Plasmablastic lymphoma: current knowledge and future directions.

Plasmablastic lymphoma (PBL) is an aggressive non-Hodgkin lymphoma associated with HIV infection and immunodeficiency. However, PBL can also be seen immunocompetent individuals in recent studies. PBL was characterized by distinct clinical and pathological features, such as plasmablastic morphology and universal expression of plasma cell markers. The clinicopathologic features were different between HIV-negative and HIV-positive patients. Gene expression analysis identified the unique molecular feature in PBL, including frequent c-MYC rearrangement and downregulation of BCR signaling pathway. Despite the recent advances in the treatment of PBL, the prognosis of PBL patients remains dismal. The objectives of this review are to summarize the current knowledge on the epidemiology, molecular profiles, clinical and pathological features, differential diagnosis, treatment strategies, prognostic factors, and potential novel therapeutic approaches in PBL patients.

A national, multicenter, retrospective study of Castleman disease in China implementing CDCN criteria.

Background: Castleman disease (CD) is a group of rare and heterogenous lymphoproliferative disorders including unicentric CD (UCD), human herpesvirus-8(HHV-8)-associated multicentric CD (HHV8-MCD), and HHV-8-negative/idiopathic multicentric CD (iMCD). Knowledge of CD mainly comes from case series or retrospective studies, but the inclusion criteria of these studies vary because the Castleman Disease Collaborative Network (CDCN) diagnostic criteria for iMCD and UCD were not available until 2017 and 2020, respectively. Further, these criteria and guidelines have not been systematically evaluated. Methods: In this national, multicenter, retrospective study implementing CDCN criteria, we enrolled 1634 CD patients (UCD, n = 903; MCD, n = 731) from 2000 to 2021 at 40 Chinese institutions to depict clinical features, treatment options, and prognostic factors of CD. Findings: Among UCD, there were 162 (17.9%) patients with an MCD-like inflammatory state. Among MCD, there were 12 HHV8-MCD patients and 719 HHV-8-negative MCD patients, which included 139 asymptomatic MCD (aMCD) and 580 iMCD meeting clinical criteria. Of 580 iMCD patients, 41 (7.1%) met iMCD-TAFRO criteria, the others were iMCD-NOS. iMCD-NOS were further divided into iMCD-IPL (n = 97) and iMCD-NOS without IPL (n = 442). Among iMCD patients with first-line treatment data, a trend from pulse combination chemotherapy toward continuous treatment was observed. Survival analysis revealed significant differences between subtypes and severe iMCD (HR = 3.747; 95% CI: 2.112-6.649, p < 0.001) had worse outcome. Interpretation: This study depicts a broad picture of CD, treatment options and survival information in China and validates the association between the CDCN's definition of severe iMCD and worse outcomes, requiring more intensive treatment. Fundings: Beijing Municipal Commission of Science and Technology, CAMS Innovation Fund and National High Level Hospital Clinical Research Funding.

[Progress in the Treatment of Adult Langerhans Cell Histiocytosis --Review].

Langerhans cell histiocytosis (LCH) is a rare proliferative disease dominated by the proliferation of Langerhans cells, which is inflammatory myeloid neoplasms. Its clinical manifestations are variable, occurring at any age and at any site, and it is rarer in adults than in children. The gold standard for diagnosis is histopathological biopsy. Due to the rarity of adult LCH and the heterogeneity of this disease, treatment of adult LCH should be developed according to the extent of the disease and risk stratification. With the discovery of MAPK, PI3K and c-KIT signaling pathway activation, especially BRAF V600E and MAP2K1 mutations, targeted therapy has become a hot spot for therapeutic research. Meanwhile, the discovery of high expression of M2-polarized macrophages and Foxp3+ regulatory T cells (Treg) in LCH has provided an important basis for the immunotherapy. In this article, we will focus on reviewing the latest research progress in the treatment of adult LCH in recent years, and provide a reference for clinical research on the treatment of adult LCH patients.

The roles of exosomal immune checkpoint proteins in tumors.

