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Zhonghua Xue Ye Xue Za Zhi = Zhonghua... Apr 2024The phenotype and genotype of a pedigree with Glanzmann thrombasthenia caused by compound heterozygous mutation in the ITGA2B gene and its molecular pathogenesis were...
The phenotype and genotype of a pedigree with Glanzmann thrombasthenia caused by compound heterozygous mutation in the ITGA2B gene and its molecular pathogenesis were explored. The platelet aggregation rate of the proband and his family was detected by using a platelet aggregation test with adenosine diphosphate, collagen, epinephrine, arachidonic acid, and ristocetin. The expression levels of CD41 (αⅡb), CD61 (β3), and CD42b (GPⅠb) on the platelet surface was detected by flow cytometry. Gene sequencing technology was used for the genetic identification of the family. RT-PCR was used in the detection of mRNA splicing, and qRT-PCR was used in detecting the relative mRNA level of the ITGA2B gene. Bioinformatics analysis was used to evaluate the pathogenicity of mutation sites and their effects on protein structure and function. The expressions of total αⅡb and β3 in platelets were analyzed by Western blot. Except ristocetin, the other four inducers could not induce platelet aggregation in the proband. Flow cytometry showed that the expression levels of αⅡb and β3 were only 0.25% and 9.76%, respectively, on the platelet surface of the proband, whereas GPⅠb expression was relatively normal. The expression levels of glycoproteins in the other family members were almost normal. c.480C>G and c.2929C>T mutations were detected in the proband through gene sequencing. The c.480C>G mutation was inherited from his mother, and the c.2929C>T mutation was inherited from his father. The RT-PCR and sequencing results showed that the c.480C>G mutation caused mRNA splicing in the proband and his mother, resulting in the deletion of 99 bases in c.476G-574A (p.S160-S192). qRT-PCR showed that the c.2929C>T variant reduced the mRNA level of the ITGA2B gene in the proband and his father. Bioinformatics analysis suggested that the c.480C>G mutation might form a binding sequence with hnRNP A1 protein and generate the 5'SS splice site. The three-dimensional structural model of the αⅡb subunit showed that the β-propeller domain of the p.S160-S192 deletion lost two β-strands and one α-helix in blade 2. The c.2929C>T nonsense mutation caused premature translation termination and produced a truncated protein with the deletion of p.R977-E1039, including the cytoplasmic domain, transmembrane domain, and a β chain of the extracellular Calf-2 domain. The total αⅡb expression of the proband was absent, and the relative expression of β3 was 11.36% of the normal level. The compound heterozygous mutation c.480C>G in exon 4 and c.2929C>T in exon 28 of the ITGA2B gene probably underlies Glanzmann thrombasthenia in this pedigree.
Topics: Humans; Integrin alpha2; Thrombasthenia; Pedigree; Mutation; Heterozygote; Male; Female; Platelet Aggregation; Genotype; Adult
PubMed: 38951065
DOI: 10.3760/cma.j.cn121090-20230816-00070 -
Zhonghua Xue Ye Xue Za Zhi = Zhonghua... Apr 2024The effect and safety of etoposide combined with G-CSF were compared with those of cyclophosphamide combined with G-CSF in autologous peripheral blood mobilization in... (Comparative Study)
Comparative Study
[Comparison of etoposide combined with G-CSF and cyclophosphamide combined with G-CSF in the mobilization of autologous peripheral blood stem cells in patients with multiple myeloma].
