scholarly journals Influence of Imidazole Carboxamide on Platelet Function

1977 ◽  
Author(s):  
P. Kubisz ◽  
P. Klener ◽  
S. Cronberg
Keyword(s):  
Platelet Function ◽  
Light Transmission ◽  
Platelet Rich Plasma ◽  
Cytostatic Drug ◽  
Bleeding Tendency ◽  
Platelet Dysfunction ◽  
Freezing And Thawing ◽  
Trade Name ◽  
Coagulation And Fibrinolysis

Imidazol carboxamide (DTIC, NSC-45388) is a cytostatic drug used in the treatment of malignant melanoma under the trade name of DacarbazinR, MSD. Its influence on platelet function, blood coagulation and fibrinolysis was investigated in vitro.At a concentration of 160 µg/ml it inhibited the increase in light transmission induced in platelet-rich plasma by standardized freezing and thawing. It also retarded the retraction of reptilase clots. This therefore indicated a stabilizing effect on the platelets at this dosage.At a concentration of 40 μg/ml the drug did not significantly influence the platelet function in vitro.This concentration corresponds to therapeutic plasma levels. At current dosage of the drug any bleeding tendency due to platelet dysfunction therefore seems unlikely.

Standardization of Light Transmission Aggregometry for Diagnosis of Platelet Disorders: An Inter-Laboratory External Quality Assessment

2019 ◽  
Vol 119 (07) ◽  
pp. 1154-1161 ◽  
Author(s):  
Karina Althaus ◽  
Barbara Zieger ◽  
Tamam Bakchoul ◽  
Kerstin Jurk ◽  
Keyword(s):  
Platelet Function ◽  
Light Transmission ◽  
Platelet Rich Plasma ◽  
Reference Ranges ◽  
Technical Problems ◽  
Platelet Function Disorders ◽  
Light Transmission Aggregometry ◽  
Laboratory Survey ◽  
Definition Of

AbstractSeveral in vitro platelet function tests are available for the diagnosis of inherited platelet function disorders. Currently, the light transmission aggregometry (LTA) is recommended as one of the first-step tests. LTA is available in most specialized hemostasis laboratories. Although the LTA is accepted as a ‘gold standard’ assay for the evaluation of platelet function, its standardization in the clinical practice is still challenging. The GTH-based THROMKID-Plus Study Group has performed an inter-laboratory trial in Germany and Austria. Five different agonists were selected according to the Scientific and Standardization Committee/International Society on Thrombosis and Haemostasis recommendations and shipped in 3 different sets (one should represent a healthy control and two should simulate platelet function disorders) to 15 specialized laboratories in Germany and Austria. Agonists were analyzed by APACT or PAP4/8 aggregometer using platelet-rich plasma from healthy donors. In addition, laboratory-internal platelet agonists were tested in platelet-rich plasma from a healthy donor. All laboratories (9 used APACT, 6 used PAP4/PAP8) showed very consistent data regarding the maximum percentage of aggregation induced by the tested agonists and identified the differential diagnosis of the simulated platelet function disorders with one exception, which was due to technical problems. In contrast, there was a high variability of the laboratory-internal inductors regarding reagent type, concentrations and pathological cut-off values. Our study showed that the shipment of agonists is suitable for an inter-laboratory survey of LTA. However, there is still a remarkable need for standardization of agonist reagents and their concentration as well as for definition of reference ranges.

Evaluation of Platelet Dysfunction In Children: Improved Detection and Efficiency

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1446-1446
Author(s):  
Diane J. Nugent ◽  
Ryan Roberts ◽  
Peggy Nakagawa
Keyword(s):  
Platelet Function ◽  
Mutational Analysis ◽  
Light Transmission ◽  
Platelet Rich Plasma ◽  
Clot Formation ◽  
Activity Levels ◽  
Food History ◽  
Platelet Dysfunction ◽  
Light Transmission Aggregometry ◽  
Arachadonic Acid

