Use Of Low Molecular Weight Heparin Research Articles

Low-molecular-weight heparins for cancer-associated thrombosis: Adherence to clinical practice guidelines and patient perception in TROPIQUE, a 409-patient prospective observational study

PurposeData on long-term treatment with low-molecular-weight heparins (LMWH) in cancer patients treated for venous thromboembolism are scarce. Study objectives were to document the long-term clinical use of LMWH and patient perception in this setting. MethodsAdult cancer patients receiving antineoplastic treatment or palliative care and LMWH for cancer associated venous thromboembolism (CAT) were eligible to participate in this prospective observational study. Main outcome was adherence to clinical practice guidelines based on recommended LMWH treatment doses for at least 3months in the absence of severe renal insufficiency. Patients' perception of the treatment was assessed in an ancillary study using the Perception Anticoagulant Treatment Questionnaire (PACT-Q). ResultsAmong 409 included cancer patients aged 65±12.1years, overall adherence to practice guidelines as defined in the protocol was 55.3% (226 patients). However, 98.0% of patients received a prescription for 3months or more and mean LMWH treatment duration for VTE was 6.27±0.15months which meets guidelines recommendations. Main patients' expectations scored on a 1–5 scale were blood clots prevention (mean 3.94±0.75), symptom relief (mean 3.98±1.04) and ease of use (mean 4.22±0.9). LMWH treatment appeared convenient (global score 79.7±17.1 on a 0 to 100 scale) and 69.1% of patients were satisfied or very satisfied. ConclusionDespite incomplete strict adherence to guidelines, treatment duration with LMWH was adequate showing substantial progress in the management of CAT patients. Patients expectations were high while treatment was perceived convenient with a high degree of satisfaction.

Prolonged low-molecular-weight heparin use during pregnancy and subsequent bone mineral density

IntroductionIn contrast to unfractionated heparin (UFH), use of low-molecular weight heparin (LMWH) during pregnancy has not been reported to be associated with a significant decrease in bone mineral density (BMD). The aim of this study was to investigate whether long-term use of LMWH during pregnancy is associated with subsequent decrease in BMD or with increased number of osteoporotic fractures. Materials and methodsIn this observational cohort study BMD was measured by dual energy X-ray absorptiometry (DEXA) 4–7years after the last delivery in 152 women. Ninety-two women had prolonged LMWH-exposure during pregnancy – 75 as prophylaxis and 17 as treatment for venous thromboembolic event (VTE). Dalteparin and enoxaparin were the LMWH-preparations used. Sixty women without LMWH-exposure served as controls. A questionnaire about lifestyle factors and medical history was filled out by the subjects. ResultsLumbar spine BMD in the LMWH users was lower than that in the controls both in the prophylactic group (1.22g/cm2 vs. 1.27g/cm2; p=0.03), and in the treatment group (1.20g/cm2 vs. 1.27g/cm2; p=0.07). BMD in femoral neck did not differ between the LMWH-users and controls. However, after adjusting for potential confounding factors, LMWH-exposure did not remain associated with decreased BMD in lumbar spine. Use of contraceptive pills was positively associated with BMD in lumbar spine. Incidence of osteopenia was 13% in the LMWH-group and 8% in the control-group, (p=0.4). No osteoporosis or osteoporotic fractures were found. ConclusionsProlonged use of LMWH during pregnancy was not associated with subsequent decrease in BMD, osteopenia, osteoporosis, or osteoporotic fractures.

Prevention of pre-eclampsia by low-molecular-weight heparin in addition to aspirin: a meta-analysis

To estimate the impact of adding low-molecular-weight heparin (LMWH) or unfractionated heparin to low-dose aspirin started ≤ 16 weeks' gestation on the prevalence of pre-eclampsia (PE) and the delivery of a small-for-gestational-age (SGA) neonate. A systematic review and meta-analysis of randomized controlled trials (RCTs) was performed by searching the medical databases PubMed, EMBASE, Web of Science and Cochrane Central. Pregnant women randomized to receive LMWH or unfractionated heparin in addition to low-dose aspirin were compared with those who received low-dose aspirin alone. Outcome measures were PE, severe PE, early-onset PE and SGA. Pooled relative risks (RRs) with 95% CI were calculated using a random-effects model. Eight RCTs met the inclusion criteria; the indication for recruitment was previous recurrent miscarriage in five studies (three included women with thrombophilia) and a history of severe or early-onset PE in three studies (including women with thrombophilia in one). LMWH was administered in seven studies and unfractionated heparin in one. In women with a history of PE, treatment with LMWH and aspirin, compared with aspirin alone, was associated with a significant reduction in development of PE (three trials (n = 379); RR, 0.54 (95% CI, 0.31-0.92); P = 0.03) and in delivery of SGA neonates (two trials (n = 363); RR, 0.54 (95% CI, 0.32-0.91); P = 0.02). These outcomes were not significantly reduced in women with recurrent miscarriage who received LMWH and aspirin, compared with aspirin alone. The small number of studies precluded sensitivity analyses and the evaluation of publication biases. Blinding to the allocation treatment was absent in all RCTs. Based on limited evidence, the addition of LMWH to low-dose aspirin could reduce the prevalence of PE and SGA in women with a history of PE. This observation should be the basis of a well-conducted future trial rather than a recommendation for immediate clinical application. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

LMWH in cancer patients with renal impairment – better than warfarin?

