Original Report: Patient-Oriented, Translational Research American

Journal of

Nephrology

Received: February 13, 2014 Accepted: August 23, 2014 Published online: October 17, 2014

Am J Nephrol 2014;40:300–307 DOI: 10.1159/000367901

Heparin Use in Hemodialysis Patients following Gastrointestinal Bleeding Jenny I. Shen a, c Aya A. Mitani b Wolfgang C. Winkelmayer a, d   

a

 

 

Division of Nephrology, b Division of General Medical Disciplines, Department of Medicine, Stanford University School of Medicine, Palo Alto, Calif., c Division of Nephrology and Hypertension, Department of Medicine, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, Calif., and d Section of Nephrology, Department of Medicine, Baylor College of Medicine, Houston, Tex., USA  

 

 

 

Abstract Background: Heparin is commonly given during hemodialysis (HD). Patients undergoing HD have a high rate of gastrointestinal bleeding (GIB). It is unclear whether or when it is safe to give heparin after acute GIB. We describe the patterns and safety of heparin use with outpatient HD following an acute GIB. Methods: We identified patients aged ≥67 who, from 2004–2008, experienced GIB requiring hospitalization within 2 days of receiving maintenance HD with heparin. We used Cox regression to estimate the risk of recurrent GIB and death associated with receiving heparin the day they resumed outpatient HD post-GIB. Results: Of the 1,342 patients who had GIB, 1,158 (86%) received heparin at a median dose of 4,000 units with their first outpatient HD session after discharge from GIB. On average, their post-GIB doses were slightly lower than their pre-GIB doses (mean change: –214 ± 3,266 units, p < 0.02). However, only 27% of patients had a decrease in their dose, while 21% had their dose increased. We did not find an increased risk of death or recurrent GIB associated with using heparin post-GIB (HR; 95% confidence interval (CI), for death: 1.01; 0.69–1.48; for recurrent GIB: 0.78; 0.39–1.57). Conclusions: The vast majority of these high-risk patients received heparin on the very first

© 2014 S. Karger AG, Basel 0250–8095/14/0404–0300$39.50/0 E-Mail [email protected] www.karger.com/ajn

day they resumed outpatient HD post-GIB, and the majority at unchanged doses to those received pre-GIB. Even if the practice was not associated with increased risks of death or re-bleeding, it highlights an area for possible system-based improvement to the care for patients on HD. © 2014 S. Karger AG, Basel

Introduction

Practitioners commonly use heparin to anticoagulate the dialysis circuit during hemodialysis (HD). Between 2004 and 2008, 93% of older U.S. patients who initiated HD with a national dialysis provider received heparin during their HD session [1]. However, patients on HD have gastrointestinal bleeding events (GIB) at a considerably high rate of 6 events per 100 person-years [2]. Yet, it is unclear whether or when it is safe to restart heparin after a GIB. In this retrospective cohort study, we describe the patterns and safety of heparin use with outpatient HD following discharge from a hospitalization for a GIB. Materials and Methods Data Source We used data merged from the United States Renal Data System (USRDS) and the electronic medical records (EMR) of a national dialysis provider using a crosswalk of anonymized patient

Jenny I. Shen, MD, MS Division of Nephrology and Hypertension, Department of Medicine Harbor-UCLA Medical Center, 1000 W. Carson St., C1 Annex Torrance, CA 90502 (USA) E-Mail jshen @ labiomed.org

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Key Words Anti-coagulation · Gastrointestinal bleeding · Hemodialysis · Heparin

Study Population We selected a contemporary cohort of patients who experienced an upper non-variceal GIB (as defined by the stringent criteria in Yang et al. [2]) requiring hospitalization sometime between January 1, 2004 and December 31, 2008. We included only those patients who were admitted within two days of receiving heparin with outpatient HD at a participating facility. This twoday window is to allow time between the onset of symptoms and presentation/admission to the hospital. We excluded patients who did not resume outpatient HD following the GIB. We restricted our study population to patients 67 years of age or older whose primary payer was Medicare for at least one year prior to the index date so that we could uniformly ascertain comorbidities from Medicare claims data. Similarly, patients must have been dialyzing with the provider for at least 30 days prior to the event so that we could ascertain lab values. We also excluded patients with a history of warfarin use in the year prior to the index date as the drug has been shown to increase the risk of hemorrhage in patients on dialysis [3–6]. Please see figure 1, which outlines the study population selection. Our final cohort included 1,342 patients. Exposure: Heparin We categorized patients as users, or exposed, if they received heparin during their first outpatient HD session following discharge from the hospitalization for GIB. We abstracted data on both the treatment date and heparin administration from the EMR of the dialysis provider. We did not consider any heparin given as catheter lock. Death and Recurrent GIB To evaluate the safety of receiving heparin post-GIB, we estimated its association with death and first recurrent GIB. These events were ascertained from inpatient Medicare claims data and the USRDS death file based on a previously validated algorithm [2].

