Rapid Assessment of Platelet Function Using Thromboelastography and Small Volumes of Citrated Whole Blood.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3995-3995 ◽  
Author(s):  
Fred G. Pluthero ◽  
Margaret L. Rand ◽  
Victor S. Blanchette ◽  
Walter H. Kahr
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Platelet Function ◽  
Whole Blood ◽  
Function Analysis ◽  
Maximum Amplitude ◽  
Ease Of Use ◽  
Platelet Response ◽  
Platelet Function Disorders ◽  
Wide Range

Abstract Platelet function disorders are a key cause of abnormal bleeding, and diagnosis is challenging because: platelet abnormalities are diverse, affecting many aspects of function; variability in platelet function testing in clinical laboratories makes it difficult to compare results; large blood volumes required for platelet function analysis make it difficult to perform in neonatal patients; manipulation of platelet rich plasma used for platelet aggregation can lead to test variability; platelet aggregation curves are difficult to interpret in thrombocytopenic patients. We describe a method of testing platelet function using citrated whole blood and thromboelastography (TEG) that overcomes some of these limitations. Commercially-available platelet mapping kits allow the effects of the platelet agonists adenosine diphosphate (ADP) and arachidonic acid (AA) to be assessed via a TEG assay where reptilase and activated factor XIII produce fibrin clots independent of thrombin in heparinized whole blood. The activation and aggregation of platelets is quantified by measuring the difference in maximum amplitude (MA) between unstimulated samples, which form weak fibrin-only clots, and samples with agonists added, which form stronger clots containing fibrin and activated/aggregated platelets. Platelet mapping was used as the basis for a TEG assay which can be used to assess platelet responses to a wide range of stimuli - including ADP, AA, epinephrine, collagen, U46619 (thromboxane-A2 receptor agonist), SFLLRN (PAR-1 thrombin receptor activating peptide) and AYPGKF (PAR-4 activating peptide) - in small samples (330μL) of citrated native (CN) blood or plasma to which heparin is added to a concentration of 20U/mL. Samples were recalcified by adding calcium chloride to 10mM (necessary for the function of reptilase and FXIIIa), and other reagent volumes were the same as in platelet mapping assays, with fibrin activator prepared at 1/2 regular strength. The concentrations of platelet agonists were: collagen 51μg/ml, epinephrine 0.27μM, ADP 5.4μM, arachidonic acid 135μg/mL, U46619 2.6μM, SFLLRN 6.76μM and AYPGKF 34μM. These concentrations produced TEG MA values in heparinated fibrin-activated CN blood from a panel of normal individuals comparable to those obtained from recalcified CN blood in the absence of heparin (the fibrin/platelet response control). The platelet response was rapid with maximum amplitudes reached within 10 minutes for all agonists except collagen, which required >30 minutes to produce maximum amplitude. We have found this TEG platelet-response assay to be useful in detecting platelet function abnormalities, producing results which correlate with and extend those of other platelet function tests. For example in one patient a weak response to epinephrine corresponded to similar platelet aggregation results, and in another the TEG assay detected a weak PAR-1 response not specifically detected in other tests. The assay has also proven useful in assessing platelet function in blood and plasma having low platelet concentrations (<50 x 10E9/L) from experimental or pathological causes (e.g. thrombocytopenia), in titrating platelet responses to agonists and in assessing the effects of antiplatelet agents in vivo and in vitro. Thus this TEG platelet function assay has the advantages of speed, ease of use, flexibility, adaptability to low platelet concentrations and sample economy, requiring small volumes of citrated blood which can be used for other coagulation assays and platelet response tests.

