Molecular Weight Heparin For Prevention Research Articles

Infective Endocarditis due to Unusual Pathogens Complicated with Pulmonary Thromboembolism: A Rare Occurrence in a Premature Infant

Background: Survival of low birth weight preterm neonates has increased with the availability of better neonatal care, however, the use of central lines for longer duration increases the risk of bacterial and fungal sepsis. Neonatal infective endocarditis (IE) is a rare presentation of neonatal sepsis and is often associated with complications and high mortality. Clinical Description: A 36 weeker, premature baby, hospitalized for early onset sepsis, was transferred to our hospital on day 15 of life, with an umbilical catheter in situ, with fever, respiratory distress, and persistent thrombocytopenia. Clinical examination revealed decreased oxygen saturation, crepitations in the right lung field, systolic murmur, and hepatomegaly. Management and Outcome: Baseline investigations revealed positive septic screen with thrombocytopenia with meningitis, neonatal cholestasis, and right sided consolidation on chest X ray. A two dimensional echocardiography (ECHO) revealed vegetation on the tricuspid valve, and blood culture from two sites revealed growth of Candida tropicalis and Serratia marcescens. Colistin, tigecycline, and amphotericin B therapy were initiated as per sensitivity along with low molecular weight heparin for prevention of embolization. The baby developed acute worsening in respiratory distress after 4 weeks of therapy. Repeat ECHO revealed increased size of cardiac vegetation and computed tomography of thorax with pulmonary angiography revealed pulmonary thromboembolism. Unfortunately, the baby succumbed to complications of IE. Conclusion: Invasive instrumentations such as umbilical catheterization and prolonged hospitalizations of premature newborns predispose them to develop IE, especially with unusual organisms. Such infections have a complicated course and may be fatal.

Efficacy and Safety of Anti-Xa-Guided Versus Fixed Dosing of Low Molecular Weight Heparin for Prevention of Venous Thromboembolism in Trauma Patients: A Systematic Review and Meta-Analysis.

Trauma patients are at high risk of venous thromboembolism (VTE). We summarize the comparative efficacy and safety of anti-Xa-guided versus fixed dosing for low molecular weight heparin (LMWH) for the prevention of VTE in adult trauma patients. We searched Medline and Embase from inception through June 1, 2022. We included randomized controlled trials or observational studies comparing anti-Xa-guided versus fixed dosing of LMWH for thromboprophylaxis in adult trauma patients. We incorporated primary data from 2 large observational cohorts. We pooled effect estimates using a random-effects model. We assessed risk of bias using the ROBINS-I tool for observational studies and assessed certainty of findings using GRADE methodology. We included 15 observational studies involving 10,348 patients. No randomized controlled trials were identified. determined that, compared to fixed LMWH dosing, anti-Xa-guided dosing may reduce deep vein thrombosis [adjusted odds ratio (aOR); 0.52, 95% CI: 0.40-0.69], pulmonary embolism (aOR: 0.48, 95% CI: 0.30-0.78) or any VTE (aOR: 0.54, 95% CI: 0.42-0.69), though all estimates are based on low certainty evidence. There was an uncertain effect on mortality (aOR: 1.06, 95% CI: 0.85-1.32) and bleeding events (aOR: 0.84, 95% CI: 0.50-1.39), limited by serious imprecision. We used several sensitivity and subgroup analyses to confirm the validity of our assumptions. Anti-Xa-guided dosing may be more effective than fixed dosing for prevention of deep vein thrombosis, pulmonary embolism, and VTE for adult trauma patients. These promising findings justify the need for a high-quality randomized study with the potential to deliver practice changing results.

Uloga aktivne perinatologije u prevenciji nepotrebnog gubitka koncepcije i pada nataliteta

Introduction: Modern perinatology demands continuous improvement of doctrines and protocols. The loss of conceptus is unforgivable when the possibility to sustain such pregnancy would elevate the level of birth rate that we aspire as a society. The aim of this study was to show the role of low molecular weight heparin in prevention of poor pregnancy outcomes. Methods: The study included all women with inherited thrombophilia referred to the Clinic for Gynecology and Obstetrics of the Clinical Centre of Serbia between 2016 and 2018 who were followed-up until delivery. The patients were divided into two groups. Results: The total number of 180 patients were pregnant for the first time, while 178 patients had had previous pregnancies. In 153 out of 178 patients, the previous pregnancy had poor outcome. 12 patients with AC therapy had FMU in previous pregnancies, 49 patients had missed abortion, 54 patients had second trimester miscarriage, 4 patients had both FMU and missed abortion, 9 patients had missed abortion and second trimester miscarriage while one patient had FMU, missed abortion and second trimester miscarriage. In previous pregnancies, 92 babies were born out of 313 pregnancies while in the current pregnancies treated with therapy there were 173 babies from 151 pregnancies. Conclusions: Patients with anticoagulant treatment in current pregnancy have had significant burden of previous pregnancy losses.

