Levels of Soluble CD30 and CD26 and Their Clinical Significance in Patients with Primary Immune Thrombocytopenia

Background. sCD30 and sCD26 are correlated with autoimmune diseases. However, little research has been done on the relationship between them and primary immune thrombocytopenia (ITP). Methods. This study enrolled 47 patients diagnosed with ITP in the Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences (Tianjin, China), from January 2015 to August 2015. The peripheral blood of all subjects was collected. The mRNA expression of CD30 was quantified by RT-PCR, and concentrations of sCD30 and sCD26 were measured by ELISA. Patient characteristics, CD30 mRNA levels, and sCD30 and sCD26 concentrations were analyzed. Results. The concentration of sCD30 was higher in active ITP patients (median, 35.82 ng/mL) than in remission ITP patients (median, 23.12 ng/mL; P=0.021) and healthy controls (median, 25.11 ng/mL; P=0.002). Plasma sCD26 levels decreased in remission ITP patients compared with that in healthy controls (median, 599.4 ng/mL vs. 964.23 ng/mL; P=0.004). Ratios of sCD26/sCD30 in active ITP patients decreased compared with those in controls (P=0.005). Increased sCD30 was positively correlated with hemorrhage (r=0.493, P=0.017) in ITP patients while little relationship was identified between sCD26 and ITP. Conclusion. Since sCD30 levels and sCD26/sCD30 ratios may contribute to the activity of the disease, they may be used to assess ITP disease activity.

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Increased miR-155 Expression in Peripheral Blood Mononuclear Cells of Primary Immune Thrombocytopenia Patients Was Correlated with Serum Cytokine Profiles

Acta Haematologica ◽

10.1159/000362150 ◽

2014 ◽

Vol 133 (3) ◽

pp. 257-263 ◽

Cited By ~ 3

Author(s):

Bao-Hua Qian ◽

Xin Ye ◽

Lei Zhang ◽

Yi Sun ◽

Jian-Rong Zhang ◽

...

Keyword(s):

Peripheral Blood Mononuclear Cells ◽

Immune Thrombocytopenia ◽

Mononuclear Cells ◽

Mrna Levels ◽

Healthy Controls ◽

Serum Cytokine ◽

Peripheral Blood Mononuclear ◽

Blood Mononuclear Cells ◽

Primary Immune Thrombocytopenia ◽

Tgf Β1

We investigated the possible pathogenic role of a microRNA (miR-155) in primary immune thrombocytopenia (ITP). We used quantitative real-time PCR to determine the relative expression of miR-155 and SOCS1 (suppressor of cytokine signaling) mRNA in peripheral blood mononuclear cells (PBMCs) from 28 ITP patients and 28 healthy controls. Cytokine plasma levels were determined by ELISA. Possible associations between miR-155 levels and serum cytokine concentrations were assessed using Spearman or Pearson correlation analysis. Seven naive ITP patients were followed and the effects of medical treatment on miR-155 levels were assessed. Compared to healthy controls, ITP patients had increased miR-155 and decreased SOCS1 mRNA levels. ITP patients also had increased plasma IL-17A and decreased IL-4, IL-10 and TGF-β1 levels. miR-155 levels were negatively correlated with platelet counts, SOCS1 mRNA levels, and the plasma levels of IL-4, IL-10 and TGF-β1, but positively correlated with plasma IL-17A levels. Medical treatment for ITP decreased miR-155 levels. Thus, our results suggest that miR-155 might be involved in the pathogenesis of ITP by regulating cytokine profiles, which may be mediated by miR-155 targeting SOCS1. © 2014 S. Karger AG, Basel

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The Ratio of Treg/Th17 Cells Correlates with the Platelet Number in Different Disease State of Primary Immune Thrombocytopenia

Blood ◽

10.1182/blood.v120.21.4649.4649 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4649-4649

Author(s):

Lili Ji ◽

Feng Li ◽

Yanxia Zhan ◽

Fanli Hua ◽

Shanhua Zou ◽

...

