Prevention Of Venous Thrombosis Research Articles

#2147 Enoxaparin dosing in advanced chronic kidney disease: importance of monitoring with anti-Xa levels

Abstract Background and Aims Enoxaparin is a low-molecular-weight heparin (LMWH) that is commonly used in the prevention of deep venous thrombosis (DVT) and the treatment of acute thomboembolic diseases. Current literature indicates that in advanced chronic kidney disease (CKD), there is a reduced clearance and increased half-life of LMWH and therefore, a dose adjustment is recommended. The prescription label recommends a dose adjustment of enoxaparin to 0.5 mg/kg/day for prophylaxis of DVT and 1 mg/kg/day for therapeutic anticoagulation when eGFR <30 ml/min. The aim of this study was to examine the accuracy of this dosing strategy to achieve the desired target of anticoagulation in advanced CKD. Method We conducted a prospective study in patients admitted from May 2019 to April 2023 in the Nephrology ward at our centre, who started anticoagulant treatment with enoxaparin during their in-hospital stay for prophylactic or therapeutic indications. We excluded patients with eGFR >30 ml/min at the onset of anticoagulation with enoxaparin. The dosing strategy was 0.5 mg/kg/day for prophylaxis of DVT and 1 mg/kg/day for therapeutic anticoagulation in all patients. Blood samples were drawn 4 hours after the third dose of enoxaparin to monitor anti-Xa levels in all cases. Results The study included 153 patients; 70 patients with stage 4-5 CKD and 83 patients on renal replacement therapy. 132 patients (86.3%) received enoxaparin for a therapeutic indication, while 21 patients (13.7%) received it as prophylaxis of DVT. In patients receiving enoxaparin for a therapeutic indication, 73 patients (55.3%) reached the therapeutic target anti-Xa levels (0.6-1), while 32.6% of patients had peak anti-Xa levels below the therapeutic target (<0.6) and 12.1% were over-anticoagulated (>1). There was an inverse relationship between the proportion of patients who were adequately anticoagulated and CKD stage; 66.7%, 58.6% and 48.6% of patients reached the target peak anti-Xa levels in CKD stage 4, 5 and 5D respectively. There was no significant association between anti-Xa levels and obesity or liver disease. In patients receiving enoxaparin for prophylaxis of DVT, 42.9% reached the target anti-Xa levels for prophylaxis (0.3-0.6), while 38.1% had anti-Xa levels below this range and 19% were over-anticoagulated. Conclusion The enoxaparin dosing recommendations indicated by its label entails a high proportion of patients with advanced CKD who do not achieve the target therapeutic levels of antiXa, especially in patients on renal replacement therapy. To ensure adequate anticoagulation in these patients, we recommend using individualized dosing adjustments based on monitoring of anti-Xa levels for the prevention of thromboembolic events and reducing the risk of hemorrhagic events.

Future of factor XI inhibitors in cardiovascular practice.

Anticoagulation is indicated for treatment and prevention of arterial and venous thrombosis. Targeting different steps of the coagulation process, currently available anticoagulants entail an increased risk of bleeding, which detrimentally impacts on prognosis and hinders the administration of an effective antithrombotic regimen. Factor XI (FXI) inhibition has emerged as a strategy to uncouple prevention of thrombosis from bleeding. Indeed, while FXI is crucial for the amplification phase in pathological thrombosis, it is ancillary in physiological hemostasis. A comprehensive search in several scientific databases has been performed to identify relevant studies in the field. In addition, ongoing trials have been searched for in proper datasets to provide an updated and comprehensive assessment of the current state of investigations on FXI inhibition. Many compounds have been tested to inhibit FXI at different stages (i.e., synthesis, activation, or interactions with target molecules and coagulation factors). These include antisense oligonucleotides, monoclonal antibodies, small molecules, natural peptides and aptamers. In phase 2 studies, FXI inhibitors reduced thrombotic complications without any corresponding increase in bleeding. FXI inhibitors were noninferior and potentially superior to low-molecular-weight heparin in orthopedic surgery and reduced bleeding compared to apixaban in patients with atrial fibrillation. FXI inhibition is also under testing in other conditions, including end-stage renal disease, cancer, or noncardioembolic stroke. FXI inhibition represents a promising and rapidly emerging approach for a number of clinical indications. This article reviews the rationale, evidence, pharmacology, and future applications of FXI inhibition.