Prophylaxis for venous thromboembolism in liver disease: a narrative literature review

Background: Patients with liver disease have traditionally been regarded as auto-anticoagulated against developing blood clots due to haemorrhage being regarded as the most significant haemostatic complication. More recently, there has been increasing recognition that hypercoagulability is a prominent aspect of cirrhosis, with an increasing number of patients developing thromboembolisms. When prescribing prophylactic low molecular weight heparin for prevention, clinicians are often concerned about the risk of bleeding, including gastrointestinal bleeding, specifically in those with decompensated liver disease and cirrhosis, due to the altered coagulopathy associated with these patients. Aim: The aim of this review was to assess if the use of prophylaxis in patients with liver disease is effective in the prevention of venous thromboembolism (VTE) and whether its use is related to an increase in bleeding episodes. Methods: A review of the literature was conducted to identify the incidence of VTE and bleeding in liver patients when given prophylactic VTE treatment. Results: The majority of evidence was inconclusive; however, the main emerging theme was that administering prophylaxis to patients with decompensated liver disease results in an increased risk of bleeding, while having little effect on reducing the risk of VTE development. Conclusion: The bleeding risk associated with VTE prophylaxis treatment and liver disease remains uncertain. Thus the ideal methods of medical prophylactic VTE prevention and monitoring in this patient population have not yet been determined. It is suggested that additional consideration should be given to serum albumin, platelet count and international normalised ratio, as well as renal function, in conjunction with risk assessment tools, when deciding whether to prescribe VTE prophylaxis or not.

Results of early administration of low molecular weight heparin for prevention of venous thromboembolism after removal of brain tumors

Introduction. Patients with brain tumors are at increased risk for the development of venous thromboembolism (VTE). The most effective prevention method today is a combination of mechanical compression of the lower extremities and the introduction of low molecular weight heparin (LMWH). In 2018, an algorithm for the prevention of VTE was introduced in our clinic, which implies the early (in the first 48 h after surgery) administration of LMWH.The study objective is to assess the effect of early LMWH administration on the incidence of intracranial hemorrhage (ICH) after removal of brain tumors.Materials and methods. From January 2014 to December 2019, 3266 patients underwent removal of brain tumors. The group 1 included 2057 patients who were treated in the period before the introduction of the VTE prevention algorithm (2014– 2017), the group 2 included 1209 patients who were treated using this algorithm (2018–2019). In each of the groups, the frequency and timing of ICH were assessed. The severity of complications was assessed according to the F.A.L. Ibanez classification. The data were compared between groups 1 and 2, as well as between patients who received LMWH at the time of ICH and those who did not receive.Results. Patients of the group 1 were prescribed LMWH in 14.3 % of cases, on average on the 4th day after surgery. In this group, 26 (1.26 %) patients developed ICH. Patients of the group 2 were prescribed LMWH in 89 % of cases, on average on the 2nd day. In this group, 15 (1.24 %) patients developed ICH. Severe complications were in 6 (85.7 %) of 7 patients who received LMWH at the time of ICH, and in 25 (73.5 %) of 34 patients who did not receive LMWH (p = 0.66).Conclusion. The widespread use of LMWH for the prevention of VTE during the first 48 h after removal of brain tumors did not lead to an increase in the frequency of ICH. At the same time, patients with ICH who developed during the use of LMWH often had a more severe clinical course.

The comparative effectiveness of direct oral anti-coagulants and low molecular weight heparins for prevention of recurrent venous thromboembolism in cancer: The CANVAS pragmatic randomized trial.

