ADP and arachidonic acid induced platelet aggregation in schizophrenia and atypical psychoses

SynopsisPlatelet aggregatory responses to adenosine diphosphate (ADP) and arachidonic acid were examined in 6 drug-free schizophrenics, 5 other drug-free psychotics, 8 ‘acute-on-chronic’ schizophrenics (on long-term neuroleptic therapy) and 38 healthy controls. Platelet aggregation and disaggregation following ADP was significantly lower in ‘acute-on-chronic’ schizophrenics (on drugs) compared with healthy controls, and disaggregation following 1 µM ADP was significantly less in drug-free schizophrenics. The difference between maximum aggregation induced by ADP and that induced by arachidonic acid was significantly greater in schizophrenics (both on drugs and drug-free) than in controls. These findings are related to possible abnormalities of central nervous system function in schizophrenia.

Download Full-text

Effects of Methylprednisolone and Hydrocortisone on Aggregation of Rabbit Platelets Induced by Arachidonic Acid and Other Aggregating Substances

Thrombosis and Haemostasis ◽

10.1055/s-0038-1653450 ◽

1981 ◽

Vol 46 (04) ◽

pp. 676-679 ◽

Cited By ~ 15

Author(s):

Frank Glass ◽

Howard Lippton ◽

Philip J Kadowitz

Keyword(s):

Arachidonic Acid ◽

Platelet Aggregation ◽

Platelet Rich Plasma ◽

Adenosine Diphosphate ◽

Actual Mechanism ◽

Dependent Inhibition ◽

Dose Dependent Inhibition ◽

The Difference ◽

Induced Aggregation ◽

Dose Dependent

SummaryThe effects of methylprednisolone and hydrocortisone on platelet aggregation induced by arachidonic acid (AA), collagen, adenosine diphosphate (ADP), prostaglandin (PG) H2, and a stable PGH2 analog, were studied in platelet-rich plasma (PRP) from the rabbit. Incubation of either steroid in PRP inhibited AA-, collagen- and ADP-induced platelet aggregation in a concentration-related manner. The dose of methylprednisolone required to inhibit 0.02 mM AA-induced aggregation was lower than that required to inhibit either 0.08 μg/ml collagen or 0.2 μM ADP-induced aggregation. Methylprednisolone produced a dose dependent inhibition of platelet aggregation induced by PGH2 and the stable PGH2 analog. In washed platelets methylprednisolone was more effective in inhibiting AA-induced aggregation than ADP- or collagen-induced aggregation; however, the difference in effect was less than in PRP. Platelet responses to AA in PRP from rabbits treated with hydrocortisone or methylprednisolone, 100 mg/kg i.v., were inhibited in a transient manner, whereas aggregation induced by ADP under similar conditions was unchanged. Since inhibition of aggregation elicited by AA occurred at concentrations which do not influence PGH2-, PGH2 analog-, collagen- or ADP-induced aggregation, the present data suggest that the steroids may inhibit the incorporation, the release, or the metabolism of arachidonic acid in platelets. The actual mechanism of this relatively specific inhibition of AA-induced aggregation by anti-inflammatory steroids is uncertain but may be related to the membrane “stabilizing” properties of methylprednisolone and hydrocortisone.

Download Full-text

Increased Response to Arachidonic Acid and U-46619 and Resistance to Inhibitory Prostaglandins in Patients with Chronic Myeloproliferative Disorders

Thrombosis and Haemostasis ◽

10.1055/s-0038-1642568 ◽

1988 ◽

Vol 59 (01) ◽

pp. 073-076 ◽

Cited By ~ 9

Author(s):

Sergio Cortelazzo ◽

Monica Galli ◽

Donatella Castagna ◽

Piera Viero ◽

Giovanni de Gaetano ◽

...

