Subcutaneous Injection Of Low Molecular Weight Heparin Research Articles

Propensity weighted analysis of chemical venous thromboembolism prophylaxis agents in isolated severe traumatic brain injury: An EAST sponsored multicenter study

BackgroundIn patients with severe traumatic brain injury (TBI), clinicians must balance preventing venous thromboembolism (VTE) with the risk of intracranial hemorrhagic expansion (ICHE). We hypothesized that low molecular weight heparin (LMWH) would not increase risk of ICHE or VTE as compared to unfractionated heparin (UH) in patients with severe TBI. MethodsPatients ≥ 18 years of age with isolated severe TBI (AIS ≥ 3), admitted to 24 level I and II trauma centers between January 1, 2014 to December 31, 2020 and who received subcutaneous UH and LMWH injections for chemical venous thromboembolism prophylaxis (VTEP) were included. Primary outcomes were VTE and ICHE after VTEP initiation. Secondary outcomes were mortality and neurosurgical interventions. Entropy balancing (EBAL) weighted competing risk or logistic regression models were estimated for all outcomes with chemical VTEP agent as the predictor of interest. Results984 patients received chemical VTEP, 482 UH and 502 LMWH. Patients on LMWH more often had pre-existing conditions such as liver disease (UH vs LMWH 1.7 % vs. 4.4 %, p = 0.01), and coagulopathy (UH vs LMWH 0.4 % vs. 4.2 %, p < 0.001). There were no differences in VTE or ICHE after VTEP initiation. There were no differences in neurosurgical interventions performed. There were a total of 29 VTE events (3 %) in the cohort who received VTEP. A Cox proportional hazards model with a random effect for facility demonstrated no statistically significant differences in time to VTE across the two agents (p = 0.44). The LMWH group had a 43 % lower risk of overall ICHE compared to the UH group (HR = 0.57: 95 % CI = 0.32–1.03, p = 0.062), however was not statistically significant. ConclusionIn this multi-center analysis, patients who received LMWH had a decreased risk of ICHE, with no differences in VTE, ICHE after VTEP initiation and neurosurgical interventions compared to those who received UH. There were no safety concerns when using LMWH compared to UH. Level of evidenceLevel III, Therapeutic Care Management

Apixaban Is Safe and Effective Thromboprophylaxis in Myeloma Patients Treated with Immunomodulatory Therapy

IntroductionPatients with myeloma are at increased risk of venous thromboembolism (VTE) and arterial thrombosis, particularly when treated with immunomodulatory drugs (IMiDs) such as thalidomide or lenalidomide. The optimal approach to prevent such potentially fatal complications has not been determined. Despite routine thromboprophylaxis with aspirin, low molecular weight heparin (LMWH) or warfarin, thrombosis rates of thrombosis of 2-8% are reported in the literature. Current agents have limited efficacy with significant associated burdens such as repeated INR monitoring or subcutaneous administration. Direct oral anticoagulants are promising due to their convenience and effectiveness in preventing VTE in other settings. They have not been extensively studied in myeloma therapy.Our baseline audit of 82 consecutive myeloma patients treated with IMiD-containing regimens and receiving thromboprohylaxis with aspirin had VTE rates of 11%. Of 31 patients treated with heparins 6.5% had VTE. These rates are consistent with data in the literature. Apixaban is cheaper than LMWH therapy in our centre.In November 2014 our policy was changed such that apixaban became standard thromboprophylaxis; the effect of this change is reported here.AimAssess the safety and efficacy of apixaban as thromboprophylaxis in patients with multiple myeloma undergoing first line therapy with IMID-containing regimens.MethodConsecutively presenting patients between 1st November 2014 and 31st December 2016 with multiple myeloma undergoing first-line therapy with IMiD-containing regimens were included in this retrospective study. All patients received apixaban 2.5mg twice daily for the first 4 months of therapy or until treatment cessation. Patients with severe renal failure (CrCl <15ml/min) or thrombocytopenia <50x10^9/L received alternative anticoagulants and were excluded from this audit. Patients already on warfarin continued on warfarin and were excluded. The primary outcome was the occurrence of arterial or venous thromboembolism. We also recorded incidence of clinically significant bleeding episodes.Results70patients were identified. 45 (64%) were male, the median age was 66 years, range 43-86. Previous thrombosis: 2 PE, 1 stroke, 1 TIA, 3 myocardial infarction. Treatment (n): Cyclophosphamide-Thalidomide-Dexamethasone (19), Bortezomib-Thalidomide-Dexamethasone (27), Lenalidomide-Dexamethasone (3), Carfilzomib-Cyclophosphamide-Lenalidomide-Dexamethasone (8), Melphalan-Prednisolone-Thalidomide (n=9), Lenalidomide-Cyclophosphamide-Dexamethasone (4).There were no DVTs or PEs within 6 months of treatment initiation. Two patients (2.9%) had arterial thrombosis. One patient had a non-haemorrhagic stroke at day 19 with no identified embolic source and she had no cardiovascular comorbidities. One patient had a non-ST elevation myocardial infarction at day 23 with no previous diagnosis of ischaemic heart disease. He had stopped both thalidomide and apixaban 21 days previously due to drug-induced rash. One patient (1.4%) had major bleeding. He had melaena during his 4th cycle of MPT that resolved on apixaban cessation. His platelet count had dropped to 21x10^9/L during this episode. He required hospital admission for blood transfusion, but no bleeding point was identified at endoscopy.Conclusion - We studied the use of apixaban for preventing IMiD-induced thrombosis in front line myeloma therapy. Rates of thrombosis appear to be very low with no cases of VTE identified and only 2 cases of arterial thrombosis. There was one episode of major bleeding in a patient with coexistent thrombocytopenia. These toxicity rates compare favourably to historical and published data with other anticoagulants. The drug is suitable for ambulatory treatment even in frail patients, and avoids the logistical and acceptability problems of subcutaneous injection of LMWH. Apixaban appears to be an attractive and safe option for thromboprophylaxis in this setting. DisclosuresNo relevant conflicts of interest to declare.