12020 Background: Previous randomized trials in cancer patients suggest that DOACs are non-inferior to LMWH for preventing recurrent VTE but have higher risk of bleeding. However, the balance of benefits and burdens remains uncertain. Objective: The CANVAS pragmatic trial compared recurrent VTE, bleeding and death in cancer patients following an initial VTE treated with either DOAC or LMWH therapy. Methods: CANVAS was an unblinded hybrid comparative effectiveness non-inferiority trial, with randomized and preference cohorts. Between 12/16 and 4/20, 671 participants were randomized and followed for 6-months. Between 12/16 and 12/17, 140 participants declined randomization, chose their preferred anticoagulant and were followed for 6-months. The preference cohort was closed when predetermined stopping criteria were met. Final follow-up was 11/30/20. Randomized patients were assigned 1:1 to receive either a DOAC or a LMWH. If assigned to LMWH, transitions to warfarin were allowed. Physicians and patients could choose among any DOAC or LMWH. Doses were suggested based on FDA-approved labeling but not mandated. Patients from 67 practices in the US with any invasive solid tumor, lymphoma, multiple myeloma or CLL and a diagnosis of symptomatic or radiographically detected VTE within 30 days of enrollment were eligible. The 1° analysis was conducted in the randomized modified-into to treat popululation, (all subjects who received study drug). The 1° outcome was recurrent VTE. The aim was to establish noninferiority of anticoagulation with a DOAC as defined by the upper limit of the 2-sided 90% CI for the difference in the event rate at 6 months of < 3%. Secondary outcomes included death and bleeding. Hypothesis testing included only the randomized cohort but propensity score adjusted results for the preference and combined cohorts are also shown. Results: The non-inferiority criteria for recurrent VTE was met. Conclusions: Among adult cancer patients with VTE, the use of a DOAC compared with a LMWH resulted in a noninferior risk of recurrent VTE with no differences in rates of bleeding or death in randomized patients. Clinical trial information: NCT02744092. [Table: see text]

Bleeding events in COVID-19: the other side of the coin?

We present three cases of patients affected by severe SARS-CoV-2-related pneumonia treated with a low molecular weight heparin for prevention or treatment of pulmonary embolism, who presented a major bleed, in particular an ileopsoas haematoma that caused severe anaemia; in one case it was fatal. In the recent outbreak of novel coronavirus infection, significantly abnormal coagulation parameters in SARS-CoV-2 infection occur very often, but complications in the opposite direction such as bleeding diathesis are very rare. In these cases, there are different levels of gravity: for one patient the major bleed required the anticoagulant therapy to be stopped until bleeding stabilized, one patient needed interventional radiology and one patient died.

Stroke and Thromboprophylaxis in the Era of COVID-19

Stroke and Thromboprophylaxis in the Era of COVID-19

Low molecular weight heparin for prevention of central venous catheter-related thrombosis in children.

The prevalence of children diagnosed with thrombotic events has been increasing in the last decades. The most common thrombosis risk factor in neonates, infants and children is the placement of a central venous catheter (CVC). It is unknown if anticoagulation prophylaxis with low molecular weight heparin (LMWH) decreases CVC-related thrombosis in children. This is an update of the Cochrane Review published in 2014. To determine the effect of LMWH prophylaxis on the incidence of CVC-related thrombosis and major and minor bleeding complications in children. Further objectives were to determine the effect of LMWH on occlusion of CVCs, number of days of CVC patency, episodes of catheter-related bloodstream infection (CRBSI), other side effects of LMWH (allergic reactions, abnormal coagulation profile, heparin-induced thrombocytopaenia and osteoporosis) and mortality during therapy. The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL databases and World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 7 May 2019. We undertook reference checking of identified trials to identify additional studies. We included randomised controlled trials (RCTs) and quasi-randomised trials comparing LMWH to no prophylaxis (placebo or no treatment), or low-dose unfractionated heparin (UFH) either as continuous infusion or flushes (low-dose UFH aims to ensure the patency of the central line but has no systemic anticoagulation activity), given to prevent CVC-related thrombotic events in children. We selected studies conducted in children aged 0 to 18 years. Two review authors independently identified eligible studies, which were assessed for study methodology including bias, and extracted unadjusted data where available. In the data analysis step, all outcomes were analysed as binary or dichotomous outcomes. The effects of interventions were summarised with risk ratios (RR) and their respective 95% confidence intervals (CI). We assessed the certainty of evidence for each outcome using the GRADE approach. One additional study was included for this update bringing the total to two included studies (with 1135 participants). Both studies were open-label RCTs comparing LMWH with low-dose UFH to prevent CVC-related thrombosis in children. We identified no studies comparing LMWH with placebo or no treatment. Meta-analysis found insufficient evidence of an effect of LMWH prophylaxis in reducing the incidence of CVC-related thrombosis in children with CVC, compared to low-dose UFH (RR 0.68, 95% CI 0.27 to 1.75; 2 studies; 787 participants; low-certainty evidence). One study (158 participants) reported symptomatic and asymptomatic CVC-related thrombosis separately and detected no evidence of a difference between LMWH and low-dose UFH (RR 1.03, 95% CI 0.21 to 4.93; low-certainty evidence; RR 1.17, 95% CI 0.45 to 3.08; low-certainty evidence; for symptomatic and asymptomatic participants respectively). There was insufficient evidence to determine whether LMWH impacts the risk of major bleeding (RR 0.27, 95% CI 0.05 to 1.67; 2 studies; 813 participants; low-certainty evidence); or minor bleeding. One study reported minor bleeding in 53.3% of participants in the LMWH arm and in 44.7% of participants in the low-dose UFH arm (RR 1.20, 95% CI 0.91 to 1.58; 1 study; 158 participants; very low-certainty evidence), and the other study reported no minor bleeding in either group (RR: not estimable). Mortality during the study period was reported in one study, where two deaths occurred during the study period. Both were unrelated to thrombotic events and occurred in the low-dose UFH arm. The second study did not report mortality during therapy per arm but showed similar 5-year overall survival (low-certainty evidence). No additional adverse effects were reported. Other pre-specified outcomes (including CVC occlusion, patency and CRBSI) were not reported. Pooling data from two RCTs did not provide evidence to support the use of prophylactic LWMH for preventing CVC-related thrombosis in children (low-certainty evidence). Evidence was also insufficient to confirm or exclude a difference in the incidence of major and minor bleeding complications in the LMWH prophylaxis group compared to low-dose UFH (low and very low certainty respectively). No evidence of a clear difference in overall mortality was seen. Studies did not report on the outcomes catheter occlusion, days of catheter patency, episodes of CRBSI and other side effects of LMWH (allergic reactions, abnormal coagulation profile, heparin-induced thrombocytopaenia and osteoporosis). The certainty of the evidence was downgraded due to risk of bias of the included studies, imprecision and inconsistency, preventing conclusions in regards to the efficacy of LMWH prophylaxis to prevent CVC-related thrombosis in children.