Keyword(s):

Bone Marrow ◽

Arachidonic Acid ◽

Platelet Aggregation ◽

Myeloproliferative Disorders ◽

Bone Marrow Stem Cell ◽

Healthy Controls ◽

Aggregation Response ◽

Thrombotic Complications ◽

Cyclic Endoperoxide ◽

Marrow Stem Cell

SummaryIn patients with myeloproliferative disorders (MPD) a group of related diseases of the bone marrow stem cell and recurrent haemorrhagic and/or thrombotic complications, the production of aggregating prostaglandins (PGs) may be normal or slightly reduced, while PGI2 production is normal. However, MPD platelet sensitivity to antiaggregatory PGs is still unknown.We studied the potency of PGD2, PGI2 and PGEi as inhibitors of platelet aggregation induced by threshold aggregating concentrations of arachidonic acid and U-46619-analogue of the cyclic endoperoxide PGH2 in 20 patients with MPD in comparison with healthy controls, with the aim of evaluating the sensitivity of MPD platelets to antiaggregatory PGs. In these patients platelet prostanoid metabolism was normal. However, the functional response of platelets to aggregating and antiaggregating prostanoids was shifted towards potentially increased platelet aggregation response. These findings could have a clinical relevance in view of the haemostatic and thrombotic complications so frequent in MPD.

Download Full-text

Progress of leukoaraiosis is inhibited by correction of platelet hyper-aggregability

International Psychogeriatrics ◽

10.1017/s104161020500164x ◽

2005 ◽

Vol 17 (4) ◽

pp. 689-698 ◽

Cited By ~ 11

Author(s):

Shigekiyo Fujita ◽

Tetsuro Kawaguchi ◽

Toshiyuki Uehara ◽

Kazuhito Fukushima

Keyword(s):

Group Versus ◽

Adenosine Diphosphate ◽

White Matter Hyperintensity ◽

Number Of Patients ◽

Mri Scans ◽

The Mean ◽

The Difference ◽

Magnetic Resonance Imaging Mri ◽

Observation Period

Background: Platelet hyper-aggregability is an important risk factor for leukoaraiosis. In this study we investigated whether aggravation of leukoaraiosis can be controlled by means of long-term correction of platelet hyper-aggregability.Methods:Twenty-one patients with leukoaraiosis and uncorrected platelet hyper-aggregability were compared with 21 controls matched for age, grade of leukoaraiosis and observation period whose platelet hyper-aggregability was corrected. Platelet aggregability was estimated by an optical analytical method with a nine-stage display using two different concentrations each of adenosine diphosphate (ADP) and collagen (the double ADP method).Results:The mean observation period between two magnetic resonance imaging (MRI) scans for both groups was 4.1 years. In the non-corrected group, moderate to severe aggravation of leukoaraiosis was observed in a large number of patients. In the corrected group, only a small number of patients showed generally mild aggravation of leukoaraiosis. The number of patients showing aggravation of periventricular hyperintensity (PVH) was 7 in 21 in the non-corrected group versus 1 in 21 (p=0.022) in the corrected group, and for aggravation of deep white-matter hyperintensity, these values were 9 in 21 versus 4 in 21, respectively. Thus, the difference was more significant if the degree of aggravation was taken into account.Conclusion:The progress of leukoaraiosis is greatly inhibited by long-term correction of platelet hyper-aggregability.

Download Full-text

Self-Esteem Evaluation in Children and Adolescents Suffering from ADHD

Clinical Practice and Epidemiology in Mental Health ◽

10.2174/1745017901309010096 ◽

2013 ◽

Vol 9 (1) ◽

pp. 96-102 ◽

Cited By ~ 19

Author(s):

Luigi Mazzone ◽

Valentina Postorino ◽

Laura Reale ◽

Manuela Guarnera ◽

Valeria Mannino ◽

...

