Elevated Platelet Count Research Articles

Utility of Assessing Primary Hemostasis By Determining Platelet Function and Von Willebrand Factor in Patients with Myeloproliferative Neoplasms

VWF Changes in primary hemostasis have been implicated in thrombotic and bleeding complications in myeloproliferative neoplasms (MPN), so their evaluation could be useful in the management of these patients. We studied primary hemostasis in 248 patients with essential thrombocythemia-type MPN (TE n=129), polycythemia vera (PV n=71) and myelofibrosis (MF n=48). Von Willebrand antigen (VWF:Ag) (normal: 60-160 U/dL), von Willebrand factor (VWF) activity (VWF:GPIbM) (normal: 60-160 U/dL) and closure time with the platelet function analyzer (PFA-200) (pathological: collagen-Epinephrine channel > 200 seconds; collagen-ADP channel > 140 seconds) were assessed. VWF:GPIbM < 60 U/dL and a VWF:GPIbM / VWF:Ag ratio < 0.7 were considered to be suggestive of acquired von Willebrand disease (aVWD). In antiplatelet patients with acetyl salicílic acid (ASA), we defined in vitro resistance as a PFA-200 Col-Epi time < 200 seconds. The results were correlated with the diagnosis, hematological values, conventional or NGS genotype (n=176) and treatment at the time of the study. Patients with thrombocytopenia < 50x10 9/L were excluded from the PFA-200 analysis. Table 1 describes the clinical variables of the patients. GPIbM was decreased in 14 cases, increased in 85 cases, and normal in the rest. We identified a direct correlation with age (β=0.29, R2=0.08, p=0.001), and an inverse correlation with the number of platelets (β=-0.45, R2=0.20, p<0.001), independent of the genotype. . We found elongated PFA-200 in the Col-Epi and Col-ADP channels in 129 (54%) and 63 (26%) cases, respectively. In 10 (4%) patients we found parameters suggestive of avWD. All of them had thrombocytosis. Elevated platelet count (>600x109/L) was associated with VWF values suggestive of aVWD, with a sensitivity and specificity of 90% and 83%, respectively (AUC: 0.938, 95%CI: 0.896-0.980). Of the 99 patients not on antiplatelet therapy, 31 (31%) had an elongated PFA-200. Elongated PFA-200 was associated with lower Hb, higher leukocytes, higher platelets, higher JAK2 mutational load, lower VWF:GPIbM, and CALR genotype. This alteration was observed in 71% of patients with the CALR genotype. In multivariate analysis, decreased VWF:GPIbM (OR: 0.98, 95%CI: 0.97-0.99, p=0.001) and CALR mutation (OR: 0.98, 95%CI: 0.97- 0.99, p=0.001), maintained their value. Of the 130 patients receiving ASA, in vitro resistance was found in 31 cases (24%) (PV 30%, TE 25%, MF 0%). ASA resistance was associated with a higher platelet count and higher VWF:GPIbM. 50% of the patients with increased VWF:GPIbM (>160 U/dL) had resistance to ASA, showing VWF:GPIbM as an independent variable in the multivariate analysis.

Risks for Venous Thromboembolism with Immune Checkpoint Inhibitor Therapy

Background: Immune checkpoint inhibitor therapy (ICI) has been variably associated with increased risk of VTE, with some reports suggesting increased risk and others suggesting risk is not different from the baseline venous thromboembolism (VTE) risk in unselected ambulatory patients with cancer. Methods: Patients treated with ICI at our institution between 2009 and 2022 were retrospectively identified. Standard baseline characteristics (age, sex, race/ethnicity, BMI), cancer type and stage, type of ICI, KS risk score variables not already captured including white cell count, hemoglobin, and platelet count at time of initiating ICI therapy, as well as other patient and treatment characteristics were collected. Those with history of VTE prior to start of ICI were removed from the analysis population; anticoagulation after starting ICI was a time dependent factor. Cumulative incidence of VTE with death as a competing risk was determined using Fine and Gray technique. Univariate analysis for baseline characteristics was completed. Characteristics that were statistically significant at the 0.1-level or less were carried forward as candidate predictors in multivariable, competing risks models of VTE. Results are presented as hazard ratios with 95% confidence intervals adjusted for multiple comparisons against a reference group. Results: Of 12,007 patients starting ICI therapy, 10,638 were analyzed with median follow-up of 25.1 months. The majority of tumor types included lung (30.3%), skin (15.8%; melanoma, squamous cell), gastrointestinal (11.7%), and genitourinary (11.6%). The most frequently used ICI agents were the anti-PD-1 monoclonal antibodies pembrolizumab (49.7%) and nivolumab (31.8%). The overall cumulative incidence estimates of VTE are summarized in Figure 1. The estimate at six months was 7.6% (95% CI: 7.1 to 8.1%); at one year: 11.1% (95% CI: 10.5 to 11.8%); and at two years 13.8% (95% CI: 13.0 to 14.5%). Among the 1,328 patients who developed VTE, the median time after starting ICI therapy was 5.4 months [IQR: 1.8 to 12.0 months]. Univariate comparison findings carried forward as candidate predictors in the multivariable analyses included sex, age, BMI, race, history of prior anticoagulant therapy (before ICI start), cancer type, disease stage, ICI therapy (by drug), KS, and platelets. The first multivariable model using all predictors identified gender, Khorana risk score, and race as no longer significant. The second model examined the inter-relationships between remaining predictors and the incidence of VTE; as the KS is partially comprised of cancer type, BMI, and platelets, having these as separate predictors removed the influence of the Khorana score since they would provide similar information. Predictors of VTE identified in this model included type of ICI with the use of ipilumumab associated with the highest risk with HR of 1.90 (95% CI: 1.33-2.71) and durvalumab the lowest HR 0.59 (95% CI:0.36-0.96), when compared with pembrolizumab. Type of cancer, stage of cancer, BMI, and high platelet count were also predictive. Starting anticoagulation at the time of or after beginning ICI but not for treatment of VTE was associated with approximately a 40% reduced hazard of VTE compared to patients who had not yet or never started anticoagulation. (HR: 0.59, 95% adj. CI: 0.48 to 0.73). (Table 1) Conclusion In this large sample of patients, the use of ICI in VTE naïve patients was associated with an increased risk of VTE, with a cumulative incidence of 7.6% at 6 months compared with a baseline 3-4% risk in general ambulatory patients with cancer. Type of ICI treatment was associated with VTE risk, as was stage of cancer. The individual KS risk predictors of cancer type and BMI were predictive but only elevated platelet count was associated with increased VTE risk-hemoglobin and white cell count were not. Importantly, those that started anticoagulation for reasons other than development of VTE had a significant reduction in VTE risk, suggesting that anticoagulant prophylaxis may be indicated in those patients with multiple risk factors in the setting of ICI treatment. Further analysis of these data will help identify at risk patients starting treatment with ICI who will benefit from VTE prophylaxis.

