Therapeutic Anti-factor Xa Levels Research Articles

Evaluation of Initial Enoxaparin Dosing and Antifactor Xa Levels in Infants Admitted to the Neonatal Intensive Care Unit

Introduction: Infants are at risk for thrombotic conditions due to multiple risk factors such as congenital heart defects and sepsis. According to the American College of Chest Physicians (ACCP) 2012 guidelines, enoxaparin may be given for thrombotic conditions at a dose of 1.5 mg/kg/dose every 12 h for patients less than 2 months of age and 1 mg/kg/dose every 12 h for those older than 2 months. Several studies have reported that infants typically require a higher initial dose of enoxaparin to reach therapeutic antifactor Xa levels than what is currently recommended. Methods: This is a single-center retrospective case-control study of hospitalized infants less than 12 months of age who received treatment with enoxaparin while admitted to the neonatal intensive care unit (NICU) at a freestanding children’s hospital. The primary objective was the difference between the initial enoxaparin dose (mg/kg) compared to the enoxaparin dose in which the patient first achieved a therapeutic antifactor Xa level of 0.5–1.0 units/mL. Results: A total of 56 infants were included in this study. The median enoxaparin dose at initiation was 1.5 mg/kg/dose, and the median enoxaparin dose at the first therapeutic antifactor Xa level was 1.9 mg/kg/dose (z = −12.7, p < 0.0001). There was no correlation between gestational age and weight with the enoxaparin dose required to reach a therapeutic antifactor Xa level. Conclusion: Infants admitted to the NICU, specifically those less than 4 months of age, require higher initial enoxaparin dosing to reach therapeutic antifactor Xa levels than what is currently recommended.

Novel fondaparinux protocol for anticoagulation therapy in adults with renal failure and suspected heparin-induced thrombocytopenia: a retrospective review of institutional protocol

IntroductionThe literature recommends against the use of fondaparinux in patients with kidney failure and dialysis as it may, with repeated dosing, accumulate and put patients at risk of bleeding. The management of patients with thrombosis in the presence of heparin-induced thrombocytopenia HIT requires the introduction of an alternative anticoagulant like bivalirudin or argatroban. When these drugs are not available, fondaparinux, remains the only alternative. In similar scenarios, there are few studies addressing how to administer it. MethodsWe developed a protocol for fondaparinux in patients with renal failure where pharmacokinetic parameters are altered, and levels changed only after hemodialysis or in cases of residual renal activity. Patients received a full first dose except for high risk of bleeding. We targeted a peak anti-factor Xa activity level of 0.6–1.3 units/ml and changed the subsequent dose accordingly. Furthermore, we monitored the patients for signs of bleeding, a drop in hemoglobin level, or clinical signs of thrombosis. DiscussionWe described 10 patients with kidney failure and suspected HIT taking fondaparinux. All the patients achieved therapeutic anti-factor Xa activity levels. However, one developed new-onset venous thromboembolism (VTE) despite therapeutic anti-factor Xa levels. Another patient experienced a bleeding episode. We believe that these two patients developed complications due to their medical conditions rather than the use of fondaparinux.ConclusionFondaparinux can be safely used in kidney failure using our protocol. However, despite its safety profile and relative success, this case series was small. More robust studies need to be conducted prior to drawing conclusions.

Successful use of rivaroxaban achieving therapeutic anti-factor xa levels in a morbidly obese patient with acute intermediate-high risk pulmonary embolism.

Direct oral anticoagulants (DOACs) have become the standard of care for acute and long-term therapy for venous thromboembolism (VTE) due to their efficacy and safety profiles. The 2021 International Society on Thrombosis and Haemostasis guidelines recommend using standard DOAC dosages in patients with BMI >40 kg/m2 or weight >120 kg. Use of DOACs remains uncertain in morbidly obese patients with VTE, including acute PE. A morbidly obese woman in her 30s who presented with acute worsening of dyspnea was diagnosed with acute intermediate-high risk acute pulmonary embolism and concomitant proximal deep vein thrombosis, constituting a clinically challenging scenario for treating her with rivaroxaban. Standard doses of rivaroxaban for acute and extended phase treatment of venous thromboembolism in individuals with morbid obesity at BMI>70 kg/m2 may be effective, and safe.

