Dose Of Low Molecular Weight Heparin Research Articles

Comparison of Low Dose Thrombolytic Therapy and Low Molecular Weight Heparin Therapy in Patients with Submassive Pulmonary Thromboembolism

Comparison of Low Dose Thrombolytic Therapy and Low Molecular Weight Heparin Therapy in Patients with Submassive Pulmonary Thromboembolism

Triple Antiphospholipid (aPL) Antibodies Positivity Is Associated With Pregnancy Complications in aPL Carriers: A Multicenter Study on 62 Pregnancies.

Objective: Antiphospholipid antibodies (aPL) are risk factors for thrombosis and adverse pregnancy outcomes (APO). The management of the so called “aPL carriers” (subjects with aPL positivity without the clinical criteria manifestations of APS) is still undefined. This study aims at retrospectively evaluating the outcomes and the factors associated with APO and maternal complications in 62 pregnant aPL carriers.Methods: Medical records of pregnant women regularly attending the Pregnancy Clinic of 3 Rheumatology centers from January 1994 to December 2015 were retrospectively evaluated. Patients with concomitant autoimmune diseases or other causes of pregnancy complications were excluded.Results: An aPL-related event was recorded in 8 out of 62 patients (12.9%) during pregnancy: 2 thrombosis and 6 APO. At univariate analysis, factors associated with pregnancy complications were acquired risk factors (p:0.008), non-criteria aPL manifestations (p:0.024), lupus-like manifestations (p:0.013), and triple positive aPL profile (p:0.001). At multivariate analysis, only the association with a triple aPL profile was confirmed (p:0.01, OR 21.3, CI 95% 1.84–247). Patients with triple aPL positivity had a higher rate of pregnancy complications, despite they were more frequently receiving combined treatment of low dose aspirin (LDA) and low molecular weight heparin (LMWH) at prophylactic dose.Conclusion: This study highlights the importance of risk stratification in pregnant aPL carriers, in terms of both immunologic and non-immunologic features. Combination treatment with LDA and LMWH did not prevent APO in some cases, especially in carriers of triple aPL positivity. Triple positive aPL carriers may deserve additional therapeutic strategies during pregnancy.

Early low-molecular-weight heparin administration is associated with shorter time to SARS-CoV-2 swab negativity.

Antiviral and immune-modulating properties of low-molecular-weight heparin (LMWH) against Coronaviridae have been reported by in vitro studies, but no in vivo evidence is yet available. We sought to know whether the timing of prophylactic doses of LMWH during the course of COVID-19 may affect the time to SARS-CoV-2 nasal-oropharyngeal swab negativization. Retrospective monocentric cross-sectional study on patients requiring sub-intensive ward admission due to first SARS-CoV-2 infection and undergoing early (EH; within 7 days from COVID-19 signs and symptoms onset) versus delayed prophylactic LMWH (DH; after 7 days). SARS-CoV-2 RNA was measured by reverse transcription real-time PCR according to scheduled time points: first swab after 2 weeks from COVID-19 onset, then at 1-week intervals until negativity. Time to SARS-CoV-2 swab negativity was shorter in EH (38 patients) compared with DH (55 patients): 22 versus 37 days (P=0.004). The number of confirmative negative swabs in EH was significantly higher compared with DH at week 2 (21.1% versus 3.6%; P=0.017) and 4 (60.0% versus 19.6%; P<0.001). At univariate, EH differed from DH for several disease severity and clinical management parameters. Nevertheless, after accounting for the differences, Cox regression showed early LMWH administration (hazard ratio [HR] 2.91 [1.51, 5.63]; P=0.002) and higher lymphocytes nadir (HR 1.04 [1.01, 1.08]; P=0.020) as predictors of shorter time to swab negativity. This potential antiviral and/or immune-modulating activity of LMWH needs further in vivo confirmations by randomized controlled trials.

Venous thrombosis in children, adolescents and young adults with acute lymphoblastic leukemia receiving chemotherapy in the Republic of Belarus

