Novel Platform Assays for the Diagnosis of Hemostatic Disorders: A Systematic Review

doi:10.21203/rs.3.rs-2086072/v1

Background

In hemostasis research the novel platform assays for the diagnosis of hemostatic disorders were limited. The purpose of the present review study would be to make a comparison between several assays for assessing the novel hemostatic techniques used in the diagnosis of coagulation disturbance and to point out the most advantageous and disadvantageous aspects of each method as a predictor of morbidity and mortality to determine hemostatic efficacy as well as biological safety.

Methods

The current systematic review follows the guidelines for observational studies in epidemiology and the PRISMA guidelines. The keywords were used to search the electronic databases (PubMed) (a novel platform to evaluate hemostasis). Searches were restricted to articles published between December 2016 and December 2021; original articles were written in English. To summarize, we collected bibliographies of abstract articles published on a novel platform to evaluate hemostasis studies,

Results

Following the removal of duplicates, articles were determined by examining the titles and abstracts. Disagreements were resolved through consensus and the application of novel hemostatic analysis methods. The researchers independently reviewed the relevant studies of the recognized records (n = 503), excluding duplicates (n = 9) and irrelevant studies (249). The remaining 254 studies were read in their entirety, and the data from the seven included studies had been extracted

Conclusion

Nanotechnology-Based Published study formulations discovered it is more optimal for some lab tests when expressed as an anticoagulant for the in vivo evaluation of nanoparticle implications on the complement system, and flow cytometer evaluation could be a promising platform approach for use in hemostasis managers.

Hematology

Biochemical Research Methods

Biomedical Engineering

Laboratory Diagnostics

Novel platform

hemostasis assays

diagnosis

hemostatic disorders

In hemostasis research the novel platform assays for the diagnosis of hemostatic disorders were limited. In 2005, an in vitro test cascade was constructed for assessing the immune response stability of nanomaterial and devices for hemostatic evaluations. [1] The hemostasis biomarker sequence was substantiated on 400 different nanotechnology devices, some of them not confined to liposomes, emulsified, nanostructured lipid carriers, and colloidal metals, but instead metal oxides, nano-tubes, fullerenes, and polymeric nanotechnology were considered for use in assessing hemostatic disorders. A few assays were conducted using either conventional anticoagulants or hirudins to protect the blood clotting of the healthy donated blood used in such lab tests. Earlier, a novel system for measuring hemostasis in whole blood that used T2 magnetic resonance was described (T2MR) [2]. One such technique uses limited blood volume (35 lL), is essentially simple since platelets are not really separated, and produces results in minutes. Adhesion strength, bacteria–host interaction, and healing are all critical aspects of fibronectin. In some studies, lower serum fibronectin levels are proposed as a possible disease risk for the forming of antiPF4/heparin antibodies and the development of professional HIT. Then, fibronectin suppressed the capabilities of HIT immunoglobulin to implement platelets through a variety of methods, which would include inhibition of PF4 and PF4/heparin complex formation on extracted platelets, complex disruption down regulation of antibody high affinity for PF4/heparin complexes, and decreased expression of anti-PF4/heparin antibody-induced immune activation. Furthermore, the International Society on Thrombosis and Hemostasis/Scientific and Standardization Committee ordering processes flow cytometer as more than just a method for processing when compared with routine diagnostic disorders, but it is shown to be preferred to light transmission aggregometry throughout the diagnosis and treatment of platelet activity dysfunction. [5, 6] Platelet granule identifiers, including P-selectin, are even used in the flow cytometer testing of mild routine diagnostic disorders, but involve platelet stimulation prior to the analysis. The fluorescence functionalized subset, something that joins receptor nuclei, is often used to determine the density of platelets. Several researchers have discovered reduced mepacrine fluorescence in patients with storage pool disorder (SPD) [7.8], and it is proposed to be included in such a screening methodology for routine diagnostic disorders. All the same, when ongoing fluorescent records are appealing, their success in a real-world medical setting remains to be seen, especially in comparison to routine SPD screening procedures. [9, 10] Natural resources abound in the oceans. Moreover, many marine products are derived from naturally occurring active components with specific properties, also including marine-appropriate peptides, which would be a critical feature of aquatic active ingredient analysis. According to some findings, marine active peptides have anti-microbial, hemostatic, and wound healing functions [11–13]. Oyster peptides (OP) are active substances found in marine organisms that include antiseptic peptides and angiotensin I, in order to convert enzyme inhibitor peptides and antioxidant peptides [14, 15]. In studies, it has been shown to have exceptional biological properties, including antibacterial, antioxidant, hypoglycemic, anti-aging, and anti-tumor activity [16, 17]. OP too has typical physical and chemical properties, such as various compositions, ease of adaptation, and non-toxic and non-harmful properties [14, 15]. Besides that, because of their readily available nutrition and poor bio stability, they are exposed to microorganism invasion, resulting in the loss of biological processes [18]. Platelet abnormalities should always be monitored in order to diagnose mild bleeding disorders (MBDs), which are characterized by grossly disproportionate bleeding after trauma, menorrhagia, severe and frequent mucocutaneous hemorrhage, and easy bruising [19, 20]. Although this technique has been used in diagnostic laboratories for more than four decades, it still lacks sensitivity for mild platelet function defects (PFDs) and does not predict the risk of bleeding health problems in patients with certain clinical diagnostic defects [21–26].The difficulties of transmission aggregometry may include poor standardization, but besides existing guidelines, the need for a large amount of fresh blood, the realization that it is periodical and time-consuming, and that it is not applicable for analyzing platelet count [27–32]. As a result, alternative techniques for measuring platelet aggregation have just been developed, but despite potential advantages, neither of these techniques raced with LTA in terms of bleeding diagnostics [33]. Alternative methods for providing additional data about mild platelet function defects are desperately needed. The whole normal platelet initiation test (WB-PACT), developed by Shattil et al. [34], is a flow cytometric approach that enables platelets to just be stimulated with various agonists and platelet stimulation to be quantified using different kinds of activation markers such as granule official launch, glycoprotein activation, and phospholipid expression. Because many research laboratories do not have both aggregometry and flow cytometer capabilities, records based on the agreed methodologies are as previously published [35, 36]. Using synthetic and natural polymers such as chitosan, electro spinning allows us to create three-dimensional porous and fibrous materials [37]. This method is used in biomedicine and tissue engineering in conjunction with 3D printing [38]. While the extracellular matrix is modeled by electrode position scaffolds for rapid cell proliferation and tissue regeneration [39], early literature has shown that electro-spun chitosan membranes have high blood clot-forming activity as well as biocompatibility. Furthermore, the composition of hydrogen bonds formed after chitosan dissolves in an acid solution complicates the spinning process, limiting the use of pure chitosan [40].Extra added polymers, like caprolactone (PCL), polyvinyl alcohol (PVA), or polyethylene oxide (PEO), are now used to improve chitosan spinning, reduce conductivity, or produce thinner fibers [41]. The best way to stabilize the chitosan electroprocessing route would have been to add PEO, a water-soluble synthetic polymer with good biocompatibility and low toxicity [42]. In a previous study, PEO was used, which binds to chitosan via hydrogen bonds, lowering the viscosity and interfacial of the chitosan solution. The purpose of the present review study would be to make a comparison between several assays for assessing the novel hemostatic techniques used in the diagnosis of coagulation disturbance and to point out the most advantageous and disadvantageous aspects of each method as a predictor of morbidity and mortality to determine hemostatic efficacy as well as biological safety.

