妊娠合并血小板减少的病因及治疗

目的探讨妊娠合并血小板减少症的病因及治疗。方法对128例妊娠合并血小板减少患者的临床资料进行回顾性分析。结果单纯由妊娠引起的血小板减少91例(71.09%),特发性血小板减少性紫癜(ITP)引起11例(8.59%),合并肝脏疾病10例(7.81%),重度妊高征引起14例(10.94%),Rh血型不合及病毒感染各1例(各占0.78%)。对血小板(50×109/L者用强的松治疗,分娩前后使用血小板制剂,同时考虑剖宫产。结论妊娠期血小板减少是最常见的妊娠合并血小板减少症类型。有合并症的血小板减少程度严重,大多<70×109/L,半数ITP有临床症状。糖皮质激素是治疗严重血小板减少的有效手段,术前血小板仍<50×109/L可输注浓缩血小板。     

妊娠合并血小板减少238例临床分析

目的探讨妊娠合并血小板减少症的病因及治疗。方法对238例妊娠合并血小板减少患者的临床资料进行回顾性分析。结果单纯由妊娠引起的血小板减少171例(71.85%),特发性血小板减少性紫癜(ITP)引起20例(8.40%),合并肝脏疾病18例(7.56%),重度妊高征引起25例(10.50%),Rh血型不合及病毒感染各2例(各占0.84%)。对血小板<50×109/L者用强的松治疗,分娩前后使用血小板制剂,同时考虑剖宫产。结论妊娠期血小板减少是最常见的妊娠合并血小板减少症类型。有合并症的血小板减少程度严重,大多<70×109/L,半数ITP有临床症状。糖皮质激素是治疗严重血小板减少的有效手段,术前血小板仍<50×109/L可输注浓缩血小板。     

新生儿血小板减少症46例临床分析

目的分析新生儿血小板减少的临床特点及可能原因,探讨其预防和治疗措施。方法回顾性分析本院2008年1月～2009年7月诊断新生儿血小板减少症所有患儿的临床资料。结果早发型血小板减少患儿临床上多无特殊表现,预后较好;迟发型血小板减少症多发生于早产儿,小于胎龄儿,通常由于合并严重感染所致,病情严重,需要输注血小板来治疗。结论围产期有高危因素母亲,其新生儿出生后要常规监测血常规,对于宫内发育不良或低出生体质量儿生后一旦合并感染要警惕血小板减少,甚至DIC的发生。     

机采冰冻血小板与新鲜血小板临床输注效果比较

目的观察冰冻血小板与新鲜血小板临床输注效果。方法95例患者输注新鲜血小板,94例患者输注冰冻血小板。观察输注后患者的出血情况及输注后1h和24h外周血血小板计数情况。结果95例患者输注新鲜血小板后1h计数12.57±4.99×109/L,24h计数28.18±11.33×109/L。结论94例患者输注新鲜血小板后1h计数12.32±5.01×109/L,24h计数29.38±13.34×109/L。二者差异无显著性(P>0.05)。     

重症特发性血小板减少性紫癜的治疗体会

目的探讨常规剂量强的松并输注浓缩血小板、大剂量静脉注射丙种球蛋白(IVIG)或大剂量甲基强的松龙(甲强龙)、或二者联合治疗重症特发性血小板减少性紫癜(ITP)的效果。方法根据病情和病人经济能力将118例次病人分为常规剂量的强的松加输注浓缩血小板组(简称血小板组)37例;用大剂量IVIG/甲强龙组(简称药物组)39例;大剂量IVIG/甲强龙联合输注浓缩血小板组(简称联合组)42例。比较3组治疗前、后血小板计数。同时观察临床出血情况。结果治疗后外周血小板计数,血小板组升高(15.40±12.14)×109/L(p<0.001),药物组升高(17.98±14.01)×109/L(p<0.001),联合组升高(43.26±13.20)×109/L,(p<0.001)。联合组高于血小板组和药物组(p<0.001)。治疗3天后临床出血改善率,血小板组60%(22/37),药物组54%(21/39),联合组90%(38/42)。5例发热病人输注浓缩血小板后外周血小板计数未见升高。结论重症ITP病人,大剂量IVIG/甲强龙联合输注浓缩血小板较单纯输注浓缩血小板或大剂量IVIG/甲强龙疗效好,手工采和机单采浓缩血小板的输注无效性的发生率尚待进一步观察。     

