–23 of illness, but more pronounced changes were found in main group reaching 16.50 [16.40; 16.60]% compared to control group (16.10 [15.80; 16.40]%). By day 16–23, thrombocrit in both groups positively correlated with illness onset. In addition, large platelet count tended to rise in main group remaining, however, below the normal limit: 0.13 [0.11; 0.20]% compared to control group (0.26 [0.21; 0.31]%). Large platelet count was quite high and increased daily in both groups; the average large platelet count throughout entire observation period was lower in the main (73.00 [59.00; 96.00]×109/L) vs. control group (81.00 [66.00; 102.00]×109/L), so that in the former it sharply decreased down to 55.00 [42.00; 78.00]×109/L on day 16–23.Conclusion. These data mirror the course of thrombotic process and may serve as the basis for assessing the prognosis of thrombotic complications and identification of high-risk groups among pregnant COVID-19 women.

Reference intervals of complete blood count and coagulation tests in Vietnamese pregnant women

BackgroundPregnancy has major effects that make hematology parameters outside of normal reference ranges. Therefore, we conducted this study to establish reference intervals for Vietnamese pregnant women.MethodsFrom June 2023 to Augst 2023, blood samples from 879 eligible pregnant women were run on DxH 900 hematology analyzer and ACL TOP 550 coagulation analyzer. The tested parameters are prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), white blood cell (WBC) and its differentials (neutrophils, lymphocytes, monocytes, eosinophils and basophils), red blood cell (RBC), hemoglobin (HGB), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), RBC distribution width (RDW), RBC distribution width standard deviation (RDW-SD), platelet count (PLT), mean platelet volume (MPV). A non-parametric method was used to establish the 2.5th and 97.5th percentile reference intervals.ResultsPT, APTT decrease but fibrinogen increases during pregnancy. Physiological adaptations of pregnancy result in a decrease in RBC count, but an increase in WBC count and no changes in platelet count. The reference intervals for PT (seconds), APTT (seconds), fibrinogen (mg/dL), in the first trimester were 10.30–12.88, 25.40–35.46, 280.28–559.00, in the second trimester were 9.80–11.66, 24.05–33.23, 347.75–593.35, in the third trimester were 9.60–11.40, 23.40–31.80, 330.28–628.56, respectively. The reference intervals for main hematology parameters which are WBC (× 109/L), RBC (× 1012/L), HGB (g/dL), HCT (%), PLT (× 109/L) in the first trimester were 6.33–15.24, 3.73–5.32, 10.33–13.95, 32.22–42.29, 169.66–413.88, in the second trimester were 6.99–15.55, 3.33–4.98, 9.71–13.17, 30.26–40.07, 172.34–372.19, in the third trimester were 6.22–14.14, 3.54–4.98, 9.80–13.97, 31.11–42.70, 151.30–417.14, respectively.ConclusionsMost established referenced intervals from each trimester differ from other trimesters. These trimester-specific reference ranges for Vietnamese pregnant women will aid clinicians in entepreting parameters and help other laboratories adopt these ranges after validating.Trial registrationThis study is registered at www.clinicaltrials.gov as NCT05929326.

Dynamic Modelling for Cancer-Associated Venous Thromboembolism

Background: Cancer-associated venous thromboembolism (VTE) is an important source of morbidity and mortality. Current risk prediction models for thrombosis are handicapped by static applicability (i.e. one-time evaluation prior to the first cycle of chemotherapy). We hypothesized that event forecasting using time series modelling could account for important changes in clinical state, variations in treatment and aspects of cancer progression over time. Methods: The cohort consisted of adult patients with a solid tumor enrolled in the MSK-IMPACT study between 2014 and 2019. VTE was defined as any symptomatic or asymptomatic pulmonary embolus or lower extremity deep vein thrombosis. We derived time series mixed-effects logistic regression models in order to predict cancer-associated VTE events using baseline patient characteristics (cancer type, time from diagnosis and age) along with time-dependent covariates including total white blood cell count, hemoglobin, platelet count, albumin, creatinine and parenteral chemotherapy type. Time-periods of one month were used and models were fitted to predict the presence or absence of a VTE episode in the following period (time = t+1) based on predictor values in the current period (time = t). The laboratory test result ascribed to a given period could be either the last value in the interval or the mean of all interval-specific values (both approaches tested). Missing laboratory results were imputed using the previously known value when available. Differences in laboratory values between periods t-1 and t were included as predictors in the initial model along with indicators of missingness (see Figure for flow of information between time-period cells). We hypothesized that absence of laboratory testing for a time-period would be a marker of stable medical state and hence associated with a lower risk of VTE. A previously defined training set comprising 80% of the cohort was used and different modelling approaches were evaluated using 5-fold cross-validation. The final selected model was evaluated in a separate dedicated validation set including the remaining 20% of the cohort. Results: The original cohort included 35,391 patients, from which 26,075 individuals with no cancer-associated VTE episode before observation start and sufficient laboratory test information could be included in the analysis, comprising 276,579 months of observation and 1,463 VTE events. The initial logistic regression model including all available predictors was fitted on the training set, revealing associations between predictors and VTE risk largely consistent with data reported by other groups (see Table). After adjusting for multiple comparisons, significant predictors of cancer-associated VTE identified included albumin, cell count result missingness (decreased risk for missing value), treatment with a platinum analogue (increased risk), hemoglobin, white blood cell count, breast cancer (decreased risk) and high-grade glioma (increased risk). Based on model metrics and prior knowledge from published literature, the set of covariates selected for inclusion in the final model consisted of cell counts along with the corresponding missingness indicator, platelet count change over time, albumin and chemotherapy types. The c-index for the final model using 5-fold cross-validation in the training set was 0.77 (95% CI = 0.75-0.80), compared to 0.77 (95% CI = 0.74-0.79) in the validation set. The latter corresponded to a specificity of 0.83 (95% CI = 0.79-0.86) when fixing sensitivity at 50%. Conclusions: A simple mixed-effects logistic regression time series model demonstrated promising potential to estimate the risk of cancer-associated VTE on a dynamic basis using routine laboratory test results and chemotherapy prescription data widely available in most electronic health record systems. Validation of this dynamic VTE risk model has the potential to optimize outpatient thromboprophylaxis during periods of high thrombotic risk.