The effect and safety of etoposide combined with G-CSF were compared with those of cyclophosphamide combined with G-CSF in autologous peripheral blood mobilization in patients with multiple myeloma (MM) . Patients with MM who received autologous peripheral blood stem cell mobilization and collection in the Department of Hematology, Beijing Chaoyang Hospital Affiliated to Capital Medical University from January 1, 2020 to July 31, 2023 were included. A total of 134 patients were screened by propensity score matching technology according to a 1∶1 ratio. A total of 67 cases were each treated with ETO combined with G-CSF mobilization scheme (ETO group) and CTX combined with G-CSF mobilization scheme (CTX group). Their clinical data were retrospectively analyzed. ①Collection results: the ETO and CTX groups [2 (1-3) d 2 (1-5) d; <0.001] and CD34(+) cells [7.62×10(6) (2.26×10(6)-37.20×10(6)) /kg 2.73×10(6) (0.53×10(6)-9.85×10(6)) /kg; <0.001] were collected. The success rate of collection was 100.0% (67/67) versus 76.1% (51/67) (<0.001). Excellent rate of collection was 82.1% (55/67) versus 20.9% (14/67; <0.001). Two patients in the ETO group switched protocols after 1 day of collection, and 11 patients in the CTX group switched protocols after 1-2 days of collection. ②Adverse reactions: granular deficiency with fever (21.5%[14/65] 10.7%[6/56]; =0.110), requiring platelet transfusion [10.7% (7/65) 1.8% (1/56) ; =0.047]. ③Until the end of follow-up, 63 cases in the ETO group and 54 cases in the CTX group have undergone autologous transplantation. The median number of CD34(+) cells infused in the two groups was 4.62×10(6) (2.14×10(6)-19.89×10(6)) /kg versus 2.62×10(6) (1.12×10(6)-5.31×10(6)) /kg (<0.001), neutrophil implantation time was 11 (9-14) d versus 11 (10-14) d (=0.049), and platelet implantation time was 11 (0-19) d 12 (0-34) d (=0.035). One case in the CTX group experienced delayed platelet implantation. The mobilization scheme of etoposide combined with G-CSF requires relatively platelet transfusion, but the collection days are shortened. The collection success rate, excellent rate, and the number of CD34(+) cells obtained are high, and the neutrophil and platelet engraftment is accelerated after transplantation.
Topics: Humans; Multiple Myeloma; Etoposide; Hematopoietic Stem Cell Mobilization; Cyclophosphamide; Granulocyte Colony-Stimulating Factor; Retrospective Studies; Transplantation, Autologous; Peripheral Blood Stem Cells; Peripheral Blood Stem Cell Transplantation; Female; Male; Middle Aged
PubMed: 38951062
DOI: 10.3760/cma.j.cn121090-20231124-00274 -
International Journal of Gynecological... Jul 2024To develop a pre-operative tool to estimate the risk of peri-operative packed red blood cell transfusion in primary debulking surgery.
A pre-operative scoring model to estimate the risk of blood transfusion over an ovarian cancer debulking surgery (BLOODS score): a Memorial Sloan Kettering Cancer Center Team Ovary study.
OBJECTIVES
To develop a pre-operative tool to estimate the risk of peri-operative packed red blood cell transfusion in primary debulking surgery.
METHODS
We retrospectively reviewed an institutional database to identify patients who underwent primary debulking surgery for ovarian cancer at a single center between January 1, 2001 and May 31, 2019. Receiver operating characteristic curve and area under the receiver operating characteristic curve (AUC) were calculated. Five-fold cross-validation was applied to the multivariate model. Significant variables were assigned a 'BLOODS' (BLood transfusion Over an Ovarian cancer Debulking Surgery) score of +1 if present. A total BLOODS score was calculated for each patient, and the odds of receiving a transfusion was determined for each score.
RESULTS
Overall, 1566 patients met eligibility criteria; 800 (51%) underwent a peri-operative blood transfusion. Odds ratios (OR) were statistically significant for American Society of Anesthesiologists scores of 3 and 4 (OR 1.34, 95% confidence interval (95% CI) 1.09 to 1.63), pre-operative levels of cancer antigen 125 (CA125) (OR 2.43, 95% CI 1.98 to 2.99), platelets (OR 1.59, 95% CI 1.45 to 1.74), obesity (OR 0.76, 95% CI 0.60 to 0.96), presence of carcinomatosis (OR 2.45, 95% CI 1.93 to 3.11), bulky upper abdominal disease (OR 2.86, 95% CI 2.32 to 3.54), pre-operative serum albumin level (OR 0.31, 95% CI 0.24 to 0.40), and pre-operative hemoglobin level (OR 0.56, 95% CI 0.51 to 0.61). The corrected AUC was 0.748 (95% CI 0.693 to 0.804). BLOODS scores of 0 and 5 corresponded to 11% and 73% odds, respectively, of receiving a peri-operative blood transfusion.
