Effect of different anticoagulants and antiplatelets on intraoral bleeding time during professional oral hygiene session.

OBJECTIVE: Patients with thromboembolic problems, prosthetic valves, or coagulation issues are commonly prescribed anticoagulants and antiplatelets. Anticoagulant and antiplatelet medication might constitute a challenge for dentists and dental hygienists since possible prolonged bleeding might interfere with dental procedures. The aim of the present study was to examine the bleeding durations associated with various anticoagulants and antiplatelets during professional dental hygiene sessions, utilizing a modified Ivy test adapted for the oral context. MATERIALS AND METHODS: Ninety-three consecutive patients undergoing professional oral hygiene were recruited. Debridement during oral hygiene was performed using ultrasonic mechanical instrumentation, and bleeding sites were assessed and treated with gentle pressure using sterile gauzes. The time for bleeding cessation was recorded. Patients were categorized into six groups based on their drug intake, Control: no anticoagulants or antiplatelets DTI: direct thrombin inhibitors (dabigatran) AntiXa: directa factor Xa inhibitors (endoxaban, apixaban, rivaroxaban) VKA: vitamin K antagonists (warfarin, acenocoumarol) SAPT: single anti-platelet therapy (acetylsalicylic acid or clopidogrel) DAPT: dual anti-platelet therapy (acetylsalicylic acid and clopidogrel). Bleeding time was measured in seconds and mean values were assessed among the different groups. Differences between groups were investigated with Kruskal-Wallis test followed by Dunn's post-hoc correction for multiple comparisons or two-way ANOVA followed by Dunnett post-hoc; RESULTS: Control patients presented the lowest bleeding time 50 s, followed by AntiXa (98), SAPT (105), DTI (120), DAPT (190) and VKA (203). A statistically significant difference was present among control and DTI (p = 0.004), VKA (p < 0.001), DAPT (p < 0.001). CONCLUSIONS: Based on the present outcomes, an increased risk of prolonged bleeding emerged in patients taking VKA and DAPT. CLINICAL SIGNIFICANCE: bleeding did not interfere with the oral hygiene session The optimal period for dental treatment of these patients should be 2-3 h before the next dose, without the need to temporarily suspend the medication.

Trauma patients have reduced ex vivo flow-dependent platelet hemostatic capacity in a microfluidic model of vessel injury.

Trauma is the leading cause of death in individuals up to 45 years of age. Alterations in platelet function are a critical component of trauma-induced coagulopathy (TIC), yet these changes and the potential resulting dysfunction is incompletely understood. The lack of clinical assays available to explore platelet function in this patient population has hindered detailed understanding of the role of platelets in TIC. The objective of this study was to assess trauma patient ex vivo flow-dependent platelet hemostatic capacity in a microfluidic model. We hypothesized that trauma patients would have flow-regime dependent alterations in platelet function. Blood was collected from trauma patients with level I activations (N = 34) within 60 min of hospital arrival, as well as healthy volunteer controls (N = 10). Samples were perfused through a microfluidic model of injury at venous and arterial shear rates, and a subset of experiments were performed after incubation with fluorescent anti-CD41 to quantify platelets. Complete blood counts were performed as well as plasma-based assays to quantify coagulation times, fibrinogen, and von Willebrand factor (VWF). Exploratory correlation analyses were employed to identify relationships with microfluidic hemostatic parameters. Trauma patients had increased microfluidic bleeding times compared to healthy controls. While trauma patient samples were able to deposit a substantial amount of clot in the model injury site, the platelet contribution to microfluidic hemostasis was attenuated. Trauma patients had largely normal hematology and plasma-based coagulation times, yet had elevated D-Dimer and VWF. Venous microfluidic bleeding time negatively correlated with VWF, D-Dimer, and mean platelet volume (MPV), while arterial microfluidic bleeding time positively correlated with oxygenation. Arterial clot growth rate negatively correlated with red cell count, and positively with mean corpuscular volume (MCV). We observed changes in clot composition in trauma patient samples reflected by significantly diminished platelet contribution, which resulted in reduced hemostatic function in a microfluidic model of vessel injury. We observed a reduction in platelet clot contribution under both venous and arterial flow ex vivo in trauma patient samples. While our population was heterogenous and had relatively mild injury severity, microfluidic hemostatic parameters correlated with different patient-specific data depending on the flow setting, indicating potentially differential mechanistic pathways contributing to platelet hemostatic capacity in the context of TIC. These data were generated with the goal of identifying key features of platelet dysfunction in bleeding trauma patients under conditions of flow and to determine if these features correlate with clinically available metrics, thus providing preliminary surrogate markers of physiological platelet dysfunction to be further studied across larger cohorts. Future studies will continue to explore those relationships and further define mechanisms of TIC and their relationship with patient outcomes.