Mice Lacking α-Actinin-1 in Megakaryocytes Display the Feature of Thrombocytopenia and Impair Platelet Functions

Cytoskeleton remodeling and mitochondrial bioenergetics play important roles in platelet biogenesis and functions. α-Actinin-1, a filament crosslinker, was widely expressed in nonmuscle cells, including megakaryocytes (MKs) and platelets. The cytoskeleton is essential for normal mitochondrial morphology, motility, and distribution. In recent years, the accumulated evidence suggests that inherited mutations in α-actinin-1 are implicated in congenital macrothrombocytopenia. However, the role and underlying mechanism of α-actinin-1 in platelet biogenesis and platelet functions remain poorly studied. In this study, we generated an MK-specific α-actinin-1 knockout mouse model (referred to herein as PF4- Actn1-/-) to investigate the contribution of α-actinin-1 in platelet biogenesis and functions. Blood count tests showed that PF4- Actn1-/- mice exhibited reduced platelet counts. The decreased platelet number in PF4- Actn1-/- mice was not attributed to accelerated platelet clearance or impaired TPO generation in vivo. Platelet count changes observed in an anti-GPIbα antibody-induced thrombocytopenia model and splenectomy indicated that the diminished platelet counts in PF4- Actn1-/- mice might be due to defects in platelet biogenesis. Compared to control mice, PF4- Actn1-/- mice had normal numbers of MK progenitors, including in LSK, MPP, CMP, GMP, MEP, and PreMegE. H&E staining and flow cytometry revealed a decrease in the number of MKs in BM, but an increase in the number of MKs in the spleen. The absence of α-actinin-1 significantly increased the proportion of 2N-4N MKs and decreased the proportion of 8N-32N MKs. CFU-MK colony formation and MK migration in response to SDF-1 signaling was inhibited in PF4- Actn1-/- mice. Furthermore, in vitro studies showed a reduced ratio of PPF-bearing MKs in fetal liver-derived PF4- Actn1-/- MKs. Collectively, these data suggest that α-actinin-1 deficiency in mouse MKs could impair platelet biogenesis, resulting in thrombocytopenia in PF4- Actn1-/- mice. Platelet adhesion and spreading on immobilized fibrinogen and collagen, thrombin-stimulated clot retraction, and platelet aggregation in response to various concentrations of ADP, thrombin, and collagen was significantly decreased in PF4- Actn1-/- platelets. PF4- Actn1-/- platelets also exhibited decreased integrin αIIbβ3 activation and reduced P-selectin exposure in response to various concentrations of ADP, ADP+EPI, thrombin, collagen, and convulxin. Notably, PF4- Actn1-/- platelets showed inhibited calcium mobilization, reactive oxygen species (ROS) generation, and actin polymerization in response to collagen and thrombin. Furthermore, PF4- Actn1-/- mice demonstrated significantly impaired hemostasis. No differences were observed in the PT, APTT, TT, and fibrinogen concentrations between PF4- Actn1-/- mice and Actn1f/f mice. However, tail, liver, and brain bleeding tests revealed that PF4- Actn1-/- mice had significantly prolonged bleeding time and increased bleeding volume. Kaolin-activated whole thromboelastography (TEG) mapping assay indicated that there were no differences in the R-time, K-time, and α-angle values, but the maximum amplitude was decreased in PF4- Actn1-/- mice. To explore the mechanism of α-actinin-1 in platelet biogenesis and platelet functions. Low- (2-4N) and high-ploidy (≥8N) Actn1f/f and PF4- Actn1-/- MKs were sorted for quantitative proteomics analysis. The results of 4D label-free quantitative proteomics revealed that protein expression was significantly decreased in high-ploidy MKs following α-actinin-1 knockdown. Functional enrichment analysis of differentially expressed proteins indicated that α-actinin-1 deletion reduced platelet activation and mitochondrial functions. PF4- Actn1-/- platelets exhibited reduced mitochondrial membrane potential, mitochondrial ROS generation, mitochondrial respiration and glycolysis, suggesting alterations in mitochondrial function in platelets. In this study, we report that mice with α-actinin-1 deficiency in MKs recapitulate the features of thrombocytopenia and exhibit impaired platelet functions.