Continuous Infusion Of Unfractionated Heparin Research Articles

To Compare the Effectiveness of Low-Molecular-Weight Heparin and Unfractionated Heparin in Reducing Lower Limb Girth in Deep Vein Thrombosis.

Treating deep vein thrombosis (DVT) using a once-daily dose of enoxaparin offers greater convenience and the possibility of home-based care for certain patients, as opposed to a continuous infusion of unfractionated heparin (UFH). The study aimed to determine the most cost-effective thromboprophylaxis between low-molecular-weight heparin (LMWH) and UFHfor hospitalized patients. After obtaining clearance from the institutional ethical committee, the study was conducted in the Departmentof General Surgery, Sri Devaraj Urs Medical College, over a period of six months. Informed consent was obtained from all 46 patients included in this study. The participants were divided into two groups: group A received LMWHand group B received UFH. The mean age in group A was 59.8 + 10.6 years and in group B was 54.9 + 12.3 years. There was no significant difference in the girth of the lower limb between the groups during the follow-up period (p > 0.05). In group A, there was a highly significant reduction in lower limb girth from day one to day five (p < 0.0001), day five to day 10 (p < 0.0001), and day one to day 10 (p < 0.0001).In group B, there was no significant reduction from day one to day five (p = 0.06), but there was a significant reduction from day five to day 10 (p = 0.001) and day one to day 10 (p = 0.001). Treatment with LMWH as an anticoagulant significantly reduced the lower extremity girth and thrombus thickness in cases of DVT when compared to UFH.

P209 HUGE AND OCCLUDING LAA THROMBUS DISSOLUTION IN A CASE OF SEVERE TACHI–CARDIOMYOPATHY

Abstract A 62–year–old man was admitted to our emergency department for worsening nocturnal dyspnea and orthopnea for 15 days. Finding of Acute Pulmonary Edema in a setting of non datable high ventricular response atrial fibrillation (AF) associated with severe LV dysfunction. NT–proBNP 8.252 pg/ml. ECG: atrial fibrillation with high ventricular response (120/bpm). TTE: Severe left ventricular systolic disfunction (EF 20%). TOE/3D TOE: evidence of voluminous oval–shaped thrombotic formation (10 x 17 mm) protruding in LA and completely occluding the left atrial appendage (LAA). LA thrombosis in patients with AF is relatively rare and represents a contraindication to rhythm control strategies. Once an LAA thrombus is identified, effective anticoagulation is recommended for at least three weeks or until LAA thrombus resolution is detected. Available evidence on left atrial thrombus dissolution largely refers to the use of vitamin K antagonist oral anticoagulant (VKAs), but their effectiveness may be influenced by variability in the level of anticoagulant activity obtained, wich may be suboptimal. In a recent prospective observational study has been evaluated the effectiveness of Edoxaban for the resolution of LA thrombosis in 25 patients with AF: it has been demonstrated a complete thrombus resolution in 56% of patients at 4 weeks, similar to studies using VKAs and the other NOACs. Use of NOACs in this setting represents a great field of interest for the near future. In our experience, indeed, after confirmed diagnosis of LAA thrombus, we started anticoagulant therapy with warfarin (currently the first choice), however due to poor INR control, we switched to continuous infusion of unfractionated heparin (UFH), wich represents, in a hospital setting, a safe and effective method for thrombus dissolution, allowing continuous monitoring of efficacy and a rapid cessation of effect in case of major bleeding. In this way we obtained complete thrombus dissolution in about 3 weeks. At the meantime we initiate a rate control therapy, an optimized treatment for HFrEF and intravenous diuretics. Our experience highlights the need of great ductility in the choice of anticoagulant therapy in patients with evidence of voluminous LAA thrombus, monitoring treatment’s efficacy parameters and being ready to change strategy if necessary and it reminds that auricular thrombosis is often inserted in a wider picture of heart disease wich requires multiple other specifics treatments.