Targeting immune checkpoints has achieved great therapeutic effects in the treatment of early-stage tumors. However, most patients develop adaptive resistance to this therapy. The latest evidence demonstrates that tumor-derived exosomes may play a key role in systemic immune suppression and tumor progression. In this article, we highlight the role of exosomal immune checkpoint proteins in tumor immunity, with an emphasis on programmed death ligand 1 (PD-L1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), as well as emerging evidence on roles of T cell immunoglobulin-3 (TIM-3), arginase 1 (ARG1), and estrogen receptor binding fragment-associated antigen 9 (EBAG9) expressed by exosomes.

LncRNA-NEAT1 promotes proliferation of T-ALL cells via miR-146b-5p/NOTCH1 signaling pathway.

BACKGROUND: T-cell acute lymphoblastic leukemia (T-ALL) is a malignant tumor of the hematopoietic system, which can develop at any age, with the symptoms of weakness, fatigue, enlarged lymph nodes, or weight loss. Nuclear paraspeckle assembly transcript 1 (NEAT1) is involved in the process of T-ALL, but the regulatory mechanism is still not known clearly. METHODS: The expression levels of NEAT1 and miR-146b-5p in T-ALL cells were performed by qRT-PCR and NOTCH1 protein level- wwWwas determined by western blot assay. Dual-luciferase reporter assay was used to detect the interaction between NEAT1 and miR-146b-5p, as well as miR-146b-5p and NOTCH1. The cell proliferation was measured by using MTT assay and colony formation assay. RESULTS: The expression levels of NEAT1 were markedly increased, but miR-146b-5p levels were reduced in T-ALL cells. Knockdown of NEAT1 or overexpression of miR-146b-5p decreased NOTCH1 expression, inhibited the proliferation of T-ALL cells. MiR-146b-5p bound both NEAT1 and NOTCH1 3'-UTR directly. Finally, inhibition of miR-146b-5p could abrogate the effects of NEAT1 knockdown on the proliferation of T-ALL cells. CONCLUSION: NEAT1 promotes the proliferation of T-ALL cells by sponging miR-146b-5p to upregulate the expression of NOTCH1. The results of this study provide new insight into the action mechanism of NEAT1 modulating T-ALL progression.

A novel STAT3 inhibitor attenuates angiotensin II-induced abdominal aortic aneurysm progression in mice through modulating vascular inflammation and autophagy.

Abdominal Aortic aneurysm (AAA) is associated with chronic inflammation, cells apoptosis, and impairment of autophagy. BP-1-102, a novel potent STAT3 inhibitor, has been recently reported to significantly block inflammation-related signaling pathways of JAK2/STAT3 and NF-κB, as well as regulate autophagy. However, its role in vascular inflammation and AAA progression remains to be elucidated. In the present study, the effect and potential mechanisms of BP-1-102 on angiotensin II (AngII) induced AAA in ApoE-/- mice were investigated. AAA was induced in ApoE-/- mice with infusion of AngII for 28 days. BP-1-102 was administrated orally to mice every other day. Mice were sacrificed on day 7, day 14, and day 28 to evaluate the treatment effects. BP-1-102 markedly decreased AAA incidence and aortic diameter, maintained elastin structure and volume, reduced the expression of pro-inflammatory cytokines and MMPs, and inhibited inflammatory cells infiltration. Moreover, BP-1-102 dramatically reduced the expression of JAK2, p-STAT3, p-NF-κB, and Bcl-xL but maintained the expression of LC3B and Beclin in AAA tissues. In vitro, vascular smooth muscle cells (VSMCs) were treated with AngII and/or BP-1-102 at indicated time and concentration. BP-1-102 inhibited AngII-induced JAK2/STAT3 and NF-κB signaling activation and maintained autophagy-related proteins expression in VSMCs. Taken together, our findings suggest that BP-1-102 inhibits vascular inflammation and AAA progression through decreasing JAK2/STAT3 and NF-κB activation and maintaining autophagy.

