Risk Of Severe Bleeding Research Articles

Risk of Severe Bleeding With Extended Rivaroxaban to Prevent Venous Thromboembolism in Acute Medically Ill Patients With Bronchiectasis.

Background: Bronchiectasis is a chronic inflammation of the bronchi with recurrent infections and hemoptysis. The MAGELLAN study compared oral rivaroxaban, 10 mg once daily (QD), for 35 ± 4 days with subcutaneous enoxaparin 40 mg QD for 10 ± 4 days followed by placebo for 25 ± 4 days to prevent venous thromboembolism in patients hospitalized with an acute medical illness. MAGELLAN included a subset of patients with bronchiectasis. In a post hoc analysis, we evaluated the incidence and severity of pulmonary bleeding in patients with bronchiectasis who were hospitalized for an acute medical illness. This analysis included MAGELLAN patients diagnosed with bronchiectasis at baseline. Patients were evaluated by treatment group for International Society on Thrombosis and Haemostasis major bleeding, non-major clinically relevant (NMCR) bleeding, and the composite of the 2 (ie, clinically relevant bleeding). Results: Medically ill patients with bronchiectasis were randomized to rivaroxaban (n = 60) or enoxaparin/placebo (n = 61). There were 2 fatal pulmonary bleeds and 1 fatal gastrointestinal bleed in the rivaroxaban arm and no fatal or major bleeding in the enoxaparin/placebo arm. The incidence of major bleeding was 5% in the rivaroxaban arm. One NMCR bleed occurred in the rivaroxaban arm and 2 NMCR bleeds occurred in the enoxaparin/placebo arm. The incidence of clinically relevant bleeding was 6.7% versus 3.3% in the rivaroxaban and enoxaparin/placebo groups, respectively (relative risk = 2.06 [95% confidence interval: 0.351-12.046]). Conclusion: In-patients hospitalized with bronchiectasis and an acute medical illness, clinically relevant bleeding, including fatal pulmonary hemorrhage, occurs more frequently with extended rivaroxaban thromboprophylaxis than with enoxaparin followed by placebo.

Intracranial hemorrhage detection

An intracranial hemorrhage is a kind of bleeding which occurs within the brain. The symptoms may vary based on the location of the hemorrhage, it may include total or limited loss of consciousness, abrupt shivering, numbness on one side of the body, loss of motion, serious migraine, drowsiness, problems with speech and swallowing. It is important to get the individual to a hospital and this condition must be treated as a medical emergency. Normally during this emergency, a Computerized Tomographic (CT) scan will be taken by the radiologist and they will identify the location of the hemorrhage and its subtypes. This process is often time consuming and complicated. Through this paper we would like to present a model which uses rich image dataset provided by Radiological Society of North America (RSNA) in collaboration with members of the American Society of Neuroradiology and MD.ai. This will help the medical community identify the presence, location and type of hemorrhage in order to quickly and effectively treat affected patients. This algorithm can provide early detection of people at high risk of severe bleeding in the brain. The algorithm comprises of a neural network architecture designed to detect intracranial hemorrhage while tackling several challenges such as relatively small bleed size and high variance within the brain, the algorithm executes this task by using InceptionV3 and DenseNet models.

Association between ionised calcium and severity of postpartum haemorrhage: a retrospective cohort study

BackgroundPostpartum haemorrhage (PPH) is often complicated by impaired coagulation. We aimed to determine whether the level of ionised calcium (Ca2+), an essential coagulation co-factor, at diagnosis of PPH is associated with bleeding severity. MethodsThis was a retrospective cohort study of women diagnosed with PPH during vaginal delivery between January 2009 and April 2020. Ca2+ levels at PPH diagnosis were compared between women who progressed to severe PPH (primary outcome) and those with less severe bleeding. Severe PPH was defined by transfusion of ≥2 blood units, arterial embolisation or emergency surgery, admission to ICU, or death. Associations between other variables (e.g. fibrinogen concentration) and bleeding severity were also assessed. ResultsFor 436 patients included in the analysis, hypocalcaemia was more common among patients with severe PPH (51.5% vs 10.6%, P<0.001). In a multivariable logistic regression model, Ca2+ and fibrinogen were the only parameters independently associated with PPH severity with odds ratios of 1.14 for each 10 mg dl−1 decrease in fibrinogen (95% confidence interval [CI], 1.05–1.24; P=0.002) and 1.97 for each 0.1 mmol L−1 decrease in Ca2+ (95% CI, 1.25–3.1; P=0.003). The performance of Ca2+ or fibrinogen was not significantly different (area under the curve [AUC]=0.79 [95% CI, 0.75–0.83] vs AUC=0.86 [95% CI, 0.82–0.9]; P=0.09). The addition of Ca2+ to fibrinogen improved the model, leading to AUC of 0.9 (95% CI, 0.86–0.93), P=0.03. ConclusionsCa2+ level at the time of diagnosis of PPH was associated with risk of severe bleeding. Ca2+ monitoring may facilitate identification and treatment of high-risk patients.

