scholarly journals Multiplate® Platelet Aggregation Findings Are Dependent on Platelet Count but Can Be Corrected by Use of a Ratio

2020 ◽  
Vol 10 (22) ◽  
pp. 7971
Author(s):  
Mohamed Soliman ◽  
Matthias Hartmann
Keyword(s):  
Platelet Count ◽  
Platelet Aggregation ◽  
Platelet Function ◽  
Platelet Rich Plasma ◽  
Platelet Aggregation Inhibitors ◽  
Impedance Aggregometry ◽  
Aggregation Inhibitors ◽  
Thrombotic Complications ◽  
Highly Correlated ◽  
Bedside Method

Impedance aggregometry (Multiplate®) detects the effects of platelet aggregation inhibitors and can predict thrombotic complications after coronary and cerebrovascular stent interventions. The bedside method uses whole blood samples not corrected for platelet count. It is claimed but not proved that the findings are unrelated to platelet count in the physiological range. We therefore investigated in the experimental study: (1) whether impedance aggregometry findings and platelet count are correlated and (2) whether the aggregation/platelet count ratio expresses platelet function independent of platelet count. Following ethics committee approval, platelet-rich plasma from healthy probands was diluted with platelet-poor plasma to obtain different platelet counts. Thereafter, platelet count was measured and samples were subjected to impedance aggregometry using thrombin receptor activating peptide (TRAP) for platelet activation. In all probands, impedance aggregometry findings and platelet count were highly correlated (r = 0.88 to 0.94; p < 0.05). The combination of all experiments revealed the proportionality between impedance aggregometry findings and platelet count (n = 31, r = 0.78, p = 0.0001). In contrast, the ratio of impedance aggregometry findings and platelet count was not significantly correlated with platelet count (r = 0.017; p = 0.3) and thus constitutes a specific measure for platelet function. In conclusion, impedance aggregometry findings subsequent to the activation with TRAP are dependent on both platelet function and platelet count. Normalization of impedance aggregometry findings for platelet count can be achieved by a ratio resulting in more specific results.

scholarly journals The MICELI (MICrofluidic, ELectrical, Impedance): Prototyping a Point-of-Care Impedance Platelet Aggregometer

2020 ◽  
Vol 21 (4) ◽  
pp. 1174 ◽  
Author(s):  
Yana Roka-Moiia ◽  
Silvia Bozzi ◽  
Chiara Ferrari ◽  
Gabriele Mantica ◽  
Annalisa Dimasi ◽  
...  
Keyword(s):  
Platelet Count ◽  
Platelet Aggregation ◽  
Platelet Function ◽  
Electrical Impedance ◽  
Platelet Rich Plasma ◽  
Point Of Care ◽  
Calcium Ionophore ◽  
Performance Comparison ◽  
Operational Performance ◽  
Impedance Aggregometry

As key cellular elements of hemostasis, platelets represent a primary target for thrombosis and bleeding management. Currently, therapeutic manipulations of platelet function (antithrombotic drugs) and count (platelet transfusion) are performed with limited or no real-time monitoring of the desired outcome at the point-of-care. To address the need, we have designed and fabricated an easy-to-use, accurate, and portable impedance aggregometer called “MICELI” (MICrofluidic, ELectrical, Impedance). It improves on current platelet aggregation technology by decreasing footprint, assay complexity, and time to obtain results. The current study aimed to optimize the MICELI protocol; validate sensitivity to aggregation agonists and key blood parameters, i.e., platelet count and hematocrit; and verify the MICELI operational performance as compared to commercial impedance aggregometry. We demonstrated that the MICELI aggregometer could detect platelet aggregation in 250 μL of whole blood or platelet-rich plasma, stimulated by ADP, TRAP-6, collagen, epinephrine, and calcium ionophore. Using hirudin as blood anticoagulant allowed higher aggregation values. Aggregation values obtained by the MICELI strongly correlated with platelet count and were not affected by hematocrit. The operational performance comparison of the MICELI and the Multiplate® Analyzer demonstrated strong correlation and similar interdonor distribution of aggregation values obtained between these devices. With the proven reliability of the data obtained by the MICELI aggregometer, it can be further translated into a point-of-care diagnostic device aimed at monitoring platelet function in order to guide pharmacological hemostasis management and platelet transfusions.

