Excessive Bleeding Research Articles

Impact of early bleeding on long-term mortality after left atrial appendage occlusion

BackgroundShort-term antithrombotic therapy is recommended after left atrial appendage occlusion(LAAO) to reduce the risk of device-related thrombosis(DRT). However, patients referred for LAAO have excess bleeding risk. Yet, short-term bleeding events post-LAAO are not well characterized. ObjectiveWe aimed to evaluate the incidence of early bleeding post-LAAO and its association with long-term mortality risk. We also sought to identify predictors of early bleeding. MethodsPatients who underwent LAAO at Mayo Clinic between 2018 and 2023 were included. Early bleeding was defined as bleeding that occurred within three months of discharge. A multivariable Cox proportional hazards model was used to assess the association between early bleeding and death and to estimate the hazard ratio(HR). Multivariable regression analysis was used to identify predictors of early bleeding. ResultsAmong the 592 patients included, 389(66%) were male, and mean age was 75.6 years. Eighty-three patients(14.0%) experienced early bleeding, with the majority having minimal(63.4%) or minor(17.3%) bleeding. At a median follow-up of 14.4 months(IQR 4.2-27.9), early bleeding after LAAO was associated with an increased risk of all-cause mortality (adjustedHR, 2.07; 95%CI, 1.15-3.75; P=0.02). A history of intracranial bleeding, non-paroxysmal atrial fibrillation, CHA2DS2VASc score, and early DRT were independent predictors of early bleeding. Anti-thrombotic therapy on discharge was not associated with early non-procedural bleeding. ConclusionsOne in seven patients experience a non-procedural bleeding event within 90 days after LAAO. Early bleeding after LAAO is associated with a higher all-cause mortality during mid-term follow-up. Further studies are needed to optimize the management of patients undergoing LAAO.

Emergency obstetrical hysterectomy among post-partum hemorrhage women in Larkana

Postpartum hemorrhage (PPH), is an excessive bleeding after giving birth, it is a major cause of maternal mortality and morbidity around the world. In the current era of obstetrics, emergency obstetric hysterectomy (EOH) is still a crucial treatment that can save lives. This study was designed to determine causes, frequency, complications of emergency cesarean /obstetrical hysterectomy in Postpartum hemorrhage (PPH) in tertiary care hospital. All the patients gave birth during 4 years (i.e. 1January 2020- 31 December 2023) were included in this study. The obstetrical patients admitted were 13532, out of which 154 underwent emergency hysterectomy. Their biodata, sign and symptoms, diagnosis, fluid/blood transfusion, morbidity, operative intervention, maternal mortality, and follow up were taken on a proforma. The data thus taken was compiled and analyzed. The incidence of EOH was 11.4/1000 obstetrical cases, mostly (85.5%) were referral from elsewhere, while 20 (13.79%) were registered as booked who took proper antenatal care. Multipara (94%) was predominantly reported with post-partum hemorrhage (n=79, 51.29%). The maternal mortality was 15.59% (n= 19). Regular and scheduled antenatal care, early diagnosis, early referral, timely decision, blood transfusion with arrangement of surgery by an experienced obstetrician are crucial to justify EOH.

Hemostatic management of von Willebrand disease during childbirth with a plasma-derived von Willebrand factor/factor VIII concentrate

BackgroundFemales with von Willebrand disease (VWD) do not show the same increases in von Willebrand factor and factor (F)VIII levels during pregnancy as females without VWD and are at higher risk of excessive bleeding associated with childbirth. Data on hemostatic management for childbirth in VWD patients are limited. ObjectivesTo evaluate the dosing, efficacy, and safety of plasma-derived von Willebrand factor/FVIII (wilate) for prevention of excessive bleeding associated with childbirth in females with any type of VWD. MethodsData for females with VWD who received wilate for hemostatic coverage for childbirth during 2 prospective clinical studies were analyzed. ResultsTen females with VWD and a mean age at enrolment of 29.6 years were treated with wilate to prevent excessive bleeding associated with childbirth. Two patients had type 1, 4 had type 2 (2 2A, 1 2B, and 1 2M), and 4 had type 3 VWD. Of the 10 deliveries, 5 were by cesarean section. Patients received a mean of 9.5 infusions of wilate over 6.8 exposure days, with a mean total dose of 234 IU/kg per delivery and 25 IU/kg per infusion. Hemostatic management for all deliveries was rated excellent or good, with no excessive bleeding during delivery and no postpartum bleeding during the period of wilate treatment in any patient. Two patients experienced 8 possible or probable treatment-related adverse events; all were mild or moderate and resolved. No thromboembolic events were observed. ConclusionThe results of this case series indicate that wilate provided effective hemostatic cover for childbirth in females with VWD during delivery and postpartum.