Risk Factors of Neonatal Immune Thrombocytopenia in Pregnant Women Previously Diagnosed with ITP: Results from a French Nationwide Prospective Study

Background : Neonatal immune thrombocytopenia (NITP) is a well described complication in newborns of women with ITP. It is reported to occur in about 15% to 30% of neonates. Previous pregnancies with NITP or ITP refractory to splenectomy have been described as associated with NITP mostly in retrospective studies. Methods: We conducted a nationwide prospective multicenter observational case-control study (ClinicalTrials.gov NCT02892630). Thirty-three centers including in the network of ITP experts in France participated in the study. Over a two years period, we enrolled 180 pregnant women with a history of ITP diagnosed before pregnancy and 171 of them were followed up until the delivery. Neonatal platelet counts were available for 136 newborns. Risk factor for developing NITP were evaluated as well as NITP treatment and complications. Results: NITP defined as a platelet count &amp;lt; 100 x 109/L was observed in 37 newborns (27.2%). More severe NITP with platelet counts &amp;lt; 50 x 109/L and &amp;lt; 30 x 109/L, were reported in 19 (14%) and 13 (9.6%) newborns respectively. Intravenous immune globulins were given to 18 newborns. Their median platelet count was 25.5 x 109/L (6; 56). Platelet transfusion was used for 8 newborns with a median platelet count of 13.5 x 109/L (6; 50). NITP was complicated by a hemorrhagic event in only 2 newborns, with a fatal bleeding in 1. Decline in disease ITP status in the mother during pregnancy and previous history of NITP were identified as predictors of NITP &amp;lt; 50 x 109/L by a univariate analysis while only previous history of NITP was confirmed in multivariate analysis (adjusted odds ratio (OR) 4.55; 95% confidence interval (CI) 1.48-13.92; p= 0.008). Decline in ITP disease status in the mother during pregnancy was the sole predictive factor for severe NITP defined as platelet &amp;lt; 30 x 109/L in multivariate analysis (adjusted OR 3.99; 95% CI 1.04-15.36; p = 0.044). Conclusion: Our study confirms that for ITP women with several pregnancies, a previous history of NITP is a risk factor for NITP. We also identify for the first time worsening of disease status during pregnancy to be a novel risk factor of severe NITP. In contrast, we did not confirm that a history of splenectomy was associated with an increased risk of NITP as suggested in retrospective studies (Loustau et al, Br J Haematol 2014; 166 929-35). Our results support that pregnancy in women with ITP is associated with an acceptable risk of severe bleeding in the newborn with NITP which is low but yet existing. Hence, close monitoring of pregnancy and delivery of mothers with ITP and their newborns is required, mainly in women who have a previous history of NITP or experienced a worsening of ITP during the pregnancy. Disclosures Haioun: Takeda: Honoraria; Novartis: Honoraria; Janssen: Honoraria; Gilead: Honoraria; Celgene: Honoraria; Amgen: Honoraria; Roche: Honoraria; Servier: Honoraria; Miltenyi: Honoraria. Mahevas:GSK: Research Funding. Michel:Rigel: Consultancy; Bioverativ: Consultancy; Alexion Pharmaceuticals: Consultancy. Godeau:Novartis: Honoraria; Amgen: Honoraria; Amgen: Research Funding; LFB: Honoraria.

