Enoxaparin Research Articles

Features of disorders and methods of correction of the hemostasis system in women with antenatal fetal death

The improvement of the providing medical services quality to pregnant women remains an urgent issue in modern obstetrics. Women with perinatal losses deserve special attention, especially in the second half of pregnancy. Changes in the hemostasis system are an integral part of the development of pregnancy. The tendency to hypercoagulation has significant pathogenetic significance and can be the cause of a number of complications – miscarriage in the I trimester of pregnancy and preeclampsia, premature birth, antenatal fetal death (AFD) – in the II and III trimesters of pregnancy. Also, pregnancy is a background process for the activation of a number of diseases, in particular hereditary thrombophilia.The objective: to evaluate the changes in the hemostasis system in women with antenatal fetal death and the effectiveness of the use of low molecular weight heparins for the correction of disorders in the hemostasis system in this category of patients during childbirth and in the postpartum period.Materials and methods. 72 women were examined, including 42 pregnant women with AFD (main group) and 30 pregnant women with a physiological course of pregnancy, childbirth and the postpartum period (control group). The state of the hemostasis system was studied using a standard coagulogram. D-dimer was determined by immunoturbometric analysis.To assess the state of the hemostasis system, the following biochemical tests were used: procoagulant link – fibrinogen content and indicators: prothrombin index, activated partial thrombin time (APTT), thrombin time (TP), ancistrone time (AT), soluble fibrinogen-monomer complex (SFMC), factor X (FX); to evaluate the antithrombin system, the content of antithrombin-III (AT-III), protein C were determined; to characterize the state of the fibrinolytic system – the amount of plasminogen, α2-antiplasmin, fibrinogen degradation products (FDC).Thrombophilia markers and antiphospholipid antibodies were also determined. The preference was given to vaginal childbirth. During childbirth, mechanical compression of the lower limbs was applied using special compression stockings (compression level 2). In 12 hours after delivery thromboprophylaxis with low molecular weight heparins was started, the drug of choice being enoxaparin sodium. After 48 hours of the postpartum period, a comparative analysis of coagulogram indicators was performed to further determine the timing of thromboprophylaxis.Results. Analysis of family thrombotic anamnesis revealed risk factors in 12 (28.6%) patients of the main group. In close relatives of the first line, the presence of peripheral vein thrombosis was found – 5 (41.7%) cases, myocardial infarction under the age of 45 – 3 (25.0%) cases, pulmonary embolism – 1 (8.3%) case, transient ischemic attack of the brain – 3 (25.0%).In the control group only 2 (6.6%) patients had a family history of venous thromboembolism in first-line relatives. The analysis of the coagulation system shows significantly higher fibrinogen values (the main group – 5.3±0.2 g/l, the control group – 4.3±0.1 g/l; p<0.05), functional FX activity (the main group – 149.3±3.1%, control group – 107.3±2.7%; p<0.05), SFMC (main group – 15.9±1.2 μg/ml, control group – 7.8±0.9 μg/ml; p<0.05) and D-dimer (main group – 4.4±0.25 μg/ml, control group – 0.7±0.2 μg/ml; p< 0.05) in pregnant women of the main group. An increase in these indicators is a predictor of thrombus formation, activation of blood coagulation by the internal pathway with a decrease in the antithrombin reserve due to FX.During the correlation analysis, a strong direct relationship (r=0.8633) was established between the indicators of SFMC and FX in the blood serum of pregnant women of the main group, the combination of which determines the tendency to clot formation. Determination of markers for the most common types of thrombophilia shows the dominance of hereditary forms (prothrombin, Leiden mutation, MTHFR) in 43% of pregnant women of the main group.The implementation of the proposed treatment approach contributed to a significant decrease in the average concentration of fibrinogen 48 hours after delivery in postpartum women of the main group (main group: before delivery – 5.3±0.2 g/l, after 48 hours after delivery – 3.9±0.3 g/l; control group: 48 hours after delivery – 3.2±0.2 g/l; p<0.05) in combination with a synergistic decrease in the average indicators of SFMC (main group: before delivery – 15.9±1.2 μg/ml, 48 hours after delivery – 6.2±0.2 μg/ml; control group: 48 hours after delivery – 5.4±0.3 μg/ml; p<0.05) and FX (main group: before delivery – 149.3±3.1%, after 48 hours after delivery – 103.1±3.6%; control group: after 48 hours after delivery – 117.1±4.1%; p<0.05).Conclusions. Increased coagulation function was confirmed in pregnant women with antenatal fetal death (AFD). Thanks to the proposed method of correcting disorders in the hemostasis system, a decrease in the frequency of postpartum thromboembolism in women with AFD is achieved, as well as an improvement in the main indicators of the hemostasis system. This prevents the emergence of a chronic form of the syndrome of disseminated intravascular blood coagulation which is developed in the cases of AFD.

