Musculo-skeletal pain treatment is inadequate in many haemophilic patients. Analgesics are used only by 36% of adult patients. FVIII/FIX intravenous infusion is mainly used to lessen pain, followed ...in frequency by usage of NSAIDS (primarily COX-2 inhibitors). In about 30% of patients, pain continues after infusion of F VIII/IX. In acute haemarthroses pain treatment must continue until total disappearance (checked by ultrasonography) and include haematologic treatment, short-term rest of the involved joint, cryotherapy, joint aspiration and analgesic medication (paracetamol in mild pain, metamizole for more intense pain, and in a few precise patients, soft opioids such as codeine or tramadol). In the circumstance of intolerable pain we should use morphine hydrochloride either by continual infusion or a patient-controlled analgesia (PCA) pump, determined by the age, mental condition and grade of observance of the patient. Epidural blocks utilizing bupivacaine and fentanyl may be very efficacious as well. Three main strategies to alleviate chronic musculo-skeletal pain secondary to haemophilic arthropathy (joint degeneration) exist: pharmacologic management, physical medicine and rehabilitation, and intra-articular injections. As for pharmacologic management, NSAIDs (ibuprofen, diclofenac, celecoxib, robecoxib) are better than paracetamol. The advantages of tramadol or tramadol/paracetamol and non-tramadol opioids are scanty. With respect to physical medicine and rehabilitation, there is insufficient confirmation that a brace has supplementary favourable effect compared with isolated pharmacologic management. Land-based curative exercise and watery exercise have at the minimum a tiny short-run benefit. Curative ultrasound can be helpful (poor quality of evidence). The efficacy of transcutaneous electrostimulation (TENS) for pain mitigation has not been proved. Electrical stimulation treatment can procure notable ameliorations. With respect to intra-articular injections, viscosupplementation appears to be a useful method for pain alleviation in the short-run (months). The short-run (weeks) advantage of intra-articular corticosteroids in the treatment of joint pain has been shown.
To investigate the blood coagulation function in COVID-19 patients, and the correlation between coagulopathy and disease severity.
We retrospectively collected 147 clinically diagnosed COVID-19 ...patients at Wuhan Leishenshan Hospital of Hubei, China. We analyzed the coagulation function in COVID-19 patients through the data including thrombin-antithrombin complex (TAT), α2-plasmininhibitor-plasmin Complex (PIC), thrombomodulin (TM), t-PA/PAI-1 Complex (t-PAIC), prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (APTT), fibrinogen (FIB), thrombin time (TT), D-Dimer (DD), and platelet (PLT).
The levels of TAT, PIC, TM, t-PAIC, PT, INR, FIB, and DD in COVID-19 patients were higher than health controls (p<0.05), and also higher in the patients with thrombotic disease than without thrombotic disease (p<0.05). What's more, the patients with thrombotic disease had a higher case-fatality (p<0.05). TAT, PIC, TM, t-PAIC, PT, INR, APTT, FIB, DD, and PLT were also found correlated with disease severity. Meanwhile, we found that there were significant difference in TAT, TM, t-PAIC, PT, INR, APTT, DD, and PLT in the death and survival group. Further using univariate and multivariate logistic regression analysis also found that t-PAIC and DD were independent risk factors for death in patients and are excellent predicting the mortality risk of COVID-19.
Most COVID-19 patients with inordinate coagulation systems, dynamic monitoring of coagulation parameters might be a key in the control of COVID-19 death.
The intricate process of wound healing involves replacing the cellular or tissue structure that has been destroyed. In recent years various wound dressings were launched but reported several ...limitations. The topical gel preparations are intended for certain skin wound conditions for local action. Chitosan-based hemostatic materials are the most effective in halting acute hemorrhage, and naturally occurring silk fibroin is widely utilized for tissue regeneration. So, this study was conducted to evaluate the potential of chitosan hydrogel(CHI-HYD) and chitosan silk fibroin hydrogel (CHI-SF-HYD) on blood clotting and wound healing.
Hydrogel was prepared using various concentrations of silk fibroin with guar gum as a gelling agent. The optimized formulations were evaluated for visual appearance, Fourier transforms infrared spectroscopy (FT-IR), pH, spreadability, viscosity, antimicrobial activity, HR-TEM analysis, ex vivo skin permeation, skin irritation, stability studies, and in vivo studies by using adult male Wistar albino rats.
Based on the outcome of FT-IR, no chemical interaction between the components was noticed. The developed hydrogels exhibited a viscosity of 79.2 ± 4.2 Pa.s (CHI-HYD), 79.8 ± 3.8 Pa.s (CHI-SF-HYD), and pH of 5.87 ± 0.2 (CHI-HYD), 5.96 ± 0.1 (CHI-SF-HYD). The prepared hydrogels were sterile and non-irritant to the skin. The in vivo study outcomes show that the CHI-SF-HYD treated group has significantly shortened the span of tissue reformation than other groups. This demonstrated that the CHI-SF-HYD could consequently accelerate the regeneration of the damaged area.
