Nadir Platelet Count Research Articles

Circulating T-lymphocyte subsets as promising biomarkers for the identification of sepsis-induced acute kidney injury.

This retrospective study investigated whether disturbances in circulating T-lymphocyte subsets could predict the incidence of acute kidney injury (AKI) and in-hospital mortality in patients with sepsis. Clinical data from patients with sepsis admitted to the intensive care unit were reviewed. Logistic regression analyses were used to identify independent predictors of in-hospital mortality and the development of AKI. Of 81 patients with sepsis, 50 developed AKI. Both non-survivors and patients with septic AKI exhibited dramatically higher Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation (APACHE) II scores. Non-survivors exhibited more organ damage, with significantly lower levels of peripheral T-lymphocyte subsets, including total circulating lymphocytes, and CD3+, CD3+CD4+, and CD3+CD8+ T-lymphocytes. Patients with septic AKI exhibited fewer total peripheral lymphocytes and fewer CD3+, CD3+CD4+, and CD3+CD8+ T-lymphocytes, with higher serum lactate levels and lower nadir platelet counts. Independent predictors of 30-day hospital mortality included maximum SOFA and APACHE II scores, occurrence of encephalopathy, and peripheral CD3+ and CD3+CD8+ T lymphocyte counts. Moreover, the maximum SOFA score and CD3+ and CD3+CD8+ T-lymphocyte counts demonstrated good predictive power for AKI in receiver operating characteristic curve (ROC) analyses, with an area under the ROC curve of 0.810 (95% confidence interval [CI] 0.712-0.908) for SOFA score, 0.849 (95% CI 0.764-0.934) for CD3+ T-lymphocytes, and 0.856 (95% CI 0.772-0.941) for CD3+CD8+ T-lymphocytes. Patients with sepsis-induced AKI experienced T lymphopenia and increased in-hospital mortality. Higher maximum SOFA scores and reduced peripheral CD3+ and CD3+CD8+ T-lymphocyte levels were associated with in-hospital mortality and the development of AKI in patients with sepsis.

Most major bleeds in preterm infants occur in the absence of severe thrombocytopenia: an observational cohort study

ObjectiveTo describe the incidence of major bleeds according to different platelet counts in very preterm infants, and to explore whether this association is influenced by other risk factors for bleeding.DesignObservational...

Prognostic significance of nadir platelet count in patients with heatstroke: A multi-center retrospective study

BackgroundHeatstroke (HS), associated with the early activation of the coagulation system and frequently presenting with thrombocytopenia, poses a significant healthcare challenge. Understanding the relationship of nadir platelet count (PLT) within 24 h for adverse outcomes in HS patients is crucial for optimizing management strategies. MethodsThis retrospective cohort study, conducted in six tertiary care hospitals, involved patients diagnosed with HS and admitted to the emergency departments. The primary and secondary outcomes included in-hospital mortality and various acute complications, respectively, with logistic regression models utilized for assessing associations between nadir PLT and outcomes. The PLT count change curve was described using a generalized additive mixed model (GAMM), with additional analyses involving body temperature (BT) at 2 h also conducted. ResultsOf the 152 patients included, 19 (12.5%) died in-hospital. The median nadir PLT within 24 h was 99.5 (58.8–145.0)*10^9/L. Notably, as a continuous variable (10*10^9/L), nadir PLT was significantly associated with in-hospital mortality (OR 0.76; 95% CI 0.64–0.91; P = 0.003) and other adverse outcomes like acute kidney and liver injury, even after adjustment for confounders. GAMM revealed a more rapid and significant PLT decline in the non-survival group over 24 h, with differential PLT dynamics also observed based on BT at 2 h. ConclusionsNadir PLT within 24 h were tied to in-hospital mortality and various adverse outcomes in HS patients. Early effective cooling measures demonstrated a positive impact on these associations, underscoring their importance in patient management.

Association between Thrombocytopenia and Outcomes in Patients Undergoing Redo Valvular Surgery Utilizing Cardiopulmonary Bypass

Objective: To figure out the incidence of postoperative thrombocytopenia among adult cases undergoing redo valvular surgery with cardiopulmonary bypass (CPB) and to discern its ramifications on early postoperative outcomes. Methods: A cohort comprising 188 cases undergoing redo valvular surgery with CPB between March 2018 and July 2023 was analyzed. It was attempted to stratify cases into two groups on the basis of presence of thrombocytopenia that was defined as a nadir platelet count <71 × 103/μL within 72 hours (n = 45), or absence of thrombocytopenia (n = 143). Comparative evaluation was performed concerning postoperative mortality and morbidity. Logistic regression models were employed to unveil the relationship of thrombocytopenia with clinical outcomes. Results: Thrombocytopenia manifested in 45 (23.94%) cases. Univariate analysis disclosed a significant association of percent change in platelet count with mortality (odds ratio (OR), 1.039, 95% confidence interval (CI), 1.005 to 1.074, p = 0.024), postoperative pneumonia (OR, 1.058, 95% CI, 1.023 to 1.095, p = 0.001), prolonged mechanical ventilation (OR, 1.048, 95% CI, 1.026 to 1.071, p < 0.001), extended intensive care unit (ICU) stay (OR, 1.029, 95% CI, 1.010 to 1.049, p = 0.003), protracted post-operative hospitalization (OR, 1.031, 95% CI, 1.011 to 1.051, p = 0.002), postoperative renal replacement therapy (OR, 1.042, 95% CI, 1.017 to 1.069, p = 0.001), and re-thoracotomy attributable to hemorrhage (OR, 1.040, 95% CI, 1.000 to 1.080, p = 0.047). Multivariate analysis demonstrated that thrombocytopenia, regarded as a categorical variable, was independently correlated with an escalated likelihood of prolonged postoperative hospital stay (OR, 4.926, 95% CI, 1.740 to 13.948, p = 0.003). Conclusions: Thrombocytopenia appeared to be closely linked to escalated in-hospital mortality and postoperative morbidity rates among cases undergoing redo valvular surgery employing CPB. Further investigations with larger, prospective cohorts are essential to validate these outcomes and unravel potential underlying mechanisms.