免疫性血小板输注无效患者交叉配合输注的研究

目的 通过比较不同血小板输注策略的输注疗效,探讨血小板抗体筛查及交叉配型对于免疫性血小板输注无效(platelet transfusion refractoriness, PTR)患者的应用价值。方法 采用固相凝集法对临床送检血小板抗体筛查的患者进行血小板抗体检测,提取患者的临床资料如性别、年龄、疾病种类、输血记录等,计算血小板抗体筛查阳性率并分析其分布特点。以血小板输注后增量(the post-transfusion platelet increment, PPI)和血小板校正后增值(the corrected count increment, CCI)为衡量指标,分析比较血小板抗体阳性以及不同输血策略(随机输注、交叉相合、交叉不相合)对患者血小板输注疗效的影响。结果 血小板抗体筛查阳性患者61例(23.55%),且多为血液系统疾病患者;其中,抗体筛查阳性组的PPI(U=18 851,P=0.0720)、CCI(U=14 585,P=0.0183)、血小板输注有效率(χ²=5.691,P=0.017)均低于抗体筛查阴性组。61例抗体阳性患者先后共输注122次血小...     

宫内输血和宫外换血治疗Rh血型不合重度溶血病并血小板减少症一例及文献复习

目的探讨宫内输血治疗Rh胎儿溶血病的疗效、Rh重度溶血病合并严重血小板减少症以及新生儿晚期增生低下性贫血的的机制和治疗对策。方法分析我院近期成功救治的1例由IgG抗D引起的胎儿重度溶血病并发严重血小板减少症的临床资料,同时结合国外资料进行文献复习。结果本例胎儿30周时脐静脉穿刺查胎儿血红蛋白低至32g/L,血小板为73×10^9/L,娩出前胎儿血小板降至52×10^9/L,先后两次经脐静脉予以宫内输血纠正胎儿贫血,生后予以换血、光疗、输注血小板和免疫球蛋白以及输浓缩红细胞和使用促红细胞生成素纠正晚期贫血等治疗,患儿治愈,出院定期随访,生后6个月生长发育良好。结论宫内输血能明显改善Rh血型不合重度溶血病预后,但应警惕Rh重度溶血病并发少见的血小板减少症,及时输注血小板防止颅内出血,同时注意纠正新生儿晚期增生低下性贫血。     

妊娠期血小板减少128例临床分析

目的探讨妊娠合并血小板减少症的临床特点及妊娠期的监护和处理.方法对128例妊娠合并血小板减少患者的临床资料进行回顾性分析.结果单纯由妊娠引起的血小板减少91例(71.09%),特发性血小板减少性紫癜(ITP)引起11例(8.59%),合并肝脏疾病10例(7.81%),重度妊高征引起14例(10.94%),Rh血型不合及病毒感染各1例(各占0.78%).血小板减少出现最早孕周为20 6周,＜28周出现34例(26.56%),＞28周出现94例(73.44%),大部分孕妇血小板减少出现在妊娠晚期.对血小板＜50×109/L者用强的松治疗,分娩前后使用血小板制剂,同时考虑剖宫产.产后出血率为2.34%.大部分PAT患者在产后1周血小板恢复正常.结论妊娠合并血小板减少一般发生在妊娠晚期,妊娠期血小板减少是最常见的妊娠合并血小板减少症类型.有合并症的血小板减少程度严重,大多＜70×109/L,半数ITP有临床症状.糖皮质激素是治疗严重血小板减少的有效手段,术前血小板仍＜50×109/L可输注浓缩血小板.妊娠合并血小板减少症不增加产后出血的发生率.母亲合并ITP时,新生儿可能血小板减少.     