Roselle Calyx (Hibiscus sabdariffa L.) Ethyl Acetate Fraction Lowering Malondialdehyde and TNF-α and Reducing Hypercoagulability in Diabetic Model.

INTRODUCTION: Traditionally and empirically, Hibiscus sabdariffa L. has been used in treating diabetes mellitus due to its antioxidant activity. This study aimed to investigate the effect of administering the ethyl acetate fraction of hibiscus calyxes (EAFHCs) on malondialdehyde (MDA) levels, tumor necrosis factor-α (TNF-α) levels, bleeding time, and platelet count in male white rats induced with streptozotocin-induced diabetes. METHOD: Thirty-six Wistar Kyoto rats were induced with intraperitoneal streptozotocin at 55 mg/kg BW and stabilized for 5 days to obtain diabetic conditions. Diabetic animals were divided into four groups; the diabetic group was given vehicle, the glibenclamide group was given 0.45 mg/kg BW of glibenclamide, and two groups were administered the EAFHCs at doses of 100 mg/kg BW and 200 mg/kg BW for 5 days. Subsequently, the MDA, TNF-α, bleeding time and platelet count levels were examined on days 1, 3, and 5, respectively. All data were analyzed using two-way ANOVA followed by the Duncan Multiple Range Test (DMRT). RESULTS: EAFHC significantly reduced MDA and TNF-α levels (p < 0.05). Additionally, this fraction appeared to shorten bleeding time and decrease platelet count in diabetic rats. Administration of the EAFHC for 5 days effectively lowered MDA and TNF-α levels significantly, decreased platelet counts and prolonged coagulation (p < 0.05) in diabetic rats. CONCLUSION: This study demonstrates that EAFHC effectively reduces MDA and TNF-α levels and reduces the risk of hypercoagulability in diabetic model.

Icaritin Sensitizes Thrombin- and TxA2-Induced Platelet Activation and Promotes Hemostasis via Enhancing PLCγ2-PKC Signaling Pathways.

BACKGROUND: Vascular injury results in uncontrollable hemorrhage in hemorrhagic diseases and excessive antithrombotic therapy. Safe and efficient hemostatic agents which can be orally administered are urgently needed. Platelets play indispensable roles in hemostasis, but there is no drug exerting hemostatic effects through enhancing platelet function. METHODS: The regulatory effects of icaritin, a natural compound isolated from Herba Epimedii, on the dense granule release, thromboxane A2 (TxA2) synthesis, α-granule release, activation of integrin αIIbß3, and aggregation of platelets induced by multiple agonists were investigated. The effects of icaritin on tail vein bleeding times of warfarin-treated mice were also evaluated. Furthermore, we investigated the underlying mechanisms by which icaritin exerted its pharmacological effects. RESULTS: Icaritin alone did not activate platelets, but significantly potentiated the dense granule release, α-granule release, activation of integrin αIIbß3, and aggregation of platelets induced by thrombin and U46619. Icaritin also shortened tail vein bleeding times of mice treated with warfarin. In addition, phosphorylated proteome analysis, immunoblotting analysis, and pharmacological research revealed that icaritin sensitized the activation of phospholipase Cγ2 (PLCγ2)-protein kinase C (PKC) signaling pathways, which play important roles in platelet activation. CONCLUSION: Icaritin can sensitize platelet activation induced by thrombin and TxA2 through enhancing the activation of PLCγ2-PKC signaling pathways and promote hemostasis, and has potential to be developed into a novel orally deliverable therapeutic agent for hemorrhages.

A Critical Reappraisal of the Bleeding Time.