Keyword(s):

Autoimmune Diseases ◽

Th17 Cells ◽

Immune Thrombocytopenia ◽

Conflicts Of Interest ◽

Disease Onset ◽

Treg Cells ◽

Healthy Controls ◽

T Helper ◽

Platelet Number ◽

Primary Immune Thrombocytopenia

Abstract Abstract 4649 Background: Primary immune thrombocytopenia (ITP) is an autoimmune heterogeneous disorder that is characterized by decreased platelet count. Regulatory T (Treg) cells and T helper type 17 (Th17) cells are two subtypes of CD4+T helper (Th) cells. They play opposite roles in immune tolerance and autoimmune diseases, while they share a common differentiation pathway. The imbalance of Treg/Th17 has been demonstrated in several autoimmune diseases. In this study, we aimed to investigate the ratio of the number of Tregs to the number of Th17 cells in ITP patients and evaluate the clinical implications of the alterations in this ratio. Methods: Thirty adult patients with newly diagnosed ITP enrolled in this study. Patients who needed treatment had been clinically followed up for 12 months. The percentages of CD4+CD25hiFoxp3+ Treg cells and CD3+CD4+IL-17-producing Th17 cells in these patients and healthy controls (n=17) were longitudinally analyzed by flow cytometry. Results: The percentage of Treg cells in ITP patients was significantly lower than that of healthy controls and the percentage of Th17 cells increased significantly at disease onset. It is suggested that the ratio of Treg/Th17 correlated with the disease activity. Conclusion: The ratio of Treg/Th17 might be relevant to the clinical diversity of ITP patients, and this Treg/Th17 ratio might have prognostic role in ITP patients. Disclosures: No relevant conflicts of interest to declare.

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Effects of Rituximab and Dexamethasone on Regulatory and Pro-Inflammatory B-Cell Subsets in Patients with Primary Immune Thrombocytopenia

Blood ◽

10.1182/blood.v128.22.1378.1378 ◽

2016 ◽

Vol 128 (22) ◽

pp. 1378-1378

Author(s):

Sif Gudbrandsdottir ◽

Marie Brimnes ◽

Tania Kollgaard ◽

Hans Carl Hasselbalch ◽

Claus Henrik Nielsen

Keyword(s):