COVID-19 Complicated with Arterial Thrombosis Resulting Acute Limb Ischemia: A Case Report from Bangladesh

COVID-19(Corona virus disease 2019), which starts from Wuhan, China on December, 2019 spread rapidly to different countries of the world including Bangladesh. It affects huge impact on health care system. It’s a new disease with multisystem involvement. Physicians are experiencing new presentation of different cases and rare complication including arterial thrombosis. Few data is available regarding arterial thrombosis in SARS-CoV-2 infected patients. We are currently fighting with a 60 year old lady suffering from COVID-19 pneumonia with other co-morbidities developed severe arterial occlusion of right leg despite of taking anti platelet for long time for another cause. Patient developed irreversible right lower limb ischemia not improving with continuous infusion of unfractionated heparin followed by severe pulmonary embolism. So further study and recommendations will need to evaluate the cases and treatment in COVID-19 Patients with rare presentation.&#x0D; Bangladesh Journal of Infectious Diseases, October 2020;7(suppl_2):S50-S56

Continuous Infusion Low-Dose Unfractionated Heparin for the Management of Hypercoagulability Associated With COVID-19

Introduction: The Coronavirus Disease 2019 (COVID-19) is associated with severe hypercoagulability. There is currently limited evidence supporting the routine use of therapeutic anticoagulation in the setting of COVID-19. Objectives: The primary objective was to compare the incidence of thromboembolic events in adult patients with COVID-19 treated with an unfractionated heparin (UFH) infusion versus prophylactic dose anticoagulation. Secondary objectives included exploration of the efficacy and safety of an UFH infusion through the evaluation of organ function and incidence of minor and major bleeding. Methods: Retrospective observational cohort study with propensity score matching of COVID-19 patients who received an UFH infusion targeting an aPTT between 40 and 60 seconds. Results: Fifty-six patients were included in this study. There was no difference in the composite of thromboembolic events comprised of venous thromboembolism, arterial thrombosis, and catheter-related thrombosis between the UFH and control group (17.9% vs. 3.6%, P = 0.19). There was a significant increase in median D-dimer concentrations from day 1 to day 7 in the control group (475 ng/mL [291-999] vs. 10820 ng/mL [606-21033], P = 0.04). Patients treated with UFH had a higher incidence of minor bleeding (35.7% vs. 0%, P < 0.005) and required more units of packed red blood cell transfusion (0.8 units ± 1.6 vs. 0 units, P = 0.01). Conclusion: Continuous infusion of UFH for patients with COVID-19 infection did not decrease the overall incidence of thromboembolic complications. UFH was associated with stabilization of D-dimer concentrations and increased rates of minor bleeding and transfusions.

Transitioning hospitalized patients from rivaroxaban or apixaban to a continuous unfractionated heparin infusion: A retrospective review.

To determine a patient's clinical course based on the use of an activated partial thromboplastin time (aPTT) or heparin anti-Xa assay when transitioning from rivaroxaban or apixaban to an unfractionated heparin infusion. A retrospective chart review was conducted to investigate how unfractionated heparin infusions were managed at a tertiary care hospital in the setting of recent apixaban or rivaroxaban administration. Patients were separated into 2 cohorts based on the chosen heparin infusion monitoring assay: heparin anti-Xa or aPTT. The primary composite outcome was total number of bleeding and thrombotic events; the secondary composite outcome was average incidence of heparin infusion holds and rate changes per patient. Data were collected from 76 patients (heparin anti-Xa = 69, aPTT = 7). Due to the limited number of patients within the aPTT cohort, this data was excluded from the analysis, and heparin anti-Xa descriptive statistics were reported without statistical comparisons. In the heparin anti-Xa group, a total of 10 bleeds and 1 thrombus were discovered. Additionally, the average number of infusion holds and rate changes was 0.841 and 2.65 times per patient, respectively, for those patients monitored via heparin anti-Xa assay. In the presence of a recently administered oral anti-Xa anticoagulant, more down-titrations occurred in the initial 6 hours of the heparin infusion when measuring anti-Xa activity, and most up-titrations occurred after 36 hours. Baseline heparin anti-Xa activity may be a useful tool to identify patients with residual plasma concentrations of apixaban and rivaroxaban to help better individualize heparin therapy.

