Key Points Ibrutinib but not zanubrutinib induces shedding of GPIb-IX complex in an ADAM17-dependent manner; GPIX has not been shown previously. Ibrutinib, but not zanubrutinib, induces shedding of integrin αIIbβ3 by an unknown sheddase.
Purpose: Anemia is one of the most common disorders affecting the population in both low-income and developing countries. This study aimed to determine the prevalence of anemia and iron deficiency in apparently normal male and female students of
Both nilotinib, a second-generation tyrosine kinase inhibitor (TKI) used in the treatment of chronic myeloid leukaemia (CML), and ponatinib, a third-generation TKI used in CML and Philadelphia positive acute lymphocytic leukaemia, have been associated with an increase in arterial occlusive events, in contrast to other TKIs such as imatinib and dasatinib. We have previously demonstrated evidence of a pro-thrombotic state associated with nilotinib, using microvascular and arterial thrombosis C57BL/6 mouse models. In this study, we examined ponatinib and determined if a calcium channel blocker could ameliorate the pro-thrombotic and pro-inflammatory phenotypes. In vitro treatment of whole human or murine blood with ponatinib and nilotinib increased platelet activation, adhesion and three-dimensional thrombi over time compared with vehicle control or other TKIs. Treatment of wild-type C57BL/6 mice with ponatinib and nilotinib but not imatinib, dasatinib or vehicle control for 4 hours significantly increased thrombus growth following ex vivo perfusion on collagen and FeCl3-induced vascular injury of mesenteric arterioles and carotid artery in vivo and increased plasma levels of soluble P-selectin, tumour necrosis factor-α, interleukin-6, interferon-γ and thromboxane B2 (TxB2). Ponatinib-treated CML patients had increased ex vivo thrombus formation and a pro-inflammatory phenotype compared with healthy controls. Pre-treatment of mice with the calcium channel antagonist, diltiazem, prior to ponatinib or nilotinib reversed the pro-thrombotic phenotype and the increase in cytokine levels. These observations suggest that the pro-thrombotic effect of nilotinib and ponatinib is partially related to calcium channel activation and TxA2 generation and this should be explored clinically as a mechanism to prevent vascular events.
Background The hypercoagulability and thrombotic tendency in coronavirus disease 2019 (COVID-19) is multifactorial, driven mainly by inflammation, and endothelial dysfunction. Elevated levels of procoagulant microvesicles (MVs) and tissue factor–bearing microvesicles (TF-bearing MVs) have been observed in many diseases with thrombotic tendency. The current study aimed to measure the levels of procoagulant MVs and TF-bearing MVs in patients with COVID-19 and healthy controls and to correlate their levels with platelet counts, D-Dimer levels, and other proposed calculated inflammatory markers. Materials and Methods Forty ICU-admitted patients with COVID-19 and 37 healthy controls were recruited in the study. Levels of procoagulant MVs and TF-bearing MVs in the plasma of the study population were measured using enzyme linked immunosorbent assay. Results COVID-19 patients had significantly elevated levels of procoagulant MVs and TF-bearing MVs as compared with healthy controls (P<0.001). Procoagulant MVs significantly correlated with TF-bearing MVs, D-dimer levels, and platelet count, but not with calculated inflammatory markers (neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, and platelet/neutrophil ratio). Conclusion Elevated levels of procoagulant MVs and TF-bearing MVs in patients with COVID-19 are suggested to be (i) early potential markers to predict the severity of COVID-19 (ii) a novel circulatory biomarker to evaluate the procoagulant activity and severity of COVID-19.
Background: The levels of procoagulant microvesicles (MVs) and tissue factor (TF)-bearing MVs may be increased in many conditions, including dengue fever (DF). This study aimed to measure the levels of MVs and TF-bearing MVs in patients with DF and matched healthy controls. Materials & methods: Levels of MVs and TF-bearing MVs in the plasma of patients with DF and matched healthy controls were measured using functional assay. Results: The patient group had significantly elevated levels of MVs (p < 0.001) and slightly increased levels of TF-bearing MVs (p = 0.454) compared with the matched healthy controls. Conclusion: Elevated levels of MVs and TF-bearing MVs could be used as biomarkers to evaluate the hemostatic function of patients with DF.
Purpose Knowledge of the prevalence of blood group antigens in a given population is important for the prevention of hemolytic reactions. The MNS blood group system (002) has four polymorphic antigens—M, N, S, and s. Anti-S and anti-s antibodies may result in immediate and delayed hemolytic transfusion reactions, and hemolytic disease of the fetus and newborn may occur. The present study investigated the frequencies of the main antigens and phenotypes of the MNS blood group system. Subjects and Methods We randomly obtained 149 samples from anonymous Saudi blood donors living in Jazan Province. Serotyping was conducted using a gel card to investigate (M, N, S, and s) antigens and phenotypes. Results The frequencies of MNS antigens were as follows: M = 89.26%, N = 51.67%, S = 61.07%, and s = 82.55%. Regarding the MNS phenotypes, nine phenotypes were observed in the study population. The most common phenotype was M+N–S+s+ (n = 36, 24.16%), in contrast to the least common phenotype M+N–S–s– (n = 1, 0.67%). The prevalence of the MNS phenotypes in the current study population was highly and significantly different from that in Europeans ( P = 0.044) and African Americans ( P = 0.000). Conclusion In summary, this study reports the frequencies of the MNS antigens and phenotypes in Jazan Province, Saudi Arabia. The most common phenotype was M+N–S+s+, whereas the least observed phenotype was M+N–S–s–. The outcomes of this study may assist the blood banks in Jazan Province to establish an extended phenotyping protocol including the MNS antigens, in particular S and s antigens, to preclude any alloimmunization events.
Purpose Glutathione S-transferases (GSTT1 and GSTM1) detoxify various endogenous and exogenous compounds and provide cytoprotective role against reactive species. This study aimed to assess the frequency of GSTT1 , and GSTM1 polymorphisms in newly diagnosed Sudanese adult patients with acute lymphoblastic leukemia (ALL) and to evaluate the association of these polymorphisms with age, gender and type of ALL. Patients and Methods This case–control study included 128 adult Sudanese, untreated newly diagnosed patients with ALL, aged 18 to 74 years and 128 age-gender matched healthy controls. Deletional polymorphisms of GSTT1 and GSTM1 genes were genotyped through a multiplex polymerase chain reaction (PCR) assay using β-globin gene as an internal positive control. Results The genotypic frequency of GSTT1 null polymorphism was 22.7% in cases and 14.8% in controls (OR = 1.68, P = 0.111). Statistically significant differences were noted in the frequencies of GSTM1 null polymorphism in cases and controls (OR = 3.7, P = <0.001). Combined GSTT1 null and GSTM1 null gene polymorphisms showed statistically significant difference in patients with ALL as compared to controls (OR = 6.5, CI 95% = 1.42–29.74, P < 0.001). Conclusion Irrespective of age at diagnosis, gender, and phenotype of ALL, GSTM1 null polymorphism either alone or in combination with GSTT1 null polymorphism poses significantly increased risk of developing ALL in adults.
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