scholarly journals Influence of Hepatocellular Carcinoma on Platelet Aggregation in Cirrhosis

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1150
Author(s):  
Alberto Zanetto ◽  
Marco Senzolo ◽  
Elena Campello ◽  
Cristiana Bulato ◽  
Sabrina Gavasso ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Platelet Count ◽  
Platelet Aggregation ◽  
Platelet Function ◽  
Adenosine Diphosphate ◽  
Compensated Cirrhosis ◽  
Impedance Aggregometry ◽  
Child Class ◽  
Von Willebrand ◽  
Willebrand Factor

Hyper-functional platelets are being proposed as a potential therapeutic target in multiple cancers. Whether this can be considered in patients with cirrhosis and hepatocellular carcinoma (HCC) is unknown as their platelet function has not yet been investigated. We evaluated platelet function in cirrhosis patients with HCC. Patients with cirrhosis with and without HCC were prospectively recruited. Platelet aggregation, a marker of platelet function, was assessed by impedance aggregometry with adenosine diphosphate (ADP), arachidonic acid (ASPI), and thrombin (TRAP) stimulation. Plasmatic levels of Von Willebrand factor antigen (VWF) were also determined. One-hundred patients were recruited (50 cirrhotics with and 50 without HCC). Cirrhosis severity by Child class and platelet count were comparable between cirrhotics with and without HCC. Cirrhotics with HCC had higher ADP- (45 vs. 28; p < 0.001), ASPI- (47 vs. 28; p < 0.001), and TRAP- (85 vs. 75; p = 0.01) induced platelet aggregation than cirrhotics without HCC, all indicative of platelet hyper-function. The relatively increased platelet aggregation in patients with HCC was confirmed after adjusting the analysis for platelet count/severity of thrombocytopenia. Levels of VWF were higher in patients with vs. without HCC (348 vs. 267; p = 0.006), particularly in compensated cirrhosis. In patients with cirrhosis, HCC is associated with increased platelet aggregation and higher VWF. The clinical implications of these findings deserve further investigation.

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.

Inhibitors of Platelet Aggregation from Diverse Haematophagous and Predaceous Hirudinea from around the World.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4116-4116
Author(s):  
Roger C. Munro ◽  
Lisa J. Wakeman ◽  
Saad Al-Ismail ◽  
Andrew Beddall
Keyword(s):  
Platelet Aggregation ◽  
Salivary Glands ◽  
Platelet Rich Plasma ◽  
Platelet Aggregation Inhibitors ◽  
Autologous Plasma ◽  
Blood Sucking ◽  
Aggregation Inhibitors ◽  
Phylogenetic Affinities ◽  
Aggregation Of Platelets ◽  
Cephalic Extracts