#2262 Renal outcomes of postpartum atypical hemolytic uremic syndrome treated with plasma exchange

Abstract Background and Aims Postpartum acute kidney injury (AKI) with features of thrombotic microangiopathy (TMA) are particularly challenging and complex cases. Causes include Preeclampsia (PE), hemolysis, elevated liver enzymes and low platelet count syndrome (HELLP) and atypical hemolytic uremic syndrome (aHUS). In a limited resource setting, it is difficult to diagnose such cases with more than standard blood tests. Therapeutic Plasma exchange (TPE) is the only available option for treatment in the absence of complement inhibitors. This study evaluates renal outcomes in patients with aHUS treated with plasma exchange. Method This is a single centre observational study conducted in a Tertiary Obstetric Intensive Care unit. The data of women who were admitted with postpartum AKI from January 2021 to October 2023 was retrospectively collected and analyzed. We used the following criteria to diagnose postpartum atypical HUS (Serum creatinine ≥1.9 mg/dL, Lactate dehydrogenase (LDH) ≥1832 U/L, or serum creatinine ≥1.9 mg/dL in combination with LDH ≥600 U/L) [1]. Inclusion criteria include women older than 18 yrs with microangiopathic hemolytic anaemia, schistocytes on peripheral blood film, negative direct antiglobulin test (DAT) and platelet count <100 /mm3.Lack of improvement of kidney functions and hemolysis 72 hours after delivery. Patients with sepsis, disseminated intravascular coagulopathy (DIC), postpartum hemorrhage (PPH) and chronic kidney disease were excluded. We identified 10 patients with postpartum aHUS. Peak creatinine, LDH, AST and Nadir platelet count and hemoglobin were recorded. Patients were followed up in the nephrology outpatient clinic. Results Fifty-two patients developed postpartum AKI in the study period. Ten patients (19%) were diagnosed with aHUS according to the above-mentioned criteria. Mean age was 24.5 ± 6.9 yrs. Median peak creatinine 5.1 (2.6-7) mg/dl, LDH 1950 (612-4000) U/L, AST 246 (150-699) U/L. Median nadir hemoglobin 7.25 (6-8.2) g/dl and platelets 57 (41-95)/mm3. All 10 patients received 3 to 6 sessions of TPE guided by platelets and LDH levels. All patients required at least 3 sessions of hemodialysis. Eight patients received TPE with plasma filter and 2 had centrifugal TPE (due to lack of plasma filters). Two patients died during ICU admission. Two months after discharge 4 (50%) patients had partial recovery of kidney functions average creatinine (3.5 ± 0.8) mg/dl and four (50%) remained dialysis dependent. Six of these patients had kidney biopsies, three biopsies showed a picture of thrombotic microangiopathy and two showed thrombotic microangiopathy with renal cortical necrosis. The other patient was lost to follow up. Conclusion It is difficult to diagnose and treat aHUS in a resource limited setting. The available treatment with therapeutic plasma exchange has poor renal outcomes.

Platelet Reduction after Transcatheter Aortic Valve Implantation: Results from the PORTRAIT Study.

Background: An unexplained condition that follows transcatheter aortic valve implantation (TAVI) is platelet count reduction (PR). According to published research, patients with balloon-expandable valves (BEVs) had a greater PR than those with self-expandable valves (SEVs). Objectives: The purpose of this study was to investigate the incidence and clinical effects of PR following TAVI. Methods: In total, 1.122 adult TAVI patients were enrolled. Propensity score matching was carried out in a 1:1 ratio between patients with BEVs and those with SEVs. The analysis included changes in platelet count, in-hospital mortality, and early postoperative adverse events. Results: Notably, 632 patients were matched (BEV:316; SEV:316). All patients' post-procedural platelet counts changed according to a parabolic curve, using a mixed regression model for repeated analyses (estimate = -0.931; standard error = 0.421; p = 0.027). The platelet count varied comparably in patients with BEVs and SEVs (estimate = -4.276, standard error = 4.760, p = 0.369). The average time for obtaining the nadir platelet count value was three days after implantation (BEV: 146 (108-181) vs. SEV: 149 (120-186); p = 0.142). Overall, 14.6% of patients (92/632) had post-procedural platelet count <100,000/µL. There was no difference between the two prosthesis types (BEV:51/316; SEV:41/316; p = 0.266). Thrombocytopenia was found to be significantly linked to blood product transfusions, lengthier stays in the intensive care unit and hospital, and in-hospital mortality. Conclusions: TAVI, irrespective of the type of implanted valve, is linked to a significant but temporary PR. Thrombocytopenia increases the risk of serious complications and in-hospital death in TAVI patients. To explore and clarify the causes and associated effects, further prospective research is necessary.