Seminars in Thrombosis and Hemostasis (STH) celebrates 50 years of publishing in 2024. To celebrate this landmark event, STH is republishing some archival material. This manuscript represents the second most highly cited paper ever published in STH. The manuscript published without an abstract, and essentially represented a State of the Art Review on the bleeding time, a relatively invasive procedure that required an incision on the skin or earlobe of a patient, and timing how long it took for the incision to stop bleeding. The bleeding time test was first described in 1901 by the French physician Milian, who presented three studies of bleeding from stab wounds made in the fingertips of healthy and diseased subjects. In 1910, Duke observed the duration of bleeding from small incisions of the ear lobe, and pointed out that the duration of bleeding was increased in instances of reduced platelet counts. The test was subsequently repeatedly modified, and numerous variants of the test, including semiautomated methods, were described by several workers. The most frequently utilised test reflected one described by Ivy and coworkers, who shifted the location of the incision to the volar aspect of the forearm and applied a blood pressure cuff to the arm to maintain a standard venous pressure. The bleeding time has been proposed for use as a diagnostic test for platelet-related bleeding disorders, a measure of efficacy in various forms of therapy, and as a prognosticator of abnormal bleeding. The authors to the current review reevaluated the bleeding time literature using methods to assess the performance of the test in 1990, locating 862 printed documents that discussed the bleeding time, the majority in peer-reviewed professional journals. As this is a republication of archival material, transformed into a modern format, we apologise in advance for any errors introduced during this transformation.

Clinical Comparison of Vascular Bleeding Time Creep Between Osseodensification and Conventional Drilling of Implant Osteotomy Sites.

This study compared the onset of vascular bleeding between osseodensification and conventional drilling of implant osteotomy sites. Patients with type III trabecular bone requiring a single missing tooth replacement were included and allocated to either Group A (test) or Group B (control). In Group A, the osseodensification group (OD), an implant osteotomy was carried out using Densah Burs (Versah) in the counterclockwise direction; in Group B, the standard drilling group (SD), Densah Burs were run in the clockwise direction. An endoscope was introduced into the osteotomy to visualize and measure the time taken for initiation of bleeding (BI) and for blood to fill the osteotomy site (BF). A total of 40 osteotomy sites (23 in the maxilla and 17 in the mandible) were included in this cross-sectional study. The mean age of study participants was 50.1 ± 8.28 years. The mean BI time for Groups A and B was 18.54 ± 2.48 seconds and 16.89 ± 1.92 seconds, respectively (P = .02); the mean BF time for Groups A and B was 41.92 ± 3.19 seconds and 37.95 ± 2.73 seconds, respectively (P < .001). Osseodensification does not seem to negatively affect or induce loss of bone vascularity. Clinicians should note that osseodensified sites might take slightly longer to fill with blood following an osteotomy.

Individual phosphatidylinositol transfer proteins have distinct functions that do not involve lipid transfer activity.

Platelets use signal transduction pathways facilitated by class I phosphatidylinositol transfer proteins (PITPs). The 2 mammalian class I PITPs, PITPα and PITPß, are single PITP domain soluble proteins that are encoded by different genes and share 77% sequence identity, although their individual roles in mammalian biology remain uncharacterized. These proteins are believed to shuttle phosphatidylinositol and phosphatidylcholine between separate intracellular membrane compartments, thereby regulating phosphoinositide synthesis and second messenger formation. Previously, we observed that platelet-specific deletion of PITPα, the predominantly expressed murine PITP isoform, had no effect on hemostasis but impaired tumor metastasis formation and disrupted phosphoinositide signaling. Here, we found that mice lacking the less expressed PITPß in their platelets exhibited a similar phenotype. However, in contrast to PITPα-null platelet lysates, which have impaired lipid transfer activity, PITPß-null platelet lysates have essentially normal lipid transfer activity, although both isoforms contribute to phosphoinositide synthesis in vitro. Moreover, we found that platelet-specific deletion of both PITPs led to ex vivo platelet aggregation/secretion and spreading defects, impaired tail bleeding, and profound tumor dissemination. Our study also demonstrated that PITP isoforms are required to maintain endogenous phosphoinositide PtdInsP2 levels and agonist-stimulated second messenger formation. The data shown here demonstrate that the 2 isoforms are functionally overlapping and that a single isoform is able to maintain the homeostasis of platelets. However, both class I PITP isoforms contribute to phosphoinositide signaling in platelets through distinct biochemical mechanisms or different subcellular domains.

