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At least 757 records · Page 42Linked to original sources
PubMed1983

Monoclonal antibodies against platelet membrane glycoproteins. Characterization and effect on platelet function.

The specificity of five monoclonal antibodies (P1-P6) against platelet surface components was determined by immunoprecipitation of surface-labelled platelets from normal donors and patients with known platelet glycoprotein defects, followed by analysis by gel electrophoresis. Three (P2, P4 and P6) precipitated glycoproteins IIb and IIIa and, in addition, P2 precipitated glycoprotein Ia. P1 precipitated normally only glycoprotein Ib also Ia when the platelets were pretreated with neuraminidase. P3 precipitated principally glycoprotein Ia but glycoprotein Ib was also weakly precipitated. The effects of the monoclonals on platelet function were tested. P1 and P2 completely inhibited and P3 slightly inhibited thrombin-induced platelet aggregation. P2 also inhibited collagen-induced aggregation and partially inhibited ADP-induced platelet aggregation. P3, P4 and P6 partially inhibited ADP-induced platelet aggregation. None had any effect on ristocetin-induced aggregation despite P1 and P3 binding to glycoprotein Ib. These results confirm the role of glycoproteins IIb and IIIa in aggregation induced by various agents and suggest that the function of glycoprotein Ib in thrombin-induced aggregation is more important than previously suspected and that glycoprotein Ia may also be involved in platelet functions.

Animals↗
PubMed2002

Quality control of platelets during storage by the PFA-100: a comparison to platelet aggregation.

BACKGROUND AND OBJECTIVES: The PFA-100 examines platelet function by measuring closure time (CT) when whole blood is passing through a capillary and a filter membrane coated with a collagen/platelet agonist. Termination of the CT is achieved when adhered and aggregated platelets of the passing blood flow occlude the membrane. Two PFA-100 test cartridges are used to measure the CT of citrated whole blood; either the collagen/ADP (PCA) or the collagen/ epinephrine (PCE). We investigated the applicability of the PFA-100 test system for quality control of platelet concentrates in comparison with platelet aggregometry. MATERIALS AND METHODS: For platelet aggregation, the combination of ADP (100 microM/l) and collagen (20 microg/ml) were used as agonists (ADP/COL). In our test system, 25 microl epinephrine (10(-3) M) were added to the PCA cartridge (CT: PCAE) and 25 microl ADP (100 microM/l) to the PCE cartridge (CT: PCEA), respectively. Red blood cells from a blood group 0 donor were adjusted to a hematocrit of 43% using platelet rich plasma (8 x 10(5)/microl) of the respective platelet concentrate. Fourteen irradiated and non-irradiated platelet concentrates were examined on days 0, 3 and 5 after platelet preparation. Swirling without a scoring system and mean platelet volume (MPV) were also tested. Statistical analyses were performed by Pearson's range coefficient, the Mann and Whitney test, and the Wilcoxon test. RESULTS: Swirling was seen in all platelet concentrates. Mean platelet volume was normal during the whole observation period like the PCAE in non-irradiated products. Only the PCAE showed finite CTs during the whole storage time. Consequently, further testing was performed exclusively with the PCAE. Weak but significant correlations could be found between the PCAE and ADP/COL (r = -0.53 for non-irradiated platelet products, r = -0.62 for irradiated platelet products, p < or = 0.0001). Platelet function significantly decreased to around 60% of the initial value in the PCAE on day 5 of storage, ADP/COL decreased to 35% of maximum amplitude. A further decrease of approximately 10% was observed in the irradiated products, a fact which was significant in the PCAE. Only in the irradiated platelet products did MPV show a weak but significant correlation with the PCAE (r = 0.45, p = 0.002). CONCLUSION: Functional features of platelets from platelet concentrates characterized by ADP/COL induced aggregation can also be measured by the PFA-100. Yet, it has a higher sensitivity to platelet lesions induced by gamma-radiation. Further clinical studies will be necessary to determine whether PFA-measurements meet the quality criteria of MPV or swirling, or is superior in predicting in vivo viability. The relatively high cost of the test cartridge remains an obstacle for routine use.

Adenosine Diphosphate↗
PubMed1989

[Modification of blood coagulation by the anti-arrhythmia drug prajmalium bitartrate in vivo].

