Higher Platelet Counts Research Articles

Platelet findings in 22q11.2 deletion syndrome correlate with disease manifestations but do not correlate with GPIb surface expression.

Prior studies have demonstrated that patients with chromosome 22q11.2 deletion syndrome (22q11.2DS) have lower platelet counts (PC) compared to non-deleted populations. They also have an increased mean platelet volume. The mechanism for this has been postulated to be haploinsufficiency of the GPIBB gene. We examined platelet parameters, deletion size and factors known to influence counts, including status of thyroid hormone and congenital heart disease (CHD), in a population of 825 patients with 22q11.2DS. We also measured surface expression of GPIB-IX complex by flow cytometry. The major determinant of PC was deletion status of GP1BB, regardless of surface expression or other factors. Patients with nested distal chromosome 22q11.2 deletions (those with GP1BB present) had higher PCs than those with proximal deletions where GP1BB is deleted. Patients with 22q11.2DS also demonstrated an accelerated PC decrease with age, occurring in childhood. These data demonstrate that genes within the proximal deletion segment drive PC differences in 22q11.2DS and suggest that PC reference ranges may need to be adjusted for age and deletion size in 22q11.2DS populations. Bleeding did not correlate with either platelet count or GPIb expression. Further studies into drivers of expression of GPIb and associations with severe thrombocytopenia and immune thrombocytopenia are needed to inform clinical care.

The safety and performance of the Spectra Optia apheresis system platelet depletion protocol in patients with elevated platelet counts.

Thrombocytosis is a presenting and progressive clinical feature found in multiple disease states. It is characterized by high platelet (PLT) counts (>450 × 109 /L) and can lead to thrombohemorrhagic events. Thrombocytapheresis or platelet depletion (PLTD) can be performed in acutely symptomatic patients suffering from thrombocytosis and may reduce or prevent acute serious complications associated with thrombocythemia thereby enabling patients to receive potentially curative high-dose chemotherapy. This report details the results from 2 clinical studies, one conducted in the European Union (EU) and one in the People's Republic of China, assessing the PLTD procedure on the Spectra Optia Apheresis System. The primary objective of both studies was to assess the safety and performance of the PLTD procedure in patients with elevated PLT counts. Data were collected from 56 participants completing 64 PLTD procedures. The mean percent change in PLT count and collection efficiency (CE1) was 55.1% and 68.5%, respectively. In the EU study, 6 participants experienced a total of 9 adverse events (AEs) and in the China study, 44 participants reported a total of 212 AEs. In both studies, the majority of AEs reported were Grade 2 or lower and no serious AEs, unanticipated adverse device effects, or AEs leading to death were reported. The data collected within these studies indicate that the PLTD procedure is well tolerated and effective at reducing circulating PLTs in patients suffering from thrombocytosis as evaluated by a percent decrease in PLT count, CE1, and AE incidence.

Role of reactive thrombocytosis after primary cytoreductive surgery in advanced ovarian cancer.

We investigated the incidence of reactive thrombocytosis after maximal cytoreductive surgery in advanced epithelial ovarian cancer (EOC) and its role in patient survival. We retrospectively reviewed the electronic medical records of patients who underwent primary cytoreductive surgery for advanced EOC from 1 January 2012 to 31 December 2017. We analyzed the serum platelet counts at various time points from before surgery, during the peri-operative period, and after each cycle of adjuvant chemotherapy. A total of 474 patients were eligible for the analysis. Among them, 401 patients (84.6%) had FIGO stage III disease status. The most common histology type was serous adenocarcinoma (405 patients, 85.4%). Seventy-nine patients (22.6%) received splenectomy, and optimal cytoreduction was achieved in 326 patients (68.8%). A week after surgery, thrombocytosis was observed in 165 patients (34.8%) in the entire cohort. Higher platelet counts were observed in patients with splenectomy compared with patients without splenectomy. In particular, thrombocytosis on the fifth cycle of adjuvant chemotherapy showed the most significant effects on overall survival in multivariate analysis. In a logistic regression model, splenectomy was significantly attributed to thrombocytosis on the fifth cycle of chemotherapy. Reactive thrombocytosis after primary cytoreductive surgery is associated with poor survival in advanced EOC, particularly when thrombocytosis is observed during adjuvant chemotherapy.

The Association Between Hematologic Indices With TIMI Flow In STEMI Patients Who Undergo primary percutaneous coronary intervention.