Chymase Inhibition Resolves and Prevents Deep Vein Thrombosis Without Increasing Bleeding Time in the Mouse Model.

Background Deep vein thrombosis (DVT) is the primary cause of pulmonary embolism and the third most life-threatening cardiovascular disease in North America. Post-DVT anticoagulants, such as warfarin, heparin, and direct oral anticoagulants, reduce the incidence of subsequent venous thrombi. However, all currently used anticoagulants affect bleeding time at various degrees, and there is therefore a need for improved therapeutic regimens in DVT. It has recently been shown that mast cells play a crucial role in a DVT murine model. The underlying mechanism involved in the prothrombotic properties of mast cells, however, has yet to be identified. Methods and Results C57BL/6 mice and mouse mast cell protease-4 (mMCP-4) genetically depleted mice (mMCP-4 knockout) were used in 2 mouse models of DVT, partial ligation (stenosis) and ferric chloride-endothelial injury model of the inferior vena cava. Thrombus formation and impact of genetically repressed or pharmacologically (specific inhibitor TY-51469) inhibited mMCP-4 were evaluated by morphometric measurements of thrombi immunochemistry (mouse and human DVT), color Doppler ultrasound, bleeding times, and enzymatic activity assays ex vivo. Recombinant chymases, mMCP-4 (mouse) and CMA-1 (human), were used to characterize the interaction with murine and human plasmin, respectively, by mass spectrometry and enzymatic activity assays. Inhibiting mast cell-generated mMCP-4, genetically or pharmacologically, resolves and prevents venous thrombus formation in both DVT models. Inferior vena cava blood flow obstruction was observed in the stenosis model after 6 hours of ligation, in control- but not in TY-51469-treated mice. In addition, chymase inhibition had no impact on bleeding times of healthy or DVT mice. Furthermore, endogenous chymase limits plasmin activity in thrombi ex vivo. Recombinant mouse or human chymase degrades/inactivates purified plasmin in vitro. Finally, mast cell-containing immunoreactive chymase was identified in human DVT. Conclusions This study identified a major role for mMCP-4, a granule-localized protease of chymase type, in DVT formation. These findings support a novel pharmacological strategy to resolve or prevent DVT without affecting the coagulation cascade through the inhibition of chymase activity.

Effect of the arterial needle bevel position on puncture pain and postremoval bleeding time in hemodialysis patients: A self-controlled, single-blind study.

AIM: This study aimed to investigate the effect of the bevel orientation (facing upwards or downwards towards the skin) of the needle inserted into the arterial limb of the arteriovenous fistula (AVF) on puncture pain and postremoval bleeding time. METHODS: This study, using a single-blind crossover design, was conducted on 35 maintenance hemodialysis patients who had been dialyzed for at least 6 months and in whom blood access was via an AVF. AVF cannulation was performed with the needle bevel pointing upward in the first six sessions and the needle bevel pointing downwards (towards the skin) in the subsequent six sessions. Needles were always inserted in the direction of blood flow. At each dialysis session, cannulation pain was measured using a visual analog scale (VAS), and the bleeding time at the end of dialysis after needle removal was recorded. FINDINGS: The VAS score and postremoval bleeding time were lower when the needle bevel pointed downwards towards the skin during insertion (P < 0.05). DISCUSSION: Insertion of the needle with the bevel pointed downward decreased puncture pain during cannulation and bleeding time postdialysis on needle removal.

Determination of bleeding time by hounsfield unit values in computed tomography scans of patients diagnosed with intracranial hemorrhage: Evaluation results of computed tomography scans of 666 patients.

OBJECTIVE: Determining the bleeding time in intracranial hemorrhage patients is one of the most critical parameters in determining the surgical or medical treatment method. Since these are trauma patients, they are essential patients in forensic medicine. In patients where the bleeding time cannot be determined, HU value measurements in CT scans can provide quantitative data. In the radiological follow-up of the patients, only the follow-up of the bleeding volume may be misleading. METHODS: CT scans of patients diagnosed with epidural, acute subdural, and intracerebral hematoma between 2016 and 2021 were evaluated. CT scans were examined in the first 2 h, 2-6 h, 6-12 h, 12-24 h, 24-36 h, 36-48 h, 48-72 h, and 72-96 h. Each time interval obtained the lowest, highest, and average HU values. HU value ranges were defined as the heterogeneity index within the same CT scan. RESULTS: CT scans of 666 patients were evaluated. In patients with extra-axial hematoma, it was determined that the heterogeneity index increased over time. It was observed that the HU value decreased most slowly in the central part in intra-axial hemorrhages. CONCLUSIONS: HU value measurements in CT imaging can provide quantitative bleeding time and process data. Evaluating only the volumetric increase of the hematoma radiologically may cause erroneous results. HU value measurements are the most rational indicator of new bleeding.