Dasatinib-Induced Platelet Dysfunction.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2941-2941 ◽  
Author(s):  
Alfonso Quintas-Cardama ◽  
Xin Han ◽  
Hagop Kantarjian ◽  
Jorge Cortes
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Platelet Function ◽  
Whole Blood ◽  
Function Analysis ◽  
Chronic Phase ◽  
Myelogenous Leukemia ◽  
Light Transmittance ◽  
P Value ◽  
Platelet Dysfunction

Abstract Dasatinib is efficacious and safe in patients (pts) with chronic myelogenous leukemia (CML) after imatinib failure. However, dasatinib therapy has been linked to bleeding in some pts, typically affecting mucosal surfaces. We analyzed the effect of dasatinib on basic coagulation tests and platelet aggregation function in 55 pts with CML in chronic phase at diagnosis (1), >8 weeks after tyrosine kinase inhibitor (TKI) discontinuation (3), or during therapy with the ABL/SRC inhibitors dasatinib (n=27) and bosutinib (n=12), or the aminopyrimidine derivatives imatinib (n=8) and nilotinib (n=4). Median age was 54 yrs (range, 22–80), WBC 5.5 ×109/L (range, 2.1–58.5), hemoglobin 12.2 g/dL (range, 9.7–15.1), and platelets 230 ×109/L (range, 80–746). Only 2 pts (both on imatinib and warfarin) had abnormal basic coagulation parameters (prolonged prothrombin time [PT]). In the remainder 53 pts, the median PT time was 11.6 sec (9.8–13), activated partial thromboplastin time (aPTT) 28.5 sec (range, 21–33.9), and fibrinogen level 495 mg/dL (range, 336–700), suggesting an intact secondary hemostasis. To evaluate the primary hemostasis status, platelet aggregation was measured by turbidometry in 1 mL of platelet-rich plasma upon stimulation with 5 μM of ADP, 1 μg/ml of collagen, 1 μM of epinephrine, 1 mM arachidonic acid, or 8 μL of ristocetin by using a Whole Blood Lumi-Aggregometer (Chrono-Log Corporation, Havertown, PA). Aggregation was expressed as the maximal percent change in light transmittance from baseline using platelet-poor plasma as a reference. Five (9%) patients (2 bosutinib, 1 nilotinib, and 2 imatinib) were on aspirin and showed an aspirin-like effect (decreased platelet aggregation with arachidonic acid [AA] and epinephrine [Epi]). Patients off-TKI or untreated had a normal platelet aggregation test. Results on the remaining 46 assessable patients demonstrate that dasatinib is strongly associated platelet aggregation defects, particularly an aspirin-like effect, when compared with other TKIs. Platelet function analysis by PFA-100 showed that addition of dasatinib (400 nM) to fresh whole blood obtained from a healthy volunteer rapidly induced platelet dysfunction. Closure times were prolonged from 100 sec (baseline) to >300 sec in response to Epi (normal <160 sec) but not in response to ADP (from 72 to 84 sec, normal <120 sec) after 30 min incubation. In summary, our data indicate that dasatinib does not interfere with secondary hemostasis. Rather, it inhibits platelet function in an aspirin-like manner. This effect, while independent, can be additive to dasatinib-induced thrombocytopenia and may account for the bleeding diathesis observed in pts with CML receiving dasatinib. Table 1. Effect of BCR-ABL kinase inhibitors on platelet aggregation Dasatinib Bosutinib Nilotinib or Imatinib Platelet aggregation test n=27 n=10 n=9 p value Normal (%) 4 (15) 8 (80) 6 (67) < 0.01 Abnormal (%) 23 (85) 2 (20) 3 (33) < 0.006 Only with Epi 7 1 0 With both Epi and AA 14 1 3 With all agonists 2 0 0

scholarly journals Congenital Aspirin-like Defect As a Result of Autosomal Recessive Variants in PTGS1

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1156-1156
Author(s):  
Suthesh Sivapalaratnam ◽  
Hayman Melissa ◽  
Claire Lentaigne ◽  
Melissa Chan ◽  
Marilena Crescente ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Platelet Function ◽  
Autosomal Recessive ◽  
Autosomal Dominant ◽  
Autosomal Recessive Inheritance ◽  
Recessive Inheritance ◽  
Dominant Inheritance ◽  
Platelet Function Disorders ◽  
First Time

