Heparin Nomogram Research Articles

Impact of as needed heparin boluses on supratherapeutic activated partial thromboplastin time in patients managed with extracorporeal membrane oxygenation.

Brigham and Women's Hospital (BWH) historically used titratable weight-based heparin nomograms with as needed boluses managed by extracorporeal membrane oxygenation (ECMO) specialists to achieve a pre-determined goal activated partial thromboplastin time (aPTT). Due to concern amongst providers that as needed boluses may lead to supratherapeutic aPTT's and subsequent bleeding, new nomograms without as needed boluses were implemented. The purpose of this retrospective observational analysis is to provide a comparison in safety and efficacy between the heparin nomograms with as needed boluses and the new nomograms without boluses. Adult patients who were cannulated on ECMO and initiated on an approved heparin bolus nomogram (January 1, 2018-December 31, 2019) or an approved heparin no bolus nomogram (October 20, 2020-March 31, 2021) were screened for inclusion. The major endpoint evaluated was the percentage of supratherapeutic aPTTs, defined as an aPTT above the upper limit of the specified nomogram goal, within the first 72 hours. A total of 23 patients were included in the bolus nomogram cohort and 9 patients in the no-bolus nomogram cohort. Within the first 72 hours of initiation, there were 11.5% supratherapeutic aPTTs in the bolus group and 5.1% in the no-bolus group (p=0.101). Overall there was one bleeding event in the no-bolus group (11.1%) and seven in the bolus group (30.4%) (p=0.26). There were no thromboembolic events in either group. Overall, there was no difference found in percentage of supratherapeutic aPTTs within the first 72 hours of heparin initation between the bolus and no-bolus nomograms.

Safety of fixed-dose heparin titration boluses in underweight patients

IntroductionAt UNC, venous thromboembolism (VTE) patients are treated with a heparin nomogram including fixed-dose titration boluses to correct subtherapeutic heparin correlation values (HCVs). The bolus dose often exceeds the recommended loading dose in underweight patients, therefore raising concern for an increased bleeding risk. This evaluation aims to assess the safety of these titration boluses for underweight patients. Materials and methodsAdult patients receiving intravenous heparin for VTE treatment and requiring at least one titration bolus were included. The underweight patients had a body mass index (BMI) <18.5 kg/m2 while the patients in the control group had a BMI of 18.5–29.9 kg/m2. The primary outcome was the percentage of patients with a supratherapeutic HCV after the first titration bolus. Secondary outcomes included the percentage of patients with a supratherapeutic HCV requiring holding of the infusion, time to stable HCV, and clinically significant bleeding. ResultsOne hundred fifty-eight patients met inclusion criteria, with similar baseline characteristics between groups. There were 13.9 % of patients in both groups who had a supratherapeutic HCV after the first titration bolus. More underweight patients required holding of heparin. All patients took over 48 h to reach a stable HCV. There was no difference in clinically significant bleeding. ConclusionsDespite finding no significant difference, there remains clinical concern for increased bleeding risk in underweight patients as this population required heparin to be held due to supratherapeutic HCVs more often. More evidence is needed to evaluate the safety of fixed-dose heparin titration boluses in underweight patients due to the limited scope of this study.

P5. Abstract Title: Characterization of Unfractionated Heparin Infusions in a Comprehensive Stroke Centre

<h3>Introduction</h3> Stroke patients with arterial or venous intraluminal thrombus (ILT) are at high risk of stroke recurrence and embolic or hemorrhagic complications. Treatment with anticoagulation remains challenging in this group of patients due to onset of action, efficacy, and risk of hemorrhage. Traditionally, unfractionated heparin (UFH) has been used due to its short half-life in the context of risk of hemorrhagic transformation of the infarct zone. Heparin nomograms and associated bolus dosing are not standardized in clinical practice across centres and patients can exhibit long epochs of time under or over the therapeutic PTT range. Thus, resulting in suboptimal protection and added risk of hemorrhage respectively. We aim to characterize the use and efficacy of UFH infusion in cerebrovascular conditions at a large academic comprehensive stroke centre. <h3>Methods</h3> A retrospective analysis from 2017 to 2019 was conducted at Sunnybrook Health Sciences Centre (SHSC) on adult patients in either critical care or stroke units with UFH infusion for ILT and other cerebrovascular etiologies. We characterized use-cases and stroke etiology. PTT values were extracted from patient profiles for the duration of UFH infusion. These values were used to find the duration of time in target PTT range (70-90.9 sec); subtherapeutic (PTT<70 sec); and supratherapeutic (PTT>90.9 sec) epochs. Duration of time above theraputic PTT and mean values were measured. Where possible, we also correlated with clinical parameters and imaging findings. <h3>Expected Results</h3> In regards to PTT, we expect a significant amount of time spent in the subtherapeutic and/or supratherapeutic ranges, compared to target range. <h3>Conclusion</h3> There is limited evidence for the scope and efficacy of UFH infusions from a therapeutic perspective in stroke patients admitted to a comprehensive stroke centre. Future research efforts should be directed towards the utilization of other anticoagulation therapies, such as low molecular weight heparins (LMWH), with appropriate dosing that offers reliable, efficacious, and safe anticoagulation.