B Cells ◽

Autoimmune Diseases ◽

B Cell ◽

Research Funding ◽

Immune Thrombocytopenia ◽

Lower Proportion ◽

Surface Markers ◽

Healthy Controls ◽

Cell Functions ◽

Primary Immune Thrombocytopenia

Abstract Background B-cell depletion with rituximab (RTX) is widely accepted as first- or second-line therapy in primary immune thrombocytopenia (ITP), but it is still unclear how RTX mediates its positive effect in ITP patients. RTX has been reported to induce a reduced titer of platelet antibodies. However, this finding is inconsistent and other B-cell functions, such as the ability to secrete cytokines or to function as antigen-presenting cells for T cells, may be involved in the pathogenesis of ITP. Evidence suggests that B cells participate in the regulation of autoimmune diseases by virtue of their ability to produce the regulatory cytokines interleukin (IL)-10, IL-35, or transforming growth factor β. The various functions of B cells involved in the pathogenesis of autoimmune diseases can in part be deducted by their phenotype as recognized by measurement of specific surface markers and cytokine secretion. Materials and Methods We previously conducted a trial involving 137 newly diagnosed adult ITP patients randomized to treatment with RTX (375 mg/m2/week for 4 weeks) + dexamethasone (DXM) (40 mg/day for 4 days repeated up to 6 cycles) or DXM monotherapy. From this cohort, we identified 16 patients with available samples of peripheral blood mononuclear cells (PBMCs) at baseline and 12 months after treatment; 9 patients from the RTX+DXM group, 7 patients from the DXM group. Seven anonymous blood donors served as healthy controls. PBMCs were incubated for 18 h at 37°C under 5% CO2 in RPMI-1640 containing 10% (v/v) serum from healthy blood group AB donors, either alone or stimulated with 10 µg/ml CpG oligodeoxynucleotides. Expression of the cell-surface markers CD5, CD27, CD25 and CD19, and intracellular content of IL-6 and IL-10 were measured by flow cytometry. Results All patients responded to therapy and were in complete or partial remission at 12 months. Patient characteristics are listed in table I. We observed a significant increase in the proportion of CD5+ B cells 12 months after treatment with RTX+DXM compared to baseline (p < 0.01, Fig. 1A). The percentage of CD27+ memory B cells was significantly decreased at 12 months compared to baseline in patients receiving RTX+DXM (p < 0.05, Fig. 1B), and there was an inverse correlation between platelet numbers and the proportion of CD27+ B cells (R = -0.71; p < 0.05). The proportion of CD25+ B cells tended to decrease in patients treated with RTX+DXM, and was lower at 12 months than in patients treated with DMX only (p < 0.05, Fig 1C). PBMCs from ITP patients contained a lower proportion of IL-10+ B cells (p < 0.01) as well as a lower proportion of B cells producing IL-6 (p < 0.01) at baseline than PBMCs from healthy controls. At 12 months the low proportions had normalized in both treatment groups (Fig. 2). Conclusion B cells from ITP patients treated with RTX+DXM contained a high proportion of CD5+ B cells and low proportions of CD25+ and CD27+ B cells. Before treatment, B cells from ITP patients contained low frequencies of IL-10+ and IL-6+ B cells. Treatment with RTX + DXM or DXM alone reverted these aberrancies to normal. The increase in IL-10+ B cells as well as CD5+ B cells, which may represent overlapping subsets, is compatible with induction of Bregs and may support Treg development. Given the role of CD5+ B cells in maintenance of tolerance, the high frequency of these cells, which has also been observed after RTX therapy in rheumatoid arthritis, is compatible with amelioration of disease. Table 1 Table 1. Disclosures Gudbrandsdottir: GSK: Research Funding; Amgen: Research Funding.

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Correlations Between Epidemiological and Clinical Characteristics, Laboratory Tests and CT Scan Reports in the Diagnosis of COVID-19: A Diagnostic Accuracy Study

ACTA MEDICA IRANICA ◽

10.18502/acta.v59i10.7761 ◽

2021 ◽

Author(s):

Bobby Branson ◽

Ramin Tavakoli ◽

Mansoor Khaledi ◽

Javad Fathi ◽

Seyed Mohammad Shafiee ◽

...

Keyword(s):

Ct Scan ◽

Clinical Information ◽

Pulmonary Involvement ◽

Medical Sciences ◽

Rt Pcr ◽

Laboratory Findings ◽

Quantitative Score ◽

Accuracy Study ◽

Hospital Comparison ◽

The Relationship

Although the relationship between laboratory parameters, radiology, CT scan scan and clinical outcomes has not been well evaluated so far, COVID-19 is still a good challenge for this purpose. These tests can be used to diagnose, monitor, and treat COVID-19. The study was conducted from February 20 to August 31, 2020, following the referral of 340 patients with coronavirus symptoms at Chamran Hospital, Shiraz University of Medical Sciences, Shiraz, Iran. Clinical information of each patient is obtained based on patient information forms when visiting the hospital. Comparison of the relationship between lung involvement in CT scan and laboratory indicators, including biochemical and hematological factors is a suitable and reliable comparison to identify people with Covid 19. Based on the results of this study, it was found that ALT, AST, CRP, NEU, LDH, and Urea could be a suitable diagnostic method in positive RT-PCR for COVID-19. In this study, we tried to investigate the relationship between clinical and laboratory findings with CT-based quantitative score of pulmonary involvement in COVID-19 pneumonia and as a suitable and reliable method in continuing COVID-19 pandemic and diagnosis of COVID-19 infection.