[Clinical Features of Patients with Blastic Plasmacytoid Dendritic Cell Neoplasm].

OBJECTIVE: To analyze the clinical characteristics, pathological features, treatment response and prognosis of patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN), so as to provide reference for reducing clinical misdiagnosis and treatment regimens. METHODS: The clinical, pathological features, treatment regimens and treatment response of 9 patients with BPDCN diagnosed and treated from January 1, 2013 to June 30,2019 in Xiangya Second Hospital of Central South University were analyzed respectively. RESULTS: The most common site of involvement in 9 patients with BPDCN was skin; the pathological features were involvement of dermis, and the highest positive immunohistochemical indexes rate were CD4, CD43, LCA, CD123, and VIM (all 100%), followed by CD56 and CD68, TDT, CD5, PAX-5, CD3, CD8, CD20; MPO and EBER of 9 patients were negative. However, Ki-67 of the 9 patients showed a medican of 77. 5% (40%-90%), which suggests that CD4, CD43, LCA, CD123, and VIM were the most sensitive antigens for diagnosing BPDCN. Of the 9 patients, 2 cases were lost to follow-up, 2 cases were untreated, and 5 cases were treated, in which 2 cases received treatment of regiment for acute lymphoblastic leukemia and 3 cases received treatment of regimen for lymphoma. The PR of clinical symptoms in the first cycle in 5 patients were 100%, and 1 patient has survived for 6 years since the disease was diagnosed. CONCLUSION: BPDCN is a rare and highly invasive lymphoid hematopoietic malignancy. The most common initial symptom of the patients is skin lesions. The most sensitive pathological indicators are CD4, CD43, LCA, VIM, and the BPDCN patients received treatment of regimens for lymphoid tumor show a better response rate.

[Analysis of Clinical Characteristics in 31 Acute Myeloid Leukemia Patients with Chromosome 21 Aberrations].

OBJECTIVE: To investigate the clinical characteristics of 31 acute myeloid leukemia (AML) patients with chromosome 21 aberrations. METHODS: Karyotypes of 168 newly diagnosed AML patients in Second Xiangya Hospital from Jan 2014 to July 2016 were reviewed for the presence of chromosome 21 aberrations (accounting for 18.45%). Clinical manifestation, as well as prognostic gene mutations distribution and immune classification were analyzed. RESULTS: Out of 168 AML newly diagnosed patients, 31 cases with chromosome 21 aberrations including t(8;21) accounting for 67.74% (21/31), and trisomy 21 (16.13%,5/31), 2 variants were found as t(1; 21) and t(1; 21; 8); 77 cases had normal karyotype, and 60 cases possessed other chromosomes aberrations. Statistically significant differences did not exist among age, sex and white blood cell count (P>0.05). However, the 21 cases in chromosome aberrations group were predisposed to lower hemoglobin and platelet count(P<0.05). 5 cases of Trisomy 21 were characterized by M5 2 cases, M1 one case, M2 one case M4 one case. And the rate of C-kit/D816V mutation was higher in t(8;21) aberrations group when 7 prognostic genes including FLT3/ITD, C-kit/D816V, NPM1, DNMT3A, TET2 were analyzed, and the immune classification of t(8; 21) aberration group inclined to CD19+, CD34+ but CD33-, CD64-. And trisomy 21 displayed a trend to CD34+ and CD7+. CONCLUSION: Chromosome 21 is easily involved in acute myeloid leukemia. The patients with involvement of this aberration have characteristic clinic changes.

[Gene Analysis of A Chinese Family with Hereditary Hemorrhagic Telangiectasia and its Curative Effect of Thalidomide].

