20008/壳聚糖球形多孔微载体支持下培养的肝细胞功能及其代谢活性检测(想明年4月之前发，想申请加急)

摘要 背景：微载体培养技术作为一项体外高浓度细胞培养技术,近年来已在肝细胞的体外培养中得到应用。 目的：对壳聚糖球形多孔微载体培养的人肝细胞L-02进行定时的形态学观察。 方法：以自制的壳聚糖球形多孔微载体样本为支架来培养人肝细胞L-02设为实验组;无壳聚糖球形多孔微载体支持下人肝细胞的培养设为对照组。对两组细胞进行定时的细胞计数,并对实验组进行形态学观察,包括倒置相差生物显微镜观察和扫描电子显微镜观察。 结果：两组培养的细胞数量均呈现前3 d增长,在第3天细胞数量达到最高值;而且实验组3个样本培养的细胞数明显高于对照组无微载体培养的细胞数量(P < 0.05),实验组各样本之间差异无显著性意义(P > 0.05);倒置相差生物显微镜下动态观察,可见前3 d微载体表面黏附生长的肝细胞则逐渐增多,第3天可见大部分微载体表面有许多肝细胞黏附成团,总的存活率均在90%以上,且肝细胞保持着良好的形态学结构;扫描电子显微镜观察,微载体表面、切面和内部均可看到有许多球状肝细胞紧密黏附。提示,以自制的壳聚糖球形多孔微载体作为一种支架,在体外三维环境下可以进行高浓度细胞培养。 关键词：微载体;壳聚糖;人工肝脏;肝细胞培养;组织工程 doi:10.3969/j.issn.1673-8225.2011.12.018     

聚乳酸乙醇酸/RNAⅢ抑制肽缓释微球的血液相容性*☆

目的：研究表明RNA Ⅲ抑制肽(RNA Ⅲ inhibiting peptide,RIP)是葡萄球菌一种有效的全面抑制剂,作用机制与传统抗菌素明显不同,有着良好的应用前景。通过实验评价聚乳酸乙醇酸(polyaiticglycolic acid,PLGA)/RIP缓释微球的血液相容性。 方法: 实验于2005-10/2007-10在解放军总医院临床药理研究所及医学动物实验中心完成。选择成年健康新西兰大白兔30只,按随机数字表法分组,每组6只。药品及试剂: PLGA,二甲基亚砜、MTT,DMEM,二硝基氟苯。实验方法：①PLGA/RIP微球制备：采用Fmoc法由C端至N端先合成粗品肽;采用反相液相色谱法对RIP粗品进行纯化分析,按紫外吸收峰收集组分,冷冻干燥,得到RIP纯品。再采用液相复乳法制备直径50～70 mm的PLGA/RIP微球。②洗提液制备：PLGA/RIP微球粉末按1 g/L在37 ℃无菌条件下用生理盐水洗提72 h,制得洗提液原液;加入同体积的无菌生理盐水制得0.5 g/L的稀释液。③溶血实验：以蒸馏水和生理盐水分别为阳性、阴性对照,观察PLGA/RIP洗提液原液和0.5 g/L洗提液的溶血率。④凝血实验及PLGA/RIP对凝血酶原时间和活化部分凝血酶时间的影响实验：以生理盐水为阴性对照,观察PLGA/RIP洗提液原液和0.5 g/L洗提液对兔凝血时间的影响和凝血酶原时间和活化部分凝血酶时间的影响。⑤PLGA/RIP对兔白细胞、红细胞和血小板及血小板聚集的影响实验：观察PLGA/RIP洗提液原液和0.5 g/L洗提液对兔白细胞、红细胞和血小板及血小板聚集的影响。 结果：纳入动物30只, 均进入结果分析。①溶血实验结果显示PLGA/RIP洗提液原液和0.5 g/L洗提液的溶血率分别为3.24%和2.67%,两者的溶血率均 < 5%,符合医用生物材料的溶血实验要求。②凝血实验结果表明PLGA/RIP洗提液原液和0.5 g/L洗提液对兔凝血时间无明显影响。③PLGA/RIP对各时间点兔凝血酶原时间和活化部分凝血酶时间均无明显作用。④PLGA/RIP对兔白细胞、红细胞和血小板无明显影响。⑤PLGA/RIP对兔血小板聚集无明显影响。 结论: PLGA/RIP缓释微球具有良好的血液相容性。     