Unfractionated heparin displaces sFlt-1 from the placental extracellular matrix

Soluble vascular endothelial growth factor receptor-1 (sFlt-1) is an anti-angiogenic protein which is secreted by numerous cell types and acts as a decoy receptor for the angiogenic protein vascular endothelial growth factor (VEGF). Despite its physiologic importance in maintaining angiogenic balance, excess sFlt-1 levels are associated with the pathogenesis of many diseases, especially those with angiogenic imbalance, endothelial dysfunction, and hypertension. Although sFlt-1 is a soluble protein, it contains a binding site for the extracellular matrix component heparan sulfate. This allows cells to retain and localize sFlt-1 in order to prevent excessive VEGF signaling. During pregnancy, placental syncytiotrophoblasts develop a large extracellular matrix which contains significant amounts of heparan sulfate. Consequently, the placenta becomes a potential storage site for large amounts of sFlt-1 bound to extracellular heparan sulfate. Additionally, it should be noted that sFlt-1 can bind to the anticoagulant unfractionated heparin due to its molecular mimicry to heparan sulfate. However, it remains unknown whether unfractionated heparin can compete with heparan sulfate for binding of localized sFlt-1. In this study, we hypothesized that administration of unfractionated heparin would displace and solubilize placental extracellular matrix(ECM)-bound sFlt-1. If unfractionated heparin can displace this large reservoir of sFlt-1 in the placenta and mobilized it into the maternal circulation, we should be able to observe its effects on maternal angiogenic balance and blood pressure. To test this hypothesis, we utilized in vitro, ex vivo, and in vivo methods. Using the BeWo placental trophoblast cell line, we observed increased sFlt-1 in the media of cells treated with unfractionated heparin compared to controls. The increase in media sFlt-1 was found in conjunction with decreased localized cellular Flt (sFlt-1 and Flt-1) as measured by total cell fluorescence. Similar results were observed using ex vivo placental villous explants treated with unfractionated heparin. Real-time quantitative PCR of the explants showed no change in sFlt-1 or heparanase-1 mRNA expression, eliminating increased production and enzymatic cleavage of heparan sulfate as causes for sFlt-1 media increase. Timed-pregnant rats given a continuous infusion of unfractionated heparin exhibited an increased mean arterial pressure as well as decreased bioavailable VEGF compared to vehicle-treated animals. These data demonstrate that chronic unfractionated heparin treatment is able to displace matrix-bound sFlt-1 into the maternal circulation to such a degree that mean arterial pressure is significantly affected. Here we have shown that the placental ECM is a storage site for large quantities of sFlt-1, and that it should be carefully considered in future studies concerning angiogenic balance in pregnancy.

Femoral Artery Thrombosis in a Very Low Birth Weight Preterm Newborn

Abstract Tromboses are considered to be rare disorders in the pediatric population. However, they occur more frequently during the neonatal period. Potential risk factors for thrombosis onset include frequent use of peripheral, umbilical or central venous / arterial catheters, inflammation, disseminated intravascular coagulation, liver disorders, hypovolemia, asphyxia, congenital heart disease, polycythemia and dehydration. On the seventh day of life in male premature infant born in 29th / 30th gestation week, we noticed an increased level of inflammatory parameters. The patient’s right leg was edematous and cold with immeasurable pulse and pressure over the femoral artery, mottled skin and no spontaneous mobility. In the following days, edema becomes generalized and abdominal meteorism with bile vomiting appeared. Vascular surgeon established a diagnosis of the acute femoral artery stenosis (CW Doppler). We initiated continuous infusion of unfractionated heparin, but due to the development of hemorrhagic syndrome, next day we replaced it with low molecular weight heparin. The hemorrhagic disease was treated with tranexamic acid, fresh frozen plasma and concentrated platelets of the corresponding blood group. Signs of recirculation were registered with a palpable femoral pulse. CW Doppler confirmed complete recovery. In spite of the fact that antithrombotic therapy can cause numerous complications, it should be considered in vital indications.