Slow versus fast subcutaneous heparin injections for prevention of bruising and site pain intensity.

Heparin is an anticoagulant medication that is usually injected subcutaneously. Subcutaneous administration of heparin may result in complications such as bruising, haematoma, and pain at the injection site. One of the factors that may affect pain, haematoma, and bruising is injection speed. Several studies have been carried out to determine if speed of injection affects the amount of pain and bruising where the injection is given; however, the results of these studies have differed, and study authors have not reached a clear final conclusion. This is the second update of a review first published in 2014. To assess the effects of duration (speed) of subcutaneous heparin injection on pain and bruising at the injection site in people admitted to hospitals or clinics who require treatment with unfractionated heparin (UFH) or low molecular weight heparin (LMWH). We also looked at haematoma at the injection site. The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL databases and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 22 June 2020. We undertook reference checking of included studies to identify additional studies. We searched for randomised controlled trials (RCTs) comparing the effects of different durations of subcutaneous injection of heparin on pain, bruising, and haematoma at the injection site. For this update, two review authors independently selected studies and extracted data via Covidence software and assessed methodological quality using Cochrane's risk of bias tool. The primary outcomes of interest were pain intensity at injection site and size and incidence of bruising. The secondary outcomes of interest were size and incidence of haematoma at injection site. We calculated the odds ratio (OR), mean difference (MD), or standardised mean difference (SMD) with corresponding 95% confidence intervals (CIs). We assessed the certainty of the evidence using GRADE criteria. We identified one new study for this update, resulting in a total of five included studies with 503 participants who received subcutaneous injections of LMWH into the abdomen. Given the nature of the intervention, it was not possible to blind participants and caregivers (personnel) in any of the included studies. Two studies described blinding of outcome assessors. Overall, the methodological quality of included studies was moderate. The duration of the fast injection was 10 seconds, and the duration of the slow injection was 30 seconds in all included studies. Four studies reported site pain intensity after each injection at different time points. Two studies assessed site pain intensity immediately after each injection; meta-analysis showed no evidence of a difference in site pain intensity immediately after slow injection when compared to fast injection (MD -1.52, 95% CI -3.56 to 0.53; 140 participants; low-certainty evidence). Meta-analysis of three studies indicated that site pain intensity may be slightly reduced 48 hours after the slow heparin injection compared to fast injection (MD -1.60, 95% CI -2.69 to -0.51; 103 participants; low-certainty evidence). Five studies assessed bruise size at 48 hours, and two studies assessed bruise size at 60 hours. Meta-analysis showed there may be a reduction in bruise size 48 hours (SMD -0.54, 95% CI -1.05 to -0.02; 503 participants; 5 studies; very low-certainty evidence) and 60 hours (SMD -0.49, 95% CI -0.93 to -0.06; 84 participants; 2 studies; low-certainty evidence) after slow injection compared to fast injection. There was no evidence of a difference in bruise size 72 hours after slow injection compared to fast injection (SMD -0.27, 95% CI -0.61 to 0.06; 140 participants; 2 studies; low-certainty evidence). Three studies evaluated incidence of bruising and showed there may be a reduction in bruise incidence 48 hours (OR 0.39, 95% CI 0.26 to 0.60; 444 participants; low-certainty evidence) and 60 hours (OR 0.25, 95% CI 0.10 to 0.65; 84 participants; 2 studies; low-certainty evidence) after slow injection compared to fast injection. We downgraded the certainty of the evidence due to risk of bias concerns, imprecision, and inconsistency. None of the included studies measured size or incidence of haematoma. Administering medication safely and enhancing patient comfort are the main aims of clinical nurses. In this review, we identified five RCTs that evaluated the effect of subcutaneous heparin injection duration on pain intensity, bruise size and incidence. We found that pain may be slightly reduced 48 hours after slow injection. Similarly, there may be a reduction in bruise size and incidence after slow injection compared to fast injection 48 and 60 hours postinjection. We downgraded the certainty of the evidence for all outcomes to low or very low due to risk of bias concerns, imprecision, and inconsistency. Accordingly, new trials with a more robust design, more participants, and a focus on different injection speeds will be useful in strengthening the certainty of the available evidence.

