Resuscitation and Care in the Trauma Bay.

Start balanced resuscitation early (pre-hospital if possible), either in the form of whole blood or 1:1:1 ratio. Minimize resuscitation with crystalloid to minimize patient morbidity and mortality. Trauma-induced coagulopathy can be largely avoided with the use of balanced resuscitation, permissive hypotension, and minimized time to hemostasis. Using protocolized "triggers" for massive and ultramassive transfusion will assist in minimizing delays in transfusion of products, achieving balanced ratios, and avoiding trauma induced coagulopathy. Once "audible" bleeding has been addressed, further blood product resuscitation and adjunct replacement should be guided by viscoelastic testing. Early transfusion of whole blood can reduce patient morbidity, mortality, decreases donor exposure, and reduces nursing logistics during transfusions. Adjuncts to resuscitation should be guided by laboratory testing and carefully developed, institution-specific guidelines. These include empiric calcium replacement, tranexamic acid (or other anti-fibrinolytics), and fibrinogen supplementation.

Self-anticoagulant sponge for whole blood auto-transfusion and its mechanism of coagulation factor inactivation.

Clinical use of intraoperative auto-transfusion requires the removal of platelets and plasma proteins due to pump-based suction and water-soluble anticoagulant administration, which causes dilutional coagulopathy. Herein, we develop a carboxylated and sulfonated heparin-mimetic polymer-modified sponge with spontaneous blood adsorption and instantaneous anticoagulation. We find that intrinsic coagulation factors, especially XI, are inactivated by adsorption to the sponge surface, while inactivation of thrombin in the sponge-treated plasma effectively inhibits the common coagulation pathway. We show whole blood auto-transfusion in trauma-induced hemorrhage, benefiting from the multiple inhibitory effects of the sponge on coagulation enzymes and calcium depletion. We demonstrate that the transfusion of collected blood favors faster recovery of hemostasis compared to traditional heparinized blood in a rabbit model. Our work not only develops a safe and convenient approach for whole blood auto-transfusion, but also provides the mechanism of action of self-anticoagulant heparin-mimetic polymer-modified surfaces.

Thromboembolic and hemorrhagic complications in patients with prosthetic heart valves cared for in a tertiary care center. What have we learned?

BACKGROUND: Heart valve replacement surgery with mechanical or biological prostheses entails a risk of thromboembolism and bleeding complications. OBJECTIVE: To determine the complications related to complementary anticoagulation therapy and the probability of risk. METHODS: One-hundred and sixty-three patients who underwent heart valve replacement between 2002 and 2016 with either mechanical or biological prostheses, and who received vitamin K antagonists after hospital discharge, were studied. Anticoagulation therapy was categorized into optimal and non-optimal according to INR values prior to the development of complications. Patients with comorbidities and other risk factors for thrombosis and/or bleeding were excluded. RESULTS: In total, 68.7 % of patients received mechanical prostheses, and 31.3 %, biological prostheses (p ≤ 0.001); 25.2 % experienced the complications that motivated the study (p ≤ 0.001), which were hemorrhagic in 48.8 %, thromboembolic in 26.8 %, and of both types in 24.4 % (relative risk = 4.229). Among the patients with complications, 95.1 % received mechanical prostheses, and 4.9 %, biological (p = 0.005); non-optimal INR was identified in 49.7 % (p ≤ 0.001). CONCLUSIONS: Given the high risk of thromboembolic and hemorrhagic complications, valve prostheses must be carefully chosen, and care priorities should include prevention and follow-up, especially in those patients who require anticoagulation therapy.

