Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Platelets”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 73 records · Page 4Linked to original sources
PubMed1989

The relationship of human platelet density to platelet age: platelet population labeling by monoamine oxidase inhibition.

The relationship between platelet density and platelet age appears to vary between species with relatively few labeling studies in humans reported. In this study, irreversible monoamine oxidase (MAO) inhibitors were used to biochemically label the circulating platelet population in 15 humans. Platelet samples were then isolated during the 15 days after drug ingestion. The platelets were separated by density on continuous linear Percoll gradients and the density distributions were divided into five fractions containing approximately equal numbers of platelets. Baseline MAO activity was strongly correlated with platelet density. Twenty-four hours after a single dose of tranylcypromine, platelet MAO activities in the density subpopulations were reduced to 14% to 17% of the baseline values. During the first five days after inhibition, the rates of recovery of MAO activity (percentage per day) were inversely proportional to platelet density. The recovery rates in the two most dense fractions were initially slow but increased after five days. Percentage recovery of MAO activity in the least dense fraction was significantly greater than the percentage recovery in the most dense fraction on days 2, 3, 5, and 8 (P less than .01, sign test). These results support the hypothesis that normal human platelets show a small increase in density with age, but they do not exclude the additional possibility that human platelet lifespan is positively correlated with platelet density.

Adult↗
PubMed1988

Occurrence of platelet basic protein, a precursor of low affinity platelet factor 4 and beta-thromboglobulin, in human platelets and megakaryocytes.

beta-thromboglobulin antigen, a platelet-specific secreted protein, occurs in three forms: platelet basic protein, low affinity platelet factor 4, and beta-thromboglobulin. The combined level of beta-thromboglobulin antigen in megakaryocytes, measured by radioimmunoassay, was 13 +/- 7 micrograms/10(6) cells (SD, n = 6). The relative proportions of the three forms of beta-thromboglobulin antigen present within platelets and megakaryocytes were determined in cells lysed with trichloroacetic acid to minimize artifactual proteolysis. Samples were analyzed by isoelectric focusing in polyacrylamide gel with quantitative immunological detection on a nitrocellulose transfer of the gel. In platelets, the major species found was low affinity platelet factor 4 with precursor platelet basic protein as only 25% +/- 11% (SD, n = 16) of total beta-thromboglobulin antigen. In megakaryocytes partially purified both from normal bone marrow aspirates and from whole marrow specimens obtained after surgery, platelet basic protein was a higher proportion of beta-thromboglobulin antigen (49% +/- 13% SD, n = 11) than was the case in platelets. beta-thromboglobulin itself was never detected under the conditions of cell lysis used. Our results suggest that platelet basic protein is synthesized in megakaryocytes and that its cleavage is associated with an earlier stage of cell development than simply maturation to platelets. Further support for the precursor status of platelet basic protein was found in the expression of predominantly this antigenic form in a human erythroleukemia cell line.

Antigens, Human Platelet↗
PubMed1985

Studies on the effect of platelet inhibitors on platelet adhesion to collagen and collagen-induced human platelet activation.

The effect of pyridoxal 5'-phosphate (PALP) and trifluoperazine (TFPZ), the calmodulin antagonist, on in vitro platelet adhesion to collagen and collagen-induced platelet activation was studied using platelet-rich-plasma (PRP) or washed platelets (WPL). Platelet aggregation and [14C]-5HT release induced by "threshold" or low concentrations of collagen (0.6 micrograms/ml) in PRP were completely abolished by PALP (24 mM), TFPZ (250 microM) as well as indomethacin (10 microM). At higher concentrations of collagen (10-15 micrograms/ml) in PRP and WPL, the use of stirred and unstirred platelets treated with collagen enabled a distinction to be made between aggregation and adhesion-mediated release reaction. Platelet aggregation and the aggregation-mediated release reaction induced by these concentrations of collagen in stirred platelets were completely abolished by PALP, TFPZ and indomethacin although neither adhesion to collagen nor the adhesion-mediated release reaction of unstirred platelets was significantly affected by these inhibitors. Interestingly, both adhesion and the adhesion-mediated release reaction were abolished by concentrations of PALP 10-40 fold higher than those required to abolish aggregation. Collagen-induced platelet aggregation, but not platelet adhesion, was inhibited in resuspended platelets pretreated with PALP and NaBH4 indicating a separation in the membrane sites involved in aggregation and adhesion. The results further emphasize the distinction between adhesion and aggregation-mediated events with regards to collagen with the latter being more susceptible to inhibition by antiplatelet agents such as PALP and TFPZ.