Приобретенная гипопротромбинемия у пациентки с лимфопролиферативным заболеванием в сочетании с волчаночным антикоагулянтом

Введение: Приобретенная гипопротромбинемия, обусловленная циркуляцией волчаночного антикоагулянта (ВА), ассоциируется с высоким риском развития тяжелого кровотечения. Клинический случай: Описан случай приобретенного дефицита протромбина и фактора IX в сочетании с положительным ВА: у пациентки Н. была диагностирована лимфома из клеток маргинальной зоны, выявлен дефицит фактора II (21%) и фактора IX (27,1%), увеличение активированного частичного тромбопластинового времени, протромбинового времени и международного нормализованного отношения, обнаружены положительные маркеры антифосфолипидного синдрома, по данным тромбоэластографии — выраженная гипокоагуляция. Выполнена абдоминальная спленэктомия. Перед операцией пациентке был введен концентрат протромбинового комплекса (КПК) Уман Комплекс Д. И. в дозе 1500 МЕ. После введения КПК мы не достигли целевого значения активности факторов свертывания: фактор II увеличился до 49%, фактор IX — до 47%. Клинически оперативное вмешательство не сопровождалось геморрагическим синдромом. Заключение: Сочетанный приобретенный дефицит протромбина и фактора IX у пациентки Н. с лимфомой при наличии ВА существенно увеличивал риск развития тяжелого интраоперационного кровотечения. Введение КПК с адекватным мониторингом гемостаза позволило избежать развития осложнений в периоперационном периоде. Background: Acquired hypoprothrombinemia due to lupus anticoagulant presence is associated with a high risk of severe bleeding. Clinical case: The article describes the case of acquired prothrombin and factor IX defi ciency combined with a positive lupus anticoagulant (LA). The patient N. was diagnosed lymphoma from marginal zone cells. She had factor II (21%) and factor IX (27.1%) deficit, increased activated partial thromboplastin time, prothrombin time and international normalized ratio, positive markers of antiphospholipid syndrome, severe hypocoagulation according to thromboelastography. An abdominal splenectomy was performed. Before surgery, prothrombin complex concentrate (PCC) Complex DI Uman in a dose of 1500 IU was administrated. After PCC administration, we did not reach the target value of coagulation factors activity: factor II increased to 49%, factor IX — to 47%. Surgery was not associated with hemorrhagic syndrome. Conclusions: The combined acquired defi ciency of prothrombin and factor IX in patient N. with lymphoma and LA significantly increased the risk of severe intraoperative bleeding. PCC administration with adequate monitoring of hemostasis allowed to avoid the development of complications in perioperative period.

Fibrin monomers and association with significant hemorrhage or mortality in severely injured trauma patients

BackgroundPost-traumatic hemorrhage is still the leading cause of potentially preventable death in patients with severe trauma. Traumatic-induced coagulopathy has been described as a risk factor for significant hemorrhage and mortality in this population. Fibrin monomers (FMs) are a direct marker of thrombin action, and thus reflect coagulation activation. This study sought to determine the association of FMs levels at admission with significant hemorrhage and 28-day mortality after a severe trauma. MethodsWe conducted a retrospective, observational study including all severe trauma patients admitted in a level-1 trauma center between January 2012 and December 2017. Patients with severe traumatic brain injury or previous anticoagulant / antiaggregant therapies were excluded. FMs measurements and standard coagulation test were taken at admission. Significant hemorrhage was defined as a hemorrhage requiring the transfusion of ≥ 4 Red Blood Cells units during the first 6 h. Multivariable analysis was applied to identify predictors of significant hemorrhage and a simple logistic regression analysis was applied to identify an association between FMs and 28-day mortality. ResultsOverall, 299 patients were included. A total of 47 (16%) experienced a significant hemorrhage. The ROC curve demonstrated that FMs had a poor accuracy to predict the occurrence of significant hemorrhage with an AUC of 0.65 (0.57–0.74). The best threshold at 92.45 µg/ml had excellent sensitivity (87%) and negative predictive value (95%), but was not independently associated with significant hemorrhage (OR = 1.5; 95%CI (0.5–4.2)). The 28-day mortality rate was 5%. In simple logistic regression analysis, FMs values ≥109.5 µg/ml were significantly associated with 28-day mortality (unadjusted OR = 13.2; 95%CI (1.7–102)). ConclusionsFMs levels at admission are not associated with the occurrence of a significant hemorrhage in patients with severe trauma. However, the excellent sensitivity and NPV of FMs could help to identify patients with a low risk of severe bleeding during hospital care. In addition, FMs levels ≥109.5 µg/ml might be predictive of 28-day mortality.