Venous thromboembolism (VTE) is one of the leading causes of death in cancer patients, which are known to have a 5- to 7-fold increased risk for VTE. The anticoagulant treatment of VTE in cancer patients is less effective with a three-fold increased risk of VTE recurrence compared to non-cancer patients, and it is less safe with more than double rates of major bleeding. Compared to vitamin-K antagonists (VKA), long-term secondary prevention with low molecular weight heparin (LMWH) has been shown to reduce the risk of recurrent VTE in cancer-associated thrombosis (CAT), and therefore, current international guidelines recommend the use of LMWH over VKA. With increasing age, cancer prevalence and VTE incidence increase while renal function decreases. Anti-cancer treatment may impair renal function additionally. Therefore, renal insufficiency is a frequent challenge in CAT patients, which is associated with a higher risk of both bleeding and recurrent VTE. Both VKA and LMWH may be associated with less efficacy and higher bleeding risk in renal insufficiency. Unfortunately, there is a lack of prospective data on renal insufficiency and CAT. A recent sub-analysis from a large randomized controlled trial shows that the bleeding risk in patients with severe renal insufficiency in CAT is not elevated with the use of LMWH compared to VKA while efficacy is maintained. In addition, LMWH treatment has several practical advantages over VKA, particularly in patients with CAT while they are receiving anti-cancer treatment.

Practice Patterns for Prophylaxis and Treatment of Venous Thromboembolism in German Cancer Patients

Background: Venous thromboembolism (VTE) is a serious threat for cancer patients. Guidelines recommend low-molecular-weight heparin (LMWH) for prophylaxis and treatment, but it is unknown to what extent specialists adhere to these recommendations. This survey assesses the current approach to patients with cancer-associated VTE in Germany. Materials and Methods: A questionnaire was sent out to members of the DGHO (Deutsche Gesellschaft für Hämatologie und Onkologie), the BNHO (Berufsverband Niedergelassener Hämatologen und Onkologen) and the DGP (Deutsche Gesellschaft für Phlebologie). For most questions, more than 1 answer was possible; therefore, the total sum of percentages may exceed 100%. Results: 275 specialists responded. 76% of them treat acute VTE with LMWH while 22% switch to oral treatments (vitamin K antagonists (VKAs) or non-VKA oral anticoagulants (NOACs)) during the acute phase. For the next 3-6 months, 55% of the specialists continue LMWH, while 31% switch to VKAs and 33% to NOACs. Among those who continue LMWH for 3-6 months, 37% continue at the full dose, 26% reduce to 75% of the initial dose, and 40% even to 50%. Important factors guiding treatment decisions were the need for injections and the availability of a partner/spouse (LMWH), the need for laboratory controls (VKAs), and the number of other oral medications (NOACs). Conclusion: This survey reveals that practice patterns often do not follow the guideline recommendations with respect to the use of LMWH for long-term treatment of VTE in cancer patients.

Low molecular weight heparin and cancer survival: clinical trials and experimental mechanisms.

The relationship between cancer and thrombosis is complex, as the hemostatic system is inextricably linked to the mechanisms of cancer growth and metastasis. The coagulation system thus appears to be a site for oncogenic events and necessary for the survival and spread of malignant cells. Although several meta-analyses on the effectiveness of unfractionated heparin and low molecular weight heparin (LMWH) in the treatment of venous thromboembolism (VTE) have suggested a lower mortality risk in cancer patients receiving LMWH, this contention has not received general acceptance. In fact, there exist no sufficiently powered studies to date supporting the routine use of LMWH to improve cancer survival. Meanwhile, the molecular mechanism underlying the anti-neoplastic effect of LMWH which is independent of its anti-coagulant function is largely unexplored and is a topic of active investigation. In this communication, we aimed to review comprehensively evidences from clinical trials, meta-analysis as well as experimental molecular research and to identify future research areas of importance so as to stimulate future research on the potential anti-tumor action of LMWH. Although benefit of LMWH on cancer patients' survival is controversial depending on the tumor type, cancer stage as well as LMWH type, it appears to be associated with a reduction in VTE and increased bleeding is minor and controllable; thus, randomized controlled trials targeting the survival benefit of certain specific LWMH are needed and justified, and more in-depth experimental researches are imperative to elucidate the anti-tumor effect of anticoagulants.

Perception of Thromboembolism Risk: Differences between the Departments of Internal Medicine and Emergency Medicine.