ANTECEDENTES: El reemplazo valvular por prótesis mecánicas o biológicas implica riesgo de tromboembolismo y complicaciones hemorrágicas. OBJETIVO: Determinar las complicaciones relacionadas con la terapia de anticoagulación complementaria y la probabilidad de riesgo en pacientes portadores de prótesis valvulares del corazón. MÉTODOS: Se estudiaron 163 pacientes entre 2002 y 2016, portadores de prótesis mecánicas y biológicas, quienes recibieron antagonistas de la vitamina K posterior al egreso hospitalario. La terapia de anticoagulación se categorizó en óptima y no óptima conforme a los valores de INR previos a las complicaciones. Fueron excluidos los pacientes con comorbilidades y otros factores de riesgo de trombosis y/o sangrado. RESULTADOS: a 68.7 % de los pacientes se les colocó prótesis mecánica y a 31.3 %, biológica (p ≤ 0.001); 25.2 % presentó las complicaciones motivo de estudio (p ≤ 0.001), hemorrágicas en 48.8 %, tromboembólicas en 26.8 % y de ambos tipos en 24.4 % (riesgo relativo = 4.229); a 95.1 % de los pacientes con complicaciones se les colocó prótesis mecánica y a 4.9 %, biológica (p = 0.005); 49.7 % presentó INR no óptimo (p ≤ 0.001). CONCLUSIONES: Ante riesgo alto de complicaciones tromboembólicas y hemorrágicas, la elección de las prótesis valvulares, la prevención y el seguimiento son prioridades, principalmente en quienes requieren terapia de anticoagulación.

Cold stored platelets in the management of bleeding: is it about bioenergetics?

When platelet concentrates (PCs) were first introduced in the 1960s as a blood component therapy, they were stored in the cold. As platelet transfusion became more important for the treatment of chemotherapy-induced thrombocytopenia, research into ways to increase supply intensified. During the late 1960s/early 1970s, it was demonstrated through radioactive labeling of platelets that room temperature platelets (RTP) had superior post-transfusion recovery and survival compared with cold-stored platelets (CSP). This led to a universal switch to room temperature storage, despite CSP demonstrating superior hemostatic effectiveness upon being transfused. There has been a global resurgence in studies into CSP over the last two decades, with an increase in the use of PC to treat acute bleeding within hospital and pre-hospital care. CSP demonstrate many benefits over RTP, including longer shelf life, decreased bacterial risk and easier logistics for transport, making PC accessible in areas where they have not previously been, such as the battlefield. In addition, CSP are reported to have greater hemostatic function than RTP and are thus potentially better for the treatment of bleeding. This review describes the history of CSP, the functional and metabolic assays used to assess the platelet storage lesion in PC and the current research, benefits and limitations of CSP. We also discuss whether the application of new technology for studying mitochondrial and glycolytic function in PC could provide enhanced understanding of platelet metabolism during storage and thus contribute to the continued improvements in the manufacturing and storage of PC.

What is the context? To transition into an activated state, platelets require a highly efficient source of energy that is met through the production of ATP ­ this is referred to as "platelet bioenergetics"Platelets can be removed from healthy donors and used to make platelet concentrates for clinical usePlatelet concentrates are used clinically either therapeutically (to halt bleeding) or prophylactically (to prevent bleeding in patients with low platelet counts)They are stored at room temperature (20­24^oC) with constant gentle agitation, in packs that allow gas exchange and have a 7-day shelf life in some jurisdictionsStoring platelets in the cold (2­6^oC) has historically been shown to improve their ability to halt bleedingWhat is new? There is a renewed interest in cold stored platelets for use in actively bleeding patientsThere are benefits to cold-storing platelets over room temperature storageCold stored platelets are licensed in the US and Norway for certain indications for 14 daysWhat is next? Cold stored platelets have the potential to improve logistics of clinical supply of platelets, enable supply of platelet concentrates where access is currently limited, such as pre-hospital care and on the battlefield and provide improved hemostatic effects for bleeding patients.New research measuring the bioenergetic profiles of cold stored platelets could advance understanding of metabolism in cold stored platelets and support decisions on their re-introduction on a wider scale.

Optimal Anticoagulation on TAVI Patients Based on Thrombotic and Bleeding Risk and the Challenge Beyond: A Systematic Review and Meta-Analysis.