Superior Mesenteric Artery Thrombosis While on Rivaroxaban in a Patient With COVID-19

A vaccinated 54 year old man who tested positive for SARS-CoV-2 11 days ago with respiratory symptoms, presented with abdominal pain. Despite being on 20 mg/day of rivaroxaban for atrial fibrillation and with therapeutic anti-factor Xa levels (26.47 ng/L), imaging revealed acute embolic occlusion (arrow) of the distal superior mesenteric and ileocolic artery on computed tomography angiography imaging (A). The patient had no symptoms of bowel ischaemia. He was treated conservatively with intravenous heparin for 14 days and converted to warfarin titrated to therapeutic levels. (B) Imaging at four weeks demonstrated recanalisation of the thrombosed arteries (arrow) with good distal opacification. The patient was symptom free and was feeding normally with no intestinal complications.Image 1

Evaluation of Unfractionated Heparin Dosing by Antifactor Xa During Targeted Temperature Management Post Cardiac Arrest.

To evaluate unfractionated heparin (UFH) dosing guided by antifactor Xa levels during targeted temperature management (TTM) post-cardiac arrest. Single-center, retrospective, observational study between January 1, 2014 and September 1, 2020. Patients initiated on TTM post-cardiac arrest and UFH were evaluated for inclusion. Patients included were ≥18 years of age and received weight-based UFH for ≥6 hours with 2 antifactor Xa levels drawn at target temperature. Excluded patients had no available temperature readings, received extracorporeal membrane oxygenation (ECMO) or factor Xa inhibitor (within 72 hours), or had hypertriglyceridemia or hyperbilirubinemia. The primary endpoint was to evaluate the proportion of patients that achieved a therapeutic antifactor Xa level between 0.3 and 0.7 IU/mL at steady state during TTM. Secondary endpoints included average UFH dose and average time to therapeutic antifactor Xa level at steady state; percent of first and total antifactor Xa levels subtherapeutic, therapeutic, and supratherapeutic during TTM. A total of 73 patients met inclusion criteria. Of these, 21 patients achieved steady-state therapeutic antifactor Xa levels during TTM. The average time and dose to steady-state therapeutic antifactor Xa levels were 8.1 ± 4.5 hours and 9.9 ± 3.2 units/kg/hour. Overall, 61.7% of first and 47.4% of all antifactor Xa levels were supratherapeutic during TTM. Three (4.1%) patients experienced a major bleeding event. Guideline recommended UFH dosing, 12 or 18 units/kg/hour, during TTM resulted in more supratherapeutic antifactor Xa levels. Reduction of UFH infusion dose to 10 units/kg/hour may be required during TTM to maintain therapeutic antifactor Xa levels.

Utilization practices of low molecular weight heparin in pediatric patients with acquired and congenital heart disease

BackgroundEnoxaparin is a commonly used anticoagulant for treatment of thrombosis in pediatric patients. Its use in pediatric cardiac patients has not been well described. We sought to examine the utilization trends, dosing, and safety of enoxaparin in pediatric cardiac patients. MethodsRetrospective study of pediatric cardiac patients treated with enoxaparin from 2011 to 2018. Starting and final doses of enoxaparin, number of dose adjustments, and time to therapeutic anti-factor Xa level were compared between age groups utilizing the Kruskal Wallis test with the Dunn test for pairwise comparisons. ResultsSeventy-one patients were treated with 77 courses of enoxaparin. Most enoxaparin courses were started on patients aged >12 months (40%) and for arterial thrombosis (22 patients, 29%). The most common cardiac diagnosis was hypoplastic left heart syndrome (12 patients, 17%). The mean final dose of enoxaparin was significantly different when comparing patients 0–3-month, 3–12 month, and >12 months (2.1 ± 0.5 mg/kg vs. 1.5 ± 0.4 mg/kg vs. 1.2 ± 1.4 mg/kg, respectively; p < 0.02). Patients 0–3 months and 3–12 months had significantly higher final to initial enoxaparin dose differences than the >12-month age group (0.4 ± 0.4 mg/kg vs. 0.4 ± 0.4 mg/kg vs. 0.1 ± 0.3 mg/kg, respectively; p < 0.01). All age groups needed 2–2.5 days to reach therapeutic anti-Xa levels. Patients aged 0–3 months had significantly more dose changes compared to those >12 months (2.2 ± 1.6 vs. 1.4 ± 1.4, p = 0.02). Antiplatelet therapy was used in 74% of courses. Adverse events were rare and had no relationship to antiplatelet use. ConclusionsEnoxaparin is an effective and safe anticoagulant in pediatric cardiac patients. Initial enoxaparin dosing should be increased from current recommended doses in patients between 3 and 12 months of age to achieve more timely therapeutic anticoagulation.