Pregnancy-Related Outcomes in Patients with Congenital Thrombotic Thrombocytopenic Purpura: Post Hoc Analysis of a Retrospective Chart Review Study

Background: Congenital thrombotic thrombocytopenic purpura (cTTP) is an ultra-rare, life-threatening inherited deficiency of the von Willebrand factor-cleaving metalloprotease, ADAMTS13, leading to consumptive thrombocytopenia due to microvascular thrombosis. Symptoms typically present either in early infancy, in adulthood during pregnancy, or in association with systemic infections, periods and conditions in life that are associated with an increased risk of acute cTTP episodes. Prophylaxis with plasma or plasma-derived therapies to replenish ADAMTS13 are commonly used. Limited evidence is available about the clinical burden of cTTP among female patients during pregnancy. Aims: A chart review was undertaken to gain insight into the natural history of cTTP, short- and long-term clinical outcomes, burden of disease, and treatment patterns. A post hoc analysis aimed to assess the clinical characteristics, treatment patterns and outcomes of patients with cTTP during pregnancy. Methods: An international, multi-center, retrospective chart review collected data from January 01, 2009 to December 31, 2020. Patients with cTTP were included if they were diagnosed with cTTP, received therapeutic intervention for cTTP, or had a cTTP-related clinical event recorded between January 01, 2009 and December 31, 2017 (index identification period). Patients were followed from their study index date until loss to follow-up, enrollment in a clinical trial, death, or the end of the study period. Ethics approval and informed consent were obtained where applicable. Data presented are from a post hoc analysis which assessed clinical characteristics and outcomes during pregnancy in female patients who were >14 years of age at study index. Results:A total of 78 patients with cTTP were identified during the index identification period and included in the analysis, 61 (78%) were female and the median (IQR) age at diagnosis was 26.5 (14.5-37.0) years. Overall, 92 acute episodes were reported by 55 of the 78 patients included in the analysis. Triggers for acute episodes were recorded in 46 of the 92 episodes, with infection (n=21/46) and pregnancy (n=17/46) being the most common. Prophylaxis was administered in 47/78 patients, with pregnancy (n=13/47) and clinical symptomatology (n=13/47) being the most common reasons to initiate prophylaxis. Information regarding pregnancy was collected from 55 female patients who were aged >14 years at study index. Of these 55 patients, 45 reported ≥1 pregnancy and 30 were diagnosed with cTTP during or immediately after pregnancy. One or more pregnancy-related complications were reported by 26/45 patients who were ever pregnant. The most common complication was fetal death or pregnancy loss which was reported in 16/45 patients (Table 1). Of the 55 female patients >14 years of age at study index, 41 had documented acute episodes during the study period, of whom 22 were pregnant at the time an episode occurred. Each of these 22 patients experienced 1 acute episode while pregnant during the study. Twenty-six pregnancy-related complications were reported during 18 of these 22 acute episodes (Table 2). The most frequently reported were fetal death or pregnancy loss (n=8), hemolysis, elevated liver enzymes and low platelet count (n=7; HELLP syndrome), and pre-eclampsia (n=6). A total of 54 treatments (plasma exchange [PEX], fresh frozen plasma [FFP], steroids, red blood cell transfusion, platelet transfusion, caesarean section, intravenous immunoglobulins, rituximab, and hemodialysis) were received by the 22 pregnant patients who experienced an acute episode while pregnant during the study period. Forty-four treatments were administered for acute episodes associated with pregnancy-related complications. Of the 54 treatments administered, PEX (n=15/54) and FFP (n=11/54) were the most common. Conclusions: Data from this chart review show that a high proportion of pregnant patients with cTTP experience pregnancy-related complications which could result in poor fetal and maternal outcomes. Pregnancy is a common trigger for acute cTTP episodes and initiation of prophylaxis. Despite current therapeutic interventions, pregnancy-related complications represent a high clinical burden for cTTP patients. Novel therapies with demonstrated efficacy and safety profiles are needed to address the poor clinical outcomes experienced by pregnant patients with cTTP.

Platelet-Derived TGF-β1 Induces Functional Reprogramming of Myeloid-Derived Suppressor Cells in Immune Thrombocytopenia

