Injection Of Low Molecular Weight Heparin Research Articles

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.

Enoxaparin-induced atraumatic acute compartment syndrome of the thigh: a case report

In this case, we present a case of atraumatic lateral compartment syndrome of the thigh in a patient undergoing anticoagulant treatment. The patient received high-dose low molecular weight heparin (LMWH) treatment due to the diagnosis of an ischemic cerebrovascular event and developed lateral compartment syndrome of the thigh after the LMWH injection into the thigh; therefore, an emergency fasciotomy was performed. After negative-pressure dressing and monitoring, the wound was closed on the sixth day and the patient was discharged. No complication occurred during the one-month follow-up. Compartment syndrome of the thigh is a rare, but potentially devastating. The purpose of the current report was to highlight this rare, but serious, complication of a routine treatment procedure.

"Part of the Ritual": Exploring Patient and Physician Decision Making Regarding Anticoagulation Use in Obstetric Antiphospholipid Syndrome.

Antiphospholipid syndrome is associated with recurrent pregnancy loss. Low-molecular-weight heparin (LMWH) and/or aspirin (ASA) prophylaxis during pregnancy to prevent future loss is based on limited trial data with mixed results. Given the clinical equipoise, we sought to understand how patients and physicians navigate the decision-making process for use of LMWH and/or ASA in pregnancy. We interviewed 10 patients and 10 thrombosis physicians in Ottawa, Canada from January 2017 to March 2018. Patients who had ≥1 late pregnancy loss or ≥2 early losses and persistently positive antiphospholipid antibodies based on the revised Sapporo/Sydney criteria were identified in the a Thrombosis Clinic. Patients were also identified by the TIPPS Study screening logs of excluded patients. Data collection and analysis occurred iteratively, in keeping with constructivist grounded theory methodology. Our analysis generated three themes, present across both patient and physician interviews, which captured a patient-led decision-making experience: (1) managing high stakes, (2) accepting uncertainty, and (3) focusing on safety. Patients and physicians acknowledged the high emotional burden and what was at stake: avoiding further pregnancy loss. Patients responded to their situation by taking action (i.e., using LMWH injections became a "ritual"), whereas physicians reacted by removing themselves from the final decision by "[leaving] it up to the patient." Our findings should be considered when designing future research on studying the role for LMWH/ASA in this population, as it suggests that the perceived benefits of treatment go beyond improving pregnancy rates. Rather, patients described potential benefit from the process of taking action, even in the absence of a guaranteed good outcome.

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.

Treatment of Cancer-Associated Venous Thromboembolism with Low-Molecular-Weight Heparin or Direct Oral Anticoagulants: Patient Selection, Controversies, and Caveats.

The treatment of venous thromboembolism (VTE) in patients with cancer is challenging because these patients have increased risks of both recurrent VTE and major bleeding, along with patient-specific and cancer-related factors that influence the approach to treatment. Historically, anticoagulant therapy with low-molecular-weight heparin (LMWH), given for both initial and long-term treatment, has been the preferred approach recommended by practice guidelines. Most recently, the National Comprehensive Cancer Network (NCCN) guidelines indicate that the direct oral anticoagulants (DOACs) apixaban, edoxaban, or rivaroxaban are preferred for patients without gastric or gastroesophageal lesions. DOACs have been associated with an increased risk of major bleeding in patients with gastrointestinal and possibly genitourinary cancers, and DOACs should either not be used (especially in those with intact intraluminal tumors) or be used with caution in patients with these cancers. Fatal or life-threatening bleeding occurs with similar frequency with DOACs or LMWH, and most major bleeding with DOACs can be managed with transfusion and standard measures. The patient's willingness and ability to comply with LMWH injections, and their treatment preference, should also be considered. Patients with cancer who have VTE should be treated with anticoagulation for a minimum of 6 months. Anticoagulation should be continued indefinitely while cancer is active or under treatment or if there are persistent risk factors for recurrent VTE. This article summarizes the evidence from clinical trials of LMWH and DOACs that underpins the NCCN guideline recommendations, addresses several controversies and caveats regarding anticoagulant treatment, and offers evidence-based, practical suggestions on patient selection for treatment with DOACs. IMPLICATIONS FOR PRACTICE: Several randomized trials support the addition of direct oral anticoagulants (DOACs) to the therapeutic armamentarium for cancer-associated venous thromboembolism (VTE). These agents come with unique risks and patient- and cancer-specific variables that must be evaluated during the course of a patient's cancer care. This narrative review discusses findings from clinical trials of low-molecular-weight heparin and DOACs for the treatment of cancer-associated VTE, evidence that supports the recent National Comprehensive Cancer Network guideline recommendations. A personalized approach to treatment is proposed that addresses patient selection for treatment with DOACs, factors that influence efficacy and safety, controversies and caveats, and suggestions for their resolution in clinical practice.