Meta-analysis of Different Pressing Time on the Incidence of Subcutaneous Hemorrhage of Low Molecular Weight Heparin Administration

To investigate the effect of different pressing time on the incidence of subcutaneous hemorrhage of low molecular weight heparin (LMWH) administration by meta-analysis. Cochrane Library, PubMed, MEDLINE, CINAHL, EMbase, Springer, EBSCO, China Biomedical Literature Database, CNKI, Wanfang Database, and VIP Database were searched. To screen the literature of randomized controlled trials with different pressing time in patients with subcutaneous LMWH injection from the establishment of the database to December 2020. The quality of the literature was evaluated and the data were extracted. Meta-analysis was performed by RevMan 5.3. A total of 17 randomized controlled trials were included. Meta-analysis showed that the bleeding rate of pressing for 5 min odds ratio (OR = 3.89, 95% confidence interval [CI]: 2.68-5.64, P < .05) or pressing for 10 min (OR = 1.99, 95% CI: 1.34-2.95) was significantly lower than that of pressing for 3 min. Moreover, the bleeding rate was significantly lower in the 5 min pressing (OR = 1.47, 95% CI: 1.18-1.82) and 10 min pressing(OR = 2.12, 95% CI: 1.61-2.77) than in the no compression group. It is the most suitable time to press 5 min after subcutaneous LMWH injection, which can better control the incidence of bleeding.

Influence of low-molecular-weight heparin injection sites on local bruising and pain: A systematic review and meta-analysis.

Subcutaneous administration of low-molecular-weight heparin (LMWH) may cause complications such as haematoma, bruising and pain at different injection sites. Several studies have been carried out to investigate whether bruising and pain depend on injection sites; however, the results have been conflicting, and a clear consistent conclusion has not been reached. The purpose of this systematic review and meta-analysis was to assess the incidence and severity of bruising and pain after subcutaneous injection of LMWH in different sites. Two reviewers independently searched the Cochrane Library, PubMed, Embase, China National Knowledge Infrastructure (CNKI) databases for randomized controlled and self-controlled trials reporting side-effects from LMWH with different subcutaneous injection sites. Cochrane bias risk assessment tools and the Newcastle-Ottawa Scale (NOS) were used to evaluate the quality of the randomized controlled and self-controlled trials, respectively. Rev Man 5.3 software was used to analyse the data that were extracted after quality assessment to determine the incidence and severity of side-effects at different subcutaneous injection sites. A total of eleven studies were included in this analysis. The meta-analysis provided evidence that subcutaneous injection in the abdominal area had a lower incidence of bruising than that in the arm area (risk ratios: 0.76; 95% confidence interval: 0.64-0.90; I2 =52%, p<.05), but the difference in the bruising size between the two injection sites was marginally significant (standardized mean difference: 0.08; 95% confidence interval: -0.45 to 0.62; I2 =85%, p>.05). There was also no significant difference in the bruising size between subcutaneous injection in the abdominal area and subcutaneous injection in the thigh area (standardized mean difference: -0.16; 95% confidence interval: -0.34 to 0.22; I2 =32%, p>.05). Subcutaneous injections in the abdominal area had a lower severity of pain than injections in the arm area (risk ratios: 0.57; 95% confidence interval: 0.48-0.67; I2 =81%; p<.05), but no statistically significant difference was shown between the pain intensity in the abdominal and arm area (mean difference: -1.64; 95% confidence interval: -4.36 to 1.08; I2 =99%; p>.05). Subcutaneous injection of LMWH in the abdominal area could reduce the incidence of side-effects at the injection site and reduce patient discomfort. The abdomen is proposed as the first choice of injection site for LMWH. The findings provide useful information to nurses in clinical practice when choosing the subcutaneous injection site for LMWH.

The effect of duration of pressure on bruising and pain in the subcutaneous heparin injection site.