聚乳酸乙醇酸/RNAⅢ抑制肽缓释微球的血液相容性*☆

目的：研究表明RNA Ⅲ抑制肽(RNA Ⅲ inhibiting peptide,RIP)是葡萄球菌一种有效的全面抑制剂，作用机制与传统抗菌素明显不同，有着良好的应用前景。通过实验评价聚乳酸乙醇酸(polyaiticglycolic acid,PLGA)/RIP缓释微球的血液相容性。 方法: 实验于2005-10/2007-10在解放军总医院临床药理研究所及医学动物实验中心完成。选择成年健康新西兰大白兔30只，按随机数字表法分组，每组6只。药品及试剂: PLGA，二甲基亚砜、MTT，DMEM，二硝基氟苯。实验方法：①PLGA/RIP微球制备：采用Fmoc法由C端至N端先合成粗品肽；采用反相液相色谱法对RIP粗品进行纯化分析,按紫外吸收峰收集组分,冷冻干燥,得到RIP纯品。再采用液相复乳法制备直径50～70 mm的PLGA/RIP微球。②洗提液制备：PLGA/RIP微球粉末按1 g/L在37 ℃无菌条件下用生理盐水洗提72 h，制得洗提液原液；加入同体积的无菌生理盐水制得0.5 g/L的稀释液。③溶血实验：以蒸馏水和生理盐水分别为阳性、阴性对照，观察PLGA/RIP洗提液原液和0.5 g/L洗提液的溶血率。④凝血实验及PLGA/RIP对凝血酶原时间和活化部分凝血酶时间的影响实验：以生理盐水为阴性对照，观察PLGA/RIP洗提液原液和0.5 g/L洗提液对兔凝血时间的影响和凝血酶原时间和活化部分凝血酶时间的影响。⑤PLGA/RIP对兔白细胞、红细胞和血小板及血小板聚集的影响实验：观察PLGA/RIP洗提液原液和0.5 g/L洗提液对兔白细胞、红细胞和血小板及血小板聚集的影响。 结果：纳入动物30只, 均进入结果分析。①溶血实验结果显示PLGA/RIP洗提液原液和0.5 g/L洗提液的溶血率分别为3.24%和2.67%，两者的溶血率均 < 5%，符合医用生物材料的溶血实验要求。②凝血实验结果表明PLGA/RIP洗提液原液和0.5 g/L洗提液对兔凝血时间无明显影响。③PLGA/RIP对各时间点兔凝血酶原时间和活化部分凝血酶时间均无明显作用。④PLGA/RIP对兔白细胞、红细胞和血小板无明显影响。⑤PLGA/RIP对兔血小板聚集无明显影响。 结论: PLGA/RIP缓释微球具有良好的血液相容性。     

负载可降解缓释微球壳聚糖支架的生物相容性

摘要 背景：负载缓释转化生长因子β1微球壳聚糖支架在体外能够促进软骨细胞生长,且可以诱导骨髓间充质干细胞向软细胞分化,有望作为软骨缺损修复的组织工程材料,然而要进行相应体内实验,其生物相容性是不容忽视的。 目的：制备负载缓释微球壳聚糖支架并对其生物相容性进行体内外评价。 方法：以溶血试验、急性毒性实验、皮内刺激实验、热源性实验、肌内植入实验,评价自制负载缓释微球壳聚糖支架的生物相容性。 结果与结论：支架溶血率为1.6%,镜下未见明显红细胞破坏;材料急性毒性评价程度为无毒;皮内原发刺激记分及原发刺激指数均为0;热源性实验体温升高为(0.17±0.06) ℃;肌内植入实验大鼠均成活,全身良好、无感染,4周左右新生毛正常分布,8周大体观察支架周围血管明显增多,与周围肌组织整合良好,心肝肺肾等内脏均无特殊变化,随时间延长,淋巴细胞浸润逐渐减少,可见血管及纤维长入支架,包裹逐渐变薄,支架渐降解。结果说明负载微球多孔壳聚糖支架具有优良的生物相容性。     

血管内栓塞材料BaFe12O19微粒血液相容性研究

目的探讨钡铁氧化合物BaFe12O19微粒的血液相容性。方法对BaFe12O19微粒进行血液相容性实验，包括溶血实验、出血和凝血时间测定、凝血实验等。结果BaFe12O19微粒对出血和凝血时间无影响，不引起溶血和凝血。结论BaFe12O19微粒具有良好的血液相容性，且能在X线下显影，悬浮性能良好，不易堵塞微导管，其有可能成为一种全新的血管内栓塞材料。     