Evaluation of Compliance with a Weight-based Nurse-driven Heparin Nomogram in a Tertiary Academic Medical Center.

Recently, our institution adopted a weight-based nurse-driven heparin titration protocol that relies on nurses ordering laboratories, adjusting doses, and initiating boluses. Numerous institutions have implemented similar protocols with reported success. A single-center retrospective analysis was conducted at the Brigham and Women's Hospital in Boston, Massachusetts that included all patients who were initiated on the weight-based nurse-driven heparin nomogram during a 30-day period. Nomogram compliance was defined as the rate of correct titrations per nomogram encounter and further separated into laboratory, titration, or dosing compliance. Spearman's coefficient was utilized to determine the correlation between noncompliance and percentage of activated partial thromboplastin time (aPTT) values in range. Overall, 211 patients were evaluated for inclusion, of which 95 patients were determined to meet criteria for evaluation. The total nomogram compliance rate was 84.6% ± 10.5%. Laboratory, titration, and dosing compliances were 77.6% ± 19.2%, 87.2% ± 14.5%, and 91.8% ± 10.6%, respectively. The percent of aPTT values in therapeutic range was 39.6% ± 24.6%. A moderate negative correlation between the percentage of aPTT values in range and the nomogram error rate was observed (r = -0.452, P < 0.001). This relationship was found to be driven by the rate of dosing error, which showed the strongest correlation with percentage of aPTT values out of range (r = -0.465, P = 0.001). Implementation of a nurse-driven heparin titration nomogram relies on compliance with the prescribed protocol. Dosing compliance had the lowest error rate, whereas dosing noncompliance had the strongest impact on percentage of aPTT values in range.

Performance of Anti-Factor Xa Versus Activated Partial Thromboplastin Time for Heparin Monitoring Using Multiple Nomograms.

The purpose of this study was to compare the performance of anti-factor Xa concentration versus activated partial thromboplastin time (aPTT) monitoring with multiple indication-specific heparin nomograms. This was a prospective, nonrandomized study with historical control at a large academic medical center. A total of 201 patients who received intravenous heparin in the cardiology units were included. The prospective cohort included patients (n = 101) with anti-factor Xa (anti-Xa) monitoring, and the historical control group included patients (n = 100) who had aPTT monitoring. Patients in the prospective group had both anti-Xa and aPTT samples drawn, but anti-Xa was used for dosing adjustment. The anti-Xa cohort achieved a significantly faster time to therapeutic range (P < .01) and required fewer dose adjustments per 24-hour period compared to the aPTT control (P = .01). Results were consistent across heparin nomograms. The overall discordance rate between the 2 tests was 49%. No significant differences in clinical outcomes were observed. In summary, anti-Xa monitoring improved the time to therapeutic anticoagulation and led to fewer dose adjustments compared to the aPTT with multiple indication-based heparin nomograms.

Description and Evaluation of the Implementation of a Weight-Based, Nurse-Driven Heparin Nomogram in a Tertiary Academic Medical Center.