Collagen↗
PubMed1976

Platelet retention in glass bead columns: adhesion to glass and subsequent platelet-platelet interactions.

In normal heparinized blood, the retention of platelets in glass bead columns was low in the first 1 or 2 ml, increasing to more than 80% by the 4th or 5th ml. Prior flushing of the columns with platelet-poor plasma or saline lowered retention in all 5 ml. Additional studies were carried out with a two-stage procedure in which a sample of blood (A) was pumped through a column, immediately flushed out with saline or plasma, and followed by a second blood sample (B). When as little as 1 ml of blood A preceded the flushing solution, retention was very high in all 5 ml of the subsequent blood B. This enhancement of retention in B occurred, providing blood A contained platelets (other than thrombasthenic), fibrinogen, and adequate divalent cations. Enhancement did not require von Willebrand factor (vWF) in A, nor was ADP necessary, since enhancement occurred even when heparinized blood as A contained prostaglendin E1 (PGE1) or creatine phosphokinase with creatine phosphate (CPK-CP). However, the presence of PGE1 or CPK-CP in the plasma used to flush the columns prevented the enhancement of retention in the first milliliter of B. Retention in the first milliliter of B (following normal blood as A and saline or normal plasma for flushing) was high when B was afibrinogenemic, moderately high when B contained PGE1 or CPK-CP, and low in thrombasthenic, EDTA, or vWF-deficient blood. Retention declined in subsequent milliliters of PGE1 or CPK-CP blood and remained low in thrombasthenic, vWF-deficient, or EDTA blood. Our findings suggest that (1) the platelets in A adhere to glass; this adhesion requires fibrinogen but not vWF or ADP; (2) the adherent platelets release ADP and become sticky; (3) adhesion of platelets in the first milliliter of B to the sticky platelets from A requires vWF and divalent cations but not ADP; (4) retention is maintained thereafter by repetitive platelet-platelet interactions involving ADP release, alteration of adherent platelets by released ADP, and adhesion of further platelets to these ADP-altered platelets which requires vWF.

Adenosine Diphosphate↗
PubMed1989

A new congenital platelet abnormality characterized by spontaneous platelet aggregation, enhanced von Willebrand factor platelet interaction, and the presence of all von Willebrand factor multimers in plasma.

A case is reported of a 49-year-old woman with a mild bleeding tendency. Her bleeding time, platelet count and size, plasma ristocetin cofactor activity, von Willebrand factor (vWF) antigen, and vWF multimeric pattern are all within normal limits. Spontaneous platelet aggregation is observed when citrated platelet-rich plasma (PRP) is stirred in an aggregometer cuvette. This aggregation is completely is only slightly diminished by an antiglycoprotein (GP) IIb/IIIa or by an anti GPIb monoclonal antibody. The patient's PRP shows increased sensitivity to ristocetin. The distinct feature of this patient, also present in two family members studied, is that platelet aggregation is initiated by purified vWF in the absence of any other agonist. The vWF-induced platelet aggregation is abolished by anti-GPIb and anti-GPIIb/IIIa monoclonal antibodies and by EDTA (5 mmol/L). Apyrase inhibits the second wave of aggregation. Patient's platelets in PRP are four to six times more reactive to asialo vWF-induced platelet aggregation than normal platelets. The amount of radiolabeled vWF bound to platelets in the presence of either low concentration of ristocetin or asialo vWF was increased 30% compared with normal. The patient's platelet GPIb was analyzed by SDS page and immunoblotting and by binding studies with anti-GPIb monoclonal antibodies showed one band with slightly increased migration pattern and a normal number of GPIb molecules. Unlike the previously reported patients with pseudo or platelet-type von Willebrand disease, this patient has normal vWF parameters.