Transcatheter Aortic Valve Replacement (TAVR) has been established as the treatment of choice for symptomatic aortic stenosis, while it is expanding in all risk-related group categories of patients, gaining gradually ground over the surgical approach. However, complications and adverse events are yet to be effectively limited and diminished with thrombotic and hemorrhagic events being rooted as a crucial topic of discussion. Favorable anticoagulation pharmacotherapy options are constantly being revised and tested, whilst guidelines are being modified to meet current clinical evidence. This review aims to systematically assess already existing guidelines on anticoagulation in post-TAVI patients and examine novel regimens for the specific use, like apixaban, rivaroxaban, and other anticoagulants, essentially constructing a holistic point of view on future progress on this matter. The added complexity brought by coagulation-affecting comorbidities such as atrial fibrillation, coronary artery disease, and more contributes to the direct association of the topic to the quality of healthcare as a public service. The literature was systematically searched to examine the effectiveness and safety of various anticoagulation treatments and cross-evaluate them based on the according category of patients that were assigned to. Clinical trials, observational studies and systematic reviews were included and, eventually, conclusive remarks and future considerations were developed and presented. In the category of patients without prior indication to anticoagulation, SAPT was proven safer and still effective, when antiplatelet therapies were compared, while a comparison of antiplatelet versus anticoagulation strategies noted the first one, with limited data, as the optimal one. Lastly, direct oral anticoagulants were shown to be safe substitutes for vitamin K antagonists for patients with prior indication to anticoagulation.

Is the folk medicine known as "The Secret" efficient in reducing bleeding after percutaneous coronary procedures?: a double-blinded, randomised trial.

AIM: Percutaneous coronary interventions require an arterial approach and administration of antithrombotic drugs. This may lead to bleeding complications. The aim of this study was to test whether "The Secret" - a pagan prayer - is effective in reducing post-interventional bleeding. DESIGN: Randomised controlled trial. SETTING: Monocentric, tertiary care centre. PARTICIPANTS: From January to July 2022, 200 patients (aged >18 years) undergoing elective coronary angiography were included in the study. INTERVENTION: The intervention group received "The Secret" in addition to the normal procedure. The control group was treated according to standard practice. MAIN OUTCOME MEASURES: The primary outcome was the rate of in-hospital bleeding according to the Bleeding Academic Research Consortium (BARC) consensus definition. RESULTS: The rate of bleeding was similar in both groups ("The Secret" group vs control group) with 16% versus 14% (p=0.69) of BARC 1, 12% versus 13% (p=0.81) of BARC 2, and 0% versus 0% of BARC 3 and 5 (p=1.00). Most (76%) of the participants believed that "The Secret" would be efficient in preventing bleeding. CONCLUSIONS: This study demonstrates no effect on bleeding after percutaneous coronary procedures. A large majority of our study population believe that "The Secret" can have a positive effect on their hospital care.

Dehydroepiandrosterone activates the GPER-mediated AMPK signaling pathway to alleviate the oxidative stress and inflammatory response in laying hens fed with high-energy and low-protein diets.

Fatty liver hemorrhagic syndrome (FLHS) seriously threatens the layer industry due to it can cause a sudden decline in egg production and acute death, and dietary supplement with bioactive substance is considered an effective way to prevent the FLHS occurrence. Dehydroepiandrosterone (DHEA) is a popular dietary supplement and it possesses anti-oxidative and anti-inflammatory functions; however, the effect and underlying mechanism about DHEA in protecting against the occurrence and development of FLHS remain elucidated. The current results showed that DHEA relieved HELP-induced decrease of egg productivity and liver injury in laying hens. Meanwhile, DHEA markedly enhanced the antioxidant capacity and then alleviated oxidative stress via activation of nuclear factor (erythroid-derived 2)-like 2 (NRF-2) signal in laying hens fed with HELP diets. In addition, DHEA significantly alleviated HELP-stimulated systemic inflammatory response by suppressing the overproduction of hepatic pro-inflammatory factors in laying hens, and further found this beneficial effect was achieved by blocking the activation of NF-κB pathway. Furthermore, we found that DHEA promoted the AMP-activated protein kinase α (AMPKα) activation and increased the G-protein-coupled estrogen receptor (GPER) expression level in laying hens fed with HELP diets. In summary, our data demonstrated that DHEA attenuates oxidative stress and inflammation through the activation of GPER-AMPK signal axis in laying hens fed with HELP diets. These results might facilitate an understanding of the benefits and mechanism of DHEA on the development of FLHS, and provide sufficient data to support it as a dietary supplement to control the FLHS-related metabolic diseases in chickens.

Hemostatic effects of traditional Inula viscosa and Capsella bursa-pastoris plant mixture extract on rat liver parenchymal bleeding model.