Weight-based, nurse-driven heparin nomograms are reported in the medical literature to improve the time it takes to reach a minimum threshold for anticoagulation without compromising patient safety in specific indications or patient populations. This is the first report in the literature of an institution-wide protocol implementation and evaluation of effectiveness with simultaneous transition to an electronic health record. The purpose of implementing this practice change at our institution was to standardize practice, improve time to reach therapeutic anticoagulation, and improve patient safety. We conducted a retrospective analysis utilizing a pre/postimplementation design to compare outcomes. The primary end point evaluated was the time to reach minimum threshold value for therapeutic anticoagulation. Additionally, we assessed the percentage of patients who reached minimum threshold therapeutic anticoagulation within 24 hours, the percentage of patients with a critically supratherapeutic activated partial thromboplastin time (aPTT) value (≥120 seconds) during therapy, and a description of heparin titration for the first 4 aPTT results with nomogram use. Overall time to therapeutic anticoagulation decreased from a mean 18.7 to 11.7 hours (hazard ratio [HR] 1.59; 95% confidence interval 1.22-2.08; P < .0005). Percentage of patients receiving therapeutic anticoagulation within 24 hours increased from 74.4 to 88.5 (odds ratio [OR 2.97, P = .002) and the percentage of patients with an aPTT ≥120 seconds remained constant at 49.9 versus 46.8 (OR 0.92, P = .73). This practice change reduced time to therapeutic anticoagulation without an increase in the proportion of patients with a critically supratherapeutic aPTT at our institution.

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Introduction: The safety and effectiveness of the use of a weight-based heparin nomogram to treat venous thromboembolism (VTE) in obese patients is controversial. Small studies have recommended smaller dosing of unfractionated heparin (UFH) in obese patients. Methods: The primary objective of this s

Abstract 238: Utilization and Safety of a Heparin Nomogram in Treating Thrombotic Comorbidities in Stroke Patients

INTRODUCTION: AHA guidelines discourage anticoagulation in acute ischemic stroke (AIS) patients to prevent stroke recurrence. However, some AIS patients have concurrent thrombotic states, such as DVT/PE, that require anticoagulation to prevent further morbidity. Little is published on the safety and efficacy of heparin titration nomograms used for thrombotic comorbidities in stroke patients. Our aim was to assess the utilization and safety of a heparin stroke infusion nomogram at a single, tertiary, academic hospital. METHODS: The heparin stroke nomogram contains no heparin bolus, a goal aPTT of 60-85, and stable “steady state” dose with 2 consecutive aPTT values at goal. Patients were identified via a retrospective, computerized order entry review for the heparin nomogram. Exclusion criteria were: baseline aPTT &gt; 50s, a hypercoagulable state, and short usage (&lt; 24 hrs) or interrupted nomogram prior to 2 consecutive “goal” aPTT values. Demographic data and aPTTs were determined from the prospectively-populated enterprise data warehouse. The aPTTs were divided into 6 hr time bins from initiation. Indication and outcomes were determined by source document review by a stroke neurologist. RESULTS: From 1/2010 - 6/2011, a heparin nomogram for any indication was initiated in 2,016 patients with 144 (7%) of these utilizing the “stroke” heparin nomogram, The nomogram was ordered by neurology (72%, n=103 ), neurosurgery (8%, n=11), other surgical specialties (9%, n=13), internal medicine (7%, n=10), and other (5%, n=7). After excluding those as above, the “stroke” heparin nomogram was used in 86 patients (40% female; mean 55 yrs SD 17), 74 with AIS, 2 with ICH, 1 with SAH, 2 with craniectomy, and 3 other. The indication for heparin included large artery near total occlusion (30%, n=26), cardiac thrombus (suspected (26%, n=22) or visualized (9%, n=8)), cerebral sinus venous thrombosis (10%, n=9), DVT/PE (5%, n=4), artery dissection (17%, n=15), and other (7%, n=6). Percent of “at-goal” aPTTs by 6 hr time bins were: 6-12 hrs: 24% (n=21/86); 12-18 hrs: 36% (n=31/ 86); 18-24 hrs: 48% (n=40/84); 24-48 hrs: 55% (n=42/77); 48+ hrs: 65% (n=29/45). At the 42-48 hrs time point, 4% of patients had aPTT&gt;150. There were 4 non-bleeding related deaths. Repeat AIS occurred in 3 patients of the 74 patients with primary AIS. Asymptomatic ICH occurred in 1 patient with primary AIS; symptomatic hemorrhage occurred in 2 patients (epistaxis, GI). Discharge anticoagulation was prescribed in 56 patients (65%). Ninety day readmission occurred in 15% of patients (n=13), 5 for bleeding. CONCLUSION: The heparin stroke nomogram appears safe in that it does not increase risk of ICH. However, therapeutic aPTTs are not reached quickly with less than half of patients therapeutic at 24 hours, nor are they maintained at steady state. This nomogram could be too conservative in cases where clinical situation requires rapid anticoagulation.