Preliminary comparative study of lower extremity pressure measurements under the conditions using former models and new lithotomy stirrups in rectal cancer surgery

BackgroundThis study aimed to investigate the effect of the use of new lithotomy stirrups-2 on the pressure dispersal on lower limbs, which may lead to the prevention of well-leg compartment syndrome (WLCS) and deep venous thrombosis (DVT), which are the most commonly associated adverse events with laparoscopic and robot-assisted rectal surgery.MethodsA total of 30 healthy participants were included in this study. The pressure (mmHg) applied on various lower limb muscles when using conventional lithotomy stirrups-1 and new type stirrups-2 was recorded in various lithotomy positions; 1) neutral position, 2) Trendelenburg position (15°) with a 0° right inferior tilt, and 3) Trendelenburg position (15°) with a 10° right inferior tilt. Using a special sensor pad named Palm Q®, and the average values were compared between two types of stirrups.ResultsThe use of new lithotomy stirrups-2 significantly reduced the pressure applied on the lower limb muscles in various lithotomy positions compared with the use of lithotomy stirrups-1. The most pressured lower limb muscle when using both lithotomy stirrups was the central soleus muscle, which is the most common site for the development of WLCS and DVT. In addition, when using the conventional lithotomy stirrups-1, the pressure was predominantly applied to the proximal soleus muscle; however, when using lithotomy stirrups-2, the pressure was shifted to the more distal soleus muscle.ConclusionThese results suggest that the new lithotomy stirrups-2 is useful in reducing the pressure load on leg muscles, especially on the proximal to central soleus, and may reduce the incidence of WLCS and DVT after rectal surgery performed in the lithotomy position. Further clinical studies are needed to determine whether the use of lithotomy stirrups-2 prevents these complications in various clinical settings.

Appraising the quality standard of clinical practice guidelines related to central venous catheter-related thrombosis prevention: a systematic review of clinical practice guidelines

ObjectiveTo evaluate the quality and analyse the content of clinical practice guidelines regarding central venous catheter-related thrombosis (CRT) to provide evidence for formulating an evidence-based practice protocol and a risk...

Effect of Implementing Evidence-Based Nursing Practices Guidelines on Prevention of Deep Venous Thrombosis among Postpartum Women

Effect of Implementing Evidence-Based Nursing Practices Guidelines on Prevention of Deep Venous Thrombosis among Postpartum Women

D-Dimers in diagnosis and prevention of venous thrombosis: recent advances and their practical implications.

D‑Dimers derive from degradation of cross‑linked fibrin by plasmin, and thus their level is a marker of coagulation and fibrinolytic system activation. Guidelines recommend that D‑dimers are determined if the pretest probability (PTP) is low or intermediate, to exclude venous thromboembolism (VTE), either deep vein thrombosis or pulmonary embolism, and to avoid imaging tests. If the PTP is high or D‑dimer level is above the suggested thresholds, imaging is recommended. D‑Dimer assays offer high sensitivity and low specificity, as D‑dimer levels can be above the threshold in several other conditions than thrombosis, and they increase with age. As a result, there have been several proposals to improve the diagnostic accuracy of D‑dimer levels by adjusting the cutoffs according to patient characteristics, such as age, PTP, pregnancy, renal function, or cancer. D‑Dimer levels can also predict clinical severity of COVID‑19, and escalated anticoagulation based on D‑dimer levels can be associated with a lower risk of mortality in patients with severe COVID‑19. Finally, D‑dimer levels have been incorporated in prediction models for recurrent VTE to help identify patients who may benefit from prolonged anticoagulation.

Heparin-induced hyperkalemia, can LMWH cause hyperkalemia? A systematic review.