Antibodies, Monoclonal↗
PubMed1995

Platelet activation in whole blood by artificial surfaces: identification of platelet-derived microparticles and activated platelet binding to leukocytes as material-induced activation events.

Because the lack of thromboresistant vascular biomaterials is in part due to platelet activation, we have attempted, by using fluorescence-activated flow cytometry, to fully characterize the platelet population after in vitro material contact with whole blood. We have used a very simple, near-physiologic system whereby whole blood, anticoagulated with D-phenylalanyl-L-prolyl-arginyl chloromethyl ketone (thrombin inhibitor), contacts materials for 1 hour at 37 degrees C, under low shear. Unlike other tests of platelet compatibility that focus on adherent platelets, this assay evaluates the platelets in the whole blood drained from the tube (1.57 mm internal diameter, 25 cm length) after material contact. We demonstrate for the first time significant materials-induced microparticle formation. One-hour contact with Silastic, polyethylene, and polyvinyl alcohol hydrogel surfaces lead to 30 +/- 1, 33 +/- 4, and 43 +/- 4 x 10(9) microparticles/L, respectively, whereas resting blood samples contained only 10 +/- 1 x 10(9) microparticles/L. In addition, significant increases in activated platelet(s) binding to neutrophils/monocytes after material contact were noted for all surfaces tested. For polyvinyl alcohol hydrogel surfaces a greater than 500% increase in the fluorescent intensity over that of resting whole blood was attained. The addition of monoclonal antibodies to GPIIb/IIIa (A2A9), the tetrapeptide adhesion ligand RGDS (arginine-glycine-aspartate-serine), or the calcium ion chelator ethyleneglycol-bis-(B-aminoethyl-ether)- N,N,N',N'-tetraacetic acid to the whole blood before material contact fully inhibited all platelet reactivity noted for all surfaces--platelet microparticles, platelet P-selectin expression, loss of platelets from bulk, and the formation of platelet/leukocyte aggregates--thereby indicating that material-induced platelet activation is a calcium-dependent process involving GPIIb/IIIa receptors.

Antibodies↗
PubMed1993

Comparison of platelet membrane markers for the detection of platelet activation in vitro and during platelet storage and cardiopulmonary bypass surgery.

Changes in the platelet plasma membrane during activation were investigated by flow cytometry in a comparative study of in vitro platelet activation during platelet storage and cardiopulmonary bypass surgery. We studied changes in the expression of the plasma membrane glycoproteins lb and llla and CD31 antigen (PECAM-1), the alpha-granule membrane proteins GMP-140 (PADGEM, CD62 antigen) and GMP-33, and lysosomal integral membrane protein-CD63. A simultaneous change in the expression of the various glycoproteins induced by platelet activation was seen after thrombin stimulation in vitro and during platelet storage. Platelet activation in vivo in patients showed a more complex change in the expression of membrane glycoproteins. During cardiopulmonary bypass the mean fluorescence values for glycoprotein llla, GMP-33, and the percentage of GMP-140 and lysosome integral membrane protein-CD63 expressing platelets increased significantly. CD31 antigen expression was significantly decreased, whereas glycoprotein lb expression did not change. We conclude that flow cytometry is useful for the detection of changes in the expression of membrane glycoproteins induced by platelet activation in vitro and during platelet storage. Application of flow cytometry as clinical tool for screening platelet activation in patients or for identification of a prethrombotic state requires evaluation of a panel of platelet membrane glycoproteins because the changes in membrane expression may be different in various clinical situations.

Antibodies, Monoclonal↗
PubMed1990

Platelet activation during preparation of platelet concentrates: a comparison of the platelet-rich plasma and the buffy coat methods.