The latest developments in emergency medicine (EM) have introduced new typologies of patients that have not been taken into account in previous studies of venous thromboembolism (VTE) risk. The aim of the current study was to evaluate by comparing the main international risk scores whether different perceptions of VTE risk exist in internal medicine (IM) departments and in EM departments. This cross-sectional observational study involved 23 IM and 10 EM departments of 21 different hospitals. The patient data were collected by physicians who were blinded to the purpose of the study. The data were analyzed using the main international risk scores. We analyzed 742 patients, 222 (30%) hospitalized in EM departments and the remaining 520 (70%) in IM departments. We found that fewer patients at risk for VTE were treated with low-molecular-weight heparin (LMWH) in EM departments than in IM departments. Moreover, there was significant statistical difference in the use of LMWH between IM and EM departments when the Padua score and immobilization criteria were used to assess the risk. The infrequent use of LMWH in EM patients may have several causes. For example, in EM departments, treatment of acute illness often takes higher priority than VTE risk evaluation. Moreover, immobilization criteria cannot be evaluated for all EM patients because of the intrinsic time requirements. For the aforementioned reasons, we believe that a different VTE risk score is required that takes into account the peculiarities of EM, and establishing such a score should be the object of future study.

ANTITHROMBOTIC THERAPY IN PATIENTS WITH METABOLIC SYNDROME AFTER ABDOMINAL DELIVERY

Objective. To assess the effectiveness for complex antithrombotic therapy with low molecular weight heparins (LMWH) after cesarean section at women with metabolic syndrome (MS). Materials and Methods. The study included 115 patients with metabolic syndrome after cesarean section. Group 1 (64 patients) with metabolic syndrome who had a complicated pregnancy in history. Group 2 (51 patient) with metabolic syndrome and no pregnancies in anamnesis. Group 3 (50 patients) – somatically healthy mothers. С omprehensive clinical and laboratory examination was conducted, including a study of indicators of hemostasis in the preoperative period and at 1-th, 3-4-th, 9-10-th day of postoperative period. To prevent thromboembolic complications all patients with metabolic syndrome were injected enoxaparin sodium 12 hours after abdominal delivery in a dose of 40 mg daily, with further dose adjustment. Results. According to the results of studies in patients with MS from 1 day of the postoperative period there was an increased prothrombotic potential, violation of indicators of coagulation, platelet hemostasis and the system of natural anticoagulants. Due to the therapy with the use of LMWH the development of thromboembolic episodes was prevented at all patients with MC in the postoperative period. Other complications of the postoperative period were detected in 17 (14.78%) of patients with MS and 7 (14.00%) somatically healthy mothers. The incidence of postoperative complications 1st and 2nd groups were comparable with 3rd group. Analysis of laboratory parameters in patients with metabolic syndrome with complicated postoperative period, showed that the aggregation capacity of platelets with ADP, the levels of TAT and D-dimer on 9-10th day were comparable with those indices in the 1st and 3-4th day. The results show prothrombotic tendencies and violations of the hemostatic system continued to 9-10 days in these patients and also indicate a pathogenetic relationship of these tendencies in the development of postoperative complications. Conclusion. The development of thromboembolic complications in patients with MC was prevented due to the therapy of LMWH.

The Treatment of Venous Thromboembolism in Patients with Cancer.

Venous thromboembolism (VTE) is a frequent complication in cancer patients and represents an important cause of morbidity and mortality. The treatment of VTE complications in cancer patients remains a difficult clinical task. Low-molecular-weight heparins (LMWH) are the cornerstone of VTE treatment in cancer patients, including the treatment of catheter-related thrombosis. LMWH dose adjustment is effective in treating recurrent thrombosis and in patients with bleeding or thrombocytopenia. The duration of treatment is dependent on several factors that need to be individually evaluated. The novel anticoagulants should be investigated more carefully before being routinely implemented in the treatment of cancer-associated VTE. Incidentally detected isolated sub-segmental pulmonary embolism is unlikely to require systematic full-dose anticoagulation. Whether the long-term use of LMWHs has the potential to prolong survival in subgroups of cancer patients requires further investigations.

Continued Use of Tinzaparin at Therapeutic Doses for Prophylaxis of Venous Thromboembolism in Patients with Intolerance to Antivitamins K