The Diagnostic Accuracy of EXTEM and HEPTEM Clotting Times Versus Standard Laboratory Tests in Cardiac Surgical Patients With and Without Normal FIBTEM Values

ObjectiveThere is extensive evidence to support the use of FIBTEM to identify hypofibrinogenemia during cardiac surgery, but less to support the use of EXTEM and INTEM Clotting Times (CTs) to identify other plasmatic coagulation factor deficiencies. The aim of the current study was to assess the diagnostic accuracy of EXTEM, INTEM, and HEPTEM CTs, using laboratory INR and aPTT as reference standards. DesignRetrospective diagnostic accuracy study. SettingTertiary Referral Hospital. Participants176 cardiac surgical patients InterventionsINR, aPTT, ROTEM EXTEM, INTEM, and HEPTEM were measured post-heparin reversal after cardiopulmonary bypass. Measurements and Main ResultsSensitivity, specificity, and positive (PPV) and negative predictive values (NPV) for EXTEM CT>80s and HEPTEM CT>280s to detect INR≥2.0, and for INTEM CT>205s to detect aPTT≥38.5s were calculated for all patients, and for the subset with normal FIBTEM A5 (>6mm). INR≥2.0 prevalence was 13%. EXTEM CT>80s had a sensitivity of 1.00, specificity 0.25, PPV 0.17 and NPV 1.00. HEPTEM CT>280s had a sensitivity of 0.91, specificity 0.38, PPV 0.18, and NPV 0.97. INTEM CT>205s had sensitivity of 0.97, specificity 0.11, PPV 0.57 and NPV 0.75 for aPTT≥38.5s. These values were similar for the subset of patients with normal FIBTEM A5. ConclusionsEXTEM CT>80s and HEPTEM CT>280s have high sensitivities and NPVs for INR>2.0, which would effectively ‘rule out’ INR>2.0 as a cause for excessive bleeding. However, the low specificities and PPVs indicate they would be less effective to rule it in. INTEM CT>205s had both low PPV and NPV to identify aPTT>38.5s.

Assessing health care resource use, outcomes, and costs among Medicaid beneficiaries receiving factor IX prophylaxis for hemophilia B.

Hemophilia B is characterized by a deficiency of clotting factor IX (FIX), leading to excessive bleeding. Hemophilia B is commonly treated using replacement FIX therapy, which may be administered prophylactically or on-demand following a bleeding episode. Previous research has found high health care resource use (HCRU) and costs among Medicare and commercially insured people with hemophilia B (PwHB), with FIX therapy being a primary driver of health care costs. To assess HCRU, outcomes, and costs among US Medicaid beneficiaries receiving FIX prophylaxis for hemophilia B. This study employed a retrospective comparative cohort design to assess HCRU, outcomes, and costs among adult male Medicaid beneficiaries receiving FIX prophylaxis for hemophilia B, relative to a matched comparator population of beneficiaries without bleeding disorders. Nationwide Medicaid claims and enrollment data from 2015 to 2020 were used for this analysis. Adult male PwHB who received FIX prophylaxis, defined as not having identified gaps in FIX therapy exceeding 60-days during a 1-year measurement period, and were continuously enrolled in Medicaid for at least 2 years, were matched 1:4 to comparator beneficiaries without bleeding disorders based on baseline demographic and clinical characteristics. Key measures of HCRU and outcomes included inpatient hospital admissions, outpatient hematologist visits, and bleeding events. Measures of health care costs were assessed among a subset of beneficiaries enrolled in fee-for-service Medicaid. PwHB receiving FIX prophylaxis were significantly more likely to have multiple inpatient hospital admissions and had a longer cumulative length of stay per person relative to comparator beneficiaries (30.2 vs 14.8 days, respectively; P = 0.0473). PwHB receiving FIX prophylaxis also had significantly higher rates of bleeding events relative to comparator beneficiaries (0.54 vs 0.02 per person, respectively; P < 0.0001) and outpatient hematologist visits (1.58 vs 0.20 per person, respectively; P < 0.0001). Annual costs among PwHB receiving FIX prophylaxis were significantly higher than costs among comparator beneficiaries ($928,370 vs $34,553 per person, respectively; P < 0.0001) and were overwhelmingly driven by costs associated with FIX therapy. This analysis found higher rates of HCRU and costs among Medicaid beneficiaries receiving FIX prophylaxis for hemophilia B relative to a matched comparator population of beneficiaries without bleeding disorders. Future research should examine hemophilia B costs and outcomes within the context of new treatments with innovative mechanisms of action, such as gene therapies, RNA interference therapies, and antitissue factor pathway inhibitor therapies.