The Primary Percutaneous Coronary Intervention (PPCI) is the preferred therapeutic strategy for patients who experienced ST-Elevation Myocardial Infarction (STEMI). We aimed to evaluate the association of hematological indices, including hemoglobin level, platelets, White Blood Cells (WBCs) count, and MPV before PPCI with the TIMI grade flow after PPCI. STEMI patients who experienced PPCI were included in the present retrospective crosssectional study. Then participants were divided into three groups based on their post-procedural TIMI flow grades. Demographic data and hematologic indices of patients before PPCI were collected and their association with the TIMI grade flow after PPCI was evaluated. To compare the quantitative and qualitative variables, chi-square and t-tests were performed, respectively. We found that elevated levels of hemoglobin and decreased levels of MPV had a significant association with an advanced grade of TIMI flow. Interestingly, in the normal range, there was a significant association between higher platelet count and TIMI-flow grade 1. Besides, TIMI flow grades 2 and 3 had a significant association with low and moderate platelets count, respectively. In conclusion, evaluating MPV, platelets, and hemoglobin levels before PPCI as easy and accessible parameters may be able to identify high-risk STEMI patients undergoing PPCI.

Prediction of patient survival from heart failure using a cox-based model

The existing heart failure risk prediction models are developed based on machine learning predictors. The objective of this study is to identify the key risk factors that affect the survival time of heart patients and to develop a heart failure survival prediction model using the identified risk factors. A cox proportional hazard regression method is applied to generate the proposed heart failure survival model. We used the dataset from the University of California Irvine (UCI) clinical heart failure data repository. To develop the model we have used multiple risk factors such as age, anemia, creatinine phosphokinase, diabetes history, ejection fraction, presence of high blood pressure, platelet count, serum creatinine, sex, and smoking history. Among the risk factors, high blood pressure is identified as one of the novel risk factors for heart failure. We have validated the performance of the model via statistical and empirical validation. The experimental result shows that the proposed model achieved good discrimination and calibration ability with a C-index (receiver operating characteristic (ROC) of being 0.74 and a log-likelihood ratio of 81.95 using 11 degrees of freedom on the validation dataset.

Estimation of Total Platelet Count From Peripheral Blood Smear Needs a Correction Factor.

BackgroundDespite many advances in platelet counting by cell counters, the problem of falsely low or falsely high total platelet counts (TPC) is common. Many laboratories estimate platelet count on the peripheral smear to cross-check the platelet counts. However, due to the lack of a standard calculation method, discrepant results are obtained from different laboratories leading to confusion among clinicians. We aimed to formulate a standard estimation method for platelet count on peripheral smear.MethodologyIn the first step (in 100 blood samples), we determined the ratio of the TPC obtained by the automated cell counter and the total number of platelets per oil immersion field (filed size: 0.22 mm) of the corresponding blood smears. The mean of the ratios thus obtained was designated as the “multiplication factor” to be used for visual platelet count estimation on the peripheral blood smear. In the subsequent step, validation of the same was done on another 100 samples. TPC on the peripheral smears of these samples was estimated using the above “multiplication factor” and compared with the corresponding TPC obtained on the automated cell counter.ResultsThe “multiplication factor” obtained was 9.4 x 103 in the first set of 100 blood samples. It was used to estimate the platelet value of the second set of 100 blood samples.ConclusionsWe found an excellent agreement between the platelet counts obtained by automated cell counters and the estimation method. We suggest the multiplication factor 9.4 x 103 may be used with correction for microscopic field size to estimate platelet count on peripheral smears. This method is, however, not so reliable for very low platelet counts.

Clinical presentation, biochemical profile, and HLA haplotype frequency of celiac disease among adults in Northwest China.

To evaluate the clinical characteristics, biochemical parameters and the distribution of HLA-DQ genotypes among adult patients with celiac disease (CD) in Northwest China. This cross-sectional study retrospectively collected clinical, biochemical, and HLA-DQ genotype of patients with CD from a tertiary hospital in Xinjiang Uygur Autonomous Region, China between March 2016 and December 2021. Small intestinal biopsy and serum-specific antibodies were used to diagnose CD. Of the 102 CD patients, 63.7% were women (female: male=1.76:1), and the mean age was 47.3 ± 14.7 years at diagnosis. Common gastrointestinal symptoms included abdominal pain (50.0%), diarrhea (39.2%), and abdominal distension (24.5%). While common extraintestinal manifestations were anemia (48.0%), osteopenia or osteoporosis (36.3%), and fatigue (35.3%). Approximately 34.3% of patients with CD had comorbidities, with the most common being thyroid diseases (18.6%). Biochemical profiles showed lower hemoglobin, higher platelet count, and 25-hydroxyvitamin D (25[OH]D) deficiency. HLA-DQ2/DQ8 was detected among all 53 patients who underwent genotype testing; the frequency of the HLA-DQ2.5, DQ2.2, and DQ8 haplotypes was 71.7%, 24.5%, and 3.8%, respectively. CD was more common among women. Clinical manifestations include primarily gastrointestinal symptoms, but extraintestinal manifestations were not uncommon. Lower hemoglobin level, higher platelet count, and 25[OH]D deficiency are the main biochemical manifestations. The HLA-DQ2.5 and DQ2.2 haplotypes are the most common genotypes in CD.