OBJECTIVESThe low molecular weight heparins (LMWH) are typically administered at fixed doses like thromboprophylaxis or at doses adjusted to the weight of the patient in order to obtain a therapeutic effect. Generally they do not require laboratory monitoring, although it could be considered in special situations (renal failure, extreme weights, pregnant women). The LMWH do not affect the APTT, so it has been proposed to determine the anti-factor Xa activity when it is necessary to monitor its effect. The anti-factor Xa activity should be determined approximately 4 hours after sc administration of the LMWH that it is employed, concurring with the peak of activity. The therapeutic range of the anti-factor Xa activity is between 0.6 and 1 IU / mL when LMWH is administered every 12 hours. At single daily dose is less clear, although it seems that lies above 1 IU / mL.Nowadays, LMWH are the anticoagulant of choice during pregnancy. Numerous in vitro and in vivo studies have shown the existence of an antineoplastic effect of heparin. LMWH is commonly used for prolonged treatment of thrombosis associated with cancer.METHODSThe main aim of our study is to evaluate the efficacy of tinzaparin sodium at therapeutic doses in preventing VTE in renal failure, active cancer and/or patients with contraindications to oral anticoagulation. The dose has been therapeutic and adjusting it has been made in terms of anti-factor Xa levels obtained monthly. Hemorrhagic or thrombotic complications and other possible side effects have been assessed.Until now, a total of 70 patients, 42 men and 28 women aged between 30 and 95 years old, have received tinzaparin sodium treatment. The main reason of anticoagulation are: atrial fibrillation and atrial flutter (with or without valve disease), VTE (with or without thrombophilia), stroke and transient ischemic attacks and mechanical prosthetic aortic and mitral valves (some of the patients carrying a double metal prosthesis). There was 1 resistance and 1 allergic reaction to anti-vitamin K. 4 of the patients were pregnant and 14 had renal failure. Prior to initiation of therapy, analytical determinations were performed, including: blood count, blood coagulation and biochemistry to assess renal function (urea and creatinine).20 patients (14 were anticoagulated by atrial fibrillation, 2 for bearing a mechanical aortic prosthesis and 4 because of DVT, 1 of which had also a TEP) had active cancer or were in remission from their neoplasia (3 multiple myeloma, 1 LAM, 1 CMML, 4 renal tumors, 1 lung cancer, 5 prostate cancers, 1 hepatocellular carcinoma, 2 colon cancer, 1 endometrial adenocarcinoma and 1 retroperitoneal leiomyosarcoma). 1 with MDS was treated with LMWH because he had intra- and extrahepatic portal vein thrombosis.RESULTSSome of the patients had received prior treatment with anti-vitamin K (INR objective depending on pathology) but, in other cases, the low molecular weight heparin was the only treatment since the beginning of their anticoagulation. All the patients had received 175 IU / Kg of Tinzaparin Sodium once a day as initial dose, then the dose was adjusted according to the anti-factor Xa levels. They were controlled until 31/07/2015.In terms of side effects, 8 patients presented complications: 3 mucosal bleeding, 2 episodes of stroke in a patient, hemoptysis, deep vein thrombosis and 2 bleeding at the puncture site of heparin, which have not required discontinuation of therapy. When these complications occurred, we proceeded to the corresponding heparin dose adjustment based on new determinations of anti-factor Xa.CONCLUSIONSAlthough only in 70 cases, the results obtained confirm the efficacy, safety and cost-effectiveness of the continuous use of LMWH. Determination of anti-factor Xa levels are considered very useful for dose adjustment parameter. In our study, tinzaparin sodium has proved to be very useful in preventing venous thromboembolism associated or not with cancer, in patients with conditions requiring anticoagulation and presenting contraindications to the use of anti-vitamin K.The results obtained have demonstrated that tinzaparin is safe and, most likely, further studies will provide valuable confirmation data to support the use of low molecular weight heparins in the prolonged treatment of patients who require oral anticoagulation and can not receive it. DisclosuresNo relevant conflicts of interest to declare.

Use of Low Molecular Weight Heparin (LMWH) in Thrombocytopenic Patients with Hematologic Malignancy-Associated Venous Thromboembolism (VTE)