Introduction: Immune thrombocytopenia (ITP) is an acquired autoimmune disease characterized by isolated thrombocytopenia and varying degrees of bleeding symptoms. Platelets are anucleate cytoplasmic cell fragments that play dual physiological roles as both cellular mediators of thrombosis and immune modulatory cells. Platelets are the largest storage pool of TGF-β1, a crucial enforcer of immune homeostasis and tolerance. Studies have shown that TGF-β1 released by platelets contributes to the pathogenesis of pulmonary arterial hypertension and cervical carcinoma. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of immature myeloid cells with potent immunosuppressive functions. Our previous studies have shown that MDSCs are impaired in number and function in patients with ITP. The objective of this study was to elucidate the underlying molecular mechanisms of MDSCs reprogramming by platelet-derived TGF-β1. Methods: A transwell assay was used to determine the impact of platelets on MDSCs induced from peripheral blood mononuclear cells (PBMCs) of ITP patients and healthy controls. The percentage of circulating MDSCs in ITP patients was detected before and after administration of thrombopoietin receptor agonists (TPO-RAs). Besides, anti-CD61 immune-sensitized splenocytes were transferred into SCID mice to establish an active murine model of ITP. Subsequently, MDSCs from TPO-RA-treated ITP mice were transplanted as cell therapy to rescue treatment-free ITP mice. In specific, adeno-associated viral (AAV) vectors efficiently infected MDSCs to enable cell-specific Smad2/3 knock-down. Finally, platelet specific TGF-β1-deficient mice were used to validate the effect of platelet-derived TGF-β1 on MDSCs. Results: TGF-β1 levels in the supernatant of MDSCs co-cultured with platelets of high concentration was significantly higher than that in MDSCs co-cultured with platelets of low concentration or alone. FACS analysis showed that platelet mass enhanced the inhibitory effects of MDSCs on the proliferation of CD4 + T cells, which could be offset by TGF-β1 inhibitor (TGF-βi). Besides, TPO-RAs treatment induced significantly increased percentage of circulating MDSCs in responders with chronic ITP. Likewise, TPO-RA significantly expanded MDSC population in active ITP murine models. Furthermore, after receiving donor MDSCs from TPO-RA-treated ITP mice, arrested differentiation of plasma cells, reduced Fas ligand expression on cytotoxic T cells, and re-balanced T cell subsets were found in the recipient mice, indicating augmented inhibitory functions of MDSCs. Mechanistically, transcriptome analysis confirmed the participation of TGF-β/Smad pathway in donor MDSCs from TPO-RA-treated ITP mice, which was offset by Smad2/3 knockdown. Finally, by constructing ITP models using Pf4 cre-Tgfb1 fl/fl and Pf4 cre+Tgfb1fl/fl mice, we found that TGF-β1 inhibition and platelet TGF-β1-deficence, both, could counteract the elevated platelet count and MDSCs percentage, as well as improved immunosuppressive capacity of MDSCs trigged by TPO-RA modulation. Conclusion: To sum up, it was demonstrated that platelet TGF-β1 induced the expansion and functional reprogramming of MDSCs via TGF-β/Smad pathway. These data indicate that platelet recovery not only serves as an endpoint of remission, but also paves the way for tolerance induction in immune-mediated thrombocytopenia. Our exploratory study deciphered immunological changes induced by TPO-RAs and helped to identify molecular mechanisms responsible for long-term remission after TPO-RA discontinuation.

Transition from temporary microaxial left ventricular assist devices to durable mechanical circulatory support systems

Abstract Background Circulatory support with a catheter-based microaxial temporary left ventricular assist device (tLVAD) plays a major role in the treatment of severe cardiogenic shock. In most patients who fail to recover while on temporary mechanical circulatory support (tMCS), durable left ventricular assist device (dLVAD) therapy is usually considered a reliable option. The aim of this study was to identify outcome predictors after the transition from a catheter-based microaxial tLVAD to dLVAD. Methods This is a retrospective analysis of data from a multicentre registry on patients who were transitioned from a catheter-based microaxial tLVAD to a dLVAD between 01/2017 and 10/2022 (n=341) from 19 European high-volume centres with regard to survival and outcome up to one year after dLVAD implantation. Results Patients were supported with an Impella 5.5 (92), 5.0 (155), CP (92), or 2.5 (2) and transitioned to Heartmate 3 (205), a HeartWare HVAD (129) or EXCOR VAD (7) during the same period. The Impella was implanted via the axillary artery in 245 (71.8%), the femoral artery in 93 (27.3%), and via direct access to the aorta in three (0.9%) patients. One hundred and thirty-three (40.5%) patients additionally required extracorporeal life support before and/or during Impella therapy. The aetiology of cardiogenic shock necessitating tMCS was most commonly acute myocardial infarction (31.7%), followed by acute decompensation of ischaemic (28.4%) or dilated cardiomyopathy (27.0%). The 30-day and 1-year survival were 87% and 70%, respectively. The uni- and multivariable analysis included 312 patients with an at least 1-year follow-up or death within the first year after dLVAD implantation. The following risk factors for 1-year mortality were identified: age (OR 1.02), specifically age over 55 years (OR 1.09), BMI >30 kg/m² (OR 2.2), female sex (OR for male sex 0.4), as well as elevated total bilirubin (OR 1.13) and low platelet counts (OR 0.996). Conclusions During preoperative conditioning, efforts should be undertaken towards normalising platelet counts and liver function. Using the identified risk factors as a basis, we created a risk score to estimate 1-year mortality to optimise patient selection for dLVAD implantation, with the aim of improving the outcome in this critical patient population.Normogram 1y-mortality prediction scoreCIF death grouped by quartiles of score

The Association between Blood Cell Counts and Thrombotic Events in Japanese Patients with Polycythemia Vera: A Retrospective Database Study