血浆TPO水平变化与血小板减少疾病的关系

目的:探讨血浆血小板生成素(Thrombopoietin,TPO)水平变化与血小板减少疾病的关系。方法:采用多抗夹心酶联免疫吸附法对68例各种不同原因致血小板减少患者通过应用白介素-11(rhIL-11)来动态检测TPO水平,rhIL-11剂量为25μg/(kg.d),皮下注射,连用10天。结果:(1)急性白血病(Acute leukemia,AL)化疗后血小板减少患者TPO水平低于正常对照组;再生障碍性贫血(Aplastic anemia,AA)及骨髓增生异常综合征(Myelodysplastic syndrome,MDS)患者TPO水平高于正常对照组;原发性血小板减少性紫癜(Idiopathic thrombocytopenic purpura,ITP)及肝硬化(Liver cirrhosis)患者TPO水平与正常对照组无明显差异。而其中的白血病化疗后血小板减少患者和AA患者的骨髓巨核细胞数较TPO正常组显著降低。(2)上述疾病患者用rhIL-11有效者TPO水平趋于正常,无效或疗效欠佳者,则TPO无变化。有效者TPO水平与血小板计数呈负相关。结论:血浆TPO检测,有助于临床鉴别各种血小板减少疾病的病因,对血小板减少患者合理应用rhIL-11提供理论的依据。     

环磷酰胺致造血损伤后血清Meg-CSA的变化

环磷酰胺(Cy)是凋亡诱导剂,通过诱导细胞凋亡,作为化疗药物发挥抗肿瘤作用,其烃化作用可使造血细胞的DNA结构受到破坏,引起造血细胞凋亡和机体体液因子改变[1].但化疗药物所致造血损伤并发症如粒细胞减少、血小板减少等症成为提高肿瘤疗效的主要障碍之一[2].越来越多的造血生长因子(hematopoietic growth factors,HGF)已用于临床,HGF可加快造血恢复,对抗加大化疗药物剂量所致的副作用,提高疗效.研究造血损伤后体内血清巨核细胞系集落刺激活性(megakaryocyte colony-stimulatiing activity,MegCSA)水平变化,可以为指导HGF(如促血小板生成素thrombopoietin:TPO)的临床应用提供实验依据.     

Platelets: preparations, transfusion, modifications, and substitutes.

OBJECTIVE: To summarize current knowledge and recent progress pertaining to platelet concentrate preparations, modifications, and future prospects for platelet substitutes. METHODS: Current publications identified through a search of an electronic literature database were evaluated and reviewed. Relevant data were abstracted into this article. Abstractions of the data were made depending on their relevance. This review starts with standard methods of platelet preparation and goes on to describe different modifications intended to optimize the product and increase its safety. The article concludes with a discussion of the use of hematopoietic growth factors and novel kinds of platelet components for future use. CONCLUSIONS: Many modifications in the preparation of platelet transfusions have occurred in recent years. Platelets prepared by standard techniques contain significant numbers of donor leukocytes, which are responsible for several adverse effects. Awareness of this problem has lead to the development of effective means for their removal. Several methods to reduce the risk of viral and bacterial transmission through platelet transfusions are emerging. New technologies in the use of platelet substitutes have attempted to prolong the platelet storage potential and prevent the development of recipient alloimmunization. As the biological activities of growth factors become better understood, the clinical applications of novel recombinant products may redefine the concept of future platelet transfusions. It is important that research continues into the optimal methods for the preparation and use of platelet transfusions to provide maximal clinical benefits with minimal risk of complications.     