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Interleukin (IL)-1 family cytokine in primary immune thrombocytopenia: a comparison with systemic lupus erythematosus-associated thrombocytopenia

10.21203/rs.3.rs-17605/v1 ◽

2020 ◽

Author(s):

Yanxia Zhan ◽

Boting Wu ◽

Chanjuan liu ◽

Luya Cheng ◽

Lili Ji ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Platelet Count ◽

Lupus Erythematosus ◽

Immune Thrombocytopenia ◽

Serum Levels ◽

Healthy Controls ◽

Systemic Lupus ◽

Primary Immune Thrombocytopenia ◽

Polymerase Chain

Abstract Background : Primary immune thrombocytopenia (ITP) is an autoimmune-mediated disorder characterized by decreased platelet count. Systemic lupus erythematosus (SLE) is also an autoimmune disease which thrombocytopenia is a common hematologic manifestation. Interleukin (IL)-1 family cytokines are major proinflammatory and immunoregulatory mediators. This study aimed to investigate the role of IL-1 cytokines in patients with ITP and SLE and the potential pathophysiologic mechanism to differentiate SLE-associated thrombocytopenia (SLE-TP) from ITP. Methods : Multiplex cytokine assay and real-time polymerase chain reaction (RT-PCR) were used to measure the IL-1 cytokines in 17 newly diagnosed ITP patients, 17 SLE-TP patients, 19 SLE patients without thrombocytopenia (SLE-NTP) and 10 healthy controls. Results : The serum levels of IL-1β, IL-18, IL-36α, IL-36β, IL-36γ and IL-33 were decreased significantly in ITP patients as compared with SLE-TP, SLE-NTP patients and healthy controls ( p <0.05). There was no significantly difference in the serum level of IL-37 between ITP and SLE-TP patients, however, there is a positive correlation between platelet count with IL-37 level in ITP patients. Our data suggested that serum IL-1β, IL-18, IL-36α, IL-36β, IL-36γ, IL-33 and IL-37 were involved in the pathogenesis of ITP. Conclusions : Serum IL-1β, IL-18, IL-36α, IL-36β, IL-36γ and IL-33 could be considered biomarkers to differentiate SLE-TP from ITP patients.

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Abnormalities of Bone Marrow B Cells and Plasma Cells in Primary Immune Thrombocytopenia

Blood Advances ◽

10.1182/bloodadvances.2020003860 ◽

2021 ◽

Author(s):

Tianshu Yu ◽

Haoyi Wang ◽

Yajing Zhao ◽

Yafei Yu ◽

Yu Hou ◽

...

Keyword(s):

Bone Marrow ◽

B Cells ◽

B Cell ◽

Immune Thrombocytopenia ◽

Plasma Cells ◽

Plasma Concentrations ◽

Mrna Levels ◽

Primary Immune Thrombocytopenia ◽

B Cell Subsets

Primary immune thrombocytopenia (ITP) is an autoantibody-mediated hemorrhagic disorder where B cells play an essential role. Previous studies have focused on peripheral blood (PB), but B cells in bone marrow (BM) have not been well characterized. We aimed to explore the profile of B cell subsets and their cytokine environments in BM of ITP patients to further clarify the pathogenesis of the disease. B cell subpopulations and their cytokine/chemokine receptors were detected by flow cytometry. Plasma concentrations of cytokines/chemokines were measured by ELISA. mRNA levels of B cell-related transcription factors were determined by qPCR. Regulatory B cell (Breg) function was assessed by quantifying their inhibitory effects on monocytes and T cells in vitro. Decreased proportions of total B cells, naïve B cells and defective Bregs were observed in ITP patients compared with healthy controls (HCs), whereas elevated frequency of long-lived plasma cells was found in BM of autoantibody-positive patients. No statistical difference was observed in plasmablasts or in short-lived plasma cells between ITP patients and HCs. The immunosuppressive capacity of BM Bregs from ITP patients was considerably weaker than that from HCs. In vivo study using an active ITP murine model revealed that Breg transfusion could significantly alleviate thrombocytopenia. Moreover, over-activation of CXCL13-CXCR5 and BAFF/APRIL systems were found in ITP patient BM. Taken together, B cell subsets in BM were skewed toward a proinflammatory profile in ITP patients, suggesting the involvement of dysregulated BM B cells in the development of the disease.