We studied the effects of prajmaliumbitartrate (PBT, Neo-Gilurytmal, Giulini Pharma, Hannover, FRG), an antiarrhythmic drug on some parameters of blood coagulation in patients. PBT, 20 mg given three times a day, significantly prolonged template bleeding time and ex vivo thrombus formation time in a modified Chandler's loop. Ex vivo platelet aggregation using different agonists and tests of the plasmatic coagulation system remained unchanged.

Ajmaline↗
PubMed1997

[Hemostasis and tests used to investigate it].

Under physiological conditions, in healthy subjects, there is a perfect equilibrium between coagulation activation and inhibition systems. During a surgical operation, dysfunction of the coagulation activation system, responsible for haemorrhage, can be induced by the extent of the anatomical lesions or the pre-existence of a quantitative or qualitative platelet abnormality and/or one or several plasma clotting factors. In contrast, the postoperative period is dominated by the risk of thrombosis and this risk is increased in subjects with a deficit of a coagulation inhibitory protein. The patient's haemorrhagic and thrombotic risk must therefore be evaluated prior to any surgical procedure. The information obtained by clinical interview concerning the patient's personal and family history, combined with a few simple clotting tests generally allows prevention of haemorrhagic or thrombotic accidents.

Blood Coagulation Tests↗
PubMed2001

Effects of a heparin-binding protein on blood coagulation and platelet function.

The objective of this study was to characterize the heparin-binding properties of a protein secreted by mouse myeloma cells. The characterization was performed using clinical assays, such as heparin activity assays and heparin-induced thrombocytopenia (HIT) platelet activation assays. The tests were performed in the presence of heparin, low-molecular-weight heparins (LMWH), or heparinoids and either heparin-binding protein (HBP) or saline to determine whether the HBP affects the activity of heparins. The characterization of the HBP using heparin activity assays showed that the HBP shortened the prolonged clotting times of the activated partial thromboplastin time (aPTT) and thrombin clotting time induced by high concentrations of unfractionated heparin. The chromogenic assays for antithrombin (AT), thrombin inhibition, and factor Xa inhibition demonstrated that this effect is related to heparin concentrations below 0.5 IU/ml. The Heptest assay did not detect these differences. The HBP did not modify the anticoagulant effect of any LMWH or low- or high-sulfated glycosaminoglycans in the aPTT assay. Activation of donor platelets in the presence of unfractionated heparin, platelet factor 4 (PF4), and HIT-serum was not counteracted by the HBP in any of the assays. The characterization of the HBP using a PF4-enzyme-linked immunosorbent assay (ELISA) confirmed the lack of structural identity with PF4. However, the optical density data indicated that the protein structure may be similar to PF4 by binding to a PF4 antibody. These data suggest that the HBP isolated from mouse myeloma cells has a low affinity to heparin and interacts with the secondary binding site to AT and also perhaps to PF4.

Animals↗
PubMed1998

Action of antitumoral platinum complexes on in vitro platelet functions.

This report presents a comparison of the effects of cis- and trans-diamminedichloroplatinum complexes on in vitro platelet functions. Pretreatment of platelets with cis-platinum (cisplatin) induced a slow, dose-dependent (0.1-0.45 mM), increase in the cytosolic Ca2+ concentration, pleckstrin (47 kDa) phosphorylation and serotonin secretion, as well as a slight shape modification with emission of a few pseudopodia. All these effects were remarkably increased in platelets exposed to trans-platinum (transplatin). The rise in cytosolic Ca2+ concentration and serotonin secretion evoked by stimulation of platelets with thrombin were not significantly influenced by cellular exposure to cis-platinum, whereas they were enhanced and inhibited, respectively, by exposure to trans-platinum. Trans-platinum also inhibited thrombin-promoted platelet aggregation to a greater extent than the cis-isomer. While the viscosity of platelet rich-plasma tended to decrease in the presence of cis-platinum, it tended to increase in the presence of trans-platinum. Taken together, these results indicate that the effects on platelet functions of the efficacious antitumor complex cis-platinum is rather different from that of the inactive complex trans-platinum. Therefore, the in vitro tests of platelet functions employed in this study might provide an index of antitumor drug toxicity and serve as a preliminary indicator of therapeutic efficacy.

Antineoplastic Agents↗