Association between postoperative nadir platelet count and postoperative cardiovascular complications following septal myectomy in patients with hypertrophic cardiomyopathy: a retrospective cohort study

BackgroundPlatelet count is associated with cardiovascular risk and mortality in several cardiovascular diseases, but the association of the nadir platelet counts post-septal myectomy with the cardiovascular complication risk in hypertrophic obstructive cardiomyopathy patients remains unclear.MethodsThis retrospective cohort study reviewed all adult patients who underwent septal myectomy at a single tertiary referral center over a 5-year period. Postoperative nadir platelet count was defined as the lowest platelet count in the first 4 postoperative days or until hospital discharge. The composite outcome included cardiovascular death, myocardial infarction, heart failure, malignant arrhythmia, cardiac tamponade, and major bleeding events within 30 days postoperatively. Univariable and multivariable logistic regression and restricted cubic spline models were used to assess the association between postoperative nadir platelet count and the 30-day postoperative cardiovascular complication risk.ResultsAmong the 113 enrolled patients, 23 (20.4%) developed cardiovascular events within 30 days postoperatively. The incidence of postoperative cardiovascular complications was significantly higher in patients with a nadir platelet count ≤ 99 × 109/L than in those with a nadir platelet count > 99 × 109/L (33.3% vs. 7.1%, crude risk ratio: 4.67, 95% confidence interval: 1.69–12.85, P < 0.001). Multivariable logistic regression revealed that postoperative nadir platelet count was negatively associated with 30-day postoperative cardiovascular complications (adjusted odds ratio: 0.97; 95% confidence interval: 0.95–0.99; P = 0.005) and the association was linear (Pnonlinearity = 0.058) after full adjustment. The association between nadir platelet count and cardiovascular complications within 30 days post-surgery was consistent in all predefined subgroups (Pinteraction > 0.05).ConclusionThe postoperative nadir platelet count was significantly associated with the 30-day post-myectomy risk of cardiovascular complications in hypertrophic obstructive cardiomyopathy patients.Trial registrationThis trial was registered at ClinicalTrials.gov (NCT04275544).

Factors Affecting Heparin Induced Thrombocytopenia: A Case Series Study

Heparin-induced thrombocytopenia (HIT) is a condition that can affect patients who are exposed to heparin across a variety of disease states. A case series study was conducted to evaluate the effect of patient age, unfractionated heparin dose and nadir platelet count on the 4T score in a multiple regression analysis. The number of cases selected was ten. The regression analysis showed that patient age and nadir platelet count were statistically significant (P&lt;.05) and the R-squared value was 0.7. A Pearson correlation coefficient analysis also revealed a low positive correlation between heparin dose and platelet count (r = 0.3). These findings add to the body of knowledge encompassing unfractionated heparin which remains a widely used anticoagulant for patients with thrombotic disease and other conditions and procedures. Future studies should continue to evaluate factors that affect HIT including outcomes between Type I and Type II HIT.

Acquired Thrombocytopenia in Contemporary Transcatheter Aortic Valve Prosthesis.

Postprocedural thrombocytopenia is a known phenomenon following transcatheter aortic valve implantation (TAVI). The aim of this study is to evaluate whether postinterventional platelet kinetics differ when comparing the current generation of balloon-expandable valve (BEV) and self-expanding valve (SEV) prostheses. We performed a retrospective analysis of patients undergoing TAVI at our facility between 2017 and 2019. Patients were stratified according to the type of prosthesis used: BEV or SEV. Hematocrit-corrected platelet counts were calculated to account for dilution. Nadir platelet counts (lowest recorded platelet count), drop platelet counts (DPC; highest relative platelet drop from baseline), and severity of thrombocytopenia during the discourse and at discharge were assessed. Of the 277 included patients, 212 received SEV and 65 BEV. BEV patients were younger (81.8 ± 4.4 years vs 79.7 ± 6.8 years, p = 0.03). Further demographic characteristics were similar between groups. Implanted SEV were larger (p < 0.001) and had shorter procedural times (p < 0.01). There were no significant differences in postprocedural discourse. Postinterventional platelet drop was more pronounced in BEV patients in several evaluated metrics: mean DPC (24.3 ± 10.9% vs 18.8 ± 14.8%, p < 0.01), patients with DPC > 30% (n = 19, 29.2%, vs n = 33, 15.6%, p = 0.02), and also when comparing platelet kinetics. Despite improvements in outcome, the current generation of balloon-expandable TAVI prostheses carries a predisposition for postprocedural thrombocytopenia even when the effects of dilution are accounted for.