The aim of this study was to determine the effect on pain and bruising of pressure applied for different durations after subcutaneous heparin injection. This research was a quasi-experimental study. The research was performed with 60 patients. Two different injection techniques were applied at an interval of 24 hr to each patient taking part in the study. Method A: after the low molecular weight heparin (LMWH) injection, pressure was applied with dry cotton for 10 s directly after the needle was withdrawn. Method B: after the LMWH injection, pressure was applied with dry cotton for 60 s directly after the needle was withdrawn. After the injection process was completed, the dimension of the bruising formed were evaluated. Also, after the injection process was completed, the patients were asked to show on a visual analog scale the severity of pain felt during the injection. Statistical analysis of the research data was performed with the statistics package IBM SPSS 22.0. The Wilcoxon signed rank test and the Mann-Whitney U test were used in the analysis of the data. The results of the statistical analysis showed no statistically significant difference between the mean size of bruising and pain level according to the duration of pressure applied to the injection area (p > .05). It was concluded in this study that the duration of pressure applied to the injection site after subcutaneous LMWH injection did not affect the size of bruising or the severity of pain, and, unlike in the literature, that 60 s of applied pressure did not have a positive effect. Also, it was found that gender had an effect on the formation of bruising and the severity of pain, and body mass index had an effect on pain severity. Ten seconds of pressure applied to the injection site after subcutaneous LMWH injection may be enough to reduce complications.

Prospective randomized comparative study on rivaroxaban and LMWH for prophylaxis of post-apheresis thrombosis in adoptive T cell immunotherapy cancer patients.

Autologous adoptive T cell immunotherapy has been recognized as an effective treatment for cancer patients. The initial qualified lymphocytes is the core element determining the immunotherapeutic outcomes clinically. Cell separator based apheresis procedure is an optimal procedure to collect adequate mono-nucleated lymphocytes to generate efficient ex vivo T cell expansions; however, potential catheter-associated femoral vein thrombosis at post-apheresis might rise an additional deteriorated morbidity for cancer patients. The emerging prophylactic medications are required at such circumstances. Therefore this study was designed to compare the prophylactic effects of rivaroxaban versus low molecular weight heparin (LMWH) in patients who had exposed during the femoral vein catheterization for apheresis. 74 Patients were randomized 1:1:1 into three groups: subcutaneous injection of LMWH, Fraxiparine (n = 23) (0.4ml, 3800IU/day) for 2 days, oral rivaroxaban 10mg/d (n = 26), and oral rivaroxaban 20mg/d (n = 25) for consecutive 2 days. The primary endpoint was to compare the venous thromboembolism (VTE) occurrence cases in one month post catheterization. There were 4 cases confirmed VTE occurrence in LMWH group with contrast to 1 case in rivaroxaban 10mg administration group. None was seen in rivaroxaban 20mg group (P = 0.02 as the comparison with LMWH). Meantime there was no bleeding events occurrence afterwards. Oral rivaroxaban 20mg/day was recommendable to be considered which superior to LMWH. Although these limited data and patient volume reached the statistical difference which was able to provide the evidence proofed to compare the potency of those two anticoagulants, it could be regarded as the preliminary data provide the clinical results for cancer patients who were placed in the condition of apheresis and subsequently undergone adoptive T cell immunotherapy.Trial registration ClinicalTrials.gov identifier, NCT03282643. Registered 16 February 2016, http://www.ClinicalTrials.gov/ NCT03282643.

Dabigatran etexilate in the treatment of localized intravascular coagulopathy associated with venous malformations

IntroductionVenous malformations (VM) are congenital slow-flow vascular malformations. A common complication is localized intravascular coagulopathy (LIC), which results from chronic, localized, intraluminal activation and consumption of clotting factors and is characterized by elevated D-dimer and, in severe cases, decreased fibrinogen levels. Therapeutic options include anti-coagulation by Low Molecular Weight Heparin (LMWH) which has been reported to improve pain, decrease thrombosis, improve laboratory parameters and reduce hemorrhagic complications. However, the use of subcutaneous injections of LMWH has several limitations and the indications for therapy remain controversial. Materials and methodsWe present the first small case series of 3 patients with VM-LIC in whom a long-term treatment by dabigatran etexilate, a direct thrombin inhibitor, was initiated in the setting of ambulatory hemostasis consultations. ResultsClinically, drug tolerance was excellent in all 3 patients. Moderate hemorrhagic complaints occurred in 2 out of 3 patients but there was no thromboembolic event under dabigatran therapy. Dabigatran provided symptomatic relief on pain, swelling and heaviness feeling. Biologically, dabigatran treatment showed various modifications in D-dimers level but the fibrinogen level and platelet count remained unchanged. ConclusionIn conclusion, dabigatran etexilate may provide a viable and more convenient alternative to LMWH in the long-term treatment of VM-LIC. The dose has to be tailored in each patient in function of the bleeding tendency and laboratory hemostasis parameters.