Anti – intercellular adhesion molecule-1(ICAM-1) nanoparticles for damaged endothelium to treat venous thromboembolism

Venous thromboembolism (VTE) is a potentially fatal vascular disease that can be successfully managed to reduce the risk of mortality and impairment. Anticoagulation therapy is frequently recommended for the treatment and prevention of venous thromboembolism. Despite breakthroughs in anticoagulant therapy using parenteral anticoagulant medications and vitamin K antagonists, limits in their usage persist, prompting research into alternative anticoagulants such as factor Xa inhibitors. Of the agents under development, edoxaban shows the most promise due to strong data confirming its therapeutic benefit for VTE. Nanoparticle drug delivery systems (NDDS) are designed technologies that employ nanoparticles to convey therapeutic drugs in a targeted and regulated manner. Intraendothelial transport of therapies in VTE is facilitated by the induction of cell adhesion molecule-mediated endocytosis upon interaction of intercellular adhesion molecule 1 (ICAM-1) on endothelium cells by ICAM-1-targeted carriers. The potential application of NDDS as nanoparticles as anticoagulant agents has been emphasized. There is proof of outstanding efficacy in preventing blood coagulation, dissolving blood clots, and improving in vivo detection of thrombus. These nanoplatforms’ growing evaluations, strong action, enhanced biocompatibility, and lack of problems from excessive bleeding are all positive signs of their possible integration in the clinical treatment of blood coagulation diseases in the future. Additionally, by avoiding biological barriers and enhancing a medication’s therapeutic index, NDDSs offer superior drug delivery to targeted treatment or even directly to the injured site as compared to standard anticoagulants. Emerging scientific and clinical data suggests that NDDS may be a safe, efficacious, and attractive treatment option for a variety of cardiovascular disorders, including thromboembolic syndromes. This study presents an updated knowledge of nanocarriers for thrombosis as well as an outline of recent significant breakthroughs in targeted thrombosis therapy.

Delayed femoral artery injury caused by heterotopic ossification: a rare case report and review of the literature

BackgroundArterial injury caused by heterotopic ossification (HO) following fractures is rarely reported, yet it can have catastrophic consequences. This case report presents a unique instance of femoral artery injury and hematoma organization, occurring a decade after intramedullary nail fixation for a femoral shaft fracture complicated by HO.Case presentationA 56-year-old male presented with right femoral artery injury and organized hematoma, a decade after suffering bilateral femoral shaft fractures with mild head injury in a traffic accident. He had received intramedullary nailing for the right femoral shaft fracture and plate fixation for the left side in a local hospital. Physical examination revealed two firm, palpable masses with clear boundaries, limited mobility, and no tenderness. Peripheral arterial pulses were intact. Radiography demonstrated satisfactory fracture healing, while a continuous high-density shadow was evident along the inner and posterior aspect of the right thigh. Computed tomography angiography identified a large mixed-density mass (16.8 × 14.8 × 20.7 cm) on the right thigh’s medial side, featuring central calcification and multiple internal calcifications. The right deep femoral artery coursed within this mass, with a smaller lesion noted on the posterior thigh. Surgical consultation with a vascular surgeon led to planned intervention. The smaller mass was completely excised, but the larger one partially, as it encased the femoral artery. The inability to remove all HO was due to excessive bleeding. Postoperatively, the patient experienced no complications, and one-year follow-up revealed a favorable recovery with restoration of full right lower limb mobility.ConclusionThis case underscores the potential gravity of vascular injury associated with heterotopic ossification. Surgeons should remain vigilant regarding the risk of vascular injury during HO excision.