Monitoring of Unfractionated Heparin Using Activated Partial Thromboplastin Time

We frequently encounter high levels of activated partial thromboplastin time (aPTT) during heparin anticoagulation. The purpose of this study is, first, to investigate the rate of achieving and maintaining therapeutic aPTT in patients treated with heparin anticoagulation and second, to assess the adequacy the current nomogram. We included 197 patients who underwent anticoagulation with unfractionated heparin (UFH) according to the standard nomogram between September 2008 and May 2010. The primary endpoints were the rate of achieving a therapeutic range (TR) at the first sample, 24 hours, or 48 hours. We also compared heparin nomograms according to age (<70 years vs ≥70 years). Of the 197 patients, 131 had heparin loading. In the heparin loading group, there were 19.1% (n=25), 69.5% (n=91), and 90.1% (n=18) achieving TR at the first aPTT, 24 hours, and 48 hours, respectively. The therapeutic aPTT proportion was 39.2%, and the rate of peak level above 90 seconds was 93.1%. Peak levels of aPTT were higher in the older age group than in the younger age group (202.3 ± 124.2 versus 152.0 ± 78.9, p=0.007). Our results indicate a high rate of achieving therapeutic aPTT at 24 hous and 48 hours, but a low success rate for maintenance within the TR. Most patients had supratherapeutic aPTT of more than 90 seconds. Therefore, the TR of aPTT that matches heparin levels of 0.3 to 0.7 IU/mL measured by antifactor Xa assay should be determined. If not, we should consider adopting a new heparin dosing nomogram.

Delayed efficient anticoagulation with heparin in patients with a weight of 110 kg and more treated for acute coronary syndrome

The use of a weight-based nomogram is considered as standard care for prescribing appropriate doses of unfractionated heparin (UFH). Because of the need for multiple other medications that may affect bleeding and that clinical data have relied on similar dosing algorithms, maximum initial bolus and infusion rates have been suggested (capped initial dose). Whether these weight-based heparin nomograms properly address therapeutic dosing in obese patients remains questionable. Thirty patients treated for acute coronary syndrome and weighing ≥110 kg were retrospectively compared with 90 controls (three groups of 30 patients, weighting 50-69.9, 70-89.9, or 90-109.9 kg), all treated with UFH, July 2008 to April 2009. The primary end point was the time required to obtain a threshold activated partial thromboplastin time (aPTT). Mean time to achieve threshold aPTT was longer for obese patients weighing ≥110 kg than for controls (31.47 vs. 12.89 hours; P < 0.0001). At 24 hours, 63% of obese patients weighing ≥110 kg had not reached threshold aPTT vs. 7% of controls (P < 0.0001). However, threshold infusion rate did not differ between weight categories (13.0 vs. 13.1 U/kg/h; P = NS) and approximated the initial infusion rate recommended by nomograms without applying the dose cap (12 U/kg/h). Adequate anticoagulation time doubled in patients weighing ≥110 kg, suggesting that these patients were not receiving appropriate heparin doses initially to achieve threshold aPTT rapidly. Using initial infusion rate recommended by a nomogram without capping for total body weight is suggested as acceptable in this study. This approach should be further evaluated in a prospective study.