The effect of low molecular weight heparin on salvaging the zone of stasis in an experimental burn model

Background/aim: Multiple zones of injuries are formed after burns, consisting of a zone of coagulative necrosis, a zone of hyperemia, and a zone of stasis, in which progressive microcirculatory thrombosis leads to degeneration and deepening of the wound. We used an experimental rat comb burn model to test the hypothesis that use of low molecular weight heparin (LMWH) may save the zone of stasis. Materials and methods: Adult female rats were randomly divided two groups: the LMWH group (n = 8) rats received subcutaneous LMWH injections, while the saline group (n = 8) rats were injected with the same volume of saline solution by the same route. The zone of stasis was evaluated macroscopically and histologically, and functional capillary density was evaluated. Results: Histological assessments revealed higher macrophage numbers and PML density, fibroblast proliferation, and angiogenesis in the LMWH group than in the saline group. Functional capillary density measurement in the stasis zones revealed no significant difference between the two groups in the first 4 days, although a significant difference in favor of the LMW group was observed in the last 3 days. Conclusion: The results of this experimental study show that LMWH is effective in saving the zone of stasis.

Slow versus fast subcutaneous heparin injections for prevention of bruising and site pain intensity.

Heparin is an anticoagulant medication that is usually injected subcutaneously. Subcutaneous administration of heparin may result in complications such as bruising, haematoma, and pain at the injection site. One of the factors that may affect pain, haematoma, and bruising is injection speed. For patients and healthcare providers, strategies that can reduce pain and bruising are considered important. Reducing patients' discomfort and concerns whenever and wherever possible is an important aim of nursing. Several studies have been carried out to see if speed of injection affects the amount of pain and bruising where the injection is given, but results of these studies have differed and study authors have not reached a clear final conclusion. This is the first update of the review first published in 2014. To assess the effects of duration (speed) of subcutaneous heparin injection on pain, haematoma, and bruising at the injection site in people admitted to hospitals or clinics who require treatment with unfractionated heparin (UFH) or low molecular weight heparin (LMWH). For this update, the Cochrane Vascular Information Specialist (CIS) searched the Specialised Register (last searched March 2017) and the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 2). The CIS also searched trials registries for details of ongoing or unpublished studies. Review authors searched two Persian databases - Iranmedex and Scientific Information Database (SID) - as well as Google Scholar. We sought randomised controlled trials (RCTs) comparing the effects of different durations of subcutaneous injection of heparin on pain, bruising, and haematoma at the injection site. Two review authors (MM, LJ), working independently, extracted data onto a structured form and assessed study quality. We used the criteria recommended by Cochrane to assess the risk of bias of included studies. For the outcomes, we calculated the mean difference (MD) or the standardised MD (SMD) with corresponding 95% confidence intervals (CIs). We pooled data using fixed-effect and random-effects models. We used GRADE to assess the overall quality of evidence supporting outcomes assessed in this review. For this update, we identified three new studies and therefore included in the Review four studies with a total of 459 participants who received subcutaneous injections of LMWH into the abdomen. Only one trial reported the injected drug volume (0.4 mL). Owing to the nature of the intervention, it was not possible to blind participants and care givers (personnel) in any included study. Two studies described blinding of outcome assessors; therefore overall, the methodological quality of included studies was moderate. The duration of the fast injection was 10 seconds and the duration of the slow injection was 30 seconds in all included studies.Three studies reported site pain intensity after each injection at different time points. Two studies assessed site pain intensity immediately after each injection, and meta-analysis on 140 participants showed no clear difference in site pain intensity immediately post slow injection when compared to fast injection (low-quality evidence; P = 0.15). In contrast, meta-analysis of two studies with 59 participants showed that 48 hours after the heparin injection, slow injection was associated with less pain intensity compared to fast injection (low-quality evidence; P = 0.007). One study (40 participants) reported pain intensity at 60 and 72 hours after injection. This study described no clear difference in site pain intensity at 60 and 72 hours post slow injection compared to fast injection.All four included studies assessed bruise size at 48 hours after each injection. Meta-analysis on 459 participants showed no difference in bruise size after slow injection compared to fast injection (low-quality evidence; P = 0.07). None of the included studies measured the incidence of haematoma as an outcome. We found four RCTs that evaluated the effect of subcutaneous heparin injection duration on pain intensity and bruise size. Owing to the small numbers of participants, we found insufficient evidence to determine any effect on pain intensity immediately after injection or at 60 and 72 hours post injection. However, slow injection may reduce site pain intensity 48 hours after injection (low-quality evidence). We observed no clear difference in bruise size after slow injection compared to fast injection (low-quality evidence). We judged this evidence to be of low quality owing to imprecision and inconsistency.