Abstract Introduction Haematophages, animals evolved to a blood sucking lifestyle as their exclusive mode of feeding secrete compounds capable of arresting haemostasis in the host. Since the discovery and subsequent characterisation and engineering of hirudin, attention is being focused on the potential anticoagulant and platelet aggregation inhibitors from an array of different species of leech from both the Rhynchobdellid and Arhynchobdellid orders. The purpose of this study was to survey the presence of inhibitors of platelet aggregation in cephalic extracts prepared from phylogenetically diverse proboscis-bearing and jawed blood-sucking leeches compared to those which are predaceous in nature. Methods Cephalic extracts from specimens of each species were prepared by homogenising in tris buffer the anterior one-third region of the bodies containing the salivary glands. In the case of the giant leech, Haementeria ghilianii, paired anterior salivary glands were excised through the oesophagus. The posterior musculature served as control material. Homogenates were double centrifuged and supernatants micro-filtered. Individual extracts or imidazole buffer as control were pre-incubated 1:4 with platelet rich plasma for 5 minutes prior to testing for inhibition of platelet aggregation. Inducers of aggregation were: ADP (5 and 10 μM/ml), Collagen (COL) (4μg/ml), Thrombin (THR) (0.2 U/ml), Ristocetin (RIS) (1.5 mg/ml) and Adrenaline (ADR) (1 μM). Maximal aggregation responses were measured over 10 minutes. All extracts were kept on ice and tested within 1 hour of preparation. Results The species of leeches examined and maximal aggregation responses (%) after 10 minutes are shown in table 1. Maximal Responses (%) to Aggregation Inducers in Haematophagous and Predaceous Leeches Species Source ADP COL THR RIS ADR Haematophagus Haementeria ghilianii Brazil &lt;10 &lt;10 &lt;10 &lt;10 &lt;10 Oothuizobdell garoui South Africa &lt;10 &lt;10 &lt;10 20 15 Placobdella parasitica Canada 10 10 &lt;10 15 20 Hirudinaria manillensis China &lt;10 &lt;10 &lt;10 &lt;10 &lt;10 Macrobdella decora North America &lt;10 &lt;10 &lt;10 &lt;10 &lt;10 Hirudinaria javanica Indonesia &lt;10 &lt;10 &lt;10 &lt;10 &lt;10 Poecilobdella granulose India &lt;10 &lt;10 &lt;10 &lt;10 &lt;10 Myxobdella Africana Kenya 15 20 &lt;10 20 25 Hirudo medicinalis Turkey &lt;10 &lt;10 &lt;10 &lt;10 &lt;10 Predaceous Haemopis sanguisuga UK 100 100 100 100 100 Helobdella stagnalis UK 90 90 95 100 100 Erpobdella octoculata UK 100 95 95 100 100 Glossiphonia complanata UK 100 100 100 100 100 None of the extracts induced the spontaneous aggregation of platelets suspended in autologous plasma. Posterior musculatures did not inhibit platelet aggregation. Conclusion Cephalic extracts from all the haematophagous leeches examined in this study contain inhibitors of platelet aggregation. Our findings suggest that anti-haemostatic properties in Hirudinea appear to have evolved in response to biological adaptations rather than in keeping with phylogenetic affinities. Further work is required to define the precise nature of such mechanisms. These new anti-platelet properties in different species could have further potential therapeutic applications.

scholarly journals Platelet Aggregation Inhibitors from Aerial Parts of Ruta Chalepensis Grown in Jordan

2007 ◽  
Vol 2 ◽  
pp. 117863370700200 ◽  
Author(s):  
Mayadah B. Shehadeh ◽  
Fatma U. Afifi ◽  
Sawsan M. Abu-Hamdah
Keyword(s):  
Platelet Aggregation ◽  
Platelet Rich Plasma ◽  
Platelet Aggregation Inhibitors ◽  
Flavonoid Glycoside ◽  
H Nmr ◽  
Dual Channel ◽  
Ruta Chalepensis ◽  
Aerial Parts ◽  
Aggregation Inhibitors ◽  
Minor Compounds

From the aerial parts of Ruta chalepensis L., grown in Jordan, two furanocoumarins (bergapten and chalepensin), one flavonoid glycoside (rutin) as well as several minor compounds have been isolated. The structural elucidation of these compounds was established based on spectral data (UV, IR, MS, 1 H-NMR and 13 C-NMR). In Jordan, R. chalepensis is recommended for the treatment of rheumatism, mental disorders and menstrual problems. Fresh and dried leaves are used as flavoring agent in food and beverages. Antiplatelet activities of the crude methanolic and ethylacetate extracts in addition to the three isolated major compounds were measured by the aggrometric method according to Beretz and Casenave. Optical aggregometer connected to dual channel recorder was used for measuring aggregation. Both, ethylacetate and methanol extracts inhibited ADP- induced platelet aggregation (ADP-IA) of human blood. However, only ethylacetate extract was able to induce 50% inhibition of collagen-induced platelet aggregation (Co-IA) platelet rich plasma. Bergapten was more active against ADP-IA compared to chalepensin while the latter was more active against Co-IA compared to bergapten.

Thrombosis Prevention by Coagulation and Platelet Aggregation Inhibitors, in Hyperlipemic Rats

1970 ◽  
Vol 24 (03/04) ◽  
pp. 577-586 ◽  
Author(s):  
S Renaud ◽  
F Lecompte
Keyword(s):  
Platelet Aggregation ◽  
Intravenous Injection ◽  
Platelet Rich Plasma ◽  
Anticoagulant Activity ◽  
Platelet Aggregation Inhibitors ◽  
Low Doses ◽  
Antithrombotic Activity ◽  
Inhibition Of Platelet Aggregation ◽  
Aggregation Inhibitors