Enoxaparin Dose Requirements to Achieve Therapeutic Low-molecular-weight Heparin Anti-factor Xa Levels in Infants and Young Children.

Enoxaparin is commonly used to treat pediatric thrombosis. Several small retrospective studies have suggested that infants and young children require higher enoxaparin doses to achieve therapeutic anti-factor Xa levels compared with adults. This is a retrospective study of hospitalized children who received enoxaparin for the treatment of thrombosis at a free-standing children's hospital. The primary objective was to ascertain the enoxaparin dose required to achieve an anti-factor Xa level of 0.5 to 1.0 U/mL among 4 age groups in a large cohort of infants and young children between 60 days and 5 years of age. A total of 176 infants and children were evaluated. The majority of patients were less than 1 year of age (n=104). An inverse relationship between enoxaparin dose needed to achieve therapeutic anti-factor Xa levels and patient age was noted, particularly in the first year of life. Patients who were 60 days to less than 7 months at the time of enoxaparin initiation (n=73) required the highest mean dose among the age groups at 1.73 mg/kg subcutaneously every 12 hours (P<0.0001). Infants and young children require higher doses of enoxaparin to achieve therapeutic anti-factor Xa levels compared with adults.

Evaluation of Heparin Anti-Factor Xa Levels Following Antithrombin Supplementation in Pediatric Patients Supported With Extracorporeal Membrane Oxygenation.

Thrombotic events are potential complications in patients receiving extracorporeal membrane oxygenation (ECMO) necessitating the use of systemic anticoagulation with heparin. Heparin works by potentiating the effects of antithrombin (AT), which may be deficient in critically ill patients and can be replaced. The clinical benefits and risks of AT replacement in children on ECMO remain incompletely understood. This single-center, retrospective study reviewed 28 neonatal and pediatric patients supported on ECMO at a tertiary care hospital between April 1, 2013, and October 31, 2014, who received at least 1 dose of AT during their ECMO course. The primary outcome of the study was the change in anti-factor Xa levels after pooled human AT supplementation. Secondary outcomes included the percentage of anti-factor Xa levels within the therapeutic range surrounding AT administration; survival to decannulation; 30 days after cannulation and discharge; time to first circuit change; and incidence of bleeding and thrombotic events. A total of 78 doses of AT were administered during the study period. The mean increase in anti-factor Xa level following AT administration in patients without a ≥10% concurrent change in heparin was 0.075 ± 0.13 international units/mL. A greater percentage of anti-factor Xa levels were therapeutic for the 48 hours following AT administration (64.2% vs 38.6%). Survival and adverse events were similar to Extracorporeal Life Support Organization averages, with the exception of a higher incidence of intracranial hemorrhage. Patients experienced a small but significant increase in anti-factor Xa level and a greater percentage of therapeutic anti-factor Xa levels following AT supplementation.