Mutations in Histone Lysine Methyltransferase Genes Are Associated with Autoimmune Cytopenias

Introduction Epigenetic mechanisms are important in regulation of gene expression by modifying chromatin structure to facilitate DNA accessibility (Lau et al Nat Immunol. 2018). DNA methylation and histone modifications are critical for the pathogenesis of hematologic malignancies and autoimmune diseases (Surace et al Front Immunol. 2019) Alterations in enzymes involved in histone modification are associated with immunodeficiencies, including Kabuki syndrome (KS), a rare genetic disorder associated with autoimmune cytopenias, such as immune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA) (Margot et al J Am Coll Med Genet 2020) caused by loss-of-function KMT2D and KDM6A mutations. Somatic mutations in the KMT2D gene have also been observed in patients with Cold Agglutinin Disease. (Małecka et al Br J Haematol. 2018). Aims: The aims of this study are: 1) to identify the frequency of mutations in histone methyltransferase genes (MT) KMT2D, KMT2A, KMT2C and KDM6A in patients with autoimmune cytopenias, and 2) to compare clinical, laboratory and immunological characteristics, and response to therapy in patients with or without mutation in MT and autoimmune cytopenias (AIC). Methods Data mining software from the electronic medical record was used to identify patients ≥ 18 years with a diagnosis of AIC, including ITP, warm and cold AIHA, autoimmune neutropenia, and Evans Syndrome (ES), who had Next Generation Sequencing (NGS) performed. Cytopenias due to malignancy, nutritional deficiency, medications, pregnancy, or infection were excluded. Patients were categorized into two groups based on the presence or absence of mutation in the MT genes (MT+, MT-) with variant allelic frequency (VAF) &amp;gt; 2%. Demographic, laboratory, and clinical characteristics, treatment outcomes, and NGS sequencing data were collected and compared between groups. Next, KMT2 mutations seen in patients with AIC were cross-referenced against the 1000 Genome Project (1000GP) population database to evaluate the frequency of polymorphisms in the general population (Auton et al Nature 2015). CADD in silico prediction algorithm was used to score the potential deleterious effect of MT mutations (Kirchner Nat Genet. 2014). Chi-Square test was used for categorical variables. Statistical analysis was completed in R software. Results Among 495 patients who underwent NGS, 79 (16%) had a mutation in MT genes. These mutations were present in 36% of patients with AIC as compared to 13% in those without AIC (p=0.0005). Among 55 patients with AIC, mutations in the MT genes were present in 20 patients (MT+), 35 patients did not have these mutations (MT-). KMT2C mutations were seen in 10 (50%) patients, KMT2D mutations in 9 patients (45%, one patient had two KMT2D mutations), 1 patient (5%) had both KMT2C &amp; KMT2D variants (Figure 1). The median VAF was 39.5% (IQR, 15.45 - 49.80). The MT+ group had a significantly higher proportion of Hispanic (60% vs 31%) and non-Hispanic White patients (25% vs 14%), p=0.038, Table 1. The median age at diagnosis for the MT+ cohort was younger compared to MT- (45.5 vs 58 years old, respectively), though not statistically significant. AIC diagnoses in both groups were ITP (44%) wAIHA (22%) cAIHA (9%) Autoimmune Neutropenia (2%), and ES (24%). Compared to the MT- group, the MT+ group had lower IgG levels (p=0.0041) and absolute lymphocyte count (p=0.041). MT+ patients with AIHA were more likely to have positive Direct Coombs and complement involvement. No significant differences were found in median nadir hemoglobin and platelet counts, need for therapy, or median number of lines of therapy. Best overall response to therapy was similar in the two groups (93%), with more complete responses in MT- group (55% vs 33%) though not statistically significant. Next, we assessed KMT2 polymorphisms in the general population. Most of the polymorphisms were not present in the 1000GP database and none had a frequency &amp;gt; 0.001. The average Phred score was 19.8; 12/20 patients had Phred score &amp;gt; 20, suggesting that most mutations are in the top 1% of the deleterious variants. Conclusion We report for the first time that patients with autoimmune cytopenias have a high frequency of variants in MT genes. Median allelic frequency close to 50% suggests potential germline predisposition to immune dysregulation and autoimmunity however further studies are needed to better understand the impact of these observations.