Objective: to clarify the conditions for the occurrence of thrombosis and assess the effect of anticoagulant therapy on the survival and outcome of thrombosis in children, adolescents and young adults with acute lymphoblastic leukemia (ALL) receiving program chemotherapy.Materials and methods. The study included 592 patients with ALL received program chemotherapy from 2008 to 2017 in the Belarusian Research Center for Pediatric Oncology, Hematology and Immunology (Minsk, Belarus). Of them, in 42 patients various localization venous thrombosis was detected at different therapy phase.Results.The cumulative detection rate of thrombosis was 7.5 ± 1.1 %. The use of pegelated asparaginase (PEG-asp) at a dose of 1000 IU/m2 in induction therapy increased the relative risk of thrombosis in the first 5 weeks of treatment by 3 times (relative risk 3.4; 95 % confidence interval 0.98–11.9), compared to patients not receiving PEG-asp. The cumulative detection rate of thrombosis in patients with the post-induction L-asparaginase (L-asp) 25,000 IU/m2 regimen was 14.7 ± 2.6 %, which was higher (p = 0.0536) than when using L-asp in other dosing regimens. In addition to ALL as the main disease, taking chemotherapy drugs, other risk factors for thrombosis (thrombophilia, the presence of antiphospholipid antibodies, a decrease of natural anticoagulants activity) in various combinations were in half (23 of 42) patients with venous thrombosis. Therapeutic dose of low molecular weight heparins (LMWH) 150–200 IU/kg received 30 patients. Reduced for the period of thrombocytopenia from 100 to 35 × 109/L for up to 4 weeks, a daily dose of LMWH was received by 12 patients. The dose of LMWH was reduced in proportion to the blood platelets count. After the recovery of the platelet count of more than 100 × 109/L, patients continued treatment of LMWH in a daily dose of 150–200 anti-Xa IU/kg. Reducing of LMWH dose during thrombocytopenia period did not affect the outcome of thrombosis (χ2 = 0.494; p = 0.78). Among 42 patients with thrombosis, 38 completed maintenance therapy, eventfree survival was 83.0 ± 8.0%, which did not differ (p = 0.654) from that (81.0 ± 2.0 %) in patients without thrombosis. Conclusion. The presence of venous thrombosis with the use of LMWH as antithrombotic therapy did not lead to a decrease in the event-free survival of ALL patients, compared with those without thrombosis. Reducing the therapeutic dose of LMWH did not affect the outcome of thrombosis in the analyzed groups.

Description of anti-Xa monitoring practices during low molecular weight heparin use.

Certain patient populations (pregnancy, cancer, renal impairment, and obesity) may be at higher risk of adverse events during low molecular weight heparin (LMWH) therapy and may benefit from anti-Xa monitoring. Yet, evidence supporting a standardized approach to anti-Xa monitoring correlated to clinical outcomes is lacking. Patients with at least one documented anti-Xa level and receiving LMWH within a 6-month period were identified. In a 6-month period, 224 adult LMWH patients with 359 anti-Xa levels were identified. Anti-Xa monitoring was most commonly performed in patients with active cancer receiving venous thromboembolism (VTE) treatment doses (57.4%) or obese patients receiving VTE prophylaxis (48.1%). Anti-Xa monitoring during renal impairment and pregnancy were infrequent (0.9% and 1.8%, respectively). Most (71.9%) anti-Xa levels were therapeutic, but only 45% were drawn correctly in relation to LMWH administration time. Compared to those with therapeutic anti-Xa levels, patients with out-of-range levels were four times as likely to receive a LMWH therapy change (odds ratio, 4.16; 95% confidence interval, 2.53-6.84). However, when levels were supratherapeutic or subtherapeutic, the LMWH doses remained unchanged in one-third to one-half of patients, respectively. Anti-Xa monitoring was most commonly performed in patients with cancer or obesity and was more common with VTE prophylaxis dosing. The majority of levels were therapeutic, indicating that anti-Xa monitoring may be unnecessary even in high-risk patient populations. Many out-of-range anti-Xa levels did not prompt a change in LMWH therapy. Further research is still needed to determine if anti-Xa- guided LMWH dosing improves clinical outcomes.

PF802 ANTICOAGULANT THERAPY IN THROMBOCYTOPENIC PATIENTS WITH BLOOD CANCER AND CATHETER‐RELATED VTE: RESULTS FROM A DELPHI CONSENSUS ON PLATELETS COUNT BELOW 50 X 109L

