Validation of a Weight Based Heparin Nomogram That Utilizes Anti-Factor Xa Levels for Monitoring.
Authors: Huh Jin-Hyeun , Leong Derek , Lau Maxine , Gavrilovic Maja 
Published: October 2019

Abstract
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.