Study selection

The current systematic review follows the guidelines for observational studies in epidemiology [8] and the PRISMA guidelines. Figure 1 depicts a high-level overview of the methodology. The keywords were used to search the electronic databases (PubMed) (a novel platform to evaluate hemostasis). Searches were restricted to articles published between December 2016 and December 2021; original articles were written in English. To summarize, we collected bibliographies of abstract articles published on a novel platform to evaluate hemostasis studies, and no attempts were made to contact the authors of the original articles for information. Because the included data is based on previously reported articles, no ethical approval is required for this study, and no identifying information about participants will be revealed. In this study, IBM (IBM Corp., USA) was used for statistical analysis.

Following the removal of duplicates, articles were determined by examining the titles and abstracts. Disagreements were resolved through consensus and the application of novel hemostatic analysis methods. The researchers independently reviewed the relevant studies of the recognized records (n = 503), excluding duplicates (n = 9) and irrelevant studies (249). The remaining 254 studies were read in their entirety, and the data from the seven included studies had been extracted (Figure 1 describes the search plan and screening procedures.). The incidence rate of new platforms to analyze hemostasis is summarized in Table 1 for the reported studies. The total number of patients considered in the present review (7 studies) was 216, with an absolute max of 161 patients and a minimum of 0.01 as follows: Fibronectin modulates formation (n = 42), T2 Magnetic Resonance (n = 1), Electrospun Chitosan-Based (n = 2), Flow cytometric mepacrine fluorescence (n =3), Chitosan-Based Thermo-Sensitive (n =1), and Nanotechnology-Based Formulation. The benefits of nanotechnology-based formulations as a novel platform would be optimal in vitro assays demonstrating anticoagulant for nanoparticle effects on the complement system, but less ideal and would require emphasis in test results dependent on the specific anticoagulant being used. While the flow cytometric analytical method has been used for many different measurements, specific, small amounts of blood have been required for such tests but depended on skilled personnel, increased cost, short-time reagents, complicated samples, low sensitivity tests, and short-term indicator molecules. While T2 magnetic resonance might indeed enable the identification of platelet disorders in whole blood to extend to assessments of hemostasis, it even had some disadvantages in basic analytic techniques. Other novel platforms for evaluating hemostasis used in the current studies may require further evaluation to determine their benefits and drawbacks in hemostasis assessment (Table 2).