Background:Management of venous thromboembolism (VTE) in patients with haematological malignancies (HM) and thrombocytopenia challenges clinicians because this scenario is encumbered with several risks. Our panel, composed by elected members of the Gruppo Italiano Malattie EMatologiche dell’Adulto (GIMEMA) Working Party on Thrombosis and Haemostasis (WPHT). has recently published a consensus,reached by RAND method, focused on the platelet cut‐off for safely administering Low Molecular Weight Heparin (LMWH) in adult patients with hematological malignancies, acute (no later than 1 month) or non‐acute VTE and thrombocytopenia (PLT&lt; 100 × 109/L).Aims:Aim of the current study was to produce a formal consensus, not achieved by the previous method, focused on anticoagulant treatment with LMWH in adult patients with HM affected by acute or non‐acute catheter‐related VTE and severe thrombocytopeniaMethods:Delphi methodology was adopted to allow members of the GIMEMA‐WPHT to achieve consensus on the above reported issue, starting from available scientific data. For each indication, the panel members (N = 21, 3 validators and 18 participants) rated the benefit‐to‐harm ratio of the indication on a scale of 1 to 5, where 1 means that the expected harms greatly outweigh the expected benefits, and 5 means that the expected benefits greatly outweigh the expected harms. The first survey consisted of 7 different statement; after analysis of the first results, it was decided to discuss and re‐formulate 3 items, panel members were then asked to rate again items for which no consensus had been achieved. The interventions considered were the administration of different doses of LMWH (therapeutic, reduced dose at 50% of full therapeutic dose, prophylactic dose) and PLT transfusions, according to platelet counts &gt;30 &lt;50 × 109/L, in patients with catheter‐related VTE. LMWH doses were defined according to the datasheet for each LMWH molecule.Results:After the first round, an agreement &gt;80%was reached for 4 out of the initial 7 items. Three items were thus reformulated nd partecipants were asked to reasses them After the second round, an agreement was reached for all items. The panel of experts expressed the following consensus: for the management of acute‐catether related VTE with platelet counts &gt;30 &lt;50 × 109/L in patients with HM, anticoagulant treatment with reduced dose to 50% of LMWH is appropriate (90%agreement); for the management of non‐acute catheter‐related VTE, treatment with reduced dose to 50% of LMWH is also appropiate. PLTs transfusions were deemed inappropriate in both,acute (90% agreement) and non‐acute (100% agreement) catheter‐related VTE. The administration of prophylactic dose of LMWH was deemed inappropriate with an agreement of 90% in patients with acute catheter‐related VTE and 80% in subjects with non‐acute catheter‐related VTE.Summary/Conclusion:Delphi method has allowed to reach consensus on a still debated issue, where scientific evidences are lacking.GIMEMA‐WPHT suggests anticoagulant treatment with reduced dose to 50% of LMWH for platelet counts &gt;30 &lt;50 × 109/L in patients with haematological malignancies and either acute or non‐acute catheter‐related VTE.

PB2179 THROMBOEMBOLIC EVENTS IN MULTIPLE MYELOMA (MM) PATIENTS. A SINGLE CENTER RETROSPECTIVE STUDY

Background:MM affects mainly patients older than 65 years. These patients are at higher risk for venous thromboembolism (VTE) because of cancer status, intrinsic risk factors and exposure to prothrombotic therapies. The risk of VTE appears higher during the first months of MM treatment (3‐4%). Exposure to immunomodulatory drugs (IMDs) such as Lenalidomide and Thalidomide in association with high dose dexametasone (HD‐DXM) or anthracyclin‐based chemotherapy is associated with increased risk of VTE (26%).There are recommendations available to guide the use of thromboprophylaxis in MM patients but progress on determining the most effective and safe strategy is low. In general, Low molecular weight heparin (LMWH) or therapeutic dose warfarin is recommended for patients the receive doxorubicin, HD‐DXM or multiagent chemotherapy, but thromboprophylaxis management is often complicated due to impaired renal function thrombocytopenia and increased bleeding risk.Aims:The goal of this single center retrospective study is to evaluate and characterize the VTE episodes in MM patients in our institution.MethodsThis single center retrospective study analyzes 84 MM patients diagnosed and treated in our center between 2008 and 2018 and describe the characteristics of 14 VTE episodes in 12/84 patients. Most of patients were assessed for risk factors, individual and related to MM, with Palumbo et al. Risk assessment model (Leukemia 2008;22:414‐23).Results:Main characteristics of the 12/84 MM patients diagnosed with 14 VTE episodes are shown in Table 1. 4/12 (33%) are female and median age is 69 years old (49‐85). 2/12 (16%) patients present 2 episodes of VTE. 4/12 (33%) patients receive thromboprophilaxis with LMWH, 6/12 (50%) with AAS, while 3/12 (25%) do not have profilaxis.3/14 (21%) VTE episodes present at the moment of diagnosis, 4/14 (28,5%) in the first months of diagnosis during hospitalization for infection or uncontrolled MM disease.All VTE episodes are diagnosed under MM treatment: 9/14 (64%) Lenalidomide+ HD DXM. 1/14 (7%) chemotherapy (DTPACE), 3/14 (21,4%) proteosome inhibitors combination. 1/14 (7%) Daratumumab‐Bortezomib‐Dexametasone. 5/14 (35%) VTE are superficial vein thrombosis (SVT), 5/14 (35%) pulmonary embolism (PE), 3/14 (21%) VTE + PE, 1/14 (7%) renal thrombosis.In all patients VTE treatment is done with HBPM during 3 o 6 months.Summary/Conclusion:In our institution the incidence of VTE in MM patients is 16%.imageIn our experience the use of IMWG assement risk does not eliminate the rate of VTE in these patients.It may be reasonable to start preventive doses of LMWH for 3 to 6 months in ambulatory MM patients receiving combined therapy with IMIDs and in all mieloma patients admited to the hospital.New risk assessment models combining clinical factors and hipercoagulability biomarkers shoud be developed.New trials are needed to explore safe thromboprophylaxis in MM patients (direct thrombin inhibitors or factor Xa inhibitors).

