Mutations of the Platelet Thromboxane A2 (TXA2) Receptor in Patients Characterized by the Absence of TXA2–induced Platelet Aggregation despite Normal TXA2 Binding Activity

1999 ◽  
Vol 82 (11) ◽  
pp. 1528-1531 ◽  
Author(s):  
Wataru Higuchi ◽  
Akira Hattori ◽  
Yoshifusa Aizawa ◽  
Ichiro Fuse
Keyword(s):  
Platelet Aggregation ◽  
Mutational Analysis ◽  
Thromboxane A2 ◽  
Binding Activity ◽  
Single Amino Acid ◽  
Mutant Type ◽  
Platelet Disorder ◽  
Group A ◽  
Txa2 Receptor ◽  
Group B

SummaryPreviously, we reported five cases of platelet dysfunction characterized by the absence of thromboxane A2 (TXA2) – induced platelet aggregation despite normal TXA2 binding activity. In this platelet disorder, patients were divided into two groups; i.e. those whose platelets lacked or did not lack phospholipase C (PLC) activation (Group A and Group B, respectively) (Thromb Haemost 1996; 76: 1080). Furthermore, in one of the patients, we showed that a single amino acid substitution (Arg60 to Leu) in the first cytoplasmic loop of the TXA2 receptor (TXR) was responsible for this platelet disorder. However, mutational analysis of the TXR in the remaining patients has not been performed. Based on this background, we investigated the mutations of the TXR in these patients, and found that all of the patients have the same abnormality of the TXR (Arg60 → Leu), although the Group A patients were homozygous and the Group B patients were heterozygous for this mutation.This mutation is the only abnormality which has been found in this platelet disorder, and in patients heterozygous for this mutation, the mutant type TXR suppresses wild-type receptor-mediated platelet aggregation by a mechanism independent of PLC activation.

Pathogenetic Analysis of Five Cases with a Platelet Disorder Characterized by the Absence of Thromboxane A2(TXA2)-Induced Platelet Aggregation in Spite of Normal TXA2 Binding Activity

1996 ◽  
Vol 76 (06) ◽  
pp. 1080-1085 ◽  
Author(s):  
Ichiro Fuse ◽  
Akira Hattori ◽  
Masao Mito ◽  
Wataru Higuchi ◽  
Kazuaki Yahata ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Phosphatidic Acid ◽  
Phospholipase C ◽  
Bleeding Time ◽  
Thromboxane A2 ◽  
Binding Activity ◽  
Normal Limits ◽  
Signaling Mechanisms ◽  
Platelet Disorder ◽  
Txa2 Receptor

SummaryFive patients with mild bleeding tendencies characterized by defective thromboxane A2 (TXA2)-induced platelet aggregation are reported. The platelets of all the patients had the ability to bind exogenous TXA2. Bleeding time was markedly prolonged in one patient. In three of the five patients, synthetic TXA2 mimetic (STA2)-induced platelet responses, including IP3 formation, Ca2+ mobilization, phosphatidic acid formation and GTPase activities were selectively defective, suggesting impaired coupling between the TXA2 receptor and phospholipase C activation. However, in the remaining two patients, these responses were all within normal limits. This suggests that the defective site of this type of platelet disorder is heterogenous and that signaling mechanisms other than the TXA2 receptor-phospholipase C pathway are also involved in TXA2-induced platelet aggregation.

Blood Viscosity and Platelet Aggregation in Male and Female Patients with Transient Ischaemic Attacks (TIA)

1979 ◽  
Author(s):  
G. Palareti ◽  
M. Poggi ◽  
G. Fortunato ◽  
S. Coccheri
Keyword(s):  
Platelet Aggregation ◽  
Blood Viscosity ◽  
Indirect Evidence ◽  
Vascular Lesions ◽  
Transient Ischaemic Attacks ◽  
Group A ◽  
Circulating Platelet Aggregates ◽  
Male Patients ◽  
Group B ◽  
Almost All