Proteomic investigation of the severe preeclampsia treatment by low molecular weight heparin

Purpose: The primary goal of this study is to investigate the mechanism of severe preeclampsia (PE) treatment by low molecular weight heparin (LMWH). Materials and Methods: Using two-dimensional difference in-gel electrophoresis (2D-DIGE) combined with matrix assisted laser desorption ionization-time-of-flight/time-of-flight mass spectrometry (MALDI-TOF/TOF) approach to identify the proteins that expressed differently in the serum samples of five patients before and after subcutaneous injection of LMWH (0.4 ml/person). Results: Seven protein spots were identified in 2D-DIGE that show significant change in expression level after LMWH treatment. Further analysis of seven protein spots with MALDI-TOF/TOF identified six different proteins. To confirm the proteomic data, two meaningful proteins of the six proteins, alpha-1-acid glycoprotein (AGP) and serotransferrin are subjected to immunoblotting. All of the proteins are obviously down-regulated after LMWH treatment. Conclusions: PE is a pregnancy-specific disease that clinically manifests as new-onset hypertension and proteinuria after 20 weeks of gestation. LMWH is an effective treatment of severe PE. The present proteomics based investigation may provide a new angle to understand the mechanism of severe PE treatment with LMWH.

Prevention effect of orally active heparin conjugate on cancer-associated thrombosis

Thrombogenesis is a major cause of morbidity and mortality in cancer patients. Prophylaxis with low-molecular-weight heparin (LMWH) is recommended for cancer patients, but requires non-parenteral delivery methods for long-term treatments. In this study, we sought to generate a new oligomeric-bile acid conjugate of LMWH that can be used for oral delivery. We first synthesized a tetramer of deoxycholic acid (tetraDOCA), which was site-specifically conjugated at the end saccharide of LMWH. When LMWH-tetraDOCA conjugate (LHe-tetraD) was orally administered at a dose of 5mg/kg in ICR mice, the maximum anti-factor Xa level was increased up to 0.62±0.05IU/mL without any evidence of liver toxicity, gastrointestinal damage, or thrombocytopenia. The cancer-associated thrombosis was induced in tumor-bearing mice by local heat application, and the fibrin deposition in tumors was evaluated. The oral administration of LHe-tetraD (either a single dose or multiple daily doses for up to 10days) in mice substantially abolished the coagulation-dependent tropism of fibrinogen in the heated tumors and significantly decreased hemorrhage, compared to the mice treated with saline or subcutaneous injection of LMWH. Thus, the anticoagulation effect of oral LHe-tetraD invokes the benefits of oral delivery and promises to provide an effective and convenient treatment for cancer patients at risk of thrombosis.

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.

Effects of intensive insulin therapy combined with low molecular weight heparin anticoagulant therapy on severe pancreatitis.

The current study explored the effects of intensive insulin therapy (IIT) combined with low molecular weight heparin (LMWH) anticoagulant therapy on severe acute pancreatitis (SAP). A total of 134 patients with SAP that received treatment between June 2008 and June 2012 were divided randomly into groups A (control; n=33), B (IIT; n=33), C (LMWH; n=34) and D (IIT + LMWH; n=34). Group A were treated routinely. Group B received continuous pumped insulin, as well as the routine treatment, to maintain the blood sugar level between 4.4 and 6.1 mmol/l. Group C received a subcutaneous injection of LMWH every 12 h in addition to the routine treatment. Group D received IIT + LMWH and the routine treatment. The white blood cell count, hemodiastase, serum albumin, arterial partial pressure of oxygen and prothrombin time were recorded prior to treatment and 1, 3, 5, 7 and 14 days after the initiation of treatment. The intestinal function recovery time, incidence rate of multiple organ failure (MOF), length of hospitalization and fatality rates were observed. IIT + LMWH noticeably increased the white blood cell count, hemodiastase level, serum albumin level and the arterial partial pressure of oxygen in the patients with SAP (P<0.05). It markedly shortened the intestinal recovery time and the length of stay and reduced the incidence rate of MOF, the surgery rate and the fatality rate (P<0.05). It did not aggravate the hemorrhagic tendency of SAP (P>0.05). IIT + LMWH had a noticeably improved clinical curative effect on SAP compared with that of the other treatments.

Abdominal Skin Necrosis after Enoxaparin Treatment

Subcutaneous low molecular weight heparin (LMWH) injection is a prophylactic treatment for deep vein thrombosis after surgery in lower limb before the patient is fully ambulated. This treatment is usually safe. One of the major and rare complications of the LMWH injection is thrombocytopenia, which is usually self-limiting. We present a rare case of patient with thrombocytopenia, induced by subcutaneous injection of LMWH (enoxaparin) that was complicated with a large hematoma at the injection site with subsequential skin necrosis, sepsis with fatal outcome. We would like to emphasize this rare complication of the common prophylactic treatment by LMWH in order to pursue this diagnosis when similar cutaneous manifestation might appear in patients who receive prophylactic treatment with LMWH.