Population Pharmacokinetic-Pharmacodynamic Modeling of Neutrophil and Platelet Count for Lower-Intensity Therapy of CPX-351 Combined with Venetoclax in Acute Myeloid Leukemia

Background: Improved survival outcomes and a comparable safety profile with CPX-351 (a dual-drug liposomal encapsulation of daunorubicin and cytarabine in a synergistic 1:5 molar ratio) vs conventional 7+3 chemotherapy in a pivotal phase 3 trial led to the approval of CPX-351 for newly diagnosed therapy-related acute myeloid leukemia (tAML) or AML with myelodysplasia-related changes (AML MRC) in adults and pediatric (aged ≥1 year) patients in the United States and in adults in Europe. The approved induction dose is 1-2 cycles of CPX-351 100 units/m 2 (daunorubicin 44 mg/m 2 and cytarabine 100 mg/m 2) as a 90-minute intravenous infusion on days 1, 3, and 5 (days 1 and 3 for second induction). In this study, we developed a population pharmacokinetic-pharmacodynamic (PK-PD) model of absolute neutrophil count (ANC) and platelet count to determine the optimal dose for a lower-intensity therapy (LiT) of CPX-351 combined with venetoclax. Methods: The CPX-351 population PK-PD analysis was based on data collected from 3 clinical studies (phase 1 study [NCT00389428; J Clin Oncol 2011; 29(8):979-85];phase 2 study [NCT02238925; Cancer Chemother Pharmacol 2019; 84(1):163-73];phase 3 study [NCT01696084; J Clin Oncol 2018; 36(26):2684-92]) in patients with newly diagnosed high-risk/secondary AML. Venetoclax population PK-PD analysis was based on data from a comprehensive safety analysis of venetoclax monotherapy ( Clin Cancer Res 2018; 24(18):4371-9). ANC and platelet data used in the analysis were from 94 patients for CPX-351 and 272 patients for venetoclax. Generalized semi-mechanistic population PK-PD analyses were performed using non-linear mixed-effects modeling to characterize the time-course of ANC and platelet count following administration of CPX-351 and venetoclax monotherapy. The majority of system parameters were shared across the 2 therapies and a limited number of treatment-specific parameters were estimated by fitting CPX-351 and venetoclax PK time-courses simultaneously. An R Shiny app was developed for the simulation of different dosing regimens with favorable safety profiles to guide optimal dose selection for LiT of CPX-351 combined with venetoclax, assuming the 2 drug effects on ANC and platelet count were additive. Results: The generalized PK-PD model included multi-compartment transit models for ANC and platelet count with separate semi-mechanistic compartments to represent proliferating, maturing, and circulating cells. The model fitted CPX-351 and venetoclax PK-PD data with shared system parameters except for the drug-specific parameter IC 50 (concentration producing 50% of maximal inhibition of cell proliferation). For ANC, the estimated IC 50 values for CPX-351 and venetoclax were 295 μM (relative standard error [RSE]: 8.96%) and 120 μM (RSE: 18.0%), respectively; the shared mean transit time (MTT) estimate for ANC maturation was 66.6 h (RSE: 4.95%), and shared maximal inhibition of cell proliferation (I max) was fixed to 1. For platelet count, the estimated IC 50 values for CPX-351 and venetoclax were 0.0109 μM (RSE: 50.2%) and 16.5 μM (RSE: 8.73%); the shared MTT estimate for platelet maturation was 87.2 h (RSE: 9.01%) and shared I max estimate was 0.313 (RSE: 11.2%). Simulations with different doses of CPX-351 in combination with 400 mg venetoclax were performed. The simulated mean nadir ANC were 2.1, 1.5, 1.1, and 0.6 × 10 9/L for CPX-351 doses of 20, 40, 60, and 100 units/m 2, respectively, when administered on days 1 and 3 and combined with venetoclax 400 mg daily for 28 days. The simulated mean nadir platelet counts were 31.0, 30.3, 30.0, and 29.7 × 10 9/L for CPX-351 doses of 20, 40, 60, and 100 units/m 2, respectively, when administered on days 1 and 3 and combined with venetoclax 400 mg daily for 28 days. Model-based simulated outcomes of ANC and platelet count were consistent with the observed trial data. C onclusions: A generalized semi-mechanistic population PK-PD model was developed to adequately describe the time-courses of ANC and platelet counts in patients with AML following the administration of CPX-351 and venetoclax monotherapy and was used to infer the impact on ANC and platelet count when given in combination. Model-based simulations supported initial dose selection in the phase 1b study of combined CPX-351 LiT plus venetoclax as first-line treatment for patients with AML who are unfit for intensive chemotherapy (NCT04038437).

Anti-PF4 immunothrombosis without proximate heparin or adenovirus vector vaccine exposure

AbstractPlatelet-activating anti-platelet factor 4 (PF4)/heparin antibodies and anti-PF4 antibodies cause heparin-induced thrombocytopenia (HIT) and vaccine-induced immune thrombocytopenia and thrombosis (VITT), respectively. Diagnostic and treatment considerations differ somewhat between HIT and VITT. We identified patients with thrombocytopenia and thrombosis without proximate heparin exposure or adenovirus-based vaccination who tested strongly positive by PF4/polyanion enzyme-immunoassays and negative/weakly positive by heparin-induced platelet activation (HIPA) test but strongly positive by PF4-induced platelet activation (PIPA) test (ie, VITT-like profile). We tested these patients by a standard chemiluminescence assay that detects anti-PF4/heparin antibodies found in HIT (HemosIL AcuStar HIT-IgG(PF4-H)) as well as a novel chemiluminescence assay for anti-PF4 antibodies found in VITT. Representative control sera included an exploratory anti-PF4 antibody-positive but HIPA-negative/weak cohort obtained before 2020 (n = 188). We identified 9 patients with a clinical-pathological profile of a VITT-like disorder in the absence of proximate heparin or vaccination, with a high frequency of stroke (arterial, n = 3; cerebral venous sinus thrombosis, n = 4), thrombocytopenia (median platelet count nadir, 49 × 109/L), and hypercoagulability (greatly elevated D-dimer levels). VITT-like serological features included strong reactivity by PIPA (aggregation <10 minutes in 9/9 sera) and positive testing in the novel anti-PF4 chemiluminescence assay (3/9 also tested positive in the anti-PF4/heparin chemiluminescence assay). Our exploratory cohort identified 13 additional patient sera obtained before 2020 with VITT-like anti-PF4 antibodies. Platelet-activating VITT-like anti-PF4 antibodies should be considered in patients with thrombocytopenia, thrombosis, and very high D-dimer levels, even without a proximate exposure to heparin or adenovirus vector vaccines.