Introduction: The primary goal of therapy for polycythemia vera (PV) is the prevention of thrombotic events (TE). Several studies conducted in the United States and Europe have indicated that elevated hematocrit (HCT) and white blood cell count (WBC) are associated with an increased risk of TE in patients with PV. However, these associations have not been reported in Japanese patients with PV. In this study, we aimed to evaluate the association between blood cell counts and TE in Japanese patients with PV using a real-world database. Methods: This retrospective cohort study was performed using the RWD database (Real World Data Co., Ltd) which is a large-scale electronic medical records database collected between 1987 and 2022. Patients who met the following criteria were included: 1) PV (ICD-10, D45) initially diagnosed at ≥18 years of age (index date is the date of initial diagnosis); 2) at least one hospital visit within 180 days after the index date; 3) no history of myelofibrosis or acute myeloid leukemia before the index date; 4) ≥2 HCT measurements since the index date, and 5) no phlebotomy or hydroxyurea therapy before the index date. The outcome was the time from the index date to the first TE or to the last day of follow-up for censored cases. The primary analysis evaluated the association between HCT and TE using a univariate time-dependent Cox proportional hazards (PH) model. In the secondary analysis, WBC, platelet count (PLT), hematocrit-to-hemoglobin ratio (HHR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), basophil-to-lymphocyte ratio (BLR), phlebotomy were used as time-dependent exposures, whereas age, sex, risk factors for cardiovascular disease, and Barbui's risk stratification were used as baseline variables to evaluate their associations with TE. A multivariable-adjusted Cox PH model with each time-dependent exposure and baseline variables was also conducted. Results: Of 1,796 patients diagnosed with PV, 1,259 met the eligibility criteria. The median age (interquartile range [IQR]) of the patients was 66 (55-74) years; 63.1% were male; 23.1% had a history of TE; 71.9% were in the high-risk group according to Barbui's stratification; and 37.5% had one or more comorbidities (diabetes mellitus, hypertension, or dyslipidemia). The median (IQR) follow-up period was 1.3 (0.1-4.6) years. Of the 1259 patients, 45.0% (566) developed TE during the follow-up period and the incidence rate was 14.4 (95% confidence interval [CI], 13.2-15.6) per 100 person-years. The median HCT at the time of the first TE was 49.5% (HCT <45%: 157 [32.4%], ≥45%: 328 [ 67.6%]); the median WBC and PLT were 10.2×10 9/L and 335.0×10 9/L, respectively. In the primary analysis, the hazard ratio (HR) and 95% CI for TE in patients with HCT ≥45% compared with patients with HCT <45% was 0.96 (0.77-1.21), with no significant association. Age, history of TE and Barbui's risk stratification were associated with the risk of TE (HR [95% CI]: 1.02 [1.01-1.03], 1.25 [1.02-1.54], 1.78 [1.39-2.27], respectively). Compared with patients with WBC <10×10 9/L, patients with WBC ≥15×10 9/L and 10-≤15×10 9/L were associated with an increased TE risk (multivariable-adjusted HR [95% CI]: 2.10 [1.65-2.68] and 2.05 [1.59-2.64], respectively). Compared with patients with PLT <400×10 9/L, patients with PLT ≥1000×10 9/L, 600-<1000×10 9/L, and 400-<600×10 9/L were associated with an increased TE risk (multivariable-adjusted HR [95% CI]: 1.98 [1.35-2.89], 2.18 [1.67-2.85], and 1.59 [1.20-2.12], respectively). High HHR, NLR, PLR, BLR values and phlebotomy were associated with an increased TE risk (multivariable-adjusted HR [95% CI]: 3.93 [2.37-6.51], 1.05 [1.03-1.06], 2.33 [1.46-3.73], 4.92 [2.27-10.71] and 1.99 [1.36-2.91]). Conclusions: This is the largest and first real-world cohort study to demonstrate the association between blood cell counts and TE in Japanese patients with PV. The results did not show that maintaining an HCT <45% is associated with a reduced risk of TE in Japanese patients with PV. In contrast, the risk of TE was associated with phlebotomy, Barbui's risk stratification, and elevated WBC, PLT, HHR, PLR, and BLR. These data support the need to consider blood cell counts other than HCT in treatment strategies for Japanese patients with PV in clinical practice. Furthermore, follow-up studies are required to identify the specific levels of blood cell counts associated with an increased TE risk.

Spontaneous hepatic rupture in pregnancy with initial intrapartum cholestasis of pregnancy

Spontaneous hepatic rupture in pregnancy or the puerperium is an extremely rare and life-threatening condition. We present a case in which the patient initially presented with intrahepatic cholestasis of pregnancy and shortly after delivery developed acute spontaneous hepatic rupture. Unlike most other cases, the patient never developed a fulminant syndrome of hemolysis, elevated liver enzymes and low platelet count (HELLP). Early recognition of the syndrome, an aggressive surgical approach with cesarean section and liver packing and blood component therapy contributed to a successful outcome and admission of 27 days.

Clinical features and outcomes of patients with preeclampsia and eclampsia at Gondar University hospital, Amhara, Ethiopia 2021

ObjectiveThe aim of this study was to investigate the clinical features, and treatment outcome of women with preeclampsia and eclampsia at Gondar University Comprehensive Specialized Hospital in Amhara, Northern Ethiopia, in 2021. MethodsAn institutional-based retrospective chart review was conducted at Gondar University Specialized Hospital from March to June 2021. The study participants were chosen using a simple, systematic random sampling method. A pretested check list was used to collect data from medical records. The collected data was coded, entered into Epi-data version 4.6, and exported to SPSS version 26 for descriptive and inferential analysis. A Fisher’s exact test was used to determine statistically significant factors at a p-value of < 0.05. ResultsOf the 311 study participants, more than half (53 %) of mothers have illiterate, nearly half (49.8 %) had preeclampsia with severe features. Eclampsia accounted for 18.6 % of females in the study setting. For various reasons, more than half of the mothers required immediate intervention to terminate the pregnancy via cesarean section. Unfavorable maternal outcomes were present in more than 25 % of cases; the observed unfavorable maternal outcomes were aspiration pneumonia (10.6 %), hemolytic elevated liver function test and low platelet count syndrome (8.7 %), and maternal death (0.6 %). The severity of the disease, mode of delivery, aspartate transaminase, gravidity, gestational age, and antenatal care were all statistically significant predictors of pregnancy outcome. ConclusionThe prevalence of unfavorable maternal and perinatal outcomes of preeclampsia and eclampsia is considerable in the study area. To prevent these perinatal and postnatal effects, maternal outcomes of pregnancy, antenatal care services, emergency obstetrics, and new born care should be expanded and strengthened.

Severe maternal morbidity surveillance, temporal trends and regional variation: A population-based cohort study.