BACKGROUND: Failure to achieve effective bleeding control and problems related to transfusion in liver surgery are the most common causes of post-operative mortality and morbidity. Various methods/drugs including topical hemostatic agents have been em-ployed for bleeding control in liver surgery. This study was aimed to investigate the hemostatic properties of the herb mixture extract of Inula viscosa and Capsella bursa-pastoris (IvCbp) in rat liver laceration model, which have been traditionally used as antiseptic and hemostatic agents public in Hatay/Tukey. METHODS: Thirty rats were divided into three groups equally and blood samples were taken from all rats for preoperative hemoglobin (Hb) measurements. Then, the standard liver resection model was applied to all rats. Sponge for the first rat group, Ankaferd Blood Stopper® Trend-Tech for the second rat group and IvCbp plant extract mixture for the third group were applied to resection areas for 3 minutes. Liver samples of all rats were evaluated in terms of inflammation and necrosis intensity on the 5th post-operative day. RESULTS: Post-operative Hb values were found as 11.0±1.1 g/dL in the sponge group, 11.9±2.0 g/dL in the Ankaferd group, and 14.1±1.2 g/dL in the IvCbp herb mixture group (p<0.001). In the histopathological examination, less necrosis was observed in the herb mixture group compared to the sponge and Ankaferd groups (p=0.001). In addition, no statistically significant necrosis difference was observed between sponge and Ankaferd groups. While less inflammation was observed in the herb mixture group compared to the other groups, Ankaferd group had the highest inflammation score (p<0.001). CONCLUSION: IvCbp herb mixture extract group provide effective hemostatic control, caused less Hb decrease and resulted in less inflammation and necrosis compared to Ankaferd and sponge groups in a rat liver resection model.

Trauma-induced hypocalcemia.

BACKGROUND: Trauma-induced hypocalcemia is an underappreciated complication of severe injury but is well known to result in the derangement of an array of physiological regulatory mechanisms. Existing literature provides a compelling link between hypocalcemia and worse trauma-induced coagulopathy and increased mortality after injury. STUDY DESIGN AND METHODS: This narrative review evaluates available data related to the risk factors, mechanisms, and treatment of hypocalcemia after severe injury. The authors did not perform a systemic review or meta-analysis. RESULTS AND DISCUSSION: The interplay of acidosis, hypothermia, and coagulopathy with hypocalcemia potentiates the bloody vicious cycle of hemorrhagic shock which has been the paradigm of trauma resuscitation for over half a century. However, current screening and treatment of postinjury hypocalcemia are relegated to a secondary consideration in trauma resuscitation. We conclude calcium supplementation should be a primary tier intervention for life-threatening injury.

An infantile case of hereditary folate malabsorption with sudden development of pulmonary hemorrhage: a case report.

BACKGROUND: Hereditary folate malabsorption-a rare disorder caused by impairment of the folate transporter-can develop into severe folate deficiency manifesting as megaloblastic anemia and occasionally thrombocytopenia. Reportedly, megaloblastic anemia can manifest with hemorrhagic episodes, possibly due to ineffective platelet production and platelet dysfunction. However, life-threatening hemorrhage events in hereditary folate malabsorption have not been well investigated. CASE PRESENTATION: A 3-month-old Japanese boy was transferred to our hospital due to thrombocytopenia and severe megaloblastic anemia. During a thorough examination of hematopoietic abnormalities, the patient suddenly went into cardiac arrest due to pulmonary hemorrhage. Although intravenous folate supplementation was started soon after the identification of folate deficiency, the patient died of circulatory defect and multiple organ failure. The cause of pulmonary hemorrhage, such as respiratory infection, could not be confirmed. Genetic investigation revealed a mutation in the SLC46A1 gene to be the cause of the hereditary folate malabsorption. CONCLUSION: We report an infantile case of hereditary folate malabsorption that progressed to lethal pulmonary hemorrhage before folate deficiency was identified. Clinicians should consider that megaloblastic anemia could lead to severe bleeding without warning, and that nutrient supplementation should be initiated as soon as possible.

Neonatal bilateral adrenal hemorrhage and adrenal insufficiency accompanied by Subgaleal hematoma: a case report with brief review of literature.