Association of hemorrhage at termination in caesarean scar pregnancy using the crossover sign of ultrasound image.

To analyze whether crossover sign (COS) can help predict the risk of bleeding during surgical evacuation in patients with caesarean scar pregnancy (CSP). This study retrospectively analyzed the clinical presentations, ultrasound images and treatment outcomes of patients with CSP. The relationship among the gestational sac, caesarean scar and the anterior uterine wall, defined as the COS, was analyzed to predict the risk of severe bleeding during surgical evacuation in these patients. All patients were categorized according to the relationship between the endometrial line and the superior-inferior diameter of the gestational sac into crossover sign-1 and crossover sign-2 groups. The Mann-Whitney U test was used to compare the data with non-normal distribution, and logistic regression analysis was performed to identify the correlates of severe bleeding. A total of 74 patients were included. In COS-1 group (n = 21), 16 (76.19%) patients suffered heavy bleeding(≥200 mL) during surgical evacuation, while COS-2 group (n = 53) had only 1(11.89%) patient complaint of heavy bleeding (≥200 mL) (P < 0.01). Adverse surgical outcomes were more common in women with COS-1. Logistic regression analysis showed that COS-1 (OR, 7.93; 95% CI, 1.35-46.67) was independently associated with severe bleeding. COS can help predict who has a higher risk of severe hemorrhage in patients with CSP and guide the clinical treatment selection for optimal management of this condition.

Novel antiplatelet targets in the treatment of acute coronary syndromes

Acute coronary syndromes (ACS) are a global cause of mortality and morbidity that affect millions of lives worldwide. Following atherosclerotic plaque rupture, platelet activation and aggregation are the two major elements that initiate thrombus formation inside a coronary artery, which can obstruct blood flow and cause myocardial ischemia; ergo, antiplatelet therapy forms a major part of the treatment strategy for ACS. Patients with ACS routinely receive dual antiplatelet therapy (DAPT), which consists of aspirin and a platelet P2Y12 inhibitor to both treat and prevent atherothrombosis. Use of platelet glycoprotein (GP) IIb/IIIa inhibitors is now limited due to the risk of severe bleeding and thrombocytopenia. Thus, administration of GPIIb/IIIa inhibitors is generally restricted to bail out thrombotic events associated with PCI. Furthermore, current antiplatelet medications mainly rely on thromboxane A2 and P2Y12 inhibition, which have broad-acting effects on platelets and are known to cause bleeding, which especially limits the long-term use of these agents. In addition, not all ACS patients treated with current antiplatelet treatments are protected from recurrence of arterial thrombosis, since many platelet mechanisms and activation pathways remain uninhibited by current antiplatelet therapy. Pharmacological antagonism of novel targets involved in platelet function could shape future antiplatelet therapies that could ultimately lead to more effective or safer therapeutic approaches. In this article, we focus on inhibitors of promising targets that have not yet been introduced into clinical practice, including inhibitors of GPVI, protease-activated receptor (PAR)-4, GPIb, 5-hydroxytryptamine receptor subtype 2A (5-HT2A), protein disulfide isomerase, P-selectin and phosphoinositide 3-kinase β.

Switching Fractioned R-CHOP Cycles to Standard R-CHOP Cycles Guided by Endoscopic Ultrasonography in Treating Patients with Primary Gastric Diffuse Large B-Cell Lymphoma.