To quantify temporal trends and regional variation in severe maternal morbidity (SMM) in Sweden. Cohort study. Live birth and stillbirth deliveries in Sweden, 1999-2019. Types and subtypes of SMM were identified, based on a standard list (modified for Swedish clinical setting after considering the frequency and validity of each indicator) using diagnoses and procedure codes, among all deliveries at ≥22 weeks of gestation (including complications within 42 days of delivery). Contrasts between regions were quantified using rate ratios (RRs) and 95% confidence intervals (95% CIs). Temporal changes in SMM types and subtypes were described. Types and subtypes of SMM. There were 59 789 SMM cases among 2 212 576 deliveries, corresponding to 270.2 (95% CI 268.1-272.4) per 10 000 deliveries. Composite SMM rates increased from 236.6 per 10 000 deliveries in 1999 to 307.3 per 10 000 deliveries in 2006, before declining to 253.8 per 10 000 deliveries in 2019. Changes in composite SMM corresponded with temporal changes in severe haemorrhage rates, which increased from 94.9 per 10 000 deliveries in 1999 to 169.3 per 10 000 deliveries in 2006, before declining to 111.2 per 10 000 deliveries in 2019. Severe pre-eclampsia, eclampsia and HELLP (haemolysis, elevated liver enzymes and low platelet count) syndrome (103.8 per 10 000 deliveries), severe haemorrhage (133.7 per 10 000 deliveries), sepsis, embolism, disseminated intravascular coagulation, shock and severe mental health disorders were the most common SMM types. Rates of embolism, disseminated intravascular coagulation and shock, acute renal failure, cardiac complications, sepsis and assisted ventilation increased, whereas rates of surgical complications, severe uterine rupture and anaesthesia complications declined. The observed spatiotemporal variations in composite SMM and SMM types provide substantive insights and highlight regional priorities for improving maternal health.

Maternal and Fetal Outcome in Cases of Preeclampsia and Eclampsia in Tertiary Care Center of Nepal

INTRODUCTION Hypertensive disorders of pregnancy includes Gestational Hypertension, Preeclampsia and Eclampsia, Chronic Hypertension and Preeclampsia superimposed in Chronic Hypertension. These condition complicates around 5 to 10 percent of pregnancies and have significant contributions on maternal and fetal adverse outcome. This study was done to find out the maternal and fetal outcome in cases of Pre-eclampsia and Eclampsia. MATERIAL AND METHODS It was a hospital based cross sectional observational study done in department of Obstetrics and Gynecology of Universal College of Medical Sciences from August 2021 to June 2022. Maternal and fetal outcome in Preeclampsia and eclampsia were studied in 116 cases. RESULTS Incidence of diseases was 5.94%, preeclampsia 33(28.4%), eclampsia 23(19.8%) and severe preeclampsia 60 (57.7%). Adverse maternal outcome were HELLP (Hemolysis, Elevated liver enzyme and Low platelets counts) syndrome 15 (12.93%), Abruption placenta 7(6.03%), need of blood transfusion 20 (17.24%), Pulmonary Oedema 3(2.58%), Post-Partum Hemorrhage 3(2.58%) and one case had maternal death. Total 121 babies were born, 42(36.20%) admitted in NICU, 10(8.26%) were intra uterine fetal death (IUFD), 3 (2.48%) were neonatal death (NND), 10(8.26%) refused treatment and leave against medical advice. Common fetal morbidities were intra uterine growth restriction (IUGR) 29 (23.76%), preterm Low birth weight 22(18.18%), anomalous baby 3(2.48%) and congenital pneumonia 1 (0.83%). CONCLUSION Proper Antenatal care and screening, timely referral and prompt management favoured the outcome in positive way.

Investigating the role of platelets and platelet-derived transforming growth factor-β in idiopathic pulmonary fibrosis.

Transforming growth factor-β1 (TGFβ1) is the key profibrotic cytokine in idiopathic pulmonary fibrosis (IPF), but the primary source of this cytokine in this disease is unknown. Platelets have abundant stores of TGFβ1, although the role of these cells in IPF is ill-defined. In this study, we investigated whether platelets, and specifically platelet-derived TGFβ1, mediate IPF disease progression. Patients with IPF and non-IPF patients were recruited to determine platelet reactivity, and separate cohorts of patients with IPF were followed for mortality. To study whether platelet-derived TGFβ1 modulates pulmonary fibrosis (PF), mice with a targeted deletion of TGFβ1 in megakaryocytes and platelets (TGFβ1fl/fl.PF4-Cre) were used in the well-characterized bleomycin-induced pulmonary fibrosis (PF) animal model. In a discovery cohort, we found significantly higher mortality in patients with IPF who had elevated platelet counts within the normal range. However, our validation cohort did not confirm this observation, despite significantly increased platelets, neutrophils, active TGFβ1, and CCL5, a chemokine produced by inflammatory cells, in the blood, lung, and bronchoalveolar lavage (BAL) of patients with IPF. In vivo, we showed that despite platelets being readily detected within the lungs of bleomycin-treated mice, neither the degree of pulmonary inflammation nor fibrosis was significantly different between TGFβ1fl/fl.PF4-Cre and control mice. Our results demonstrate for the first time that platelet-derived TGFβ1 does not significantly mediate inflammation or fibrosis in a PF animal model. Furthermore, our human studies revealed blood platelet counts do not consistently predict mortality in IPF but other platelet-derived mediators, such as C-C chemokine ligand 5 (CCL5), may promote neutrophil recruitment and human IPF.NEW & NOTEWORTHY Platelets are a rich source of profibrotic TGFβ; however, the role of platelets in idiopathic pulmonary fibrosis (IPF) is unclear. We identified that patients with IPF have significantly more platelets, neutrophils, and active TGFβ in their airways than control patients. Using an animal model of IPF, we demonstrated that platelet-derived TGFβ does not significantly drive lung fibrosis or inflammation. Our findings offer a better understanding of platelets in both human and animal studies of IPF.

Biological Predictors of Osteoarticular Infection Due to K. kingae-A Retrospective Cohort Study of 247 Cases.