Introduction:The management of hematologic malignancy-associated VTEin patients with moderate to severe thrombocytopenia is unclear. Clinical trials of anticoagulants in VTE exclude such patients, hence do not inform the risk of bleeding or clot progression. Consensus-based guidelines recommend case-by-case consideration for either platelet transfusion to maintain platelet count >50,000/µL and therapeutic anticoagulation, or 50% dose reduction in LMWH (J Thromb Haemost. 2013 Jan;11(1):56-70.; Curr Oncol. 2015 Apr;22(2):144-55). At our institution, our approach is to use prophylactic dose LMWH for patients with platelet count ≤50,000/µL.Method:This is a single-center retrospective study of 128 adult patients with hematologic malignancies, who were diagnosed with VTE. Patients were identified from hospital research database. The diagnoses were verified after the review of medical records. The platelet count was assessed during the period of anticoagulation for VTE. The outcomes of patients with significant thrombocytopenia (≤50,000/µL) was compared with those without. Bleeding and clot recurrence was assessed until the last follow-up (median of >1 month). Fisher's Exact test was used to test the association between two categorical variables, and Analysis of Variance (ANOVA) was used to test the association between a continuous variable and a categorical variable.Results:Characteristics of the study population were as follows: 51% male, 47% non-Hodgkin lymphoma, 20% acute leukemia/myelodysplastic syndrome, 40% status-post hematopoietic stem cell transplant, 9% with creatinine >2 mg/dl, 36% with pulmonary embolism and 28% with catheter-related VTE. Forty six patients (36%) had a platelet count ≤50,000/µL during a period of time of perceived need for new or continued anticoagulation. The median nadir platelet count in those with significant thrombocytopenia was 9000/µL( range 2000-45,000/µL) versus 166,000/µL (range 50,000-389,000/µL) in those without (p<0.001). The median duration of significant thrombocytopenia in the first group was 10 days (range 1-68 days). Therapy during the period of significant thrombocytopenia included prophylactic dosing of LMWH (46%), therapeutic dose of LMWH or heparin (30%), warfarin (2%), inferior vena cava filter (2%) and observation (17%). Patients without thrombocytopenia were managed with the standard of care therapy. At last follow-up, the risk of bleeding (p=0.65) and clot progression (p=0.81) were similar in the two groups (Table 1).Conclusion:Within the limits of this retrospective study, cautious use of dose-adjusted LMWH in thrombocytopenic patients with hematologic malignancy-associated VTE may be safe. A prospective trial of prophylactic dose LMWH in patients with VTE during thrombocytopenia is required to confirm the safety and, to some extent, efficacy of such an approach.Table 1Outcome of patients with VTEOutcomeThrombocytopenic cohort (Platelet count ≤50,000/µL)Patients without significant thrombocytopenia (Platelet count >50,000/µL)p-valueBleeding after VTE treatment0.65No38 (82.6%)75 (91.5%)Minor (without significant clinical implications)1 (2.2%)1 (1.2%)Clinically significant (causing drop in hemoglobin; requiring transfusion or other interventions)4 (8.7%)5 (6.1%)Missing3 (6.5%)1 (1.2%)Clot progression or recurrence at last follow-up0.81No35 (76.1%)67 (81.7%)Yes9 (19.6%)15 (18.3%)Missing2 (4.3%)0 DisclosuresVose:Allos Therapeutics/Spectrum: Research Funding; US Biotest, Inc: Research Funding; Janssen Biotech: Research Funding; Celgene: Research Funding; Genentech: Research Funding; Bristol-Myers Squibb: Research Funding; Incyte Corp: Research Funding; Acerta Pharma: Research Funding; GlaxoSmithKline: Research Funding. Armitage:Celgene: Consultancy; Ziopharm: Consultancy; Spectrum: Consultancy; Roche: Consultancy; GlaxoSmithKline: Consultancy, Membership on an entity's Board of Directors or advisory committees; Conatus: Consultancy, Membership on an entity's Board of Directors or advisory committees; Tesaro Bio, Inc: Membership on an entity's Board of Directors or advisory committees. Lunning:Spectrum: Consultancy; Genentech: Consultancy; BMS: Consultancy; Juno: Consultancy; Gilead: Consultancy; TG Therapeutics: Consultancy.

Comparative Effectiveness and Safety of Direct Oral Anticoagulants (DOAC) Versus Conventional Anticoagulation for the Treatment of Cancer-Related Venous Thromboembolism: A Retrospective Analysis

IntroductionCancer is a risk factor for the development of venous thromboembolism (VTE). There is significant morbidity and mortality associated with VTE, and the treatment for these events can be painful, lengthy, and expensive. The development of DOACs has offered several new options for the treatment of VTE. Recent data suggested that the safety and effectiveness of DOACs in patients with cancer is equivalent to that of traditional oral therapies. The standard of care for the treatment of cancer-related VTE is a low molecular weight heparin (LMWH) formulation. If equivalent to LMWH, the use of DOACs in the treatment of cancer-related VTE would reduce the risk of VTE recurrence while potentially giving patients freedom from subcutaneous injections.MethodsWe performed a retrospective analysis of the electronic medical records (EMR) of adult patients with newly diagnosed or recurrent cancer-related VTE, who were treated with therapeutic dose of an anticoagulant for the index VTE and did not have other underlying thrombophilia or indication for long-term anticoagulation. Patients were treated at the benign hematology clinic during 2014. We screened a sample of 197 patients; 89 were selected in our final analysis according to the inclusion criteria. We used EMR to collect demographic data, laboratory values, details of cancer diagnosis, and details of VTE diagnosis. We documented patients who experienced recurrent VTE as well as those who experienced anticoagulant-associated clinically relevant bleeding. We used a multivariate analysis of this data to account for demographic, clinical, and tumor-related variables associated with this study. The primary outcome was the rate of recurrence of VTE after the initiation of anticoagulation. Secondary outcomes were the rate of anticoagulant-associated clinically relevant bleeding, as well as event-free survival for VTE recurrence.ResultsAmong the 89 patients that were included in our final analysis, 63 (71%) were treated with subcutaneous formulations of low molecular weight heparin (LMWH), 20 (22%) were treated with DOACs, and 6 (7%) were treated with warfarin. The Eastern Cooperative Oncology Group (ECOG) score for these patients ranged from 0 to 3. The majority (69%) of VTE occurred in patients with stage III or IV disease. Almost all of the patients (91%) were diagnosed with VTE in the setting of active cancer; a small percentage of cases occurred in patients with a recent or remote history of malignancy. Patients had 36 different histological types of cancer, but the most common were invasive ductal carcinoma of the breast (21%), lymphoma (9%), and adenocarcinoma of the colon or rectum (6%). Most of the patients (91%) were free of primary or metastatic disease of the central nervous system, but nearly 1 in 5 (17%) had evidence of hepatic metastases at the time of the index event. The most common index event was pulmonary embolism (53%) followed by catheter-associated deep venous thrombosis (DVT) (28%) and proximal lower limb DVT (12%). Recurrence of VTE occurred in 10.0% of patients receiving DOACs and 11.1% of patients receiving LMWH (P=NS). When VTE recurrence occurred, it was most likely in the form of pulmonary embolism (44%), splanchnic vein thrombosis (22%), or proximal lower limb DVT (11%). Clinically relevant bleeding was slightly higher with the use of DOACs (20%) versus LMWH (17%). Interestingly, major bleeding occurred more often with the use of DOACs (15%) than with LMWH (6.3%), although clinically relevant non-major bleeding was more common in patients receiving LMWH (11%) than in those receiving DOACs (5%). There was no mortality attributed to bleeding complications. The VTE recurrence-free survival rates were not statistically different (P=0.222) among patients treated with LMWH versus DOACs (Figure 1)ConclusionCancer-associated VTE is associated with significant morbidity and mortality. Recurrence of VTE is not uncommon, and caution must be exercised throughout the treatment of VTE due to the significant anticoagulant-associated hemorrhagic risks. LMWHs are effective for the treatment of cancer-related VTE, but injections are cumbersome and painful for many patients. Our analysis suggests that there is no significant difference in the rate of VTE recurrence when using oral DOACs versus subcutaneous LMWH. DOACs appeared to be at greater risk of major bleeding. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Post-operative use of Low Molecular Weight Heparin: Are patients doing their bit?