BackgroundPrimary gastric diffuse large B-cell lymphoma (PG-DLBCL) is a common subtype of extranodal non-Hodgkin lymphoma (NHL), with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) as the commonly used treatment regimen. However, full cycles of standard R-CHOP present the risk of severe bleeding or perforation, even leading to emergency surgery, especially for those with deep lesions in their first 1–2 cycles of treatment. This study aims to explore the safety and efficacy of fractioned R-CHOP (rituximab d0, 50% dose of CHOP d1 and d5) followed by standard R-CHOP cycles in PG-DLBCL patients guided by endoscopic ultrasonography (EUS).Patients and MethodsThirty-one PG-DLBCL patients were analyzed in this retrospective study. All patients had lesions infiltrated to at least the 3rd layer of the stomach under EUS at baseline. Patients switched to standard R-CHOP if they showed the reduced infiltrated layers and restricted lesions after fractioned R-CHOP cycles.ResultsThe overall response rate, 5-year progression-free survival (PFS) and overall survival (OS) of patients in our study were 93.5%, 75% and 84%, respectively. No treatment delay or dosage reduction from gastric adverse event was observed. None of the patients in our study suffered from severe bleeding or perforation during the treatment. Kaplan–Meier analyses showed that PG-DLBCL patients characterized by multiple localization, lesions ≥3cm, having B symptoms, lower serum albumin level, and elevated LDH level were associated with worse PFS and OS.ConclusionOur data indicate that it might be an effective approach in treating deeply infiltrated PG-DLBCL patients by switching fractioned R-CHOP to standard R-CHOP cycles guided by EUS.

Racial and Gender Disparity in Aortoiliac Disease Open Revascularization Procedures

BackgroundThe impact of race and gender on surgical outcomes has been studied in infrainguinal revascularization for peripheral arterial disease. The aim of this study is to explore how race and gender affect the outcomes of suprainguinal bypass (SIB) for aortoiliac occlusive disease. Materials and methodsPatients who underwent SIB were identified from the procedure-targeted National Surgical Quality Improvement Program data set (2011-2016). Patients were stratified into four groups: nonblack males, black males (BM), nonblack females, and black females (BF). Primary outcomes were 30-d major adverse cardiac events, a composite of myocardial infarction, stroke, or death; postoperative bleeding requiring transfusion or intervention; major amputation and prolonged length of stay (>10 d). Predictors of outcomes were determined by multivariable logistic regression analysis. ResultsAbout 5044 patients were identified. BM were younger, more likely to be smokers, less likely to be on antiplatelet drug or statin, and to receive elective SIB (all P ≤ 0.01). BFs were more likely to be diabetic and functionally dependent (all P ≤ 0.02). Major adverse cardiac events were not significantly different among all groups. BM had a threefold higher risk of amputation (adjusted odds ratio [OR] [95% confidence interval (95% CI)], 3.10 [1.50-6.43]; P < 0.002). Female gender was associated with bleeding in both races, that association was more drastic in BF (OR [95% CI], 2.43 [1.63-3.60]; P < 0.0001), whereas nonblack females (OR [95% CI], 1.46 [1.19-1.80]; P < 0.0001). BF had higher odds of prolonged length of stay (OR [95% CI]: 1.62 [1.08-2.42]; P < 0.019). ConclusionsIn this large retrospective study, we demonstrated the racial and gender disparity in SIB outcomes. BM had more than threefold increase in amputation risk as compared with nonblack males. Severe bleeding risk was more than doubled in BF. Race and gender consideration is warranted in risk assessment when patients are selected for aortoiliac disease revascularization, which in turn necessitate preoperative risk modification and optimization in addition to enhancing their access to primary preventive care measures.

Risk factors for severe bleeding events during warfarin treatment: the influence of sex, age, comorbidity and co-medication

PurposeTo investigate risk factors for severe bleeding during warfarin treatment, including the influence of sex, age, comorbidity and co-medication on bleeding risk.MethodsPatients initiating warfarin treatment between 2007 and 2011 were identified in the nationwide Swedish Prescribed Drug Register, and diagnoses of severe bleeding were retrieved from the National Patient Register. Hazard ratios (HR) with 95% confidence intervals (CI) for severe bleeding were estimated using multiple Cox regression adjusting for indications and including covariates age, sex, comorbidities and co-medications. Interactions between sex and other covariates were investigated.ResultsThe study cohort included 232,624 patients ≥ 18 years (101,011 women and 131,613 men). The incidence rate of severe bleeding was 37 per 1000 person-years, lower among women than men with an adjusted HR (95% CI) of 0.84 (0.80–0.88). Incidence of bleeding increased with age, HR 2.88 (2.37–3.50) comparing age ≥ 80 to < 40 years, and comorbidities associated with the highest risk of severe bleeding were prior bleeding, HR 1.85 (1.74–1.97); renal failure, HR 1.82 (1.66–2.00); and alcohol dependency diagnosis, HR 1.79 (1.57–2.05). Other comorbidities significantly associated with bleeding events were hypertension, diabetes, peripheral vascular disease, congestive heart failure, liver failure, stroke/TIA, COPD and cancer.ConclusionMost of the well-established risk factors were found to be significantly associated with bleeding events in our study. We additionally found that women had a lower incidence of bleeding. Potential biases are selection effects, residual confounding and unmeasured frailty.