Computer-assisted open exposure of palatally impacted canines for orthodontic eruption: A randomized clinical trial

ObjectiveThis randomized clinical trial aimed to assess the feasibility of computer-assisted open exposure of palatally impacted canines. Materials and methodsPatients aged 11–30 years who required orthodontic eruption for the full palatal impaction of their canines were included in this study. Exclusion criteria were psychosocial and dental contraindications of orthodontic treatment, congenital craniofacial disorders, and trauma in the patient's history in the vicinity of the surgical site. Virtual planning software was used to register the intraoral scans and cone-beam computed tomography data and to design a surgical template. In the test group, exposure of the canines was guided by a surgical template, whereas in the control group, the surgeon relied on the surgical plan to localize the impacted canine. The success of the intervention, duration of surgery, and complications, including excessive hemorrhage, damage to the canine or neighboring anatomical landmarks, and postoperative inflammation of the surgical site were assessed. Postoperative pain was reported by the patients using the visual analog pain scale (VAS). ResultsSurgery was deemed successful in all patients in both groups. During healing, no complications were observed. The duration of surgery decreased significantly in the test group (4 min 45.1 s ± 1 min 8.4 s) compared to that in the control group (7 min 22.3 s ± 56.02 s). No statistically significant differences were observed between the VAS scores of the two study groups. ConclusionsThe application of virtual planning and static navigation is a viable approach for the open exposure of palatally impacted canines. Clinical trial registration numberNCT05909254. Clinical significanceComputer-assisted surgery is a feasible method for open exposure of palatally impacted canines, which decreases the duration of surgery compared to the freehand method.

Platelet-Rich Plasma-Embedded Porous Polycaprolactone Film with a Large Surface Area for Effective Hemostasis.

Uncontrollable and widespread bleeding caused by surgery or sudden accidents can lead to death if not treated with appropriate hemostasis. To prevent excessive life-threatening bleeding, various hemostatic agents based on polymeric biomaterials with various additives for accelerated blood coagulation have been adopted in clinical fields. In particular, platelet-rich plasma (PRP), which contains many blood coagulation factors that can accelerate blood clot formation, is considered as one of the most effective hemostatic additives. We investigated a PRP-embedded porous film using discarded (expired) PRP and a film with a leaf-stacked structure (FLSS), as a hemostatic agent to induce rapid hemostasis. The film, which contained an LSS on one side (PCL-FLSS), was fabricated by a simple heating-cooling technique using tetraglycol and polycaprolactone (PCL) film. Activated PRP was obtained by the thawing of frozen PRP at the end of its expiration date (the platelet cell membrane is disrupted during the freezing and thawing of PRP, thus releasing various coagulation factors) and embedded in the PCL-FLSS (PRP-FLSS). From in vitro and in vivo experiments using a rat hepatic bleeding model, it was recognized that PRP-FLSS is not only biocompatible but also significantly accelerates blood clotting and thus prevents rapid bleeding, probably due to a synergistic effect of the sufficient supply of various blood coagulants from activated PRP embedded in the LSS layer and the large surface area of the LSS itself. The study suggests that PRP-FLSS, a combination of a porous polymer matrix with a unique morphology and discarded biofunctional resources, can be an advanced hemostatic agent as well as an upcycling platform to avoid the waste of biofunctional resources.