Revisiting the Heparin Nomogram: Leveraging Technology to Improve Quality

AbstractAbstract 1168Continuous infusions of unfractionated heparin (UFH) are still commonly used in the initial treatment of venous thromboembolism (VTE). As a result of UFH's high risk profile and common usage, weight-based UFH nomograms were developed more than two decades ago to standardize its dosing. Since that time, there has been scant literature on improving UFH administration. Specifically, upgrading current UFH nomograms, improving therapeutic monitoring, and exploring and expanding the role of Computerized Physician Order Entry (CPOE) and the Electronic Health Record (EHR) to achieve optimal delivery methods have little published research or quality improvement work.Several factors previously identified contributing to sub-optimal UFH therapy at our institution include timing of aPTT lab ordering and reporting, errors in dose adjustments, lack of boluses when clinically indicated, pharmacy and nursing administration errors, and suboptimal design and use of CPOE order sets.A multidisciplinary team at this academic medical center designed an intervention to improve the quality and safety of continuous UFH infusions in hospitalized patients. The aims were two-fold: reduce the time to initial therapeutic aPTT values and increase the overall time patients spent in therapeutic range without increasing time supra-therapeutic. To determine the percent time spent in different therapeutic ranges, linear averaging was used between aPTT values over time. As UFH is given continuously and monitoring aPTT values has inherent variability, we proposed that looking at time spent in therapeutic ranges gives a more realistic and meaningful clinical picture than current accepted metrics that look at single point-in-time aPTT values. We feel that these historic metrics, which focus on the percentage of patients with a therapeutic aPTT at 24 hours and time to therapeutic aPTT, do not provide sufficient information to impact optimal therapeutic dosing.The intervention involved four core changes to our existing UFH nomogram: 1.Dedicated UFH order set for treatment of VTE incorporating weight-based initial and subsequent boluses, and further dosage adjustments.2.Built-in online weight-based dosing calculator.3.Development of a new lab order aPTTAC (activated partial thromboplastin time anticoagulant) which prompted a priority lab draw and lab processing.4.Nursing dual sign-off on all dosage adjustments.We extracted data from the EHR of 8629 patients that were on continuous infusion UFH for VTE from January 2010 through February 2012. There were 5759 patients in the pre-intervention group and 2870 patients in the post-intervention group. All patients on therapy for greater than 8 hours who had at least one aPTT were included in the analysis.Post-intervention, the proportion of patients who were therapeutic within 24 hours increased 16% (67% to 78%, p value <0.0001), and time to therapeutic aPTT decreased by 18% (13.9 hours to 11.4 hours, p value <0.0001). (Figure 1)Additionally, post-intervention, the proportion of time spent inside the therapeutic range increased from 47% to 53% (p value <0.0001). There was a small increase in percentage time supra-therapeutic from 20% to 21%, (p value <0.0001), however, this was not associated with increased bleeding events.Safety analysis, which involved the manual review of 131 pre-intervention and 127 post-intervention charts revealed a trend towards lower bleeding rates with the new UFH nomogram. The rate of major bleeding was 3.9% post intervention compared to 6.9% before the upgrade (p value 0.4116).This safety initiative demonstrates a significant improvement in the safe and effective use of continuous UFH infusion in the treatment of VTE. Through creative utilization of technology and improved process of care we have brought high reliability to this high-risk medication. To our knowledge, this is the largest cohort of patients evaluated for safe VTE treatment with a UFH nomogram. Further retrospective analysis of this data evaluating patient specific characteristics should shed light on opportunities to improve the UFH nomogram and further leverage the EHR and CPOE to improve patient care. While our evaluation looks at a single center, these interventions could easily be implemented in other hospital systems with EHR and CPOE capabilities. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Substitution of a heparin correlation value for activated partial thromboplastin time in heparin nomograms

PURPOSE. Use of nomograms based on the "heparin correlation value" (HCV)-a value that corresponds to measured activated partial thromboplastin time (aPTT) and that removes the need to revise nomograms in response to a change in the aPTT reagent or coagulometer used-was evaluated as an alternative to traditional aPTT-based anticoagulation nomograms. SUMMARY. Data were collected on patients receiving heparin therapy for selected indications (thrombotic disorders, cardiac conditions, and acute coronary syndromes) during four-month periods before (n = 59) and after (n = 60) implementation of the HCV-based nomograms. The primary endpoints were the rate at which coagulation laboratory measurements were obtained at the appropriate time and the rate of appropriate dosage adjustment in response to reported laboratory values; secondary endpoints included the time to attainment of the first target anticoagulation value. After implementation of HCV-based nomograms, coagulation laboratory measurements were obtained at the appropriate time in (mean ± S.D.) 92.9% ± 12.8% of patients, compared with 80.1% ± 15.5% of patients who received aPTT-based monitoring (p < 0.0001). After implementation of HCV-based monitoring, the rate of correct heparin dosage adjustments was improved (mean ± S.D. 94.7% ± 7.8% versus 89.3% ± 14.0%, p = 0.01), and the time to attainment of the first target anticoagulation value was shorter (mean ± S.D. 16.4 ± 10.6 hours versus 21.5 ± 14.8 hours, p = 0.03). CONCLUSION. The HCV, which relates measured aPTT values to corresponding antifactor Xa concentrations, was substituted for aPTT in heparin nomograms and appeared to be a viable alternative to the aPTT.