Introduction: Current National Institute for Health and Care Excellence (NICE) guidelines recommend the use of Low Molecular Weight Heparin (LMWH) for one month post-operatively in abdominal and pelvic cancer surgery to reduce risk of venous thromboembolism. We audited the prescription of LMWH at discharge and the compliance of patients with LMWH post-operatively and instigated measures to improve compliance. Materials and Methods: All patients undergoing major urological surgery from November 2011 to April 2012 were audited, with data collected on evidence of post-operative prescription (from discharge summaries). Patients within this 3-month period were questioned regarding compliance following discharge. Following this, changes were instigated to improve compliance (earlier discussion of post-operative LMWH administration in clinic, improved patient and junior doctor education). All patients undergoing surgery from November 2012 to June 2013 were identified and a re-audit completed. Results: Post-operative prescription of LMWH improved overall from 73% to 88%. Patient compliance to complete LMWH course improved from 23% to 88%. At re-audit, 97% of patients felt that training was adequate, and 94% of patients understood the rationale for taking LMWH at re-audit. Conclusion: Education of junior doctors improved prescription of LMWH at discharge. Improved patient education improves community LMWH use compliance post-discharge.

Does Use of Low-Molecular-Weight Heparin during Pregnancy Influence the Risk of Prolonged Labor: A Population-Based Cohort Study.

BackgroundThe use of low-molecular-weight heparins (LMWHs) during pregnancy is increasing. In vitro studies and small clinical studies support the hypothesis that LMWH treatment during pregnancy may reduce duration of labor. The aim of this study was to investigate if use of LMWH is associated with a reduced risk of diagnosis of prolonged labor, after taking maternal, fetal and other delivery characteristics into account.Methods and FindingsA population-based cohort study from the Swedish Medical Birth Register from April 2006 through December 2011. We identified 514 875 term (≥37 weeks) deliveries of live singleton infants in cephalic presentation with spontaneous or induced onsets of labor. The Birth Register was linked to the Prescribed Drug Register to retrieve information on dispensed LMWH during pregnancy and to the Patient Register for information on underlying diagnosis for use of LMWH. Diagnosis of prolonged labor in the Birth Register was retrieved from diagnosis at discharge from the delivery hospital. The risk of diagnosis of prolonged labor in relation to treatment with LMWH was assessed using logistic regression analysis to estimate unadjusted and adjusted odds ratios. A total of 5 275 (1.0%) of the pregnant women used LMWH. The absolute risk of diagnosis of prolonged labor for nulliparous women was 19.9% among women using LMWH in third trimester, and 21.2% in women without use of LMWH. For parous women the corresponding absolute risks were 4.3% and 4.7%, respectively. Compared to nulliparous women without use of LMWH, nulliparous women with LMWH during third trimester had an odds ratio (OR) of 0.92 (95% CI 0.81–1.05, p-value: 0.051) for diagnosis of prolonged labor in unadjusted analyses and after adjustments for maternal characteristics, gestational age and epidural analgesia the OR was 1.00 (95% CI 0.87–1.15, p-value: 0.673). Parous women treated with LMWH in third trimester presented the same pattern, unadjusted OR for diagnosis of prolonged labor was 0.92 (95% CI 0.76–1.12, p-value: 0.418) and after adjustments OR was 0.99 (95% CI 0.80–1.22, p-value: 0.892). One limitation with the study was that information on prolonged labor was based on discharge diagnoses from the delivery hospital according to the International Classification of Diseases (ICD).ConclusionsTreatment with LMWH during pregnancy is not associated with a risk of diagnosis of prolonged labor after adjustments for maternal, fetal and delivery characteristics.