#3232 ANTICOAGULANT RELATED NEPHROPATHY – AN UNDERDIAGNOSED COMPLICATION

Abstract Background and Aims Anticoagulant-related nephropathy (ARN) is an underdiagnosed complication of anticoagulant therapy (AT). Method We report 3 cases of ARN. Patient 1: 31 year-old male (M), kidney transplanted for reflux nephropathy, with normal renal function (Rfx) and urinalysis (U), on therapy with tacrolimus (FK), everolimus and mycophenolate. He started edoxaban (E) (60 mg od) for deep vein thrombosis (DVT). After 10 days he developed hematuria and Acute Kidney Injury (AKI). Ruled out urological and infectious causes, we performed kidney biopsy (KB) which showed extensive tubular necrosis (TN), erythrocyte casts (cRBC) and glomerular hemorrhage (EG). Perl's stain (PS) showed iron deposits in tubular cells released by erythrocytes lysis (Fig. 1). Although E posology was adequate the concomitant intake of FK by reducing CYP3A4 metabolism of E resulted in over anticoagulation (OAC), demonstrated by the dosage of the factor Xa (FXa) at peak. Upon withdrawal of AT, Rfx and U normalized. Patient 2: 73-year-old M with hypertension and mild chronic kidney disease (CKD) on antiplatelet therapy (ASA 100 mg od) for biological valve prosthesis and AT with Enoxaparin sodium (Es) (4000UI od) for DVT prophylaxis. He was admitted to the hospital for fever and hypotensive episodes. Microbiological, neoplastic and immune investigations were negative. A progressive worsening of Rfx associated with macro-hematuria was observed, requiring renal replacement therapy (RRT). KB showed a post-infectious glomerulonephirits, but in the hypothesis that tubular damage was enhanced by antiplatelet/AT, PS was performed and resulted positive. OAC was confirmed by the dosage of the factor Xa (FXa) at peak. After withdrawal of therapy, progressive improvement of the Rfx and hematuria were observed, such as to allow the suspension of the RRT. Patient 3: 54 year-old M with kidney and lung involvement of ANCA-associated vasculitis. After rituximab induction therapy he showed marked improvement on lung and renal function and antibody titer (c-ANCA PR3 positive). He experienced an unusual worsening of Rfx and hematuria after starting a AT (Es 6000 UI BID) to treat a DVT. A KB was performed in the suspicion of ARN. The histology revealed an extensive TN, numerous cRBC with extracapillary glomerulonephritis and PS positive. IF was negative. OAC was confirmed and adjustment of anticoagulation dose for glomerular filtration rate resulted in improvement of Rfx. Results ARN is a not uncommon occurrence in cases of OAC and glomerular fragility (Table 1). Conclusion ARN should be suspected in predisposed patients in whom glomerular hyperfiltration or preexisting GN during OAC facilitate EG. Attention should be given to drug interactions that can induce an unrecognized OAC. The cases described underline the need for careful monitoring of U, RFx and FXa activity to promptly treat this complication, avoiding permanent damage.

CO144 Enoxaparin Sodium Biosimilar in the Prophylactic Treatment of Veinous Thromboembolism and Thromboembolic Disease: Prophyvar Study

Varenox® is the first locally manufactured and approved biosimilar in Algeria. It is an enoxaparin sodium (ES) with established good analytical characterization and manufacturing quality control. The aim of the PROPHYVAR study was to generate real-life data in routine practices and to assess the safety and tolerability in the prophylaxis of venous thromboembolism (VTE).

Enoxaparin sodium bone cement plays an anti-inflammatory immunomodulatory role by inducing the polarization of M2 macrophages

