Chronic isolated macrothrombocytopenia with autosomal dominant transmission: a morphological and qualitative platelet disorder

Abstract: We studied 47 subjects belonging to 13 unrelated families with a history of mild haemorrhagic diathesis and chronic thrombocytopenia. 36 patients presented some degree of thrombocytopenia: 7/36 (19%) had slight thrombocytopenia (100–150×10⁹/L); 26/36 (72%) had mild thrombocytopenia (50–100×10⁹/L) and 3/36 (8%) had severe thrombocytopenia (<50×10⁹/L). No correlation was observed between platelet count and the degree of haemorrhagic diathesis, which was mild in the majority of patients. Transmission was autosomal dominant. Platelet anisocytosis, increased percentage of large platelets and absence of leukocyte inclusions were observed in 26/30 (87%) of the examined blood smears. The ultrastructural appearance of platelets was normal. Megakaryocytes appeared normal in number in 10/10 patients, but showed asynchronous nuclear-cytoplasm maturation and mainly nonlobulated nuclei. Platelet aggregation was studied in 26 patients and either increased or decreased curves were variably observed in response to different aggregating agents. Platelet-associated IgG (PAIgG) was increased in 18/31 (58%) patients, while serum autoantibodies against platelet glycoproteins Ib/IX or IIb/IIIa were demonstrable in only 1 case. An increased expression of platelet surface glycoproteins Ib and IIb/IIIa, as studied by murine monoclonal antibodies binding in 17 cases, was observed. Platelet survival performed by 111In-oxine-labelled autologous platelets was normal in the 3 studied patients. Congenital macrothrombocytopenia confirms to be a distinct clinical disorder for which the name of “chronic isolated hereditary macrothrombocytopenia” is proposed.     

Efficient RT-PCR on platelet mRNA after long-term storage

We have developed a procedure permitting RT-PCR from mRNA even after a long-term storage (1 year) of platelet samples in ethanol (EtOH-platelets) at −80°C. To validate our method, we have analysed the human platelet alloantigen system (HPA-1) which is coded by β₃ mRNA. We have also demonstrated the efficiency of amplification of part of the coding region for (i) α_IIb subunit mRNA, (ii) α_v subunit mRNA, and (iii) the seven transmembrane domain thrombin receptor mRNA.     

Triflavin, an Arg-Gly-Asp containing snake venom peptide, inhibits aggregation of human platelets induced by human hepatoma cell line

Triflavin, an Arg-Gly-Asp (RGD)-containing peptide, purified from snake venom of Trimeresurus flavoviridis, inhibits human platelet aggregation through the blockade of fibrinogen binding to fibrinogen receptors associated with glycoprotein IIb/IIIa complex. In this report, we examined the effect of triflavin on tumor cells (human hepatoma J-5)-induced platelet aggregation (TCIPA) of heparinized platelet-rich plasma (PRP). ADP-scavenger agents, apyrase (10 U/ml) and creatine phosphate (5 mM)/creatine phosphokinase (5 U/ml) did not inhibit TCIPA while hirudin (5u/ml) completely inhibited it. J-5 cells initially induced platelet aggregation, then blood coagulation occurred. J-5 cells concentration-dependently shortened the recalcification time of normal as well as Factor VIII, IX-deficient human plasmas, while it was inactive at shortening the recalcification time of Factor VII-deficient plasma, suggesting J-5 cells induced platelet aggregation through activation of extrinsic pathway, leading to thrombin formation as evidenced by the amidolytic activity on S-2238 by expressing tissue factor-like activity. Triflavin inhibited TCIPA in a dose-dependent manner (IC₅₀, 0.02 μM). When compared on molar ratio, triflavin was approximately 30,000 times more potent than GRGDS (IC₅₀,0.58 mM). On the other hand, GRGES showed no significant effect on TCIPA, even its concentration was raised to 4 mM. Additionally, the monoclonal antibodies, raised against glycoprotein IIb/IIIa complex (i.e., 7E₃ and 10 E₅) inhibited J-5 TCIPA. In conclusion, we suggest the inhibitory effect of triflavin on J-5 TCIPA may be chiefly mediated by the binding of triflavin to the fibrinogen receptor associated with glycoprotein IIb/IIIa complex on platelet surface membrane.     