Predictive effects of platelet-to-lymphocyte ratio on neonatal thrombocytopenia in primary immune thrombocytopenic mothers: a retrospective cohort study

BackgroundPrimary immune thrombocytopenia (ITP) can increase the risk of neonatal thrombocytopenia (NT). This study aimed to investigate the key factors for predicting the risk of NT.MethodsData were retrospectively collected from all pregnant women with ITP from 2015 to 2021. Newborns were divided into two groups according to the presence or absence of NT. The parameters between the two groups were then compared. Next, the correlation between maternal platelet-to-lymphocyte ratio (PLR) and neonatal platelet count was analyzed by logistic regression and generalized additive model. Additionally, the relationships among the platelet counts of siblings were also determined.ResultsA total of 147 maternal cases were included. NT was observed in 46 (31.72%) neonates. A history of previous children with NT appeared to have predictive value for NT (OR 16.484, 95% CI 2.212–122.858, P < 0.001), as the nadir gestational platelet (OR 0.958, 95% CI 0.93–0.988, P < 0.001). Correlation analysis of platelet count on postnatal day 1 and the nadir platelet count in 36 sibling neonates showed a positive correlation (r=0.684, P<0.001; r=0.900, P<0.05). PLR was divided into 3 groups via tertiles, and the incidence of NT was dramatically higher in the group with lower PLR during the second and third trimesters than in the other two groups (48.5% vs 33.3% vs 22%, P<0.05; 50% vs 21.3% vs 26.7%, P<0.001). Moreover, the risk of NT was markedly higher in the first trimester (PLR < 78.51; OR 0.975, 95% CI 0.951–0.999, P<0.05) and the second trimester (PLR < 20.41; OR, 0.899, 95% CI 0.820–0.985, P<0.05) compared to the third trimester.ConclusionOur findings suggest that a history of previous children with NT is a significant factor for predicting NT in subsequent pregnancies. PLR in the first, second and third trimesters can also be used as a reference to predict NT risk.

Association between IDEAL-IQ MRI fat fraction quantification and pelvic bone marrow reserve function in concurrent chemoradiotherapy for cervical cancer

ObjectiveTo analyze the association between iterative decomposition of water and fat with echo asymmetry and least-squares estimation quantification sequence (IDEAL-IQ) magnetic resonance imaging (MRI) of bone marrow fat fraction and bone marrow reserve function during concurrent chemoradiotherapy for cervical cancer. MethodsThe study retrospectively analyzed twenty-six patients with stage IB1 to IVA cervical cancer treated between February 2020 and November 2020. All patients received concurrent chemoradiotherapy that included platinum alone or combined paclitaxel and platinum. Pelvic IDEAL-IQ MRI (plain and enhanced) was performed before and after treatment. Regions of interest, including the fifth lumbar vertebra, sacrum, ilium, ischium, and femoral neck, were manually delineated, and the bone marrow fat fraction was measured. Peripheral blood cell counts were recorded during treatment, and the relationship between the fat fraction values and changes in the blood cell counts was explored. ResultsIDEAL-IQ MRI bone marrow fat fraction was associated with platelet nadir and platelet decline during treatment. The average pelvic bone marrow fat fraction before chemoradiotherapy was moderately negatively correlated with platelet count nadir during concurrent chemoradiotherapy (r ​= ​−0.450, P ​= ​0.021). The change in average pelvic bone marrow fat fraction through chemoradiotherapy was moderately positively correlated with the degree of thrombocytopenia (r ​= ​0.399, P ​= ​0.044). ConclusionBone marrow fat content quantified by IDEAL-IQ was associated with platelet count nadir and the degree of thrombocytopenia in patients with cervical cancer undergoing concurrent chemoradiotherapy.

Sex differences in cerebral venous sinus thrombosis after adenoviral vaccination against COVID-19.