The differences of hemogram, myelogram, and driver gene mutations in classic myeloproliferative neoplasms

The aim of this study was to explore and compare routine blood features and pathological characteristics of bone marrow tissues in essential thrombocythemia (ET), polycythemia vera (PV), primary myelofibrosis, prefibrotic stage (prePMF) and overt fibrotic stage (overtPMF), and the correlation between common driver gene mutations and clinical manifestations of myeloproliferative neoplasms (MPN). Methods: We analyzed 259 MPN patients treated at Tongji Hospital of Huazhong University of Science and Technology from January 2016 to December 2020. Results: Among ET, PV, prePMF, and overtPMF, the median leukocyte counts of PV and prePMF were significantly higher than those of ET. The average hemoglobin level of overtPMF was significantly lower than that of ET, PV, and prePMF. ET and prePMF had higher platelet counts than PV and overtPMF, whereas ET had the lowest platelet distribution width. Regarding hematopoietic tissues in the bone marrow, enlarged megakaryocytes were easily found in ET, PV, and prePMF, whereas the average diameter of megakaryocytes in prePMF was smaller than in ET, and PV showed various sizes of megakaryocytes. An increased M/E ratio and dilation of sinus were seen more frequently in PMF. Additionally, JAK2-positive patients tended to have significantly higher leukocyte counts than CALR-positive patients in ET and PMF.

Early thrombocytopenia is associated with an increased risk of mortality in patients with traumatic brain injury treated in the intensive care unit: a Finnish Intensive Care Consortium study

BackgroundCoagulopathy after traumatic brain injury (TBI) is associated with poor prognosis.PurposeTo assess the prevalence and association with outcomes of early thrombocytopenia in patients with TBI treated in the intensive care unit (ICU).MethodsThis is a retrospective multicenter study of adult TBI patients admitted to ICUs during 2003–2019. Thrombocytopenia was defined as a platelet count < 100 × 109/L during the first day. The association between thrombocytopenia and hospital and 12-month mortality was tested using multivariable logistic regression, adjusting for markers of injury severity.ResultsOf 4419 patients, 530 (12%) had early thrombocytopenia. In patients with thrombocytopenia, hospital and 12-month mortality were 26% and 48%, respectively; in patients with a platelet count > 100 × 109/L, they were 9% and 22%, respectively. After adjusting for injury severity, a higher platelet count was associated with decreased odds of hospital mortality (OR 0.998 per unit, 95% CI 0.996–0.999) and 12-month mortality (OR 0.998 per unit, 95% CI 0.997–0.999) in patients with moderate-to-severe TBI. Compared to patients with a normal platelet count, patients with thrombocytopenia not receiving platelet transfusion had an increased risk of 12-month mortality (OR 2.2, 95% CI 1.6–3.0), whereas patients with thrombocytopenia receiving platelet transfusion did not (OR 1.0, 95% CI 0.6–1.7).ConclusionEarly thrombocytopenia occurs in approximately one-tenth of patients with TBI treated in the ICU, and it is an independent risk factor for mortality in patients with moderate-to-severe TBI. Further research is necessary to determine whether this is modifiable by platelet transfusion.

Predicting the Risk of Diabetic Foot Ulcers From Diabetics With Dysmetabolism: A Retrospective Clinical Trial.