聚丙烯酰胺接枝改性聚丙烯膜的血液相容性

背景：绝大多数高分子材料在与血液接触时都导致不同程度凝血，使其应用受到限制。因此研制有优良抗凝血性能的高分子材料成为生物人工肝材料临床研究中的关键问题。 目的：体外检测新型人工肝反应器材料——聚丙烯酰胺接枝改性聚丙烯膜(PP-g-AAm)的血液相容性。 方法：对改性前、后的聚丙烯膜行溶血试验、凝血酶原时间和活化部分凝血激酶时间试验，用流式细胞术检测血小板CD62P和CD63的表达率，扫描电镜观察两种膜上血小板的黏附情况。 结果与结论：聚丙烯膜和PP-g-AAm膜的溶血率分别为1.32%和1.46%；聚丙烯膜的凝血酶原时间和活化部分凝血激酶时间较PP-g-AAm膜明显缩短(P < 0.05)；PP-g-AAm膜激活血小板表达CD62P、CD63的百分率都明显少于聚丙烯膜(P < 0.05)；扫描电镜观察两种材料表面黏附的血小板都有明显变形，但PP-g-AAm膜表面黏附的血小板明显少于聚丙烯膜。提示PP-g-AAm膜具有良好的血液相容性。 关键词：人工肝；血液相容性；生物相容性；聚丙烯；膜生物材料 doi:10.3969/j.issn.1673-8225.2010.08.045     

金属医用材料表面微磁场改善的血液相容性

摘要 背景：在316L不锈钢、NiTi合金的表面用溶胶凝胶法制备含SrFe12O19磁性粉末的TiO2薄膜,磁化后在材料表面形成微磁场,可以延长其动态凝血时间,降低其溶血率,改善材料的血液相容性。 目的：讨论材料表面微磁场与血液相互作用的机制。 方法：用柠檬酸法制备SrFe12O19粉末,用X射线衍射仪(XRD)、扫描电镜(SEM)等分析了磁性粉末的成分及形貌,用磁强计检测了SrFe12O19粉末的磁性能;用溶胶凝胶法在316 L不锈钢、NiTi合金的表面制备含SrFe12O19磁性粉末的TiO2薄膜,并用X射线衍射仪分析了薄膜成分;通过动态凝血时间和溶血率的测定结果分析材料表面微磁场与血液相容性的关系。 结果与结论：材料表面产生的磁场阻碍了血液中Ca2+、和纤维蛋白原、血小板及红细胞等分子在材料表面上的黏附,从而抑制了凝血反应的进行,因而具有抗血栓的作用,提高了材料与血液之间的相容性。     

短碳纤维增强聚醚醚酮为全髋假体材料的生物相容性及力学性能

背景：聚醚酮类聚合物具有良好的生物相容性,但在玻璃化转变温度后其模量、力学强度下降严重,不能为骨骼生长提供一个稳定的环境。 目的：评价短碳纤维增强聚醚醚酮作为全髋假体材料的生物相容性及生物力学性能。 方法：以MTT法、溶血试验、急性全身毒性试验、热原试验评价短碳纤维增强聚醚醚酮浸提液的体外生物相容性;将短碳纤维增强聚醚醚酮接骨板植入兔体内,观察骨板周围包膜形成情况和一般组织情况;对短碳纤维增强聚醚醚酮试件行应力测试。 结果与结论：短碳纤维增强聚醚醚酮材料的细胞相对存活率大于75%,溶血率小于5%,说明其血液相容性较好;植入兔肌肉内未引起明显炎症反应,早期有少量淋巴细胞聚集,植入体为纤维组织包裹,随着时间的延长,淋巴细胞逐渐减少直至消失,纤维包膜逐渐稳定,周围肌肉组织始终保持正常结构,表明短碳纤维增强聚醚醚酮材料无任何毒性,组织相容性好。应力测试显示短碳纤维增强聚醚醚酮材料符合人体髋关节的生物力学强度需要。     

低温去合金化镍钛形状记忆合金血液相容性研究

【摘要】 目的 测定低温去合金化处理后的NiTi形状记忆合金血液相容性指标,评价其血液相容性。方法 通过模拟体内血液环境,以未处理的低温去合金化处理后的NiTi形状记忆合金为对照,对低温去合金化处理后的NiTi形状记忆合金与血液接触后其溶血率、血小板粘附、动态凝血时间以及接触角的测定进行测定。结果 低温去合金化处理后的NiTi形状记忆合金溶血率低,血小板粘附减少,动态凝血时间延长,接触角变小。结论 低温去合金化处理后的NiTi形状记忆合金的血液相容性得到了极大的改善,具有良好的血液相容性,在矫形外科领域具有广阔的应用前景。     