Mesh-shaped absorbable hemostatic hydrogel patch fabricated with marine organism-derived protein biomaterials with contact-activated blood coagulation for application in visceral surgery

The utilization of efficacious hemostatic agents in surgical procedures has the potential to enhance operational efficacy, expedite patient recovery, and diminish the need for blood transfusions. However, in cases of excessive bleeding, few commercial hemostatic agents can maintain contact with the bleeding site and perform hemostatic functions effectively. In the present work, we propose a mesh-shaped absorbable lyophilized hemostatic hydrogel patch with excellent biodegradability, wet tissue adhesion ability, strong structural properties, and good blood coagulation activity by integrating the beneficial properties of two marine organism-derived bioengineered protein biomaterials, sea anemone silk-like protein (aneroin) and mussel adhesive protein (MAP). The hemostatic efficacy of the developed hydrogel patch was thoroughly evaluated using in vitro and in vivo experiments. The mesh-shaped hemostatic hydrogel patch exhibited the ability to absorb plasma upon contact with blood, adhere to surfaces, and facilitate aggregation of blood components, hence enhancing the process of blood coagulation. Using animal liver damage models, we confirmed that the hemostatic hydrogel patch could significantly enhance hemostatic capabilities by reducing clotting time and blood loss while exhibiting minimal inflammation and toxicity when remaining within the body. Thus, our proposed absorbable hemostatic hydrogel patch demonstrated great potential for use as a novel adhesive hemostatic agent for application in visceral surgery.

Temperature effect on coagulation function in mild hypothermic patients undergoing thoracic surgeries: thromboelastography (TEG) versus standard tests

PurposeOur previous research has revealed that mild hypothermia leads to excessive bleeding in thoracic surgeries, while the underlying mechanism stayed unrevealed by the standard coagulation tests. The research question in this study was as follows: “How does mild hypothermia impair the hemostatic function in patients receiving thoracic surgeries?”. The purpose was to detect the disturbed coagulation processes by comparing the TEG parameters in patients receiving active vs. passive warming during thoracic surgeries.MethodsStandard coagulation tests and thromboelastography (TEG) were adopted to compare the hemostatic functions in patients receiving active vs. passive warming during thoracic surgeries. Furthermore, blood samples from passive warming group were retested for TEG at actual core body temperatures.ResultsSixty-four eligible patients were included in this study. TEG revealed that mild hypothermia significantly disturbed coagulation by decreasing MA (59.4 ± 4.5 mm vs. 64.2 ± 5.7 mm, p = 0.04) and α angle (70.4 ± 5.2° vs. 74.9 ± 4.4°, p = 0.05) and prolonging ACT (122.2 ± 19.3 s vs. 117.3 ± 15.2 s, p = 0.01) and K time (1.9 ± 1.0 s vs. 1.3 ± 0.4 min, p = 0.02). TEGs conducted under core body temperatures revealed more impaired coagulation than those incubated at 37 °C. Furthermore, postoperative shivering and waking time were significantly increased in mild hypothermic patients.ConclusionMild hypothermia significantly impaired coagulation function in patients receiving thoracic surgeries, which could be detected by TEGs other than the standard coagulation tests. Temperature-adjusted TEGs may provide a preferable method of hemostatic monitoring and transfusion guidance in thoracic surgeries, which warrants further clinical investigations.

A Common OXTR Risk Variant Alters Regulation of Gene Expression by DNA Hydroxymethylation in Pregnant Human Myometrium

Postpartum hemorrhage, or excessive bleeding after birth, is a leading cause of maternal morbidity. A major cause of postpartum hemorrhage is uterine atony, tiring of the uterus which leads to ineffective contractions. Uterine contractions depend on oxytocin signaling in the myometrium, which in turn depends on expression of the oxytocin receptor (OXTR). Both genetic and epigenetic factors related to the oxytocin receptor are associated with risk of postpartum hemorrhage, but a mechanism relating these factors to oxytocin receptor activity in myometrium remains unclear. We report a genetic by epigenetic interaction whereby the relationship between DNA hydroxymethylation and OXTR gene expression depends on a common OXTR gene variant (rs53576). We also provide evidence that a similar genetic by epigenetic interaction using blood-derived DNA methylation is associated with relevant clinical outcomes: quantity of oxytocin administration and odds for postpartum hemorrhage. These results provide new avenues for predicting how women will respond to pharmacological agents in the prevention and treatment of postpartum hemorrhage.

Reduced doses of emicizumab achieve good efficacy: Results from a national-wide multicentre real-world study in China.