A series of 40 patients with TIA (25 males and 15 females) was thoroughly investigated by means of angiography and computerized tomography, and divided into a group (A) of 15 “sine materia”, and a group (B) of 25 with direct or indirect evidence of vascular occlusive or stenotic changes. Blood viscosity at 230 sec-1 37° was cp 4.2 ± 0.3 in the controls, cp 4.7 ± 0.7 in all patients (p < 0.05) cp 4.98 ± 0.7 in all male patients (p < 0.01 versus male controls), and cp 4.75 ± 0.8 in group B (p < 0.02). Haematocrit and Fibrinogen were also significantly increased in all male patients and in group B. Circulating platelet aggregates (CPA) were increased in 40% of the patients. Almost all patients with elevated CPA were males, with a slight prevalence in group B. Changes in blood viscosity parameters and in platelet aggregation in TIA patients were therefore related both to evidence of vascular lesions, and to sex, since they were found to prevail in male patients of both groups.

Different training schedules influence platelet aggregation in show jumping horses

2017 ◽  
Vol 20 (1) ◽  
pp. 149-154
Author(s):  
C. Giannetto ◽  
F. Arfuso ◽  
F. Fazio ◽  
E. Giudice ◽  
S. Di Pietro ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Training Program ◽  
Initial Velocity ◽  
Platelet Activity ◽  
Animal Blood ◽  
High Intensity Training ◽  
Group A ◽  
Group B ◽  
Show Jumping ◽  
Exercise And Training

Abstract Depending on the intensity, duration and type of physical exercise, equine metabolism has to adapt to nervous, cardiovascular, endocrine and respiratory system requirements. In horses, exercise and training are known to have considerable effects on the mechanisms of hemostatic system involving platelet activity. The aim of the present study was to evaluate the effect of different training schedules on platelet aggregation in 15 Italian Saddle jumping horses. Animals were divided into three equal groups: Group A was subjected to a high intensity-training program; group B to a light training program, group C included sedentary horses. From each animal, blood samples were collected by jugular venipuncture at rest on the 1st, 3rd and 5th days, and afterwards, once a week, for a total of 5 weeks data recording, in order to assess the maximum degree of platelet aggregation and the initial velocity of aggregation (slope) platelet aggregation. Two-way analysis of variance (ANOVA) showed a significant effect of the different training schedules on studied parameters. The results revealed a different degree of platelet aggregation and a different initial velocity of platelet aggregation that changes during the different training schedules in horses that could represent a different protective endothelial mechanism. These findings could have an important role for a clearer knowledge of the physiological reference values of platelet aggregation and for a better interpretation of these variations during the training.

Platelet Function and Adrenoceptors during and after Induced Hypotension using Nitroprusside

1996 ◽  
Vol 85 (6) ◽  
pp. 1334-1340. ◽  
Author(s):  
Gerald V. Dietrich ◽  
Michael Heesen ◽  
Joachim Boldt ◽  
Gunter Hempelmann
Keyword(s):  
Platelet Aggregation ◽  
Blood Loss ◽  
Sodium Nitroprusside ◽  
Sinus Surgery ◽  
Controlled Hypotension ◽  
Lower Shear ◽  
Lower Blood ◽  
Group A ◽  
Group B ◽  
Spontaneous Platelet Aggregation

Background Hypotension induced by sodium nitroprusside can minimize intraoperative blood loss. The release of endogenous catecholamines can influence adrenoceptors of platelets and thus might change the ability of platelets to aggregate. Methods Forty patients undergoing nasal septum, tympanoplastic, or sphenoid sinus surgery were randomly divided into two groups, those having controlled hypotension (A) and those serving as controls (B). Blood samples were drawn before the operation, after induction of anesthesia, 1 h after the start of the operation, and on the day after surgery. Results Epinephrine-induced platelet aggregation only increased in the controls on the day after surgery (A: from 49 +/- 25% to 47 +/- 29%; B: from 53 +/- 24% to 72 +/- 14%; mean +/- SD; P &lt; 0.01). Spontaneous platelet aggregation increased in the controls from a median of 1.2 omega/h to 2.4 during the operation and 2.9 on the day after surgery but not after hypotension. On the day after surgery, alpha 2 receptors reached their maximum (A: 238 +/- 164; B: 234 +/- 80 per platelet). During the operation, the norepinephrine concentrations were significantly greater in group A (median, 419 pg/ml) than in group B (median, 217 pg/ml; P &lt; 0.05). Blood loss was greater in the controls (A: 180 +/- 75; B: 379 +/- 120 ml; P &lt; 0.05). Conclusions Controlled hypotension using sodium nitroprusside reduces epinephrine-induced and spontaneous platelet aggregation. Even on the day after hypotension, the usual postoperative reactive increase in platelet aggregation did not occur. These results may be explained by the direct effect of nitroprusside on platelets, the augmented stress response, lower shear stress on platelets due to the lower blood pressure, or the decreased blood loss compared with the controls.