BACKGROUND: Neonatal adrenal hemorrhage (NAH) is an almost infrequent phenomenon (0.2-0.55%). Mechanical compression and alterations of venous pressure during delivery are considered the most probable explanations. Approximately 10% of the cases might have bilateral involvement. Clinical symptoms include abdominal mass, poor feeding, vomiting, prolonged jaundice, and anemia. Subgaleal hemorrhage (SGH) is one of the most clinically remarkable and potentially hazardous postnatal cranial injuries. CASE PRESENTATION: An early-term Iranian male neonate who was born through spontaneous vaginal delivery and experienced shoulder dystocia was diagnosed with bilateral NAH leading to adrenal insufficiency requiring glucocorticoid and mineralocorticoid supplementation. The SGH and jaundice were other postnatal complications. Serial monthly abdominal and brain ultrasound revealed complete regression of lesions after 70 days. However, after 16 months, the neonate has been still treated with hydrocortisone and fludrocortisone for the adrenal insufficiency diagnosis. He has a lower limit weight for age; however, developmental milestones have been appropriate for age. DISCUSSION AND CONCLUSION: Adrenal hemorrhage and SGH should be examined and looked for, particularly with proven evidence of difficult delivery and asphyxia in at-risk newborns. Clinical and ultrasound follow-up is mandatory for the assessment of hemorrhage resolution and conservative management. The early detection and treatment of adrenal insufficiency by laboratory examination is strongly recommended in bilateral cases. Furthermore, the early recognition of postnatal SGH to prevent clinical and neurological outcomes seems essential.

Endovascular Management of Hematomas in Pediatric Transplant Patients.

OBJECTIVES: Transcatheter arterial embolization is used to control active hemorrhage at different anatomic locations. Because hematomas can suddenly deteriorate and become life threatening for transplant patients, they require prompt diagnosis and intervention rather than conservative management. Here, we evaluated computed tomography in treatment planning and transcatheter embolization effectiveness for hematoma management in pediatric liver transplant patients. MATERIALS AND METHODS: Between June 2012 and December 2021, 10 pediatric liver transplant patients were referred to our interventional radiology unit. Computed tomography and angiograms were reviewed for hematoma location and presence of extravasation. We analyzed correlations between computed tomography and angiography findings and technical and clinical success of the endovascular interventions. RESULTS: Active leak of contrast material during arterial phase was detected on 9/10 CT scans. Although there was no active bleeding on CT in 1 patient, active arterial bleeding was detected on angiography. On the contrary, in 2 patients, although active bleeding was observed on computed tomography, it was not detected on angiography. Source of bleeding was superior mesenteric artery branches in 4, hepatic artery branch in 2, superior epigastric artery in 1, and phrenic artery in 1 patient. Six of 8 patients with active bleeding were treated with endovascular procedures. The remaining 2 patients received surgery: 1 had bleeding from liver cut surface originating from a hepatic artery branch and received open surgery because the bleeding branch was too thin for catheterization, and 1 was hemodynamically unstable and selective catheterization of the internal thoracic artery would take time. Two patients received embolization procedures with N-butyl 2-cyanoacrylate (glue) diluted with iodized oil, and 1 patient had coil and glue with iodized oil. Embolization with coils was performed in 3 patients. Rate of success with transcatheter arterial embolization was 75%. No complications related to patient comorbidities or embolization procedures were shown. No deaths occurred due to progression of the hematoma. CONCLUSIONS: Transcatheter arterial embolization is effective and safe for treatment of pediatric liver transplant patients with hematomas. Computed tomography has value in identifying the bleeding source and its anatomic relationships and may enhance our intervention abilities to become quicker, more effective, and more secured.

Uncontrollable bleeding after tooth extraction from asymptomatic mild hemophilia patients: two case reports.

BACKGROUND: Uncontrollable bleeding after tooth extraction usually occurs in patients with coagulation diseases, including hemophilia, von Willebrand's disease, vitamin K deficiency, platelet deficiency, and taking anticoagulant drugs. Hemophilia A is an X-linked recessive disorder caused by insufficiency of coagulation factor VIII. Mild hemophilia, defined by factor level between 0.05 and 0.40 IU/mL, is characterized by uncontrollable hemorrhage after trauma or invasive operations. Some mild hemophiliacs may remain undiagnosed until late adulthood. Therefore, surgical management of these patients may be relatively neglected. These case reports describe two uncontrollable bleeding patients with unknown mild hemophilia A after tooth extraction. CASE PRESENTATION: This paper reports 2 cases of persistent bleeding after tooth extraction under local anesthesia which could not be completely stopped by routine treatments. Both of them denied prior illness and injury, allergies, anticoagulant medication history, systemic and family illness. The APTT and other coagulation screening tests of the two patients before surgery were normal. Finally, they were diagnosed with mild hemophilia A via coagulation factor assays. The patients acquired complete hemostasis by receiving coagulation factor supplement therapy in hematologic department. CONCLUSION: Mild hemophilia is marked by subclinical, asymptomatic and even normal coagulation test results. The purpose of these case reports is to bring dental professionals' attention that APTT test alone cannot be used to exclude mild hemophilia, and provide reasonable evaluation and treatment procedures of bleeding patients after tooth extraction.