Identifying Optimal Initial Infusion Rates for Unfractionated Heparin in Morbidly Obese Patients

Most literature available for unfractionated heparin (UFH) supports the use of actual body weight for dosing all patients, yet a small proportion of the patients in these studies were morbidly obese. The most appropriate dosing strategy for therapeutic UFH in this patient population is not clearly defined. To better define appropriate UFH dosing strategies in morbidly obese patients and to evaluate the safety of a weight-based heparin nomogram in this patient population. Patients with class III (morbid) obesity receiving therapeutic doses of a UFH infusion for greater than 24 hours were evaluated. Two comparator groups of overweight/class I -II obesity and normal/underweight patients were created by matching patients to the class III obesity group. Doses and times to therapeutic activated partial thromboplastin time (aPTT), bleeding rates, and mortality were assessed. The mean infusion rate required to obtain a first therapeutic aPTT was 11.5 units/kg/h in the class III obesity group (n = 94) versus 12.5 units/kg/h and 13.5 units/kg/h for the overweight/class I-II obesity (n = 92) and normal/underweight (n = 87) groups, respectively (p = 0.001). The mean times to a first therapeutic aPTT were 21.3, 22.1, and 29.9 hours, respectively (p = 0.421). There was a statistically significant difference in the infusion rate required to obtain 2 consecutive therapeutic aPTTs between groups (p = 0.016), with higher weight groups requiring smaller (per kilogram actual body weight) infusion rates, but there was no significant difference in the time to reach 2 consecutive therapeutic aPTTs (p = 0.776). There was no significant difference in bleeding (p = 0.517) or mortality (p = 0.475) among groups. Morbidly obese patients require smaller UFH infusion rates per kilogram actual body weight compared to patients with lower body mass indices. UFH dosing recommendations should be modified to reflect body mass index classification.

Association of age, gender, and weight on maintenance dose of intravenous unfractionated heparin

Unfractionated heparin (UFH) therapy is commonly used for the management of acute coronary syndrome (ACS), atrial fibrillation (AF) or atrial flutter (A-Flutter). Weight based heparin nomogram is widely used to determine the dosage of continuous intravenous infusion. Frequent monitoring is required due to the variable responses to its anticoagulant effects. We investigated factors that may influence the dose of UFH. We performed a retrospective cohort study of all patients who received continuous UFH for ACS, AF, or A-Flutter from January 2008 to December 2008 and reached maintenance dose of UFH within 48 hr. A total of 199 patients were included in this study: 42.7% were females and mean age was 66.6 ± 2.0 years. Univariate analysis revealed that age, gender, weight, serum albumin, and serum protein level were significantly associated with maintenance of UFH dose. After adjustment with multivariate analysis, age (R = ―0.27, P ≤ 0.001), gender (R = -0.14, P ≤ 0.044), and weight (R = 0.54, P ≤ 0.001) remained to have significant association with maintenance UFH dose. In conclusion, we have identified not only weight but also age and gender as significant factors that may affect the maintenance of heparin dose in clinical setting.

Predictors of Initial Nontherapeutic Anticoagulation With Unfractionated Heparin in ST-Segment Elevation Myocardial Infarction

Although weight-based nomograms have improved the efficacy and safety of dosing unfractionated heparin in ST-segment elevation myocardial infarction, achieving therapeutic anticoagulation in practice remains challenging. In the Enoxaparin and Thrombolysis in Reperfusion for Acute Myocardial Infarction Treatment-Thrombolysis in Myocardial Infarction (ExTRACT-TIMI) 25 study, 20 506 patients with ST-segment elevation myocardial infarction were randomized to enoxaparin or unfractionated heparin, the latter dosed according to the American College of Cardiology/American Heart Association weight-based nomogram with centrally monitored activated partial thromboplastin times (aPTTs). A total of 6055 patients received study unfractionated heparin and a fibrin-specific lytic and had an initial aPTT drawn within 4 to 8 hours of starting therapy. Despite close adherence to recommended dosing, only 33.8% of initial aPTTs were therapeutic (1.50 to 2.00 times control); 13.2% were markedly low (<1.25 times); and 16.3% were markedly high (> or =2.75 times). Markedly high aPTTs were more likely in patients who were older (adjusted risk ratio [RR(adj)], 1.14 per decade; P=0.001), were female (RR(adj), 1.46; P<0.001), were of lower weight (RR(adj), 1.19 per 10-kg decrease; P<0.001) or had renal dysfunction (RR(adj), 1.08 per 0.2-mg/dL increase in serum creatinine; P=0.006). Markedly high aPTTs were associated with increased risk of TIMI major or minor bleeding by 48 hours (odds ratio, 2.11; P=0.004); markedly low aPTTs tended to be associated with increased risk of fatal or nonfatal reinfarction by 48 hours (odds ratio, 2.19; P=0.057). Despite the use of a standard weight-based unfractionated heparin nomogram in ST-segment elevation myocardial infarction, nontherapeutic anticoagulation is frequent and more likely among certain vulnerable patient groups, with excess anticoagulation associated with increased bleeding and inadequate anticoagulation associated with reinfarction. These findings should be considered when dosing unfractionated heparin in support of fibrinolytic therapy.