Low molecular weight heparin for prevention of microvascular occlusion in digital replantation.

Microvascular surgery refers to any surgery involving small sized blood vessels that is performed under the operating microscope, allowing the repair of arteries and veins of the digits. These are typically 1 mm to 2 mm in diameter. Replantation is the reattachment of a completely detached body part, with fingers and thumbs being the most commonly replanted body parts. This is often referred to as digital replantation. In principle, digital replantation involves not only restoring the blood flow through the arteries and veins but also restoring the bony skeleton of the toes, fingers or thumbs, along with repairing the tendons and nerves as indicated. Occlusion of one or more of the repaired vessels due to the formation of a clot (thrombus) within the blood vessel results in failure of the replantation. Anticoagulant medications are used to reduce clotting, and they could potentially prevent such a complication. Anticoagulants such as unfractionated heparin (UFH) have therefore been used to prevent clot formation after digital replantation. It is unclear if low molecular weight heparin (LMWH) has similar benefit. This systematic review identified only two randomised controlled trials comparing UFH with LMWH, with a total of 114 patients. No studies were identified that compared LMWH with placebo, no treatment or other anticoagulants. The limited data from the two trials showed no difference between LMWH and UFH in the success rate for digital replantation but there were less frequent anticoagulation-related adverse events (such as bleeding) with LMWH. The available evidence is insufficient to make a firm conclusion.

How does fondaparinux compare with low molecular weight heparin for prevention of venous thromboembolism?

How does fondaparinux compare with low molecular weight heparin for prevention of venous thromboembolism?

European guidelines on perioperative venous thromboembolism prophylaxis: Aspirin.

: There is a good rationale for the use of aspirin in venous thromboembolism prophylaxis in some orthopaedic procedures, as already proposed by the 9th American College of Chest Physicians' guidelines (Grade 1C). We recommend using aspirin, considering that it may be less effective than or as effective as low molecular weight heparin for prevention of deep vein thrombosis and pulmonary embolism after total hip arthroplasty, total knee arthroplasty and hip fracture surgery (Grade 1C). Aspirin may be less effective than or as effective as low molecular weight heparins for prevention of deep vein thrombosis and pulmonary embolism after other orthopaedic procedures (Grade 2C). Aspirin may be associated with a low rate of bleeding after total hip arthroplasty, total knee arthroplasty and hip fracture surgery (Grade 1B). Aspirin may be associated with less bleeding after total hip arthroplasty, total knee arthroplasty and hip fracture surgery than other pharmacological agents (Grade 1B). No data are available for other orthopaedic procedures. We do not recommend aspirin as thromboprophylaxis in general surgery (Grade 1C). However, this type of prophylaxis could be interesting especially in low-income countries (Grade 2C) and adequate large-scale trials with proper study designs should be carried out (Grade 1C).