SummaryPhenylbutazone, oxyphenbutazone, and sulfinpyrazone were equally effective at the dosage of 100 mg/kg (per os) in inhibiting thrombin- and ADP-induced platelet aggregation in hyperlipemic rats, and in preventing the development of thrombosis initiated by the intravenous injection of an endotoxin. Despite a slight anticoagulant effect of these substances, their antithrombotic activity appears to be due mostly to inhibition of platelet aggregation.Thrombosis in hyperlipemic rats could also be prevented by a dicoumarol derivative, acenocoumarin, which only inhibits coagulation. Therefore, both platelet aggregation and fibrin formation appear to be essential for the occurrence of large thrombi under these conditions. Nevertheless, although acenocoumarin has no direct effect on platelet aggregation, it could indirectly affect this phenomenon by blocking the formation of thrombin, which is suspected of being the agent responsible for initiating thrombosis in hyperlipemic rats.Low doses of phenylbutazone and acenocoumarin, in condition, which when given alone were ineffective in inhibiting thrombosis, could decrease the severity of thrombosis by 33%. The substance GP45840, when added in vitro to platelet-rich plasma as well as given per os to hyperlipemic rats, was no more effective than sulfinpyrazone in inhibiting platelet aggregation. Nevertheless, this substance was significantly more efficient in reducing thrombosis than was sulfinpyrazone, apparently through some additional anticoagulant activity. The results of these experiments suggest that it could be beneficial to affect both coagulation and platelet aggregation in order to satisfactorily prevent thrombosis.

scholarly journals Structure Activity Relationship of 4-Amino-2-thiopyrimidine Derivatives as Platelet Aggregation Inhibitors

2019 ◽  
Vol 15 (8) ◽  
pp. 863-872 ◽  
Author(s):  
Barbara Cacciari ◽  
Pamela Crepaldi ◽  
Chun Yan Cheng ◽  
Elena Bossi ◽  
Giampiero Spalluto ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Carboxylic Acid ◽  
Platelet Rich Plasma ◽  
Arterial Occlusion ◽  
Phosphodiesterase Inhibitors ◽  
Platelet Aggregation Inhibitors ◽  
Thrombin Inhibitors ◽  
P2y12 Inhibitors ◽  
Structure Activity ◽  
Aggregation Inhibitors

Background: Platelet aggregation plays a pathogenic role in the development of arterial thrombi, which are responsible for common diseases caused by thrombotic arterial occlusion, such as myocardial infarction and stroke. Much efforts are directed toward developing platelet aggregation inhibitors that act through several mechanisms: The main antiplatelet family of COXinhibitors, phosphodiesterase inhibitors, and thrombin inhibitors. Recently, the important role in the platelet aggregation of adenosine diphosphate (ADP)-activated P2Y12 and P2Y1 receptors, Gprotein coupled receptors of the P2 purinergic family, has emerged, and their inhibitors are explored as potential therapeutic antithrombotics. P2Y12 inhibitors, i.e. clopidogrel, prasugrel, ticagrelor, and cangrelor, are already used clinically to reduce coronary artery thrombosis risk and prevent acute coronary syndromes. The search for new P2Y12 inhibitors, with better risk-to-benefit profiles is still ongoing. Methods: Several years ago, our group prepared a series of 6-amino-2-thio-3H-pyrimidin-4-one derivatives that displayed an interesting platelet aggregation inhibiting activity. In order to probe the structure-activity relationships and improve their inhibitory effects of these compounds, we synthesized variously substituted 6-amino-2-thio-3H-pyrimidin-4-one derivatives and substituted 4-amino-2-thiopyrimidine-5-carboxylic acid analogues. All the synthesized compounds were tested by light trasmission aggregometry (LTA) as inducers or inhibitors of platelet aggregation in citrated platelet-rich plasma (PRP). Results: Among the 6-amino-2-thio-3H-pyrimidin-4-one derivatives, compounds 2c and 2h displayed marked inhibitory activity, with a capability to inhibit the ADP(10-6M)-induced platelet aggregation by 91% and 87% at 10-4M concentration, respectively. Selected 4-amino-2- thiopyrimidine-5-carboxylic acid derivatives were tested as P2Y12 and P2Y1 antagonists and found to display negligible activity. Conclusion: These negative findings demonstrated that this heterocyclic nucleus is not a useful common pharmacophore for developing P2Y-dependent inhibitors of platelet aggregation. Nevertheless, compounds 2c and 2h could represent a new chemotype to further develop inhibitors of platelet aggregation.