Thromboprophylaxis in congenital nephrotic syndrome: 15-year experience from a national cohort

IntroductionCongenital nephrotic syndrome (CNS) is an ultra-rare disease associated with a pro-thrombotic state and venous thromboembolisms (VTE). There is very limited evidence evaluating thromboprophylaxis in patients with CNS. This study aimed to determine the doses and duration of treatment required to achieve adequate thromboprophylaxis in patients with CNS.MethodsFrom 2005 to 2018 children in Scotland with a confirmed genetic or histological diagnosis of CNS were included if commenced on thromboprophylaxis. The primary study endpoint was stable drug monitoring. Secondary outcomes included VTE or significant haemorrhage.ResultsEight patients were included; all initially were commenced on low-molecular weight heparin (enoxaparin). Four patients maintained therapeutic anti-Factor Xa levels (time 3–26 weeks, dose 3.2–5.07 mg/kg/day), and one patient developed a thrombosis (Anti-Factor Xa: 0.27 IU/ml). Four patients were subsequently treated with warfarin. Two patients maintained therapeutic INRs (time 6–11 weeks, dose 0.22–0.25 mg/kg/day), and one patient had two bleeding events (Bleed 1: INR 6, Bleed 2: INR 5.5).ConclusionsAchieving thromboprophylaxis in CNS is challenging. Similar numbers of patients achieved stable anticoagulation on warfarin and enoxaparin. Enoxaparin dosing was nearly double the recommended starting doses for secondary thromboprophylaxis. Bleeding events were all associated with supra-therapeutic anticoagulation.

Cirrhosis, Thrombosis, Finding FaXts about Doses: Dosing of Unfractionated Heparin for Venous Thromboembolism in Cirrhosis.

Background: Despite known disease-specific alterations to anti-factor Xa (AXA) levels, the physiological response of patients with cirrhosis to unfractionated heparin (UFH) infusions is not well established in clinical settings. Objective: The purpose of this study was to characterize the dosing and safety profile of UFH in patients with varying degrees of cirrhosis when treated for venous thromboembolism (VTE). Methods: This retrospective observational study was conducted at a single academic medical center in the United States. Patients with a diagnosis of cirrhosis who received UFH infusions for greater than 48 hours for treatment of VTE were included. Comparisons between heparin infusion rates, AXA levels, and safety outcomes based on severity of cirrhosis were made to define differences between those groups. Results: When compared by compensation status or by Child-Turcotte-Pugh (CTP) class, patients with more severe disease trended toward lower initial AXA levels on heparin initiation and higher heparin requirements to achieve therapeutic levels and were significantly less likely to achieve therapeutic levels than patients with less severe disease (P = 0.001 for compensation, P = 0.017 for CTP). Additionally, bleeding rates were higher in patients with more severe disease, without reaching statistical significance. Conclusion and Relevance: Patients with severe cirrhosis required higher doses of heparin to achieve the same therapeutic AXA levels, but also tended to have higher rates of bleeding compared with less severe cirrhosis. These results represent further evidence of changes in heparin response as cirrhosis severity increases and may suggest that current monitoring methods are suboptimal in this patient population.

Feasibility and safety of enoxaparin whole milligram dosing in premature and term neonates.

The objective of our study was to determine the feasibility and safety of enoxaparin whole milligram dosing in premature and term neonates, and to assess response to treatment. Retrospective study of neonates with thrombosis treated between January 2008 and December 2014. Nineteen premature and 21 term neonates were treated with whole milligram doses of enoxaparin. The mean starting and therapeutic enoxaparin doses were 1.72±0.17 and 1.86±0.17 mg kg(-1), respectively. Twenty-five (64%) reached therapeutic antifactor Xa (anti-Xa) levels with the starting dose, whereas 14 (36%) required dose adjustments. One neonate reached a supratherapeutic anti-Xa level (>1.0 IU ml(-1)) in the loading phase. No bleeding episodes occurred. The mean treatment duration was 12 weeks. Among 34 (85%) evaluable patients, 23 (68%) had a complete response, 9 (26%) partial and 2 (6%) had a stable thrombotic state. Whole milligram dosing of enoxaparin for thrombosis is feasible, safe and effective in premature and term neonates.