载微球骨水泥的体内生物相容性

背景：课题组在前期实验中已经证实了载聚乳酸-聚羟基乙酸共聚物微球骨水泥具有较高的强度,良好的注射性能和体外可降解性能,但其生物相容性如何还不清楚。 目的：选择急性毒性试验,溶血试验,微核试验等检测载微球骨水泥的生物相容性。 方法：首先合成柱状骨水泥和包裹微球骨水泥,取1 g材料加入到100 mL的磷酸缓冲液中无菌条件下浸泡3 d后提取的上清液即为骨水泥浸提液和微球骨水泥浸提液。以急性毒性实验、溶血试验、微核试验和热原试验来考察材料的体内毒性。 结果与结论: 急性毒性实验结果显示,骨水泥浸提液组和微球骨水泥浸提液组(除高浓度微球骨水泥组外)与阴性对照组均无明显差异,说明该材料浸提液没有对小鼠产生明显的毒性反应。溶血实验显示,各组材料对健康人血的溶血率均未超过5%。微核实验结果显示除0.4 mL骨水泥组和0.4 mL微球骨水泥组的微核率与阴性对照组差异有显著性意义,其余各组差异无显著性意义,说明该微球骨水泥的浸提液无明显细胞遗传毒性作用,但是高浓度和高剂量组的微球骨水泥仍有较低的毒性作用,主要表现为溶血率和微核率的提高,因此在应用时要适当控制微球骨水泥的剂量和浓度。热原试验显示,注射后家兔平均体温升高为0.06 ℃,小于1.4 ℃,说明材料无致热作用。 关键词：聚乳酸-聚羟基乙酸共聚物;骨水泥;微球;体内生物相容性;生物材料 doi:10.3969/j.issn.1673-8225.2010.12.007     

Effects of the non-selective beta-adrenoceptor blocking agent, carteolol, on platelet function, blood coagulation and viscosity

We have studied the effect of a new beta-adrenergic blocker, carteolol, on platelet function, blood coagulation and viscosity in 10 healthy male volunteers. Following carteolol (5 mg orally) we were able to demonstrate significant inhibition of platelet aggregation to ADP (p less than 0.05) and adrenaline (p less than 0.01) after 5 hours, but not at 2 or 24 hours. This maximum inhibition of platelet aggregation corresponded to peak plasma concentrations of carteolol measured. The platelet release reaction, as measured by plasma levels of the platelet specific protein beta-thromboglobulin (BTG) was unaltered and there was no significant effect on a panel of coagulation tests or on blood viscosity.     

In vivo platelet release in myeloproliferative disorders

The in vivo platelet release reaction in 22 patients with myeloproliferative disorders has been studied by measuring plasma concentrations of the platelet release product beta-thromboglobulin (beta TG). Mean beta TG and mean beta TG: whole blood platelet count ratio were significantly raised in the patient group taken as a whole compared to an age matched control group. No significant increases were observed in the plasma concentrations of thrombin and plasmin sensitive fibrinogen fragments fibrinopeptide A (FpA) and B beta 1-42. The patients were divided into those who had normal, increased or decreased responses to in vitro ADP-induced platelet aggregation. Mean beta TG and the mean beta TG: whole blood platelet count ratio were higher in the increased and decreased responders to ADP than in the normal aggregation group, but the differences in means were not statistically significant. Aspirin given to six patients at a dose sufficient to eliminate the secondary phase of ADP-induced platelet aggregation reduced mean beta TG and the mean beta TG: whole blood platelet count ratio but did not alter mean FpA and B beta 1-42. It is concluded that the enhanced platelet release reaction seen in myeloproliferative disorders is independent of plasma protease activity that arises when coagulation and fibrinolytic systems are activated.     