BackgroundDiabetic foot ulcer (DFU) in patients with type 2 diabetes mellitus (T2D) often leads to amputation. Early intervention to prevent DFU is urgently necessary. So far, there have been no studies on predictive models associated with DFU risk factors. Our study aimed to quantify the predictive risk value of DFU, promote health education, and further develop behavioral interventions to reduce the incidence of DFU.MethodsData from 973 consecutive patients with T2D was collected from two hospitals. Patients from the Guangxi Medical University First Affiliated Hospital formed the training cohort (n = 853), and those from the Wuming Hospital of Guangxi Medical University formed the validation cohort (n = 120). Independent variable grouping analysis and multivariate logistic regression analysis were used to determine the risk factors of DFUs. The prediction model was established according to the related risk factors. In addition, the accuracy of the model was evaluated by specificity, sensitivity, predictive value, and predictive likelihood ratio.ResultsIn total, 369 of the 853 patients (43.3%) and 60 of the 120 (50.0%) were diagnosed with DFUs in the two hospitals. The factors associated with DFU were old age, male gender, lower body mass index (BMI), longer duration of diabetes, history of foot disease, cardiac insufficiency, no use of oral hypoglycemic agent (OHA), high white blood cell count, high platelet count, low hemoglobin level, low lymphocyte absolute value, and high postprandial blood glucose. After incorporating these 12 factors, the nomogram drawn achieved good concordance indexes of 0.89 [95% confidence interval (CI): 0.87 to 0.91] in the training cohort and 0.84 (95% CI: 0.77 to 0.91) in the validation cohort in predicting DFUs and had well-fitted calibration curves. Patients who had a nomogram score of ≥180 were considered to have a low risk of DFU, whereas those having ≥180 were at high risk.ConclusionsA nomogram was constructed by combining 12 identified risk factors of DFU. These 12 risk factors are easily available in hospitalized patients, so the prediction of DFU in hospitalized patients with T2D has potential clinical significance. The model provides a reliable prediction of the risk of DFU in patients with T2D.

Laboratory Rat Thrombi Lose One-Third of Their Stiffness When Exposed to Large Oscillating Shear Stress Amplitudes: Contrasting Behavior to Human Clots

Rats impress by their high platelet count resulting in hypercoagulability, which protects the animals from severe bleeding. However, platelets also import numerous stiff junction points into the fibrous system of a clot, also enhancing the pre-stress of the fibrin fibers, which lowers their deformability. Clot deformation is clinically important since large strains are present in the arterial tree (caused by the propagation of pressure and pulse waves), and a clot is considered “safe” when it can deform over a long range of strain amplitudes. We tested clot formation and the behavior of fully formed blood clots of laboratory rats at large sinusoidal shear stress amplitudes by rheometry and compared outcomes to human reference data. We found that fiber density (by scanning electron microscopy) and clot stiffness (by rheometry) was pronounced compared to humans and differed with sexual dimorphism and with rat strain. Using our large amplitude oscillation (LAOS) protocol, we detected that rat clots yielded with a frustrated attempt to stiffen instead of showing the macroscopic stiffening response that is typical for human clots. We attribute this behavior to the appearance of multiple microfractures until, finally, a few leading fibers uptake the load. Rat clots also failed to align fibers in shear direction to initiate affine deformation. The rat clot phenotype differs substantially from the human one, which must be considered in research and toxicological testing. If microfractures in the fiber meshwork are concentrated in vivo, parts of a clot may break off and be washed away. However, homogenously distributed microfractures may open pores and allow the penetration of plasminogen activators. What occurs in the rat vasculature depends on the on-site clot composition.

Increased cleavage of von Willebrand factor by ADAMTS13 may contribute strongly to acquired von Willebrand syndrome development in patients with essential thrombocythemia

BackgroundPatients with essential thrombocythemia (ET) often experience bleeding associated with acquired von Willebrand syndrome (AVWS) when the platelet count is markedly increased. ObjectiveWe investigated whether von Willebrand factor (VWF) degradation is enhanced in patients with ET. MethodsSeventy patients with ET underwent VWF multimer (VWFM) analysis and measurement of VWF‐related parameters. We calculated the VWFM index, defined as the ratio of intensities of a patient's molecular weight‐categorized VWFMs, and those of a healthy subject's, using densitometric analysis. VWF degradation product (DP) was measured via ELISA using a monoclonal antibody that specifically recognizes Y1605 at the C‐terminal boundary, which is exposed following ADAMTS13‐mediated cleavage of the Y1605‐M1606 bond of the VWF A2 domain. ResultsPatients with higher platelet counts had a significantly reduced high molecular weight (HMW)‐VWFM index and an increased VWF‐DP:VWF antigen (Ag) ratio compared to those with lower platelet counts. On multivariate analysis, the VWF‐DP/VWF:Ag ratio was an independent predictor of the HMW‐VWFM index. Patients who underwent cytoreductive therapy had a significantly higher HMW‐VWFM index and lower VWF‐DP/VWF:Ag ratio than those who did not. Among individual patients, there was also a significant increase in the HMW‐VWFM index and a decrease in the VWF‐DP/VWF:Ag ratio after cytoreductive therapy compared to pre‐therapy values. ConclusionIn patients with ET, an increased platelet count is associated with enhanced cleavage of VWF at the Y1605‐M1606 bond, primarily by ADAMTS13, leading to AVWS. Cytoreductive therapy reduces the platelet count, prevents excessive VWF cleavage, and improves VWFM distributions.