In brief

Prophylaxis for venous thromboembolism is routinely performed for all patients undergoing bariatric surgery. However, there is disagreement regarding the optimal dosing and duration of anticoagulant therapy. Furthermore, there is little data regarding the incidence of asymptomatic deep venous thrombosis (DVT) in this population. Our objective was to conduct a pilot randomized double blind study to evaluate the pharmacodynamic parameters of 2 different anticoagulation medications (enoxaparin and fondaparinux) administered to patients undergoing bariatric surgery.From July 2010 to August 2013, 198 consecutive bariatric surgery patients from an academic institution were randomized in a double blinded manner to receive either 40mg enoxaparin twice daily or 5mg fondaparinux sodium once daily. Antifactor Xa activity was measured on all patients in both study arms, 3 hours after the first dose (on the day of the operation), immediately before the second dose (postoperative day one), and 3 hours after the second dose. At the routine 2 week postoperative visit, patients underwent magnetic resonance venography (MRV) to detect DVT.The primary outcome was attainment of therapeutic antifactor Xa levels. The secondary outcome was DVT, as detected by MRV. Safety outcomes were perioperative bleeding, perioperative complications, and death.Of 198 patients randomized, 177 underwent MRV and 137 had interpretable antifactor Xa levels. Nearly half of the patients (47.4%) did not attain target prophylactic antifactor Xa levels. Adequate antifactor Xa levels were more common with fondaparinux (74.2%) than with enoxaparin (32.4%). Antifactor Xa levels were also associated with preoperative D-dimer level. 4 of the 175 patients who underwent MRV developed DVT, 2 in each arm of the study. No major adverse events occurred in either arm.Fondaparinux was much more likely to produce target prophylactic antifactor Xa levels than enoxaparin. Both regimens appear to be equally effective at reducing the risk of DVT. Further prospective studies are needed to determine the optimal DVT prophylaxis regimen in the bariatric surgical population.

The EFFORT trial: Preoperative enoxaparin versus postoperative fondaparinux for thromboprophylaxis in bariatric surgical patients: a randomized double-blind pilot trial

BackgroundProphylaxis for venous thromboembolism is routinely performed for all patients undergoing bariatric surgery. However, there is disagreement regarding the optimal dosing and duration of anticoagulant therapy. Furthermore, there is little data regarding the incidence of asymptomatic deep venous thrombosis (DVT) in this population. Our objective was to conduct a pilot randomized double blind study to evaluate the pharmacodynamic parameters of 2 different anticoagulation medications (enoxaparin and fondaparinux) administered to patients undergoing bariatric surgery. MethodsFrom July 2010 to August 2013, 198 consecutive bariatric surgery patients from an academic institution were randomized in a double blinded manner to receive either 40mg enoxaparin twice daily or 5mg fondaparinux sodium once daily. Antifactor Xa activity was measured on all patients in both study arms, 3 hours after the first dose (on the day of the operation), immediately before the second dose (postoperative day one), and 3 hours after the second dose. At the routine 2 week postoperative visit, patients underwent magnetic resonance venography (MRV) to detect DVT.The primary outcome was attainment of therapeutic antifactor Xa levels. The secondary outcome was DVT, as detected by MRV. Safety outcomes were perioperative bleeding, perioperative complications, and death. ResultsOf 198 patients randomized, 177 underwent MRV and 137 had interpretable antifactor Xa levels. Nearly half of the patients (47.4%) did not attain target prophylactic antifactor Xa levels. Adequate antifactor Xa levels were more common with fondaparinux (74.2%) than with enoxaparin (32.4%). Antifactor Xa levels were also associated with preoperative D-dimer level. 4 of the 175 patients who underwent MRV developed DVT, 2 in each arm of the study. No major adverse events occurred in either arm. ConclusionFondaparinux was much more likely to produce target prophylactic antifactor Xa levels than enoxaparin. Both regimens appear to be equally effective at reducing the risk of DVT. Further prospective studies are needed to determine the optimal DVT prophylaxis regimen in the bariatric surgical population.

(43) - Anti-factor Xa Levels Versus Activated Partial Thromboplastin Time for Monitoring Unfractionated Heparin in Patients with Continuous Flow Left Ventricular Assist Devices

Activated partial thromboplastin time (aPTT) is the gold standard for monitoring IV unfractionated heparin (UFH) therapy for anticoagulation. However, several biologic factors, including von Willebrand Factor (vWF) syndrome observed after implantation of CF-LVADs can influence the aPTT independent of the effects of UFH. Hypothesis: In patients with a CF-LVAD receiving UFH, simultaneous measurement of anti-factor Xa levels and aPTT will demonstrate discordant levels of aPTT despite therapeutic anti-factor Xa levels.