Delayed prophylaxis with unfractionated heparin increases the risk of venous thromboembolic events in patients with moderate to severe traumatic brain injury: a retrospective analysis.

Venous thromboembolism (VTE) is a recognized complication in patients with traumatic brain injury (TBI) and is associated with increased morbidity and mortality. Currently, no standard exists for optimal timing or a pharmacological agent for VTE prophylaxis (pharmacological thromboprophylaxis - PTP) in patients with TBI. PTP is often delayed out of fear of causing extension of intracranial hemorrhage (ICH). The purpose of this study was to report the frequency of VTE and ICH progression after initiation of PTP with a continuous infusion of unfractionated heparin in patients with moderate to severe TBI, and to identify risk factors associated with development of VTE. In this single-center retrospective study, patients with moderate to severe TBI admitted to the ICU of a Swiss Level I Trauma Center over a three-year period were analyzed. In 23 (13%) of the 177 patients included in the study a VTE episode occurred during the hospital stay. ICH progression after initiation of PTP occurred in 7 (4%) patients. In a multivariable logistic regression model, only the timing of initiation of PTP was identified as an independent predictor of VTE. In this study population, the risk of developing VTE increased with the delay of initiation of a pharmacological VTE prophylaxis, while ICH progression after initiation of PTP was a rare event.

Activated Clotting Time (ACT) for Monitoring of Low-Dose Heparin: Performance Characteristics in Healthy Adults and Critically Ill Patients.

Dose adjustment of unfractionated heparin (UFH) anticoagulation is an important factor to reduce hemorrhagic events. High doses of heparin can be monitored by Activated Clotting Time (ACT). Because of limited information about the monitoring of low-dose heparin we assessed monitoring by ACT, aPTT and anti-Xa. Blood samples from healthy volunteers (n = 54) were treated ex vivo with increasing UFH doses (0-0.4 IU/ml). Samples from ICU-patients (n = 60), were drawn during continuous UFH infusion. Simultaneous ACT measurements were performed using iSTAT and Hemochron. In UFH treated blood, iSTAT and Hemochron showed a significant change of ACT at ≥0.075 IU/ml and ≥0.1 IU/ml UFH, respectively. In ICU-patients no relationship between ACT and either UFH dose, aPTT and anti-Xa was observed. Hemochron was affected by antithrombin and platelet count. iSTAT was sensitive to CRP and hematocrit. A moderate correlation was identified between UFH dose and aPTT (R2 = 0.196) or anti-Xa (R2 = 0.162). In heparin-spiked blood, ACT is sensitive to heparin at levels of ≥0.1 IU/ml heparin. In ICU-patients, ACT did not correlate with UFH dose or other established methods. Both systems were differently influenced by certain parameters.

The Dilemma of Resuming Antithrombotic Therapy After Intracranial Hemorrhage in Patients With Left Ventricular Assist Devices.

Antithrombotic therapy is administered after left ventricular assist device (LVAD) implantation to prevent thromboembolic events. Intracranial hemorrhage (ICH) is a life-threatening adverse event requiring immediate discontinuation of antithrombotics. We investigated the timing of antithrombotic resumption after ICH in patients with LVADs and the association between timing and risk of recurrent hemorrhage and thrombotic events. We performed a multicenter, retrospective analysis of patients with ICH occurrence during LVAD antithrombotic regimen with subsequent resumption of antithrombotics from January 1, 2010, to December 31, 2017. Covariates included age, international normalized ratio, antithrombotic dosing, timing of resumption, modified Rankin score, and subsequent hemorrhagic and thrombotic events within 1year post-ICH. Patients who did not resume anticoagulation were excluded. Of 673 patients with LVADs, 85 (12.6%) developed ICH while being treated with antithrombotics. Forty-three were excluded due to death prior to resumption and one due to lack of resumption. The remaining 41 patients were on antithrombotics with a median (interquartile range [IQR]) international normalized ratio at ICH onset of 2.6 (1.8-3.6). Aspirin and warfarin were resumed at a median (IQR) of 5.5 (1.3-8.8) and 6.5 (4.0-15.5) days post-ICH, respectively. A continuous unfractionated heparin infusion was initiated in 16 (39.0%) patients at a median (IQR) of 2.5 (1.0-7.8) days post-ICH. During the 1-year follow-up after anticoagulation resumption, 11 (26.8%) patients suffered secondary hemorrhages and two (4.9%) suffered secondary thrombotic events. Using Kaplan-Meier method and log-rank test, we compared all patients who resumed anticoagulation by 6days post-ICH to those who resumed after 6days. There was no difference in freedom from secondary hemorrhagic event between the two groups (P = 0.75). Despite timing of resumption of antithrombotic therapy after ICH, recurrent hemorrhagic events can be expected in one-quarter of these patients over the subsequent year.