131,252 patients >65 years of age underwent HD with the national dialysis provider from 2004–2008

10,464 were –67 years old and hospitalized with a GIB 9,227 had Medicare as primary payer for –\HDU continuously prior to the GIB 6,055 dialyzed with the provider –GD\VSULRUWRWKH*,%

1,896 received HD with heparin in the 2 days prior to the GIB

1,639 were hospitalized for the GIB

1,558 had no history of warfarin use –\HDUSULRUWRWKH*,%

1,342 resumed outpatient HD

Fig. 1. Study population selection from the United States Renal

Data System. We selected a cohort of patients 67 years of age or older whose primary payer was Medicare who, between 2004 and 2008, experienced a gastrointestinal bleeding event requiring hospitalization within two days of receiving heparin with outpatient HD. GIB = Gastrointestinal bleeding event; HD = hemodialysis.

days apart in the year prior to the index date [2]. GIB characteristics were abstracted from Medicare claims data; the time to restarting outpatient HD was also calculated using EMR data. Vital signs, laboratory measurements, and dialysis characteristics were abstracted from the EMR. Facility factors were taken from USRDS (see table 1 footnotes for more detail). Variables were categorized into clinically relevant ranges, except for weight and facility size, which were categorized by quartile.

Other Variables Demographics, comorbidities, GIB characteristics, vital signs, laboratory measurements, dialysis characteristics, and facility factors were chosen a priori as potentially and clinically relevant confounders. All variables are listed in table 1. Demographic factors were obtained from the USRDS. Comorbidity status was derived from both the Medical Evidence Report (CMS form 2728) and Medicare claims data predating the index date by up to one year. The comorbidity definitions, which were derived from both previously validated algorithms and a comprehensive search of ICD-9 diagnosis codes, are provided in online suppl. table 1 (for all online suppl. material, see www.karger.com/ doi/10.1159/000367901). Comorbidities were assigned if coded in at least one inpatient claim or two outpatient claims more than 30

Statistical Analysis We described baseline characteristics of the cohort using means and standard deviations for normally distributed continuous data, medians and 25th and 75th percentile values for non-normally distributed data, and counts and proportions for categorical data. Differences between those who received heparin post-GIB and those who did not were compared using the Student’s t test, Wilcoxon ranksum test, or χ2 test, as appropriate. Paired t test was used to compare heparin doses pre- and post-GIB in those who restarted heparin. We used proportional hazards regression to estimate the hazard ratio for (1) death and (2) recurrent GIB in those who received heparin post-GIB vs. those who did not. We defined the index date as the day that they resumed outpatient HD and followed patients for a year after the index date. We censored patients for change in heparin user status (i.e., when heparin users

Heparin in Hemodialysis Post GI Bleeding

Am J Nephrol 2014;40:300–307 DOI: 10.1159/000367901

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identifiers that the USRDS Center generated upon approval by the Centers for Medicare and Medicaid Services (CMS) and the National Institutes of Diabetes and Digestive and Kidney Diseases (NIDDK). The USRDS contains demographic information for almost all Americans with end-stage renal disease, billing claims to Medicare (Parts A and B), which are available for the vast majority of Americans from the age of 65, as well as comorbidities and dialysis facility information from forms submitted to the CMS. The EMR includes records on heparin and warfarin use, vital signs, laboratory measurements, and HD prescriptions.

Table 1. Baseline characteristics of patients who resumed outpatient hemodialysis (HD) after a gastrointestinal

bleeding event (GIB), categorized by whether they received heparin post-GIB Received heparin post-GIB (n = 1,158)

p value

77±6 573 (49)

0.02 0.99 0.04

Demographics Age, years, mean ± SD Male, sex, n (%) Race, n (%) Black White Other1 Hispanic ethnicity Years on dialysis (median & IQR)

46 (25) 129 (70) – (5) 20 (11) 1.7 (0.6–3.4)

372 (32) 701 (61) 85 (7) 150 (13) 1.8 (0.7–3.5)

0.43 0.49

Reported comorbidities, n (%) Arrhythmia Cancer Coronary artery disease Deep vein thrombosis1 Diabetes mellitus Previous gastrointestinal bleeding Heart failure Hemorrhagic stroke1 Ischemic stroke Liver disease1 Peripheral vascular disease Pulmonary disease Pulmonary embolism1

40 (22) 15 (8) 82 (45) – (4) 100 (54) 22 (12) 85 (46) – (1) 42 (23) – (4) 56 (30) 37 (20) – (

Heparin use in hemodialysis patients following gastrointestinal bleeding.

Heparin is commonly given during hemodialysis (HD). Patients undergoing HD have a high rate of gastrointestinal bleeding (GIB). It is unclear whether ...
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