Effectiveness of Unfractionated Heparin in Normal Saline versus Dextrose for Achieving and Maintaining Therapeutic Anti-Factor Xa Levels in Patients with Non-ST-Elevation Acute Coronary Syndrome.

Unfractionated heparin (UFH) administered by IV infusion is effective in preventing myocardial infarction and death after non-ST-elevation acute coronary syndrome. At the authors' centre, preparations of UFH in 0.9% sodium chloride (normal saline; UFH-NS) were used during a shortage of commercially available UFH in dextrose 5% in water (UFH-D5W), the usual preparation. Anecdotal observations raised concerns about the effectiveness of the saline-based preparation in achieving minimally therapeutic anticoagulation. To compare the effectiveness of UFH-NS and UFH-D5W for achieving and maintaining therapeutic anti-factor Xa levels in patients with non-ST-elevation acute coronary syndrome. A retrospective cohort study was conducted with 2 groups of 100 consecutive patients who received either UFH-NS or UFH-D5W for a minimum of 24 h after non-ST-elevation acute coronary syndrome in accordance with a weight-based dosing nomogram. A minimally therapeutic level of anti-Xa (≥ 0.31 IU/mL) was achieved within 24 h for 92% of the patients receiving UFH-D5W and 67% of those receiving UFH-NS (absolute risk difference 25%, 95% confidence interval [CI] 13.4%-36.6%; p < 0.001). Infusion of UFH-NS was associated with lower probability of achieving minimally therapeutic anticoagulation (hazard ratio [HR] 2.30, 95% CI 1.68-3.15; p < 0.001) and maintaining therapeutic anticoagulation (HR 2.31, 95% CI 1.69-3.17; p < 0.001) relative to UFH-D5W. Significant differences in the numbers of patients with subtherapeutic and therapeutic anticoagulation, favouring UFH-D5W, were observed at each of the first, second, and third anti-Xa measurements (p < 0.05). Patients receiving UFH-NS required a greater median number of adjustments to the infusion rate during the first 48 h (1.0 v. 0.5 adjustment per day, p < 0.001). There was no difference between groups in terms of major reductions in hemoglobin. Infusion of UFH-NS was inferior to UFH-D5W for achieving and maintaining therapeutic anticoagulation in patients with non-ST-elevation acute coronary syndrome. Until further study, saline-based heparin infusions should be used with caution, and patients should be monitored closely to ensure timely achievement and maintenance of therapeutic anticoagulation.

New aspects on efficient anticoagulation and antiplatelet strategies in sheep

BackgroundAfter addressing fundamental questions in preclinical models in vitro or in small animals in vivo, the translation into large animal models has become a prerequisite before transferring new findings to human medicine. Especially in cardiovascular, orthopaedic and reconstructive surgery, the sheep is an important in vivo model for testing innovative therapies or medical devices prior to clinical application. For a wide variety of sheep model based research projects, an optimal anticoagulation and antiplatelet therapy is mandatory. However, no standardised scheme for this model has been developed so far. Thus the efficacy of antiplatelet (acetylsalicylic acid, clopidogrel, ticagrelor) and anticoagulant (sodium enoxaparin, dabigatran etexilate) strategies was evaluated through aggregometry, anti-factor Xa activity and plasma thrombin inhibitor levels in sheep of different ages.ResultsResponses to antiplatelet and anticoagulant drugs in different concentrations were studied in the sheep. First, a baseline for the measurement of platelet aggregation was assessed in 20 sheep. The effectiveness of 225 mg clopidogrel twice daily (bid) in 2/5 sheep and 150 mg bid in 3/5 lambs could be demonstrated, while clopidogrel and its metabolite carboxylic acid were detected in every plasma sample. High dose ticagrelor (375 mg bid) resulted in sufficient inhibition of platelet aggregation in 1/5 sheep, while acetylsalicylic acid did not show any antiplatelet effect. Therapeutic anti-factor Xa levels were achieved with age-dependent dosages of sodium enoxaparin (sheep 3 mg/kg bid, lambs 5 mg/kg bid). Administration of dabigatran etexilate resulted in plasma concentrations similar to human ranges in 2/5 sheep, despite receiving quadruple dosages (600 mg bid).ConclusionHigh dosages of clopidogrel inhibited platelet aggregation merely in a low number of sheep despite sufficient absorption. Ticagrelor and acetylsalicylic acid cannot be recommended for platelet inhibition in sheep. Efficient anticoagulation can be ensured using sodium enoxaparin rather than dabigatran etexilate in age-dependent dosages. The findings of this study significantly contribute to the improvement of a safe and reliable prophylaxis for thromboembolic events in sheep. Applying these results in future translational experimental studies may help to avoid early dropouts due to thromboembolic events and associated unnecessary high animal numbers.