Venous thromboembolism prophylaxis during and following caesarean section: a survey of clinical practice.

Caesarean section (CS) is a significant risk factor for venous thromboembolism; however, the optimal method of thromboprophylaxis around the time of CS is unknown. To examine current thromboprophylaxis practice during and following CS in Australia and New Zealand, and the willingness of obstetricians to participate in a randomised controlled trial (RCT) comparing different methods of thromboprophylaxis after CS. An online survey was sent to fellows and trainees of the Royal Australian and New Zealand College of Obstetricians and Gynaecologists. There were 488 responses from currently practising obstetricians (response rate 23.4%). During CS, 48% and 80% of obstetricians recommended intermittent pneumatic compression (IPC) and elastic stockings (ES), respectively. Following CS, 96-97% of obstetricians recommended early ambulation, 87-90% recommended ES, 23-36% recommended IPC, and 42-65% recommended low molecular weight heparin (LMWH) depending on clinical factors. Increased BMI (OR 3.42; 95% CI 2.87-4.06), emergency CS (OR 1.88; 95% CI 1.67-2.16) and older maternal age (OR 1.37; 95% CI 1.26-1.49) were associated with more frequent LMWH use. Of obstetricians who prescribed LMWH, 70% adjusted the dose depending on maternal weight. LMWH therapy was most commonly recommended until discharge from hospital (31%), <5days (24%) and 5-7days (15%). Most obstetricians (58-79%) were willing to enrol women in a RCT, but less likely if the woman had an increased BMI or emergency CS. There is considerable variation in clinical practice regarding thromboprophylaxis during and following CS. Obstetricians support a RCT to assess different methods of thromboprophylaxis following CS.

L-asparaginase and venous thromboembolism in acute lymphocytic leukemia.

The occurrence of venous thromboembolism (VTE) in acute lymphocytic leukemia patients receiving L-asparaginase therapy may cause significant morbidity, neurological sequela and possibly worse outcomes. The prophylactic use of antithrombin infusion (to keep antithrombin activity >60%) or low molecular weight heparin (LMWH) may reduce the risk of VTE. The decision to continue L-asparaginase therapy after the development of VTE should be based on anticipated benefits, severity of VTE and the ability to continue therapeutic anticoagulation. In patients receiving asparaginase rechallenge, the use of therapeutic LMWH, monitoring of anti-Xa level and antithrombin level are important. Novel oral anticoagulants are not dependent on antithrombin level, hence offer theoretical advantages over LMWH for the prevention and therapy of asparaginase-related VTE.

Unfractionated or low-molecular weight heparin for induction of remission in ulcerative colitis.