Keyword(s):

Children And Adolescents ◽

Treatment Strategies ◽

Well Being ◽

Self Esteem ◽

Control Group ◽

Healthy Controls ◽

Adhd Symptoms ◽

The Relationship ◽

Drug Free

Background: Several recent studies investigated the relationship between self-esteem and ADHD, however, the results are still controversial. In the present study we analyze the characteristics of self-esteem in a sample of children and adolescents suffering from ADHD, with a particular focus on the relationship between ADHD symptoms severity and treatment strategies. Methods: A total of 85 patients with ADHD (44 drug-free and 41 drug-treated, 23 of which atomoxetine-treated and 18 Methylphenidate-treated) and 26 healthy controls were enrolled in the study in order to evaluate self-esteem using the Self-esteem Multidimensional Test (TMA). Results: ADHD subjects revealed lower scores on all self-esteem domains compared to controls. Both ADHD drug-free (47.1%) and ADHD drug-treated (44.1%) groups showed significantly higher rates of subjects in the pathological range as compared to normal control group (8.8%) (p <.001) with a higher percentage of subjects in the pathological range. Among ADHD drug-treated subjects, the methylphenidate group showed higher self-esteem scores as compared to the atomoxetine group. Conclusion: A lower self-esteem profile is more common in subjects suffering from ADHD than in healthy controls, suggesting the importance of an early detection of psychological well-being in these children in order to reduce the ADHD symptoms long-term impacts.

Download Full-text

Effect of alteplase on platelet function and receptor expression

Journal of International Medical Research ◽

10.1177/0300060519829991 ◽

2019 ◽

Vol 47 (4) ◽

pp. 1731-1739 ◽

Cited By ~ 1

Author(s):

Jun Lu ◽

Peng Hu ◽

Guangyu Wei ◽

Qi Luo ◽

Jianlin Qiao ◽

...

Keyword(s):

Arachidonic Acid ◽

Platelet Aggregation ◽

Platelet Activation ◽

Platelet Function ◽

Adenosine Diphosphate ◽

Receptor Expression ◽

Light Transmittance ◽

Dependent Manner ◽

Clot Retraction ◽

Platelet Receptors

Objective To investigate the role of alteplase, a widely-used thrombolytic drug, in platelet function. Methods Human platelets were incubated with different concentrations of alteplase followed by analysis of platelet aggregation in response to adenosine diphosphate (ADP), collagen, ristocetin, arachidonic acid or epinephrine using light transmittance aggregometry. Platelet activation and surface levels of platelet receptors GPIbα, GPVI and αIIbβ3 were analysed using flow cytometry. The effect of alteplase on clot retraction was also examined. Results This study demonstrated that alteplase significantly inhibited platelet aggregation in response to ADP, collagen and epinephrine in a dose-dependent manner, but it did not affect ristocetin- or arachidonic acid-induced platelet aggregation. Alteplase did not affect platelet activation as demonstrated by no differences in P-selectin levels and PAC-1 binding being observed in collagen-stimulated platelets after alteplase treatment compared with vehicle. There were no changes in the surface levels of the platelet receptors GPIbα, GPVI and αIIbβ3 in alteplase-treated platelets. Alteplase treatment reduced thrombin-mediated clot retraction. Conclusions Alteplase inhibits platelet aggregation and clot retraction without affecting platelet activation and surface receptor levels.

Download Full-text

High Prevalence of Sticky Platelet Syndrome in Patients with Infertility and Pregnancy Loss

Journal of Clinical Medicine ◽

10.3390/jcm8091328 ◽

2019 ◽

Vol 8 (9) ◽

pp. 1328 ◽

Cited By ~ 2

Author(s):

Eray Yagmur ◽

Eva Bast ◽

Anja Susanne Mühlfeld ◽

Alexander Koch ◽

Ralf Weiskirchen ◽

...