An Investigation of ABO Blood Type and the Platelet Delta Granule Storage Pool.

Individuals with bleeding tendencies are more likely to have blood type O than blood types A, B, or AB. Platelet storage pool deficiencies are a lesser-known group of bleeding disorders which often go undiagnosed and may account for a significant number of patients with unexplained bleeding defects. We hypothesized that patients with platelet δ-storage pool deficiency might also have a predominance of type O blood. A retrospective review of medical records of 2,020 patients with unexplained bleeding and evaluated for δ-storage pool deficiency was performed. Correlations between dense granule numbers, blood type, and von Willebrand factor were analyzed for statistical differences. 51.5% of blood samples were blood type O compared to an incidence of 44.0% in the U.S. population. There was a significant association of vWF and blood type O but not with the delta storage pool. There is a preponderance of blood type O in the study population compared to the U.S. population. There is no statistically significant link between blood type O and lower dense granule numbers in this study.

Clopidogrel-herb Interactions: A Pharmacokinetic and Pharmacodynamic Assessment in a Rat Model.

BACKGROUND: Herbs usually contain a mixture of biologically active constituents, which can interact with numerous prescribed drugs and alter their safety profiles. OBJECTIVES: The current investigation was aimed to evaluate the effect of commonly used herbal products including black seed (Nigella sativa), garden cress (Lepidium sativum), and fenugreek (Trigonella foenum-graecum) on the pharmacokinetics and pharmacodynamics of clopidogrel using a Wistar rat model. METHODS: A GC-MS analysis revealed the presence of several phytoconstitutents (polyphenols) in the extracts of black seed, garden cress, and fenugreek. These polyphenols have the potential to interfere with clopidogrel effect. Plasma concentrations of clopidogrel were measured at different time points in the absence and presence of the concurrent use of tested herbal products and the pharmacokinetic parameters were calculated. Bleeding time was measured in various groups as a measure of the antiplatelet effect of clopidogrel. RESULTS: Area under the plasma concentration-time curves (AUC0-∞) of clopidogrel were 35.53 ±0.89 µg/ml*h (p<0.05), 26.01 ±0.90 µg/ml*h (p>0.05) and 32.80 ±2.51 µg/ml*h (p<0.05) in the black seed, garden cress and fenugreek group, respectively, compared with that of the control group (27.02 ±0.42 µg/ml*h). Treatment with black seed also caused an increase in clopidogrel Cmax by 31.52% (p<0.05) and with fenugreek by 21.42% (p<0.05); Cmax, did not changed with garden cress treatment (6.48 ±0.15 µg/ml versus 6.12 ±0.21 µg/ml, p>0.05). The pharmacodynamic evaluation of the antiplatelet effect of clopidogrel in the presence of herbal products treatment showed a significant prolongation in the bleeding time from a control baseline by ~22-26%, and by added ~8-12% in reference to clopidogrel therapeutic effect (p<0.05). CONCLUSION: The concurrent use of black seed, fenugreek, or garden cress can alter the pharmacokinetics and pharmacodynamics of clopidogrel to varying degrees due to the presence of various bioactive polyphenols. This is probably due to changes in drug disposition and its antiplatelet action. Further confirmation can determine the clinical relevance of these observations and identify the exact constituents responsible for such activities.