Oral Administration Of Eicosapentanoic Acid (EPA) Stimulates Production Of Prostacyclin By Rat Aorta

1981 ◽  
Author(s):  
T Hamazaki ◽  
A Hirai ◽  
T Terano ◽  
Y Tamura ◽  
A Kumagai ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Blood Vessels ◽  
Plasma Lipids ◽  
Plasma Lipid ◽  
Diet Group ◽  
Normal Diet ◽  
Platelet Aggregability ◽  
Significant Difference ◽  
Group A ◽  
Group B

Prostacyclin (PGI2) which is mainly produced in blood vessels has the most potent platelet antiaggregatory activity of any substance yet found. It is therefore thought that PGI2 is a preventive agent for cardiovascular diseases (CVD). We found that EPA orally administered to rats stimulated rat thoracic aorta to produce a PGl2like substance at 3 times normal levels. While there are several reports suggesting that EPA may contribute to the prevention of CVD by inhibiting platelet functions and improving plasma lipid concentrations, this is the first report that shows the relationships between orally administered EPA and PGl2~like substance production from aorta. METHODS: Two groups of Wistar rats were fed either a normal diet (group A) or a normal diet plus 74% pure EPA, 60 mg/kg/day (group B), for 8 weeks. Thoracic aortas were excised, cut into rings, and incubated in 50 mM Tris-HCl buffer, pH 7.5, for 10 min. The activity of the PGl2-like substance was measured by inhibition of human platelet aggregation. Platelet aggregability of rats in both groups was also checked with ADP as an aggregant. RESULTS: The rate of production of the PGl2~like substance by the aortas of group B was 4.0±1.4 ng/mg wet aorta/10 min (calibrated with authentic Na-PGI2), while that of group A was 1.4±0.5 (P<0.001). Platelet aggregability was depressed in group B rats. There was no significant difference in concentrations of plasma lipids such as total and HDL-cholesterol, triglycerides, and phospholipid. DISCUSSION: It has been suggested that EPA could prevent CVD through its antiaggregatory property. Now we suggest a new possibility that EPA could prevent CVD by stimulating blood vessels to produce more PGI2-like substance as well as by inhibiting platelet aggregation directly.

Platelet Function in Alcoholics Treated with Disulfiram

1996 ◽  
Vol 2 (1) ◽  
pp. 51-54
Author(s):  
Maria Luigia Randi ◽  
Ilia Zanella ◽  
Piero Pujatti ◽  
Barbara Soini ◽  
Antonio Girolami
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Bleeding Time ◽  
Alcohol Intoxication ◽  
Adenosine Diphosphate ◽  
Human Platelets ◽  
Thromboxane Synthetase ◽  
Group A ◽  
Group B ◽  
Normal Controls

Disulfiram is usually used in alcoholics as aversion therapy. It binds to various enzymes and pro teins in blood and in tissues. In particular, it inhibits the thromboxane synthetase in human platelets and, for this reason, it has been surmised that disulfiram has a possible effect on platelet function. So far, disulfiram failed to confirm this hypothesis in healthy volunteers. However, it appears able to decrease the threshold collagen concen tration for platelet aggregation. Our aim was to evaluate the effect of disulfiram on the platelet function of alco holics. In this study, 24 alcoholics, divided in group A (12 abstinent patients with disulfiram 200 mg/day), group B (12 abstinent patients without treatment), and 17 normal controls, are reported. Different tests were performed at time 0 (acute alcohol intoxication), time 2, and time 15 after the beginning of abstinence. A significant increase was observed in bleeding time (BT) of group B and in platelet count of both groups. No modification was seen in prothrombin time. In group A, a significant increase of platelet aggregation under adenosine diphosphate (ADP; 2 μ M) stimulus was observed. Whereas no difference was seen in platelet 5-hydroxytryptamine (5-HT), serum 5-HT increased significantly at time 15 in group A. We con clude that the increase in serum 5-HT was probably due to the inhibition of monoamine oxidase (MAO) promoted by disulfiram, followed by an activation of MAO induced by disulfiram.