Platelet gels

Platelet gels (PG) are blood-derived biomaterials that are generally obtained through the activation of a platelet-rich plasma or a platelet concentrate by thrombin or calcium chloride, resulting in the simultaneous conversion of fibrinogen into a fibrin gel and in the generation of a platelet releasate rich in a physiological cocktail of growth factors. To reinforce the physical strength of the fibrin network, a fibrinogen-rich fraction – generally cryoprecipitate – can be added to the platelet fraction prior to activation, resulting in the generation of platelet fibrin glue (PFG). PG and PFG, prepared from single donations, either autologous or allogeneic, are increasingly used, alone or in combination with grafting materials, in various field of regenerative medicine where the presence of growth factors is expected to stimulate the healing of soft or hard tissues. Being obtained from human blood, they are physiological and biodegradable preparations and do not induce tissue necrosis. So far, the viral safety of most allogeneic PG and PFG relies on donors selection and donation testing, as is the case for all non-virally inactivated blood components for transfusion. Major fields of clinical applications of PG and PFG in osseous tissue regeneration include maxillo-facial surgery, implantology, reconstructive and plastic surgery. Platelet gels are also used for enhancing the healing of soft tissues, most particularly recalcitrant lower extremity ulcers of various aetiologies, and burns. Newer promising indications include the treatment of osteo-arthritis and joint inflammation, and the repair of musculoskeletal tissue lesions in sports medicine. Autologous PG and PFG are mostly ‘home-made’ single-donor preparations prepared using medical devices. They suffer from the variability in donor characteristics and in isolation procedures of the platelet fraction. Clinical application methods are not standardized. Variability in autologous product characteristics is high, and optimal content of growth factors is unknown, confusing the analysis of product efficacy. The evidence of clinical benefits of these products based on controlled clinical studies is lacking in most indications, although many case studies do support an objective benefit in soft and probably hard tissues healing. Improvement in the standardization and formulation of PG and PFG is a mandatory step forward for improving the reliability and the predictability of clinical outcomes of these interesting blood preparations.     

Characteristics of platelet gels combined with silk

Platelet gel, a fibrin network containing activated platelets, is widely used in regenerative medicine due the capacity of platelet-derived growth factors to accelerate and direct healing processes. However, limitations to this approach include poor mechanical properties, relatively rapid degradation, and the lack of control of release of growth factors at the site of injection. These issues compromise the ability of platelet gels for sustained function in regenerative medicine. In the present study, a combination of platelet gels with silk fibroin gel was studied to address the above limitations. Mixing sonicated silk gels with platelet gels extended the release of growth factors without inhibiting gel-forming ability. The released growth factors were biologically active and their delivery was modified further by manipulation of the charge of the silk protein. Moreover, the silk gel augmented both the rheological properties and compressive stiffness of the platelet gel, tuned by the silk concentration and/or silk/platelet gel ratio. Silk-platelet gel injections in nude rats supported enhanced cell infiltration and blood vessel formation representing a step towards new platelet gel formulations with enhanced therapeutic impact.     

Computational analysis of platelet adhesion and aggregation under stagnation point flow conditions

The clinical relevance of platelet function assessment with stagnation point flow adhesio-aggregometry (SPAA) has been verified. Quantitative analysis of platelet adhesion and aggregation is possible by means of mathematical analysis of the dark-field, light intensity curves (growth curves) obtained during the SPAA experiment. We present a computational procedure for evaluating these curves, which was necessitated by, and is based on, actual clinical application. A qualitative growth curve classification, corresponding to a basic and distinct pattern of platelet deposition and characteristic of a regularly occurring clinical state is also presented.     

The effect of platelet lysate supplementation of a dextran-based hydrogel on cartilage formation