The activation of platelets during the preparation of platelet concentrates (PCs) by two methods was compared. To eliminate interdonor differences, 2 units of whole blood were pooled and subsequently divided into two batches. From one batch, the platelets were harvested as pelleted platelets from platelet-rich plasma (PRP) and from the other as nonpelleted platelets from the buffy coat (BC). The activation of platelets in these PCs was studied immediately after preparation and during storage for up to 9 days at 22 degrees C with gentle agitation. The binding of monoclonal antibodies (MoAbs) against the GP IIb/IIIa complex and against activation-dependent antigens (GMP 140 from the alpha granules and a 53-kDa glycoprotein from the lysosomal granules) was measured. Beta-thromboglobulin (beta-TG) release was also determined. Disc-to-sphere transformation was quantitated by measuring on an aggregometer the difference in light transmission during stirring at different rates and also by light microscopy. Immediately after preparation, platelets derived from PRP had a more spheric morphology (p less than 0.01), had a higher beta-TG release (p less than 0.01), bound more MoAbs against GP IIb/IIIa (p less than 0.01), and expressed more GMP 140 and 53-kDa glycoprotein (p less than 0.01) than did BC-derived platelets. However, these differences had disappeared after 2 days of storage. It was concluded that, immediately after preparation, PRP-derived platelets are more activated than BC-derived platelets. This is most likely a result of the pelleting that follows the second high-speed centrifugation of the PRP.

Antibodies↗
PubMed1993

The platelet-stimulating effect of adrenaline through alpha 2-adrenergic receptors requires simultaneous activation by a true stimulatory platelet agonist. Evidence that adrenaline per se does not induce human platelet activation in vitro.

The stimulating effect of adrenaline on human platelet phospholipase C (PLC) activation and responses in vitro (shape change, aggregation and dense granule secretion) was investigated with respect to its dependence on exogenously added agonists. All experiments were performed with human gel-filtered platelets pretreated with acetylsalicylic acid to prevent endogenous stimulation by the arachidonate pathway. (1) Preliminary experiments demonstrated the presence of trace amounts of extracellular ADP (0.05-0.58 microM) in non-stimulated platelet suspensions; ADP was effectively converted to ATP by the enzyme system creatine phosphate (CP)/creatine phosphokinase (CPK). (2) The adrenaline-induced optical aggregation and single particle (platelet) disappearance in the presence of trace amounts of ADP were almost abolished by the ADP-scavenger system CP/CPK. (3) The response of CP/CPK-treated thrombin- or platelet-activating factor (PAF)-stimulated platelets was markedly increased by a subsequent addition of adrenaline. When hirudin or BN 50726 was added just prior to adrenaline to terminate the activation by thrombin or PAF, respectively, the stimulating effect of adrenaline was also abolished. (4) CP/CPK-treated, PAF-stimulated platelets rapidly developed decreased responsiveness to a subsequent addition of PAF. When adrenaline was added instead of a second addition of PAF, the stimulating effect of adrenaline was gradually decreased and prevented in parallel with the homologous desensitization of PAF. (5) The weak platelet agonist serotonin by itself induced only shape change in CP/CPK-treated platelets. Adrenaline failed to enhance the extent of this serotonin-induced platelet activation. (6) These results strongly suggest that adrenaline per se is not a platelet agonist in vitro but acts to enhance the stimulation induced by true agonists.

Adenosine Diphosphate↗
PubMed1980

Platelet function studies in coronary heart disease. IX. Increased platelet prostaglandin generation and abnormal platelet sensitivity to prostacyclin and endoperoxide analog in angina pectoris.

Platelet prostaglandin generation (malondialdehyde production) and platelet sensitivity to prostacyclin (a vasodilator and platelet aggregation inhibitor) and to epoxymethanodienoic acid (EMA) (a vasoconstrictor and platelet aggregation stimulant endoperoxide analog) were studied in patients with angina pectoris and in control subjects. Platelet malondialdehyde production was higher in patients than in control subjects (mean +/- standard error of the mean 2.50 +/- 0.30 versus 1.70 +/- 0.13 nmol/10(9) platelets, p < 0.02). Platelets from patients were significantly less sensitive to prostacyclin's antiaggregatory effects than were those from control subjects (amount of prostacyclin required for 50 percent platelet aggregation inhibition 1.90 +/- 0.35 versus 0.68 +/- 0.05 ng, p < 0.02). Furthermore, less EMA was required to induce 50 percent platelet aggregation in patients with angina pectoris than in the normal subjects (133 +/- 8 versus 194 +/- 16 ng, p < 0.001). These observations suggest that increased platelet prostaglandin generation and abnormal platelet sensitivity to prostacyclin and endoperoxide analog in certain patients with coronary artery disease are important potential mechanisms in the pathogenesis of myocardial ischemia.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1995

Tokaracetin, a new platelet antagonist that binds to platelet glycoprotein ib and inhibits von Willebrand factor-dependent shear-induced platelet aggregation.