Low molecular weight heparin for prevention of venous thromboembolism in patients with lower-limb immobilization.

Immobilization of the lower limb is a risk factor for venous thromboembolism (VTE). Low molecular weight heparins (LMWHs) are anticoagulants, which might be used in adult patients with lower-limb immobilization to prevent deep venous thrombosis (DVT) and its complications. This is an update of the review first published in 2008. To assess the effectiveness of low molecular weight heparin for the prevention of venous thromboembolism in patients with lower-limb immobilization in an ambulatory setting. For this update, the Cochrane Vascular Information Specialist searched the Specialised Register, CENTRAL, and three trials registers (April 2017). Randomized controlled trials (RCTs) and controlled clinical trials (CCTs) that described thromboprophylaxis by means of LMWH compared with no prophylaxis or placebo in adult patients with lower-limb immobilization. Immobilization was by means of a plaster cast or brace. Two review authors independently selected trials, assessed risk of bias and extracted data. The review authors contacted the trial authors for additional information if required. Statistical analysis was carried out using Review Manager 5. We included eight RCTs that fulfilled our criteria, with a total of 3680 participants. The quality of evidence, according GRADE, varied by outcome and ranged from low to moderate. We found an incidence of DVT ranging from 4.3% to 40% in patients who had a leg injury that had been immobilized in a plaster cast or a brace for at least one week, and who received no prophylaxis, or placebo. This number was significantly lower in patients who received daily subcutaneous injections of LMWH during immobilization, with event rates ranging from 0% to 37% (odds ratio (OR) 0.45, 95% confidence interval (CI) 0.33 to 0.61; with minimal evidence of heterogeneity: I² = 26%, P = 0.23; seven studies; 1676 participants, moderate-quality evidence). Comparable results were seen in the following groups of participants: patients with below-knee casts, conservatively treated patients (non-operated patients), operated patients, patients with fractures, patients with soft-tissue injuries, and patients with distal or proximal thrombosis. No clear differences were found between the LMWH and control groups for pulmonary embolism (OR 0.50, 95% CI 0.17 to 1.47; with no evidence of heterogeneity: I² = 0%, P = 0.56; five studies, 2517 participants; low-quality evidence). The studies also showed less symptomatic VTE in the LMWH groups compared with the control groups (OR 0.40, 95% CI 0.21 to 0.76; with minimal evidence of heterogeneity: I² = 16%, P = 0.31; six studies; 2924 participants; low-quality evidence). One death was reported in the included studies, but no deaths due to pulmonary embolism were reported. Complications of major adverse events were rare, with minor bleeding the main adverse events reported. Moderate-quality evidence showed that the use of LMWH in outpatients reduced DVT when immobilization of the lower limb was required, when compared with no prophylaxis or placebo. The quality of the evidence was reduced to moderate because of risk of selection and attrition bias in the included studies. Low-quality evidence showed no clear differences in PE between the LMWH and control groups, but less symptomatic VTE in the LMWH groups. The quality of the evidence was downgraded due to risk of bias and imprecision.

Использование низкомолекулярных гепаринов в профилактике плацентарной недостаточности

Использование низкомолекулярных гепаринов в профилактике плацентарной недостаточности

Low Molecular Weight Heparin for Prevention of Placenta-Mediated Pregnancy Complications: An Individual Patient Data Meta-Analysis