Abstract Inherited defects of platelet function disorders are rare and difficult to diagnose due to lack of standardized platelet tests. An aspirin-like platelet defect is characterised by reduced thromboxane A2 (TXA2) signalling due to a defect in the arachidonic acid (AA) pathway in platelets. Patients with aspirin-like defect present with mild to moderate bleeding symptoms and impaired platelet aggregation responses to AA and ADP. This is similar to the irreversible effect of aspirin on platelets, which is mediated through inhibition of prostaglandin H synthase-1 also known as cyclooxygenase-1 (PTGS1/COX1). We for the first time report platelet function disorders due to autosomal recessive inheritance of variants in PTGS1. In a total of 3563 cases with bleeding disorders, comprising 1169 whole genome sequenced probands of the BRIDGE-BPD study and 2394 panel sequenced index cases of the ThromboGenomics cohort, we identified 15 unrelated cases of each cohort with an aspirin-like platelet function defect. Two of these cases had rare a variants in PTGS1, the gene encoding COX-1, which catalyses the conversion of arachidonic acid to prostaglandin H2. The first case presented with epistaxis and peri-operative bleeding. She had reduced platelet aggregation responses to arachidonic acid, ADP, collagen and epinephrine. Incubation of control blood with collagen resulted in enhanced levels of thromboxane B2, PGD2, PGE2, 11-HETE and 15-HETE which was absent in the index case.We identified a homozygous missense variant in PTGS1, p.Trp322Ser with a Combined Annotation Dependant Depletion Score (CADD) of 31.0. This variant was absent from GnomAD. The variant co-segregated in an autosomal recessive inheritance mode, with aspirin-like defect phenotype in the seven family members who were investigated. PTGS1 was not expressed on the platelets by western blot. Immunophenotyping demonstrated absence on the platelet surface but presence on neutrophils. The second case of the presented with menorrhagia, nosebleeds, easy bleeding and bruising. She had reduced aggregation responses to arachidonic acid, ADP, collagen and epinephrine. We identified two variants in cis: a splice-donor variant (g. 125133553 T>A), CADD 24.3; and an upstream non-coding variant (g. 125132069 C>G), CADD 16.63. The frequency of these variants were respectively; 1.7 x 10-5 and 8 x 10-3 in GnomAD. Platelet RNA and protein expression studies in the propositus revealed alternative splicing with the generation of a smaller protein due the splice variant. In contrast, the non coding variant had no effect on promoter or enhancer activity and therefore, is likely benign. In this case, the mode of inheritance is autosomal dominant with a dominant negative effect, which has been reported previously. For the other 13 cases of the Bridge-BPD study we also interrogated the non-coding space and interactors in the arachidonic acid pathway, none of which had genetic variants explaining the phenotype. For the 15 ThromboGenomics cohort cases because they were sequenced on targeted platform similar investigations could not take place. These cases could have a non inherited cause for the platelet defect or it is also permissible that variation in a hitherto undefined pathways unique to individual cases might be causal. In conclusion, we for the first time report autosomal recessive inheritance of variants in PTGS1 as cause for a rare inherited bleeding disorder. The effect of the mutation are selective loss of expression of PTGS1 within platelets and decreased enzyme function. Two previous reports demonstrated autosomal dominant inheritance. The first demonstrated autosomal dominant inheritance of variants in PTGS1 as modifier in a well characterized family with haemophilia A and platelet function disorder (Nance et al JTH 2016). The second reported rare heterozygous variants in PTGS1 in two cases with a bleeding tendency which was not further specified in the report (Bastida et al Haematologica 2018). Disclosures Laffan: Pfizer: Honoraria; Roche: Consultancy, Speakers Bureau.