Platelet function in experimentally induced pancreatitis in the dog

Evidence suggests that changes in prostaglandins and disseminated intravascular coagulation accompany pancreatitis. Both may induce changes in platelet function. We wished to determine if experimentally induced pancreatitis in the dog was associated with altered platelet number and function, and whether there were concomitant changes in prostaglandins. Evidence for disseminated intravascular coagulation in the dogs with pancreatitis were red blood cell fragmentation, increased platelet turnover indicated by macro-platelets and the transient presence of fibrin degradation products in urine. There were no significant changes in platelet count. The platelets from dogs with pancreatitis showed a functional defect characterized by significantly decreased aggregation in response to adenosine diphosphate, arachidonic acid, and collagen. Release of adenosine triphosphate from platelets was reduced in collagen-stimulated aggregation. There were no changes in the plasma concentrations of thromboxane B2, 6-Keto-PGF1a, and PGE2. This defect may have been due to the generation of fibrin degradation products and platelet "exhaustion".     

Effect of oral delta-9-tetrahydrocannabinol on coagulation

To test if marijuana might impair blood coagulation, A-9-Tetrahydrocannabinol was administered orally to twelve healthy males in a dose of 210 mgs per day for 12 to 16 days. Platelet count, platelet adhesion, platelet aggregation, bleeding time, Factors V, VII, and VIII were measured. No clinically significant changes were observed, although a minimal increase in Factor VII activity (p=0.05) did occur.     

Improved blood compatibility of a stent graft by combining heparin coating and abciximab

The aim of this study was to assess the combined effect of heparin coating of a stent graft and administration of abciximab, on platelet and coagulation activity in vitro. METHODS: Stent grafts with an expanded polytetrafluoroethylene (ePTFE) membrane interfoliated between two stents were deployed in tubings to form Chandler loops. Fresh human blood with a low concentration of heparin and various doses of abciximab was rotated for 1 h, then collected and used for measurements of platelets, thrombin-antithrombin complex (TAT), CD11b, complement and contact activation of coagulation. In the first set of experiments, all stent grafts were heparin coated. There were three study groups: Group 1a (no abciximab, n=5); Group1b (abciximab in a concentration of 3.3 microg/ml, n=5); Group 1c (abciximab in a concentration of 8.3 microg/ml, n=5). In the second set of experiments, the concentration of abciximab was 3.3 microg/ml. There were three study groups: Group 2a (untreated stent grafts, n=4); Group 2b (heparin-coated stent grafts, n=4); Group 2c (heparin-coated PVC tubings with no stent grafts, n=4). RESULTS: In the first set of experiments, there was a significant reduction in platelet count in Group 1c compared to Group 1a and Group 1b. There was a significant reduction in TAT in Group 1b and Group 1c as compared to Group 1a. In the second set of experiments, TAT was reduced in Group 2b and Group 2c compared to Group 2a. Contact activation was lowered in Group 1b and Group 1c as compared to Group 1a for both FXIa-AT (0.088 and 0.088 vs. 0.115) and FXIIa-AT (0.12 and 0.12 vs. 0.19). CONCLUSION: Heparin coating of a stent graft was shown to improve blood compatibility and this was further enhanced by addition of abciximab.     

Effects of alcohol ingestion post-exercise on platelet aggregation

The present study examined the influence of ingesting a moderate dose of alcohol on platelet count and platelet aggregation during recovery following exercise. Nineteen subjects (11 male and 8 female) were studied immediately after a standardised cycle ergometer test and during the 24-h period of recovery. In random order, alcohol (0.7 g/kg body mass) was given 1 h after exercise on one test occasion, while an equal volume of alcohol-free solution was administered on the other. Venous blood samples were obtained at baseline, post-exercise, and at 1, 5, and 22 h post-alcohol ingestion. Blood alcohol level increased significantly 1 h after the ingestion of alcohol, but decreased and returned to the resting baseline level at 5 h during recovery. Males and females subjects exhibited similar mean values of platelet count, platelet aggregation, and beta-thromboglobulin concentration at rest and following exercise and recovery. A significant increase in platelet count and a decrease in platelet aggregation using adenosine diphosphate (ADP) was found following exercise. Although plasma beta-thromboglobulin level (pooled data for males and females) showed an increase by 26.0% (from a mean pre-exercise value of 22.3-28.1 IU/ml), this rise was not significant (P>.05). The post-exercise increase in platelet count was mainly due to exercise-induced plasma volume loss. During recovery, while the increase in platelet count post-exercise returned to the baseline level in control and alcohol trials, the optical density of platelet aggregation remained significantly depressed at 5-h during recovery in the alcohol trial but not in the normal control condition. It is concluded that exercise induces significant reduction in platelet aggregation and the consumption of alcohol after physical exercise delays the normal return of platelet aggregation to the resting baseline levels during recovery.     