Overall, the positive outcomes revealed improved blood coagulation and re-epithelialization. This indicates that the CHI-SF-HYD could be used to develop novel wound-healing devices.
Blood draws for laboratory investigations are essential for patient management in neonatal intensive care units (NICU). When blood samples clot before analysis, they are rejected, which delays ...treatment decisions and necessitates repeated sampling.
To decrease the incidence of rejected blood samples taken for laboratory investigation as a result of clotted sample.
This retrospective observational study used routine data on blood draws from preterm infants collected between January 2017 and June 2019 in a 112-cot NICU in Qatar. Quality improvement interventions to reduce the rate of clotted blood samples included: awareness raising and safe sampling workshops with NICU staff, involvement of the neonatal vascular access team, development of a complete blood count (CBC) sample collection pathway, review of sample collection equipment, introducing the Tenderfoot® heel lance, establishment of benchmarks and provision of dedicated blood extraction equipment.
First attempt blood draw occurred in 10 706 cases, representing a 96.2% success rate. In 427 (3.8%) cases, the samples were clotted requiring repeat collection. The overall rate of clotted specimens decreased from 4.8% in 2017 and 2018 to 2.4% in 2019, with odds ratios of 1.42 (95% confidence interval CI 1.13-1.78, p = .002), 1.46 (95% CI 1.17-1.81, p < .001) and 0.49 (95% CI 0.39-0.63, p < .001), respectively. The majority (87%-95%) of blood samples were by venepuncture using an intravenous (IV) catheter or the NeoSafe™ blood sampling device. Heel prick sampling was the second (2%-9%) most common method. Clotted samples were most frequently associated with needle use, 228 of 427 (53%), and IV cannula, 162 of 427 (38%), with odds ratios of 4.14 (95% CI 3.34-5.13, p < .001) and 3.11 (95% CI 2.51-3.86, p < .001), respectively.
Our interventions over 3 years were associated with reduced rates of sample rejection due to clotting, and this led to improved patient experience through fewer repeated samplings.
The insights gained from this project can help to improve patient care. Interventions that reduce the rate of blood sample rejection by clinical laboratories can lead to economic savings, timelier diagnostic and treatment decisions, and contribute to an improved quality care experience for all critical care patients, irrespective of age, by reducing the need for repeated phlebotomy and the risk of related complications.
In sepsis, fibrinolysis resistance correlates with worse outcomes. Practically, rotational thromboelastometry (ROTEM) is used to report residual clot amplitude relative to maximum amplitude at ...specified times after clot formation clot lysis indices (CLIs). However, healthy individuals can exhibit similar CLIs, thus making it challenging to solely diagnose the low fibrinolytic state. Furthermore, CLI does not include the kinetics of clot formation, which can affect overall fibrinolysis. Therefore, a more nuanced analysis, such as time to attain maximal clot amplitude after reaching maximal clot formation velocity (t-AUCi), is needed to better identify fibrinolysis resistance in sepsis.
To evaluate the correlation between the degree of fibrinolytic activation and t-AUCi in healthy or septic individuals.
Whole blood (n = 60) from septic or healthy donors was analyzed using tissue factor-activated (EXTEM) and nonactivated (NATEM) ROTEM assays. Lysis was initiated with tissue-type plasminogen activator, and CLI and t-AUCi were calculated. Standard coagulation tests and plasma fibrinolysis markers (D-dimer, plasmin-α2-antiplasmin complex, plasminogen activator inhibitor type 1, and plasminogen) were also measured.
t-AUCi values decreased with increasing fibrinolytic activity and correlated positively with CLI for different degrees of clot lysis both in EXTEM and NATEM. t-AUCi cutoff value of 1962.0 seconds in EXTEM predicted low fibrinolytic activity with 81.8% sensitivity and 83.7% specificity. In addition, t-AUCi is not influenced by clot retraction.
Whole-blood point-of-care ROTEM analyses with t-AUCi offers a more rapid and parametric evaluation of fibrinolytic potential compared with CLI, which can be used for a more rapid and accurate diagnosis of fibrinolysis resistance in sepsis.
Piezo1 is a mechanosensitive cationic channel that boosts intracellular Ca
. Compression of red blood cells (RBCs) during platelet-driven contraction of blood clots may cause the activation of ...Piezo1.
To establish relationships between Piezo1 activity and blood clot contraction.
Effects of a Piezo1 agonist, Yoda1, and antagonist, GsMTx-4, on clot contraction in vitro were studied in human blood containing physiological Ca
. Clot contraction was induced by exogenous thrombin. Activation of Piezo1 was assessed by Ca
influx in RBCs and with other functional and morphologic features.