Reduced doses of emicizumab improve the affordability among patients in developing countries. However, the relationship between variant dose selection and efficacy in the real world of China is still unclear. This study aimed to investigate the efficacy and safety of emicizumab especially in those on reduced dose regimens in a real-world setting. We carried out a multicentre study from 28 hospitals between June 2019 and June 2023 in China and retrospectively analysed the characteristics including demographics, diagnosis, treatment, bleeding episodes, and surgical procedures. In total, 127 patients with haemophilia A, including 42 with inhibitors, were followed for a median duration of 16.0 (IQR: 9.0-30.0) months. Median age at emicizumab initiation was 2.0 (IQR: 1.0-4.0) years. Median (IQR) consumption for loading and maintenance was 12.0 (8.0-12.0) and 4.2 (3.0-6.0) mg/kg/4weeks, respectively. While on emicizumab, 67 (52.8%) patients had no bleeds, whereas 60 (47.2%) patients had any bleeds, including 26 with treated bleeds. Compared to previous treatments, patients on emicizumab had significantly decreased annualized bleeding rate, annualized joint bleeding rate, target joints and intracerebral haemorrhage. Different dosages had similar efficacy except the proportion of patients with treated spontaneous bleeds and target joints. Adverse events were reported in 12 (9.4%) patients. Postoperative excessive bleeding occurred following two of nine procedures. This is the largest study describing patients with HA receiving emicizumab prophylaxis on variant dose regimens in China. We confirmed that nonstandard dose is efficacious and can be considered where full-dose emicizumab is ill affordable.

Magnitude and associated factors of thrombocytopenia, among pregnant women at Mizan Tepi university teaching hospital south west Ethiopia

BackgroundThrombocytopenia in pregnancy is a common multifactorial abnormality of the hematological system, next to anemia. It leads to more increased risk of bleeding during delivery, labour, or the postpartum period. Despite being a significant public health concern, there are limited studies done concerning thrombocytopenia during pregnancy.ObjectiveTo assess the magnitude and associated factors of thrombocytopenia among pregnant women at Mizan Tepi University Teaching Hospital from September 2023 to November 2023.MethodsAn institutional-based cross-sectional study was carried out on 230 systematic randomly selected pregnant women who attended antenatal visits from September 2023 to November 2023 G.C using data collection tools. The pretested structured questionnaires were employed to obtain clinical, nutritional, and sociodemographic information. Additionally, three millilitres of venous blood were collected from each participant and analyzed using a Sysmex hematology analyzer. The data was entered into Epidata version 4.6 and analyzed using STATA version 14. Descriptive statistics were computed, and logistic regression was used to identify predictors with a significance level of less than 0.05.ResultsTwo hundred thirty pregnant women participated in the study. Among study participants, the magnitude of thrombocytopenia was 55(24.35%) with 32 (57.14%) mild, 19 (33.93%) moderate, and 5 (8.93%) severe thrombocytopenia. The determinant factors which shown significant association were Malaria parasite infection (AOR 9.27 at 95% CI 7.42, 10.87), one-year Inter-birth interval (AOR 1.7 at 95% CI 1.24, 2.14), History of abortion (AOR 3.94 95% CI 3.13, 4.86), History of hypertension (AOR 3.12 95% CI 1.56, 4.12), HIV infection (AOR 1.81 95% CI 1.32.2.52) and HBV infection (AOR 3.0 95% CI 2.82, 3.34).ConclusionThrombocytopenia is a public health problem and mild type of thrombocytopenia was the most predominant. The determinant factors that showed significant association with thrombocytopenia were Malaria Parasitic infection, one-year Inter-birth interval, History of abortion, History of hypertension, HIV infection, and HBV infection. Therefore, pregnant women should be continuously screened for thrombocytopenia to avoid excessive bleeding. Increasing Inter-birth interval, preventing abortion as well as timely diagnosis and treatment of underlying causes such as malaria infection, hypertension, HBV, and HIV is important to reduce the burden of thrombocytopenia.

Clot-Targeted Nanogels for Dual-Delivery of AntithrombinIII and Tissue Plasminogen Activator to Mitigate Disseminated Intravascular Coagulation Complications.