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Effect of PHAP1 and SUMO2 on biological characteristics of Cervical squamous cell carcinoma

10.21203/rs.2.18625/v1 ◽

2019 ◽

Author(s):

Qian Liu ◽

Xiaohong Li ◽

Song Qin

Keyword(s):

Expression Patterns ◽

Cervical Squamous Cell Carcinoma ◽

Biological Characteristics ◽

Tumor Promoter ◽

Mrna Levels ◽

Rt Pcr ◽

Tissue Samples ◽

Normal Tissues ◽

The Relationship ◽

Hpv16 Infection

Abstract Background This study aimed to investigate the biological characteristics of PHAP1 and SUMO2 in CSCC and the relationship between the expression of the 2 genes and HPV16 infection. Method To detect the function of PHAP1 and SUMO2 in the occurrence and development of CSCC, we first compared their expression patterns in CSCC tissue samples, CIN and matched normal tissues through IHC, and RT-PCR. In addition, we carried on WB assay to test the expression of PHAP1 and SUMO2 in the SiHa, C33A and Ect1 cell lines. We analyzed the relationship between the expression of PHAP1 and SUMO2 and HPV16 infection. Result The results demonstrated that PHAP1 and SUMO2 expression at both the protein and mRNA levels was elevated in CSCC tissues compared with CIN and normal tissues. The expression of SUMO2 was significantly associated with lymph node metastasis (P=0.02), AJCC stage(p=0.024), but not other clinicopathological factors. The expression of PHAP1 and SUMO2 protein in SiHa, C33A cells was obviously higher than that in Ect1 cells. The expression of PHAP1 and SUMO2 was associated with a susceptibility to HPV16 infections. Conclusion Our results imply that PHAP1 and SUMO2 may be potential tumor promoter genes and may provide the biological basis for diagnosis, prognosis and treatment for CSCC.

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Preliminary Study of the Autoantigens on the Membrane of Erythropoietic Cells of the Patients with BMMNC- Coomb’s Test(+) Hemocytopenia

Blood ◽

10.1182/blood.v118.21.4382.4382 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4382-4382

Author(s):

Rong Fu ◽

Hui Liu ◽

Zonghong Shao ◽

Jun Wang ◽

Lijuan Li

Keyword(s):

Western Blot ◽

Conflicts Of Interest ◽

Healthy Controls ◽

Newly Diagnosed ◽

Rt Pcr ◽

Glycine Buffer ◽

Preliminary Study ◽

The Relationship ◽

Epor Expression ◽

Normal Controls

Abstract Abstract 4382 Objective To observe the relationship between EPO receptor(EPOR) and autoantibodies-IgG/IgM(auto-Ab) on the membrane of erythropoietic cells of the patients with IRP and then explore the probable autoantigens of auto-Ab in IRP. Methods 46 newly diagnosed IRP patients(15 with auto-Ab on erythropoietic cells and 31 without auto-Ab on erythropoietic cells) and 18 healthy controls were enrolled in this study. EPOR expression on their nuclear erythrocytes were tested with FCM to observe the relationship between EPOR and auto-Ab; EPOR mRNA were tested by RT-PCR; Stat5 and P-Stat5 proteins in nucleared erythrocytes were measured by Western blot; EPOR expression on the nucleared erythrocytes membrane were tested again after stripping autoantibodies with glycine buffer. Results (1)EPOR of auto-Ab(+) arm(1.59±0.87)% was significantly lower than that of auto-Ab (−) arm(4.58±4.09)%(P<0.01)and the latter was significantly higher than that of normal controls(2.27±1.76)%(P<0.05); GEPOR of IRP patients was inversely correlated with their auto-Ab (r=−0.543,P=0.000).(2) EPOR mRNA of auto-Ab(+) arm(0.685±0.136)was significiantly higher than that of auto-Ab (−) arm(0.554±0.116)(P<0.01)and normal controls(0.580±0.119)(P<0.05);(3) Protein Stat5 of auto-Ab(+) arm(1.45±0.94) was significantly higher than that of normal controls(0.54±0.36)(P<0.05). While P-Stat5 of auto-Ab(+) arm(0.42±0.18) was significantly lower than that of normal controls(0.85±0.38)(P<0.05). (4) EPOR expression increased significantly after auto-Ab stripped from nucleared erythrocytes with glycine buffer. Conclusion The auto-Ab of some IRP patients might block or competitively inhibit the EPOR on the membrane of erythropoietic cells. EPOR might be one of autoantigens in IRP. Disclosures: No relevant conflicts of interest to declare.