Observing the mechanical and physical properties of clotting blood is perhaps the most effective method for monitoring blood coagulation. In fact, the formation of blood clots is monitored in order to prevent platelet aggregation from interfering with the coagulation process [43. 44]. Coagulation can also be caused by an individual's inner stimulation reagent, including ellagic acid or phospholipid [45], an extrinsic inducer solution, such as tissue factor [46], or all of these can be triggered by clotting inhibitors, such as cytochalasin D in combination with an exterior activator [47]. Previous analyses [48. 49] evaluated various point-of-care (POC) devices for test results but instead briefly described their scanning principles, although this systematic looked into other blood clotting checking methodologies. Experimental measurements of various technologies can provide biologists with ideas on the obvious benefits of certain tools in identifying disorders and future performance for clinical management and treatments. Furthermore, the role of nanotechnology in detection and diagnosis, as well as commonly available devices, future trends in checking of novel treatments, artificial intelligence in diagnostic testing, and monitoring for greater predictive value have both been explained. As a result, both industrial and academic parts have been enclosed, allowing for the filling of present gaps in blood coagulation monitoring as well as new plans for prolonged hemostasis monitoring. HIT Serum monitoring research of heparin-treated patient population’s shows that only a subset of patients develops platelet-activating anti-PF4/heparin antibodies, [50, 51] another initially described a novel T2 magnetic resonance platform for measuring hemostasis for whole blood (T2MR) requires small blood (35 lL), and was indeed basically simple, but since platelets are not separated, it actually works in minutes. [2] As a result, the aim of this systematic review would be to contrast certain novel methods for evaluating hemostasis and platelet advantages and disadvantages of this platform for evaluating blood clotting. [8, 52] Another request was made to assess the biocompatibility and hemostatic and tissue properties by using the regeneration performance of copolymers prepared by electro spinning technique in order to develop new techniques to reduce the biodegradation time of their based material properties for hemostatic application. Flow cytometer fluorescence is being used to rule out platelet dense granule shortage, but this test is time-consuming and requires a large blood volume. [53] It can also be used for the analysis of platelets as a potential alternative, but it lacks confirmation, preventing it from being used in a diagnostic setting. [54] Another of the leading causes of death in trauma emergency cases is unregulated massive hemorrhage. At a specific temperature, chitosan-based thermo-sensitive hydrogel loading oyster peptides was prepared using catechol-modified chitosan (CS-C) as the matrix material as a thermo-sensitive agent. Hemostasis performance has been measured in vivo and in vitro, as well as its biological safety. The findings revealed that hemostasis experiments, the hemostasis time, and indeed the amount of blood loss in post-operative models were improved due to the small quantities of Nano-materials usable for such studies. In vitro analysis of novel nanotechnology-based pharmaceutical formulations is of vital importance, particularly during the product development phase. Almost all immune tests necessitate the use of blood donors. [54] To perform such test results, blood must be kept from coagulating, which itself is an attachment, by adding an anticoagulant to blood testing tubes. The most widely used anticoagulants are heparin, ethylene diamine tetra acetic acid (EDTA), and citrate. [55] New anticoagulants, including hirudin, are also available but rarely used. Although certain anticoagulants may influence assay results, there is currently very little systematic correlation of traditional and novel anticoagulants in in vitro experiments aimed at immunological identification of Nano medicine formulations, whereas traditional anticoagulants, such as citrate and heparin, are more relevant for coagulation and cytokine secretion assays. The research suggests that this technology is likely to be favorable mostly in the medical field of hemostasis, and those variations in lab tests between and traditional mechanisms involving blood for nanostructures have all been observed at a time when no such results were observed with traditional controls. [56] As a result, it is critical to understand the benefits and drawbacks of each anticoagulant and to establish appropriate nanoparticles on a case-by-case basis. Introduction Light transmission aggregometry (LTA) has been the gold standard for identifying bleeding disorders and might be useful in standardizing diagnostic work-up studies. A parameter estimation that excluded single studies had no effect on the significance of this association. Several limitations of the research must be considered carefully. First, our findings are useful because of confounding factors such as patient clinical characteristics, sample size, and hemostatic defect estimation procedure. [1, 55] The aforementioned confounders, on the other hand, fully described the observed. As a result, some authors suggested that some studies have not been provided, and we have had to estimate the value based on the data. There may be small variations between the precise methodology used and the extrapolated data obtained using the laboratory method. Despite the fact that we did not impose a language restriction, only studies in English were included in the review. Subsequently, studies with insufficient data have been omitted. Besides this, several more investigations were unable to be published based on negative or null findings; these studies were indeed excluded from the current analysis. Each of these factors could play a role in the limitations encountered in this review study.