A new platelet antagonist, tokaracetin, was isolated from the venom of Trimeresurus tokarensis by ion-exchange chromatography, heparin-Sepharose chromatography and hydrophobic HPLC. The purified protein showed an apparent molecular mass on SDS/PAGE of 28.9 kDa under non-reducing conditions. On reduction, 16.1 and 15.4 kDa subunits were observed, suggesting that the molecule is a heterodimer. Tokaracetin inhibited the binding of 125I-labelled bovine von Willebrand factor (vWF) and 125I-labelled human vWF in the presence of botrocetin to fixed human platelets. It did not block ADP-, collagen- or thrombin receptor agonist peptide-induced platelet aggregation in human platelet-rich plasma (PRP), or induce platelet agglutination in PRP. On reduction, tokaracetin lost its inhibitory activity on the agglutination of fixed human platelets by bovine vWF. 125I-Tokaracetin specifically bound to washed human platelets with high affinity (Kd 3.9 +/- 1.4 nM) at 47,440 +/- 2780 binding sites per platelet. Binding of tokaracetin to fixed human platelets was reversible, and was inhibited by monoclonal antibody GUR83-35, which is directed against the N-terminal vWF-binding domain of human glycoprotein Ib (GPIb). Tokaracetin completely inhibited vWF-dependent shear-induced platelet aggregation in PRP at 3 micrograms/ml. The N-terminal amino acid sequences of tokaracetin subunits showed a high degree of identity with those of alboaggregin-B. These results suggest that this new platelet antagonist may be a useful tool in the development of specific inhibitors of the vWF-GPIb interaction.

Amino Acid Sequence↗
PubMed1992

DDAVP-induced enhancement of platelet retention: its dependence on platelet-von Willebrand factor and the platelet receptor GP IIb/IIIa.

Although DDAVP has been shown to be haemostatically efficacious in patients with various congenital or acquired platelet disorders, no reasonable explanation has been found for this effect. We have previously shown DDAVP to increase platelet adhesiveness as measured with a platelet retention test. The aim of the present study was to investigate the mechanism of action responsible for the increased platelet retention in response to DDAVP. Patients with vWD type III and type Ia, severe haemophilia and severe thrombasthenia, as well as healthy controls, were included in the study. The effect of different concentrations of vWF in plasma and platelets was explored, as was the effect on platelet function of apyrase and monoclonal antibodies against GP IIb/IIIa and GP Ib. We found the effect of DDAVP on platelet retention to be unaffected by changes in the plasma concentration of vWF. The enhanced platelet retention after DDAVP is apparently dependent on the presence of platelet-vWF and on a normal function of the GP IIb/IIIa. The effect is not mediated via ADP or thrombin. The platelet-stimulating effect of DDAVP may be one explanation for the positive haemostatic effect in patients with certain platelet disorders.

Adolescent↗
PubMed1975

Platelet antiheparin activity. The isolation and characterisation of platelet factor 4 released from thrombin-aggregated washed human platelets and its dissociation into subunits and the isolation of membrane-bound antiheparin activity.