Hyperkalemia, an elevated blood potassium concentration exceeding 5.0mEq/L, is associated with adverse outcomes and is frequently observed in hospitalized patients. Drug-induced hyperkalemia accounts for a significant proportion of cases, with heparin, commonly used for venous thrombosis prevention, suspected to contribute, though less recognized than other heparin-related side effects. Both unfractionated heparin (UFH) and low molecular weight heparin (LMWH) have been implicated in inducing hyperkalemia, primarily through the suppression of aldosterone levels and modulation of angiotensin II receptors. This systematic review examines the relationship between heparin, particularly LMWH, and hyperkalemia. Thirteen studies involving 1407 patients were analyzed. Findings indicated a lack of highquality evidence, with no significant increase in potassium levels associated with LMWH use. LMWH did not exhibit a dose-response relationship with hyperkalemia incidence. Additionally, mechanisms underlying the hypothetical LMWHinduced hyperkalemia remained inconclusive. While this suggests that LMWH is unlikely to be a primary cause of hyperkalemia, caution is warranted, especially in patients with elevated baseline potassium levels.

Effect of Traditional Chinese Medicine fumigation combined with acupoint massage in the prevention of deep venous thrombosis of lower limbs in elderly hospitalized patients in the Internal Medicine Department

Effect of Traditional Chinese Medicine fumigation combined with acupoint massage in the prevention of deep venous thrombosis of lower limbs in elderly hospitalized patients in the Internal Medicine Department

Retracted: A Cohort Study of Rivaroxaban Combined with D-Dimer Dynamic Monitoring in the Prevention of Deep Venous Thrombosis after Knee Arthroplasty.

[This retracts the article DOI: 10.1155/2022/3965039.].

Retracted: Clinical Study of Neuromuscular Electrical Stimulation in the Prevention of Deep Venous Thrombosis of Lower Extremities after Anterior Cruciate Ligament Reconstruction.

[This retracts the article DOI: 10.1155/2022/7857272.].

Comparative evaluation of preventive anticoagulant therapy regimens in the wounded

Introduction. Currently, the issues of prescribing anticoagulant therapy to the wounded are poorly studied, the doses of drugs and the timing of its implementation have not been determined.Aim. To study various modes of anticoagulant therapy for the prevention of venous thrombosis of the lower extremities in the wounded after surgery using the parameters of the plasma hemostasis system and the Thrombodynamics test.Materials and methods. A prospective study was conducted, which included 90 wounded with mine-explosive/gunshot injury receiving anticoagulant therapy in preventive doses. The studies were carried out on the equipment of the Thrombodynamics recorder (HemaCor, Moscow). The patients were divided into 3 groups: 1 group, which included 30 patients taking rivaroxaban at a dose of 10 mg/day, 2 group of 30 patients receiving enoxaparin sodium at a dose of 40 mg once a day, 3 group consisting of 30 patients receiving enoxaparin sodium 40 mg 2 times a day. In the dynamics of treatment, the parameters of the plasma hemostasis system and the parameters of the Thrombodynamics test were evaluated.Results. It was revealed that during preventive anticoagulant therapy, there were no significant differences in the standard parameters of the coagulogram, when studying the parameters of the Thrombodynamics test, significant differences wereobserved between groups 1 and 3 in values (V/VSt, Vi, Tlag, СS), between group 2 and 3 in parameter (V/VSt, Vi, Tlag, СS), between group 1 and group 2 in the value of D. A statistically significant relationship was found between the Thrombodynamics parameter D and the indicators of TV, prothrombin by Quick, and fibrinogen content.Conclusion. The Thrombodynamics test can be used as a potential tool for a personalized approach to monitoring the hemostasis system in the wounded.

Primary prevention of cancer-associated venous thrombosis: Rationale and challenges in clinical practice

Cancer-associated venous thrombosis (CAT) is a common, multifactor event known to complicate the course of cancer and jeopardize a patient's prognosis. The current guidelines regarding the prevention of CAT are sometimes considered insufficiently precise about specific situations, or are poorly applied. The expected benefits of thromboprophylaxis are balanced by the risk of major bleeding induced by anticoagulation, which implies a need to accurately identify ambulatory patients at high risk of thrombosis or hemorrhage. The Khorana score is commonly used for this, but is limited by the non-reproducibility of predicted performance across cancer types, and by the fact that antitumor treatment and cardiovascular risks are not included. The COMPASS-CAT score, which includes those two aspects, was found to be a more accurate predictor of venous thromboembolism in patients with lung cancer, and to better distinguish between patients at low or high risk of thrombosis. The frailty of patients with cancer is also a major issue, and should be taken into account when thromboprophylaxis is considered. According to current guidelines, CAT prophylaxis should be considered for hospitalized patients, those for whom surgery is scheduled, or those with pancreatic cancers. In ambulatory patients, decisions should be made according to patient, cancer and antitumoral treatment characteristics. Low molecular weight heparin is the gold standard of CAT prophylaxis. Despite increased risks of bleeding or drug-drug interactions in cancer patients, direct oral anticoagulants could be alternate options for high-risk ambulatory patients that should be accompanied by a careful global analysis of benefits, harms, and patient preferences.