Double or Triple Antithrombotic Treatment in Atrial Fibrillation Patients with Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention.

Patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) have traditionally received triple antithrombotic therapy (TAT) consisting of aspirin and a P2Y12 inhibitor plus an oral anticoagulant (OAC) to reduce atherothrombotic events, even though this strategy is associated with a high risk of severe bleeding. Recent trials have indicated that dual antithrombotic therapy (DAT), consisting of a P2Y12 inhibitor plus an OAC, may be superior to TAT in terms of bleeding risk; however, thetrade-off regarding ischemic complications may be questionable. Patients who have had a myocardial infarction (MI) before undergoing PCI warrant special consideration because of the accompanying high ischemic risk, including stent thrombosis, which might be exacerbated by an aspirin-free strategy such as DAT. In particular, in the acute phase of ST-segment elevation MI (STEMI), the highly prothrombotic milieu may necessitate initial TAT, though durations may vary, making a tailored antithrombotic regimen for this high-risk subset of patients a fairly challenging and difficult scenario for clinicians. Since patients with MI, especially STEMI, are underrepresented in randomized trials, data regarding the optimal antithrombotic treatment in such patients are sparse. This review aims to analyze the outcomes of different antithrombotic regimens in patients with MI and AF undergoing PCI, define the role of DAT versus TAT regarding safety and efficacy outcomes, and address controversial issues and future perspectives.

How I Manage Thrombotic/Thromboembolic Complications in Myeloproliferative Neoplasms.

Patients with myeloproliferative neoplasms (MPNs), such as polycythemia vera, essential thrombocythemia, and primary myelofibrosis, are at increased risk for arterial and venous thrombosis/thromboembolism. In particular, the risk of splanchnic venous thrombosis, such as portal vein thrombosis or Budd-Chiari syndrome, is significantly higher in patients with MPN than in the normal population. At the same time, MPN patients are at increased risk for severe bleeding. Therefore, the treatment of patients with MPN must be based on their suspected probability of thrombosis/thromboembolism and bleeding. For this purpose, patient and MPN-specific risk factors are used. Patients at expected high risk of thrombosis should receive adequate primary or secondary thromboprophylaxis in addition to cytoreductive therapy. This may consist of antiplatelet agents and/or anticoagulant agents and must be balanced with the individual bleeding risk. The goal is to increase the quality of life and life span of patients with MPNs by preventing (re-)thrombosis and severe bleeding.

Novel deep intronic mutation in the coagulation factor XIII a chain gene leading to unexpected RNA splicing in a patient with factor XIII deficiency

BackgroundCoagulation factor XIII (FXIII) plays an essential role in maintaining hemostasis by crosslinking fibrin. Deficiency in FXIII affects clot stability and increases the risk of severe bleeding. Congenital FXIII deficiency is a rare disease. Recently, we identified a Chinese family with FXIII deficiency and investigated the pathogenesis of congenital FXIII deficiency, contributing non-coding pathogenic variants.MethodsWe performed common tests, coding sequencing by targeted next-generation sequencing (NGS), whole-genome sequencing and splice-sites prediction algorithms. The pathogenesis was investigated via minigene and nonsense-mediated mRNA decay (NMD) by experiments in vitro.ResultsThe proband is homozygote for a novel deep intronic c.799-12G > A mutation in the F13A1 gene. Through direct sequencing of the minigenes mRNA, we found 10 bases of intron 6 insert in the mRNA of mutant minigenes mRNA. The relative expression of EGFP-F13A1 was higher by suppression of NMD in vitro. Furthermore, we found the proband with enhanced thrombin generation (TG).ConclusionWe reported a novel deep intronic c.799-12G > A mutation of F13A1 which produced a new acceptor site and frame shifting during translation introducing a premature termination codon. Our results support the premature termination codon triggered NMD. We need to pay attention to the position of potential alterable splicing sites while counselling and genetic test. The finding of enhanced TG indicated that we should be aware of the risk of thrombosis in patients with FXIII deficiency during replacement therapy.