ObjectiveThe implantation of PMMA bone cement results in an immune response and the release of PMMA bone cement particles causes an inflammatory cascade. Our study discovered that ES-PMMA bone cement can induce M2 polarization of macrophages, which has an anti-inflammatory immunomodulatory effect. We also delved into the molecular mechanisms that underlie this process.MethodsIn this study, we designed and prepared samples of bone cement. These included PMMA bone cement samples and ES-PMMA bone cement samples, which were implanted into the back muscles of rats. At 3, 7, and 14 days after the operation, we removed the bone cement and a small amount of surrounding tissue. We then performed immunohistochemistry and immunofluorescence to observe the polarization of macrophages and the expression of related inflammatory factors in the surrounding tissues. The RAW264.7 cells were exposed to lipopolysaccharide (LPS) for 24 h to establish the macrophage inflammation model. Then, each group was treated with enoxaparin sodium medium, PMMA bone cement extract medium, and ES-PMMA bone cement extract medium, respectively, and cultured for another 24 h. We collected cells from each group and used flow cytometry to detect the expressions of CD86 and CD206 in macrophages. Additionally, we performed RT-qPCR to determine the mRNA levels of three markers of M1 macrophages (TNF-α, IL-6, iNOS) and two M2 macrophage markers (Arg-1, IL-10). Furthermore, we analyzed the expression of TLR4, p-NF-κB p65, and NF-κB p65 through Western blotting.ResultsThe immunofluorescence results indicate that the ES-PMMA group exhibited an upregulation of CD206, an M2 marker, and a downregulation of CD86, an M1 marker, in comparison to the PMMA group. Additionally, the immunohistochemistry results revealed that the levels of IL-6 and TNF-α expression were lower in the ES-PMMA group than in the PMMA group, while the expression level of IL-10 was higher in the ES-PMMA group. Flow cytometry and RT-qPCR analyses revealed that the expression of M1-type macrophage marker CD86 was significantly elevated in the LPS group compared to the NC group. Additionally, M1-type macrophage-related cytokines TNF-α, IL-6, and iNOS were also found to be increased. However, in the LPS + ES group, the expression levels of CD86, TNF-α, IL-6, and iNOS were decreased, while the expression of M2-type macrophage markers CD206 and M2-type macrophage-related cytokines (IL-10, Arg-1) were increased compared to the LPS group. In comparison to the LPS + PMMA group, the LPS + ES-PMMA group demonstrated a down-regulation of CD86, TNF-α, IL-6, and iNOS expression levels, while increasing the expression levels of CD206, IL-10, and Arg-1. Western blotting results revealed a significant decrease in TLR4/GAPDH and p-NF-κB p65/NF-κB p65 in the LPS + ES group when compared to the LPS group. Additionally, the LPS + ES-PMMA group exhibited a decrease in TLR4/GAPDH and p-NF-κB p65/NF-κB p65 levels when compared to the LPS + PMMA group.ConclusionES-PMMA bone cement is more effective than PMMA bone cement in down-regulating the expression of the TLR4/NF-κB signaling pathway. Additionally, it induces macrophages to polarize towards the M2 phenotype, making it a crucial player in anti-inflammatory immune regulation.Graphical

Complications and outcomes of pregnancy in patients with antiphospholipid antibodies during various treatment methods

Introduction. Antiphospholipid antibodies (APAs) exert multifaceted effects on the course of pregnancy by disrupting microcirculation, affecting the hemostasis, as well as damaging the endothelial membranes, leading to early reproductive loss and development of placenta-associated complications depending on the affected gestation stage. Planning and management of pregnancy in women in the absence of criteria for complete antiphospholipid syndrome (APS) currently remains unresolved issue. The absence of generally accepted treatment standards for this category of patients and inability to substantiate the diagnosis according to the APS classification criteria complicate selection of therapeutic tactics.Aim: to conduct a comparative analysis of therapy-based complications and outcomes of pregnancy in APA carriers.Materials and Methods. During the period 2019–2021 a prospective study of 150 patients who entered pregnancy with aggravated obstetric and gynecological history, serum APA level was examined. Considering the risks of developing obstetric and thrombotic complications, all patients were prescribed prophylactic doses of low molecular weight heparins (LMWHs) and low doses of acetylsalicylic acid (ASA). The patients were divided into 3 groups using a random number generator. Group 1 (n = 50), in addition to the prescribed LMWH (enoxaparin sodium 40 mg 1 time per day) and ASA (150 mg 1 time per day), also underwent plasmapheresis (PF) 4 sessions per 1 course in 6–8, 12–14 and 22–24 weeks of pregnancy; group 2 (n = 50) received courses of intravenous immunoglobulins (IVIG) at a course dose of 300 ml (15 g) simultaneously; group 3 (n = 50) received no additional therapies. Rate of pregnancy complications was comparatively assessed – development of fetal growth retardation (FGR), low birth weight fetus, gestational arterial hypertension (AH), moderate and severe preeclampsia (PE), anemia and delivery outcomes.Results. It was found that in group 3 there was a higher incidence of gestational hypertension (p2,3 < 0.0001), moderate PE (p 1,3 =0.071; p 2,3 = 0.0019), low weight fetus for gestational age (p2,3 = 0.0002) and FGR (p2,3 = 0.003). In group 1, compared with group 2, there were more often observed small weight for gestational age fetus (p1,2 = 0.018) and FGR (p1,2 = 0.024), gestational hypertension (p1,2 = 0.0008), anemia (p1,2 < 0.0001) and latent iron deficiency (p1,2 < 0.0001). Also, groups 2 and 3 vs. group 1 were more likely to have intrahepatic cholestasis during pregnancy (p1,2 = 0.013; p1,3 = 0.003).Conclusion. In the group of patients receiving complex therapy consisting of LMWHs prophylactic doses, low ASA doses and IVIG courses, the risks of developing placenta-associated complications and iron deficiency were reduced compared to other groups indicating about a higher efficiency of this therapy regimen. However, the development of intrahepatic cholestasis during pregnancy was less common in the group of patients receiving PF courses, in contrast to using IVIG courses, which can be accounted for by additional effect of efferent therapeutic methods and should be taken into account in a differentiated approach for management of patients with liver and gallbladder pathology.