Enhancement of ADP-induced Platelet Aggregation by Adrenaline in Vivo and Its Prevention

1973 ◽  
Vol 29 (02) ◽  
pp. 490-498 ◽  
Author(s):  
Hiroh Yamazaki ◽  
Itsuro Kobayashi ◽  
Tadahiro Sano ◽  
Takio Shimamoto
Keyword(s):  
Platelet Count ◽  
Platelet Aggregation ◽  
Platelet Rich Plasma ◽  
The Other ◽  
Endothelial Surface ◽  
Important Interaction ◽  
Blood Coagulability ◽  
The Difference

SummaryThe authors previously reported a transient decrease in adhesive platelet count and an enhancement of blood coagulability after administration of a small amount of adrenaline (0.1-1 µg per Kg, i. v.) in man and rabbit. In such circumstances, the sensitivity of platelets to aggregation induced by ADP was studied by an optical density method. Five minutes after i. v. injection of 1 µg per Kg of adrenaline in 10 rabbits, intensity of platelet aggregation increased to 115.1 ± 4.9% (mean ± S. E.) by 10∼5 molar, 121.8 ± 7.8% by 3 × 10-6 molar and 129.4 ± 12.8% of the value before the injection by 10”6 molar ADP. The difference was statistically significant (P<0.01-0.05). The above change was not observed in each group of rabbits injected with saline, 1 µg per Kg of 1-noradrenaline or 0.1 and 10 µg per Kg of adrenaline. Also, it was prevented by oral administration of 10 mg per Kg of phenoxybenzamine or propranolol or aspirin or pyridinolcarbamate 3 hours before the challenge. On the other hand, the enhancement of ADP-induced platelet aggregation was not observed in vitro, when 10-5 or 3 × 10-6 molar and 129.4 ± 12.8% of the value before 10∼6 molar ADP was added to citrated platelet rich plasma (CPRP) of rabbit after incubation at 37°C for 30 second with 0.01, 0.1, 1, 10 or 100 µg per ml of adrenaline or noradrenaline. These results suggest an important interaction between endothelial surface and platelets in connection with the enhancement of ADP-induced platelet aggregation by adrenaline in vivo.

A Comparison of the Effect of Decorsin and Two Disintegrins, Albolabrin and Eristostatin, on Platelet Function

1995 ◽  
Vol 74 (05) ◽  
pp. 1316-1322 ◽  
Author(s):  
Mary Ann McLane ◽  
Jagadeesh Gabbeta ◽  
A Koneti Rao ◽  
Lucia Beviglia ◽  
Robert A Lazarus ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Sequence Similarity ◽  
Platelet Aggregation Inhibitors ◽  
Antiplatelet Drug ◽  
Rgd Sequence ◽  
Fibrinogen Receptor ◽  
Activated Platelets

SummaryNaturally-occurring fibrinogen receptor antagonists and platelet aggregation inhibitors that are found in snake venom (disintegrins) and leeches share many common features, including an RGD sequence, high cysteine content, and low molecular weight. There are, however, significant selectivity and potency differences. We compared the effect of three proteins on platelet function: albolabrin, a 7.5 kDa disintegrin, eristostatin, a 5.4 kDa disintegrin in which part of the disintegrin domain is deleted, and decorsin, a 4.5 kDa non-disintegrin derived from the leech Macrobdella decora, which has very little sequence similarity with either disintegrin. Decorsin was about two times less potent than albolabrin and six times less potent than eristostatin in inhibiting ADP- induced human platelet aggregation. It had a different pattern of interaction with glycoprotein IIb/IIIa as compared to the two disintegrins. Decorsin bound with a low affinity to resting platelets (409 nM) and to ADP-activated platelets (270 nM), and with high affinity to thrombin- activated platelets (74 nM). At concentrations up to 685 nM, it did not cause expression of a ligand-induced binding site epitope on the (β3 subunit of the GPIIb/IIIa complex. It did not significantly inhibit isolated GPIIb/IIIa binding to immobilized von Willebrand Factor. At low doses (1.5-3.0 μg/mouse), decorsin protected mice against death from pulmonary thromboembolism, showing an effect similar to eristostatin. This suggested that decorsin is a much more potent inhibitor of platelet aggregation in vivo than in vitro, and it may have potential as an antiplatelet drug.

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