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Regulation of Th1/Th2 and Th17/Treg by pDC/mDC imbalance in primary immune thrombocytopenia

Experimental Biology and Medicine ◽

10.1177/15353702211009787 ◽

2021 ◽

pp. 153537022110097

Author(s):

Qinzhi Li ◽

Yang Liu ◽

Xiujuan Wang ◽

Mingling Sun ◽

Lei Wang ◽

...

Keyword(s):

Dendritic Cells ◽

Platelet Count ◽

Th17 Cells ◽

Immune Thrombocytopenia ◽

Serum Levels ◽

Mrna Levels ◽

Significant Difference ◽

Primary Immune Thrombocytopenia ◽

Healthy Control ◽

Ifn Γ

This study investigates the regulatory effect of plasmacytoid dendritic cells (pDC)/myeloid dendritic cells (mDC) imbalance on balance of Th1/Th2 and Th17/Treg in primary immune thrombocytopenia (ITP). A total of 30 untreated ITP patients and 20 healthy controls were recruited. Compared with healthy control, the pDC proportion of ITP patients was significantly reduced ( P = 0.004), while the mDC proportion was not significantly changed ( P = 0.681), resulting in a decrease in the pDC/mDC ratio ( P = 0.001). Additionally, compared with controls, serum levels of interleukin (IL)-6, IL-12, and IL-23 were increased in ITP patients ( P < 0.001), and mRNA levels of IL-12p40, IL-12p35, and IL-23p19 were also increased ( P =0.014, P = 0.043, P < 0.001). Compared with the healthy control, the proportion of Th1 and Th17 cells in ITP patients increased ( P = 0.001, P = 0.031). Serum levels of interferon gamma (IFN-γ) and IL-17 in ITP patients also increased ( P = 0.025, P = 0.005). Furthermore, T-bet and RORγt mRNA levels were increased in peripheral blood of ITP patients ( P = 0.018, P < 0.001). Correspondingly, the proportion of Th2 and Treg cells decreased ( P = 0.007, P < 0.001), along with a decrease in serum IL-4 and transforming growth factor beta (TGF-β) ( P = 0.028, P = 0.042), and an increase in GATA-3 mRNA ( P < 0.001). However, there was no significant difference in Foxp3 mRNA levels ( P = 0.587). Pearson correlation analysis showed that the proportion of total dendritic cells (DCs) was positively correlated with IL-12 ( r = 0.526, P = 0.003) and IL-23 ( r = 0.501, P = 0.005) in ITP patients. Th1/Th2 ratio, IFN-γ, and IL-12 levels were negatively correlated with platelet counts ( r = −0.494, P = 0.009; r = –0.415, P = 0.028; r = –0.492, P = 0.032). However, IL-23 was positively correlated with IL-17 ( r = 0.489, P = 0.006) and negatively correlated with platelet count ( r = –0.564, P = 0.001). The ratio of IL-6 and Th17 cells was negatively correlated with platelet count ( r = –0.443, P = 0.014; r = –0.471, P = 0.011). The imbalance of pDC/mDC and the increase of IL-6, IL-12, and IL-23 lead to the increased differentiation of CD4+ T cells into Th1 and Th17 cells, which might be the important mechanisms underlying the imbalance of Th1/Th2 and Th17/Treg in ITP patients.

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Delayed Plasma Clot Lysis in Adult Patients with Primary Immune Thrombocytopenia (ITP)

Blood ◽

10.1182/blood-2021-152261 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 3162-3162

Author(s):

Theresa Schramm ◽

Jennifer Machacek ◽

Michael Fillitz ◽

Barbara Dixer ◽

Peter Quehenberger ◽

...