Comparison Between Standard and High Dose of G-CSF for Mobilization of Hematopoietic Progenitors Cells in Patients and Healthy Donors.

A standard dose of 10 µg/kg/day granulocyte colony stimulating factors (G-CSF) is currently recommended for hematopoietic progenitor cells (HPCs) mobilization. Our aim was to analyze whether certain patients or healthy donors could benefit from high dose of G-CSF.We performed a retrospective multicenter analysis of HPCs mobilization procedures (2015-2020) in patients and healthy donors. Those who received standard dose of G-CSF (10 µg/Kg/day for 4 days to patients and healthy donors) and those that received higher dose (24 µg/Kg/day for 4 days to patients and 16 µg/Kg/day for 4 days to healthy donors) were compared.496 individuals were included (201 standard dose and 295 higher dose). Between standard or higher dose, we did not find significant differences in median number of mobilized CD34+ cells/mL, neither among healthy donors (77 100 vs 75 500 respectively, P=.895), nor in patients (34 270 vs 33 704 respectively, P=.584). Additionally, among those with the same underlaying pathology the comparison between standard and higher dose did not showed differences. High G-CSF dose was not associated with a less frequent incidence of poor mobilizers (<20 000 CD34+ cells/mL) neither in healthy donors (1 [1.3%] vs 0; P=.218) nor patients (30 [24.4%] vs 32 [18.1%]; P=.165). Multivariate analysis showed that age, gender, and G-CSF dose did not influence median number of mobilized CD34+ cells/mL in healthy donors or patients. However, the underlying pathology among patients significantly influenced the CD34+ cells mobilization. In healthy donors, cellular blood count showed significantly higher leukocytes and platelets count with G-CSF high-dose, while in patients just a higher platelets count was found. To conclude, high dose of G-CSF compared to standard dose did not show significant benefit in terms of mobilization of CD34+ cells in healthy donors or in patients, also without a decrease in the incidence of poor mobilizers.

Clinical characteristics of Kawasaki disease in Polish children: A retrospective study.

Kawasaki disease (KD), an acute, generalized vasculitis, is associated with an increased risk of coronary heart disease and is the most common cause of acquired heart disease in childhood. The incidence of KD is increasing worldwide. Our study aims to analyze KD's clinical course in children and to evaluate risk factors for persistent changes in coronary vessels after 6-8 weeks of treatment. The retrospective analysis included patients with KD hospitalized in a single tertiary carehospital. The diagnosis, as well as treatment, were based on the current worldwide treatment standards. The clinical course, selected laboratory parameters, the treatment effect, and following cardiac complications were analyzed in different age groups. In the years 2006-2019, 140 patients aged from two months to 16 years: 52 girls and 88 boys, were diagnosed with KD. Coronary artery aneurysms (CAA) at weeks 6-8 of disease were found in 16% of patients. Boys and infants were more likely to develop aneurysms at weeks 6-8 of the disease (P = 0.045; P = 0.03; respectively). The CAA frequency was related to the atypical course (P = 0.02), late diagnosis (P = 0.04), presence of changes in the coronary arteries at the time of diag nosis (P<0.001), immunoglobulin resistance (P = 0.002), a lower hemoglobin concentraction (P<0.001), and a higher platelet count (P = 0.02). There were 28% of patients resistant to first-line time treatment. In this group, we found CAA in 31% of children. We found that late diagnosis, low hemoglobin level, high platelet count, CAA presence at diagnosis, atypical course of KD, and resistance to intravenous immunoglobulins are predictors of CAA after 6-8 weeks in KD patients.

Serum Markers Associated with Disease Severity in a Bosnian Hemorrhagic Fever with Renal Syndrome Cohort.

Puumala orthohantavirus (PUUV) is endemic in Europe and can cause hemorrhagic fever with renal syndrome (nephropathia epidemica). Disease features include fever, thrombocytopenia, and acute kidney injury (AKI). This retrospective cohort study of forty PUUV patients aims to characterize associations of serum immunological, hemostatic or kidney injury markers to disease severity. While interleukin-18 (IL-18) was significantly increased in severely thrombocytopenic patients (<100 × 109 platelets/L) compared to patients with higher platelet counts, RANTES was significantly decreased in these patients. These data suggest that patients with significant thrombocytopenia might have experienced pronounced Th1 immune responses. When kidney dysfunction was used as the primary disease outcome, recently identified AKI biomarkers (Cystatin C, insulin-like growth factor-binding protein 7, Nephrin, and trefoil factor 3) were significantly upregulated in patients with severe PUUV infection, defined as the estimated glomerular filtration rate (eGFR) below 30 m/min/1.73 m2. The increased expression of these markers specifically indicates pathology in glomeruli and proximal tubuli. Furthermore, E-selectin was significantly higher while interferon gamma-induced protein 10 (IP-10) was significantly lower in PUUV patients with more severe kidney dysfunction compared to patients with higher eGFR-values. Increased E-selectin illustrates the central role of endothelial cell activation, whereas decreased IP-10 could indicate a less important role of this cytokine in the pathogenesis of kidney dysfunction.