Introduction Placenta-mediated pregnancy complications (PMPC) include pre-eclampsia, late pregnancy loss, placental abruption, and the small-for-gestational age (SGA) newborn. They are leading causes of maternal, fetal, and neonatal morbidity and mortality. Affected women are at an elevated risk of recurrence in subsequent pregnancies. We completed a pooled summary-based (i.e. study level) meta-analysis that strongly suggests that low-molecular-weight heparin (LMWH) reduces the risk of recurrent PMPCs. However, our study-level meta-analysis was limited by high clinical and statistical heterogeneity likely due to the inclusion of women with heterogeneous prior PMPCs and trial designs (e.g. single vs multi-center trials). To address these limitations, the trialists agreed to conduct an individual patient data meta-analysis to identify sources of heterogeneity including exploring which patients benefit from LMWH and which outcomes are prevented. Methods We conducted a systematic review to identify randomised controlled trials that were eligible to contribute individual patient data to a meta-analysis to evaluate the effectiveness of LMWH for reducing the risk of PMPC in women with prior PMPCs. The primary outcome was a composite of early-onset or severe pre-eclampsia, birth of an SGA newborn 20 weeks), or placental abruption leading to delivery. Individual patient data from eligible women were re-coded in a prescribed format and combined in a common dataset for analysis. All studies were assessed for risk of bias. Results Data from 1049 women in nine trials were analysed; Participants were mostly Caucasian (88%) with a mean age of 31.518 had thrombophilia. 525 women were randomised to LMWH and 524 to no LMWH. In our primary outcome analysis, LMWH did not significantly reduce the risk of recurrent PMPCs (LMWH 60/459 (13.1%) vs. no LMWH 92/449 (20.5%) p=0.1). Significant heterogeneity was noted between single center and multi-center trials. In multi-center trials, LMWH reduced HELLP (p=0.03) but none of the other secondary outcomes, whereas in single center trials LMWH reduced all of the secondary outcomes. In sub-group analysis, in multi-center trials LMWH reduced the primary outcome in women with prior abruption (p Conclusions In this individual patient data meta-analysis, LMWH does not appear to reduce the risk of recurrent PMPC in women with prior PMPC. Promising results suggest that women with prior abruption may benefit from LMWH but this should be replicated in future multi-center trials. PROSPERO registration:CRD42013006249 Disclosures Rodger:Biomerieux: Honoraria, Research Funding. Off Label Use: Low Molecular Weight Heparin to prevent pregnancy complications. de Vries:Pfizer: Research Funding. Rey:Leo Pharma: Other: Travel Grant. Gris:Sanofi: Consultancy, Membership on an entity9s Board of Directors or advisory committees, Research Funding; Stago: Consultancy, Membership on an entity9s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Leo Pharma: Consultancy, Speakers Bureau; LFB: Consultancy, Membership on an entity9s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Baxter: Research Funding; BI: Speakers Bureau; Bayer: Speakers Bureau; BMS: Speakers Bureau. Schleussner:Bayer: Speakers Bureau; Pfizer: Research Funding, Speakers Bureau; Merck: Research Funding, Speakers Bureau. Middeldorp:GSK/Aspen: Research Funding; Bayer: Consultancy, Speakers Bureau; BI: Consultancy, Speakers Bureau; BMS: Consultancy, Research Funding, Speakers Bureau; Pfizer: Consultancy, Research Funding, Speakers Bureau; Daiichi-Sankyo: Consultancy, Speakers Bureau. Bates:Eli Lilly Canada: Other: I hold the Eli Lilly Canada/May Cohen Chair in Women9s Health. Eli Lilly Canada provides unrestricted funding for partial salary support through this Chair. Eli Lilly Canada does not manufacture/distribute drugs relevant to the topic to be discussed..

Low molecular weight heparin for prevention of venous thromboembolism in patients with lower-leg immobilization.

Immobilization of the lower leg is associated with venous thromboembolism (VTE). Low molecular weight heparin (LMWH) is an anticoagulant treatment which might be used in adult patients with lower-leg immobilization to prevent deep venous thrombosis (DVT) and its complications. This is an update of the review first published in 2008. To assess the effectiveness of low molecular weight heparin for the prevention of venous thromboembolism in patients with lower-leg immobilization in an ambulant setting. For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched June 2013) and CENTRAL (2013, Issue 5). Randomized controlled trials (RCTs) and controlled clinical trials (CCTs) that described thromboprophylaxis by means of LMWH compared with no prophylaxis or placebo in adult patients with lower-leg immobilization. Immobilization was by means of a plaster cast or brace. Two authors independently assessed trial quality and extracted data. The review authors contacted the trial authors for additional information if required. Statistical analysis was carried out using Review Manager (RevMan 5). We included six RCTs fulfilling the above criteria with a total of 1490 patients. We found an incidence of VTE ranging from 4.3% to 40% in patients who had a leg injury that had been immobilized in a plaster cast or a brace for at least one week and who received no prophylaxis, or placebo. This number was significantly lower in patients who received daily subcutaneous injections of LMWH during immobilization (event rates ranging from 0% to 37%; odds ratio (OR) 0.49; fixed 95% confidence interval (CI) 0.34 to 0.72; with minimal evidence of heterogeneity with an I(2) of 20%, P = 0. 29). Comparable results were seen in the following subcategories: operated patients, conservatively treated patients, patients with fractures, patients with soft-tissue injuries, patients with proximal thrombosis, patients with distal thrombosis and patients with below-knee casts. Complications of major bleeding events were extremely rare (0.3%) and there were no reports of heparin-induced thrombocytopenia. Use of LMWH in outpatients significantly reduces VTE when immobilization of the lower leg is required.