Abstract Abstract 1446 Currently, there is no single assay that will detect platelet function abnormalities in all individuals. We prospectively studied 369 patients with a strong history of bruising and mucosal membrane bleeding for possible platelet dysfunction following documentation of normal Von Willebrand antigen and activity levels. In an effort to evaluate platelet function under more diverse conditions we chose to simultaneously evaluate 1) aggregation using platelet rich plasma and light transmission aggregometry (LTA), 2) adhesion under high shear using the Platelet Function Analyzer (PFA-100, ADP-collagen, and Epinephrine-collagen cartridges) and 3) platelet initiated clot formation using heparinized whole blood and the two standard mapping agonists, arachadonic acid (AA) and ADP (Hemascope Thromboelastograph Analyzer). Of the 369 platelet evaluations performed, 87 patients (24%) were found to be normal in all three assays with all agonists. On repeated assays with increased attention to medication and food history, an additional 152 patients were felt to have a transient or acquired dysfunction which improved or normalized on further testing. Leaving 130 patients with persistent bleeding and documented abnormalities on one or more of the assays used. There were no patients with only Collagen (CN) or arachadonic acid (AA) aggregation alone on LTA. Using LTA, there was one patient with combined CN and ADP aggregation defect only, another with AA and EPI absent aggregation only, and one with only AA and Thrombin receptor agonist peptide (TRAP) aggregation abnormalities. A summary of the remaining 127 patients are displayed in the table below:Abnormal AssayLTA EPILTA ADPLTA ADP + EPILTA ADP, EPI CNLTA ADP, EPI, AALTA ADP, EPI CN, AAPFA and PLT Mapping ONLYNumber201240841825M/F3M/17F6M/6F16M/24F1M/7F1M/3F8M/10F12M/13FPFA1M/2F4M7M/4F01M01M/3FPlt Mapping2M/2F1M/2F3F1F009M/7FBoth PFA and Mapping1M0001F2M/9F2M/3F Summary: By using a combination of three assays, we were able to identify 25 additional patients with significant platelet dysfunction detected with abnormal platelet mapping or PFA-100 despite normal light transmission aggregometry. Patients with the most abnormalities on aggregation, also demonstrated abnormal adhesion and platelet initiated clot formation. However, the use of PFA-100 and/or platelet mapping alone would miss the majority of patients with aggregation defects. In the future, the unique combination of platelet function defects as measured by these assays, and future technologies, will not only improve detection, but also facilitate phenotype to genotype associations and expedite mutational analysis. Disclosures: Off Label Use: Rituximab to treat ITP.

Effect of Aspirin on the Thrombelastogram of Human Blood

1973 ◽  
Vol 30 (03) ◽  
pp. 494-498 ◽  
Author(s):  
G de Gaetano ◽  
J Vermylen
Keyword(s):  
Oral Dose ◽  
Single Oral Dose ◽  
Platelet Function ◽  
Human Blood ◽  
Platelet Rich Plasma ◽  
Plasma Samples ◽  
Release Reaction ◽  
Platelet Release

SummaryThrombelastograms of both native blood and re-calcified platelet-rich plasma samples taken from subjects given a single oral dose of aspirin (1 gram) were not significantly different from the pretreatment recordings. Aspirin also did not modify the thrombelastogram when preincubated in vitro with platelet-rich plasma at concentrations inhibiting the platelet “release reaction” by collagen. Thrombelastography therefore cannot evaluate the effect of aspirin on platelet function.

The Effect of Barbituric Acid Derivatives on Platelet Function in Vitro and in Vivo

1973 ◽  
Vol 30 (02) ◽  
pp. 315-326
Author(s):  
J. Heinz Joist ◽  
Jean-Pierre Cazenave ◽  
J. Fraser Mustard
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Barbituric Acid ◽  
Platelet Rich Plasma ◽  
Inhibitory Effect ◽  
Primary Response ◽  
Sodium Pentobarbital ◽  
Barbituric Acid Derivatives

SummarySodium pentobarbital (SPB) and three other barbituric acid derivatives were found to inhibit platelet function in vitro. SPB had no effect on the primary response to ADP of platelets in platelet-rich plasma (PRP) or washed platelets but inhibited secondary aggregation induced by ADP in human PRP. The drug inhibited both phases of aggregation induced by epinephrine. SPB suppressed aggregation and the release reaction induced by collagen or low concentrations of thrombin, and platelet adherence to collagen-coated glass tubes. The inhibition by SPB of platelet aggregation was readily reversible and isotopically labeled SPB did not become firmly bound to platelets. No inhibitory effect on platelet aggregation induced by ADP, collagen, or thrombin could be detected in PRP obtained from rabbits after induction of SPB-anesthesia.

Interactions of Staphylokinase with Human Platelets

1995 ◽  
Vol 73 (03) ◽  
pp. 472-477 ◽  
Author(s):  
H R Lijnen ◽  
B Van Hoef ◽  
D Collen
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Specific Binding ◽  
Platelet Rich Plasma ◽  
Human Platelets ◽  
Normal Plasma ◽  
Atp Secretion ◽  
Platelet Disaggregation ◽  
Activation Rate