Evaluation of Almitrine Infusion During Veno-Venous Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome in Adults.

This single-center case series investigated the effect of almitrine infusion on PaO2/fraction of inspired oxygen (FIO2) in 25 patients on veno-venous extracorporeal membrane oxygenation for severe acute respiratory distress syndrome. A positive trial was defined as an increase of PaO2/FIO2 ratio ≥20%. Thirty-two trials were performed. Twenty (62.5%, 95% confidence interval, 37.5%-75%) trials in 18 patients were positive, with a median PaO2/FIO2 ratio increase of 35% (25%-43%). A focal acute respiratory distress syndrome and inhaled nitric oxide therapy were more frequent in patients with a positive response to almitrine. We observed no complications of almitrine use.

The use of activated partial thromboplastin time versus antifactor Xa assay in monitoring continuous unfractionated heparin infusion therapy in obstetric intensive care unit

BackgroundUnfractionated heparin (UFH) infusion therapy needs accurate tight control to prevent overanticoagulation that may result in hemorrhagic complications and also to prevent sub therapeutic level that may result in thrombotic complications. The aim of this study was to compare the most popular monitoring tool activated aPTT versus antifactor Xa to reach accurate monitor to UFH therapy in critically ill pregnant females.ResultsTime to reach therapeutic level as well as total heparin dose required to reach this therapeutic level were much lower in the anti-Xa group when compared to aPTT group.ConclusionThe use of anti-Xa-based protocol to monitor UFH infusion therapy resulted in better therapeutic control as it resulted in earlier achievement of therapeutic level and lower heparin dose requitments.

METHYLENETETRAHYDROFOLATE REDUCTASE POLYMORPHISM AND PREMATURE CORONARY ARTERY DISEASE

SESSION TITLE: Cardiovascular Disease 1 SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/09/2018 01:15 PM - 02:15 PM INTRODUCTION: Methylenetetrahydrofolate reductase (MTHFR) catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a co-substrate for homocysteine remethylation to methionine. Its deficiency leads to increased homocysteine levels. Elevated serum levels of homocysteine have been associated with premature coronary artery disease (CAD). we present a case of recurrent acute coronary syndrome in patient with heterozygote mutation for methylenetetrahydrofolate reductase (MTHFR) with normal homocysteine level. CASE PRESENTATION: A 23 year-old man with history of MTHFR polymorphism and anterior wall ST segment elevation myocardial infarction requiring drug eluting stent (DES) in the left anterior descending artery (LAD) presented to the emergency department with substernal chest pain, T wave inversions in inferior leads on his ECG and elevated troponin levels. Coronary angiography demonstrated an acute occlusion of the proximal right coronary artery (RCA) and a chronic total occlusion of the proximal LAD with collaterals from the circumflex territory. Aspiration thrombectomy of the RCA lesion was partially successful and required continuous infusion of unfractionated heparin and tirofiban for 48 hours in addition to aspirin and ticagrelor. He underwent a successful deployment of 3 DES to his RCA. His left ventriculogram showed a mildly reduced left ventricular ejection fraction of 45 % with hypokinesis of the basal inferior wall segment. DISCUSSION: Hypercoagulability workup was unrevealing. Homocysteine levels were normal at the time of his first myocardial infarction two years prior. Repeat homocysteine level was 11.7 mg/dl (n <11.2mg/dl). His total cholesterol was 153mg/dl, LDL 80mg/dl, Apo lipoprotein B was 67 (n 52-109mg/dl), Lp(a) <10(n <75nmol/L). He was then discharge on folic acid. He was brought back to the cardiac catheterization laboratory a month later to reassess the LAD lesion but the angiogram showed complete re-occlusion of RCA. The patient was referred for coronary artery bypass surgery. CONCLUSIONS: This case demonstrates the association of MTHFR polymorphism with premature CAD and myocardial infarction despite normal homocysteine levels. Screening for MTHFR polymorphisms in addition to homocysteine levels should be considered for patients presenting with premature CAD and a normal lipid profile. Aggressive risk reduction with lifestyle modification, guideline-driven medical therapy and folic acid might be necessary for secondary cardiovascular disease prevention until more specific therapeutic options are available for this subgroup of patients. Reference #1: Frosst P, Blom HJ, Milos R, et al. A candidate genetic risk factor for vasculardisease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet.1995; 10: 111–113 Reference #3: DISCLOSURES: No relevant relationships by Corina Iorgoveanu, source=Web Response No relevant relationships by Ahmed Zaghloul, source=Web Response