Pediatric osteoarticular infections (OAIs) are serious conditions that can lead to severe septic complications, prolonged morbidity with long-term impaired function, and perturbed subsequent bone development. Kingella kingae (K. kingae) is currently accepted as the predominant pathogen in pediatric OAIs, especially among 6-48 month olds. The present study aimed to identify clinical and biological markers that would refine the detection of patients with an OAI due to K. kingae. We retrospectively studied every consecutive case of pediatric OAI admitted to our institution over 17 years. Medical records were examined for patient characteristics such as temperature at admission, affected segment, and biological parameters such as white blood cell (WBC) count, left shift, platelet count (PLT), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). The 247 patients included 52.2% males and 47.8% females and mean age was 18.5 ± 10 months old. Four patients were older than 48 months; none were younger than 6 months old. Mean temperature at admission was 37.4 ± 0.9 °C. Regarding biological parameters, mean WBC count was 12,700 ± 4180/mm3, left shift was only present in one patient, mean PLT was 419,000 ± 123,000/mm3, mean CRP was 26.6 ± 27.8 mg/L, and mean ESR was 35.0 ± 18.9 mm/h. Compared to the modified predictors of OAI defined by Kocher and Caird, 17.2% of our cases were above their cut-off values for temperature, 52.3% were above the WBC cut-off, 33.5% were above the ESR cut-off, and 46.4% were above the CRP cut-off. OAIs due to K. kingae frequently remain undetected using the classic biological parameters for investigating bacterial infections. As an addition to the predictors normally used (°C, WBC, CRP, and ESR), this study found that elevated platelet count was frequently present during OAIs caused by K. kingae. Although this biological characteristic was inconstant, its presence was highly significant and very suggestive of an invasive infection due to K. kingae.

Platelets exacerbate cardiovascular inflammation in a murine model of Kawasaki disease vasculitis.

Kawasaki disease (KD) is the leading cause of acquired heart disease among children. Increased platelet counts and activation are observed during the course of KD, and elevated platelet counts are associated with higher risks of developing intravenous immunoglobulin resistance and coronary artery aneurysms. However, the role of platelets in KD pathogenesis remains unclear. Here, we analyzed transcriptomics data generated from the whole blood of patients with KD and discovered changes in the expression of platelet-related genes during acute KD. In the Lactobacillus casei cell wall extract (LCWE) murine model of KD vasculitis, LCWE injection increased platelet counts and the formation of monocyte-platelet aggregates (MPAs), upregulated the concentration of soluble P-selectin, and increased circulating thrombopoietin and interleukin 6 (IL-6). Furthermore, platelet counts correlated with the severity of cardiovascular inflammation. Genetic depletion of platelets (Mpl-/- mice) or treatment with an anti-CD42b antibody significantly reduced LCWE-induced cardiovascular lesions. Furthermore, in the mouse model, platelets promoted vascular inflammation via the formation of MPAs, which likely amplified IL-1B production. Altogether, our results indicate that platelet activation exacerbates the development of cardiovascular lesions in a murine model of KD vasculitis. These findings enhance our understanding of KD vasculitis pathogenesis and highlight MPAs, which are known to enhance IL-1B production, as a potential therapeutic target for this disorder.

HS-CRP Modifies the Prognostic Value of Platelet Count for Clinical Outcomes After Ischemic Stroke.

Background We examined whether the relationship between baseline platelet count and clinical outcomes is modulated by HS-CRP (high-sensitivity C-reactive protein) in patients with ischemic stroke. Methods and Results A total of 3267 patients with ischemic stroke were included in the analysis. The primary outcome was a combination of death and major disability at 1 year after ischemic stroke. Secondary outcomes included major disability, death, vascular events, composite outcome of vascular events or death, and an ordered 7-level categorical score of the modified Rankin Scale at 1 year. Multivariate logistic regression and Cox proportional hazards regression models were used to assess the association between the baseline platelet count and clinical outcomes stratified by HS-CRP levels when appropriate. There was an interaction effect of platelet count and HS-CRP on the adverse clinical outcomes after ischemic stroke (all Pinteraction<0.05). The elevated platelet count was significantly associated with the primary outcome (odds ratio [OR], 3.14 [95% CI, 1.77-5.58]), major disability (OR, 2.07 [95% CI, 1.15-3.71]), death (hazard ratio [HR], 2.75 [95% CI, 1.31-5.79]), and composite outcome of vascular events or death (HR, 2.57 [95% CI, 1.38-4.87]) among patients with high HS-CRP levels (all Ptrend<0.05). Conclusions The HS-CRP levels had a modifying effect on the association between platelet count and clinical outcomes in patients with ischemic stroke. Elevated platelet count was significantly associated with adverse clinical outcomes in patients with ischemic stroke with high HS-CRP levels, but not in those with low HS-CRP levels. These findings suggest that strategies for anti-inflammatory and antiplatelet therapy should be developed according to the results of both platelet and HS-CRP testing.

Essential Thrombocythemia and Ischemic Stroke: A Case Series of Five JAK2-Positive Patients.

Background and Objectives: Essential thrombocythemia (ET) is a chronic myeloproliferative neoplasm characterized by elevated platelet counts and an increased risk of thrombotic events, including ischemic strokes. Materials and Methods: We conducted a retrospective analysis of data from consecutive ischemic stroke patients with ET between March 2014 and February 2023. Results: This case series describes the clinical presentation, radiological features, and management of five patients with ET-associated ischemic strokes, all harboring the JAK2 mutation. The diverse radiological findings suggest that both large and small vessel diseases may be influenced by the prothrombotic state induced by ET. A significant elevation in platelet count was observed to correlate with the emergence of new acute infarctions in some cases. Conclusions: The study highlights combined use of antiplatelet and cytoreductive therapy in preventing secondary stroke events in patients with ET and JAK2 mutations. The heterogeneity of stroke patterns in this population necessitates a comprehensive understanding of the underlying pathophysiological mechanisms and tailored therapeutic approaches.