P213 A COMPLICATED STEMI : POISED BETWEEN THROMBOSIS AND HEMORRHAGE

Abstract The introduction of more effective and powerful antithrombotic therapies has allowed the progressive reduction of ischemic events associated however with an increase in haemorrhagic events. What we are describing is an example of how iatrogenic and non–iatrogenic complications can add up, making routine therapeutic management difficult during and after hospital stay.We are talking about a 50–year–old male patient, a smoker and with a history of dyslipidemia under treatment, who arrived at our cath–lab with a diagnosis of anterior SCA–STEMI, after loading ticagrelor 180 mg from the spoke center where he had gone for chest pain. At coronary angiography, evidence of critical disease of the median anterior interventricular artery treated by primary angioplasty and for the high thrombotic load by thromboaspiration, DES and Tirofiban bolus and 18–hour continuous infusion. Approximately 15 hours after the event, the patient appeared confused and aphasic. A brain CT scan with and without contrast agent was performed which documented the presence of a hemorrhagic focus in the atypical left temporal site, in the absence of arteriovenous malformations not susceptible to surgical therapy (BARC–3). Therefore, in view of the high risk of bleeding, de–escalation therapy with cardioaspirin and clopidogrel was practiced. Five days after the event, the clinical picture was complicated again by the finding of apical thrombosis on the transthoracic ultrasound. For this reason, given the stability of the haemorrhagic lesion on CT scans and control MRIs, Enoxaparin sodium 4000 IU was introduced in therapy once, with resolution of the formation in the imaging control after one month. The patient was then discharged with indication for short–DAPT in consideration of the high PRECISE–DAPT score. The arduous task of managing this case led us to reflect on the importance of the pre– and post–PCI clinical picture of the patient in order to seek the appropriate antithrombotic treatment by dynamically balancing the ischemic and haemorrhagic risk during hospitalization through numerous standardized tools at our disposal.

Identification of prophylaxis and treatment for hospitalized patients associated with venous thromboembolism.

Identification of prophylaxis and treatment for hospitalized patients associated with venous thromboembolism.

The Effect of a Patient Education Multimodal Digital Platform on Knowledge Acquisition, Self-efficacy, and Patient Satisfaction.

This study examined the impact of digital training instrument based on multimodal learning approach on surgical ward hospitalized patient education-related variables. The study was conducted as a multisite study in a large medical center as a two-arm, controlled trial with randomized cluster sampling. All patients meeting the inclusion criteria were offered the opportunity to participate. The control group (n = 40) received nurse explanation on home self-injection of enoxaparin sodium, whereas the intervention group (n = 40) received a tablet for multimodal learning specifically developed for this study. All participants completed before-and-after questionnaires evaluating knowledge acquisition, change in self-efficacy, and patient satisfaction. Results showed that the intervention group gained significantly more knowledge than the control group ( P < .01). There was no significant difference in the level of self-efficacy change between the groups, and it was found that the control group patients were more satisfied with the training process ( P = .01). This study shows that the use of a digital application for the benefit of patients' self-injection learning is effective in achieving educational goals such as knowledge acquisition and therefore can be a helpful resource for caregivers. Yet, these applications are not a substitute for attention provided by professionals, which is highly valued by patients.

Obtaining the substance enoxaparin sodium equivalent to the original Clexane® and Lovenox®. Selection of technological parameters of the key stage of the synthesis

The aim: to carry out the key stage of synthesis to obtain a substance equivalent to the original drugs Clexane® and Lovenox® by determining the technological parameters of the synthesis that are critical from the point of view of the formation of the molecule and studying the correlation between the structural characteristics of Enoxaparin samples and the experimental conditions of the technological process. Materials and methods: samples of the Enoxaparin sodium substance were synthesized according to the method described in the patent, as well as with a variation of the selected critical technological parameters. The obtained samples of Enoxaparin sodium were analyzed according to pharmacopoeial requirements, as well as by non-pharmacopoeial methods, such as two-dimensional NMR spectroscopy and size exclusion chromatography for detailed structural characterization of the molecule. Results: determination and variation of technological parameters critical for the formation of the molecule, such as temperature, the amount of alkali for the depolymerization reaction, and the reaction time of the reaction mass, were determined and varied. Enoxaparin sodium samples were developed according to the selected parameters and a detailed analysis of the structure of the obtained samples was carried out, followed by a comparison with the original Clexane® and Lovenox®. It was established that with an increase in the temperature of the reaction mass, the amount of alkali and the holding time individually and in combination, the degree of depolymerization increases, which makes the composition of the molecule unbalanced in comparison with the original drugs Clexane® and Lovenox®. Conclusions: As a result of the experiments, the technological parameters of the synthesis of a sample of Enoxaparin sodium were evaluated and determined, allowing to obtain a substance comparable to the originator in terms of chemical structure (alkali/ heparin benzyl ester ratio 0.06; temperature – 57 °C, reaction mixture holding time - 1.5 hours)