Stroke propensity in the Th3+/ mouse model of β-thalassemia intermedia

β-thalassemia is associated with multiple hematological and cerebrovascular symptoms linked to a hypercoagulable state that has not been fully replicated in animal models for the development of stroke treatments. Herein we compared the physiological properties and responses to transient cerebral hypoxia-ischemia (tHI) between six-month-old wildtype and heterozygous Th3/+ mice, a model of non-transfusion-dependent β-thalassemia intermedia (β-TI). We found that Th3/+ mice developed microcytic anemia, splenomegaly, higher platelet counts, and increased platelet-erythrocyte plus erythrocyte-leukocyte aggregates. Furthermore, Th3/+ mice showed diminished cerebrovascular reactivity (CVR) and cortical oxygen saturation under repetitive hypercapnic challenges. When subjected to a sub-threshold tHI insult, platelets and leukocytes in Th3/+ mice adhered to the cerebrovascular wall or formed aggregates, while their counterparts flew through smoothly in wildtype mice. Subsequently, Th3/+ mice showed increased fibrin deposition around cerebral blood vessels and larger infarction than wildtype mice, especially in female Th3/+ mice. Collectively these results showed that Th3/+ mice mimic key clinical features and a propensity to thromboembolism in β-TI patients. The hypercoagulable state in Th3/+ mice is likely caused by multiple hematological and CVR anomalies that are similar, but are not identical to those in the mouse model of sickle cell anemia. As such, we suggest that Th3/+ mice are a useful model to study the pathological mechanisms and prophylactic stroke treatments in thalassemia patients.

PB2042: CLINICAL AND MOLECULAR CORRELATION OF PATIENTS WITH ESSENTIAL THROMBOCYTHEMIA: A RETROSPECTIVE ANALYSIS FROM A TERTIARY CARE CENTER IN INDIA.

Background: Approximately 50–70% of patients of ET harbor JAK2 mutation while about 20–30% patients carry CALR mutations. Data from developed countries has shown that CALR mutated patients have higher platelet count and lower thrombotic risk compared to JAK2 mutated patients. In India, testing for CALR and MPL mutation and next generation sequencing has become available only in last 5 years. There is lack of data regarding mutation status and its clinical correlation. We studied clinical features of ET patients presented to our hospital according to their mutation status. Aims: To study the molecular mutations and correlate them with the clinical features in ET patients Methods: We did the retrospective analysis of the patients diagnosed as ET from January 2016 to December 2021. Allele Specific PCR and fragment analysis was done to detect JAK2 (V617F), MPL (W515L/K) and CALR exon-9 mutations. Risk stratification done as per revised IPSET (International Prognostic Scoring for thrombosis in Essential Thrombocythemia) score. Therapy was started in all the patients according to their risk score with hydroxyurea or aspirin as the standard of care. Results: A total of 39 diagnosed cases of ET were identified. Median age was 55 years (30-83), 20/39 males (51.3%) and 19/39 females (48.7%). JAK2 mutation was found in 25.6% (10/39), CALR in 38.5% (15/39) and MPL in 5.1% (2/39) cases. Triple negativity was found in 30.8% (12/39) cases. Very low, low, intermediate and high-risk patients as per IPSET score were 53.9% (21/39), 10.2% (4/39), 20.5% (8/39) and 15.4% (6/39) respectively. The median age was statistically significantly lower in CALR positive cases compared to the JAK2 positive cases (45.9 vs 60.9years, p=0.011). The median Hemoglobin and platelet counts were slightly higher in CALR positive group (12.3 g/dL and 10.15x109/l) compared to JAK2 mutated and triple negative groups but the difference was not statistically significant. Three patients (7.7%) presented with thrombosis; two with cerebral venous thrombosis both CALR positive, one with arterial stroke and MPL gene mutation. Ten (25.6%) patients were lost to follow up. One (2.6%) died to pulmonary infection. Median follow up period was 24 months. None of the patient transformed to acute myeloid leukemia or myelofibrosis. None of the patient developed thrombotic event after diagnosis and appropriate treatment. Summary/Conclusion: We observed that CALR was the most common mutation in our study. The CALR mutated patients were younger in age but the median platelet counts, WBC count and Hemoglobin were not statistically different among different mutation groups. In contrast to western studies, thrombosis was observed to be higher in CALR mutated group than others in our patient population. We recommend larger multicenter study for further elucidation of these observations.

