Treatment of thalassaemia: a review of the new approaches on transfusion safety and the novel therapeutics

Lifetime red cell concentrate (RCC) transfusions still account for significant iron overload‐related morbidity and mortality despite chelation therapy in thalassaemia. The cumulative risk of transfusion‐transmitted infections is substantial for thalassaemia patients. Pathogen reduction technologies for RCC may imply a proactive approach against new/re‐emerging pathogens and may be an ultimate safeguard for transfusion safety in the developing countries. Red cell alloimmunization may become a significant clinical challenge in thalassaemia. The availability of high‐throughput molecular blood group antigen typing in the donors may allow perfect match transfusion, beyond ABO‐D and CEK antigen‐matched transfusions. Allogeneic stem cell transplantation (A‐SCT) is the only available curative therapy in thalassaemia, but carries a substantial risk of serious adverse events and mortality. Gene addition therapy for correction of the α‐globin chain imbalance overcomes the problems of donor availability and immunological complications of A‐SCT. Gene editing by either gene disruption or correction emerged as a potential alternative to gene addition therapy in beta‐thalassaemia. A new era of novel therapeutics targeting α/β imbalance, ineffective erythropoiesis or iron dysregulation is unfolding in thalassaemia management, and a number of those now have agents in preclinical and clinical development. Hydroxyurea (HU) may improve globin chain imbalance and be beneficial for reducing or omitting transfusion requirement. Ruxolitinib has allowed steady decrease in spleen volume that may serve for avoiding splenectomy in beta‐thalassaemia. Luspatercept may restore normal erythroid differentiation and improve anaemia. Hepcidin mimetics or TMPRSS6 inhibitors may modulate ineffective erythropoiesis by iron restriction and improve anaemia and organ iron loading.     

急性心肌缺血时红细胞变形性的变化及其机理

本实验观察了犬急性心肌缺血时体循环血与缺血区局部静脉血中红细胞变形性（ＲＣＤ）的变化。结果表明，阻断冠脉血流后高切变率下全血粘度（ηｂｈ）和红细胞刚性指数（ＥＲＩ）明显增高，而缺血区局部血液中此二者的变化明显大于体循环静脉血。事先切断内脏大神经，可使阻断冠脉后体循环血（而不是局部静脉血）的ηｂｈ和ＥＲＩ变化基本消失。缺血区局部血液ｐｈ和ｐＯ２明显降低，ｐＣＯ２明显增高，红细胞内ＡＴＰ含量减少和钙含     

血液胆碱酯酶活力测定方法的进一步研究Ⅰ．红细胞／全血胆碱酯酶活力比例及红细胞计数校正酶活力值的研究

应用硫代乙酰胆碱－联硫代双硝基苯甲酸（ＡＳＣｈ－ＤＴＮＢ）比色测定法，测定了４０名健康者及５名贫血者血样的全血胆碱酯酶（ｂｌ－ＣｈＥ）活力值、红细胞胆碱酯酶（ｅ－ＣｈＥ）活力值及血浆胆碱酯酶（ｐ－ＣｈＥ）活力值，探讨它们之间的比例关系并用红细胞计数值（ＲＢＣ）校正酶活力。结果表明：ｅ－ＣｈＥ与ｂ１－ＣｈＥ之间关系密切（ｒ＝０．９４８，Ｐ＜０．００１），ｅ－ＣｈＥ稳定地占ｂｌ－ＣｈＥ的８４．９７％，在质和量两方面验证了以ｂｌ－ＣｈＥ值表示ｅ－ＣｈＥ值的可靠性和可信程度，血液胆碱酯酶（ｂ１ＣｈＥ）活力主要取决于ｅ－ＣｈＥ活力，ＲＢＣ值的离散对ｅ－ＣｈＥ值有极大影响，故用ＲＢＣ值校正ｅ－ＣｈＥ活力，这样可缩小人群测定值的变异度，得到较难确的群体均值；消除男女之间测定值的差异，建立更合理和通用的临界参比值，极大地方便了使用，使血液胆碱酯酶（ＣＨＥ）活力测定法在防治有机磷农药中毒中的应用，更为敏感和特异。     

Prostaglandin E1 and dibutyryl cyclic AMP enhance platelet resistance to deformation