Thromboprophylaxis in adult and paediatric burn patients: A survey of practice in the United Kingdom

IntroductionPatients with burn injuries are at an increased risk of venous thromboembolism (VTE). This predisposition is secondary to the endothelial injury, hyper-coagulable state and stasis (Virchow’s triad) associated with burn injury. Although the true incidence of VTE in burn patients has not been adequately quantified, symptomatic VTE occurs in 0.2–7% of this population.VTE prophylaxis has proven clinical effectiveness and affords a reduction in the morbidity associated with such events, but the benefits and risk of complications need to be balanced in order to provide the best quality of care.Owing to the lack of prospective data on VTE in burns, practice varies greatly, not only internationally, but also between local burns services. Our aim was to better understand current VTE practice within United Kingdom (UK) burn care services by performing a comprehensive survey. MethodsWe contacted all the inpatient burn care services in the UK and collected data on current VTE practice via a standardised questionnaire. Services were given the choice to complete the survey by telephone or email and a follow-up plan was formulated. ResultsTwenty-five burn care services were contacted and 23 agreed to participate (92% response rate). Responding services treated adults, children or both and lead burn nurses or senior medical staff familiar with current VTE practice were interviewed.Routine VTE prophylaxis was provided in 84% of burn services and the majority utilised a combination of chemoprophylaxis and thromboembolic deterrent stockings (TEDS). All used low molecular weight heparin (LMWH) as their choice of chemoprophylaxis. Of those treating adults, all used a VTE prophylaxis protocol, but none of these applied to children. Only 56% of services treating children had such a protocol. The majority discontinued prophylaxis once patients were mobile. Discussion and conclusionAlthough the true burden of VTE in burn patients is unknown, we recognise that they are a population at risk. In addition to changes in the inflammatory and clotting pathways associated with thermal injury, prolonged hospital stay, ventilatory support, multiple surgeries, numerous central venous cannulations and reduced mobility all multiply this risk.The risk associated with the administration of heparin (bleeding complications and heparin-induced thrombocytopaenia) is low and can be reduced even further to 0.1% by the use of LMWH. The risk of symptomatic VTE is far greater, therefore the benefits of VTE prophylaxis would seem to outweigh the risks of not undertaking prophylactic measures. A higher LMWH dose and routine monitoring of anti-factor Xa levels are useful for acute burn patients.Two previous surveys, performed in Canada and the United States of America (USA), found routine administration of VTE prophylaxis to be 50% and 76% respectively. Of the 71 centres in the USA participating in the survey, 30% used a combination of sequential compression devices (SCD) and heparin and 24% did not provide VTE prophylaxis at all.A lack of prospective data on VTE in burn patients appears to be associated with diverse practice, and consensus on this topic could ensure that the potential morbidity caused by VTE is reduced. A clinical tool for identifying patients at risk and guidelines for management will standardise practice, which in turn should allow us to improve and maintain high quality care for burn patients.

Safety and Outcome of Intravenous Thrombolysis in Stroke Patients on Prophylactic Doses of Low Molecular Weight Heparins at Stroke Onset.

Background and Purpose- There are limited data on intravenous thrombolysis treatment in patients with ischemic stroke who have received prophylactic doses of low molecular weight heparins (LMWHs). We aimed to evaluate the safety and outcomes of intravenous thrombolysis treatment in stroke patients taking thromboprophylactic doses of LMWH. Methods- We analyzed 109 291patients treated with intravenous thrombolysis, recorded in the Safe Implementation of Treatments in Stroke International Thrombolysis Register between 2003 and 2017 not taking oral anticoagulants or therapeutic doses of heparin at stroke onset. One thousand four hundred eleven patients (1.3%) were on prophylactic LMWH for deep venous thrombosis prevention. Outcome measures were symptomatic intracerebral hemorrhage, parenchymal hematoma, death within 7 days and 3 months, and functional dependency at 3 months. Results- Patients on LMWH were older, had more severe strokes, more prestroke disability, and comorbidities than patients without LMWH. There was no significant increase in adjusted odds ratios (aOR) for symptomatic intracerebral hemorrhage (aOR, 1.02 [95% CI, 0.48-2.17] as per Safe Implementation of Treatments in Stroke -MOST, aOR, 0.95 [0.59-1.53] per ECASS II]), nor for 7-day mortality (aOR, 1.14 [0.82-1.59]), in the prophylactic LMWH group. The LMWH group had a higher aOR for 3-month mortality (aOR, 1.94 [1.49-2.53]) and functional dependency, aOR, 1.44 (1.10-1.90). Propensity score analysis matching patients on baseline characteristics removed differences between groups on all outcomes except 3-month mortality. Conclusions- Intravenous thrombolysis in patients with acute ischemic stroke on treatment with prophylactic doses of LMWH at stroke onset is not associated with an increased risk of symptomatic intracerebral hemorrhage or early death.