Neonatal outcome of second-stage cesarean delivery versus vacuum extraction among neonates <34 weeks.

OBJECTIVE: Among deliveries <34 weeks, there is inconclusive evidence regarding the preferred route of delivery when there is a need to expedite delivery during the second stage of labor. As it is unreasonable that future randomized controlled trials will be conducted to settle this query, every clinical data concerning this topic, may be helpful. We aim to compare neonatal outcomes among women undergoing emergent cesarean delivery (ECD) versus vacuum-assisted delivery (VAD) during the second stage of labor among singleton gestations <34 weeks. METHODS: A retrospective cohort study including all women who underwent either ECD or VAD at the second stage of labor between 30°/7 and 336/7 weeks, during 2011-2019. The primary outcome was the rate of adverse neonatal outcomes, defined as intrapartum death, mechanical ventilation, asphyxia, respiratory distress syndrome, subgaleal hemorrhage, intraventricular hemorrhage, necrotizing enterocolitis, and phototherapy. RESULTS: Of the 153,672 live singleton deliveries during the study period, 2871 (1.9%) delivered before 34°/7. Of those 1674 (58.3%) delivered vaginally unassisted and 1137 (39.6%) delivered by a CD during the first stage of labor. A total of 60 deliveries were analyzed, with a median gestational age of 32 weeks, interquartile range (IQR) 31-33. Median birth weight at delivery was 1845 g, IQR 1574-2095. Overall 25 (42%) of women were delivered by VAD and 35 by CD (58%). Indications for expeditious delivery did not differ between the study groups. Neonates delivered by VAD had a higher median birth weight (1940 vs. 1620 g, p = .02). Second stage of labor was longer in the ECD group as compared to the VAD group (median 200 vs. 52 min, p = .01). The rate of Apgar score at 1 min <7 was higher among the CD group (10 (40%) vs. 5 (14%), OR [95% CI]: 4.0 (1.1-13.8), p = .03). Longer length of stay was evident in the CD group as compared to the VAD group (median 30 vs. 21 days, p = .001). The rate of composite neonatal adverse outcome was comparable between the study groups. Adverse outcomes were associated with lower body mass index (median 27.7 vs. 34.9, p = .04), higher rate of premature preterm rupture of membranes (40 (91%) vs. 5 (31%), OR [95% CI]: 22.0 (5.0-91.1), p < .001) and labor dystocia as the indication for expedited delivery (38 (86%) vs. 7 (44%), OR [95% CI]: 8.1 (2.1-30.1), p = .001). CONCLUSIONS: Cesarean delivery during the second stage of labor of gestations <34 weeks was associated with a higher rate of lower Apgar scores and longer length of stay. SYNOPSIS: Delivery by second stage CD of premature neonates <34 weeks is associated with a higher rate of lower Apgar score.

2021 Focused Update Consensus Guidelines of the Asia Pacific Heart Rhythm Society on Stroke Prevention in Atrial Fibrillation: Executive Summary.

The consensus of the Asia Pacific Heart Rhythm Society (APHRS) on stroke prevention in atrial fibrillation (AF) has been published in 2017 which provided useful clinical guidance for cardiologists, neurologists, geriatricians, and general practitioners in the Asia-Pacific region. In these years, many important new data regarding stroke prevention in AF were reported. The practice guidelines subcommittee members comprehensively reviewed updated information on stroke prevention in AF, and summarized them in this 2021 focused update of the 2017 consensus guidelines of the APHRS on stroke prevention in AF. We highlighted and focused on several issues, including the importance of the AF Better Care pathway, the advantages of non-vitamin K antagonist oral anticoagulants (NOACs) for Asians, the considerations of use of NOACs for Asian AF patients with single one stroke risk factor beyond gender, the role of lifestyle factors on stroke risk, the use of oral anticoagulants during the "coronavirus disease 2019" pandemic, etc. We fully realize that there are gaps, unaddressed questions, and many areas of uncertainty and debate in the current knowledge of AF, and the physician's decision remains the most important factor in the management of AF.