Keyword(s):

Platelet Aggregation ◽

Pregnancy Loss ◽

Low Dose ◽

Light Transmission ◽

Previous History ◽

Adenosine Diphosphate ◽

Healthy Controls ◽

Live Births ◽

Aggregation Response ◽

History Of

Platelet hyperaggregability, known as sticky platelet syndrome (SPS), is a prothrombotic disorder that has been increasingly associated with pregnancy loss. In this retrospective study, we aimed to investigate the clinical and diagnostic relevance of SPS in 208 patients with infertility and unexplained pregnancy loss history. We studied 208 patients that had been referred to undergo a dose-dependent platelet aggregation response to adenosine diphosphate and epinephrine using light transmission aggregometry modified by Mammen during an 11-year period. Patients’ platelet aggregation response was compared with platelet function in 29 female healthy controls of fertile age with no previous history of pregnancy loss. We found a prevalence of SPS type II (33.2%) in 208 female patients with infertility and pregnancy loss. ∆-epinephrine-induced platelet aggregation in patients with SPS was significantly decreased (median 7% and range −21 to 43%) compared to patients without SPS (median 59%, range 7–88% and p < 0.0001) and healthy controls (median 57%, range 8–106% and p < 0.0001). The optimum SPS-diagnostic cutoff value for ∆-epinephrine aggregation was ≤32% (sensitivity 95.7%, specificity 95.2%). SPS patients with low-dose acetylsalicylic acid (ASA) therapy (n = 56) showed improved pregnancy outcome (32 pregnancies; live births n = 18 (56%)) compared to SPS patients without low-dose ASA (n = 13) (3 pregnancies; live births n = 1 (33%)). Our study demonstrates the clinical and diagnostic relevance of platelet hyperaggregation in women with infertility and pregnancy loss history. Further studies should investigate the potential of SPS as a novel decisional tool with both diagnostic and clinical implications in infertility and pregnancy loss.

Download Full-text

A Study of Intravascular Platelet Aggregation in the Rat

10.1055/s-0039-1687231 ◽

1979 ◽

Author(s):

G. G. Duncan ◽

G. M. Smith

Keyword(s):

Arachidonic Acid ◽

Platelet Count ◽

Platelet Aggregation ◽

Thromboxane A2 ◽

Adenosine Diphosphate ◽

Residual Response ◽

Induced Aggregation ◽

Anaesthetized Rat

Intravascular platelet aggregation can be studied by measuring the fall in the circulating platelet count induced by aggregating agents in anaesthetized animals. The Technicon Auto-counter was modified and connected via a double cannula to an anaesthetized rat to give a continuous count of the number of circulating platelets (1). Adenosine diphosphate (ADP), Collagen, Arachidonic acid (AA) and 5-Hydroxytryptamine (5-HT) were given at 15 minute intervals over a period of 2-3 hours. Aspirin (10 mg/Kg IV ) and Indomethacin (1-8 mg/Kg IV) partially inhibited collagen-induced aggregation and Indomethacin (2 mg/Kg IV) completely inhibited AA-induced aggregation. Adenosine (0.25 mg/min) inhibited the ADP-induced aggregation but did not inhibit aggregation produced by collagen or the residual response to collagen that remains after the addition of indomethacin.Reproducible responses to ADP and collagen were obtained but responses to AA and 5-HT were not reliable. Collagen-induced aggregation is thought to be mediated by the liberation of ADP, 5-HT and the formation of prostaglandin (PG ) endoperoxides and thromboxane A2. This study has shown that collagen-induced aggregation is reduced by inhibition of PG synthesis but the involvement of ADP or 5-HT could not be shown.

Download Full-text

The Aptamer ARC1779 Potently and Specifically Inhibits the Excessive von Willebrand Factor (vWF) Activity and vWF-Mediated Ex Vivo Platelet Function of Patients with Thrombotic Thrombocytopenic Purpura (TTP).

Blood ◽

10.1182/blood.v110.11.279.279 ◽

2007 ◽

Vol 110 (11) ◽

pp. 279-279 ◽

Cited By ~ 1

Author(s):

Bernd Jilma ◽

Florian B. Mayr ◽

Paul Knoebl ◽

Alexander O. Spiel ◽

Patricia G. Merlino ◽

...