Plasma and Urinary FGF-2 and VEGF-A Levels Identify Children at Risk for Severe Bleeding after Pediatric Cardiopulmonary Bypass: A Pilot Study.

Severe bleeding after cardiothoracic surgery with cardiopulmonary bypass (CPB) is associated with increased morbidity and mortality in adults and children. Fibroblast Growth Factor-2 (FGF-2) and Vascular Endothelial Growth Factor-A (VEGF-A) induce hemorrhage in murine models with heparin exposure. We aim to determine if plasma and urine levels of FGF-2 and VEGF-A in the immediate perioperative period can identify children with severe bleeding after CPB. We performed a prospective, observational biomarker study in 64 children undergoing CPB for congenital heart disease repair from June 2015 - January 2017 in a tertiary pediatric referral center. Primary outcome was severe bleeding defined as ≥ 20% estimated blood volume loss within 24-hours. Independent variables included perioperative plasma and urinary FGF-2 and VEGF-A levels. Analyses included comparative (Wilcoxon rank sum, Fisher's exact, and Student's t tests) and discriminative (receiver operator characteristic [ROC] curve) analyses. Forty-eight (75%) children developed severe bleeding. Median plasma and urinary FGF-2 and VEGF-A levels were elevated in children with severe bleeding compared to without bleeding (preoperative: plasma FGF-2 = 16[10-35] vs. 9[2-13] pg/ml; urine FGF-2= 28[15-76] vs. 14.5[1.5-22] pg/mg; postoperative: plasma VEGF-A = 146[34-379] vs. 53 [0-134] pg/ml; urine VEGF-A = 132 [52-257] vs. 45[0.1-144] pg/mg; all p < 0.05). ROC curve analyses of combined plasma and urinary FGF-2 and VEGF-A levels discriminated severe postoperative bleeding (AUC: 0.73-0.77) with mean sensitivity and specificity above 80%. We conclude that the perioperative plasma and urinary levels of FGF-2 and VEGF-A discriminate risk of severe bleeding after pediatric CPB.

Plastibell circumcision: Comparison between neonates and infants.

Background:The Plastibell circumcision technique has gained popularity worldwide. It has a low bleeding risk which makes it suitable for a vulnerable population and in late circumcision. However, several problems resulting from prolonged retention of the Plastibell ring were reported.Objectives:The objectives of this study were to assess the outcomes of circumcision performed using Plastibell devices, report ring-related complications, and compare the complications of the technique between neonates and infants.Methods:This was a retrospective cohort study that was conducted in a total of 989 male neonates and infants who had Plastibell circumcision performed by a single surgeon between June 2006 and February 2018. Postoperative complications were reported and compared between the two age groups. The indications of the Plastibell technique were religious in 988 patients and urinary tract infection in 1 patient.Results:During the study period, Plastibell circumcision was performed in 633 neonates and 356 infants. The average ages of neonates and infants were 14 ± 2 days and 3 ± 0.5 months, respectively. Complications developed in 89 cases, 4.4% in neonates and 17% in infants (P < 0.001). The retained ring was the most common complication in 46 cases (4.6%), followed by excess skin in 21 cases (2%). Bleeding occurred in 10 cases (1%), infection in 7 cases (0.7%), and hematoma in 2 cases (0.2%).Conclusion:Complications of Plastibell circumcision are significantly higher in infants than in neonates, and ring retention is the most common complication in both the groups. However, the risk of severe hemorrhage is low making it a good option for infants in the outpatient setting.

Bronchial arterial embolization may reduce the risk of severe bleeding in central airway obstruction due to renal cell carcinomas during bronchoscopic procedures.