OBJECTIVE: To analyze a hereditary hemorrhagic telangiectasia(HHT) family Activin receptor-like kinase 1(ACVRL1), Endoglin (ENG) and Mothers against decapentaplegic homolog 4 (MADH4, SMAD4) gene mutation, meanwhile, to observe the curative effect of thalidomide in treatment of HHT patients. METHODS: The clinical feature of the HHT family was analyzed, the polymerase chain reaction (PCR) combined with Sanger sequencing of ACVRL1, ENG and SMAD4 were used to investigate the proband. The suspicious mutations were further detected in the other 7 family members. Proband was treated with thalidomide (100 mg/day) for 6 months, and the frequency and quantity of bleeding and blood transfusion frequency were assayed to evaluate the curative efficacy. RESULTS: One ACVRL1 mutation (c.1231C>T) was identified in proband(II-1) and the other 4 family members(II-2, III-1, III-2, III-3), which was reported as a pathogenic gene and revealed cosegregation with HHT clinical phenotype. One ENG mutation (c.1096G>C) was previously reported as gene polymorphism, which was identified in some family members(II-1, II-3, III-1, III-2) without cosegregation with clinical phenotype. No gene mutation was found in SMAD4. After thalidomide treatment, the frequency and quantity of bleeding and blood transfusion frequncy in the proband were reduced, hemoglobin concentration and serum iron level were increased. CONCLUSION: There is phenotypic heterogeneity in hereditary hemorrhagic telangiectasia and the features are age-dependent, the pathogenic gene of this pedigree is ACVRL1 mutation (c.1231C>T;p. R 411 W). Thalidomide is effective for the treatment of hemorrhage in hereditary hemorrhagic telangiectasia.

Rejuvenation of Cardiac Tissue Developed from Reprogrammed Aged Somatic Cells.

Induced pluripotent stem cells (iPSCs) derived via somatic cell reprogramming have been reported to reset aged somatic cells to a more youthful state, characterized by elongated telomeres, a rearranged mitochondrial network, reduced oxidative stress, and restored pluripotency. However, it is still unclear whether the reprogrammed aged somatic cells can function normally as embryonic stem cells (ESCs) during development and be rejuvenated. In the current study, we applied the aggregation technique to investigate whether iPSCs derived from aged somatic cells could develop normally and be rejuvenated. iPSCs derived from bone marrow myeloid cells of 2-month-old (2 M) and 18-month-old (18 M) C57BL/6-Tg (CAG-EGFP)1Osb/J mice were aggregated with embryos derived from wild-type ICR mice to produce chimeras (referred to as 2 M CA and 18 M CA, respectively). Our observations focused on comparing the ability of the iPSCs derived from 18 M and 2 M bone marrow cells to develop rejuvenated cardiac tissue (the heart is the most vital organ during aging). The results showed an absence of p16 and p53 upregulation, telomere length shortening, and mitochondrial gene expression and deletion in 18 M CA, whereas slight changes in mitochondrial ultrastructure, cytochrome C oxidase activity, ATP production, and reactive oxygen species production were observed in CA cardiac tissues. The data implied that all of the aging characteristics observed in the newborn cardiac tissue of 18 M CA were comparable with those of 2 M CA newborn cardiac tissue. This study provides the first direct evidence of the aging-related characteristics of cardiac tissue developed from aged iPSCs, and our observations demonstrate that partial rejuvenation can be achieved by reprogramming aged somatic cells to a pluripotent state.

Bone marrow-derived innate macrophages attenuate oxazolone-induced colitis.

Previous studies have shown that a subpopulation of granulocyte macrophage colony-stimulating factor (GM-CSF)-dependent F4/80high CD11bhigh innate macrophages could be derived from bone marrow cells by continuous in vitro culturing. These cells could be induced to differentiate into M1 or M2 macrophages in vitro. In the current study, we sought to determine whether bone marrow cell-derived innate macrophages (BMIMs) could be used to fulfill an anti-inflammatory purpose by intravenous transplantation in vivo after being stimulated to differentiate into M2 macrophages. Because Th2 cytokines, such as interleukin IL-4 and IL-13, can induce macrophage polarization into M2 macrophages, we treated the BMIMs with IL-4 and IL-13 in vitro. Next, the M2 macrophages were intravenously transplanted into a typical Th2-mediated inflammatory disease model, oxazolone (OXZ)-induced colitis, to assess the anti-inflammatory activity of BMIM-derived M2 macrophages (BMIM-M2Ms) in vivo. After transplantation, the severity of intestinal inflammation was attenuated. In addition, colon lengths and mouse body weights were noticeably improved. F4/80+ CD206+ double-positive cells (displaying the markers of M2 macrophages) had accumulated in the colon tissue of BMIM-M2M-transplanted mice. This evidence demonstrated that bone marrow-derived BMIM-M2Ms could be used to alleviate OXZ-induced Th2-mediated inflammation in a mouse model in vivo.