Validation of a Weight Based Heparin Nomogram That Utilizes Anti-Factor Xa Levels for Monitoring.

PURPOSE: This study documented consecutive patients receiving continous intravenous (IV)unfractioned heparin(UFH) infusion during the introduction of an Anti-Xa level and weight based nomogram to evaluate 1)the ability of the new nomogram to achieve a therapeutic Anti-Xa level with the first level drawn. 2) the ability of the new nomogram to achieve Anti-Xa levels within the therapeutic range by 24 hours from initiation. After review of the current literature, the therapeutic anti-Xa level were defined as 0.4–0.6 and 0.4–0.5 for standard and low dose anticoagulation respectively.METHODS: IV UFH initiations between September 1 to December 31, 2005 from 2 academic sites in Canada were identified from pharmacy records. Patients' indication for UFH therapy, demographics, dose of UFH (bolus, infusion rates) were retrieved from heparin monitoring forms. Anti-Xa levels along with specific drug management prior to admission and documented episodes of thrombosis and bleeding were retrieved from the patients medical chart. Patients receiving less than 6 hrs of therapy were excluded from analysis. A chromogenic anti-Xa assay was used for this study.RESULTS: One hundred and ninety-six IV UFH initiations in 186 patients were identified during the 4 month period. Approximately 1400 anti-Xa levels were measured during the study period. The average age of the total cohort was 63 with an average weight of 76 kg and 68% of patients were male. The percentage of patients receiving any anti-platelet or anticoagulant prior to starting or during IV heparin was 86 %. The average duration of IV UFH therapy was 4.8 days. Compliance with nomogram was found in 70 %(n=136) of initiations.In respect to the primary endpoint of the percentage of nomogram compliant initiations achieving a therapeutic first anti-Xa level was 14.7 %. The majority of patients were supra-therapeutic (anti-Xa>0.6) with respect to the first level and with 3% of initiations resulting in sub-therapeutic levels. The first anti-Xa level was taken on average at 6 hours after start of infusion. The percentage of patients achieving therapeutic anti-Xa level within the first 24 hrs was 39%. The administration of an initial bolus before infusion did not effect the likelihood of achieving either endpoint. There were no thrombotic events in the nomogram compliant group. Two episodes (3.8%) of major bleeding and 8 episodes (15.1%) of minor bleeding were documented during IV heparin administration.Sixty heparin IV initiations which were deemed non-compliant with the nomogram achieved similar rate of 10%(n=6) for the therapeutic anti-Xa levels at first sampling and 40% (n=24) for therapeutic anti-Xa levels at 24 hrs. There were 2 episodes of major bleeding and 2 episodes of minor bleeding. Thirty-eight percent of initiations resulted in supratherapeutic levels, while 23.33% resulted in subtherapeutic levels.CONCLUSION: The Anti-Xa and weight based nomogram to initiate and titrate IV UFH was found be effective in a small number of patients. The target anti-Xa level (0.4–0.6) utilized in this study is different than mentioned in American College of Chest Physicians 2006 Antithrombotic guidelines. The narrow therapeutic window may account for low percentage of patient achieving therapeutic anti-Xa level at first sampling. If the therapeutic Anti-Xa level was defined as 0.3–0.7 the percentage of patients achieving therapeutic levels in the compliant cohort would be 55.9%. Compliance with the nomogram was associated with substantial decrease in sub-therapeutic anti-Xa levels.