SummaryThe interactions of recombinant staphylokinase (SakSTAR) with human platelets were investigated in a buffer milieu, in a human plasma milieu in vitro, and in plasma from patients with acute myocardial infarction (AMI) treated with SakSTAR.In a buffer milieu, the activation rate of plasminogen by SakSTAR or streptokinase (SK) was not significantly altered by addition of platelets. Specific binding of SakSTAR or SK to either resting or thrombin- activated platelets was very low. ADP-induced or collagen-induced platelet aggregation in platelet-rich plasma (PRP) was 94 ± 2.7% or 101 ± 1.7% of control in the presence of 0.1 to 20 μM SakSTAR, with corresponding values of 95 ± 2.8% or 90 ± 4.6% of control in the presence of 0.1 to 4 μM SK. No effects were observed on platelet disaggregation. ATP secretion following collagen-induced platelet aggregation was 4.3 ± 0.26 μM for SakSTAR (at concentrations of 0.1 to 20 μM) and 4.4 ± 0.35 μM for SK (at concentrations of 0.1 to 4 μM), as compared to 3.4 ± 0.70 μM in the absence of plasminogen activator.Fifty % lysis in 2 h (C50) of 60 μl 125I-fibrin labeled platelet-poor plasma (PPP) clots prepared from normal plasma or from plasma of patients with Glanzmann thrombasthenia and immersed in 0.5 ml normal plasma, was obtained with 12 or 16 nM SakSTAR and with 49 or 40 nM SK, respectively. C50 values for lysis of 60 μl PRP clots prepared from normal or patient plasma were also comparable for SakSTAR (19 or 21 nM), whereas SK was 2-fold more potent toward PRP clots prepared from Glanzmann plasma as compared to normal plasma (C50 of 130 versus 270 nM).No significant effect of SakSTAR on platelet function was observed in plasma from patients with AMI treated with SakSTAR, as revealed by unaltered platelet count, platelet aggregation and ATP secretion.Thus, no effects of high SakSTAR concentrations were observed on human platelets in vitro, nor of therapeutic SakSTAR concentrations on platelet function in plasma.

Human Platelet Acetylcholinesterase: The Effects of Anticholinesterases on Platelet Function

1979 ◽  
Vol 42 (05) ◽  
pp. 1615-1619 ◽  
Author(s):  
Martin J Smith ◽  
Boyd Braem ◽  
Kent D Davis
Keyword(s):  
Platelet Function ◽  
Ache Activity ◽  
Room Temperature ◽  
Platelet Rich Plasma ◽  
Complete Inhibition ◽  
Clot Retraction ◽  
Plasma Clot ◽  
Normal Platelet ◽  
Aggregation Factor

SummaryPlatelet acetylcholinesterase (AChE) activity was measured in gel-filtered platelet preparations. Three different anticholinesteratic agents (eserine, neostigmine, and diiso- propylphosphorofluoridate) at final concentrations of 10 μM caused complete inhibition of AChE activity after 30 min incubation at room temperature with either platelet-rich plasma or gel-filtered platelets. Complete inhibition of platelet AChE had no effect on platelet aggregation, factor-3 availability, and plasma clot retraction. We conclude that platelet membrane AChE activity is not required for normal platelet function as measured by these in vitro parameters.

scholarly journals Are Platelet Aggregation Tests the Best Way to Assess New Drugs for Arterial Disease

2018 ◽  
Vol 1 (1) ◽  
pp. 01-03
Author(s):  
Mark I. M. Noble
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Platelet Rich Plasma ◽  
New Drugs ◽  
In Vitro Test ◽  
In Vivo Efficacy ◽  
Experimental Animals ◽  
Stenosed Artery

Over many years, laboratory testing of platelet aggregability have been carried out in attempts to develop drugs that would prevent thrombosis in arteries. The problems encountered included the question of methodology. Blood samples have to be anticoagulated in order to study the platelets. Anti-coagulation with citrate and tests on derived platelet rich plasma did not correlate at all well with thrombus growth in the stenosed coronary arteries of experimental animals and citrate removes the calcium ions which are vital for platelet function. Anticoagulation with heparin also interfered with platelet function, so that now, hirudins are the preferred anticoagulant. However it was observed that if, instead of stimulating platelet aggregation with adrenaline or ADP, serotonin was applied to the preparation, very little aggregation took place in spite of serotonin 5HT2A antagonists being the most potent inhibitors of thrombus growth in experimental animals. Another indicator that primary platelet agggregation is not a predictor of in vivo efficacy was the finding that 5HT2A antagonism inhibited aggregate growth. In a stenosed artery the platelets are activated by increased shear stress and blood turbulence with release of platelet serotonin causing positive feedback activation of more platelets. At present, there does not seem to be a bench in vitro test that accurately predicts in vivo efficacy in stenosed artery occlusive thrombosis.