Piezo1 channels in compressed RBCs are activated naturally during blood clot contraction and induce an upsurge in the intracellular Ca
, followed by phosphatidylserine exposure. Adding the Piezo1 agonist Yoda1 to whole blood increased the extent of clot contraction due to Ca
-dependent volumetric shrinkage of RBCs and increased platelet contractility due to their hyperactivation by the enhanced generation of endogenous thrombin on activated RBCs. Addition of rivaroxaban, the inhibitor of thrombin formation, or elimination of Ca
from the extracellular space abrogated the stimulating effect of Yoda1 on clot contraction. The Piezo1 antagonist, GsMTx-4, caused a decrease in the extent of clot contraction relative to the control both in whole blood and in platelet-rich plasma. Activated Piezo1 in compressed and deformed RBCs amplified the platelet contractility as a positive feedback mechanism during clot contraction.
The results obtained demonstrate that the Piezo1 channel expressed on RBCs comprises a mechanochemical modulator of blood clotting that may be considered a potential therapeutic target to correct hemostatic disorders.
Of the new direct oral anticoagulants, direct factor Xa inhibitors are limited by the absence of a proven reversal agent. We assessed the safety, tolerability and impact on anticoagulation reversal ...of ciraparantag (PER977) alone and following a 60 mg dose of the FXa inhibitor edoxaban. Escalating, single IV doses of ciraparantag were administered alone and following a 60 mg oral dose of edoxaban in a double-blind, placebo-controlled fashion to healthy subjects. Serial assessments of the pharmacokinetics and pharmacodynamic effects of ciraparantag were performed. Eighty male subjects completed the study. Following edoxaban (60 mg), a single IV dose of ciraparantag (100 to 300 mg) demonstrated full reversal of anticoagulation within 10 minutes and sustained for 24 hours. Fibrin diameter within clots was restored to normal 30 minutes after a single dose of 100 to 300 mg ciraparantag as determined by scanning electron microscopy and change in fibrin diameter quantified by automated image analysis. Potentially related adverse events were periorbital and facial flushing and cool sensation following IV injection of ciraparantag. Renal excretion of ciraparantag metabolite was the main elimination route. There was no evidence of procoagulant activity following ciraparantag as assessed by D-dimer, prothrombin fragments 1.2, and tissue factor pathway inhibitor levels. In conclusion, ciraparantag in healthy subjects is safe and well tolerated with minor, non-dose limiting adverse events. Baseline haemostasis was restored from the anticoagulated state with doses of 100 to 300 mg ciraparantag within 10-30 minutes of administration and sustained for at least 24 hours.
Nanotechnology is proven to provide certain benefits in drug delivery by improving solubility, increasing uptake to target sites and changing pharmacokinetics profiles of traditional drugs. Since ...properties of many materials change tremendously at the nanoscale levels, nanotechnology is also being explored in various industrial applications. As such, nanoparticles are rapidly entering various areas of industry, biology and medicine. The benefits of using nanotechnology for industrial and biomedical applications are often tempered by concerns about the safety of these new materials. One such area of concern includes their effect on the immune system. While nanoparticle interactions with various constituents of the immune system have been reviewed before, little attention was given to nanoparticle effects on the blood coagulation system. Nanoparticle interface with the blood coagulation system may lead to either benefits to the host or adverse reactions. This article reviews recent advances in our understanding of nanoparticle interactions with plasma coagulation factors, platelets, endothelial cells and leukocytes. Part I is focused on desirable interactions between nanoparticles and the coagulation system, and discusses benefits of using nanotechnology to intervene in coagulation disorders. Undesirable interactions posing safety concerns are covered in part II, which will be published in the June issue of Nanomedicine.
In this paper, the microbial transglutaminase (MTGase) was used as a catalyst to graft the collagen peptide (COP) molecules on the amino group of chitosan to obtain water-soluble chitosan-collagen ...peptide (CS-COP) derivatives. The preparation of composite hydrogel was via the Schiff-base reaction between the amino of CS-COP and the aldehyde of oxidized konjac glucomannan (OKGM). The hydrogels were characterized by various techniques including Fourier transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). The results of SEM showed that the hydrogel sample had a clear and stable three-dimensional network structure. Meanwhile, these effects of the addition of OKGM on gelation time, swelling behaviors, water evaporation rate and blood coagulation capacity were investigated. The shortest gelation time for hydrogels was 99.3s. The hydrogels showed a good swelling ability and appropriate water retention capacity. The maximum swelling ratio of the hydrogel was 265%. Dynamic blood clotting test showed that the hydrogels materials had good blood coagulation capacity. Moreover, The biocompatibility of hydrogels was evaluated with NIH-3T3 cells by MTT method. The results indicated that the hydrogels exhibited better biocompatibility. Therefore, this hydrogel has a promising potential to be applied as wound dressing.
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