Low molecular weight heparin for prevention of central venous catheterization-related thrombosis in children

The prevalence of children diagnosed with deep vein thrombosis or pulmonary embolism has been increasing in the last decade. The most common thrombosis risk factor in neonates, infants and children is the placement of a central venous catheter (CVC). To date, it is unknown if the practice of anticoagulation prophylaxis with low molecular weight heparin (LMWH) decreases CVC-related thrombosis in children. The primary objective of this review was to determine the effect of LMWH prophylaxis on reducing the incidence of CVC-related thrombosis in children.Secondary objectives were to determine the effect of LMWH on occlusion of CVCs, number of days of CVC patency, episodes of catheter-related sepsis, side effects of LMWH (allergic reactions, major and minor bleeding complications, abnormal coagulation profile, osteoporosis) and mortality during therapy. The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched June 2013), CENTRAL (2013, Issue 5) and clinical trial databases. The authors searched MEDLINE and EMBASE (July 2013). Bibliographies of identified articles were searched. There were no language restrictions. Randomised and quasi-randomised trials comparing LMWH prophylaxis to standard care given to prevent CVC-related thrombotic events in children were included. We selected studies conducted in children aged 0 to 18 years. Two review authors independently identified eligible studies, which were assessed for study quality including bias, and extracted unadjusted data where available. In the data analysis step, all outcomes were analysed as binary or dichotomous outcomes. The effects of interventions were summarised with risk ratios (RR) and their respective 95% confidence intervals (CI). One of 17 studies retrieved for full-text assessment for eligibility was included in the final analysis. This study included a total of 186 participants and investigated the effect of LMWH to prevent CVC-related thrombosis compared to standard care. The risk of bias of the study was assessed to be low, except for the unclear risk of selection bias (allocation concealment not reported) and detection bias since it was an open-label study. Nonetheless, outcome adjudication was blinded. However, overall the quality of the evidence was low due to the fact that the study was underpowered. The CIs for the risk of CVC-related thrombosis (symptomatic and asymptomatic events) were compatible with benefits of either LMWH (reviparin) or the control (RR for symptomatic thrombosis 1.03, 95% CI 0.21 to 4.93; RR for asymptomatic thrombosis 1.17, 95% CI 0.45 to 3.08). Similarly, only one patient in the standard care group suffered a major bleeding event, while minor bleeding was found in 53.3% of patients in the reviparin arm and in 44.7% of patients in the standard care arm (major bleeding RR 0.34, 95% CI 0.01 to 8.26; minor bleeding RR 1.20, 95% CI 0.91 to 1.58). Lastly, there were two deaths within the study and neither were the result of a venous thrombotic event (VTE), occurring in the standard care arm. No additional adverse effects were reported. Other pre-specified outcomes for this review were not reported. A single study reported imprecise effects for the risk of CVC-related thrombosis in children on a CVC anticoagulant prophylaxis regimen. The quality of the evidence was low due to the fact that the included study was clearly underpowered, hampering any conclusions in regards to the efficacy of LMWH prophylaxis to prevent CVC-related thrombi in children. Further prospective randomised studies are highly encouraged.

Prophylaxis with Low Molecular Weight Heparin for Prevention of Placenta-related Recurrent Adverse Pregnancy Outcomes

Aims: To determine whether antenatal administration of low-molecular-weight-heparin (LMWH) reduces the recurrence of adverse pregnancy outcomes (APO). Study Design: Retrospective cohort study. Place and Duration of the Study: Inova Alexandria Hospital, Alexandria, VA and Georgetown University Medical Center, Washington, DC during the period of January 1, 2006 and December 31, 2009. Methodology: All pregnant women with history of APOs, including preeclampsia or abruption at <35 weeks, birth weight <5th centile, fetal loss at ≥20 weeks, or ≥2 spontaneous losses between 12 and 20 weeks, were administered LMWH or not at the discretion of the managing physician. Excluded were cases with antiphospholipid Original Research Article Kamda et al.; IBRR, Article no. IBRR.2014.005 141 syndrome. The independent effect of LMWH on recurrence was assessed using logistic regression analysis with odds ratios (OR) having 95% confidence interval (CI) not inclusive of the unity considered significant. Results: Of the 140 women in the cohort, 44 (31%) received LMWH during the subsequent pregnancy and the remainder did not. APO recurred in 23.6% (33/140). Logistic regression analysis demonstrated that LMWH significantly and independently lowered the risk of recurrent APO (adjusted OR=0.08, 95% CI 0.01-0.45), whereas history of fetal growth restriction (OR=3.88, 95% CI 1.51-9.99) and positive results for inherited thrombophilias (OR=6.96, 95% CI 1.58-30.67) increased the risk. Conclusion: In patients with rigorously defined history of severe APO, prophylaxis with LMWH is associated with a significant reduction in recurrence of severe APO.