Thromboelastography and Traditional Coagulation Testing in Non-ICU-Admitted Patients with Acute Kidney Injury: An Observational Cohort Study

Introduction: This study aimed to elucidate the coagulation disorders in non-ICU patients with acute kidney injury (AKI) and their contribution to clotting-related outcomes of intermittent kidney replacement therapy (KRT). Methods: We included non-ICU-admitted patients with AKI requiring intermittent KRT, clinically having a risk of bleeding and against systemic anticoagulant use during KRT between April and December 2018. The premature termination of treatment due to circuit clotting was considered a poor outcome. We analyzed the characteristics of thromboelastography (TEG)-derived and traditional coagulation parameters and explored the potential-affecting factors. Results: In total, 64 patients were enrolled. Hypocoagulability was detected in 4.7%–15.6% of patients by a combination of the traditional parameters, i.e., prothrombin time (PT)/international normalized ratio, activated partial PT, and fibrinogen. No patient had hypocoagulability observed on TEG-derived reaction time; only 2.1%, 3.1%, and 10.9% of patients had hypocoagulability on TEG-derived kinetic time (K-time), α-angle, and maximum amplitude (MA), respectively, which were also platelet-related coagulation parameters, despite 37.5% of the cohort having thrombocytopenia. In contrast, hypercoagulability was more prevalent, involving 12.5%, 43.8%, 21.9%, and 48.4% of patients on TEG K-time, α-angle, MA, and coagulation index (CI), respectively, although thrombocytosis was only in 1.5% of the cohort. Patients with thrombocytopenia showed lower fibrinogen level (2.6 vs. 4.0 g/L, p = 0.00), α-angle (63.5° vs. 73.3°, p = 0.00), MA (53.5 vs. 66.1 mm, p = 0.00), and CI (1.8 vs. 3.6, p = 0.00) but higher thrombin time (17.8 vs. 16.2 s, p = 0.00) and K-time (2.0 vs. 1.2 min, p = 0.00) than those with a platelet count over 100 × 10⁹/L. 41 patients were treated with heparin-free protocol, and 23 were treated with regional citrate anticoagulation (RCA). The premature termination rate was 41.5% on heparin-free patients, while 8.7% of patients underwent an RCA protocol (p = 0.006). Heparin-free protocol was the strongest adverse factor to poor outcomes. A heparin-free subgroup analysis found that the circuit clotting risk was increased by 61.7% with a 10 × 10⁹/L elevation in platelet count (odds ratio [OR] = 1.617, p = 0.049) and decreased by 67.5% following a second increase of PT (OR = 0.325, p = 0.041). No significant correlation was found between TEG parameters and premature circuit clotting. Conclusions: Most non-ICU-admitted patients with AKI had normal-to-enhanced hemostasis and activated platelet function based on TEG results, as well as a high rate of premature circuit clotting when receiving heparin-free protocol despite thrombocytopenia. Further studies are needed to better determine the use of TEG in respect to management of anticoagulation and bleeding complications in AKI patients with KRT.

Platelet count and risk of severe illness in hospitalised children with Influenza-Like illness.

To examine the clinical significance of thrombocytosis (platelets > 500 × 109 /L) in admitted children with an influenza-like illness. We performed a database analysis consisting of patients evaluated at our medical centers with an influenza-like illness between 2009 and 2013. We included paediatric patients and examined the association between platelet count, respiratory viral infections, and admission outcomes (hospital length of stay and admission to the paediatric intensive care unit) using regression models adjusting for multiple variables. A total of 5171 children were included in the study cohort (median age 0.8 years; interquartile range, 0.2-1.8; 58% male). Younger age, and not the type of viral infection, was associated with a high platelet count (p < 0.001). Elevated platelet count independently predicted admission outcomes (p ≤ 0.05). The presence of thrombocytosis was associated with an increased risk for a prolonged length of stay (odds ratio = 1.2; 95% Confidence interval = 1.1 to 1.4; p = 0.003) and admission to the paediatric intensive care unit (odds ratio = 1.5; 95% Confidence interval = 1.1 to 2.0; p = 0.002). In children admitted with an influenza-like illness, a high platelet count is an independent predictor of admission outcomes. Platelet count may be used to improve risk assessment and management decisions in these paediatric patients.

Multiple cardiac surgical procedures in a case of an octogenarian with essential thrombocythemia

BackgroundEssential thrombocythemia (ET) is a chronic myeloproliferative disorder characterized by an elevation of platelet counts with a tendency for thrombosis and hemorrhage. The perioperative management of cardiovascular surgery of an ET patient is complicated. There is limited literature on the perioperative management of patients with ET undergoing cardiovascular surgery, particularly those requiring multiple procedures.Case presentationAn 85-year-old woman with a history of essential thrombocythemia (ET), which resulted in an abnormally high platelet count, was diagnosed with aortic valve stenosis, ischemic heart disease and paroxysmal atrial fibrillation. She underwent aortic valve replacement, coronary artery bypass grafting, and pulmonary vein isolation. The postoperative course was uneventful, nor hemorrhage and thrombosis.ConclusionsWe represent a case of perioperative management and successful treatment of three combined cardiac surgery for an octogenarian ET patient who is the oldest case ever reported.