Platelet Antagonists

2006 ◽  
Author(s):  
Richard C. Becker ◽  
Frederick A. Spencer
Keyword(s):  
Platelet Function ◽  
Bleeding Time ◽  
Cell Function ◽  
Light Transmission ◽  
Platelet Rich Plasma ◽  
Blood Flow Rate ◽  
Von Willebrand Disease ◽  
Platelet Glycoprotein ◽  
Primary Hemostasis ◽  
Monitoring Tools

Platelet antagonists play an important role in both primary and secondary prevention of atherothrombotic events. Despite their proven benefit, individual response (and protection) varies considerably, emphasizing the importance of developing monitoring tools (tested prospectively in clinical trials) that can better determine the degree of platelet inhibition that is both safe and effective. Platelet function studies were developed originally for the evaluation of patients with unexplained bleeding and have contributed greatly to the understanding, diagnosis, and management of hereditary abnormalities such as von Willebrand disease and Glanzmann’s thrombasthenia (platelet glycoprotein [GP] IIb/IIIa receptor deficiency). Although conventional platelet function studies (turbidimetric aggregometry) have technical limitations that preclude their routine use for gauging antithrombotic therapy, they may provide guidance when hemorrhagic complications arise and in determining pretreatment risk in individuals suspected of having an intrinsic platelet abnormality. The bleeding time, considered an indicator of primary hemostasis (platelet plug formation), is defined as the time between making a small standardized skin incision and the precise moment when bleeding stops. The test is performed with a template, through which the medial surface of the forearm is incised under 40 mmHg standard pressure. A normal bleeding time is between 6 and 10 minutes. Although considered a “standardized” test of platelet function, the bleeding time can be influenced by a variety of factors, including platelet count, qualitative abnormalities, and features intrinsic to the blood vessel wall (George and Shattil, 1991). Platelet adhesion is the initiating step in primary hemostasis. Although platelet binding is an important component of this process, there are many others, including blood flow rate, endothelial cell function, adhesive proteins, and the subendothelial matrix. The original test used for assessing adhesion, platelet retention, was based on adherence to glass bead columns. The current laboratory evaluation of platelet function is based predominantly on turbidimetric platelet aggregometry (also known as light transmission aggregometry). This test is performed by preparing platelet-rich plasma (with platelet-poor plasma as a control) and eliciting an aggregation response with adenosine diphosphate, epinephrine, collagen, arachidonic acid, and ristocetin (Born, 1962).

Platelet Function in Various Haemorrhagic Disorders

1975 ◽  
Author(s):  
T. Mandalaki ◽  
C. Dimitriadou
Keyword(s):  
Platelet Aggregation ◽  
Density Gradient ◽  
Platelet Function ◽  
Factor Xiii ◽  
Platelet Rich Plasma ◽  
Bleeding Tendency ◽  
Factor Xiii Deficiency ◽  
Haemorrhagic Diathesis

Platelet aggregation by ADP, collagen, thrombin and ristocetin was studied systematically both in citrate platelet rich plasma and isolated platelets by density gradient using albumine (according to Nicholls and Hampton) in various cases of congenital haemorrhagic diathesis, namely v. Willebrand disease, Glanzmann disease (thrombasthenia), Thrombopathy (PF3, defect), Factor XIII deficiency and in unclassified hereditary haemorrhagic disorders as well as in acquired bleeding tendency. According to the platelet abnormalities found during this study a classification of “Thrombopathies” observed in Greece is attempted.

Altered Platelet Shape Change in Hereditary Gelsolin Asp187Asn-related Amyloidosis

2000 ◽  
Vol 83 (03) ◽  
pp. 491-495 ◽  
Author(s):  
Kaija Javela ◽  
Hannu Somer ◽  
Riitta Kekomäki ◽  
Sari Kiuru
Keyword(s):  
Factor Viii ◽  
Light Transmission ◽  
Platelet Rich Plasma ◽  
Shape Change ◽  
Coagulation Factor ◽  
Coagulation Factor Viii ◽  
Bleeding Tendency ◽  
Knock Out ◽  
Ristocetin Cofactor ◽  
Platelet Shape

SummaryHereditary gelsolin-related amyloidosis (AGel amyloidosis) is a systemic disorder caused by a G654A or G654T mutation in the gene coding for gelsolin, an actin-modulating protein. Altered platelet shape change has been demonstrated in gelsolin-deficient knock-out mice, but this has not been studied in humans with gelsolin deficiency. We measured platelet shape change, characterized by maximal decrease in light transmission (D) and reaction time (T), and aggregation, associated with stimulation of platelets with different agonists in platelet rich plasma, as well as coagulation factor VIII and ristocetin cofactor activities in 20 patients, 10 healthy sibs and 20 healthy control subjects. Statistically significant alterations of parameters describing platelet shape change (D, T) were observed after stimulation with adenosine diphosphate and collagen in patients when compared to healthy subjects, but not in maximal aggregation responses, platelet counts, coagulation factor VIII or ristocetin cofactor activity levels. Patients had more haemostatic derangements. Our results suggest that, in addition to amyloid deposition, the G654A gelsolin gene defect causes altered gelsolin-mediated cellular mechanisms, which may contribute, e. g., to bleeding tendency in AGel amyloidosis patients.

Sign in / Sign up

Export Citation Format

Share Document