EFfect Of Platelet Aggregation Inhibitor On Foetal Outcome In Cases Of Eph Gestosis

1981 ◽  
Author(s):  
N Bhattacharya ◽  
S Bhattacharya ◽  
K Mukherjee ◽  
N Bose ◽  
B Das ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Diastolic Pressure ◽  
Platelet Aggregation Inhibitor ◽  
Double Blind ◽  
Placental Perfusion ◽  
Group A ◽  
Foetal Outcome ◽  
The Mean ◽  
Aggregation Inhibitor ◽  
Group B

42 mothers with clinical features of mild to moderate specific gestosis (Oedema, Proteinuria, Hypertension) with mean age 29.6±2.8 yrs SD, mean diastolic pressure at 28 weeks 98±4.4, mean parity 2.1±1.1, were enrolled in a placebo controlled double blind trial to see the effect of Dipyridamole (a platelet aggregation inhibitor mainly) in 100 mg t.i.d. on the augmentation of the placental perfusion, by changing the microplatelet thrombi, from 28 weeks up to term. Mothers randomized and grouped equally. Group A received placebo and Group B received drugs in the schedule mentioned. Two cases started premature labour (Group A) and excluded from study. The mean foetal wt in Group B 2700±67 and in Group A 2462±142, expressed in Gms with SD. Fibrinoid area stained with Phosphotungstic acid Aniline Blue of Mallory, was estimated for point counting of W. Ahere (The Placenta, pp. 83-84, Ed. P. Gruenwald, MTP, 1975). The result of the counting suggested a positive physiological correlationship with the outcome of the foetal weight in this tentative study.

scholarly journals A Single Amino Acid Change within Antigenic Domain II of the Spike Protein of Bovine Coronavirus Confers Resistance to Virus Neutralization

2001 ◽  
Vol 8 (2) ◽  
pp. 297-302 ◽  
Author(s):  
Dongwan Yoo ◽  
Dirk Deregt
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Spike Protein ◽  
Single Amino Acid ◽  
Single Point Mutation ◽  
Bovine Coronavirus ◽  
Single Amino Acid Change ◽  
Group A ◽  
Escape Mutants ◽  
Group B

ABSTRACT The spike glycoprotein is a major neutralizing antigen of bovine coronavirus (BCV). Conformational neutralizing epitopes of group A and group B monoclonal antibodies (MAbs) have previously been mapped to two domains at amino acids 351 to 403 (domain I) and amino acids 517 to 621 (domain II). To further map antigenic sites, neutralization escape mutants of BCV were selected with a group A MAb which has both in vitro and in vivo virus-neutralizing ability. The escape mutants were demonstrated to be neutralization resistant to the selecting group A MAb and remained sensitive to neutralization by a group B MAb. In radioimmunoprecipitation assays, the spike proteins of neutralization escape mutants were shown to have lost their reactivities with the selecting group A MAb. Sequence analysis of the spike protein genes of the escape mutants identified a single nucleotide substitution of C to T at position 1583, resulting in the change of alanine to valine at amino acid position 528 (A528V). The mutation occurs in domain II and in a location which corresponds to the hypervariable region of the spike protein of the coronavirus mouse hepatitis virus. Experimental introduction of the A528V mutation into the wild-type spike protein resulted in the loss of MAb binding of the mutant protein, confirming that the single point mutation was responsible for the escape of BCV from immunological selective pressure.

scholarly journals Platelet reactivity with a third generation thienopyridine drug versus with a second-generation thienopyridine drug