Keyword(s):

Arachidonic Acid ◽

Platelet Aggregation ◽

Platelet Function ◽

Ex Vivo ◽

Healthy Controls ◽

Citrate Anticoagulation ◽

Closure Time ◽

A1 Domain ◽

Plug Formation ◽

Novel Therapeutic

Abstract Background: ARC1779 is an aptamer which blocks the binding of the vWF A1 domain to platelet GPIb receptors. In TTP there is an excess of ultra-large multimers of vWF which are especially avid for binding GPIb and give rise to disseminated platelet thrombi which are fibrin-poor and vWF-rich in composition. ARC1779 is being evaluated for use as front-line therapy of acute TTP in conjunction with plasma exchange. ARC1779 has already been demonstrated in healthy volunteers to inhibit vWF activity and vWF-dependent platelet function. ARC1779 has no anticoagulant effect and does not inhibit other pathways of platelet activation. ARC1779 is expected to normalize platelet dysfunction and prevent the thrombotic end-organ complications of TTP based upon the mechanism of action defined for ARC1779 and the mechanism of thrombosis defined for TTP. Methods: We first assessed vWF activity (vWF:RiCO) and platelet function in blood samples taken from TTP patients and age-matched, healthy controls. We then studied the ex vivo dose response curves for ARC1779 on vWF activity (free A1 domain sites) and on platelet function assessed by the Platelet Function Analyzer (PFA-100®), cone and plate analyzer (IMPACT®), and agonist-induced impedence platelet aggregometry (Multiplate®) of TTP patients (N=10, 2 in acute phase and 8 in remission) and healthy age-matched controls (N=23). Results: vWF:RiCO activity (p=0.002) and vWF-dependent platelet plug formation (p=0.001) were increased in TTP patients relative to healthy controls, but agonist-induced platelet aggregation (ADP, arachidonic acid, collagen, TRAP) was not. ARC1779 fully blocked platelet plug formation as measured by PFA-100® with an IC100 of ∼ 1 mcg/mL with citrate anticoagulation, and ∼ 3–4 mcg/mL with hirudin anticoagulation in both TTP patients and in healthy controls. ARC1779 fully blocked shear-dependent platelet adhesion measured by the IMPACT® analyzer with an IC100 of ∼ 1 mcg/mL with citrate anticoagulation in both TTP patients and in healthy controls. ARC1779 fully blocked vWF activity (free A1 domain sites) with an IC90 of ∼ 6 mcg/mL in TTP patients and ∼ 2 mcg/mL in young controls (p<0.001 between groups). ARC1779 did not inhibit platelet aggregation by ADP, collagen or arachidonic acid at concentrations (10mcg/mL) that fully inhibited vWF dependent platelet function. Conclusions: ARC1779 potently and specifically inhibits vWF activity and vWF dependent platelet function in the setting of TTP where vWF activity is increased. ARC1779 represents a novel therapeutic principle (vWF antagonism) and a novel therapeutic class (aptamers) with potential for the treatment of TTP. vWF Activity and Platelet Function in TTP Patients and Age-Matched Controls Population Healthy Controls TTP Patients values shown as mean +/− standard deviation Sample Size N=23 N=10 vWF:RiCO (%) 94.9 +/− 60.4 153.3 +/− 55.9 PFA-100® Closure Time in Citrate (sec) 90.9 +/− 16.0 66.8 +/− 12.7 PFA-100® Closure Time in Hirudin (sec) 84.0 +/− 12.9 64.6 +/− 11.9 ARC1779 IC100 PFA in Citrate (ARC1779 mcg/mL) 0.9 +/− 0.4 1.4 +/− 0.6 ARC1779 IC100 PFA in Hirudin (ARC1779 mcg/mL) 3.2 +/− 1.5 4.4 +/− 2.7 IC100 IMPACT in Citrate (ARC1779 mcg/mL) 0.8 +/− 1.2 0.8 +/− 0.8 IC90 vWF free A1 domain sites (ARC1779 mcg/mL) 1.8 +/− 0.8 6.2 +/− 2.7

Download Full-text

Platelet malondialdehyde production and aggregation responses induced by arachidonate, prostaglandin-G2, collagen, and epinephrine in 12 patients with storage pool deficiency