Comparison of Rapid Platelet Function Assay with Whole Blood Platelet Impedance Aggregometry for the Definition of Aspirin Resistance.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4018-4018
Author(s):  
Anna M. Dyszkiewicz-Korpanty ◽  
Anne Kim ◽  
James D. Burner ◽  
Eugene P. Frenkel ◽  
Ravindra Sarode
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Platelet Function ◽  
Whole Blood ◽  
Platelet Rich Plasma ◽  
Blood Platelet ◽  
Aspirin Resistance ◽  
Impedance Aggregometry ◽  
Definition Of ◽  
Induced Aggregation

Abstract The reported incidence of aspirin (ASA) resistance ranges from 5 to 30%. Various platelet function assays have been employed to detect aspirin resistance in patients with cardio- and cerebrovascular disease. Such a high proposed incidence of ASA resistance poses a critical need for a rapid point-of -care (POC) platelet function test. Unfortunately, no uniformly accepted definition of ASA resistance exists. Platelet aggregation studies that have been used to define ASA resistance are time consuming and require special technical expertise. The Ultegra Rapid Platelet Function -ASA (RPFA-ASA) has been developed as a POC test that is performed without sample processing. This optical method measures agglutination of fibrinogen-coated beads upon platelet activation with arachidonic acid. In the presence of aspirin effect, however, the agglutination of the beads is inhibited. The described cutoff of ≥ 550 Aspirin Reaction Units (ARU) is termed non-responsiveness to ASA based on a preclinical study and subsequent correlation with epinephrine-induced platelet aggregation in platelet rich plasma. Since RPFA-ASA uses whole blood, we validated its performance characteristics against a classic whole blood platelet aggregation assay (WBA). We studied 50 healthy volunteers, aged 25–75 (24 men, 26 women) with normal CBC, who had not ingested anti-platelet drugs for 14 days prior to the study. Baseline studies included WBA (dual channel aggregometer, Chrono-log Inc., Havertown, PA) using both arachidonic acid (AA -0.5; 0.25 mM) and collagen (1; 2 μg/mL) as well as an RPFA-ASA assay (Accumetrics Inc., San Diego, CA). These studies were repeated after 3 days of ASA (325 mg/d) intake. Based on a review of the literature, we defined an adequate ASA response as a completely inhibited AA-induced platelet aggregation and at least 30% inhibition of collagen-induced aggregation (both concentrations of the agonist). Thus, those with &lt; 30% inhibition of aggregation response to collagen were considered ASA resistant. Eleven subjects were ASA resistant by WBA (20%; 8 females and 3 males (aged 25–63). In contrast, since all 50 subjects achieved ARU values of &lt; 550 ARU, none were recognized as an ASA non-responder by the RPFA-ASA. While the current cutoff of &lt; 550 ARU posed by the Ultegra RPFA-ASA does identify those who have taken ASA, the assay is unable to recognize ASA non-responders. Thus, based on these data, the appropriate cutoff for the recognition of ASA resistance by the RPFA-ASA should be re-adjusted to a significantly lower level to ensure appropriate assay results.

Whole Blood Impedance Aggregometry: A New Tool for Severe Inherited Platelet Disorder Diagnosis?

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5266-5266 ◽  
Author(s):  
Celine Desconclois ◽  
Vincent Valarche ◽  
Tewfik Boutekedjiret ◽  
Martine Raphael ◽  
Marie Dreyfus ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Whole Blood ◽  
Von Willebrand Disease ◽  
Fast Method ◽  
Normal Ranges ◽  
Platelet Function Disorders ◽  
Platelet Disorder ◽  
Platelet Disorders ◽  
Von Willebrand