A comparative study of plateletpheresis using Baxter Autopheresis C and Haemonetics PCS Plus

SUMMARY. This study compared plateletpheresis on the Haemonetics PCS Plus (PCS Plus) and the Baxter Autopheresis C (Auto C) using the same 100 selected donors. The number of packs meeting UK BTS/NIBSC specification (>2.2 times 10¹¹ platelets per pack) was achieved by 99% of PCS Plus and 82% of Auto C procedures. The positive correlation found between donor precount and final platelet yield was better for the PCS Plus. Both machines met U.K. specification for white-cell contamination but this was significantly greater for the Auto C. Plasma yields were similar.
As a result of this study we chose to use the PCS Plus for routine plateletpheresis in our unit. This has enabled us not only to comply with UK BTS/NIBSC specifications for apheresis platelets easily and cost effectively but also to meet our own higher specification (2.75 times 10¹¹ platelets per pack) using existing staff and without extending the working day.     

水蛭注射液对大白鼠血小板粘附和血小板聚集功能的影响

目的　探讨水蛭注射液对大白鼠血小板粘附性和聚集性的影响。方法　采用大白鼠 2 4只 ,随机分成两组 ,实验组给药 ,对照组以实验组同样的方法和剂量给予生理盐水 ,5d后由颈总动脉取血 ,做血小板粘附性和聚集性试验。结果　水蛭注射液对大鼠血小板粘附性和聚集性具有显著的抑制作用 ,实验组与对照组抑制率有显著的统计学意义 (P <0 0 0 1)。结论　水蛭注射液能够抑制大白鼠血小板的粘附和聚集。     

尿毒症患者的血小板聚集功能变化及血液透析的影响

本文应用 ADP、肾上腺素及复合诱聚剂对30例慢性肾功能不全(尿毒症期)病人的血小板聚集功能进行了检测,其中5例在血液透析前后分别测定。结果表明尿毒症患者血小板聚集功能障碍,血液透析有助于改善血小板功能。通过相关性检验,发现尿毒症病人的血小板聚集率与血肌酐值呈负相关性,其意义尚需进一步探讨。     

血小板活化与冠心病关系的研究进展

病理性血小板活化与血栓性疾病密切相关,在心血管疾病中,这一病理生理过程不仅与冠心病的发生、发展有着非常重要的联系,而且对于该病的治疗策略的优化和近、远期预后等方面都有直接的影响。     

RELATIONSHIP BETWEEN PLATELET CYTOSOLIC FREE CALCIUM CONCENTRATION AND PLASMA RENIN ACTIVITY

1. Plasma renin activity (PRA) and platelet cytosolic free calcium concentration ([Ca2+]i) were simultaneously determined in 18 untreated essential hypertensive subjects and 17 normotensive controls. A significant positive correlation was found between [Ca2+]i and PRA (slope = 42 nmol/l/ng/ml/h) in these 35 subjects. 2. Two determinations more than one week apart in nine subjects confirmed the parallel fluctuations of [Ca2+]i and PRA. A strict sodium restriction produced a progressive PRA elevation associated with a parallel rise in [Ca2+]i in one subject. 3. These results are consistent with the hypothesis that angiotensin II causes a concentration-dependent calcium mobilization.     

Alterations of the levels of glycoproteins Ib-IX and IIb-IIIa in platelets stored at 22°C

Platelets stored in CLX™ blood bags, under normal blood banking conditions, were studied for up to 7 days to determine if changes ocurred in the levels of membrane glycoproteins (GP) Ib-IX and IIb-IIIa. Radiolabeled monoclonal antibodies (MAB) were used to estimate the number of glycoprotein molecules on the surface membrane of intact platelets. GP IX and GP IIb-IIIa levels remained essentially unaltered during storage. In contrast, the content of GP Ib at day 7 decreased by 45% of the total when fresh. The aggregation response to ristocetin, which requires GP Ib, was also diminished after 7 days. Addition of protease inhibitors, leupeptin and/or aprotinin did not appear to influence the degradation of this glycoprotein. We conclude that storage at 22°C has deleterious effects on the GP Ib content of platelets.     

Platelet 3H-imipramine binding during recovery from depression.

Decreased binding of tritiated imipramine to platelets has been considered to be a potential biological marker of depression. However, it has been unclear how binding values alter during treatment and recovery. This study investigated imipramine binding parameters and depressive symptoms in 25 patients suffering from major depression at entry to the study and 1, 3 and 6 months later. Although the initial Bmax values were significantly lower in the depressed patients than in healthy subjects, it was not possible to establish a clear relationship between recovery from depression and Bmax. The power of this study to detect an effect of at least 10% of the variance in Bmax due to factors related to recovery from depression was 0.78.