A TET2 rs3733609 C/T genotype is associated with predisposition to the myeloproliferative neoplasms harboring JAK2(V617F) and confers a proliferative potential on erythroid lineages.

Common germline single-nucleotide polymorphisms (SNPs) at JAK2 locus have been associated with Myeloproliferative neoplasms (MPN). And, the germline sequence variant rs2736100 C in TERT is related to risk of MPN, suggesting a complex association between SNPs and the pathogenesis of MPN. Our previous study (unpublished data) showed that there was a high frequency distribution in rs3733609 C/T genotype at Ten-Eleven Translocation 2 (TET2) locus in one Chinese familial primary myelofibrosis. In the present study, we evaluate the role and clinical significance of rs3733609 C/T genotype in JAK2V617F-positive sporadic MPN (n = 181). TET2 rs3733609 C/T genotype had a higher incidence (13.81%; 25/181) in JAK2V617F-positive sporadic MPN patients than that in normal controls (n = 236) (6.35%; 15/236), which was predisposing to MPN (odds ratio(OR) = 2.361; P = 0.01). MPN patients with rs3733609 C/T genotype had increased leukocyte and platelets counts, elevated hemoglobin concentration in comparison with T/T genotype. Thrombotic events were more common in MPN patients with rs3733609 C/T than those with T/T genotype (P < 0.01). We confirmed that rs3733609 C/T genotype downregulated TET2 mRNA transcription, and the mechanism may be involved in a disruption of the interaction between CCAAT/enhancer binding protein alpha (C/EBPA) and TET2 rs3733609 C/T locus.TET2 rs3733609 C/T genotype stimulated the erythroid hematopoiesis in MPN patients. Altogether, we found a novel hereditary susceptible factor-TET2 rs3733609 C/T variant for the development of MPN, suggesting the variant may be partially responsible for the pathogenesis and accumulation of MPN.

[Soil water reservoir properties and influencing factors of typical newly-established green belts of Shanghai Chenshan Botanical Garden, China.] / å ¸åž‹æ–°å»ºç»¿åœ°ä¸Šæµ·è¾°å±±æ¤ç‰©å›­åœŸå£¤æ°´åº“ç‰¹å¾åŠå ¶å½±å“å› å­.

The effects of different vegetation types, compaction ways and soil basic physico-chemical properties on soil water reservoir in the typical newly-established green belts of Shanghai Chenshan Botanical Garden were studied. The results showed that the total reservoir capacity, detention capacity and effective storage for the Botanical Garden were lower than those of natural forests. However, the dead storage was very high accounting for 60.6% of the total reservoir capacity, resulting in reduced flood storage and drainage capacity for the greens. The total reservoir capacity and detention capacity of different vegetation types were in order of brush land> tree land> grassland> bamboo land> bare land. The effective storages of the brush land and the tree land were relatively high, whereas those of the bare land and the bamboo land were lower. The ratios of the dead storage over the total re-servoir capacity in the bare land and the bamboo land were relatively high with the values 65.5% and 67.6%, respectively. The total reservoir capacity, detention capacity and effective storage of the brush land were significantly different from those of the bare land. The vegetation significantly improved the water storage and retention capacity for the soil, while the compaction by large machinery and man-caused trampling reduced the total reservoir capacity, detention capacity and effective storage of soils. The water reservoir properties were influenced by soil bulk density, saturated hydraulic conductivity, capillary porosity, non-capillary porosity, total porosity, clay and organic matter contents. Therefore, improving the soil physico-chemical properties might increase the soil reservoir capacity of the urban green belt effectively.

