Platelets as targets of snake venom metalloproteinases

For centuries snake venoms have been known to interfere with haemostasis and this is now known basically due either to toxins activating/inhibiting clotting factors, having effects on blood vessels or interfering with platelet function. In this short review, the interaction of one major group of toxins, the snake venom metalloproteinases, with platelets is considered. This is relevant for understanding the mechanism of haemorrhage induced by these toxins.     

In Vitro Evaluation of Platelet/Biomaterial Interactions in an Epifluorescent Video Microscopy Combined with a Parallel Plate Flow Cell

Abstract: Suitable evaluation systems are critical for ranking various biomaterials in order to develop a method to design and synthesize nonthrombogenic biomaterials. We have recently developed an in vitro test system to evaluate platelet/biomaterial interactions in whole blood. The system consists of a parallel plate flow cell and epifluorescent video microscopy (EVM). A glass coverslip coated with a polymer was incorporated into the flow cell, and blood was perfused using a syringe pump via a polymer–coated PVC tubing connected to the flow cell. Whole human blood was anticoagulated with heparin (2 U/ml), and the platelets were labeled with the fluorescent dye mepacrine (5 μM). This system permitted real–time and dynamic observations of platelet/biomaterial interactions in whole blood under a defined flow condition. In order to evaluate the feasibility of this system, two different segmented polyether–polyurethanes (SPEUs), PU–PTMG(650) and PU–PTMG(2000), were chosen as test polymers. Surface characteristics verified with electron spectroscopy for chemical analysis (ESCA) and contact angle measurements showed similar results in both SPEUs. Blood was perfused at a wall shear rate of 200 s^–1 for 20 min. Excitation light was applied for 2 s at 1 min intervals. The real–time image was then analyzed at each time point for the percentage of surface area of platelet coverage. Plasma β–thromboglobulin (β–TG) levels were also measured before and after each run. PU–PTMG(650) showed a significantly higher number of adhered platelets than PU–PTMG(2000) at each time point. β–TG levels of PU–PTMG(650) were also higher than those of PU–PTMG(2000), which is comparable to the results of EVM. Thus, this EVM system has been proven to be an excellent and highly sensitive in vitro analytical method for evaluating platelet/biomaterial interactions.     

Blood platelets in severely injured burned patients

Unbelievable decrease of blood-platelet in the severely burned patients during the treatment of skingrafting caused two patients to unexpected death. From the records of changes of platelet number, a certain ‘platelet curve’ was made. By observing the curve, our treatments of skingrafting were carried out during the stable period and from then on we had no death cases.     

脾切除后血小板聚集及ATP释放增高机制的探讨

测定了32例脾切除患者血小板聚集(PAg),其中包括16例同步测定PAg及ATP释放(ATP-R)的结果。脾切除组由ADP、Coll及ADR所致5分钟内最大聚集率(M~1)及ATP-R的均值较脾切除前组及正常对照组均有一定程度升高,其中以肝硬化代偿期脾切除组升高最明显(P<0.05～0.001)。其发生机制与血小板数增多、凝血因子增加、抗凝活性减低、继发性纤溶活性增加及血小板代谢活性指标TXB_2增高等因素有关,提示脾切除患者PAg及ATP-R升高与临床存在的高凝状态有关。     

股骨多段闭合骨折病人术前凝血功能的变化

目的 探讨股骨多段闭合骨折病人术前凝血功能的变化。方法 选择创伤股骨多段闭合骨折后当天入院的病人20例,年龄19-45岁,ASA Ⅰ级,为试验组(Ⅰ组);选择健康成年人15人,年龄21-39岁,作为对照组(Ⅱ组);Ⅱ组于清晨空腹采上肢静脉血标本,Ⅰ组病人入院后于骨折的第2天、第6天(手术当天清晨)空腹采上肢静脉血样本,检测血栓弹力图(TEG)指标[R时间、K时间、α角、血栓最大幅度(MA)、血栓硬度(G)]、D-二聚体浓度(D-Di)、血小板计数(PLC)及血小板聚集率(PAgR)的变化。结果 Ⅱ组TEG指标、D-Di、PLC及PAgR均在正常范围。与Ⅱ组比较,Ⅰ组骨折后第2天,K时间缩短(P<0.05),α角、MA、G及D-Di增高(P<0.01);骨折后第6天,R时间缩短(P<0.05),α角、MA、G、D-Di、PLC及PagR增高(P<0.01)。与骨折后第2天比较,Ⅰ组骨折后第6天MA、G、PLT及PAgR增高(P<0.05或0.01)。结论 病人创伤骨折后凝血功能24 h内增强,随时间的延长至术日呈高凝状态,应加强术中管理,并采取相应措施预防术中静脉血栓的发生。     

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.     

4-芳杂环胺甲基酚衍生物的体外抗血小板聚集活性

血小板体内聚集可使心肌微循环功能产生障碍,导致心律失常或心肌梗塞,血小板聚集在心脑血管疾病的发病机理中起着重要作用,因而对抗血小板聚集药物的研究日益引起人们     

A double-blind cross-over study of nifedipine retard in patients with Raynaud's phenomenon

Summary The effectiveness of nifedipine retard as a treatment for Raynaud's phenomenon was assessed in 15 patients in a placebo controlled double blind study. An associated connective tissue disease was evident in 7 patients. Changes in finger and forearm blood flow (venous occlusion plethysmography), digital skin temperature and digital systolic pressure were measured acutely before and after a 2-week treatment period. Subjective assessment of efficacy was based on patient diary data. In addition alpha₂-adrenoceptor density on platelets was measured before and after chronic nifedipine therapy in both the patient group and in an age-and-sex-matched control group. No significant haemodynamic changes were observed. Nifedipine retard significantly reduced the frequency (p<0.05) with no change in either the duration or severity of vasospastic attacks. Side effects were commono following nifedipine retard. A reduction in alpha₂-adrenoceptor density on platelets was observed in patients compared to a control group (p<0.05). Alpha₂-adrenoceptor density was unchanged following a 2-week treatment period with nifedipine retard. This study concludes that nifedipine retard is not effective in the treatment of Raynaud's phenomenon over a short time course. Patients with Raynaud's phenomenon have reduced alpha₂-adrenoceptor densities on their platelets.     

人参总甙对正常家兔血液流变学的影响

本实验采用小剂量、长期给药的方法观察了人参总甙对正常家兔血液流变学的影响。结果表明人参总甙具有降低正常家兔血液粘度和血小板聚集性的作用,这可能是人参增加组织血流量、防治心血管疾患的重要依据。