Blood ◽

10.1182/blood.v58.1.27.bloodjournal58127 ◽

1981 ◽

Vol 58 (1) ◽

pp. 27-33

Author(s):

HJ Weiss ◽

B Lages

Keyword(s):

Arachidonic Acid ◽

Platelet Aggregation ◽

Adenosine Diphosphate ◽

Synthetic Pathway ◽

Dense Granules ◽

Storage Pool ◽

Increased Sensitivity

We assessed the integrity of the prostaglandin synthetic pathway by measuring malondialdehyde (MDA) production and studied platelet aggregation responses to arachidonic acid and PGG2 in 12 patients with storage pool deficiency (SPD). Eight patients were deficient only in dense granules (delta-SPD) and four were deficient in both dense and alpha-granules (alpha delta-SPD). Production of MDA in response to arachidonic acid (AA), epinephrine, and collagen suggested that the transformation of AA to prostaglandin metabolites was normal in delta- SPD but abnormal in alpha delta-SPD and that the liberation of AA from phospholipids were abnormal in the majority of patients with SPD. Since the content of secretable adenosine diphosphate (ADP) is diminished in SPD platelets, the aggregation responses of these platelets to AA and PGG2 were studied to help answer the question whether these agents aggregate platelets directly or through release of endogenous ADP. Among patients with delta-SPD, aggregation by both AA and PGG2 was decreased in four albinos whose platelets were markedly deficient in ADP. In contrast, normal, or less strikingly abnormal, responses were observed in patients whose platelets either contained higher levels of platelet ADP or showed increased sensitivity to ADP. The more marked impaired responses to AA and PGG2 in patients with alpha delta-SPD suggest that substances derived from alpha-granules may also play a role in platelet aggregation by these agents. The aggregation responses in these patients with various types of SPD is consistent with a theory that granule-derived ADP mediates platelet aggregation by AA and PGG2.

Download Full-text

Monitoring the entry of new platelets into the circulation after ingestion of aspirin

Blood ◽

10.1182/blood.v61.6.1081.bloodjournal6161081 ◽

1983 ◽

Vol 61 (6) ◽

pp. 1081-1085

Author(s):

G Di Minno ◽

MJ Silver ◽

S Murphy

Keyword(s):

Arachidonic Acid ◽

Platelet Aggregation ◽

Adenosine Diphosphate ◽

Normal Subjects ◽

In Vitro Experiments ◽

Early Entry ◽

Cyclooxygenase Activity ◽

Aspirin Ingestion ◽

Thromboxane Formation

There have been reports of a 24–48-hr delay in the recovery of platelet cyclooxygenase activity and platelet function after the ingestion of aspirin. However, these studies employed a single aggregating agent to stimulate enzymatic or functional activity. We investigated the effects of some pairs of aggregating agents on 14 platelet-rich plasmas (PRP) from normal subjects 2 and 4 hr after ingestion of 650 mg aspirin and daily up to 72 hr. We studied platelet aggregation and secretion with a lumiaggregometer and thromboxane-B2 formation by radioimmunoassay. Aggregation and secretion occurred as early as 4 hr after aspirin ingestion in response to combinations of arachidonic acid with epinephrine, collagen, or adenosine diphosphate (ADP). Thromboxane formation was detected as early as 4 hr after ingestion of aspirin in response to 1 mM arachidonic acid in combination with 1 microgram/ml collagen. Up to 72 hr, there was a linear return of thromboxane formation stimulated by this combination, reflecting the entry of new platelets into the circulation. In vitro experiments with mixtures of aspirin-free and aspirin-treated platelets showed that the combination of collagen and arachidonic acid (AA) could produce full aggregation and secretion when only 2.5% of aspirin-free platelets were present. Use of the combination of collagen plus AA demonstrates the early entry into the circulation of platelets originating from megakaryocytes whose cyclooxygenase has not been completely acetylated.

Download Full-text