Reproductive outcomes after previous cesarean scar pregnancy: Follow up of 189 women.

OBJECTIVE: To investigate the reproductive and pregnancy outcomes of women after previous Cesarean Scar Pregnancy. MATERIALS AND METHODS: From January 2009 to December 2013, a total of 214 patients with CSP received surgical evacuation treatment by means of dilation and suction evacuation and local resection of the ectopic gestational mass. A telephone follow-up was conducted every year after CSP treatment. The follow-up was ended on December 2014. RESULTS: Twenty-five patients were lost to follow-up due to loss of contacts. The previous medical records of the remaining 189 women were reviewed. Fifty-eight women wished to give birth again. However, 48 (82.8%, 48/58) of them stopped the attempts to get pregnant because they were afraid of recurrent CSP and the high risk of uterine rupture during the subsequent pregnancy. The other 10 women spontaneously attempted to get pregnant again, among whom 6 (60%, 6/10) succeeded with the birth of 7 healthy babies. A total of 32 women conceived again, either in plan or by chance. Five women (15.6%, 5/32) experiencing recurrent CSP. CONCLUSION: Even though our result did not necessarily represent the true recurrence rate, our study provided some evidence about the likelihood of fertility and recurrence risk for future pregnancies after previous CSP.

Thalidomide Effects in Patients with Hereditary Hemorrhagic Telangiectasia During Therapeutic Treatment and in Fli-EGFP Transgenic Zebrafish Model.

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease characterized by recurrent epistaxis, mucocutaneous telangiectasia, and arteriovenous malformations. The efficacy of traditional treatments for HHT is very limited. The aim of this study was to investigate the therapeutic role of thalidomide in HHT patients and the effect in FLI-EGFP transgenic zebrafish model. METHODS: HHT was diagnosed according to Shovlin criteria. Five HHT patients were treated with thalidomide (100 mg/d). The Epistaxis Severity Score (ESS), telangiectasia spots, and hepatic computed tomography angiography (CTA) were used to assess the clinical efficacy of thalidomide. The Fli-EGFP zebrafish model was investigated for the effect of thalidomide on angiogenesis. Dynamic real-time polymerase chain reaction assay, ELISA and Western blotting from patient's peripheral blood mononuclear cells and plasma were used to detect the expression of transforming growth factor beta 3 (TGF-ß3) messenger RNA (mRNA) and vascular endothelial growth factor (VEGF) protein before and after 6 months of thalidomide treatment. RESULTS: The average ESS before and after thalidomide were 6.966 ± 3.093 and 1.799 ± 0.627, respectively (P = 0.009). The "telangiectatic spot" on the tongue almost vanished; CTA examination of case 2 indicated a smaller proximal hepatic artery and decreased or ceased hepatic artery collateral circulation. The Fli-EGFP zebrafish model manifested discontinuous vessel development and vascular occlusion (7 of 10 fishes), and the TGF-ß3 mRNA expression of five patients was lower after thalidomide therapy. The plasma VEGF protein expression was down-regulated in HHT patients. CONCLUSIONS: Thalidomide reverses telangiectasia and controls nosebleeds by down-regulating the expression of TGF-ß3 and VEGF in HHT patients. It also leads to vascular remodeling in the zebrafish model.

Dramatic response to itraconazole in central nervous system aspergillosis complicating acute promyelocytic leukemia.

Abstract Fungal infection is a rare complication of acute leukemia, in which a combination of voriconazole and amphotericin B is a first-line regimen of treatment. Here administration of itraconazole plus caspofungin resulted in a dramatic response in a patient with acute promyelocytic leukemia (APL).

Effects of BRCA1- and BRCA2-related mutations on ovarian and breast cancer survival: a meta-analysis.