Comparison of the methods of the correction of the venous thromboembolism in bariatric surgery using the low-frequency thromboelastography: our experience

Introduction. In the world of obesity and its complications annually dies about 2.8 million people. Obesity is an independent factor of the risk of venous thromboembolism (VTE), as it interferes with the internal and external pathways of coagulation, as well as in anticoagulant mechanisms, which leads to a hypercoagulation state. Reducing excess body weight in patients with morbid obesity by bariatric surgery is becoming increasingly popular, as barium therapy is an effective means of treating obesity and related concomitant diseases. Advantages of bariatric surgery are undeniable, as well as risks. Despite many blood coagulation studies, cases of thromboembolism in such patients are becoming more frequent, especially during surgical interventions and in the postoperative period, given that the operation is a trigger factor in the development of thromboembolism.&#x0D; Materials and methods. A hemostasis system was studied in 63 patients with BMI&gt; 35 kg / m2. All patients were divided into 3 groups. 1 group (n=20) - patients who received combined therapy: Enoxaparin sodium 0.1% 0.2 ml / kg 2 times a day every 12 hours and Pentoxifylline 100 mg 2 times a day every 12 hours; The 2nd group (n= 17) - patients treated with: Enoxaparin sodium 0.1% 0.2 ml / kg 2 times daily for every 12 hours; Group 3 (control): 26 people with obesity, BMI&gt; 35, not subject to bariatric surgery. The study of the hemostasis system was carried out using low-frequency piezoelectric thromboelastography (LPTEG) immediately after hospitalization and on 1,3,5 days after bariatry. The following blood coagulation constants were checked: Contact Coagulation Intensity; intensity of coagulation drive; maximum bunch density; Fibrinolytic activity is the index of retraction and lysis of the clot.&#x0D; Results. In patients of group 1 (anticoagulants + antiplatelet agents) the risk of thrombotic complications is lower, since this therapy has reduced the value at all stages of hemocoagulation to the reference values; Patients in group 2 (anticoagulants), despite the normalization of the coagulation unit, had an increase in the values of aggregation and fibrinolysis, relative to the norm, which means the risk of thrombotic complications remains high.&#x0D; Conclusions. The instrumental method of NPTEG allowed to adequately estimate the system of hemocoagulation in dynamics in patients with morbid obesity, with BMI ≥ 35 kg / m2; This category of patients has shown a high risk of VTE; It has been proved that for an adequate prevention of VTE in obese patients undergoing bariatric surgery, the combination of anticoagulants and antiplatelet agents is more effective than monotherapy with anticoagulants.

Heparan Sulfate and Enoxaparin Interact at the Interface of the Spike Protein of HCoV-229E but Not with HCoV-OC43

It is known that the spike protein of human coronaviruses can bind to a secondary receptor, or coreceptor, to facilitate the virus entry. While HCoV-229E uses human aminopeptidase N (hAPN) as a receptor, HCoV-OC43 binds to 9-O-acetyl-sialic acid (9-O-Ac-Sia), which is linked in a terminal way to the oligosaccharides that decorate glycoproteins and gangliosides on the surface of the host cell. Thus, evaluating the possible inhibitory activity of heparan sulfate, a linear polysaccharide found in animal tissues, and enoxaparin sodium on these viral strains can be considered attractive. Therefore, our study also aims to evaluate these molecules' antiviral activity as possible adsorption inhibitors against non-SARS-CoV. Once the molecules' activity was verified in in vitro experiments, the binding was studied by molecular docking and molecular dynamic simulations confirming the interactions at the interface of the spike proteins.

Development and Validation of Analytical HPLC Method for Identification and Assay of Enoxaparin Sodium in Injectable Preparations

Introduction. Enoxaparin sodium-containing drugs are included in relevant protocols for COVID-19 therapy. An increase in the production volume of such drugs leads to a demand for available and precise methods of identification and quantitative measurement of the active ingredient in the preparations. Considering the fact that pharmacopoeial methods require significant amount of expensive standards and reagents that are unavailable for numerous laboratories, it is relevant to develop a more available method that will accelerate and make cheaper the process of quality control for enoxaparin sodium-containing preparations.Aim. To develop and validate a simple, economic, and precise method of gel-permeation HPLC with the application of a refractive index detector for the evaluation of enoxaparin sodium in preparations for injection.Materials and methods. Samples of enoxaparin sodium-containing substances and commercial preparations were studied. The identification and quantitative content of the active ingredient were performed by the method of gel-permeation HPLC using a 1260 Infinity (Agilent Technologies, USA) chromatograph equipped with a refractive index detector.Results and discussion. The authors analyzed standard validation characteristics: specificity, linearity, precision, and accuracy of the method. The analysis revealed high specificity and suitability of the proposed method to chromatographic symmetrical multiprocessing systems. The method is recommended for routine control of finished and semi-finished pharmaceutical preparations containing from 25 to 200 mg/ml of enoxaparin sodium-containing.Conclusion. The proposed method can be used for routine quality control of enoxaparin sodium-containing preparations for injection.