Comparative evaluation of oral corticosteroids versus low molecular weight heparin in the treatment of lichen planus

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; Lichen planus (LP) is an immunologically mediated inflammatory disorder involving the skin, nails, hair follicles and mucous membranes. Though several drugs and phototherapy are tried and mentioned in the literature, dermatologists are still depending on corticosteroids, which have various serious side effects on long term usage. Thus, in search for an alternative therapy, the present study is conducted to compare the efficacy of systemic corticosteroids and low dose low molecular weight heparin in management of lichen planus.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; 60 patients with biopsy proven LP were selected and divided randomly into two groups with 30 patients each. Group 1 was treated with oral corticosteroids and group 2 was treated with low molecular weight heparin for 8 weeks. Follow up was done for a period of 6 months, at monthly intervals in all patients and any relapses if any were noted.&lt;strong&gt;&lt;/strong&gt;&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; 60 patients with biopsy proven LP were selected and divided randomly into two groups with 30 patients each. Group 1 was treated with oral corticosteroids and group 2 was treated with low molecular weight heparin for 8 weeks. Follow up was done for a period of 6 months, at monthly intervals in all patients and any relapses if any were noted.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; Low dose enoxaparin in the treatment of lichen planus could be considered as an alternative to oral corticosteroids because of equal efficacy and fewer side effects.&lt;/p&gt;

Effect of Sildenafil Citrate When Added to Low Molecular Weight Heparin and Small Dose Aspirin on Uteroplacental Perfusion in Cases of High-Risk Pregnancy

Background: incubation with sildenafil citrate limits the effects of vasoconstrictors on myometrial small arteries of normal pregnancy women and pregnant women with fetal growth restriction. So that phosphodiesterase inhibitors seem to improve uterine perfusion safely in pregnancies with fetal growth restriction. Objective: the main aim of this study was to demonstrate the effect of sildenafil citrate when added to low dose aspirin and low molecular weight heparin on the uterine and umbilical artery Doppler to improve neonatal outcome in patients with high risk pregnancy. Subjects and Methods: the study was conducted at Al-Azhar University Hospitals, Cairo, Egypt. From March 2017 to March 2019 over a period of two years duration. One hundred patients (50 in each arm of the study), who had or have a high-risk pregnancy, were selected and enrolled into a randomized clinical trial. Results: there was significant increase in amniotic fluid index (AFI) and umbilical artery Doppler parameters. Group B (heparin/aspirin) also showed significant improvement in fetal biometry and Doppler parameters but when comparing the differences between the two groups, none of these changes were statistically significant except for the femur length measurement and the uterine artery resistance index. Conclusion: from the results of our study we concluded that heparin and aspirin combination or when sildenafil is also added have beneficial effects in the treatment of pregnant women whom vascular impairment is expected showing improvement in the fetal growth parameters and reduction of admission.

Prophylactic Measures in Early Recurrent Pregnancy Loss in Women with Polycystic Ovary Syndrome and Hyperhomocysteinemia

AbstractBackground: The Polycystic Ovary Syndrome (PCOS) is the commonest endocrine disturbance affecting women, several complications of pregnancy in women with Polycystic Ovary Syndrome (PCOS) including recurrent pregnancy loss, the exact mechanisms that may cause RPL in PCOS patients are obscure. Several etiologies have been proposed, hyperhomo-cysteinemia is a common finding in women with PCOS and was found to be associated with both RPL and PCOS.Aim of Study: Aim of the study is to evaluate prophylactic measures against early recurrent pregnancy loss before 20 weeks of gestation in women with polycystic ovary syndrome and hyperhomocysteinemia by either Low Dose Aspirin (LDA), LMWH or both.Patient and Methods: The present study was carried out on 120 pregnant women in reproductive period, their age ranged between 20 and 35 years. They were classified into three groups, group I treated with Low Dose Aspirin (LDA) (40), group II treated with low molecular weight heparin (40) and group III treated with low dose aspirin and low molecular weight heparin (40).Result: Hyperhomocysteinemia is a common finding in women with PCOS and was found to be associated with both RPL and PCOS. It was shown that combined treatment with aspirin and Low Molecular Weight Heparin (LMWH) in women with hyperhomocysteinemia improved successful pregnancy rates.Conclusion: The use of clexane or Clexane with LDA prevent early recurrent pregnancy loss in patients with PCOS and hyperhomocysteinemia better than LDA alone.