Keyword(s):

Research Funding ◽

Immune Thrombocytopenia ◽

Clot Lysis ◽

Lag Phase ◽

Healthy Controls ◽

Plasma Clot ◽

Significant Difference ◽

Primary Immune Thrombocytopenia ◽

Pai 1 ◽

Bleeding Severity

Abstract Introduction: Primary immune thrombocytopenia (ITP) is an orphan disease characterized by very low platelet counts. Patients have heterogeneous bleeding phenotypes, which are not only determined by platelet counts, also a paradoxically increased thrombotic risk has been observed. Aim: To investigate, whether the fibrinolysis inhibitors plasminogen activator inhibitor-1 (PAI-1) and α2-antiplasmin are associated with impaired plasma clot lysis in primary ITP patients in comparison to non-immunologic thrombocytopenic controls (TPC) and healthy controls (HC). Furthermore, associations with bleeding severity and previous thrombotic events were investigated. Methods: Patients from the Vienna ITP biobank (EC 1843/2016), a multi-centric study including adult patients with primary ITP were investigated and compared to age- and sex-matched control groups: TPC with thrombocytopenia after chemotherapy and HC. Informed consent was obtained from all individuals before study inclusion. A clot formation and lysis assay (CLA) was performed according to the recommendations of the ISTH SSC. Platelet poor plasma samples were measured in duplicates for each patient and control. PAI-1 (PAI-1 Actibind ELISA, Technoclone, Vienna, Austria) and α2-antiplasmin by the chromogenic STA Stachrom antiplasmin assay (Diagnostic Stago, Asnieres, France) were measured. Bleeding severity was measured using the ITP-specific ITP-ISTH BAT (Rodeghiero et al. 2013). Results: In total, 37 primary ITP patients, 18 TPC and 156 healthy controls were analyzed (Table 1). Primary ITP patients had a higher BMI than HC. Bleeding severity was higher and more ITP patients had a thrombosis history compared to HC, whereas there was no difference in comparison to TPC. PAI-1 activity was highest in ITP patients, with a statistically significant difference in comparison to HC. α2-antiplasmin activity was higher in ITP patients than in TPC, whereas there was no difference in comparison to HC. After adjustment for sex, age, BMI and fibrinogen, primary ITP patients had a reduced clot formation rate (V max) and significantly delayed plasma clot lysis compared to TPC and HC (Table 2). Also, the lag phase and time to peak absorbance (TTP) were prolonged with a significant difference in comparison to HC. To investigate outliers of PAI-1 and α2-antiplasmin, we calculated cut-offs at the 75 th percentile of healthy controls (PAI-1: ≥ 3.1 U/mL, α2-antiplasmin: ≥ 107.0 %). 14 (37.8 %) ITP patients had PAI-1 levels and 10 (27.0 %) ITP patients had α2-antiplasmin activity above the cut-off. ITP patients with high PAI-1 levels had mildly delayed clot lysis in comparison to those below with a significantly lower maximal lysis rate (mLR). ITP patients with α2-antiplasmin activity above the cut-off had a significantly shorter lag phase, faster V max and shorter TTP than patients below the cut-off, whereas there was no difference in clot lysis. No differences between ITP patients above or below the respective cut-offs of PAI-1 and α2-antiplasmin regarding their bleeding severity and thrombosis incidence were observed (Table 3). Conclusion: Primary ITP patients have a tendency towards increased PAI-1 activity, which is associated with considerably delayed plasma clot lysis. Albeit an association with the bleeding score could not be identified, this impaired lysis could be seen as a counter-regulation and at least contribute to the relatively mild bleeding tendency in patients with ITP. Figure 1 Figure 1. Disclosures Pabinger: CSL Behring: Consultancy, Honoraria, Research Funding; NovoNordisk: Consultancy, Research Funding; Bayer: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Daiichi Sanchyo: Consultancy, Honoraria; Alexion: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria.

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