Nanotechnology-Based Published study formulations discovered it is more optimal for some lab tests when expressed as an anticoagulant for the in vivo evaluation of nanoparticle implications on the complement system, and flow cytometer evaluation could be a promising platform approach for use in hemostasis mangers. However, because of the limitations identified in the current study, the results of the systematic review may be estimated. To clarify our outcomes, linearly increasing basic study is needed in the future. One of the most serious issues with both of these novel assays would be a lack of consistency and variation in marker parameters. If we try to describe and select patient groups with different reports focusing on assay factors, the actual increase might not have been large enough here to impair clinical benefit. Several of the novel assays show improvement in terms of increased sensitivity, though their clinical efficacy remains unknown. There are various designs of each strategy, and clinical studies frequently use diverse perspectives, and assay response is heavily dependent on the procedure used. As a result, the findings of the various papers cited in this analysis may be hard to interpret and reproduce. The ongoing efforts at quality control for several of the stronger organizations mean that it can be settled mostly in the nearest future.

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Table 1: The estimated prevalence of a new platform for analyzing hemostasis in the studies investigated

Novel platform	Study	No. of Patients	Positive (%)	Negative (%)
Fibronectin modulates formation	Krystin, et al., 2019	42	18(42.8)	24(57.2)
T2 Magnetic Resonance	Adam, et al., 2016	1	1(100)	0(0.00)
Electrospun Chitosan-Based	Volodymyr, et al., 2021	2	2(100)	0(0.00)
Flow cytometric mepacrine fluorescence	Asten, et al., 2019	3	3(100)	0(0.00)
Chitosan-Based Thermo-Sensitive	Zhang, et al., 2020	1	1(100)	0(0.00)
Nanotechnology-Based Formulations	Cedrone, et al., 2018	6	5(83.3)	1(16.7)
Flow cytometric analysis	Huskens, et al., 2020	161	116(72.0)	45(28.0)

Table 2: The advantages and disadvantages of a new platform for evaluating hemostasis

Method platform	Advantages	Disadvantages
Fibronectin modulates formation	The decline in fibronectin leads to an increase in PF4, potentially immunizing PF4/heparin complexes in heparin-treated patients.	Fibronectin inhibits platelet activation by anti-PF4/heparin antibodies by interfering with the formation of PF4/heparin complexes.
T2 Magnetic Resonance	T2MR may subsequently facilitate the identification and identification of platelet disorders in whole blood, extending to global haemostatic assessments.	Basic and clinical research is required to determine that whether latest technique will provide a more biological systems and quantifiable measure of poor platelet activation.
Electrospun Chitosan-Based	Particles with significantly higher porosity also show high biocompatibility and adequate in vitro blood clotting blood interaction.	The application really wasn't useful for parenchymal bleeding because it had a lower immunogenicity with an acceptable host-tissue response.
Flow cytometric mepacrine fluorescence	It has the ability to be used in the testing of platelet dense granules.	It is not a quick screening and contains a low amount of whole blood.
Chitosan-Based Thermo-Sensitive	It rapidly takes up water and stays focused on blood, resulting in extremely rapid platelet aggregation, which can be used to identify patients with severe laboratory tests.	The safety evaluations required to ensure the specific hemostasis pathways remain a significant challenge.
Nanotechnology-Based Formulations	In vitro analysis has shown that nanoparticles have anticoagulant consequences on the signaling pathway.	It's much less ideal but also necessary to distinguish differences throughout findings depending on the nature of the anticoagulant in use.
Flow cytometric analysis	So several various measurements were recorded with this device, and only a smaller amount is required for the test.	Short-term reagents, processing conditions, higher sensitivity check, short-term highlighter molecule, specialized workers, and higher prices

Competing Interests: The authors declare no competing interests.

Novel Platform Assays for the Diagnosis of Hemostatic Disorders: A Systematic Review

Status:

Version 1

Abstract

Background

Methods

Results

Conclusion

Figures

Introduction

Methods

Study selection

Results

Discussion

Conclusion

References

Tables

Declarations

Status:

Version 1