Preventing Venous Thromboembolism in Ambulatory Patients with Cancer: A Narrative Review.

Venous thromboembolism (VTE) is frequent among patients with cancer. Ambulatory cancer patients starting chemotherapy have a 5% to 10% risk of cancer associated thrombosis (CAT) within the first year after cancer diagnosis. This risk may vary according to patient characteristics, cancer location, cancer stage, or the type of chemotherapeutic regimen. Landmark studies evaluating thrombophrophylaxis with low molecular weight heparin (LMWH) for ambulatory cancer patients have shown a relative reduction in the rate of symptomatic VTE of about one half. However, the absolute risk reduction is modest among unselected patients given a rather low risk of events resulting in a number needed to treat (NNT) of 40 to 50. Moreover, this modest benefit is mitigated by a trend towards an increased risk of bleeding, and the economic and patient burden due to daily injections of LMWH. For these reasons, routine thromboprophylaxis is not recommended by expert societies. Advances in VTE risk stratification among cancer patients, and growing evidence regarding efficacy and safety of direct oral anticoagulants (DOACs) for the treatment and prevention of CAT have led to reconsider the paradigms of this risk–benefit assessment. This narrative review aims to summarize the recent evidence provided by randomized trials comparing DOACs to placebo in ambulatory cancer patients and its impact on expert recommendations and clinical practice.

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.

Predictability of the Caprini Risk Assessment Model for Postoperative Venous Thromboembolism may be Increased by Global Test of Haemostasis

Introduction - Postoperative venous thromboembolism (VTE) is still a challenge. Standard preventive protocol, that includes elastic compression stockings and low-molecular-weight heparin (LMWH) injection, may be not equally effective in different patients at high risk. Previously it has been shown that patients with 11 and more Caprini scores have a dramatically increased risk of VTE at the background of elastic compression and LMWH injections. The way to improve such situation is to understand, why standard prophylaxis does not work properly in some individuals. To achieve this goal may be used modern global tests of hemostasis. The aim of this study was to compare predictability for postoperative deep vein thrombosis (DVT) of the classic Caprini 2005 RAM and its modified version, considering the results of TD test in surgical patients at high risk. Methods - This was a prospective observational clinical study involving 80 patients (33 men and 47 women, mean age - 73,9±7,2 years), undergoing major (79 cases) or minor (1 case) surgery for colorectal cancer. Patients were at high risk of postoperative venous thromboembolism: 5-15 Caprini scores (mean - 9,9±2,0) and received combined prophylaxis: anti-embolic above-knee compression stockings and LMWH injections (enoxaparin 40 mg once daily) until discharge. LMWH was administered in a fixed hour according to the time of blood shambling for TD. Before and after the surgery (0 day, 5-7 day and 1 month) duplex ultrasound was performed to detect postoperative DVT. Results - DVT was found in 21 of 80 patients (26.3%; 95% CI: 17,9-36,8%) at 5-7 day after surgery. No new venous thromboembolism events were detected at 1 month. Regression analysis and ROC-curve showed a significant predictability of Caprini scores for DVT (p<0,0001, S=0,839±0,045). Analysis of ROC-curve coordinates showed a cut-off point of 11 scores, which with the sensitivity of 76.2% and a specificity of 74.6% predicted DVT. The results of TD test showed significant hypercoagulation at the background of LMWH administration in patients with DVT. Regression analysis and ROC-curves demonstrated that TD parameters as stationary velocity of clot growth, measured at 2 hours after surgery (Vst), and initial velocity of clot growth, measured 24 hours after the LMWH injection (Vin), had the greatest predictability for postoperative DVT: S=0,764 ± 0,109, p=0,049 and S=0,946±0,047, p=0,001, respectively. The cut-off points for DVT prediction with high sensitivity/specificity appeared to be Vst>32,5 (normal range 20-29) μm/min and Vin>64,5 (normal range 36-56) μm/min. Identified thresholds for TD parameters have been integrated into Caprini RAM under the item "other congenital or acquired thrombophilia" (score of 3). Total Caprini scores were recalculated in patients who had one or both TD parameters exceeded the cut-off, followed by re-analysis of the ROC-curves. It was found that the Caprini RAM with integrated Vin>64,5 μm/min characterized by the highest predictability for DVT (S=0,876±0,038, p<0,0001) and increased cut-off up to 12 scores with sensitivity of 85,7% and specificity of 72.9%. Conclusion - The integration of TD parameters into Caprini RAM allows increasing predictability for postoperative DVT.

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.

Effects of Vapocoolant Spray Prior to SC LMWH Injection: An Experimental Study.