Cerebral venous sinus thrombosis associated with vaccine-induced immune thrombotic thrombocytopenia (CVST-VITT) is a severe disease with high mortality. There are few data on sex differences in CVST-VITT. The aim of our study was to investigate the differences in presentation, treatment, clinical course, complications, and outcome of CVST-VITT between women and men. We used data from an ongoing international registry on CVST-VITT. VITT was diagnosed according to the Pavord criteria. We compared the characteristics of CVST-VITT in women and men. Of 133 patients with possible, probable, or definite CVST-VITT, 102 (77%) were women. Women were slightly younger [median age 42 (IQR 28-54) vs 45 (28-56)], presented more often with coma (26% vs 10%) and had a lower platelet count at presentation [median (IQR) 50x109/L (28-79) vs 68 (30-125)] than men. The nadir platelet count was lower in women [median (IQR) 34 (19-62) vs 53 (20-92)]. More women received endovascular treatment than men (15% vs 6%). Rates of treatment with intravenous immunoglobulins were similar (63% vs 66%), as were new venous thromboembolic events (14% vs 14%) and major bleeding complications (30% vs 20%). Rates of good functional outcome (modified Rankin Scale 0-2, 42% vs 45%) and in-hospital death (39% vs 41%) did not differ. Three quarters of CVST-VITT patients in this study were women. Women were more severely affected at presentation, but clinical course and outcome did not differ between women and men. VITT-specific treatments were overall similar, but more women received endovascular treatment.

Characteristics of the post-surgical decrease in platelet counts in orthopedic surgery patients, observations and insights

IntroductionA reduced platelet count (PLT) is a frequent post-operative finding in orthopedic surgery patients. Despite its prevalence, the characteristics of post-surgical thrombocytopenia have not been well described. MethodsA retrospective chart review was conducted on patients who underwent a knee or hip replacement from 2012 to 2015. Patients who received heparin were excluded. ResultsA total of 56 patients were analyzed on post-operative days 0 to 4. By day 1, 90.9% of the patients experienced a reduction in their platelet counts. The lowest mean platelet count (nadir) occurred on day 2 (201.3 × 109/L). The average decrease in the platelet count from the baseline was 24% (95%CI: 20.6 - 27.2). The change in the platelet count from the baseline ranged from a 49.6% drop to a 14.2% increase. A substantial portion of patients experienced thrombocytopenia, with 28% occurring on day 2. Platelet counts less than 100 × 109/L occurred only once. The percent decrease in the platelet count from the baseline to any other time point was significantly larger in patients aged > 65 years, compared to patients aged ≤ 65 years (p = 0.007). Specifically, the average drop in the platelet count at the nadir (day 2) relative to the baseline was 27.8% in patients aged > 65 years, compared to 19.5% in patients aged ≤ 65 years. ConclusionsA reduction in the platelet count is a frequent post-operative finding in orthopedic surgery patients, even after removing confounding factors, such as heparin exposure, but clinical thrombocytopenia is uncommon. Alternative etiologies should be considered when the platelet count is less than 100 × 109/L. Vigilance should also be considered regarding elderly patients.

Association between Area under the Curve Estimated from Carboplatin Dose and Incidence of Severe Thrombocytopenia in Patients with Non-Hodgkin's Lymphoma on DeVIC Therapy.

The degrees of adverse effects with carboplatin (CBDCA) are influenced by interindividual differences in the area under the curve (AUC), whereas renal function is not considered in the CBDCA dose design for dexamethasone, etoposide, ifosfamide, and CBDCA (DeVIC) therapy. We conducted this study to evaluate the association between the AUC and incidence of severe thrombocytopenia in patients treated with DeVIC with or without rituximab (DeVIC ± R). We retrospectively analyzed clinical data for 36 patients with non-Hodgkin's lymphoma who received DeVIC ± R between May 2013 and January 2021 at the National Hospital Organization Hokkaido Cancer Center. The AUC of CBDCA (AUCactual) was calculated backward using a variant of the Calvert formula. The median AUCactual was 4.6 (interquartile range: 4.3-5.3) min mg/mL and AUCactual was negatively correlated with the nadir platelet count (r = -0.45; P < 0.01). Multivariate analysis showed that AUCactual ≥ 4.3 versus < 4.3 was an independent factor predictive of severe thrombocytopenia (odds ratio: 19.3, and 95% confidence interval: 1.45-258; P = 0.02). This study suggests that the CBDCA dosing design considering renal function can reduce the risk of severe thrombocytopenia in DeVIC ± R therapy.

Significance of heparin induced thrombocytopenia (HIT) in COVID-19: a systematic review and meta-analysis.

Heparin-induced thrombocytopenia (HIT) occurs in approximately 3% of patients receiving heparinoids. About 30-75% of patients with type 2 of HIT develop thrombosis as a result of platelet activation. The most important clinical symptom is thrombocytopenia. Patients with severe COVID-19 are among those receiving heparinoids. This meta-analysis performed to picture the current knowledge and results of published studies in this field. Three search engines were searched and 575 papers were found. After evaluation, 37 articles were finally selected of which 13 studies were quantitatively analyzed. The pooled frequency rate of suspected cases with HIT in 13 studies with 11,241 patients was 1.7%. The frequency of HIT was 8.2% in the extracorporeal membrane oxygenation subgroup with 268 patients and 0.8% in the hospitalization subgroup with 10,887 patients. The coincidence of these two conditions may increase the risk of thrombosis. Of the 37 patients with COVID-19 and confirmed HIT, 30 patients (81%) were treated in the intensive care unit or had severe COVID-19. The most commonly used anticoagulants were UFH in 22 cases (59.4%). The median platelet count before treatment was 237 (176-290) x 103/µl and the median nadir platelet count was 52 (31-90.5) x 103/µl.