Disseminated intravascular coagulation (DIC) is a pathologic state that follows systemic injury and other diseases. Often a complication of sepsis or trauma, DIC causes coagulopathy associated with paradoxical thrombosis and hemorrhage. DIC upregulates the thrombotic pathways while simultaneously downregulating the fibrinolytic pathways that cause excessive fibrin deposition, microcirculatory thrombosis, multiorgan dysfunction, and consumptive coagulopathy with excessive bleeding. Given these opposing disease phenotypes, DIC management is challenging and includes treating the underlying disease and managing the coagulopathy. Currently, no therapies are approved for DIC. We have developed clot-targeted therapeutics that inhibit clot polymerization and activate clot fibrinolysis to manage DIC. We hypothesize that delivering both an anticoagulant and a fibrinolytic agent directly to clots will inhibit active clot polymerization while also breaking up pre-existing clots; therefore, reversing consumptive coagulopathy and restoring hemostatic balance. To test this hypothesis, we single- and dual-loaded fibrin-specific nanogels (FSNs) with antithrombinIII (ATIII) and/or tissue plasminogen activator (tPA) and evaluated their clot preventing and clot lysing abilities in vitro and in a rodent model of DIC. In vivo, single-loaded ATIII-FSNs decreased fibrin deposits in DIC organs and reduced blood loss when DIC rodents were injured. We also observed that the addition of tPA in dual-loaded ATIII-tPA-FSNs intensified the antithrombotic and fibrinolytic mechanisms, which proved advantageous for clot lysis and restoring platelet counts. However, the addition of tPA may have hindered wound healing capabilities when an injury was introduced. Our data supports the benefits of delivering both anticoagulants and fibrinolytic agents directly to clots to reduce the fibrin load and restore hemostatic balance in DIC.

Impact of Piezo and other Osteotomy Models on Soft Tissue, Blood Oxidative Stress, and Proinflammatory Markers

Background: Rhinoplasty is a common surgical procedure used in nose esthetics and pathologies. Shaping the nasal bones is a crucial step in achieving successful rhinoplasty surgery. However, complications such as excessive bleeding, edema, mucosal damage, and periosteal damage may occur during osteotomy for nose shaping. Aim: To investigate the damage to soft tissue and the effects on oxidative stress and proinflammatory cytokines in the blood caused by osteotomy performed on rabbits, using different osteotomy methods. Methods: Thirty-two albino New Zealand rabbits were divided into four groups. Group A was the sham group (n = 8), Group B the piezoelectric device group (n = 8), Group C the manual saw group (n = 8), and Group D the classical osteotomy group (n = 8). About 3 ml of blood was drawn to compare preoperative and postoperative interleukin-1ß (IL-1ß), thiobarbituric acid-reactive substances (TBARS), tumor necrosis factor-alpha (TNF-alpha), nitric oxide (NO), interleukin-10 (IL-10), and glutathione (GSH) levels. A 1 mm3 piece of soft tissue from the nasal bone of each animal in the study groups was sent for histopathological examination. The Chi-square test was used to analyze the incidence of postoperative necrosis, inflammation, and edema in the groups. Results: Histopathologically, edema was significantly higher in Group C and Group D compared to Group B. Inflammation was increased in all groups. The necrosis was significantly higher in Group B compared to Group C and Group D. Except for two parameters, no significant changes were found in the biochemical markers for all groups. Conclusions: The piezoelectric device was found to be a better option for reducing edema and inflammation, while manual saws and classical osteotomy may lead to more tissue damage.

Thrombin - A Molecular Dynamics Perspective.

Thrombin is a crucial enzyme involved in blood coagulation, essential for maintaining circulatory system integrity and preventing excessive bleeding. However, thrombin is also implicated in pathological conditions such as thrombosis and cancer. Despite the application of various experimental techniques, including X-ray crystallography, NMR spectroscopy, and HDXMS, none of these methods can precisely detect thrombin's dynamics and conformational ensembles at high spatial and temporal resolution. Fortunately, molecular dynamics (MD) simulation, a computational technique that allows the investigation of molecular functions and dynamics in atomic detail, can be used to explore thrombin behavior. This review summarizes recent MD simulation studies on thrombin and its interactions with other biomolecules. Specifically, the 17 studies discussed here provide insights into thrombin's switch between 'slow' and 'fast' forms, active and inactive forms, the role of Na+ binding, the effects of light chain mutation, and thrombin's interactions with other biomolecules. The findings of these studies have significant implications for developing new therapies for thrombosis and cancer. By understanding thrombin's complex behavior, researchers can design more effective drugs and treatments that target thrombin.