The effect of prostaglandin E₁ (PGE₁) on platelets is mediated through the PGE₁ receptor and the consequent maintenance of the platelet's discoid shape. The effects of PGE₁ and dibutyryl cAMP (dbcAMP) on the deformability of human platelets were studied. Deformability tests based upon the micropipette aspiration on the platelets were performed by using pipettes with radii (Rp) of 0.26-0.36 gm. The time course of the extension length (Dp, in μg) of the platelets in response to aspiration with a negative pressure (ΔP) of 5 cm H₂ O (ΔP × Rp = 0.15 dynes/cm) was analyzed. PGE₁ treatment (0.1 μM) resulted in a decrease of platelet deformability as compared with results obtained for apparently non-activated, control platelets. The deformation index, i.e., Dp/Rp (PGE₁ -treated) / Dp/Rp (control), was significantly reduced to 0.90 ± 0.04. DbcAMP treatment also significantly decreased the deformability of platelets and this decrease was dbcAMP dose dependent. In contrast, colchicine- or cytochalasin D-treated platelets increased deformability. PGE₁ -treated platelets had a higher [cAMP]_i than controls. Platelets treated with PGE₁ or dbcAMP showed a reduced [Ca²⁺]i increment induced by thrombin as compared to non-treated controls. These results indicate that PGE₁ and dbcAMP treatment of platelets is accompanied by an enhancement of platelet resistance to deformation. The increased [cAMP]_i and low [Ca²⁺]_i after PGE₁ treatment may limit the rearrangement of cytoskeleton and thus enhance platelet resistance to deformation.     

甘糖酯和胰岛素对体外孵育红细胞变形性的影响

目的：观察甘糖酯及胰岛素对体外孵育红细胞变形性（ＥＤ）的影响。方法：对１２例ＩＩ型糖尿病（ＮＩＤＤＭ）病人（男性６例，女性６例，年龄６０±ｓ１０ａ）取血观察其ＥＤ，并与正常人比较。将红细胞分别与甘糖酯和胰岛素共同孵育２４ｈ观察ＥＤ变化。结果：病人的ＥＤ明显低于正常人。孵育２４ｈ后，ＥＤ进一步降低。但与甘糖酯孵育后ＥＤ较孵育前改善。与胰岛素共同孵育后，ＥＤ较孵育前降低，但较不加药物孵育者降低程度小。结论：甘糖酯在体外可使ＮＩＤＤＭ病人ＥＤ改善。胰岛素的作用较弱。     

血液透析对红细胞还原型谷胱甘肽及红细胞变形性的影响

为了研究血液透析对红细胞还原型谷胱甘肽(GSH)及红细胞变形性(RBC IF)的影响,我们对16名肾衰透析患者的上述指标进行了研究。血透患者的上述指标(GSH和IF)较正常对照组显著异常。铜仿膜透析器单次使用,在透析过程中,尤其是在前30分钟内,可对患者的GSH和IF产生极为不良的影响。当铜仿膜透析器复用后,则可改善上述指标。     

慢性肺心病红细胞变形性与红细胞膜流动性变化（附17例病例分析）

用荧光偏振法测定17例慢性肺心病急性发作期患者及17名健康人红细胞膜流动性,用微孔泸膜法测定其中10例红细胞变形性。结果,肺心病患者及正常人红细胞膜微粘度分别为4.64±1.56及3.51±1.05η(p<0.05);红细胞滤速分别为384±136及233±97(p<0.01)。红细胞滤速与红细胞膜粘度间呈明显正相关(r=0.802,p<0.01)。结果提示,肺心病患者红细胞膜流动性下降可能对红细胞变形性下降起一定作用。     

Determination of Red Blood Cell Velocity by Video Shuttering and Image Analysis

A novel modification of conventional video imaging techniques has been developed to determine the velocity of red blood cells (RBCs), which offers compatibility with existing video-based methods for determining blood oxygenation and hemoglobin concentration. Traditional frame-by-frame analysis of video recordings limits the maximum velocity that can be measured for individual cells in vivo to about 2 mm/s. We have extended this range to about 20 mm/s, by electronic shuttering of an intensified charge-coupled device camera to produce multiple images of a single RBC in the same video frame. RBCs were labeled with fluorescein isothiocyanate and the labeled cells (FRBCs) were used as probes to determine RBC velocities in microvessels of the hamster retractor muscle. Velocity was computed as the product of the distance between centroids of two consecutive image positions of a FRBC and the shuttering frequency of the camera intensifier. In vitro calibrations of the system using FRBC and Sephadex beads coated onto a rotating disk yielded an average coefficient of variation of about 6%. Flow conservation studies at bifurcations indicated that the maximum diameter of microvessels below which all the FRBCs in the lumen could be detected was 50 m. The technique was used to estimate mean-FRBC velocity distributions in vessels with diameters ranging from 8 to 50 m. The mean-FRBC velocity profiles were found to be blunter than would be expected for Poiseuille flow. Single FRBCs tracked along an unbranched arteriole exhibited significant temporal variations in velocity. © 1999 Biomedical Engineering Society. PAC99: 8719Tt, 8717Jj, 4279Pw, 8780Tq, 8719Ff, 4230Va, 0705Pj