CONCLUSIONS
We developed a universal pre-operative scoring system, the BLOODS score, to help identify patients with ovarian cancer who would benefit from surgical planning and blood-saving techniques. The BLOODS score was directly proportional to the American Society of Anesthesiologists score, presence of upper abdominal disease, carcinomatosis, CA125 level, and platelets level. We believe this model can help physicians with surgical planning and can benefit patient outcomes.
Topics: Humans; Female; Retrospective Studies; Ovarian Neoplasms; Middle Aged; Cytoreduction Surgical Procedures; Aged; Blood Transfusion; Risk Assessment; Adult
PubMed: 38950927
DOI: 10.1136/ijgc-2024-005660 -
Vox Sanguinis Jul 2024Quantifying the contribution of individual coagulation factors to haemostasis may aid our understanding of the haemostatic function in patients with rare coagulation...
BACKGROUND AND OBJECTIVES
Quantifying the contribution of individual coagulation factors to haemostasis may aid our understanding of the haemostatic function in patients with rare coagulation deficiencies (RCDs) and the exploration of suitable treatments.
MATERIALS AND METHODS
Reconstituted blood prepared from specific coagulation factor-deficient plasma (factor [F]II; prothrombin, FV, FVII, FVIII, FIX, FX, FXI or FXII) and red blood cell/platelet products were used to simulate the whole blood of patients with RCD. We prepared in vitro treatment models for patients with prothrombin deficiency using coagulation factor agents and fresh frozen plasma. Haemostatic function was measured using a microchip flow chamber system at 600 s.
RESULTS
The haemostatic function was low, especially in blood samples reconstituted with prothrombin- and FX-deficient plasma. In a plasma transfusion model of prothrombin deficiency, haemostatic function recovered after 10% replacement with normal plasma and reached a plateau at ≧60% replacement. A treatment model of prothrombin deficiency with prothrombin complex concentrates revealed dose-dependent therapeutic effects in the range of 0-50 IU/kg.
CONCLUSION
Microchip flow chamber system-based quantification of haemostatic function using reconstituted blood could predict haemostasis and therapeutic effects of treatments in patients with prothrombin deficiency.
PubMed: 38950904
DOI: 10.1111/vox.13709 -
Journal of Ethnopharmacology Jun 2024Shegan-Mahuang Decoction (SMD) is a classical formula that has been used to effectively treat cold-induced asthma (CA) for 1800 years. Airway smooth muscle cells (ASMCs)...
Shegan-Mahuang Decoction ameliorates cold-induced asthma via regulating the proliferation and apoptosis of airway smooth muscle cells through TAS2R10: An in vivo and in vitro study.
ETHNOPHARMACOLOGICAL RELEVANCE
Shegan-Mahuang Decoction (SMD) is a classical formula that has been used to effectively treat cold-induced asthma (CA) for 1800 years. Airway smooth muscle cells (ASMCs) play a crucial role in airway remodeling of CA and can be modulated through bitter taste-sensing type 2 receptors (TAS2Rs). Given that SMD contains numerous bitter herbs and TAS2R10 expression in ASMCs remains consistently high, it is pertinent to explore whether SMD regulates ASMCs via TAS2R10 to exert its CA mechanism.
AIM OF THE STUDY
This study investigated the efficacy as well as the potential mechanism of SMD in CA.
MATERIALS AND METHODS
In this study, experiments in vivo were conducted using the CA rat model induced by ovalbumin (OVA) along with cold stimulation. The effects of SMD and TAS2R10 expression in CA rats were evaluated using the following methods: clinical symptoms, weights, pathological staining, immunofluorescence staining (IF), enzyme-linked immunosorbent assay (ELISA), real-time quantitative polymerase chain reaction (RT-qPCR) and western blot (WB). Assays in vitro including cell counting Kit-8 (CCK-8), ELISA, flow cytometry, TUNEL staining, RT-qPCR and WB were performed to investigate potential mechanism of SMD on the proliferation and apoptosis of ASMCs through upregulation of TAS2R10.