The association of obesity and dengue severity in hospitalized adult patients.

Obesity is associated with unfavorable outcomes for infectious diseases. Most researches exploring the association between nutritional status and dengue severity have focused on pediatric populations, with only few studies assessing adult patients. Adult patients with laboratory-confirmed dengue admitted to a tertiary hospital in southern Taiwan between 2014 and 2015 were enrolled retrospectively. Demographics, comorbidities, clinical presentation, laboratory findings, and outcomes were obtained from case-record forms. Patients were categorized into obese group and nonobese group. The obese group comprised patients with a body mass index of ≥27.5kg/m2. A total of 1417 hospitalized patients with dengue were evaluated. The mean age was 57.9 years (range: 18-92 years). The obese and nonobese groups comprised 333 (23.5%) and 1084 (76.5%) patients, respectively. The obese group included more patients with hypertension (85%, p<0.001), diabetes mellitus (33%, p<0.001), and congestive heart failure (6.3%, p=0.049). Multivariate analysis revealed that the obese group had more petechiae (AOR: 1.353, 95% CI: 1.025-1.786, p=0.033), more dyspnea (AOR: 1.380, 95% CI: 1.015-1.876, p=0.040), and more severe hepatitis (AOR: 2.061, 95% CI: 1.050-4.048, p=0.036). The obese group also had higher peak hematocrit values (44.1%, p<0.001) and lower nadir platelet count (45.3×103/μL, p=0.049) than the nonobese group. In adult patients with dengue, obese group had more petechiae, dyspnea, severe hepatitis, lower nadir of platelet count, and higher peak hematocrit level. We observed no difference in severe dengue or mortality between obese and nonobese group.

5599228 PITFALLS IN DIAGNOSING THROMBOTIC THROMBOCYTOPENIC PURPURA IN SICKLE CELL DISEASE

Background: Thrombotic microangiopathies are diagnosed by thrombocytopenia, microangiopathic haemolytic anaemia and evidence of end organ damage. In TTP this includes neurological symptoms, renal impairment and cardiac microthrombi. Confirmation of the diagnosis is severe deficiency (<10%) of the metalloproteinase ADAMTS13 and/or the presence of an inhibitor. The diagnosis of TTP in sickle cell disease (SCD) can be challenging as SCD is characterised by a chronic state of haemolysis often with very abnormal peripheral blood morphology so clinical features suggestive of TTP can be due to complications of SCD. More specifically, the coexistence of neurological impairment and thrombocytopenia seen in fat embolism syndrome (FES) complicating SCD can lead to an erroneous diagnosis of TTP. FES typically affects non-homozygous patients and those with a previously mild course of their illness manifesting with respiratory failure, neurological signs, thrombocytopenia and potential involvement of any system leading to high morbidity and mortality. Peripheral blood morphology typically shows very high number of nucleated red blood cells (nRBC). Aims: To identify published cases of TTP in patients with SCD and review the diagnostic approach. Methods: A PubMed literature search was performed using the terms “sickle cell” and “thrombotic thrombocytopenic purpura”/”TTP”. Results: Of 19 cases identified, 9 were individual case reports and a case series of 10. All patients had very mild course of their SCD. The median nadir platelet count was 38 x 109/L (7-70). 84% had neurological involvement either at presentation or shortly afterwards; primarily altered sensorium/drop in GCS. 79% patients also had severe type I respiratory failure either preceding or occurring simultaneously with the development of neurological signs and associated with extensive changes on chest imaging. Schistocytes were identified in all cases but in the vast majority at relatively low levels; at the same time, all showed large numbers of nRBCs. 18 of the 19 cases were published after 1998; in 15 there was no mention of ADAMTS13 testing at all. In the 3 cases with ADAMTS13 levels, all were normal; 2 samples were obtained before therapeutic plasma exchange (TPE) and 1 after. 18 patients received TPE and 1 an infusion of donor plasma. However, prior to TPE, all patients had already received red cell transfusion achieving Hb S levels of 30% or less. There were 2 (11%) deaths while the remainder of patients achieved complete recovery. One due to intracranial haemorrhage and the other, sepsis in the context of immunosuppression for prevention of TTP recurrence. The presence of early respiratory failure, the inconclusive morphological findings, the degree of thrombocytopenia, and the complete absence of confirmatory ADAMTS13 results bring the diagnosis of TTP to question in all cases. Given the clinical presentations, we suspect that some of these patients had FES. The positive outcomes may be explained by the fact that all patients received adequate red cell transfusion, but also the possible beneficial effect of TPE in acute complications of SCD with a hyper inflammatory component such as FES. Conclusion: The diagnosis of TTP in patients with SCD is challenging due to many overlapping features. It should not be made without confirmatory ADAMTS13 results and the possibility of alternative diagnoses should be explored.