Cerebral venous thrombosis and B12 deficiency

Infants with prematurity and necrotizing enterocolitis (NEC) are at increased risk for short bowel syndrome and subsequent nutritional deficiencies. In particular, ileal resection is associated with vitamin B12 malabsorption, which interferes with normal myelination and homocysteine metabolism.1, 2 Vitamin B12 deficiency is associated with neurodevelopmental delay as well as hyperhomocysteinemia, which increases the risk for venous thrombosis.2, 3 This eight-year-old boy presented with severe headache, dehydration, and lethargy. He developed acute onset severe frontal headache followed by decreased oral intake, decreased urine output, and recurrent vomiting. The headache was dull and radiating to the back of his head. At the same time, he appeared to be sleepy and less active. These symptoms lasted for two to three days before he was brought to the primary doctor's office and then referred to the emergency department. On assessment, he was tired-looking and exhibited mild microcephaly, but his neurological examination was normal, as was an examination by an ophthalmologist. He experienced mild global developmental delay. He was born at 25 weeks gestational age and had a prolonged stay in the neonatal intensive care unit, complicated by NEC and a hemicolectomy with ileostomy and removal of ileocecal valve. He had low normal levels of B12 for several years prior to presentation and was not treated (151 pg/ml after surgery [normal 160-950]). Brain magnetic resonance imaging and magnetic resonance venography (MRV) showed filling defects in the inferior sagittal, straight, torcula, and proximal transverse sinuses consistent with cerebral venous sinus thrombosis (CVST) with no evidence of acute infarction (Figure 1). Dehydration was initially considered to be the cause. Enoxaparin sodium was started at 1 mg/kg every 12 h with the goal of anti-Xa level between 0.5 and 1.0 U/ml. The hypercoagulation evaluation was normal. The B12 level was 86 pg/ml. His hematocrit was 33.3, and his mean corpuscular volume (MCV) was 87.4. He was not treated at that time. He was discharged within a week after the repeat imaging remained stable with the goal to continue enoxaparin sodium for three months. After three months, he again developed headache and lethargy, and MRV showed a new thrombus. Enoxaparin was switched to warfarin. After a year of warfarin, the clot resolved but he still had headaches. Two B12 levels were obtained, both below 200. His anemia worsened (hematocrit 24.7) and his MCV increased to 96.9. The homocysteine level was 184 μmol/L (normal <11.4). At this point, he began B12 injections (1000 mcg daily for one week followed by monthly and then quarterly injections thereafter). His B12 levels normalized and remained normal throughout his course. The warfarin was discontinued and thrombus has not recurred. Our patient had a difficult-to-treat CVST secondary to a condition predisposing to nutritional deficiency. His chronic B12 deficiency was overlooked by his treating physicians until he presented with a profound deficiency with megaloblastic anemia. The association between B12 deficiency and CVST has been described in children with nutritional deficiency and megaloblastic anemia.4 Previous authors suggested that testing for hyperhomocysteinemia and with B12 supplementation should be considered in pediatric patients with CVST.5 The diagnosis becomes even more crucial in patients with conditions known that promote nutritional deficiencies, such as a history of NEC and ileal surgery. In such children, early recognition of vitamin B12 deficiency and timely vitamin supplementation may prevent the occurrence of CVST as well as other manifestations of B12 deficiency, such as developmental delay.6, 7 In this patient, the B12 deficiency was chronic. While it is difficult to prove that the deficiency caused the CVST, it likley played a substantial role. Hyperhomocysteinemia can damage the vascular endothelium, predisposing to thrombus formation.8, 9 Consequently, vitamin B12 deficiency is a potential risk factor in children with CVST. Fatemeh Mohammadpour Touserkani: Conceptualization; supervision; writing – original draft; writing – review and editing. Theodora Andriotis: Conceptualization; investigation; writing – original draft; writing – review and editing. Yaoping Zhang: Conceptualization; supervision; writing – original draft; writing – review and editing. Steven Pavlakis: Conceptualization; supervision; writing – original draft; writing – review and editing. We would like to thank the patient's parents for their consent for this publication. The authors declare no conflict of interest.

Comparative Analysis of Two Enoxaparin Sodium Drugs by Heptest.