Are low-molecular-weight heparins appropriately dosed in patients with CKD stage 3 to 5?

The aims of this study were to determine the serum antifactor Xa levels in patients with impaired glomerular filtration receiving low-molecular-weight heparins (LMWHs), monitor efficacy and complications during treatment, and determine the approach to dose adjustments of LMWH by using antifactor Xa levels in different levels of kidney dysfunction in a real world clinical practice. Patients with chronic kidney disease who had subcutaneous enoxaparin administration during hospitalization were included in this study. We obtained data on patient demographics, glomerular filtration rate, bleeding complications, and antifactor Xa levels. Patients were divided into four groups based on glomerular filtration rate (>60 ml/min, 30-59 ml/min, 15-29 ml/min, <15 ml/min). Target levels for antifactor Xa were accepted as 0.1-0.4 IU/ml for prophylactic use and 0.4-1.1 IU/ml for therapeutic use. There were 61 patients and 18 controls (40 women, 39 men, mean age 68 ± 12 years) available for analysis. Interpretation of antifactor Xa with regard to target levels has shown that levels were in therapeutic range in 33 patients (41.8%), subtherapeutic range in 38 patients (48.1%), and supratherapeutic range in eight patients (10.1%). Less than half of the patients at each level of kidney dysfunction had antifactor Xa levels within the therapeutic range. Three patients suffered major bleeding, two with supratherapeutic, and one with therapeutic antifactor Xa level. There were no complications of ineffective anticoagulation in patients with subtherapeutic levels. Inappropriate dosing of LMWH suggested by subtherapeutic and supratherapeutic antifactor Xa levels were very high in patients with different levels of kidney dysfunction.

Enoxaparin Dose Adjustment is Associated With Low Incidence of Venous Thromboembolic Events in Acute Burn Patients

Inadequate antifactor Xa levels have been documented in critically ill patients given prophylactic enoxaparin and may result in increased risk of venous thromboembolic (VTE) events. The objective of this study was to examine the impact of dose adjustment of enoxaparin and associated incidence of VTE in acute burn patients. All acute burn patients who were treated with prophylactic enoxaparin on a burn/trauma intensive care unit were prospectively followed. Patients with subtherapeutic antifactor Xa levels had enoxaparin doses increased as per unit protocol with the goal of obtaining a therapeutic antifactor Xa level. Eighty-four acute burn patients who were treated with enoxaparin had at least one appropriately obtained antifactor Xa level between June 2009 and October 2010. Initial antifactor Xa levels in 64 patients (76.2%) were below 0.2 U/mL, resulting in increased enoxaparin dose. Fifteen patients never achieved the target antifactor Xa level before enoxaparin was discontinued. Median final enoxaparin dose required to achieve therapeutic antifactor Xa levels was 40 mg every 12 hours (range, 20-70 mg). Using linear regression, final enoxaparin dose correlated with burn size (%total body surface area) and weight. No episodes of hemorrhage, thrombocytopenia, or heparin sensitivity were documented. Two patients (2.4%) had VTE complications despite adequate prophylaxis. Frequent occurrence of low antifactor Xa levels observed in this study demonstrated the inadequacy of standard dosing of enoxaparin for VTE prophylaxis in many patients with acute burns. Enoxaparin dose adjustment was associated with a low incidence of VTE events and no bleeding complications.