Placental Pathological Findings following Adjusting Enoxaparin Dosage in Thrombophilic Women: Secondary Analysis of a Randomized Controlled Trial.

Randomized trials showed no improvement in pregnancy outcomes with the use of low molecular weight heparin (LMWH) to prevent placenta-mediated pregnancy complications (PMPCs) among thrombophilic women. However, the effect of treatment on placental findings was not examined. We aimed to examine the occurrence of placental vascular lesions in thrombophilic women treated with LMWH dose adjusted according to anti-factor Xa compared with a fixed dose. This study was a secondary analysis of a randomized trial designed to examine whether LMWH dose adjusted according to anti-factor Xa levels compared with a fixed dose would reduce the risk of PMPC. Eligible women were randomly allocated in a 1:1 ratio to either a fixed dose of 40 mg daily LMWH (fixed dose group) or adjusted dose according to anti-factor Xa levels (adjusted dose group). Placentas were examined by the same perinatal pathologist who was blinded to group allocation. The primary outcome for this analysis was the incidence of maternal placental vascular lesions. During the study period, 88 placentas were examined; 41 and 47 from the fixed and adjusted dose groups, respectively. Demographics, obstetrics and types of thrombophilias were similar between the groups. Maternal placental vascular lesions were observed in 23 (56.1%) and 21 (44.68%) placentas (p = 0.28) and foetal placental vascular lesions in 2 (4.88%) and 1 (2.13%) placentas (p = 0.59) in the fixed and adjusted groups, respectively. Adjusted dose of enoxaparin according to anti-factor Xa levels compared with a fixed dose did not affect placental vascular lesions in thrombophilic women.

Impact of a Pharmacist Driven Anti-Xa Level Monitoring Protocol on Therapeutic Drug Monitoring Practice Patterns

Introduction:Low molecular weight heparin (LMWH) has a favorable pharmacokinetic profile which precludes the need for routine laboratory monitoring. However, certain patient populations, including those with extreme body weight (overweight or underweight), renal dysfunction, history of bleeding event while receiving LMWH, or previous failure of therapy, may benefit from therapeutic monitoring. Suboptimal drug monitoring of enoxaparin due to incorrect timing of anti-Xa levels, delayed blood sample draws, and/or lack of follow up once the anti-Xa level has resulted has been documented in the literature and may lead to toxicity or suboptimal efficacy (Hosp Pharm. 2017 Mar; 52(3): 214-220.). A retrospective chart review conducted at our institution in 2015 evaluated 100 adult patients who were prescribed LMWH and were ordered an anti-Xa level over a ten month period. In 36% of patients, there was no documented indication for therapeutic monitoring of the LMWH. The study also demonstrated that 35% of anti-Xa levels were drawn outside of the recommended 3 to 5 hour time frame after the previous LMWH dose, and follow up action to abnormal levels was only performed for 39% of patients. In October 2018, our institution implemented a pharmacist driven protocol for anti-Xa level monitoring, including restriction of ordering of anti-Xa levels by a pharmacist, and recommendations for dose adjustments in response to non-therapeutic levels. The purpose of this analysis was to evaluate the impact of a pharmacist driven anti-Xa level monitoring protocol on compliance with institutional guidelines for LMWH monitoring, including indication for drug monitoring, timing of levels, and follow up to abnormal anti-Xa levels.Methods:We conducted a retrospective chart review of adult patients who received therapeutic enoxaparin and were ordered for an anti-Xa level between October 17, 2017 and July 1, 2018. Pediatric patients (<18 years of age) and patients receiving prophylactic enoxaparin were excluded. Levels were assessed for each patient encounter in patients who had more than one hospital admission during the study period, however only the first anti-Xa level on each admission was evaluated. Data analyzed included patient demographics, enoxaparin dose and indication, ordering service, presence of a Hematology consult, indication for anti-Xa level monitoring, timing of the level after previous enoxaparin dose, timing of sample collection by nursing staff, appropriate number of doses prior to level, appropriateness of follow up action to abnormal levels, bleeding events, and recurrent thrombosis.Results:During the study period, a total of 109 anti-Xa levels were ordered for 102 patients who met inclusion criteria. The most common indication for enoxaparin therapy was for venous thromboembolism (81%), followed by atrial fibrillation (9%). The most common indication for assessment of anti-Xa levels were for body weight ≥150 kg and/or BMI ≥40 kg/m2 (28%), creatinine clearance <30 ml/min or renal replacement therapy (23%), and previous failure of anticoagulation (19%). Of the 109 anti-Xa levels assessed, 93% were ordered appropriately (3-5 hours post scheduled dose and after ≥3 doses of enoxaparin). Of the 97 total anti-Xa levels scheduled correctly, 87% were drawn at the appropriate time by nursing staff. Of the 57 levels that were not within the therapeutic range, 75% had a documented follow up facilitated by the pharmacist, which included a recommendation of follow up action.Conclusion:Appropriate monitoring of enoxaparin and correct timing of anti-Xa levels is crucial to facilitate proper clinical decision making and dose adjustments. Timely follow up to drug levels is also critical when the values are out of range, which may increase the risk of toxicity or decreased efficacy. The implementation of a pharmacist driven anti-Xa level protocol at our institution dramatically increased the number of correctly drawn anti-Xa levels, from 65% to 87% (p=0.00016). Follow up to non-therapeutic levels also increased significantly from 39% to 75% (p=0.0001) after implementation of the protocol. Further analysis and assessment of levels from a larger time period may be necessary to determine the clinical impact of implementation of a pharmacist driven anti-Xa monitoring protocol. DisclosuresNo relevant conflicts of interest to declare.