Hemostasia en fístulas arteriovenosas: comparación de la presión manual con la ejercida por un dispositivo regulable / Hemostasis of arteriovenous fistula: Comparison of direct two-finger pressure to an adjustable device

Antecedentes y objetivo: Valorar la presión generada por una pinza ajustable en fístulas arteriovenosas (FAV) durante el proceso de hemostasia y compararla con la generada por la compresión manual. Evaluar las variaciones de la compresión manual durante el proceso de hemostasia. Métodos: Se analizaron los datos de 51 sesiones de hemodiálisis de 15 pacientes. Se utilizó la presión intraacceso como indicador indirecto de la presión generada por ambos métodos sobre la FAV. La misma se registró antes de retirar la aguja venosa (PBasal), tras retirar la aguja y colocar la pinza (P1), tras ajustar la pinza (P2), al comenzar el paciente a ejercer compresión manual (M0), a los 3min del inicio de la presión manual (M3) y a los 6min del inicio de la presión manual (M6). Resultados: La presión intraacceso fue menor al aplicar la pinza y ajustarla (P2) que al aplicar presión manual (M0), con una diferencia media de −9,43mmHg (variación −18,57%, IC95%: −14,09 a −4,77mmHg, p<0,001). La presión manual mostró una tendencia descendente durante el proceso de hemostasia (M3-M0: −8,82mmHg, p<0,001; M6-M0: −12,55mmHg, p<0,001). Conclusión: La compresión ejercida por una pinza ajustable es inferior o similar a la ejercida de forma manual por el paciente. Esta última muestra una intensidad decreciente durante el proceso de hemostasia. Estos datos sugieren que algunas de las premisas sobre las que se basan algunas de las recomendaciones presentes en las guías clínicas podrían ser imprecisas. (AU)

Background and objectives: To evaluate the pressure generated by an adjustable hemostasis clamp on arteriovenous fistulas (AVF) during the hemostasis proccess, and compare it with the direct two-finger pressure applied by the patient. To evaluate the variations of the direct two-finger pressure along the hemostasis process. Methods: We analyzed data obtained in 51 hemodialysis procedures from 15 patients. AVF intra-access pressure was used as indirect indicator of the pressure generated by both methods. It was recorded before venous needle removal (PBasal), at clamp application (P1), after clamp adjustement by a nurse (P2), at the beginning of the direct two-finger pressure by the patient (M0), after 3min of two-finger pressure (M3) and after 6min of two-finger pressure (M6). Results: Intra-access pressure was lower with the adjusted clamp (P2) than with the direct two-finger pressure by the patient (M0) (variation of −18.57%, 95%CI: −14.09 to −4.77mmHg, P<.001). Intra-access pressure generated by the direct two-finger pressure method showed a decreasing trend along the hemostasis process (M3-M0: −8.82mmHg, P<.001; M6-M0: −12.55mmHg, P<.001). Conclusion: An adjustable fistula arm clamp generates a lower pressure in AVF than the direct two-finger pressure applied by the patient. The latter showed a decreasing trend along the hemostasis process. These data suggest that some of the recommendations from clinical guidelines could be based on inaccurate premises. (AU)

Characterization of the spontaneous degenerative mitral valve disease in FVB mice.

BACKGROUND: The development of new non-surgical treatments dedicated to mitral valve degeneration is limited by the absence of relevant spontaneous and rapidly progressing animal experimental models. ANIMALS: We characterized the spontaneous mitral valve degeneration in two inbred FVB mouse strains compared to C57BL/6J and investigated a contribution of the serotonergic system. METHODS: Males and females FVB/NJ and FVB/NRj were compared to the putative C57BL/6J control at 12, 16, 20 and 24 weeks of age. Body weight, systolic blood pressure, heart rate, urinary 5-hydroxyindoleacetic acid (5-HIAA), whole blood and plasma serotonin, tail bleeding time, blood cell count, plasma TGF-ß1 and plasma natriuretic peptide concentrations were measured. Myocardium and mitral valves were characterized by histology. mRNA mitral expression of 5-HT2A and 5-HT2B receptors was measured in the anterior leaflet. Cardiac anatomy and function were assessed by echocardiography. RESULTS: Compared to C57BL/6J, FVB mice strains did not significantly differ regarding body weight increase, arterial blood pressure and heart rate. A progressive augmentation of plasma pro-ANP was observed in FVB mice. Nevertheless, no cardiac hypertrophy or left-ventricular fibrosis were observed. Accordingly, plasma TGF-ß1 was not different among the three strains. Conversely, FVB mice demonstrated a high prevalence of fibromyxoid highly cellularized and enriched in glycosaminoglycans lesions, inducing major mitral leaflets thickening without increase in length. The increased thickness was correlated with urinary 5-HIAA and blood platelet count. Whole blood serotonin concentration was similar in the two strains but, in FVB, a reduction of plasma serotonin was observed together with an increase of the bleeding time. Finally, echocardiography identified left atrial and left ventricular remodeling associated with thickening of both mitral leaflets and mitral insufficient in 30% of FVB mice but no systolic protrusion of mitral leaflets towards the atrium. CONCLUSION: The FVB mouse strain is highly prone to spontaneous mitral myxomatous degeneration. A contribution of the peripheral serotonergic system is suggested.