PURPOSE: To estimate the effects of BRCA1 and BRCA2 mutations on ovarian cancer and breast cancer survival. EXPERIMENTAL DESIGN: We searched PubMed and EMBASE for studies that evaluated the associations between BRCA mutations and ovarian or breast cancer survival. Meta-analysis was conducted to generate combined HRs with 95% confidence intervals (CI) for overall survival (OS) and progression-free survival (PFS). RESULTS: From 1,201 unique citations, we identified 27 articles that compared prognosis between BRCA mutation carriers and noncarriers in patients with ovarian or breast cancer. Fourteen studies examined ovarian cancer survival and 13 studies examined breast cancer survival. For ovarian cancer, meta-analysis demonstrated that both BRCA1 and BRCA2 mutation carriers had better OS (HR, 0.76; 95% CI, 0.70-0.83 for BRCA1 mutation carriers; HR, 0.58; 95% CI, 0.50-0.66 for BRCA2 mutation carriers) and PFS (HR, 0.65; 95% CI, 0.52-0.81 for BRCA1 mutation carriers; HR, 0.61; 95% CI, 0.47-0.80 for BRCA2 mutation carriers) than noncarriers, regardless of tumor stage, grade, or histologic subtype. Among patients with breast cancer, BRCA1 mutation carriers had worse OS (HR, 1.50; 95% CI, 1.11-2.04) than noncarriers but were not significantly different from noncarriers in PFS. BRCA2 mutation was not associated with breast cancer prognosis. CONCLUSIONS: Our analyses suggest that BRCA mutations are robust predictors of outcomes in both ovarian and breast cancers and these mutations should be taken into account when devising appropriate therapeutic strategies.

Analysis of clinical and laboratory characteristics in 42 patients with thrombotic thrombocytopenic purpura from a single center in China.

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease characterized by microvascular platelet deposition and thrombus formation with resulting microangiopathic hemolytic anemia. Deficiency of the von Willebrand factor cleavage protease, also known as ADAMTS 13, has been implicated as an important etiological factor in TTP. Little studies were obtained on Chinese patients with TTP until now. Our aim was to analyze the clinical features, outcome and laboratory characteristics of Chinese TTP patients, and determine whether plasma ADAMTS 13 activity is decreased in TTP and its diagnostic value for TTP. Forty-two TTP patients (29 females; 13 males) admitted to our hospital from 1998 to 2010 were analyzed. There were 34 patients (81%) with the triad of TTP, including hemolytic anemia, thrombocytopenia and neurologic abnormalities; 7 (16.7%) had the classical pentad of TTP. Major etiologic factors were acquired autoimmunological abnormalities (31%); no familial TTP was identified in this series. The schistocytes of peripheral blood smears were present in all cases with a mean frequency of 4.6% (range from 0.3% to 13.4%). Plasma ADAMTS 13 activity was determined in 22 patients with the FRET-vWF86 assay. Only 4 idiopathic TTP patients (18.2%) had severe ADAMTS 13 deficiency (activity<10%); 9 (40.9%) had moderate decrease of ADAMTS 13 activity (activity: 10-40%); another 9 (40.91%) had normal ADAMTS 13 activity (>40%). T lymphocyte subpopulation was measured in 23 TTP patients with FACS Calibur; 14 of the 23 (60.9%) had significantly decreased CD4 cells count and CD4/CD8 ratio, suggesting cellular immune dysfunction may be involved in the pathogenesis of TTP. In the studies, plasmapheresis is the main therapeutic method. 26 of 31 patients (83.9%) accepting plasmapheresis achieved complete remission; those patients who only underwent plasma infusion had low remission rate (18.2%) and high mortality (9/11; 81.8%). Four patients with packed RBC infusion manifested transient exacerbation of neurologic or psychiatric symptoms. In conclusion, the diagnosis of TTP in China is still based on clinical features including evidence of microangiopathic hemolysis. Severe ADAMTS 13 activity deficiency might be a valuable indicator for idiopathic TTP diagnosis. Further studies are needed to determine the real value of ADAMTS 13 activity for TTP diagnosis and whether T lymphocytes subset dysregulation plays important role in TTP pathogenesis.