Platelet factor 4 was isolated by gel filtration from the soluble release products of thrombin-aggregated washed human platelets as a proteoglycan-platelet factor 4 complex of molecular weight 358 000, Stokes radius (r-s) of 14.0 nm, sedimentation coefficient (s) of 7.1 S and frictional ratio (f/f-o) of 3.04. The complex was dissociated at high ionic strength (I equals 0.75) and the proteoglycan separated from platelet factor 4 by gel filtration. Platelet factor 4 had a molecular weight of 27 100, r-s of 2.52 nm, s of 2.4 S and f/f-o of 1.26, was insoluble under physiological conditions but readily soluble at pH 3. Under these conditions platelet factor 4 dissociated into four subunits with a molecular weight of 6900, r-s of 1.92 nm, s of 0.8 S, and f/f-o of 1.52. Qualitative N-terminal amino acid analysis showed the presence of glutamic acid or glutamine as the major end group. Platelet factor 4 was compared with protamine sulphate, which has similar biological properties, by electrophoresis at pH 2.2, in which both migrated as single bands but with differing mobility, and by amino acid analysis which showed a more normal distribution of residues than occurred in protamine sulphate. Of the basic amino acids platelet factor 4 (molecular weight 27 100) contained 5.97% arginine, 3.18% histidine, and 12.31% lysine compared to protamine sulphate with 64.2% arginine, 0.6% lysine and no histidine. A partial specific volume (v) of 0.747 was calculated for platelet factor 4 from its amino acid analysis. A membrane fraction with antiheparin activity, an isopycnic density of 1.090-1.110 and r-s of 15-35 nm, was also isolated by sucrose density gradient centrifugation from the ultrasonicated insoluble platelet residue remaining after thrombin-induced aggregation of washed human platelets. Trypsin treatment of the membrane fraction neither solubilised nor destroyed the activity.

Amino Acid Sequence↗
PubMed1996

Low incidence of specific anti-platelet antibodies detected by the MAIPA assay in the serum of thrombocytopenic MDS patients and lack of correlation between platelet autoantibodies, platelet lifespan and response to danazol therapy.

We prospectively studied the mechanism of thrombocytopenia in 30 patients with myelodysplastic syndrome (MDS), who had a platelet count <or= 70 x 10(9)/l, and marrows blasts <or= 10% by analysis of platelet lifespan, platelet-bound IgG antibodies by platelet radioactive antiglobulin test (PRAT), and circulating and platelet-bound autoantibodies specifically directed against platelet glycoproteins by indirect and direct MAIPA test. PRAT analysis was positive in 21/30 patients (70%), but antiplatelet antibodies were found in only eight by the MAIPA test. Platelet lifespan was shortened in five cases, only one of whom had a positive MAIPA test. Patients were treated by danazol (600 mg/d), and 9/26 evaluable patients (35%) responded, including three of the five patients with shortened platelet lifespan. No correlation between platelet lifespan, results of PRAT and MAIPA tests, and response to danazol was found. In conclusion, specific antiplatelet autoantibodies, reduced platelet lifespan, and efficacy of androgen therapy on platelets were seen in 20%, 17% and 35% of MDS with thrombocytopenia, respectively, but no correlation between these findings was found in this study.

Adolescent↗
PubMed1992

Defective platelet aggregation in response to platelet-activating factor in uremia associated with low platelet thromboxane A2 generation.

The bleeding tendency associated with uremia is likely due to a qualitative platelet dysfunction. So far the data available on platelet aggregation are conflicting. Since platelet-activating factor (PAF) plays a role in primary hemostasis, we studied platelet aggregation in response to PAF in 40 patients with chronic uremia on regular hemodialysis and 12 control subjects. Our results showed that in 28 of 40 uremics, platelet aggregation response to PAF was normal, whereas in the remaining 12 it was defective in that no second wave of aggregation was elicited even if the PAF concentrations were increased by a factor of 10,000. This abnormal response was peculiar to PAF and only partially related to factor(s) of plasma origin. The number of platelet PAF receptors and their affinity for the agonist were comparable in controls and "PAF-unresponsive" patients. The defective platelet aggregation in response to PAF was associated with a statistically significant reduction (P less than 0.01) in thromboxane A2 (TxA2) generation in platelet-rich plasma (PRP) challenged with PAF (10 and 100 nmol/L). When PRPs from PAF-unresponsive patients were preincubated with a stable analogue of prostaglandin endoperoxides/TxA2 U-46619, an irreversible platelet aggregation in response to PAF was obtained. Thus in a subpopulation of uremics, platelet aggregation in response to PAF is selectively abnormal as a consequence of a reduced TxA2 generation.