Cost-Effectiveness Analysis of Treatment Acute Deep Vein Thrombosis in Clinic of Vascular Surgery Sarajevo

AIM:To compare hospital costs of acute deep vein thrombosis (ADVT) treatment in two periods of time. Evidence of repercussions on reducing costs during successful treatment. Attention was given to the necessity, costs and effectiveness of diagnostic procedures, treatment and complications.METHODS:A retrospective analysis of data obtained from patients medical history in a period from 2000 to 2016. Model management and safe practice of ADVT care consisted of clinical examination, laboratory, colour Doppler and invasive diagnostics. In a treatment was used continuous infusion un-fractionated heparin for 40 patients from 2000th till 2006th and low molecular weight heparin for 40 patients from 2006th till 2016th. All patients were converted to oral anticoagulants.RESULTS:When we look at the overall picture of improving the management model, safe practices and economic rationalization, we conclude that we offer better health service for the patients with ADVT at the moment, which relies on proven medical treatment trends. While we do not forget responsibility towards a society of which depends on treatment funding.CONCLUSION:The implementation of a conceptually new model of management of ADVT did not contribute rise of the desired outcomes, but it justified the positive economic viability of introduced changes at the Clinic of Vascular surgery than the previous concept.

Population pharmacokinetics of human antithrombin concentrate in paediatric patients.

Antithrombin is increasingly used in paediatric patients, yet there are few age-specific pharmacokinetic data to guide dosing. We aimed to describe the pharmacokinetic profile of human (plasma-derived) antithrombin concentrate in paediatric patients. A 5-year retrospective review was performed of patients <19years of age admitted to our institution who received antithrombin concentrate, were not on mechanical circulatory support and had baseline (predose) and postdose plasma antithrombin activity levels available for analysis. Demographic and laboratory variables, antithrombin dosing information and data on the use of continuous infusion unfractionated heparin were collected. Population pharmacokinetic analysis was performed with bootstrap analysis. The model developed was tested against a validation dataset from a cohort of similar patients, and a predictive value was calculated. A total 184 patients met the study criteria {46.7% male, median age [years] 0.35 [interquartile range (IQR) 0.07-3.9]}. A median of two antithrombin doses (IQR 1-4) were given to patients (at a dose of 46.3 ± 13.6units kg-1 ), with median of three (IQR 2-7) postdose levels per patient. Continuous infusion unfractionated heparin was administered in 87.5% of patients, at a mean dose of 34.1 ± 22.7units kg-1 h-1 . A one-compartment exponential error model best fit the data, and significant covariates included allometrically scaled weight on clearance and volume of distribution, unfractionated heparin dose on clearance, and baseline antithrombin activity level on volume of distribution. The model resulted in a median -1.75% prediction error (IQR -11.75% to 6.5%) when applied to the validation dataset (n = 30). Antithrombin pharmacokinetics are significantly influenced by the concurrent use of unfractionated heparin and baseline antithrombin activity.