A retrospective study on the evaluation of the appropriateness of oral anticoagulant therapy for patients with atrial fibrillation.

BACKGROUND: The incidence of atrial fibrillation (AF) is increasing, and effective anticoagulation therapy can prevent adverse events. Selecting the appropriate OAC based on patient characteristics has become a challenge. Interventions are going to be a potential area of focus. OBJECTIVES: To explore the discrepancies between clinician prescriptions and recommended guidelines of oral anticoagulants (OACs) for patients with atrial fibrillation (AF), and to provide direction for improving anticoagulation strategies for treating patients with AF. MATERIALS AND METHODS: Data were collected from the electronic medical record system of Fuwai Yunnan Cardiovascular Hospital between July 2019 and January 2020. The suitability of prescribed OACs for patients with AF was assessed according to the Rules for Avoiding Prescription Inappropriateness, the prescribed medicine label, and any relevant antithrombotic guidelines for treating patients with AF. RESULTS: A total of 460 patients met the inclusion criteria. Of these, 53.7% received an appropriate prescription and 46.3% received an inappropriate prescription. Of the patients who received inappropriate prescriptions, 15.4% were prescribed without the presenting appropriate indicators, 1.3% were prescribed inappropriate drug selection, and 29.6% were prescribed inappropriate drug doses. For patients prescribed without providing appropriate indicators, 2.2% had no indication for medication and 13.3% had an indication for medication, but not a specific OAC. For patients with inappropriate drug selection, 1, 5 patients were on rivaroxaban, dabigatran respectively. The distribution of NOAC doses was as follows: dabigatran standard dose (45.2%), the low dose (54.8%). Rivaroxaban standard dose (58.9%), low dose (36.8%), high dose (4.3%). A total of 44 patients (9.6%) experienced bleeding events, 12 patients (2.6%) experienced embolic events, and 7 patients experienced other adverse events after dosing. CONCLUSIONS: In clinical practice, it is common for patients with AF to receive inappropriate prescriptions of OACs. Therefore there is a need to enhance anticoagulation management in patients with AF to improve the appropriate use of OACs.

Real-world experience on the tolerability and safety of emicizumab prophylaxis in paediatric patients with severe haemophilia A with and without FVIII inhibitors.

BACKGROUND: Emicizumab is a bispecific monoclonal antibody that bridges activated factor (F) IX and FX, and maintains haemostasis in patients with haemophilia A (PwHA). As a novel agent, many questions remain unanswered about the loss of emicizumab efficacy due to anti-drug antibody (ADA) development, the incidence of inhibitor recurrence in previously tolerized patients, and the risk of de novo inhibitor development. AIM: To present real-world experience regarding tolerability, side effects, and outcomes of adverse events of emicizumab prophylaxis in paediatric PwHA. METHODS: Data on tolerability, compliance, adverse events, and laboratory results of paediatric patients receiving emicizumab prophylaxis, treated at the Haemophilia Comprehensive Care Centre, at Birmingham Children's Hospital between March 2018 and June 2021, were collected. RESULTS: Our results showed that out of 52 patients, four experienced minor adverse events, two developed headaches, one developed abdominal pain and nausea, and one developed injection site reactions. Moreover, four patients experienced major adverse events, including severe headaches, major bleeding events, development of ADAs, and recurrence of inhibitors. Emicizumab prophylaxis was discontinued in three patients (5.7% of the cohort) due to adverse events. In addition, emicizumab was discontinued in one patient because of poor compliance. No adverse events were reported in previously untreated/minimally treated patients, represented by four patients in our cohort. CONCLUSIONS: The real-world experience of emicizumab prophylaxis in our cohort showed that emicizumab was safe and well tolerated in paediatric PwHA with and without inhibitors. Long-term assessment is crucial to monitor major adverse events, recurrence of inhibitors, and development of ADAs.

[Hemorrhage risk and countermeasures of acupuncture treatment in patients undergoing administration of anticoagulants and antiplatelets].