Abstract Abstract 5266 Diagnosis and characterization of platelet function disorders may be challenging. It requires multiple laboratory data including the assessment of platelet functions. Platelet function analysis is most commonly performed using light transmission aggregometry (LTA). LTA is a time-consuming method requiring centrifugation steps and large blood volumes. It is difficult to perform in children and in cases of thrombocytopenia. In contrast, platelet aggregation in whole blood using impedancemetry (WBI) is a fast method, allows omission of centrifugation steps and performance of platelet function studies under more physiological conditions with small samples size. It is based on the change of resistance proportional to the amount of platelets sticking to two electrodes where an alternating current is applied. Multiplate® (for “multiple electrode aggregometry”, Dynabite Medical) is a new generation of WBI aggregometer using diluted blood and single-use test cells containing twin electrodes that reduce the variation of results. We have already showed the good Multiplate® performance concerning ristocetin-induced platelet aggregation in a population of 30 patients with characterized von Willebrand disease (Valarche et al, 2011). Our aim in this ongoing study was to assess the performance of WBI in patients with inherited platelet function disorders. We tested 8 patients including 2 unrelated patients with Glanzmann Thrombasthenia (GT), 2 unrelated patients with Bernard-Soulier Syndrome (BSS), 1 patient with Gray Platelet Syndrome (GPS) and 3 patients from the same family with a platelet type von Willebrand disease (PTVWD). GT, BSS, and PTVWD diagnosis were confirmed using genotyping. BSS and GPS patients had chronic thrombocytopenia. GT, BSS, GPS and 1/3 PTVWD had platelet function tests with LTA in parallel. WBI was performed on heparinized whole blood diluted at ½ in NaCl at 37°C and triggered using high (0.77 mg/mL, WBI RH) and low (0.5 mg/mL, WBI RL) final ristocetin concentrations, ADP (6.5 Âμ Mol, WBI ADP) and collagen (3.2 Âμg/mL, WBI Coll). Results were expressed in arbitrary unit (AU) corresponding to the area under the aggregation curve observed during 6 min. Normal ranges indicated in brackets were based on the mean +/− 2 SD of 30 healthy volunteers' results. Results highlighted in grey are those out of the normal ranges (Table 1).Table 1:Results of the 8 patients with inherited platelet disorders.PatientsPlatelet count (109/L)WBI RH (AU) [>500]WBI RL (AU) [<150]WBI ADP (AU) [>550]WBI Coll (AU) [>500]GT 116923441443GT 224955417ND7BSS 134371119129BSS 230254733582GPS7916217ND42PTVWD22099493ND338PTVWD231116560ND1092PTVWD2341174168ND852 All patients except those with PTVWD had decreased results with WBI. However, as expected, patients with GT had flat traces using WBI ADP and WBI Coll but normal or only decreased curves (234 – 554 AU) using WBI RH. On the opposite, BSS patients had flat traces using WBI RH but detectable curves using WBI ADP (191 – 335 AU) despite decreased platelet count. The thrombocytopenic GPS patient has a flat trace using WBI Coll and decreased WBI RH (162 AU). Members of the PTVWD family had normal results except a slightly increased result with WBI RH in 1/3 patients. Finally, LTA results performed in 6/8 patients were all in accordance with those of the WBI. In conclusion, in 8 patients with well characterized inherited platelet disorders, WBI was able to detect all abnormalities except PTVWD. In such cases, different ristocetin concentrations use might be critical to increase sensitivity. In our hands, WBI was able to discriminate disorders involving platelet glycoprotein (GP) IIb-IIIa from GP Ib-IX-V: GT patients exhibited flat traces using WBI ADP and WBI Coll, whereas patients with BSS exhibited flat traces with ristocetin. These preliminary results need to be confirmed on a larger population of patients with various characterized platelet function disorders. They suggest that WBI using the Multiplate® analyzer, which is a fast, easy and blood-preserving test, could be a valuable extra step before or in addition to the classic LTA for the diagnosis of severe inherited platelet disorders. Disclosures: No relevant conflicts of interest to declare.

scholarly journals The Role of Whole Blood Platelet Aggregation Studies in the Diagnosis of Unexplained Bleeding Tendencies