Circuit life span of continuous renal replacement therapy in critically ill patients with or without conventional anticoa-gulation: an observational prospective study

The aim of this study was to describe the efficacy, security and viability of an anticoagulation system with continuous infusion of unfractionated heparin (UFH) versus one without any type of anticoagulant using 0.9% physiological saline washings, in critically ill patients with continuous renal replacement therapy (CRRT) and different risks of bleeding. From October 2013 to April 2015 we conducted an observational prospective study in the intensive care unit (ICU). Sixty-one patients with acute kidney injury (AKI) and requiring CRRT were included, with 122 filters. Patients and filters were divided in two groups: anticoagulated (AC) and not anticoagulated (No AC). The main outcome measure was filter life span. Different analytical parameters were also collected at the beginning of treatment and at the moment of circuit coagulation Results. The number of patients was similar in both groups. We did not find statistically significant differences between the two groups in filter life span (30.5 hours AC vs 34.9 hours No AC). Patients with increased morbidity (severe thrombocytopenia, coagulopathy, etc.) were included in the group that did not received anticoagulation but saline flushes. CRRT without anticoagulation with saline flushes is a viable, safe and effective strategy in critically ill patients with high risk of bleeding. This approach achieves a circuit life span similar to that observed in anticoagulated patients with UFH; avoiding the risks and costs associated with anticoagulation.

Comparison of Time to Therapeutic aPTT in Patients Who Received Continuous Unfractionated Heparin After Implementation of Pharmacy-wide Intervention Alerts.

Background: For patients on continuous IV unfractionated heparin (UFH), failing to achieve a therapeutic aPTT by 24 hours can be associated with increased morbidity. A pharmacy clinical surveillance system (PCSS) subtherapeutic aPTT alert was implemented at our institution to improve achievement of therapeutic aPTT goals by 24 hours. Objective: The primary objective was the time to achieve the minimum goal aPTT before and after the alert implementation. The secondary objectives were to examine the percentage of patients who achieved the minimum goal aPTT by 24 hours and the number of dose changes to achieve the minimum goal aPTT. Methods: A single-center retrospective study was conducted to include all adult inpatients receiving a continuous UFH infusion during a 3-month period prior to the implementation of a subtherapeutic aPTT alert and a 3-month period after implementation. Results: 317 patients were included in the analysis. The average time to achieve the minimum goal aPTT was 21.8 hours prior to alert implementation and 15.4 hours after implementation (p = .002). The percent of patients who achieved the minimum goal aPTT by 24 hours was 65.7% prior to alert implementation and 82.4% after implementation (p = .035). The average number of dose changes necessary to achieve aPTT value to the minimum goal aPTT prior to alert implementation was 1.67 and 1. 98 after implementation (p = .68). Conclusion: This analysis showed that implementation of a PCSS subtherapeutic aPTT alert for patients on continuous UFH infusions may ensure patients reach goal aPTT faster and facilitate a higher percent of patients who achieve the minimum goal aPTT by 24 hours.

Prevalence of "Flat-Line" Thromboelastography During Extracorporeal Membrane Oxygenation for Respiratory Failure in Adults.