Acupuncture therapy is widely used in the treatment of various clinical problems, but has some contraindications which should be highly noted. For example, patients with potential hemorrhagic tendency owing to administration of necessary anticoagulants and antiplatelets should be paid more attention when acupuncture therapy was performed. Usually, anticoagulants and antiplatelets combined with nonsteroidal anti-inflammatory hormones, antibiotic agents and vasodilators significantly increased the risk of bleeding. Chinese herbal medicines for activating blood circulation to arrest pain, and improper medication including the dosage and frequency should be avoided. Patients with chronic liver diseases, acute and severe liver and kidney function impairment due to inability to secrete coagulation factor in time to initiate coagulation mechanism are also unsuitable for acupuncture the-rapy. For this reason, we put forward some necessary countermeasures: a) collecting the patient's medical history in detail, b) paying attention to the coagulation related tests, c) taking the patient's blood volume and platelet related parameters seriously, and d) enacting reasonable diagnosis and treatment ideas.

Investigation of platelet function in patients with chronic kidney disease stages IV-V.

INTRODUCTION: Patients with renal failure are at increased risk of both bleeding and thrombosis. Further descriptions of laboratory investigations in these patients are required. METHODS: Investigation of 24 patients with chronic kidney disease (CKD) stages IV-V with light transmission aggregometry, platelet secretion assays and platelet nucleotide analysis. Patients were in a nonbleeding state and not on antiplatelet medication. Results were compared with our local reference range used within the clinical haematology service. RESULTS: Of the 24 patients, two had decreased responses to arachidonic acid, adenosine diphosphate, collagen, thrombin receptor activator peptide-6 and one had decreased responses to high dose ristocetin, and one had increased response to low dose ristocetin. 11 and 13 out of 24 had abnormal platelet secretion release to collagen and thrombin, respectively. Platelet nucleotide analysis in patients was normal with the exception of a reduction in ADP content in one patient and ATP/ADP ratio in one patient. CONCLUSIONS: In our collection of patients with CKD investigated for platelet function in the nonbleeding state, they generally had normal light transmission aggregometry and nucleotide analysis but around 50% had decreased platelet secretion assays. These results could be important in determining the significance of platelet function tests in patients with bleeding symptoms and renal failure. Further characterization of platelet function tests in future will help characterize haemostasis in renal failure further.

Association Between Omega-3 Fatty Acid Levels and Risk for Incident Major Bleeding Events and Atrial Fibrillation: MESA.

Background Randomized trials of pharmacologic strength omega-3 fatty acid (n3-FA)-based therapies suggest a dose-dependent cardiovascular benefit. Whether blood n3-FA levels also mediate safety signals observed in these trials, such as increased bleeding and atrial fibrillation (AF), remains uncertain. We hypothesized that higher baseline n3-FA levels would be associated with incident bleeding and AF events in MESA (Multi-Ethnic Study of Atherosclerosis), which included a population free of clinical cardiovascular disease at baseline. Methods and Results We examined the association between baseline plasma n3-FA levels (expressed as percent mass of total fatty acid) with incident bleeding and AF in MESA, an ongoing prospective cohort study. Bleeding events were identified from review of hospitalization International Classification of Diseases, Ninth Revision (ICD-9), and International Classification of Diseases, Tenth Revision (ICD-10), codes, and AF from participant report, discharge diagnoses, Medicare claims data, and study ECGs performed at MESA visit 5. Separate multivariable Cox proportional hazard modeling was used to estimate hazard ratios of the association of continuous n3-FA (log eicosapentaenoic acid [EPA], log docosahexaenoic acid [DHA], log [EPA+DHA]) and incident hospitalized bleeding events and AF. Among 6546 participants, the mean age was 62.1 years and 53% were women. For incident bleeding, consistent statistically significant associations with lower rates were seen with increasing levels of EPA and EPA+DHA in unadjusted and adjusted models including medications that modulate bleeding risk (aspirin, NSAIDS, corticosteroids, and proton pump inhibitors). For incident AF, a significant association with lower rates was seen with increasing levels of DHA, but not for EPA or EPA+DHA. Conclusions In MESA, higher plasma levels of n3-FA (EPA and EPA+DHA, but not DHA) were associated with significantly fewer hospitalized bleeding events, and higher DHA levels (but not EPA or EPA+DHA) with fewer incident AF events.