Role of tranexamic acid in reducing peri-operative blood loss in open spine surgeries.

Spine surgeries are associated with significant blood loss due to the extensive soft tissue dissection, bony decompression, and prolonged surgical time. Excessive bleeding may require blood transfusions and thereby increase the risk of adverse transfusion reactions. Therefore, minimizing peri-operative bleeding is important for spine surgeons to reduce post-operative morbidity. Tranexamic acid (TXA) is a synthetic anti-fibrinolytic drug, which helps in reducing perioperative blood loss in major surgeries. The evidence on the efficacy of this agent in all manner of spine surgeries is not sufficient. Hence this study was conducted to determine the efficacy of TXA on perioperative blood loss in major spinal surgeries. In a prospective study, two groups of patients with similar surgical profiles who were posted for all manner of open spine surgeries were included. One group received one gram of intravenous TXA while the others did not. Intra- and post-operative assessments included noting levels of surgery, duration of surgery, assessment of blood loss, intra- and/or post- operative blood transfusion, and blood collected in surgical drain at the end of 24h. The intra-operative blood loss, frequency of intra-operative blood transfusion, post-operative Hemoglobin drop, and surgical drain output were found to be significantly lower in patients who received TXA. In spine surgeries, TXA was found to be effective in reducing intra-operative blood loss, need for intra-operative blood transfusion and post-operative Hb drop. Also, TXA had reduced surgical drain output significantly between the two groups.

Nurse's Knowledge Regarding Active Management of The Third Stage of Labor to Control Postpartum Hemorrhage

Background: Postpartum hemorrhage is a leading cause of maternal mortality and morbidity globally. The third stage of labor begins after the baby is born and ends with the delivery of the placenta. During this stage, the uterus needs to contract effectively to prevent excessive bleeding. Active Management of the Third Stage of Labor was introduced as a strategy to reduce the risk of postpartum hemorrhage. The study aimed to investigate nurses' knowledge of active management of the third stage of labor to control postpartum hemorrhage and investigate associated factors. Results: The study examined participant characteristics, revealing an average age of 35.93 (SD=8.52). Around 65.0% of nurses in the study had graduated from preparatory nursing. Most nurses (56.7%) had 5-10 years of hospital experience. A majority (65.0%) worked in postpartum areas. Over half (58.3%) had 4-6 years of experience without training. The study evaluated nurses' knowledge of active management of the third stage of labor, with responses on a scale ranging from 37-64. The overall expertise indicates that 75.0% of nurses needed a better understanding. The results highlighted that factors like nurses' education level (p= .024) and training courses (p= .041) predicted their knowledge of active management of the third stage of labor. Conclusions: The study found that nurses' knowledge of active management of the third stage of labor varied, overall indicating a poor understanding of nurses. The results highlighted significant predictors of this knowledge, including education level and participation in training courses. To enhance nurses' proficiency in active management of the third stage, it is recommended to focus on targeted educational programs and regular training opportunities.

Economic Cost of Secondary Postpartum Hemorrhage: A Case-Control Study at a Tertiary Hospital in Australia

(Aust N Z J Obstet Gynaecol. 2023;63:308–313) Secondary postpartum hemorrhage (PPH) is excessive vaginal bleeding occurring up to 12 weeks after childbirth. The incidence ranges from 0.2% to 3.0%, usually presenting 1 to 2 weeks postnatally and commonly caused by endometritis and retained products. Despite its impact on health, evidence for managing and understanding its cost burden is lacking compared with primary PPH. Australian public hospitals are subsidized, but reproductive care costs were $8.7B in 2018 to 2019. Effective resource allocation is vital amidst rising health care expenses. Limited evidence guides secondary PPH treatment, potentially leading to multiple presentations and increased costs. Consequences include resuscitation, transfusion, surgery, and hysterectomy, elevating health care expenses. This study sought to analyze the economic impact of secondary PPH.