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2260-2260
Author(s):  
Nicole De Simone ◽  
Ravi Sarode ◽  
Sean Yates ◽  
Karen Matevosyan ◽  
Manasa Reddy ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Platelet Function ◽  
Whole Blood ◽  
Selective Serotonin ◽  
Impedance Method ◽  
Platelet Dysfunction ◽  
Atp Secretion ◽  
Abnormal Results

Abstract Introduction: Platelet aggregation studies (PAS) are an important and underutilized diagnostic test (due to non-availability in most clinical laboratories and the requirement to be performed within 4 hours of sample collection) used in the evaluation of unexplained mucocutaneous type of bleeding after ruling out von Willebrand disease. Platelet aggregation studies are typically performed by one of two methods: impedance method using whole blood aggregometry (WBA) and light transmission aggregometry (LTA) using platelet rich plasma (PRP). WBA confers several advantages over LTA. First, it does not require centrifugation, which not only reduces testing time by half, but also avoids platelet activation and loss of giant thrombocytes. Second, in vivo conditions are better replicated reflecting the natural milieu including red and white blood cells, which are known to affect platelet function in vivo. In addition, WBA requires smaller blood volume making testing feasible for neonates and pediatric patients. Lastly, simultaneous assessment of platelet ATP release is performed to assess secretion defects. Despite these advantages, WBA is not commonly used. Aims: To analyze our data to further support the diagnostic utility of WBA in identifying platelet dysfunction as the etiology of bleeding tendencies. Methods: A retrospective chart review of patients on whom PAS were performed between June 2011 and September 2014. Results: We performed 202 PAS on 162 patients. 82% of patients were females and the average age was 28 years (range 9 months-87 years). 24 (15%) patients were pediatric (range 9 months-18 years). 83 of 162 (51%) patients had abnormal results (52% of adults and 50% of the pediatric cases). 26 of the 162 (16%) patients had repeat studies performed. Of these patients, 77% (20/26) had reproducible findings that confirmed the previous results. 8% (2/26) had normalized platelet function after discontinuation of medications (e.g. statins, fish oil, selective serotonin reuptake inhibitor) known to induce platelet dysfunction. 15% (4/26) had different responses to agonists on repeat testing. Abnormal WBA studies revealed decreased to absent responses to various agonists described in table 1. In patients on selective serotonin release inhibitors (SSRIs), there was a spectrum of responses to agonists; the most common abnormality was global dysfunction. Abnormalities to single agonists, such as ADP and AA, were also seen in patients taking SSRIs. Non-steroidal anti-inflammatory drugs affected aggregation with arachidonic acid (AA) and AA+ADP. Statins affected aggregation with AA alone, AA+ADP and AA+ATP secretion. 3 patients had platelet dysfunction consistent with Acquired Glanzmann's Syndrome due possibly to autoantibodies in the setting of chronic lymphocytic leukemia. Conclusion: Over 50% patients tested by WBA had abnormal platelet function giving high positive predictive value for this test in a selected group of patients who otherwise would have carried a non-specific bleeding diagnosis with non-specific treatment. Table 1. Distribution of Agonists Eliciting Impaired Responses Agonists Eliciting Impaired Response Number of Studies with Abnormal Results AA+Collagen (Aspirin like defect) 27 (23%) AA+Collagen+ADP 22 (18%) AA+ADP 21 (17%) AA+Collagen+ADP+Ristocetin (Global dysfunction) 19 (15%) ADP 11 (9%) AA 7 (6%) ADP+Collagen 4 (3%) AA+ADP+Ristocetin 3 (2%) Decreased ATP Secretion 8 (7%) AA=Arachidonic Acid Disclosures No relevant conflicts of interest to declare.