Cardiovascular manifestations of systemic lupus erythematosus: the significance of heart failure

The involvement of the cardiovascular system is a typical manifestation of systemic lupus erythematosus (SLE), which determines the high level of mortality and disability of patients. A serious clinical problem is the development of heart failure (HF), which frequency in SLE is 3–4 times more than in the population. The development of this pathology is a complex process that occurs under the influence of systemic autoimmune inflammation and associated with heart damage (pericarditis, myocarditis, endocarditis, сcoronary artery disease, myocardial infarction), disorders of the cardiac conduction system (various arrhythmias), atherosclerosis, arterial hypertension, pulmonary hypertension, thrombosis against connected with bleeding disorders (especially associated with antiphospholipid syndrome), traditional risk factors, as well as the negative effect of anti-rheumatic therapy. Mostly HF in SLE occurs in a subclinical form with a preserved ejection fraction, and is detected using instrumental methods in more than 60% of patients. The management of patients with SLE and HF requires early diagnosis of this pathology, to do this, various diagnostic methods are used (particularly, echocardiography with speckle tracking imaging technique) and the identification of biomarkers such as NT-proBNP. HF therapy in SLE patients is based on the maximal reduction o f the activity of the disease due to rational pathogenetic therapy, also the control of traditional risk factors – antihypertensive therapy, the use of statins and the prevention of arterial and venous thrombosis.

Development and validation of knowledge, attitude and practice questionnaire for pediatric nurses to prevent central venous device-related thrombosis in hospitalized children

AimThis study aimed to develop and validate a scientific and standardized knowledge, attitude and practice questionnaire of pediatric nurses’ preventive care for central venous device-related thrombosis among hospitalized children. BackgroundPediatric nurses play a significant role in the prevention of central venous device-related thrombosis for hospialized children. However, the status of pediatric nurses’ knowledge, attitude and practice of central venous device-related thrombosis prevention has not been revealed due to the lack of assessment tools. MethodsThis questionnaire was framed by the theory of knowledge, attitude and practice. The item pool was compiled through a literature review and a preliminary questionnaire was formed based on expert consultation. A total of 457 pediatric nurses from 10 tertiary class A general hospitals and specialized pediatric hospitals in China were selected for pre-survey. Item analysis, reliability and validity test were conducted to refine and evaluate the items to form a formal questionnaire. ResultsA total of 54 items were proposed in three dimensions of knowledge, attitude and practice. In the exploratory factor analysis, five, three and three common factors were extracted for each dimension, accounting for 60.552%, 89.829% and 84.258% of the total variance, respectively. The content validity index of the three dimensions ranged from 0.968 to 1.000 at the scale level and from 0.833 to 1.000 at the item level. The Cronbach's α coefficients for the total questionnaire and each dimension were between 0.926 and 0.973. The retest reliability for the total questionnaire and each dimension was between 0.688 and 0.898. ConclusionThe proposed questionnaire has good reliability and validity and it can be applied to evaluate pediatric nurses' knowledge, attitude and practice in preventing central venous device-related thrombosis for hospitalized children.

Retracted: Prevention of Venous Thrombosis of Lower Limbs after Cesarean Section Based on Smart Medical Air Pressure Therapy Instrument.

[This retracts the article DOI: 10.1155/2022/1451881.].

Knowledge, attitude, and practice of pediatric nurses in prevention of central venous access device-related thrombosis in hospitalized children: a nationwide cross-sectional survey.

