Prolonged aPTT Relative to Anti-Xa Is Associated with Increased 30-Day Mortality in Hospitalized Patients Treated with Unfractionated Heparin

Abstract Abstract 1248 BACKGROUND: Historically, unfractionated heparin (UFH) has been monitored using the aPTT, a global measurement of the ability of the heparin-antithrombin complex to inactivate the relevant clotting factors. However, the aPTT response to heparin depends on patient variables and reagent and instrument factors. Anti-Xa activity is routinely used to calibrate aPTT for heparin therapy nomograms, and some institutions use anti-Xa activity directly in heparin dosing nomograms. In general, there is a lack of data correlating these methods of measuring heparin effect in patients and outcome data validating any particular approach. We sought to determine the concordance of aPTT and anti-Xa measurements and its impact on patient outcomes in adult hospitalized patients treated with UFH. METHODS: All simultaneously drawn aPTT and anti-Xa values from patients 18 years and older receiving UFH while hospitalized at Stanford between February 2009 and August 2009 were extracted from Stanford's patient database. We created an aPTT/anti-Xa reference curve using normal pooled plasma with heparin added at increasing concentrations from 0.05 u/mL to 1.0 u/mL, with simultaneous measurement of aPTT and anti-Xa activity. We designed a polynomial fit correlating aPTT and anti-Xa activity with a 99% confidence limit. We then grouped paired aPTT/anti-Xa values into one of three groups according to whether the paired values fell within or outside of the correlation area: 1) aPTT anti-Xa: discordant pairs, with high aPTT to anti-Xa value, and 3) aPTT= anti-Xa: concordant pairs, with aPTT and anti-Xa values within the correlation area. In addition, each aPTT/anti-Xa data pair which had an INR from the same date was categorized as associated with either a low (= 1.5) INR. Because individual patients could have data pairs that fell into multiple groups, we further narrowed the aPTT > anti-Xa and aPTT= anti-Xa groups into patient subgroups to assess outcomes, wherein each patient had data pairs only in one group. RESULTS: A total of 2321 paired values from 539 patients were studied. Data pairs were frequently discordant: 413 (18%) data pairs were in the aPTT anti-Xa group, and 937 (40%) were in the aPTT=anti-Xa group.1337 of 2321 (58%) aPTT/anti-Xa data pairs had an INR value from the same date. The aPTT>anti-Xa group had the highest proportion of data pairs associated with an INR >= 1.5 (68%, see Figure, p anti-Xa and aPTT=anti-Xa patient subgroups. The 30-day mortality was 19 of 87 (21%) in the aPTT > anti-Xa patient group, higher than in the aPTT=anti-Xa group (6 out of 112, 5%) (p anti-Xa on heparin alone had the highest 30-day mortality (16 of 39, 41%), compared to a 30-day mortality of 6% (3 of 48) for aPTT > anti-Xa patients who were on both heparin and warfarin (p 0.05), nor was the 30-day mortality significantly different between those in the aPTT>anti-Xa on heparin and warfarin (3 of 48, 6%) compared to those in the aPTT=anti-Xa on heparin and warfarin (1 of 23, 4%, p>0.05). DISCUSSION: Simultaneously measured aPTT and anti-Xa values in a large cohort of hospitalized adult patients treated with UFH were discordant the majority of the time. The most common discordant pattern was a high aPTT to anti-Xa value. This group was associated with an INR >= 1.5 68% of the time, indicating that a baseline prolongation of the PT is associated with an increased sensitivity of the aPTT to UFH. Increased sensitivity to heparin as demonstrated by an aPTT > anti-Xa in the absence of warfarin appeared to be an indicator of poor health with significantly higher 30-day mortality from underlying disease conditions. Further study is needed to determine whether the aPTT or anti-Xa should preferentially be used in heparin dosing nomograms when the values are discrepant. Disclosures: No relevant conflicts of interest to declare