Platelet Aggregation in Whole Blood - Studies with a Platelet Counting Technique - Methodological Aspects and Some Applications

1989 ◽  
Vol 61 (03) ◽  
pp. 423-428 ◽  
Author(s):  
C Falcon ◽  
J Arnout ◽  
J Vermylen
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Whole Blood ◽  
Platelet Rich Plasma ◽  
High Sensitivity ◽  
Optimal Concentration ◽  
Counting Technique ◽  
Platelet Function Disorders ◽  
Methodological Aspects ◽  
Storage Times

SummaryWe describe a method for measuring platelet aggregation in whole blood by single platelet counting. The importance of a low stirring speed (100 rpm) to obtain agonist-specific aggregation is stressed. Despite this low stirring speed, the sensitivity to agonists equals that of the turbidometric technique in platelet-rich plasma. The optimal concentration of formaldehyde for fixing the aggregates, the effects of storage times and anticoagulant are studied. Applicability to the study of platelet function inhibitors or of inherited platelet function disorders is illustrated. It is concluded that this technique, used under the appropriate conditions, combines the advantage of measuring platelet aggregation in a more physiologtc environment with the advantages of the turbidometric technique such as high sensitivity.

Effectiveness of Standard Platelet Aggregation Studies in Diagnosing Platelet Function Disorders in Adolescents With Menorrhagia

2011 ◽  
Vol 24 (2) ◽  
pp. e48-e49
Author(s):  
Lawrence Amesse ◽  
Teresa Pfaff-Amesse ◽  
William T. Gunning ◽  
Nancy Duffy ◽  
James French
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Platelet Function Disorders

scholarly journals Inhaled NO inhibits platelet aggregation and elevates plasma but not intraplatelet cGMP in healthy human volunteers

2003 ◽  
Vol 285 (2) ◽  
pp. H637-H642 ◽  
Author(s):  
Maurice Beghetti ◽  
Catherine Sparling ◽  
Peter N. Cox ◽  
Derek Stephens ◽  
Ian Adatia
Keyword(s):  
Nitric Oxide ◽  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Platelet Function ◽  
Human Platelet ◽  
Healthy Human ◽  
Human Volunteers ◽  
Independent Mechanism ◽  
Inhaled No ◽  
Maximal Extent

Effects of inhaled nitric oxide (NO) on human platelet function are controversial. It is uncertain whether intraplatelet cGMP mediates the effect of inhaled NO on platelet function. We investigated the effect of 30 ppm inhaled NO on platelet aggregation and plasma and intraplatelet cGMP in 12 subjects. We performed platelet aggregation studies by using a photooptical aggregometer and five agonists (ADP, collagen, epinephrine, arachidonic acid, and ristocetin). During inhalation, the maximal extent of platelet aggregation decreased by 75% with epinephrine ( P < 0.005), 56% with collagen ( P < 0.005), and 20% with arachidonic acid ( P < 0.05). Responses to ADP (8% P > 0.05) and ristocetin (5% P > 0.05) were unaffected. Platelet aggregation velocity decreased by 64% with collagen ( P < 0.005), 60% with epinephrine ( P < 0.05), 33% with arachidonic acid ( P < 0.05), and 14% with ADP ( P > 0.05). Plasma cGMP levels increased from 2.58 ± 0.43 to 9.99 ± 5.57 pmol/ml ( P < 0.005), intraplatelet cGMP levels were unchanged (means ± SD: 1.96 ± 0.58 vs. 2.71 ± 1.67 pmol/109platelets; P > 0.05). Inhaled NO inhibits platelet aggregation via a cGMP independent mechanism.