The optimal conditions for analysis of low-molecular-weight heparin (LMWH) drugs by the Heptest and the metrological characteristics of the Heptest method were determined. The effects of two LMWH preparations of enoxaparin sodium, the domestic drug Enoxaparin sodium (Technologiya Lekarstv, Russia) and the original drug Clexane (Sanofi, France), on the clotting time of human plasma in the Heptest were comparatively analyzed. The mean blood clotting times were calculated for each dilution of each series of Enoxaparin sodium and Clexane based on the results of the Heptest. Graphs of the dependence of the plasma clotting time on the degree of dilution of these drugs were plotted. The shapes of the curves of the dependence of the blood plasma clotting time on the activity of enoxaparin sodium were shown to be similar for both Enoxaparin sodium and Clexane. The Heptest method showed that Enoxaparin sodium (Technologiya Lekarstv, Russia) was comparable to the original drug Clexane (Sanofi, France).

Medications mostly associated with hematuria: assessment of the EudraVigilance and Food and Drug Administration pharmacovigilance databases entries.

Drugs may have a direct causative role in triggering hematuria. The range of medications which may be responsible for hematuria is wide, but little is known on those which are most frequently involved. The aim of our study was to identify and compare drugs mostly related with hematuria. The Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database and the EudraVigilance (EV) database were queried to identify the drugs which were associated the most with hematuria individual reports till 30 September 2021. Rivaroxaban, aspirin, warfarin sodium, clopidogrel bisulfate, dabigatran etexilate mesylate, apixaban, warfarin, cyclophosphamide, lansoprazole, enoxaparin sodium, and ibuprofen were analyzed. Analysis per gender, age and severity was performed. Disproportional analysis was performed to compare drugs. Overall, 15,687 reports of hematuria were recorded in the FDA database and 15 007 in the EV database. Rivaroxaban and Warfarin appear to be the most dangerous medications in terms of hematuria when compared to the other medications (PRR>1, P<0.05) while apixaban is the safest one (PRR<1, P<0.05) when compared to the other medications. In terms of severity only 162/15 007 (1.08%) were fatal. Between the drugs analyzed cyclophosphamide 7.2%, enoxaparin (3%) and dabigatran (2.5%) presented a higher number of fatal hematuria episodes when compared to the other drugs (<1%). Anticoagulants and antiplatelets are more frequently related to hematuria episodes however some differences exist between them. Particularly warfarin and rivaroxaban should be prescribed with caution in patients at increased risk of hematuria. Prescribers should inform those treated with these medications about the risk of hematuria and its sequelae.

No difference in Oxford Knee Score between medial and lateral unicompartmental knee arthroplasty after two years of follow-up: a clinical trial

PurposeIn patients with monocompartmental knee osteoarthritis, unicompartmental knee arthroplasty (UKA) can be performed. This study compared the medial versus lateral UKA in patients with monocompartimental knee arthroplasty. It was hypothesised that both implants achieve a similar outcome in OKS.MethodsThe UKAs were fixed-bearing medial PPK (Zimmer-Biomet, Warsaw, Indiana, USA) and fixed-bearing lateral Zuk (Lima Corporate, Udine, Italy). An intraarticular drain was placed and removed on the first postoperative day. Enoxaparin sodium 4000 units subcutaneously daily for 45 days was used as thromboembolic prophylaxis. The Italian version of the OKS was used for the clinical assessment. The following complications were also recorded: anterior knee pain, infection and revision surgeries.ResultsData from 203 patients were collected. The mean age of the patients was 68.9 ± 6.7 years and the mean BMI was 28.1 ± 4.1 kg/m2. The mean OKS on admission was 22.1 ± 4.5 points. On admission, women, patients older than 70 years, and those with a BMI lower than 28 kg/m2 who underwent lateral UKA evidenced lower OKS. At the last follow-up, 26.7 and 26.9 months for the lateral and medial UKA, respectively, no between groups difference in OKS was evidenced. No patients experienced complications.ConclusionMedial and lateral UKA achieve similar outcomes in OKS at a minimum of two years of follow-up.

Anticoagulation for mechanical heart valves during pregnancy: A case report and a literature review

Most previous treatment guidelines for pregnant women with mechanical heart valves recommend that low molecular weight heparin (LMWH) should be applied once every 12 hours and only as required to reach peak anti-Xa levels of approximately 1.0 to 1.2 IU/mL, but it is commonly associated with subtherapeutic trough levels, consequently with an inadequate level of anticoagulation. Our case report here together with a literature review suggests that dose-adjusted (Target trough anti-Xa levels of 0.6 to 0.7 IU/mL and with peak anti-Xa levels of around 1.0 to 1.2 IU/mL or < 1.5 IU/mL) LMWH should be given thrice daily throughout pregnancy. In addition, the findings of this rare case indicate that a combination of LMWH and warfarin is effective in the treatment of small thromboses in pregnancy. In the 1st trimester of pregnancy, a 28-year old pregnant female with a mechanical valve had a significant increase in the aortic valve flow rate and suspected mechanical valve thrombosis. The peak velocity of the pregnant female aortic mechanical valve increased, and mechanical valve thrombosis was suspected. We adjusted the enoxaparin sodium dose every 12 hours to 1 injection every 8 hours, with a total daily dose of 160 mL. Based on the original application of LMWH, warfarin (3 mg/day) was recommended. The pregnant woman delivered a live baby by cesarean section, and the peak flow velocity of the mechanical valve in the aortic position was reduced to nearly equivalent to the patient's pre-pregnancy status. The mother and the baby were in good health at the time of discharge. LMWH is administered twice daily, and anti-Xa trough levels are mostly in a subtherapeutic state, which may lead to insufficient anticoagulation and thrombosis. Dose-adjusted LMWH thrice daily throughout pregnancy is the recommended treatment for pregnant women with mechanical heart valves. The combination of LMWH and warfarin exhibited good efficacy for the treatment of small thromboses.