Evaluation of enoxaparin dosing requirements in infants and children

Increasing the starting dose of enoxaparin results in the early achievement of therapeutic anti-factor Xa levels in children receiving enoxaparin which is critical for effective therapy and the reduction of venipunctures. The aim of this study was: i) to determine the enoxaparin dose required to achieve therapeutic anti-factor Xa levels in infants and children, and ii) to establish whether increasing the starting dose of enoxaparin influenced the time required to reach the therapeutic range and the number of venipunctures required for dose-adjustment, and iii) the radiographic outcome of the thrombosis, where applicable. A retrospective chart review of children who received enoxaparin was carried out at the Stollery Children's Hospital, Edmonton, Alberta, Canada. Patients treated with standard-dose enoxaparin (1.5 mg/kg for children < or =3 months of age, 1.0 mg/kg for children > or =3 months of age), were compared with children who received a higher initial starting dose of enoxaparin (1.7 mg/kg for children > or =3 months of age, 1.2 mg/kg for children > or =3 months of age). Infants <3 months required an enoxaparin dose of 1.83 mg/kg, and those who received an increased initial enoxaparin dose resulted in faster attainment of therapeutic anti-factor Xa levels requiring significantly fewer venipunctures. Similarly, infants > or =3-12 months, 1-5 years, and 6-18 years, require enoxaparin 1.48 mg/kg, 1.23 mg/kg and 1.13 mg/kg, respectively, in order to achieve a therapeutic anti-factor Xa level. In conclusion, increasing the starting dose of enoxaparin may result in more rapid attainment of therapeutic range with fewer venipunctures, dose adjustments, and without an increase in adverse events.

Enoxaparin Use in the Neonatal Intensive Care Unit: Experience Over 8 Years

To evaluate the effectiveness and safety of enoxaparin therapy in a neonatal intensive care unit (NICU). Retrospective chart review. Level III NICU in a Canadian academic center. All neonates treated with enoxaparin while in the NICU between January 1, 1998, and June 1, 2006. Data abstracted included patient demographics, diagnosis of thrombosis and its progression, enoxaparin dosages with corresponding antifactor Xa levels, and adverse events. Sixteen neonates (four term, 12 preterm) were treated with enoxaparin at a mean +/- SD initial subcutaneous dose of 1.41 +/- 0.15 mg/kg every 12 hours. The target therapeutic range (antifactor Xa level 0.5-1.0 U/ml) was achieved by 12 infants at a mean +/- SD dose of 1.92 +/- 0.43 mg/kg every 12 hours, after a mean of 5.6 days (range 1-15 days). Preterm infants required a higher dose (per kilogram) compared with term infants to maintain therapeutic antifactor Xa levels (mean +/- SD 1.94 +/- 0.39 vs 1.65 +/- 0.14 mg/kg every 12 hrs, p<0.001). Enoxaparin doses were more strongly correlated to antifactor Xa levels in term infants (r(2)=0.51, p<0.001) compared with preterm infants (r(2)=0.20, p<0.001). Ten (71%) of 14 thromboembolic events resolved, either partially or completely, at a mean of 39 days (range 8-61 days) of enoxaparin therapy. Nine infants (56%) experienced minor local adverse effects at the site of the indwelling subcutaneous catheter (induration, bruises, hematomas, or leakage). Systemic adverse events that were possibly related to enoxaparin therapy included osteopenia (one infant), scleral hemorrhage (one), and minor gastrointestinal tract bleeding (three) found in gastric feeding tubes. No adverse effects were associated with antifactor Xa levels greater than 1.0 U/ml. Enoxaparin may be effective in the treatment of neonatal thrombosis. An initial dosage of 1.5 mg/kg every 12 hours is likely inadequate to obtain therapeutic antifactor Xa levels rapidly and differs for term and preterm neonates. Therapeutic levels in preterm infants may be more variable, and the pharmacokinetics of this drug in preterm infants requires further evaluation. Future studies in neonates should prospectively evaluate a higher starting dose of enoxaparin to document effectiveness, acceptance, compliance with treatment guidelines, and adverse effects.