Management of flap venous congestion: The role of heparin local subcutaneous injection

The study aimed to propose an alternative salvage technique based on local subcutaneous injection of low molecular-weight heparin (LMWH) for the management of venous congested pedicle and free flaps in which venous outflow could not be surgically restored. A retrospective review of all patients who received the proposed protocol at a single centre was performed. Fifteen patients were treated (six free flaps and nine regional flaps). The LMWH protocol was applied for a mean of 11 days (10-14 days). Thirteen patients required transfusions with a mean number of 5 U (0-12 U) of packed red blood cells (PRBCs) transfused per patient. All flaps were successfully salvaged (seven totally and eight partially). There were two associated complications: one patient developed a recipient-site haematoma and another patient suffered a syncope episode, related to anaemia. Local subcutaneous injection of LMWH was proven to be an effective alternative in improving flap venous congestion. The main advantages of this procedure are availability, easy application and local limited action. However, the associated morbidity should be balanced against the risk of flap loss and a judicious application is mandatory.

Low Molecular Weight Heparin Overdose: A 10 Year Case Series

Background: Low molecular weight heparin (LMWH) is used for the treatment and prevention of coagulative disorders. Few patients receiving therapeutic doses of LMWH develop major hemorrhage. Currently there are few reports in the literature on acute overdose on adults. In this study, clinical profile, treatment and outcome of 21 patients who acutely overdosed enoxaparin are described. Methods: A retrospective chart review of California Poison Control System (CPCS) database: Visual Dot Lab during 1997 to 2007 was obtained. All patients with a definite reported overdose of subcutaneous injection of LMWH were included. Results: In total, 21 patients who were all exposed to enoxaparin were studied. The reasons for overdose included medical miscalculation (3 cases, all infants), intentional misuse (2 patients), accidental overdose (7 cases), suicidal attempt (7 cases) and unknown in 2 patients. 7 cases were documented to have overdosed more than 2 times the therapeutic dose. The overdose ranged from 50 mg to 1300mg (0.1-80 times the therapeutic range). No patients were documented to experience bleeding or have thrombocytopenia although complete follow-up was only available for 11 patients. Reassurance was given to patients with less than 0.14 times the therapeutic dose. The 2 patients who received protamine were overdosed with more than 2.5 times the therapeutic dose of enoxaparin. Conclusion: Most patients had no complications and were not treated with protamine. This study suggests that a large dosage of LMWH is unlikely to result in any life threatening complications, though further studies are needed to certainly conclude about this. The use of protamine in LMWH overdose seems to remain controversial.

Catheter Ablation of Atrial Fibrillation in Patients at Low Thrombo‐Embolic Risk: Efficacy and Safety of a Simplified Periprocedural Anticoagulation Strategy

To prevent thrombo-embolic (TE) events during ablation of atrial fibrillation (AF), warfarin is recommended in all patients irrespective of baseline TE risk. We evaluated the efficacy and safety of a simplified periprocedural anticoagulation strategy of aspirin (ASA) and low molecular weight heparin (LMWH) in patients at low TE risk. We collected data from 214 low TE risk patients (CHADS2 score ≤1 and no warfarin at baseline) undergoing pulmonary vein isolation. After discontinuation of ASA, periprocedural antithrombotic therapy consisted of therapeutic subcutaneous LMWH injections (nadroparin 1 mL/kg once daily) from 10 days before until 10 days after the procedure, followed by ASA in all patients. At the time of procedure, transesophageal echocardiography (TEE) was not performed on a routine basis. During the procedure, unfractionated heparin was administered to achieve an ACT between 350 and 400 seconds. Data on TE events (stroke or transient ischemic attack), cardiac tamponade/perforation, and major vascular access complications within 3 months after the procedure were collected. Mean CHADS2 was 0.3 ± 0.5. TEE was performed in 3% of patients. No periprocedural TE events occurred. No cardiac tamponade/perforation was observed. Major vascular access complications occurred in 3 patients (1.4%). No permanent injury was observed (0%). In selected low TE risk patients undergoing ablation for AF, a short period of periprocedural therapeutic anticoagulation with LMWH together with aspirin is an effective and safe strategy to prevent TE events. If confirmed in a randomized trial, this approach might simplify periprocedural antithrombotic management in ablation of selected AF patients.