Low molecular weight heparin for prevention of microvascular occlusion in digital replantation

The success of digital replantation is highly dependent on the patency of the repaired vessels after microvascular anastomosis. Antithrombotic agents are frequently used for preventing vascular occlusion. Low molecular weight heparin (LMWH) has been reported to be as effective as unfractionated heparin (UFH) in peripheral vascular surgery, but with fewer adverse effects. Its benefit in microvascular surgery such as digital replantation is unclear. To assess whether subcutaneous LMWH treatment improves the salvage rate of the digits in patients with digital replantation after traumatic amputation. The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator (TSC) searched the Specialised Register (October 2012), CENTRAL (2012, Issue 10) and trials databases. In addition, the authors searched PubMed, CNKI (China National Knowledge Infrastructure) and CEPS (Chinese Electronic Periodical Services), and sought additional trials from reference lists of relevant publications. We selected randomised or quasi-randomised controlled trials of LMWH in patients who received digital replantation. Two review authors independently extracted data and assessed the risk of bias of the included trials. Disagreements were resolved by discussion. Two randomised trials involving 114 patients with at least 122 replanted digits met the inclusion criteria and were included. Both trials compared the efficacy and safety of LMWH with UFH. We found no trials comparing LMWH with placebo or other anticoagulants. The data from the two included studies were insufficient for meta-analysis. The overall success rate of replantation did not differ between the LMWH and UFH groups, 92.3% versus 89.2% in one trial (risk ratio (RR) 1.03; 95% confidence interval (CI) 0.87 to 1.22) and 94.3% versus 94.15% in the other trial (RR 1.00; 95% CI 0.89 to 1.13). The incidence of both postoperative arterial and venous insufficiency were reported in one trial and did not significantly differ between the LMWH and UFH groups (RR 1.08; 95% CI 0.16 to 7.10 and RR 0.81; 95% CI 0.20 to 3.27, respectively). Direct and indirect causes of microvascular insufficiency were not reported in the trials. Different methods were used to monitor the adverse effects related to anticoagulation in the two trials. Bleeding tendency was monitored for the LMWH and UFH groups in one trial and was reported by the incidence of wound haemorrhage (11.5% versus 17.9%; RR 0.65; 95% CI 0.17 to 2.44), ecchymoses (3.8% versus 10.7%; RR 0.36; 95% CI 0.04 to 3.24), haematuria (3.8% versus 7.1%; RR 0.54; 95% CI 0.05 to 5.59), nasal bleeding (0% versus 7.1%; RR 0.21; 95% CI 0.01 to 4.28), gingival bleeding (0% versus 10.7%; RR 0.15, 95% CI 0.01 to 2.83) and faecal occult blood (0% versus 3.6%; RR 0.36; 95% CI 0.02 to 8.42). The bleeding tendency was increased in the UFH group but this was not statistically significant. This trial also monitored coagulability changes using parameters such as antithrombin activity, factor Xa activity, bleeding time, clotting time and activated partial thromboplastin time (aPTT). No comparison was made between the LMWH and UFH groups but all data consistently showed that coagulability was reduced more in the UFH group than in the LMWH group. The other trial reported a postoperative decrease in platelet count in the UFH group (preoperative 278.4 ± 18.7 x 10(9)/L, postoperative 194.3 ± 26.5 x 10(9)/L; P < 0.05) but not in the LMWH group (preoperative 260.8 ± 32.5 x 10(9)/L, postoperative 252.4 ± 29.1 x 10(9)/L; P > 0.05). Current limited evidence based on two small-scaled low-to-medium quality randomised trials found no differences in the success rate of replantation between LMWH and UFH, but a lower risk of postoperative bleeding and hypocoagulability after the use of LMWH. Further well-designed and adequately powered clinical trials are warranted.

Review: Direct thrombin inhibitors are similar to LMWH and vitamin K antagonists for preventing VTE after hip or knee replacement

Source Citation Salazar CA, Malaga G, Malasquez G. Direct thrombin inhibitors versus vitamin K antagonists or low molecular weight heparins for prevention of venous thromboembolism following total ...