In situ gelating dextran-tyramine (Dex-TA) injectable hydrogels have previously shown promising features for cartilage repair. Yet, despite suitable mechanical properties, this system lacks intrinsic biological signals. In contrast, platelet lysate-derived hydrogels are rich in growth factors and anti-inflammatory cytokines, but mechanically unstable. We hypothesized that the advantages of these systems may be combined in one hydrogel, which can be easily translated into clinical settings. Platelet lysate was successfully incorporated into Dex-TA polymer solution prior to gelation. After enzymatic crosslinking, rheological and morphological evaluations were performed. Subsequently, the effect of platelet lysate on cell migration, adhesion, proliferation and multi-lineage differentiation was determined. Finally, we evaluated the integration potential of this gel onto osteoarthritis-affected cartilage. The mechanical properties and covalent attachment of Dex-TA to cartilage tissue during in situ gel formation were successfully combined with the advantages of platelet lysate, revealing the potential of this enhanced hydrogel as a cell-free approach. The addition of platelet lysate did not affect the mechanical properties and porosity of Dex-TA hydrogels. Furthermore, platelet lysate derived anabolic growth factors promoted proliferation and triggered chondrogenic differentiation of mesenchymal stromal cells.     

Platelet‐rich plasma (PRP) and platelet derivatives for topical therapy. What is true from the biologic view point?

Background PubMed accessed on January 23 revealed 160 items about ‘platelet gel or releasate’ associated to topical therapy. Yahoo! provided 8580 items; Altavista 8650; Google 25 300. Companies providing blood separators are going to offer devices to prepare platelet‐rich plasma (PRP) for topical therapy. Several devices are filling the marketplace aiming to produce platelet gels for human therapy. Never‐ending lists of clinical conditions supposed to benefit from platelet gel application are published. Clinical benefits include bactericidal activity, pain reduction, tissue repair and regeneration. Are platelet derivatives the magic bullet for topical therapy? Methods Many in vitro studies account for clinical benefit from platelet gel. Several in vivo studies provide clinical evidence about healing of tissue repair induced by platelet derivatives. Nevertheless, systematic reviews reveal inadequate studies providing enough methodological strength to confirm evidence‐based efficacy. At present we must deal the subject with care using mostly inductive criteria. Only reproducible scientific data are to be considered. Every effort should be made for commercial, private and personal popularity‐related scenarios to be rejected from our consideration. Sometimes, this is not so simple to be done. Results There is a list of more than 60 biologically active platelet‐derived factors directly involved in tissue repair mechanisms: chemotaxis, cell proliferation, angiogenesis, extracellular matrix deposition and remodelling. Biological functions are also indirectly mediated by platelet‐derived growth factors; such functions are triggered by chemokines and cytokines produced by bystander cells such as fibroblasts, macrophages, endothelial cells, lymphocytes, under platelet‐derived factor stimulation. All of this is well demonstrated. Clinical studies endorsed with stringent randomized controlled trials are lacking. However, several serious studies have been published reporting clinical efficacy of platelet derivatives in many clinical areas. Considering these papers seriously, we maintain that in most cases, clinical efficacy is by far more than just a suggestion. Discussion Although we consider evidence‐based medicine (EBM) highly meaningful, we emphasize that medicine moved forwards also before EBM was conceived. We do not consider platelet gel and releasate such as a ‘magic bullet’, but we are strongly impressed by the results our group, and other groups have obtained treating a variety of tissue lesions in a variety of clinical conditions. Clinical benefits are a composite result of the lesion state, severity and duration, coexisting pathologies, patient's age and product characteristics. From our point of view, the last is a pivotal variable that has strong influence over the clinical outcome. Platelet‐rich plasma, platelet gel and platelet releasate need stringent definitions. Too many methods are used to prepare these products. Both methods and product need definition, validation, specific quality parameters and clinical indications. Further biologic and biochemical studies are needed as well to understand (if possible to modulate) the inner mechanisms of healing induced by topical treatment with platelet derivatives.     

The irrelevance of adhesive platelet estimations after thrombosis

It has been found that adhesive platelet counts are not of clinical use either after surgical operation or during long-term anticoagulant therapy in the detection of thrombosis. Calculation of the theoretical risk of development of platelet thrombi related to the platelet count suggests a possible reason for this absence of clinical significance. The evidence that platelet adhesiveness alters because of uncontrollable platelet variables and is controlled at least in part by plasma factors is discussed. The possibility of measuring the plasma factors is considered briefly.     