An unexpected result of a routine cardiac consultation in a patient with nephrological problems

A 17.5-year-old boy, previously treated in a nephrology clinic due to chronic proteinuria, was referred for a routine cardiology consultation before being transferred to an adult clinic for further care. Physical examination and echocardiography showed no circulatory abnormalities and normal blood pressure, while echocardiography revealed an abnormal tumour-like structure measuring 1.3 × 1.5 cm in the left atrium, remaining in contact with the interatrial septum. Continuous infusion of heparin was started, after which no change in tumour size was obtained. The diagnosis was extended to include computed tomography, which showed a soft 1.5 × 2.1 × 2.1 cm tissue structure connecting with the interatrial septum with uneven contours, and magnetic resonance imaging, which indicated that the left atrial structure corresponded to myxoma, and the presence of enhancement spoke against the suspicion of a thrombus, although the presence of a small thrombus on the tumour could not be clearly excluded. The boy was qualified for a cardiac surgery, during which the pathological structure was removed and then sent for histopathological analysis, which revealed a heart tumour with myxoma. After the surgery, the patient was transferred to the department of paediatric cardiology for further treatment, where he received enoxaparin sodium, antibiotics and acetylsalicylic acid. After a few days, an about 1 cm layer of fluid appeared in the pericardium, which regressed after the incorporation of ibuprofen and dehydrating agents. After 2 weeks, the boy was discharged home in good condition, with a recommendation to continue care at a nephrology, cardiology and genetic clinic due to MTHFR mutation, which may be associated with hereditary hypercoagulability, detected during hospital stay.

A massive stroke in a pregnant woman following COVID-19 infection: A case report

Background and aims: COVID-19 infection increases the risk of pathological thrombotic events in venous and arterial circulation. COVID-19 patients are reported, a wide range of neurovascular symptoms is highlighted, such as cerebral vascular accidence. This study aimed to report a massive stroke in a pregnant woman with COVID-19 infection. Case Report: We report a 41-year-old pregnant woman, gravid 5 para 2 living 2 abortion 2 at gestational age 22 weeks and 4 days with Covid-19 infection, which developed into a massive stroke in the Basilar artery despite receiving a therapeutic dosage of Enoxaparin Sodium. Conclusion: The possibility of thrombosis should be considered in COVID-19 patients with symptoms indicating an increase in intracranial pressure (ICP) such as decreased consciousness, strabismus, and agitation. Considering the higher risk of thrombotic events in COVID-19 patients, cerebral venous sinus thrombosis (CVST) could be a possible consequence. Thus, the precise observation of neurologic manifestations in covid-19 patients, especially in pregnant women, is recommended.

Evaluation and Treatment of Vulvodynia: State of the Science.

Vulvodynia affects 7% of American women, yet clinicians often lack awareness of its presentation. It is underdiagnosed and often misdiagnosed as vaginitis. The etiology of vulvodynia remains unknown, making it difficult to identify or develop effective treatment methods. The purpose of this article is to (1) review the presentation and evaluation of vulvodynia, (2) review the research on vulvodynia treatments, and (3) aid the clinician in the selection of vulvodynia treatment methods. The level of evidence to support vulvodynia treatment varies from case series to randomized controlled trials (RCTs). Oral desipramine with 5% lidocaine cream, intravaginal diazepam tablets with intravaginal transcutaneous electric nerve stimulation (TENS), botulinum toxin type A 50 units, enoxaparin sodium subcutaneous injections, intravaginal TENS (as a single therapy), multimodal physical therapy, overnight 5% lidocaine ointment, and acupuncture had the highest level of evidence with at least one RCT or comparative effectiveness trial. Pre to posttest reduction in vulvar pain and/or dyspareunia in non-RCT studies included studies of gabapentin cream, amitriptyline cream, amitriptyline with baclofen cream, up to 6 weeks' oral itraconazole therapy, multimodal physical therapy, vaginal dilators, electromyography biofeedback, hypnotherapy, cognitive behavioral therapy, cold knife vestibulectomy, and laser therapy. There is a lack of rigorous RCTs with large sample sizes for the treatment of vulvodynia, rendering it difficult to determine efficacy of most treatment methods. Clinicians will be guided in the selection of best treatments for vulvodynia that have the highest level of evidence and are least invasive.