There are a limited number of treatment options for patients with ulcerative colitis (UC). An increased risk of thrombosis in UC coupled with an observation that UC patients being treated with anticoagulant therapy for thrombotic events had an improvement in their bowel symptoms led to trials examining the use of unfractionated heparin (UFH) and low molecular weight heparins (LMWH) in patients with active UC. To review randomized trials examining the efficacy of unfractionated heparin (UFH) or low molecular weight heparins (LMWH) for remission induction in patients with ulcerative colitis. We searched MEDLINE, EMBASE, CENTRAL, and the Cochrane IBD/FBD group specialized trials register up to June 2014. We also searched review papers on ulcerative colitis and references from identified papers in an effort to identify additional randomized trials studying UFH or LMWH use in patients with ulcerative colitis. We searched abstracts from major gastroenterological meetings to identify research published in abstract form. Randomized controlled trials comparing UFH or LMWH to placebo or a control therapy for induction of remission in ulcerative colitis were included. Studies published in abstract form only were included if the authors could be contacted for further information. A data extraction form was developed and used to extract data from included studies. Two authors independently extracted data. Any disagreements were resolved by consensus. The Cochrane Risk of Bias tool was used to assess study quality. Data were analyzed on an intention-to-treat basis. The primary outcome was induction of remission, as defined by the studies. Secondary outcomes measures included: endoscopic remission as defined by the authors; clinical, histological or endoscopic improvement as defined by the authors; the occurrence of adverse events; the occurrence of bleeding; and improvements in quality of life as measured by a validated instrument. We calculated the risk ratio (RR) and corresponding 95% confidence interval for dichotomous outcomes. Data were combined for analysis if they assessed the same treatments (UFH or LMWH versus placebo or other therapy). The overall quality of the evidence supporting the outcomes was evaluated using the GRADE criteria. Five studies were eligible for inclusion (329 patients). Three studies (270 patients) compared low molecular weight heparin to placebo, one study (34 patients) compared LMWH in addition to standard therapy, and one study (25 patients) compared UFH to corticosteroids. The study comparing UFH to corticosteroids was rated at high risk of bias due to a single-blind design. The study that compared the addition of LMWH to standard therapy to standard therapy alone was rated at high risk of bias due to open-label design. The other three studies were rated as low risk of bias. LMWH administered subcutaneously showed no benefit over placebo for any outcome, including clinical remission (very low quality of evidence), and clinical, endoscopic, or histological improvement. High dose LMWH administered via an extended colon-release tablet demonstrated benefit over placebo for clinical remission (RR 1.39; 95% CI 1.09 to 1.77 ; P = 0.008; very low quality of evidence), clinical improvement (RR 1.28; 95% CI 1.06 to 1.55; P = 0.01; very low quality of evidence), and endoscopic improvement (RR 1.21; 95% CI 1.00 to 1.47 ; P = 0.05) but not endoscopic remission or histologic improvement. LMWH was not beneficial when added to standard therapy for clinical remission, clinical improvement, endoscopic remission or endoscopic improvement. LMWH was well-tolerated but provided no significant benefit for quality of life. One study examining UFH versus corticosteroids for the treatment of severe UC demonstrated the inferiority of UFH for clinical improvement. More patients assigned to UFH had rectal hemorrhage as an adverse event. There is evidence to suggest that LMWH may be effective for the treatment of active UC. When administered by extended colon-release tablets, LMWH was more effective than placebo for treating outpatients with mild to moderate disease. This benefit needs to be confirmed by further randomized controlled studies. The same benefits were not seen when LMWH was administered subcutaneously at lower doses. There is no evidence to support the use of UFH for the treatment of active UC. A further trial of UFH in patients with mild disease may also be justified. Any benefit found would need to be weighed against a possible increased risk of rectal bleeding in patients with active UC.

Interventions for prophylaxis of hepatic veno-occlusive disease in people undergoing haematopoietic stem cell transplantation.

Interventions for prophylaxis of hepatic veno-occlusive disease in people undergoing haematopoietic stem cell transplantation.

Thromboprophylaxis with low-molecular-weight heparins: an assessment of the methodological quality of studies.

Low-molecular-weight heparin (LMWH) represents the standard of care for prophylaxis of venous thromboembolism (VTE). We conducted a review of the evidence supporting the use of the different LMWHs employed in VTE prophylaxis, in different clinical settings, and analyzed its progression over time. To evaluate the standards of methodological quality of studies, we elaborated a quality assessment tool. By electronic databases, PubMed, MEDLINE, and Scopus databases, 249 articles deemed eligible for the analysis were selected. Several LMWHs did not have publications in all clinical settings. Extended duration of prophylaxis was documented only for a few LMWH. The quality score yielded statistically significant differences between the medians of the four settings (p = 0.0021) with a higher score in major orthopedic surgery (median, 16; 95% confidence interval [CI], 15-16) when compared with general surgery (median, 14; 95% CI, 13-14; p < 0.001). Median score for studies published after the year 1990 was higher than for those published earlier (p < 0.001). We conclude that the quality of the studies supporting LMWH for VTE prophylaxis in the different clinical settings is not homogeneous and inferior for studies performed before the year 1990. Clinical interchangeability of LMWHs in clinical practice remains a critical issue, and the selection of a product should be based on evidence available for each agent, and for each clinical indication derived from clinical trials.

Assessment of the Adminstration of Low Molecular Weight Heparin for Hemodialysis Anticoagulation in Comparison to Standard Unfractionated Heparin

Background and Aim of Study : The use of Low - molecular - weight heparin (LMWH) for hemodialysis anticoagulation has been proposed as effective and safe for hemodialysis (HD) anticoagulation as standard unfraction ated heparin (UFH). The aim of our study was to assess the use of LMWH for hemodialysis anticoagulation in comparison to UFH, including hemorrhagic events and clotting of the extracorporeal dialysis circuit and their effect on lipids profile. Method s : This prospective, randomized study conducted on 44 patients (31 males, 13 females; mean age 53.7.9±14.2 years ) with end - stage renal disease on regular hemodialysis. The hemodialysis patients were subjected to UFH and followed prospectively for 16 weeks (4 8 dialyses sessions) and the same patients were subjected to LMWH (enoxaparin sodium; 40 mg) for a further 16 weeks , clotting of the extracorporeal dialysis circuit and hemorrhagic events were evaluated by visual inspection of the air trap, blood lines and dialyzers and the time required for arterio - venous fistula compression. Kt/V was calculated to determine whether UFH or LMWH had any effect on the adequacy of dialysis and lipid profile were measured at the end of each arm of the study to determine whethe r UFH or LMWH had any effect on the lipid profile levels. Results : The present study showed that, compared with UFH, the effect of LMWH (enoxaparin Original Research Article