PB2039: CLINICAL FEATURES AND NEXT-GENERATION SEQUENCING LANDSCAPE OF ESSENTIAL THROM-BOCYTHEMIA，PREFIBROTIC PRIMARY MYELOFIBROSIS, AND OVERT FIBROTIC PRIMARY MYELOFIBROSIS: A CHINESE RETROSPECTIVE STUDY

Background: Since prefibrotic primary myelofibrosis (pre-PMF) was recognized as a separate enti-ty in the 2016 revised classification of MPN differed from essential thrombocythemia (ET) or overt fibrotic primary myelofibrosis (overt PMF), it has been a subject of de-bate among experts due to its indefinite diagnosis. Aims: We conducted a retrospective study of patients with myeloproliferative neoplasms (MPNs) in China, including 56 ET pa-tients, 19 pre-PMF patients, and 43 overt PMF patients. Methods: We conducted a retrospective study of patients with BCR-ABL-negative MPN from October 2014 to May 2021 in the Fourth Affiliated Hospital of Zhejiang University School of Medicine. Patients who were diagnosed with ET, pre-PMF or overt PMF according to the 2016 WHO revised Classification of MPN were included. Patients with incomplete information from laboratory tests and medical records were excluded. This study was approved by the Ethics Committee of the Fourth Affiliated Hospital of Zhejiang University School of Medicine in line with the principles of the Declaration of Helsinki.Statistical analyses were performed using SPSS statistics 26.0 and GraphPad Prism 8.0 software. Results: Pre-PMF patients exhibited higher leukocyte counts[14.2(6.0-28.1)×109/L vs 9.6(4.0-55.0)×109/L, P=0.003], LDH values[307(233-479)U/L vs 241(129-1182)U/L, P<0.001], onset ages[67(32-76)years vs 50(16-79) years, P=0.006], a higher frequen-cy of splenomegaly(47.4% vs 16.7%, P=0.018) and hypertension(57.9% vs 23.2%, P=0.005) than ET patients. On the other hand, pre-PMF patients had higher platelet counts[960(500-2245)×109/L vs 633(102-1720)×109/L, P=0.017], haemoglobin levels[152(115-174)g/L vs 119(71-200)g/L, P=0.003], lower LDH val-ues[307(233-479)U/L vs 439(134-8100)U/L, P=0.007] and a lower frequency of splenomegaly(47.4% vs 75.6%, P=0.031) than overt PMF patients. Next-generation sequencing landscape was performed in 50 patients, revealed the frequency of EP300 mutations was significantly increased in pre-PMF patients compared with ET and overt PMF patients (60% vs 10% vs 15.79%, P=0.033), and WT1 was more often overexpressed (WT1/ABL1 copies≥1.0%) in patients with overt PMF than in those with ET or pre-PMF(54.55% vs 16.67% vs 17.65%, P=0.009). In terms of outcome, male sex, along with symptoms including MPN10, anaemia (haemoglobin<120g/L), thrombocytopenia (platelet count<100×109/L), leucocytosis (leukocyte counts>13×109/L), high LDH value (>350U/L), splenomegaly, WT1 overexpres-sion(WT1/ABL1 copies≥1.0%), KMT2A, ASXL1 and TP53 mutations, indicated a poor prognosis for PMF patients. The research was supported by the Key R&D Program of Zhejiang, No. 2022C03137; Public Technology Application Research Program of Zhejiang, China, No. LGF21H080003; the Key Project of Jinhua Science and Technology Plan, China, No. 2020-3-011; the 2019–2024 Academician Workstation of the Fourth Affiliated Hospi-tal of the Zhejiang University School of Medicine; the 2019–2022 Key Medical Dis-cipline (Hematology) Fund of Jinhua, China. *Correspondence to: Dr Jian Huang, Department of Hematology, The Fourth Affiliated Hospital of Zhejiang University School of Medicine. N1 Shangcheng Road. Yiwu, Zhejiang, Peoples R China. E-mail: [email protected] Image:Summary/Conclusion: In summary, the results of this study indicated that comprehensive evaluation of BM features, clinical phenotypes, haematologic parame-ters, and molecular profiles is needed for the accurate diagnosis and treatment of ET, pre-PMF, and overt PMF patients.