Evaluation of Bleeding Rate and Time in Therapeutic Range in Patients Using Warfarin Before and During the COVID-19 Pandemic-Warfarin Treatment in COVID-19.

The treatment process of patients using warfarin is expected to be hindered during the COVID-19 pandemic. Therefore we investigated whether the time in therapeutic range (TTR) and bleeding complications were affected during the COVID-19 pandemic. 355 patients using warfarin were included between March 2019 to March 2021. Demographic parameters, INR (international normalized ratio), and bleeding rates were recorded retrospectively. The TTR value was calculated using Rosendaal's method. The mean age of the patients was 61 ± 12 years and 55% of them were female. The mean TTR value during the COVID-19 pandemic was lower than the pre-COVID-19 period (56 ± 21 vs 68 ± 21, P < 0.001). Among the patients, 41% had a lack of outpatient INR control. During the COVID-19 pandemic, 71 (20%) patients using VKA suffered bleeding. Among patients with bleeding, approximately 60% did not seek medical help and 6% of patients performed self-reduction of the VKA dose. During the COVID-19 pandemic, TTR values have decreased with the lack of monitoring. Furthermore, the majority of patients did not seek medical help even in case of bleeding.

Negatively charged nanoparticles of multiple materials inhibit shear-induced platelet accumulation.

Platelet accumulation by VWF under high shear rates at the site of atherosclerotic plaque rupture leads to myocardial infarction and stroke. Current anti-platelet therapies remain ineffective for a large percentage of the population, while presenting significant risks for bleeding. We explore a novel way to inhibit arterial thrombus formation. Theoretically, a negative charge may influence the tertiary structure of VWF to favor the globular configuration by biophysical means without the use of platelet inactivating drugs. We tested this hypothesis experimentally for charged nanoparticles (CNPs) to inhibit thrombus formation in a microfluidic thrombosis assay (MTA). Several different CNPs demonstrated the ability to retard thrombotic occlusion in the MTA. A preliminary study in mice shows that thrombus stability is weaker with CNP administration and bleeding times are not markedly prolonged. The CNPs tested here show promise as a new class of antithrombotic therapies that act by biophysical means rather than biochemical pathways.

Does tranexamic acid reduce risk of mortality on patients with hemoptysis?: A protocol for systematic review and meta-analysis.

BACKGROUND: Although tranexamic acid (TXA), a readily accessible antifibrinolytic agent, is widely adopted in hemorrhage scenarios, its role on mortality in patients with hemoptysis remains uncertain. New evidence is yet to be generated to evaluate the risk of mortality after using TXA in patients with hemoptysis. METHODS: PubMed, EMBASE, Cochrane Library, Web of Science, and Scopus databases were searched from inception to May 2020. Randomized controlled trials and observational studies that evaluated the effect of TXA on patients with hemoptysis were included. Data were independently extracted by 2 reviewers and synthesized using a random-effects model. MAIN RESULTS: Five studies with a total of 20,047 patients were analyzed. When compared with the control, administration of TXA was associated with a reduction in short-term mortality (risk ratio = 0.78, 95% confidence interval [CI] 0.72-0.85; I2 = 0), shorter bleeding time (mean difference = - 24.61 hours, 95% CI - 35.96 to -13.26, I2 = 0), shorter length of hospital stay (mean difference = -1.94 days, 95% CI -2.48 to -1.40, I2 = 0), and lower need for intervention (risk ratio = 0.38, 95% CI 0.16-0.87, I2 = 0) in patients with hemoptysis. Compared with control, administration of TXA did not cause increased major or minor adverse effects. CONCLUSIONS: TXA provided benefits in terms of a lower short-term mortality rate, less bleeding time, shorter length of hospital stays, and less need for intervention in patients with hemoptysis. Use of TXA was not associated with increased adverse effects.