THE EFFECT OF A 5HT2 RECEPTOR ANTAGONIST SARPOGRELATE (MCI-9042) TREATMENT ON PLATELET FUNCTION IN BUERGER''S DISEASE

The effect of a new, specific 5-HT₂ receptor antagonist sarpogrelate (MCI-9042) treatment on platelet function and serotonin levels in both plasma and whole blood in Buerger's disease, was assessed in a pilot study. We investigated 10 patients suffering from Buerger's disease. Sarpogrelate in a dose of 3 × 100mg a day was given p.o. for a period of 8 weeks. It was well tolerated and no major side effects were noted. It was judged to be effective in some patients as assessed by its effect on both subjective complaints and objective evaluation of ankle pressure index (API). Sarpogrelate induced a significant decrease in plasma serotonin (5-HT) concentration starting after the 4th week which lasted through to the 8th week of the study, whereas plasma tryptophan concentration increased significantly after 2 and 4 weeks. There were no changes in plasma 5-HIAA concentration. On the other hand whole blood 5-HT concentration increased significantly after 2 weeks, and there was also a tendency to increase in whole blood tryptophan concentration (p=0.052). Platelet aggregation induced by ADP and collagen did not show any statistically significant changes. Surprisingly, platelet aggregation induced by serotonin increased significantly after 2 weeks and even more so after 4 weeks of treatment, and then it returned to baseline values after 8 weeks. There was no effect on platelet count, APTT, TT and fibrinogen concentration. Copyright © 1996 Elsevier Science Ltd     

The association of platelet and red cell count with platelet impedance changes in whole blood and light-scattering changes in platelet rich plasma: evidence from the Caerphilly Collaborative Heart Disease Study

This epidemiological study was undertaken to explore possible relationships among various haematological indices, prevalent ischaemic heart disease and platelet "function" as measured by two rather different methods. ADP-induced platelet impedance changes in whole blood were strongly associated with prevalent ischaemic heart disease in a general population of 49-66 year men at increased risk. Adenosine diphosphate (ADP) induced platelet aggregation in platelet rich plasma (PRP) at a constant platelet count and also the whole blood platelet count and red cell (RBC) count were strongly and independently related to ADP-induced platelet impedance changes. Both platelet count and platelet aggregation in PRP assessed by changes in optical density were directly related to increasing platelet "sensitivity" as measured by impedance changes in whole blood but RBC count was inversely related. Positive independent relationships between platelet impedance changes and plasma viscosity and fibrinogen were markedly attenuated when platelet count was taken into account, but this finding does not discount a role for these factors in platelet aggregation. No relationship was noted between white blood cell (WBC) count and platelet impedance changes; however, a significant inverse relationship was noted with platelet aggregation in PRP. These findings indicate that laboratory-based experimental findings can be observed in population based studies, and that these haematological factors may be important indicators of ischaemic disease in the population.     

Influence of cytotoxic drugs on platelet functions and coagulation in vitro. IV. Melphalan

Influence of melphalan on some platelet functions, plasmatic coagulation and fibrinolysis "in vitro" was investigated, using different concentrations of the drug (25, 50 and 250 mug/ml). The lowest concentration slightly inhibited adrenaline and/or collagen-induced platelet aggregation. Following the highest concentration of the drug, strong inhibition of aggregation was recorded, regardless of the inducer used. Melphalan was also shown to inhibit release of aggregating activity and release of platelet factor 4, as well as availability of platelet factor 3 and platelet acid phosphatase. The intensity of inhibition depended on both, melphalan concentration and the time of preincubation. In contrast to this, adhesion of platelets to glass slide was not found to be influenced by melphalan. Similarly, melphalan did not induce (in any concentration) loss of LDH from platelet cytoplasma, while triton X-100 or freezing and thawing of platelets caused significant increase of LDH activity. From coagulation tests studied, only thrombin time and reptilase time was found to be moderately prolonged in the presence of melphalan. Authors assumed that melphalan acts as a specific inhibitor of release reaction and can induce an acquired thrombocytopathy. The platelet membrane is not damaged by the drug, as was confirmed by the investigation of LDH activity. Influence on coagulation indicates some antithrombin effect of the drug. Although presented results were obtained in vitro, analogous changes in vivo could be suspected. Thus, impairement of platelet functions might play a part in haemorrhagic complications accompanying, in some cases, melphalan therapy.