Central venous access device-related thrombosis (CRT) is a common complication in hospitalized children. The pediatric nurses' knowledge, attitude, and practice are of great significance for CRT prevention in hospitalized children. The purpose of this study was to elaborate on the level and influencing factors of pediatric nurses' knowledge, attitude, and practice on the prevention related to CRT in hospitalized children. This national cross-sectional study was carried out in China from January 16, 2021, to April 23, 2021. A multi-stage sampling method was adopted, and 1060 pediatric nurses from 21 hospitals participated in this study. The current situation and influencing factors of pediatric nurses' knowledge, attitude, and practice were investigated by descriptive statistics, approximate t test or independent-sample t test, nonparametric Kruskal-Wallis H test, one-way analysis of variance, and multiple linear regression analysis. The relationship among pediatric nurses' knowledge, attitude, and practice was explored by the Pearson correlation analysis. Among all pediatric nurses involved in this study, 25% had insufficient knowledge, 18% had negative attitudes, and 24% had poor behaviors. The main influencing factors on the knowledge, attitude, and practice included the highest education level of pediatric nurses (β = 0.10, P = .001), whether received training related to CRT prevention (β = 0.09-0.14, P < .01), whether CRT-related knowledge was enough for dealing with clinical work (β = 0.18-0.21, P < .001), and the importance of hospitals/departments on children CRT prevention (β = 0.16-0.24, P < .001). There was a positive correlation between knowledge, attitude, and practice (r = 0.24-0.77, P < .01). Conclusion: Pediatric nurses' CRT-prevention knowledge and practice are unsatisfactory, while their preventive attitude toward CRT prevention is optimistic. This study assists the formulation of comprehensive intervention strategies for pediatric nurses in preventing CRT in hospitalized children by hospital-related organizations and nursing managers, so as to improve the participation of pediatric nurses in CRT prevention and reduce the occurrence of CRT for hospitalized children. What is Known: • As a common complication in hospitalized children, CRT can induce many potentially serious complications. • A professional nursing team is an important prerequisite for reducing CRT incidence. What is New: • The levels of pediatric nurses' knowledge and practice are not satisfactory, while pediatric nurses' preventive attitude toward CRT prevention is optimistic. • Hospital-related organizations and nursing managers should highlight the importance of CRT prevention and encourage pediatric nurses to improve their expertise and strengthen the training related to CRT prevention.

Clinical Study on Prevention and Treatment of Venous Thrombosis in Puerperium

Objective: To analyze the risk factors of venous thromboembolism and the correlation between serum markers and thrombosis, so as to provide scientific basis for the early diagnosis, prevention and treatment of the disease. Methods: A total of 108 pregnant women diagnosed with thrombosis after delivery in the First People's Hospital of Yunnan Province from January 2020 to December 2021 and 540 pregnant women with the same gestational age who delivered in the same period were selected for the study. The risk factors of VTE and the correlation between VTE and serological markers were statistically analyzed. Results: The risk factors of venous thrombosis include parity (≥3 times), postpartum hemorrhage, pregnancy complications, perinatal surgery, intestinal obstruction and rheumatic immune system. There were significant differences in NLP, RDW, FDP, FIB, ATⅢ and D-dimer between the thrombosis group and the normal group (P＜0.05). Conclusions: Prophylactic anticoagulant therapy was actively performed during puerperal period according to the VTE rating scale, and at the same time pay attention to the changes of serum markers, which is of significance for early identification and intervention of VTE in pregnant women.

The effect of low molecular weight heparin combined with air pressure in the prevention of lower extremity venous thrombosis after cesarean section: A single-center retrospective study.

In this study, we investigated the effect of low-molecular-weight heparin combined with pneumatic pressure in preventing lower extremity deep vein thrombosis after cesarean section, as well as on the visual analog scale (VAS) score. 120 women who underwent cesarean sections at full term in our hospital from January 2019 to January 2022 were included and divided into a control group (55 cases) and an observation group (65 cases) based on the different treatment methods: the control group was treated with low-molecular-weight heparin and the observation group was treated with pneumatic compression therapy based on the control group. The 2 groups were analyzed for thrombosis, clinical efficacy of the treatment methods, and VAS scores. The incidence of deep vein thrombosis in the observation group were significantly lower than in the control group (4.62% vs 21.82%, P < .05). There were no statistically significant differences in activated partial thromboplastin time, prothrombin time, and thrombin time between the 2 groups (P > .05) before treatment; however, after treatment, activated partial thromboplastin time, prothrombin time, and thrombin time in the observation group were significantly higher than those in the control group (P < .05). The clinical efficacy was significantly higher in the observation group compared with the control group (95.38% vs 78.18%, respectively). The VAS scores in the observation group were significantly lower than those in the control group (P < .05). Hence, low-molecular-weight heparin combined with pneumatic pressure therapy significantly reduces the incidence of lower limb deep vein thrombosis after cesarean section. It also improves the coagulation index and reduces post-operative pain. Therefore, it should be considered for use in clinical practice.