The role of platelet growth factors in cancer therapy

The use of myeloid growth factors has markedly reduced the complications of chemotherapy-induced neutropenia, however, abrogation of severe thrombocytopenia remains a major clinical problem. Platelet transfusions remain the standard method of preventing or treating thrombocytopenia but are associated with a variety of complications and are a limited resource. A number of cytokines have been clinically investigated for their thrombopoietic activity, the most promising of which is the recently cloned ligand to the hematopoietic growth factor receptor, c-Mpl. The c-Mpl ligand, also referred to as thrombopoietin, megakaryocyte growth and development factor (MGDF) and megapoietin, is a potent lineage-specific agent that promotes growth and maturation of megakaryocytes and their progenitors. It holds promise for clinical use in the treatment of iatrogenic or disease-associated bone marrow failure states and possibly in syndromes of excessive platelet consumption. Early clinical trials assessing the safety and activity of recombinant human MGDF are now underway.     

Controversy concerning platelet dose

The highest level of support for evidence based decisions is the randomized controlled trial (RCT); however, RCT results are only useful if the study has strong internal and external validity. There have been a number of clinical trials that have addressed the issue of the optimal platelet dose; however, none of these studies have provided definitive data on the optimal platelet dose due to a variety of methodological issues associated with the study designs. Currently two randomized controlled trials have been implemented to address the issue of optimal platelet dose. The results of these trials will not be available until 2007–2008. The BEST (Biomedical Excellence for Safer Transfusion) Collaborative has initiated a platelet dose study comparing the frequency of WHO bleeding Grade 2 with low and standard dose platelets. The Transfusion Medicine/ Haemostasis Clinical Trials Network (CTN) is also performing a platelet dose study comparing three treatment strategies (high, standard and low dose platelets). There were numerous methodological issues that had to be considered when designing these two studies. More recently some European investigators have questioned the need for prophylactic platelet transfusions and several studies are currently underway to investigate the efficacy of changing this practice.     

Platelet-rich plasma: quantification of growth factor levels and the effect on growth and differentiation of rat bone marrow cells

Platelet-rich plasma (PRP) is a new application of tissue engineering and a developing area for clinicians and researchers. It is a storage vehicle of growth factors (GFs) such as platelet-derived growth factor (PDGF)- AA, -BB, -AB; transforming growth factor (TGF)-beta1 and -2; platelet-derived epidermal growth factor (PDEGF); platelet-derived angiogenesis factor (PDAF); insulin growth factor-1 (IGF-1); and platelet factor- 4 (PF-4), which are known to influence bone regeneration. However, animal and clinical studies reveal different results with the use of PRP and its effect on bone healing. This could be due to the differences between species, that is, differences between species in GF concentrations or variation in presence of GFs between the various PRPs. In this study, rat bone marrow cells were cultured in PRP-coated wells or in uncoated wells for 16 days in osteogenic medium, and analyzed on cell growth (DNA content) and cell differentiation (alkaline phosphatase [ALP] activity, calcium content, scanning electron microscopy, and QPCR). The concentrations of TGF-beta1, PDGF-AA, PDGF-AB, and PDGF-BB in rat, goat, and human PRP were subsequently determined. The results showed that PRP stimulated initial cell growth and had no effect on ALP activity. The calcium measurements showed a significant increase in calcium at days 8, 12, and 16. The real-time PCR results showed that PRP upregulated osteocalcin at day 1 and collagen type I at day 8. Overall, the immunoassays revealed that human PRP contained higher concentrations of growth factors per platelet compared to rat and goat PRP. Goat PRP showed higher concentrations of growth factors per platelet as compared to rat PRP except for PDGF-BB, which had a higher concentration in rat PRP. TGF-beta1 was the most abundant growth factor in all 3 PRPs. On the basis of our results, we conclude that platelet-rich plasma contains osteo-inductive growth factors, which are probably species related. However, we cannot generalize the results because of large intraspecies variations. Further, we conclude that rat PRP gel stimulates initial growth and differentiation of rat bone marrow cells in vitro.