The aim of this study was to evaluate the effects of vapocoolant spray administration prior to subcutaneous (SC) low molecular weight heparin injection on local ecchymosis, hematoma, and pain. This randomized controlled study was carried out on 64 patients (n = 128 injections) in an orthopedics and traumatology clinic. After randomization, vapocoolant spray and then heparin injection was applied on one arm. The second necessary dose of heparin was applied to his or her other arm as a placebo by a water spray. Then, the pain of the patients was assessed. After 2 days, ecchymosis and hematoma were evaluated. Significant lower pain scores were determined in applications in which the vapocoolant spray was used. There was no statically significant difference between the mean diameter values of ecchymosis in both arm groups. There was no hematoma on the injection site after injections. However, this method did not create any significant reductive effect on ecchymosis. Nurses are advised to take advantage of vapocoolant spray effects prior to SC heparin injection.

“Part of the Ritual”: a Qualitative Study of Patient and Physician Perspectives on the Use of Anticoagulation for Improving Pregnancy Outcomes in Obstetrical Antiphospholipid Syndrome

INTRODUCTIONAntiphospholipid syndrome is an acquired thrombophilia associated with recurrent pregnancy loss. Treatment with low-molecular-weight heparin (LMWH) and/or aspirin (ASA) during pregnancy to prevent future loss is based on limited trial data with mixed results. Given the clinical equipoise, we sought to understand how patients and physicians navigate the decision-making process for use of antepartum LMWH and/or ASA. This research is needed to inform the feasibility of future research that seeks to resolve the question of treatment efficacy in this patient population. METHODSFollowing constructivist grounded theory (CGT) methodology, we interviewed 10 patients and 10 thrombosis physicians in Ottawa, Canada from January 2017 to March 2018. Patients were drawn from women included in the TIPPS (Thrombophilia in Pregnancy Prophylaxis Study) screening logs and from consecutive women attending a specialty Thrombosis Clinic who met the revised Sapporo/Sydney laboratory criteria and had at least 1 prior late loss or 2 early losses (<10 weeks gestation). Data collection and analysis occurred iteratively, in keeping with CGT methodology. RESULTSOur analysis generated three predominant themes, present across both patient and physician interviews, which captured a patient-led decision-making experience: (1) Accepting Uncertainty, (2) Focusing on Safety and (3) Managing High Stakes. Many patients accepted the uncertainty of their situation; they felt hopeful but were also reluctant to expect a better pregnancy outcome. This was echoed in the physician interviews, which emphasized the uncertainty of LMWH/ASA in improving outcomes when counselling patients on their options. Both groups focused on the low-risk nature and safety of these medications. Patients focused on safety to the fetus, with little concern for maternal risk. Finally, patients and physicians acknowledged the high emotional burden and what was at stake: avoiding further pregnancy loss. Patients responded to their situation by taking action (i.e. using LMWH injections became a “ritual”) whereas physicians reacted by removing themselves from the final decision and “[leaving] it up to the patient”. CONCLUSIONIn this setting of clinical equipoise and in the absence of serious safety concerns, decision-making around antepartum LMWH/ASA was largely directed by informed patient choice. These findings should be considered when designing future research on the role for LMWH/ASA in this population, as it suggests that the perceived benefits of treatment go beyond improving pregnancy rates. Rather, patients seem to derive psychological benefit from the process of taking action, even in the absence of a guaranteed good outcome. DisclosuresSkeith:Leo Pharma: Honoraria; CSL Behring: Research Funding. Rodger:Biomerieux: Research Funding.