A guideline for the management of specific situations in polycythaemia vera and secondary erythrocytosis: A British Society for Haematology Guideline.

The previous BSH guideline for the management of erythrocytosis was published in 2005 (McMullin et al, 2005) and amended in 2007 (McMullin et al, 2007). Here, we re‐evaluate the literature formulate guidance on the management of specific situations encountered in polycythaemia vera (PV) and the management of the other types of secondary erythrocytosis. Recommendations for the diagnostic pathway of investigation of an erythrocytosis, risk stratification and management of PV are in the accompanying guideline (McMullin et al, 2018). We review evidence and outline guidance on management of acute thrombotic events and secondary prevention of thrombosis in PV. The unusual thrombotic events, splanchnic vein and cerebral vein thromboses are discussed and haemorrhage. The specific situations of surgery and pregnancy and guidance on management of pruritus are included. The evidence for the management of other causes of erythrocytosis, including idiopathic erythrocytosis, congenital erythrocytosis, hypoxic pulmonary disease and post‐transplant erythrocytosis, is reviewed and recommendations made.

Problematic issues surrounding deep vein treatment

Deep vein thrombosis (DVT) considered as a severe clinical problem. It caused by the formation of thrombi in deep veins, particularly in the lower limbs. Confirmation of DVT involving the use of Wells score, d-dimers examination and venous compression ultrasound. Anticoagulation proved to decrease mortality rate along with thrombus progression. However, despite major advances, clinician in daily care still poses various issues regarding optimal and best treatment for DVT patients. Anticoagulation (AC) is the backbone for the treatment during all phases of DVT treatment (acute, short term and long term) with the goals is to prevent thrombus progression and DVT complications. Unfractionated heparin (UFH) or low molecular weight heparin (LMWH) commonly used for in-hospitalized patient due to their short duration of action and anticipated antidote availability. Direct oral anticoagulants (DOACs) are also an option for the treatment of DVT patients. DOACs are preferred because they do not require monitoring and more practical in daily care. Furthermore, DVT in obese patients possess unique challenges to clinicians. Difficulty also exist in prescribe treatment for obese patient in term of appropriate dose of LMWH. The same also goes for cancer patients with thrombosis. It should be noted that all cancer-associated thrombosis (CATs) are different therefore, the optimal anticoagulant type, duration, and intensity for the treatment of CAT should probably be individualized. Travel-related DVT has been supported by scientific studies however, more aspects must be understood in order to present more accurate advice for travelers.

Feasibility and safety of delivering full-dose anticoagulation therapy in children treated according to Dana-Farber Cancer Institute acute lymphoblastic leukemia consortium therapy protocols.

The literature is void of an evidence-based anticoagulation therapy (ACT) management strategy in the context of thrombocytopenia. We examined the impact of thrombocytopenia on low-molecular-weight heparin (LMWH) dosing and incidence of bleeding in children with acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LL) who developed thromboembolism (TE) during therapy according to DFCI ALL protocols. Patient records from our tertiary care center were reviewed for demographics, details of diagnoses and therapy of ALL/LL and TE diagnoses, platelet counts during ACT, LMWH dosing, and bleeding episodes. Thirty-nine TEs were diagnosed in 33 patients [mean age 9 years (range, 2.5-18); 16 males and 31 with ALL] during the study period. A majority (85%) of patients were diagnosed with TE in the consolidation phase with mean time to TE 5.75 months from ALL/LL diagnosis. All patients received LMWH, and the median duration of ACT was 5.9 months (range, 1-11 months). Platelets were measured weekly. On 29 occasions, platelet nadir was<50×109 /L, and twice it was<20×109 /L. One (3%) patient had major bleeding episode while on ACT. Platelet count at the time of bleeding was 222×109 /L. Ninety-two procedures [83 lumbar punctures (LPs), 9 central venous line (CVL) insertion/revision] were completed without bleeding complications. Asparaginase was held temporarily with TE diagnosis in 48% of patients; most (88%) patients completed all scheduled doses as per protocol. Ability to administer full-dose LMWH, expected bleeding rate, and completion of asparaginase doses while on ACT suggest full-dose ACT is feasible and safe in children with ALL/LL who develop TE during DFCI ALL consortium therapy protocols.