Clinical features and next-generation sequencing landscape of essential thrombocythemia, prefibrotic primary myelofibrosis, and overt fibrotic primary myelofibrosis: a Chinese monocentric retrospective study.

Since prefibrotic primary myelofibrosis (pre-PMF) was recognized as a separate entity in the 2016 revised classification of MPN differed from essential thrombocythemia (ET) or overt fibrotic primary myelofibrosis (overt PMF), it has been a subject of debate among experts due to its indefinite diagnosis. We retrospectively reviewed the clinical parameters, haematologic information, and genetic mutations of patients who were diagnosed withmyeloproliferative neoplasms (MPNs)according to the WHO 2016 criteria in China, including 56 ET patients, 19 pre-PMF patients, and 43 overt PMF patients. Pre-PMF patients exhibited higher leukocyte counts [14.2(6.0-28.1) × 109/L vs 9.6(4.0-55.0) × 109/L, P = 0.003], LDH values [307(233-479)U/L vs 241(129-1182)U/L, P < 0.001], onset ages [67(32-76) years vs 50(16-79) years, P = 0.006], a higher frequency of splenomegaly(47.4% vs 16.7%, P = 0.018) and hypertension (57.9 vs 23.2%, P = 0.005) than ET patients. On the other hand, pre-PMF patients had higher platelet counts [960(500-2245) × 109/L vs 633(102-1720) × 109/L, P = 0.017], haemoglobin levels [152(115-174)g/L vs 119(71-200)g/L, P = 0.003], lower LDH values [307(233-479)U/L vs 439(134-8100)U/L, P = 0.007] and a lower frequency of splenomegaly(47.4 vs 75.6%, P = 0.031) than overt PMF patients. Next-generation sequencing landscape was performed in 50 patients, revealed the frequency of EP300 mutations was significantly increased in pre-PMF patients compared with ET and overt PMF patients (60 vs 10 vs 15.79%, P = 0.033), and WT1 was more often overexpressed (WT1/ABL1 copies ≥ 1.0%) in patients with overt PMF than in those with ET or pre-PMF(54.55 vs 16.67 vs 17.65%, P = 0.009). In terms of outcome, male sex, along with symptoms including MPN10, anaemia (haemoglobin < 120g/L), thrombocytopenia (platelet count < 100 × 109/L), leucocytosis (leukocyte counts > 13 × 109/L), high LDH value (> 350U/L), splenomegaly, WT1 overexpression(WT1/ABL1 copies ≥ 1.0%), KMT2A, ASXL1 and TP53 mutations, indicated a poor prognosis for PMF patients. The results of this study indicated that a comprehensive evaluation of BM features, clinical phenotypes, haematologic parameters, and molecular profiles is needed for the accurate diagnosis and treatment of ET, pre-PMF, and overt PMF patients.

Coagulation parameters in lung cancer patients: A systematic review and meta-analysis.

BackgroundHypercoagulability in lung cancer patients is associated with a high incidence of mortality and morbidity in the world. Therefore, this meta‐analysis aimed to explore the correlation of the basic coagulation abnormalities in lung cancer patients compared with the control.MethodPubMed, Scopus, and other sources were employed to identify eligible studies. The outcome variable was expressed using mean ± standard deviation (SD). Heterogeneity among studies and publication bias were evaluated. The quality of included studies was also assessed based on Newcastle–Ottawa Scale checklist.ResultFinally, through a total of eight studies, prolonged prothrombin time (PT; standard mean difference [SMD]: 1.29; 95% CI: 0.47–2.11), plasma D‐dimer value (SMD 3.10; 95% CI 2.08–4.12), fibrinogen (SMD 2.18; 95% CI:1.30–3.06), and platelet (PLT) count (SMD 1.00; 95% CI 0.84–1.16) were significantly higher in lung cancer patients when compared with the control group. The single‐arm meta‐analysis also showed that compared with control, lung cancer patients had high pooled PT 13.7 (95% CI:12.2–15.58) versus 11.79 (95% CI = 10.56–13.02), high D‐dimer 275.99 (95% CI:172.9–11735.9) versus 0.2 (95% CI:0.20–0.37), high plasma fibrinogen 5.50 (95% CI:4.21–6.79) versus 2.5 (95% CI:2.04–2.91), and high PLT count 342.3 (95% CI:236.1–448.5) versus 206.6 (95% CI:176.4–236.7).ConclusionIn conclusion, almost all the coagulation abnormalities were closely associated with lung cancer, and hence coagulation indexes provide an urgent clue for early diagnosis and timely management.