2020 ◽  
Vol 11 (3) ◽  
pp. 3704-3709
Author(s):  
Feryal Hashim Rada
Keyword(s):  
Platelet Aggregation ◽  
Second Generation ◽  
Clinical Laboratory ◽  
Platelet Reactivity ◽  
Laboratory Data ◽  
Minor Bleeding ◽  
Third Generation ◽  
Group A ◽  
Treatment Analysis ◽  
Group B

Prasugrel is a third generation thienopyridine drug and Clopidogrel is a second-generation thienopyridine drug. Both drugs used for reducing platelet aggregation in patients with coronary artery diseases.The aim of this study is to investigate the antiplatelet efficacy and safety of Prasugrel 5mg daily as compared to Clopidogrel 75 mg daily for period along to 12 days treatment.Fifty patients, (10 females, 40 males), their ages ranging from (50- 60) years with stable angina were recruited from IbnAlbitar Center for Cardiac Surgery and enrolled in this case study.Of whom 25 patients (group A) received a dose of 75 mg daily of Clopidogrel and other 25 patients (group B) were on a dose of 5 mg daily of Prasugrel for a period of 12 days .Clinical laboratory data of lipid profile, renal function, and prothrombine time obtained at baseline (before treatment). While Platelet aggregation percent measured at the baseline and after 12 days of treatment.The maximal platelet aggregation percent for group A was fell from 78 % ± 6.3 (baseline) to 43.5% ± 5.8 (after 12 days treatment).While patients of group B showed dropping in the maximal platelet aggregation percent from 76 % ± 7.4 (baseline) to 27.3 % ± 5.7 (after 12 days treatment). Analysis of adverse events showed three patients with minor bleeding occurred during Prasugrel treatment, and no bleeding occurred during Clopidogrel treatment. Compared with Clopidogrel 75mg treatment, Prasugrel 5mg treatment for 12 days averted platelets accumulation more quickly and steadily.

In Vivo Inhibition of Acute Platelet-Dependent Thrombosis in a Baboon Model by BAY U3405, a Thromboxane A2-Receptor Antagonist

1993 ◽  
Vol 70 (04) ◽  
pp. 672-675 ◽  
Author(s):  
H F Kotzé ◽  
S Lamprecht ◽  
P N Badenhorst ◽  
V van Wyk ◽  
J P Roodt ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Receptor Antagonist ◽  
Ex Vivo ◽  
Thrombus Formation ◽  
Thromboxane A2 ◽  
Arterial Blood Flow ◽  
Scintillation Camera ◽  
Graft Material ◽  
Txa2 Receptor

SummaryBay U3405 is a thromboxane A2 (TxA2)-receptor antagonist that inhibits the binding of TxA2 to its target cells. The aim of this study was to determine if Bay U3405 could be used to inhibit arterial thrombosis. A thrombogenic de vice, consisting of uncrimped Dacron vascular graft material (0.5 cm2) built into the wall of silicone rubber tubing with 4 mm inside diameter, was exposed to native flowing blood under arterial blood flow conditions (100-140 ml/min) by interposing the devices as extension segments into permanent femoral arteriovenous shunts implanted in baboons. Thrombus formation was quantified in vivo by measuring the deposition of 111In-labelled platelets onto the graft material with a scintillation camera. In six baboons, a bolus injection of Bay U3405, calculated to attain an initial plasma concentration of 300 ng/ml, reduced the maximum thrombus formation measured over a 2 h study period. Platelet deposition was reduced by 33 ± 14% (SD) at 2 h as compared to control studies done in the same baboons. The accumulation of additional platelets onto a thrombus that was allowed to form for 1 h, was reduced by 58 ± 28% at 2 h. Ex vivo platelet aggregation in response to ADP, activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT) were not affected by the treatment. Ex vivo platelet aggregation in response to collagen was markedly inhibited for 2 h after treatment. The results demonstrated that selective blocking of the TxA2-receptor on platelets reduced platelet-dependent thrombus formation and the accumulation of additional platelets in a freshly formed thrombus. This may provide a viable approach for preventing excessive thrombus formation in patients undergoing arterial reconstructive surgery.

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