Background:Hemorrhage is a life-threatening complication during bronchoscopic intervention in patients with central airway obstruction (CAO) due to metastatic renal cell carcinoma (RCC). Whether pre-bronchoscopic bronchial arterial embolization (BAE) can reduce the risk of severe bleeding in CAO patients due to metastatic RCC remains unclear.Methods:A total of 31 CAO patients due to metastatic RCC were included retrospectively and divided into a BAE group (receiving pre-bronchoscopic BAE) and non-BAE group in this study. Based on computed tomography (CT) and bronchoscopic findings, tumor debulking was used to reconstruct the airway during interventional bronchoscopy. The primary outcome was the incidence of severe bleeding during bronchoscopic procedures. Bleeding-related complications, Karnofsky performance score (KPS) and dyspnea score were also analyzed over a 1-month observation period.Results:There were no significant differences between the two groups in baseline characteristics, including patients’ features, tumor morphology under CT scannings, tumor site, and obstruction degree under bronchoscopic examination. Procedure-related bleeding occurred in all 31 patients. Pre-bronchoscopic BAE significantly reduced the incidence of moderate and major bleeding when compared with that in the non-BAE group. The incidence of poor visualization and hypoxia was also reduced significantly in the BAE group. There was no significant difference in KPS and dyspnea score between the BAE and non-BAE groups at 1 month follow up.Conclusion:Pre-bronchoscopic BAE might be a feasible option to reduce the risk of severe bleeding for CAO patients due to metastatic RCC during bronchoscopic intervention. Interventional bronchoscopy was a safe and effective procedure for CAO due to metastatic RCC. The reviews of this paper are available via the supplemental material section.

EFFECT OF SCLEROTHERAPY USING COPPER WIRES ASSOCIATED WITH CORTICOSTEROIDS IN THE TREATMENT OF VASCULAR LESIONS

Vascular injuries in the oral cavity cause anesthetic and functional problems, and a high risk of severe hemorrhages in simple surgical treatments; therapy with copper wires and corticosteroids generates local coagulation and fibrosis and are effective for an uncomplicated resection. Through a series of cases, clinical and anatomopathologic characteristics of the combined sclerotherapy effects are described, as an alternative for the treatment of vascular malformations performed on 7 patients, using intralesional corticoid (0.2 mL/cm2) for 2 or 3 weeks, followed by a cerclage with copper wires, for 1 week, until color change from red or purple to lighter color and a fibrous consistency was observed. Continued resection of the lesion occurred in the absence of bleeding. Histologic studies were performed, which revealed neoformation of fibrous tissue, hyalinization of blood vessels, and loss of endothelial continuity. The result was favorable in 100% of the cases.

Platelets level response after three days therapy in children with acute Immune Thrombocytopenic Purpura (ITP): a 10 years’ experience at the tertiary hospital

Background: Immune thrombocytopenic purpura (ITP) is the most common cause of thrombocytopenia in children that characterized by isolated thrombocytopenia that vary in bleeding manifestations. The onset of disease is sudden and a self-limiting condition that requires treatment when clinically significant bleed occurs. A treatment goal is to increase platelet level above safety level and reduce the risk of severe bleeding. This study aims to evaluate the platelets level increment after three days treatment among children with acute ITP.Methods: An analytic retrospective cross-sectional study was conducted in Haematology-Oncology Paediatric Division Sanglah General Hospital, Bali, Indonesia from October 2008 to October 2018 in ITP patients. Diagnosis of ITP was evaluated based on the clinical manifestation and laboratory finding. Oral corticosteroid medication with dosage 2 mg/kg/day or 4 mg/kg/day with or without platelets transfusion were enrolled in this study from medical records. Data were analyzed using SPSS version 20 for Windows.Results: There were 93 children met the inclusion criteria and included in this study. A median platelets level at admission was 6.81(1-86.8) x 109/L. Majority symptoms of children with ITP in our tertiary care centre presented with mild to moderate clinical bleeding symptoms. Only 5.6% children with platelets level below 10x109/L had intracranial bleeding. Median platelets level was 31(2.47-382) x 109/l and there was a significant platelets level increment after three days of therapy (P&lt;0.05).Conclusion: The platelets level increment significantly in children with acute ITP after three days of therapy.

The cardiovascular benefits of low-dosage acetylsalicylic acid.

The increased risk of severe bleeding with use of acetylsalicylic acid (ASA) (odds ratio 2.2, 95% confidence interval [CI] 1.4–3.4) is outweighed by the 21% reduction (95% CI 0.72–0.88) in the odds of recurrent atherosclerotic events (coronary artery disease, ischemic stroke or transient