RESULTS
The administration of SMD resulted in a notable improvement in the symptoms, trends in weight, airway inflammation and airway remodeling observed in CA rats with upregulated TAS2R10. Mechanistically, we furtherly confirmed that SMD inhibits p70S6K/CyclinD1 pathway by upregulating TAS2R10. SMD furthermore blocked the G0/G1 phase, suppressed the proliferation and inducted apoptosis in ASMCs induced by platelet-derived growth factor-BB (PDGF-BB). Erythromycin (EM), a TAS2R10 agonist, can intensify these effects.
CONCLUSIONS
SMD significantly ameliorates CA by upregulating TAS2R10 and inhibiting the p70S6K/CyclinD1 pathway, thereby modulating ASMCs' proliferation and apoptosis. Inspired by the Five Flavors Theory of Traditional Chinese Medicine, this study provides an updated treatment perspective for treating CA.
PubMed: 38950796
DOI: 10.1016/j.jep.2024.118504 -
International Journal of Cardiology Jun 2024
PubMed: 38950785
DOI: 10.1016/j.ijcard.2024.132312 -
World Neurosurgery Jun 2024Hematoma expansion in small/medium-sized acute epidural hematoma (AEDH) cases upon emergency admission is critical. Predicting hematoma expansion can lead to early...
BACKGROUND
Hematoma expansion in small/medium-sized acute epidural hematoma (AEDH) cases upon emergency admission is critical. Predicting hematoma expansion can lead to early surgical interventions, improving outcomes and eliminating the need to check for expansion via computed tomography (CT). This study aimed to identify the most reliable predictors of AEDH expansion.
METHODS
We retrospectively collected data from patients with pure AEDH not requiring surgical treatment upon emergency admission from 2012-2022. We assessed clinical and laboratory data, time from injury to the first CT, and time to follow-up CT. Factors predictive of hematoma expansion on the second follow-up CT, including the leakage sign (LS), were analyzed.
RESULTS
A total of 23 patients with pure AEDH without surgery at admission were included, and LS was positive in 18. Thirteen patients showed hematoma expansion. The hematoma expansion group showed a significantly higher rate of positive LS and lower mean platelet count than the group without hematoma expansion. LS's predictive value for AEDH expansion showed 100% sensitivity and 50% specificity. All patients with negative LS and normal platelet counts showed no hematoma expansion. Analyzing the time from injury to the first CT suggested that LS (+) within 120 min strongly predicted hematoma expansion. Reconstructed three-dimensional images of the leakage point on the skull revealed multiple mottled bleeding points on the dural surface.
CONCLUSION
LS can predict hematoma expansion in patients with pure AEDH for whom emergency surgery is unnecessary at admission. The time from injury and platelet counts must also be considered.
PubMed: 38950651
DOI: 10.1016/j.wneu.2024.06.144 -
Hamostaseologie Jul 2024Bleeding disorder of unknown cause (BDUC) is a diagnosis of exclusion after exhaustive evaluation of plasmatic coagulation and platelet function. This review explores...
Bleeding disorder of unknown cause (BDUC) is a diagnosis of exclusion after exhaustive evaluation of plasmatic coagulation and platelet function. This review explores the utility of global hemostatic assays as confirmatory tests and in elucidating the pathophysiology of BDUC. Unlike traditional hemostatic tests that focus on coagulation factors, global assays are conducted both in plasma and also whole blood. These assays provide a more comprehensive understanding of the cell-based model of coagulation, aid in the identification of plasmatic factor abnormalities that may reduce hemostatic capacity, and allow for the assessment of impaired platelet-endothelial interactions under shear stress, as well as hyperfibrinolytic states. While clinical tests such as skin bleeding time and global assays such as PFA-100 exhibit limited diagnostic capacity, the role of viscoelastic testing in identifying hemostatic dysfunction in patients with BDUC remains unclear. Thrombin generation assays have shown variable results in BDUC patients; some studies demonstrate differences compared with healthy controls or reference values, whereas others question its clinical utility. Fibrinolysis assessment in vitro remains challenging, with studies employing euglobulin clot lysis time, plasma clot lysis time, and fluorogenic plasmin generation yielding inconclusive or conflicting results. Notably, recent studies suggest that microfluidic analysis unveils shear-dependent platelet function defects in BDUC patients, undetected by conventional platelet function assays. Overall, global assays might be helpful for exploring underlying hemostatic impairments, when conventional hemostatic laboratory tests yield no results. However, due to limited data and/or discrepant results, further research is needed to evaluate the utility of global assays as screening tools.