Modulation of platelet function by reactive oxygen metabolites

1994 ◽  
Vol 267 (1) ◽  
pp. H308-H318 ◽  
Author(s):  
G. Ambrosio ◽  
P. Golino ◽  
I. Pascucci ◽  
M. Rosolowsky ◽  
W. B. Campbell ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Platelet Function ◽  
Guanylate Cyclase ◽  
Reactive Oxygen Metabolites ◽  
Cyclic Monophosphate ◽  
Cgmp Formation ◽  
Oxygen Metabolites ◽  
Exogenous H2o2

Reactive oxygen metabolites have been reported to affect platelet aggregation. However, this phenomenon is still poorly understood. In the present study we investigated the effects of superoxide radical and hydrogen peroxide (H2O2) on platelet function in vitro and correlated those effects to possible changes of platelet concentrations of cyclic nucleotides and thromboxane, since these systems play a key role in the response of platelets to activating stimuli. Human platelets were exposed to xanthine-xanthine oxidase (X-XO), a system that generates both superoxide radicals and H2O2. Sixty seconds of incubation with X-XO impaired aggregation in response to ADP (by 48%), collagen (by 71%), or the thromboxane mimetic U-46619 (by 50%). This effect was reversible and occurred in the absence of cell damage. Impairment of aggregation in platelets exposed to X-XO was due to H2O2 formation, since it was prevented by catalase but not by superoxide dismutase. Similarly, incubation with the pure H2O2 generator glucose-glucose oxidase also markedly inhibited ADP-induced platelet aggregation in a dose-dependent fashion. Impaired aggregation by H2O2 was accompanied by a > 10-fold increase in platelet concentrations of guanosine 3',5'-cyclic monophosphate (cGMP), whereas adenosine 3',5'-cyclic monophosphate levels remained unchanged. The inhibitory role of increased cGMP formation was confirmed by the finding that H2O2-induced impairment of platelet aggregation was largely abolished when guanylate cyclase activation was prevented by incubating platelets with the guanylate cyclase inhibitor, LY-83583. Different effects were observed when arachidonic acid was used to stimulate platelets. Exposure to a source of H2O2 did not affect aggregation to arachidonate. Furthermore, in the absence of exogenous H2O2, incubation with catalase, which had no effects on platelet response to ADP, collagen, or U-46619, virtually abolished platelet aggregation and markedly reduced thromboxane B2 production (to 44% of control) when arachidonic acid was used as a stimulus. In conclusion, our data demonstrate that H2O2 may exert complex effects on platelet function in vitro. Low levels of endogenous H2O2 seem to be required to promote thromboxane synthesis and aggregation in response to arachidonic acid. In contrast, exposure to larger (but not toxic) concentrations of exogenous H2O2 may inhibit aggregation to several agonists via stimulation of guanylate cyclase and increased cGMP formation.

scholarly journals Comparison of effect of aloe Vera gel with aspirin and celecoxib on platelet aggregation.

2020 ◽  
Vol 27 (05) ◽  
pp. 973-978
Author(s):  
Sidra Mushtaq ◽  
Zobia Mushtaq ◽  
Javeria Arif ◽  
Mufakhara Fatima ◽  
Sadida Bahawal ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Whole Blood ◽  
Blood Count ◽  
Complete Blood Count ◽  
Platelet Rich Plasma ◽  
Aloe Vera ◽  
Medical Institute ◽  
Aloe Vera Gel ◽  
Study Setting

Objective: This study was designed to compare the effect of Aloe vera gel with aspirin and celecoxib on platelet aggregation. Study Design: Comparative Study. Setting: Post graduate Medical Institute Lahore, Children Hospital, Lahore. Period: September 2015 to September 2016. Material & Methods: Blood was withdrawn from anti-cubital vein, complete blood count was checked, platelet rich plasma was prepared by centrifuging citrated whole blood and then incubated with  Aloe vera low (AVL), Aloe vera high (AVH), aspirin and celecoxib for 30 minutes at 37C. After adding the agonist arachidonic acid, reading was then taken for 3 minutes and percentage aggregation was recorded. Results: Platelet aggregation with aspirin, AVH and AVL was statistically significantly lower as compared to control and celecoxib groups. Conclusion: This study has demonstrateda dose dependentanti-platelet effect of Aloe vera gel which is comparable to aspirin.

Sign in / Sign up

Export Citation Format

Share Document