Adult↗
PubMedDate not supplied

Platelet factor 4 release from the platelets stored in platelet concentrates.

Many consider that granular components of platelets should remain intact during storage of platelet concentrates (PCs) in order to participate in hemostasis when infused. The present investigations were done to determine factors affecting the release of an alpha-granular component, platelet factor 4 (PF-4), from platelets stored as PCs. Sedimentation of the pelleted platelet button and stronger flat-bed agitation induced a significant PF-4 release. After 1 day of storage at 22 degrees C, the percent PF-4 release correlated roughly with a pH fall in PCs (r = 0.520, y = 0.014 + 7.204). Rates of pH fall were roughly proportional to the platelet count. In addition, there was a positive relationship between PF-4 release and the platelet count per unit volume (r = 0.615, y = 0.045 + 1.327). The results indicated that one of the critical factors which determines the amount of PF-4 release during storage is concentrated pH. Lowering the platelet count per unit volume in PCs is better for the maintenance of granular components in platelets during storage because of the intact platelet metabolism.

Adolescent↗
PubMed1978

Impairment of platelet thromboxane A2 generation and of the platelet release reaction in two patients with congenital deficiency of platelet cyclo-oxygenase.

Two cases of thrombocytopathia with congenital deficiency of platelet cyclo-oxygenase were investigated. The platelet release reaction was impaired. There was a marked decrease of aggregation with collagen and with adrenalin and a total absence of aggregation with sodium arachidonate. The platelet response to labile aggregation stimulating substance (LASS, mostly thromboxane A2) was normal. There was no biosynthesis of prostaglandin cyclic endoperoxides or of thromboxane A2 from arachidonic acid. Basal levels of platelet PGE1 were lowered although plasma levels were normal. Thrombin decreased the cyclic AMP content of patients' platelets and also that of control platelets pretreated with aspirin. The patients platelets showed no ultrastructural difference when compared with control platelets, except for a slight decrease of granule volume, but, in contrast to control platelets, thrombin (0.02 U/ml) did not provoke contraction of the patients' platelets.

Adult↗
PubMed1989

Collagen-platelet interactions: evidence for a direct interaction of collagen with platelet GPIa/IIa and an indirect interaction with platelet GPIIb/IIIa mediated by adhesive proteins.

Using intact human platelets as the immunogen and a functional, collagen-coated bead agglutination assay, we have produced a murine monoclonal antibody (6F1) that blocks the interaction between platelets and collagen in the presence of Mg++. 6F1 affinity-purified the platelet glycoprotein Ia/IIa complex, and approximately 800 molecules of 6F1 bound per platelet at saturation. 6F1 nearly completely inhibited collagen-induced platelet aggregation and inhibited platelet adhesion to collagen by greater than 95% when plasma proteins were absent. Antibody 10E5, which blocks the binding of adhesive glycoproteins to GPIIb/IIIa, produced only minor inhibition (approximately 25%) of adhesion under the same circumstances. In contrast, when tested in platelet-rich plasma (PRP), 6F1 had only a minor effect on collagen-induced platelet aggregation, prolonging the lag phase but not the slope or maximum aggregation. Similarly, when collagen was precoated with plasma, 6F1 caused less inhibition of platelet adhesion (53%) than without the precoating (greater than 95%). Antibody 10E5 inhibited this adhesion by 32%, and the combination of 6F1 and 10E5 was more effective than either alone, inhibiting it by 90%. Time course studies of platelet agglutination of collagen-coated beads using PRP containing physiologic concentrations of divalent cations showed early inhibition by 6F1, indicating that the GPIa/IIa receptor operates in this environment. With more prolonged incubation, however, 6F1 was less effective; this later agglutination could be partially prevented by adding 10E5 or PGE1 to the 6F1. These data support a model wherein collagen can directly interact with GPIa/IIa and can indirectly interact with GPIIb/IIIa via intermediary adhesive proteins. The physiological significance of these interactions, and potential interactions with other receptors, remains to be established.

Antibodies, Monoclonal↗