Heparin dosing and therapeutic activated partial thromboplastin times (aPTT) in acute coronary syndrome (ACS)

This study assessed the current practices of heparin dosing and determined the extent of therapeutic activated partial thromboplastin times (aPTT) achieved, utilising a standard heparin nomogram in the coronary care unit and step-down cardiac ward of a health care facility in South Australia. The study also examined the effect of actual body weight (ABW), body mass index (BMI), smoking, concomitant intravenous glycerine trinitrate, age, gender and creatinine levels, individually, on the time taken to attain a therapeutic aPTT in acute coronary syndrome (ACS) patients receiving a heparin infusion. A retrospective correlational research design was utilised to include the collection of quantitative data from 66 men and women of all ages and background consecutively admitted into the coronary care unit and the step-down cardiac ward and receiving a continuous heparin infusion. The quantitative data included demographic details plus all information regarding treatment and results of heparin therapy from the patients' medical records. Descriptive analysis of the data revealed 32% of the participants attained a therapeutic level with the first aPTT taken and that, successively, 35% and 45% of the participants attained a therapeutic level with the second and third aPTT taken. The majority of participants were found to be outside of the therapeutic range at any one time during the study. A generalised linear model (log-binomial model) applied to the data revealed that increased ABW (p=0.002), creatinine levels (p=0.033) and, in particular, BMI (p=0.000) were significant risk factors that contributed to the failure of participants attaining a therapeutic aPTT level. Age (p=0.668), gender (p=0.623), smoking (p=0.993) and the use of concomitant intravenous glycerine trinitrate (p=0.897) did not have a significant effect on the time to reach a therapeutic aPTT. The results provide noteworthy information for the re-evaluation of the use of the standard heparin nomogram. A robust randomised clinical trial is required to further examine BMI as the best predictor for heparin requirements in ACS patients receiving a heparin infusion.

Use of a Modified Dosing Weight for Heparin Therapy in a Morbidly Obese Patient

To report a case of successful anticoagulation using a modified dosing weight (DW) for unfractionated heparin (UFH) therapy in a morbidly obese female. A 54-year-old morbidly obese (182.4 kg, 155 cm) white female presented to the emergency department with tachycardia, shortness of breath, and chest pain, and was diagnosed with a pulmonary embolism. Anticoagulation with UFH was initiated. A modified DW of 120 kg was obtained from the average of the actual body weight (ABW) and ideal body weight ( approximately 50 kg). We selected this modified DW to account for heparin's altered volume of distribution in an obese patient and avoid potentially supratherapeutic activated partial thromboplastin times (aPTTs) using ABW and subtherapeutic aPTTs using DW. Therapy was initiated with a bolus dose of 9600 units (80 units/kg x 120 kg) and continuous infusion rate of 2160 units/h (18 units/kg/h x 120 kg). This infusion rate was maintained throughout the course of heparin therapy and was successful in maintaining therapeutic aPTTs. Proper diagnosis and rapid initiation of therapy prevent mortality in patients with PE. Although weight-based heparin nomograms provide standardization through initial bolus and continuous infusion recommendations, many do not address dosing in morbidly obese patients. Several retrospective studies have evaluated actual, dosing, and ideal body weights for heparin therapy in obese patients; however, none has evaluated modified DW. In our patient, successful anticoagulation was objectively confirmed. Further investigation is necessary to determine the optimal DW for UFH in morbidly obese patients presenting with acute thrombosis.

Effectiveness of a Computerized System for Intravenous Heparin Administration: Using Information Technology to Improve Patient Care and Patient Safety

To overcome errors in prescribing, calculating doses, and monitoring intravenous heparin, a computerized heparin nomogram system (HepCare) was developed to improve heparin safety using interactive cues between the prescriber, nurse, pharmacist, and the laboratory. The frequency of deviations decreased from 0.5 per patient before HepCare with the protocol to 0.006 per patient with HepCare and the protocol. The goal activated partial thromboplastin time results of the HepCare system (group I) were compared with patients who were not treated using the HepCare system (group II). There was a higher mean percentage of activated partial thromboplastin times within goal range in group I vs. II-44% vs. 27% (p<0.01). There were reminders of a drop in platelet count in 6% of patients, hemoglobin drop in 0.7%, and validation activated partial thromboplastin time values in 7% of patients by HepCare. HepCare-guided intravenous heparin resulted in significant improvements in safety, quality assurance, and targeted activated partial thromboplastin time values.

Redesign of a weight-based heparin protocol for improved outcomes in a community hospital.

Heparin has long been used to minimize complications of a variety of disorders and reaching a therapeutic level within 24 hours has been shown to improve patient outcomes. However, the dosing of heparin to reach a therapeutic level has been controversial. At our institution a weight based heparin nomogram was in place, however an initial data analysis revealed a large percent of the initial aPTT levels were above therapeutic range. This article will describe the performance improvement process and the overall goal to decrease the percentage of patients exceeding the initial therapeutic aPTT levels without compromising daily therapeutic aPTT levels.