Clinical Predictors of Pathologically Positive Temporal Artery Biopsy

Temporal arteritis (TA) can present with a wide spectrum of symptoms and lab findings, including temporal headaches, vision changes, jaw or tongue claudication, fevers, and elevated serum inflammatory markers. Here, we review a large series of patients who have undergone temporal artery biopsies. A retrospective review of all patients who underwent temporal artery biopsies within our health system from January 2005 to January 2022 was performed. Patients were selected using the Current Procedural Terminology code for temporal artery biopsy (37609). Chart review was performed to determine demographic, clinical, laboratory, and operative characteristics, as well as pathologic outcome. The primary outcome was the final pathology result of the biopsy. Patients with non-diagnostic pathology reports were excluded from the study. Variables that met a P-value < .1 in univariate analysis were included in the final multivariable logistic regression analysis. A separate sensitivity analysis was performed on a cohort with complete lab data. We identified 613 patients who underwent temporal artery biopsies across three hospitals within our health system from January 2005 to January 2022. The average age of the cohort was 73.2 ± 11.2 years. The majority of the patients, 70.5% (n = 430), were female. The most common presenting symptom was a headache, which was present in 254 (41.4%) of patients. Older age (>65), white race, lower body mass index (BMI), presence of jaw claudication, lack of blurry vision, elevated erythrocyte sedimentation rate, elevated C-reactive protein, elevated platelet count, and longer biopsy length were associated with a positive biopsy on univariate analysis (P < .05) (Table I). Specimen length did not differ significantly between groups with positive and negative pathology, nor by bilateral versus unilateral biopsy or surgeon specialty. On multivariate analysis, the presence of jaw claudication (odds ratio [OR], 3.69; P < .001) was associated with a positive biopsy. Black race was associated with a lower odds of a positive biopsy (OR, 0.27; P < .001). On sensitivity analysis, erythrocyte sedimentation rate levels above 40 were significantly associated with increased odds of a positive biopsy (OR, 7.53; P = .009). Platelet counts of 401 to 600 (OR, 7.60; P < .001) and above 600 (OR, 7.15; P = .006) were also significantly associated with a positive biopsy. Clinical and patient features including the symptom of jaw claudication, elevated erythrocyte sedimentation rate, elevated platelet count, and white race are associated with positive temporal artery biopsy. Further work is needed to determine who benefits most from this procedure.TablePatient characteristics and biopsy outcomesTotalNegative biopsy resultPositive biopsy resultP-valueN = 613n = 523n = 90Age, years <5011 (1.8)10 (1.9)1 (1.1).009 50-64109 (17.8)103 (19.7)6 (6.7) 65-79313 (51.1)266 (50.9)47 (52.2) 80+180 (29.4)144 (27.5)36 (40.0)Sex Female430 (70.5)374 (71.8)56 (62.9).090 Male180 (29.5)147 (28.2)33 (37.1)Race/ethnicity White322 (52.8)250 (48.1)72 (80.0)<.001 Black229 (37.5)216 (41.5)13 (14.4) Other/unknown59 (9.7)54 (10.4)5 (5.6)BMI Underweight (BMI <18.5)11 (1.8)7 (1.3)4 (4.4)<.001 Healthy (18.5 ≤ BMI < 25)168 (27.4)123 (23.5)45 (50.0) Overweight (25 ≤ BMI < 30)172 (28.1)150 (28.7)22 (24.4) Obese (BMI ≥30)262 (42.7)243 (46.5)19 (21.1)Preoperative steroid use Yes392 (68.7)330 (67.8)62 (73.8).27Preoperative aspirin use Yes254 (45.3)218 (45.5)36 (43.9).79Past medical history of other rheumatic disease Yes147 (25.2)130 (26.1)17 (20.2).26History of polymyalgia rheumatica Yes62 (26.6)53 (26.4)9 (28.1).83Bruit Yes3 (0.5)3 (0.6)0 (0.0).47Fever Yes41 (6.7)32 (6.1)9 (10.0).17Headache Yes254 (41.4)216 (41.3)38 (42.2).87Tenderness Yes130 (21.2)111 (21.2)19 (21.1).98Bilateral tenderness Yes26 (4.2)19 (3.6)7 (7.8).072Jaw claudication Yes95 (15.6)64 (12.3)31 (34.8)<.001Tongue claudication Yes0 (0.0)0 (0.0)0 (0.0)Blurry vision Yes111 (18.1)102 (19.5)9 (10.0).030Double vision Yes18 (2.9)13 (2.5)5 (5.6).11Tinnitus Yes6 (1.0)5 (1.0)1 (1.1).89Erythrocyte sedimentation rate at diagnosis <2050 (9.4)48 (10.6)2 (2.5).008 20-4059 (11.1)55 (12.1)4 (5.1) 40+423 (79.5)350 (77.3)73 (92.4)C-reactive protein at diagnosis <3140 (33.5)128 (36.1)12 (19.0)<.001 3-1083 (19.9)68 (19.2)15 (23.8) 11-2060 (14.4)58 (16.3)2 (3.2) 20+135 (32.3)101 (28.5)34 (54.0)Platelet count at diagnosis <200112 (20.5)104 (22.3)8 (9.9)<.001 200-400356 (65.1)314 (67.4)42 (51.9) 401-60063 (11.5)38 (8.2)25 (30.9) 601-800+16 (2.9)10 (2.1)6 (7.4)Alk-Phos (continuous)93.1 (65.9)92.9 (66.8)94.2 (62.1).90White blood cells (continuous)11.0 (17.8)10.8 (19.0)11.6 (8.1).71Longest length of biopsy specimen, cm (continuous)1.9 (0.9)1.9 (0.9)2.1 (1.0).057Boldface P indicates P-value < .1, used in multivariate analysis.Data are presented as number (%) or mean (standard deviation). Open table in a new tab

Surgical management of spontaneous hepatic rupture associated with HELLP syndrome. Case presentation and literature review

Background: HELLP syndrome is a serious complication in pregnancy characterized by hemolysis, elevated liver enzymes and low platelet count occurring in 0.2 to 0.6% of all pregnancies and in 10–20% of cases with severe preeclampsia. Spontaneous hepatic capsular rupture is a rare (0,015% of all pregnancies), but a life-threatening complication of HELLP syndrome with a mortality rate of up 50% for both mother and infant. Methods: We present the case of a 34-year-old nulliparous woman with a second trimester gestational hepatic rupture associated with HELLP syndrome. A systematic literature search was conducted on database of PubMed, Scopus, Medline and Embase. Results: Spontaneous hepatic rupture is an infrequent but life-threatening condition of pregnancy associated with severe pre-eclampsia and HELLP syndrome. Diagnosis is based on clinical suspicion. Abdominal CT with intravenous contrast is considered to be the best diagnostic method. The management of this pathology requires a multidisciplinary approach between gynecologists, general surgeons and intensive care physicians. The main therapeutic objectives are: eliminate the causal factor, end the pregnancy and control hemorrhage. If there is not hepatic rupture and the patient is hemodynamically stable, conservative nonoperative management for selected patients has been recommended. However, if the patient presents hemodynamic instability despite adequate resuscitation or hemoperitoneum, it has been seen that surgery significantly reduces the mortality associated with this pathology. Conclusions: Hepatic subcapsular hematoma and hepatic rupture are infrequent but life-threatening complications that can occur during pregnancy and are fundamentally related to pathologies such as preeclampsia and HELLP syndrome. The first step is to end the pregnancy and subsequently control the acute liver problem. Different surgical techniques have been described that should be individualized for each patient according to damage control principles. A high index of suspicion and prompt recognition allows a multidisciplinary approach and mortality can be reduced. Study type: Therapeutic/care management.