Antithrombotic Effects of the Novel Small-Molecule Factor XIa Inhibitor Milvexian in a Rabbit Arteriovenous Shunt Model of Venous Thrombosis

Background Factor XIa (FXIa) is an emerging therapeutic target, and FXIa inhibition is a promising mechanism to improve therapeutic index over current anticoagulants. Milvexian (BMS-986177/JNJ-70033093) is an oral small-molecule FXIa inhibitor. Objective Milvexian's antithrombotic efficacy was characterized in a rabbit arteriovenous (AV) shunt model of venous thrombosis and compared with the factor Xa inhibitor apixaban and the direct thrombin inhibitor dabigatran. Methods The AV shunt model of thrombosis was conducted in anesthetized rabbits. Vehicle or drugs were administered as intravenous bolus plus a continuous infusion. Thrombus weight was the primary efficacy endpoint. Ex vivo activated partial thromboplastin time (aPTT), prothrombin time (PT), and thrombin time (TT) were measured as the pharmacodynamic responses. Results Milvexian dose dependently reduced thrombus weights by 34.3 ± 7.9, 51.6 ± 6.8 ( p < 0.01; n = 5), and 66.9 ± 4.8% ( p < 0.001; n = 6) versus vehicle at 0.25 + 0.17, 1.0 + 0.67, and 4.0 ± 2.68 mg/kg bolus + mg/kg/h infusion, respectively. Ex vivo clotting data supported a dose-dependent prolongation of aPTT (with 1.54-, 2.23-, and 3.12-fold increases from baseline upon the AV shunt start), but no changes in PT and TT. Dose-dependent inhibition in thrombus weight and clotting assays was also demonstrated for both apixaban and dabigatran as the references for the model validation. Conclusion Results demonstrate that milvexian is an effective anticoagulant for prevention of venous thrombosis in the rabbit model, which supports the utility of milvexian in venous thrombosis, as seen in the phase 2 clinical study.

Highly stereoselective synthesis of heparin tri- and tetra-saccharide derivatives

<p indent="0mm">Heparin, a naturally highly sulfated glycosaminoglycan, mediates various physiologic and pathophysiologic processes, and is mainly used for the prevention and treatment of venous thrombosis in clinic. Here we report an efficient synthesis of heparin oligosaccharides with different degrees of 6-<italic>O</italic>-sulfonation modification, employing orthogonal protective group strategy. <italic>tert</italic>-Butyldiphenylsilyl (TBDPS) group is used as the protective group of 6-OH of the 2-azide-glucose donors, and highly α-selective construction of the key GlcN-(1→4)-GlcUA glycosidic bond was achieved with the corresponding <italic>N</italic>-phenyl trifluoroacetimidate donors. Thus, tri- and tetra-saccharides are synthesized by the convergent [1 + 2] and [2 + 2] glycosylation. The fully elaborated oligosaccharides have then been successfully transformed into the target heparin oligosaccharides <bold>28</bold>–<bold>34</bold> <italic>via</italic> an optimal sequence of manipulation of the protecting groups. The post-assembly manipulations include desilylation with HF·Py (for removal of TBDPS group), delevulinoylation with hydrazine hydrate (for removal of levulinoyl group), saponification under Zemplén conditions (for removal of methyl ester and benzoyl group), <italic>O</italic>-sulfonation with sulfur trioxide pyridine complex (for hydroxyl groups), reduction and <italic>N</italic>-sulfonation (for azido group), and atmospheric pressure hydrogenation (for removal of benzyl and Cbz groups). The availability of these heparin oligosaccharide derivatives which bear amino linker shall facilitate the preparation of glycan chips for studies on the interaction between heparin oligosaccharides with proteins, such as the heparanase.