Anticoagulation therapy prevents portal-splenic vein thrombosis after splenectomy with gastroesophageal devascularization

To compare the incidence of early portal or splenic vein thrombosis (PSVT) in patients treated with irregular and regular anticoagulantion after splenectomy with gastroesophageal devascularization. We retrospectively analyzed 301 patients who underwent splenectomy with gastroesophageal devascularization for portal hypertension due to cirrhosis between April 2004 and July 2010. Patients were categorized into group A with irregular anticoagulation and group B with regular anticoagulation, respectively. Group A (153 patients) received anticoagulant monotherapy for an undesignated time period or with aspirin or warfarin without low-molecular-weight heparin (LMWH) irregularly. Group B (148 patients) received subcutaneous injection of LMWH routinely within the first 5 d after surgery, followed by oral warfarin and aspirin for one month regularly. The target prothrombin time/international normalized ratio (PT/INR) was 1.25-1.50. Platelet and PT/INR were monitored. Color Doppler imaging was performed to monitor PSVT as well as the effectiveness of thrombolytic therapy. The patients' data were collected and analyzed retrospectively. Among the patients, 94 developed early postoperative mural PSVT, including 63 patients in group A (63/153, 41.17%) and 31 patients in group B (31/148, 20.94%). There were 50 (32.67%) patients in group A and 27 (18.24%) in group B with mural PSVT in the main trunk of portal vein. After the administration of thrombolytic, anticoagulant and anti-aggregation therapy, complete or partial thrombus dissolution achieved in 50 (79.37%) in group A and 26 (83.87%) in group B. Regular anticoagulation therapy can reduce the incidence of PSVT in patients who undergo splenectomy with gastroesophageal devascularization, and regular anticoagulant therapy is safer and more effective than irregular anticoagulant therapy. Early and timely thrombolytic therapy is imperative and feasible for the prevention of PSVT.

Effects of heparin and low molecular weight heparin on serum level of pregnancy associated plasma protein A in patients with cerebrovascular disease

Objecfive To investigate the effects of treatment for cerebrovascular disorder patients with heparin and low molecular weight heparin(LMWH) on serum PAPP-A concentrations and provide the basis for evaluating the clinical significance of PAPP-A in the following study.Methods Forty cases with cerebrovascular disease from Qilu Hospital from November 2009 to May 2010 were collected in this study.Blood samples were taken before and after drug administration.All cases were divided into four groups according to situation of medication.Group A consisted of 10 patients who received subcutaneous LMWH anticoagulation therapy, and blood samples were collected before LMWH injection, three hours after subcutaneous LMWH anticoagulation therapy in the first day, the second day and the seventh day and 24 hours after the last injection. Group B consisted of 10 patients who did not receive LMWH therapy, and blood samples were collected immediately after admission, the first day, the second day and the seventh day after admission. Group C consisted of 10 patients with percutaneous carotid intervention who received intravenous heparin at the beginning of stenting, and blood samples were collected from the arterial sheath just before angiography and heparin administration, and at 3, 5, 15, 40 and 100 min after heparin administration. Group D consisted of 10 patients who received carotid angiography but LMWH-free therapy,and blood samples were collected from the arterial sheath just before and after angiography. Serum PAPP-A concentrations were analyzed by ELISA to evaluate the differences of intra-groups and differences at different time points of inter-groups. Results In group A, PAPP-A concentrations were time dependent and elevated gradually from 12. 36 (9. 90-14. 32) mIU/L before LMWH injection to 21.80 (23.50-19.73) mIU/L at the seventh day after injection (M=38. 72, P < 0.01 ). In group C, there was a rapid increase of PAPP-A concentration from 12. 86 ( 9. 67-14. 05 ) mIU/L to 51.56 ( 44. 20-66. 00 ) mIU/L within 5 min after intravenous heparin injection (M=46. 06, P <0. 01 ). The PAPP-A concentration of one week after LMWH administration in group A was 21.80 (23.50-19.73) mIU/L, significantly higher than that in group B [11.81 (9. 21-12. 89) mIU/L] (U<0. O01, P<0.01). The PAPP-A concentration at 15 min after heparin administration in group C was 43.70 (37.70-54. 30) mIU/L, significantly higher than that after angiography in group D [14. 18 (11.25-15. 86) mIU/L] ( U<0. 001, P <0. 01 ). The peak level of blood PAPP-A after subcutaneous LMWH injection was significantly lower than that after intravenous heparin injection. The concentrations in group A and C were 21.80 ( 23.50-19. 73 ) and 51.56 (44. 20-66. 00) mIU/L respectively, and had a significant difference ( U=0. 999, P < 0. 01 ) . Conclusions Both intravenous heparin and subcutaneous LMWH administration induce an increase in serum PAPP-A concentration. The effect of drug should be considered when PAPP-A is selected as an evaluation indicator. Key words: Heparin; Heparin,low-molecular-weight; Pregnancy-associated plasma protein-A; Cerebrovascular disorders