CATHETER DIRECTED THROMBOLYSIS FOR MASSIVE PULMONARY EMBOLISM IN A PREGNANT PATIENT

SESSION TITLE: Critical Care 2 SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/09/2018 01:15 PM - 02:15 PM INTRODUCTION: Pulmonary embolism (PE) is a leading cause of maternal mortality in the United States [1]. CASE PRESENTATION: We report a 27-year-old female at 13 weeks gestation who presented with massive PE and circulatory shock and was successfully treated with catheter directed thrombolysis. History of syncope prior to arrival combined with EKG changes and findings on bedside ultrasound led to a high clinical suspicion for PE with diagnosis confirmed by computed tomography. The patient was admitted to the intensive care unit on systemic anticoagulation with unfractionated heparin. Subsequent circulatory shock led to the decision for catheter directed thrombolytic therapy. The advantage of our treatment choice was rapid clot lysis, return of normal hemodynamics, and avoidance of the risk of complications associated with higher doses of thrombolytic agents [2]. The patient remained hospitalized for 5 days without complication and was discharged on low-molecular weight heparin injections. DISCUSSION: The morbidity and mortality associated with PE during pregnancy demands prompt diagnosis and treatment. In general, thrombolytic agents are relatively contraindicated during pregnancy because of the presumed risk of maternal bleeding and fetal loss. The teratogenicity for these agents in humans is also uncertain [3]. CONCLUSIONS: Ultimately, all life-saving measures must be considered in the face of hemodynamic collapse. Our case demonstrates a positive outcome from catheter directed thrombolytic therapy and contributes to the growing literature in outcomes of treatment in massive PE in pregnancy. Reference #1: 1 Creanga, Andreea A., et al. “Pregnancy-Related Mortality in the United States, 2006-2010.” Obstetrics & Gynecology, vol. 125, no. 1, Jan. 2015, pp. 5–12., https://doi.org/10.1097/aog.0000000000000564. Reference #2: 2 Brandt, Kimberly, et al. “Low-Dose Systemic Alteplase (TPA) for the Treatment of Pulmonary Embolism.” Annals of Pharmacotherapy, vol. 49, no. 7, Sept. 2015, pp. 818–824., https://doi.org/10.1177/1060028015579988. Reference #3: 3 Ahearn GS, Hadjiliadis D, Govert JA, Tapson VF. Massive Pulmonary Embolism During Pregnancy Successfully Treated With Recombinant Tissue Plasminogen ActivatorA Case Report and Review of Treatment Options. Arch Intern Med. 2002;162(11):1221–1227. https://doi.org/10.1001/archinte.162.11.1221 DISCLOSURES: No relevant relationships by daniel goldbach, source=Web Response

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.

Comparison of modified versus conventional injection techniques of low-molecular-weight heparin in elderly.

Objective:To analyze the clinical values of modified injection of low-molecular-weight heparin in reducing subcutaneous bleeding and pain.Methods:Two hundred and sixty patients with cerebral infarction, acute myocardial infarction or pulmonary embolism who underwent subcutaneous injection of low-molecular weight heparin in the hospital between December 2015 and December 2016 were selected. They were randomly divided into a control group and a research group, 130 each. Patients in the control group were given conventional injection, while patients in the research group were given modified injection. The occurrence of subcutaneous bleeding and pain was observed and compared between the two groups.Results:The incidence of subcutaneous hemorrhage in the research group was 46.9%, significantly lower than 83.1% in the control group, and the difference had statistical significance (P<0.05). Twenty-six patients in the control group had severe pain, which was much more than 5 patients in the research group, and the difference was statistically significant (P<0.05). The number of cases of severe hemorrhage in the control group was significantly larger than that of the research group (31 vs. 3), and the difference was also statistically significant.Conclusion:Modified low-molecular weight heparin injection can effectively reduce the incidence of bleeding and pain, which is beneficial to the compliance and quality of life of elder patients.

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.

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.

Is a therapeutic anticoagulation window needed for delivery when using prophylactic low molecular weight heparin during pregnancy? A retrospective monocentric study

ObjectivesThe aim of the study was to evaluate the usefulness of therapeutic window for delivery for patients under prophylactic anticoagulation by low molecular weight heparin (LMWH) by comparing those who had a planned delivery versus those who delivered spontaneously. Study designThis retrospective monocentric study included pregnant patients with prophylactic anticoagulation (one injection per day of enoxaparin 4000UI), who delivered after 24 weeks of gestation. We collected data on pregnancy characteristics and on the delivery. We divided patients in two groups: GROUP S were patients who delivered spontaneously and GROUP P were patients who had a planned delivery for a therapeutic anticoagulant window. Our primary endpoint was the neuraxial anaesthesia rate. We compared the two groups with the student test for quantitative data and the Chi-2 test or the exact test of Fisher for qualitative data. ResultsOver a 3.5 years period, we included 100 pregnant patients with prophylactic anticoagulation. Indications of prophylactic LMWH were patients with a low risk of thrombosis, mostly personal history of cured deep venous thrombosis (36%) prior to pregnancy or non-thrombotic antiphospholid syndrome (37%). The overall rate of neuraxial anaesthesia during delivery was 86%. Twenty-six patients were included in GROUP S and 74 in GROUP P. In GROUP P, all patients had access to neuraxial anaesthesia versus 88.4% (23/26) in the GROUP S (p<0.0001). For the three remaining patients, the contraindication was a short delay between the last injection of LMWH and the need for anaesthesia. The mean delay between the last injection of LMWH and neuraxial anaesthesia was 42.6+/−24.1 (13–123)h in the GROUP P and 22.7+/−9.9 (11–42)h in the GROUP S (p<0.0001). One patient had deep venous thrombosis in the 6 weeks postpartum, in the GROUP P. ConclusionWith a planned induced delivery between 38 and 39 weeks of gestation, 11.5% of patients who went into spontaneous labour before induction would not have a neuraxial anaesthesia when respecting the 12h delay between the last injection of low molecular weight heparin and the need for anaesthesia.