Platelet cut-off for anticoagulant therapy in thrombocytopenic patients with blood cancer and venous thromboembolism: an expert consensus.

Management of venous thromboembolism (VTE) in patients with haematologic malignancies and thrombocytopenia is clinically challenging due to the related risks. No prospective studies or clinical trials have been carried out and, therefore, no solid evidence on this compelling issue is available. Given this, an expert panel endorsed by the Gruppo Italiano Malattie Ematologiche dell'Adulto Working Party on Thrombosis and Haemostasis was set up to produce a formal consensus, according to the RAND method, in order to issue clinical recommendations about the platelet (PLT) cut-off for safe administration of low molecular weight heparin (LMWH) in thrombocytopenic (PLT <100×109/L) adult patients with haematologic malignancies affected by acute (<1 month) or non-acute VTE. In acute VTE, the panel suggests safe anticoagulation with LMWH at therapeutic doses for PLT between ≥50<100×109/L and at 50% dose reduction for PLT ≥30<50×109/L. In acute VTE for PLT <30×109/L, the following interventions are recommended: positioning of an inferior vena cava (IVC) filter with prophylactic LMWH administration and platelet transfusion. In non-acute VTE, anticoagulation with LMWH at therapeutic doses for PLT between ≥50<100×109/L or over and at 50% dose reduction for PLT ≥30<50×109/L is considered appropriate. The discontinuation of full or reduced therapeutic dose of LMWH is recommended for PLT <30×109/L, both in acute and non-acute VTE. We suggest using dose-adjusted LMWH according to PLT to optimise anticoagulant treatment in patients at high bleeding risk.

Early low molecular weight heparin for postpartum hemorrhage in women with pre-eclampsia. Is it effective to prevent consumptive coagulopathy?

Background: Postpartum hemorrhage has been one of the most common cause of maternal morbidity and mortality. An association between pre-eclampsia (PE) and postpartum hemorrhage has been shown in previous studies. The aim of this study was to compare some characteristics of postpartum hemorrhage between women with and without PE.Methods: Some characteristics of postpartum hemorrhage were compared between women with (n = 34) and without PE (n = 34). Majority of the cases underwent low molecular heparin administration at postpartum eighth hour, however, in cases who did not give satisfactory responses to blood product transfusions, to block suspected disseminated intravascular coagulation (DIC) secondary to the PE induced vascular injury, low molecular weight heparins were started within 2 h of postpartum hemorrhage. Some characteristics of cases with and without PE and with and without early low molecular weight heparin administration were compared.Results: There were five cases who needed massive transfusions in group with PE, conversely, no case required massive transfusion in group without PE (p < .05), in these five cases prophylactic dose low molecular weight heparin was started within 2 h of postpartum period, these cases determined according to the changes in hematocrit, platelet, and fibrinogen levels with corresponding transfusions. Mean systolic and diastolic blood pressures were significantly higher in PE group. Highest lactate dehydrogenase (LDH) level during follow up was significantly higher in group with PE. Mean numbers of erythrocyte, thrombocyte, and fibrinogen transfusions were significantly higher in PE group. Duration of hospital stay was also significantly higher in group with PE.Conclusions: Postpartum hemorrhage in women with PE may be resistant to blood product transfusions due to DIC and vicious cycle can be blocked by early low molecular weight heparin administration.

Prevention of Deep Venous Thromboembolism.

The nature of many combat wounds puts patients at a high risk of developing deep venous thrombosis (DVT) and pulmonary embolism (PE), which fall under the broader disease category of venous thromboembolism (VTE). In addition to the hypercoagulable state induced by trauma, massive injuries to the extremities, prolonged immobility, and long fixed wing transport times to higher echelons of care are unique risk factors for venous thromboembolism in the combat-injured patient. These risk factors mandate aggressive prophylaxis for DVT and PE that can effectively be achieved by the use of lower extremity sequential compression devices and low dose unfractionated heparin or low molecular weight heparin. In addition, inferior vena cava filters are often used for PE prophylaxis when chemical DVT prophylaxis fails or is contraindicated. The following Department of Defense (DoD) Joint Trauma System (JTS) Clinical Practice Guideline (CPG) discusses the current recommendations for the prevention of DVT and PE including the use of inferior vena cava filters (IVCFs).