We evaluated the prevalence of a thromboelastography reaction time (R time) >90 min ("flat-line") reversible with heparinase during extracorporeal membrane oxygenation (ECMO). We evaluated the association between "flat-line" thromboelastography, other coagulation tests, and risk of bleeding during ECMO. Thirty-two consecutive patients on ECMO were included. Anticoagulation was provided by continuous infusion of unfractionated heparin to maintain an activated partial thromboplastin time (aPTT) ratio between 1.5 and 2.0. Activated clotting times (ACTs) thromboelastography without and with heparinase were measured. Occurrence of bleeding was recorded. Median heparin infusion rate was 16 (12-20) IU/kg/h, aPTT ratio was 1.67 (1.48-1.96), and ACT was 173 (161-184) sec. One hundred forty-five (46%) of 316 paired thromboelastography samples were "flat lines" all reversed with heparinase. Patients with "flat-line" thromboelastography received more heparin (p = 0.001) but had similar platelet count (p = 0.164) and fibrinogen level (p = 0.952) than those without. Activated partial thromboplastin time, ACT, and R time without heparinase weakly correlated between each other (Spearman correlation ≤0.36) with poor agreement (Cohen's κ ≤0.10). Major bleeding occurred in seven (22%) patients. Bleeding during ECMO was not predicted by any of the used test. In conclusion, adjusting heparin infusion to maintain aPTT ratio between 1.5 and 2.0 frequently resulted in "flat-line" thromboelastography.

Post-dilution hemodiafiltration with a heparin-grafted polyacrylonitrile membrane.

The aim of this multicenter, prospective study was to explore the possibility of carrying out routine sessions of post-dilution hemodiafiltration with a polyacrylonitrile membrane grafted with heparin (HeprAN) and reduced anticoagulation. Forty-four patients from eight centers were included in the study and treated by means of post-dilution on-line hemodiafiltration with automatic control of TMP, according to three different modalities tested consecutively: phase 1, polyethersulfone filter primed with heparinized saline and anticoagulated with continuous infusion of unfractionated heparin 1000/h; phase 2, HeprAN membrane filter primed with saline without heparin. Anticoagulation: a 1000-unit bolus of unfractionated heparin at the start of session followed by a second one at the end of the second dialysis hour; phase 3, same filter and priming procedure as in phase 2; anticoagulation with nadroparin calcium at the beginning of treatment. Partial or massive clotting of the dialyzer occurred in less than 1% of sessions in phase 1; 10% and 7% in phase 2; and 1% and 2% in phase 3. Clotting limited to the drip chambers was observed in 13%, 34% and 12%, respectively. The study of coagulation parameters showed a better profile when low-molecular weight heparin (LMWH) was used in association with HeprAN membrane, while the generation of TAT complexes did not differ from that observed with the standard anticoagulation modality used in phase 1. Our results suggest that the HeprAN membrane can be used safely in routine post-dilution hemodiafiltration with reduced doses of LMWH.

Evaluation of Weight-Based Dosing of Unfractionated Heparin in Obese Children

To determine whether pediatric patients with obesity receiving weight-based dosages of unfractionated heparin (UFH) exhibit an enhanced response when dosed by actual body weight compared with nonobese patients as assessed primarily by the frequency of supratherapeutic anticoagulation. Secondary measures included UFH doses associated with therapeutic anticoagulation. This single-institution retrospective case-matched study included children with and without obesity, matched on a 1:1 basis, who received a weight-based continuous infusion of UFH. Therapeutic monitoring values were defined for activated partial thromboplastin time (aPTT) level (70-101 seconds) and anti-activated factor X (Xa) level (0.35-0.7 U/mL). The study included 50 children. The percentage of patients with supratherapeutic anticoagulation at any point in the study, as measured by either aPTT or anti-Xa level, was similar in the obese and nonobese groups (76% vs 72%; P = 1.0). However, compared with patients without obesity, those with obesity received a lower mean starting dose (17.4 vs 20.2 U/kg/hour; P = .013) and a lower mean maintenance dose (19.1 vs 24.3 U/kg/hour; P = .033) to achieve stable therapeutic monitoring test values. There was no difference in mean initial post-UFH aPTT between the 2 groups, but the mean initial anti-Xa level was higher in the obese group (0.45 vs 0.29 U/mL; P = .045). Compared with children without obesity, those with obesity who received actual body weight-based continuous UFH infusions did not exhibit a higher frequency of supratherapeutic anticoagulation, but did require lower dosages to achieve comparable anticoagulation. Our results highlight recognized discrepancies between aPTT and anti-Xa monitoring assays.