PubMed: 38950624
DOI: 10.1055/a-2330-9112 -
Seminars in Thrombosis and Hemostasis Jul 2024The American Society of Hematology-International Society on Thrombosis and Haemostasis-National Hemophilia Foundation-World Federation of Hemophilia 2021 International...
The American Society of Hematology-International Society on Thrombosis and Haemostasis-National Hemophilia Foundation-World Federation of Hemophilia 2021 International Guidelines (IGL) on von Willebrand disease (VWD) have pointed out many challenges, mainly in the diagnostic approach of VWD patients. To determine the impact of these IGL on the current clinical and laboratory diagnosis of Italian VWD patients, we have recently conducted a survey among 43 centers affiliated with the Italian Association of Hemophilia Centers (AICE). Directors and colleagues responsible for the management of VWD patients were invited to report in a detailed questionnaire how IGL recommendations about the assessment of the specific activities of von Willebrand Factor (VWF) could be applied at their local sites. Results from such a survey showed that bleeding assessment tools, VWF antigen, and factor VIII procoagulant are currently in use in all centers. The automated assays for platelet-dependent VWF activity with or without ristocetin described in IGL have been used since 2021 in 37/43 (86%) centers. Among other laboratory tests, VWF collagen binding, ristocetin-induced platelet agglutination, multimeric analysis, VWF propeptide, VWF:FVIII binding assay were available in 49, 63, 26, 7, and 28% of AICE, respectively. Analyses of VWF gene defects are available only at 3/43 (7%) centers. Desmopressin (DDAVP) infusion trials at diagnosis, with measurements of VWF activities at 1 and 4 hours post-DDAVP, is currently performed at 38/43 (88%) centers. Based on this information, a simplified clinical diagnosis using a few automated tests before and after DDAVP has been proposed. Such a diagnostic approach will be validated prospectively in a large cohort of Italian VWD patients.
PubMed: 38950597
DOI: 10.1055/s-0044-1787841 -
Seminars in Thrombosis and Hemostasis Jul 2024Inherited disorders of primary hemostasis, such as von Willebrand disease and congenital platelet disorders, can cause extensive, typically mucocutaneous bleeding....
Inherited disorders of primary hemostasis, such as von Willebrand disease and congenital platelet disorders, can cause extensive, typically mucocutaneous bleeding. Assays to diagnose and monitor these disorders, such as von Willebrand factor activity assays and light transmission aggregometry, are performed in specialized hemostasis laboratories but are commonly not available in local hospitals. Due to the complexity and relative scarcity of these conventional assays, point-of-care tests (POCT) might be an attractive alternative in patients with hereditary bleeding disorders. POCTs, such as thromboelastography, are increasingly used to assess hemostasis in patients with acquired hemostatic defects, aiding clinical decision-making in critical situations, such as during surgery or childbirth. In comparison, the use of these assays in patients with hereditary hemostasis defects remains relatively unexplored. This review aims to give an overview of point-of-care hemostasis tests in patients with hereditary disorders of primary hemostasis. A summary of the literature reporting on the performance of currently available and experimental POCTs in these disorders is given, and the potential utility of the assays in various use scenarios is discussed. Altogether, the studies included in this review reveal that several POCTs are capable of identifying and monitoring severe defects in the primary hemostasis, while a POCT that can reliably detect milder defects of primary hemostasis is currently lacking. A better understanding of the strengths and limitations of POCTs in assessing hereditary defects of primary hemostasis is needed, after which these tests may become available for clinical practice, potentially targeting a large group of patients with milder defects of primary hemostasis.
PubMed: 38950596
DOI: 10.1055/s-0044-1787976