Impact of Heparin Hemodialysis Catheter Lock on Partial Thromboplastin Time Assays in Inpatients on Therapeutic Intravenous Heparin

ABSTRACT

Objective

Multiple in vitro and in vivo studies indicate that there is a significant amount of dialysis catheter lock leak with tunneled and nontunneled dual lumen hemodialysis (HD) catheters. The impact of heparin 1000 unit/mL HD catheter lock on outcomes in patients on therapeutic heparin has not been previously reported.

Methods

Twenty‐nine patients with 42 patient events on HD or continuous renal replacement therapy (CRRT) via double lumen catheters were retrospectively analyzed. Study patients received heparin 1000 unit/mL HD catheter lock while on therapeutic intravenous heparin. All patients had stable activated partial thromboplastin times (PTT) prior to catheter locking and had a PTT drawn within 6 h after administration of the heparin HD catheter lock.

Results

The average prelock PTT was 56 s and postlock PTTs increased on average to 85 s (p < 0.0001). PTTs were significantly higher when drawn closer to the administration time of the heparin catheter lock. Major bleeding occurred in many surgical patients after heparin HD catheter lock administration.

Conclusion

Citrate or saline HD catheter lock may be preferable to heparin HD catheter lock in patients on intravenous heparin infusions, especially in high‐bleed‐risk surgical patients.

1. Introduction

Observation of supratherapeutic anticoagulation assays and subsequent bleeding requiring intervention after administration of heparin 1000 unit/mL hemodialysis (HD) catheter lock in several patients on intravenous therapeutic heparin (Figure 1) led to the hypothesis that significant heparin lock leak may occur, resulting in supratherapeutic anticoagulation and potential bleeding events. Multiple in vitro and in vivo studies indicate that there is a significant amount of dialysis catheter lock leak with tunneled and nontunneled dual lumen HD catheters [1, 2, 3, 4]. HD catheter lock with heparin 5000 unit/mL solution has been associated with supratherapeutic anticoagulation assays and bleeding complications without therapeutic antiocagulation [5, 6]. The American Society of Diagnostic and Interventional Nephrology guidelines recommend heparin 1000 units/mL or citrate 4% lock be used to maintain HD tunneled catheter patency [7]. The Kidney Disease Outcomes Quality Initiative Clinical Practice Guidelines for Vascular Access suggests that either citrate or heparin be used as HD central venous catheter locking solution [8]. The impact of heparin 1000 unit/mL HD catheter lock on outcomes in patients on therapeutic heparin has not been previously reported.

FIGURE 1.

Impact of heparin lock on PTT.

2. Methods

An IRB‐approved retrospective analysis was performed in 29 patients with 42 patient events, 18 years and older, who received HD or continuous renal replacement therapy (CRRT) while on therapeutic heparin had a double lumen catheter placed for HD/CRRT, had a stable activated partial thromboplastin time (PTT) prior to catheter locking, and received heparin catheter lock with heparin 1000 unit/mL (0.2 mL overfill/lumen) within 6 h of a subsequent PTT. PTTs exceeding our laboratory reporting threshold of 150 s were capped at 150 s. Patients were excluded from bleeding assessment if they had documented bleeding in the 24 h preceding heparin HD lock. The primary outcome was the comparison between PTT values of patients on therapeutic heparin before and after they received heparin HD lock. A secondary outcome was the incidence of major bleeding events, defined as hemoglobin drops that required interventions including cessation of therapeutic heparin, blood transfusions, or transition to a higher level of care. A paired t‐test was utilized to compare differences in both pre and post heparin lock PTT values.

3. Results

The average age of study patients was 59 years. Males represented 64% of the study group. Sixty‐four percent was white, and 9.5% was African American. HD was performed in 52% of the patients, and 48% received CRRT. Seventy‐six percent of patients had acute kidney injury, with the remainder having end stage renal disease. Nontunneled catheters were used in 72% of patients with the other patients utilizing tunneled catheters. Internal jugular vein access was used in 69% of the events with the remainder utilizing femoral vein access. Patients were on a stable heparin dose with therapeutic PTTs an average of 24.5 h prior to heparin HD lock administration.

There was a 51% increase in PTT assays in the overall cohort when assessed within 6 h of HD lock administration (Table 1). The institutional therapeutic heparin goal PTT range was 44–65 s. The average prelock PTT was 56 s and post‐lock PTTs increased on average to 85 s (p < 0.0001). PTTs were stratified into 2‐h segments after heparin HD lock administration. PTTs drawn within 2 h of heparin HD lock were noted to have the highest degree of elevation at 90 s on average. Six patients had PTTs greater than 150 s. These six patients exceeded our laboratory reporting level for elevated PTTs.

TABLE 1.

Impact of heparin HD lock timing on PTT assays.

PTT timing and result	Prelock PTT result	Postlock PTT result	p‐value (two‐tail)
PTT within 6 h of lock	(n = 42)	(n = 42)
Mean PTT (s)	56.3	85.0	0.0000002
PTT within 2 h of lock	(n = 15)	(n = 15)
Mean PTT (s)	54.0	90.3	0.0008
PTT 2–4 h after lock	(n = 17)	(n = 17)
Mean PTT (s)	58.6	87.5	0.002
PTT 4–6 h after lock	(n = 10)	(n = 10)
Mean PTT (s)	55.6	72.8	0.018

Major bleeding was assessed in 29 patients overall. There were 22 surgical patients and 7 medical patients. Overall major bleeding occurred in 41% of these patients. Twelve (55%) surgical patients met study criteria for major bleeding. Blood transfusions were administered to 23% of surgery patients due to bleeding that occurred after administration of heparin HD lock.

4. Discussion

In vitro and in vivo studies of HD catheter lock volume leak indicate that dual lumen catheters leak a significant amount of volume within seconds of administration. An in vitro analysis of three different dual lumen HD catheters of multiple lengths revealed a total lock leak volume of 0.96–1.43 mL within 5 s when a 20% overfill lock volume was used [1]. An in vitro analysis of two different dual lumen HD catheters noted a lock leak volume of 0.59–0.71 mL within seconds when a total lumen volume lock solution was used [2]. An in vivo study of two tunneled and one nontunneled dual lumen HD catheters identified a lock leak volume 0.48–0.91 mL assessed within minutes of total lock volume administration [3].

Studies in HD patients not receiving therapeutic heparin have noted increased anticoagulation assays and bleeding events associated with HD lock leak when heparin 5000 unit/mL lock solution was utilized. An analysis of 20 patients in which heparin 5000 unit/mL total lumen volume was used to lock catheters after HD and noted that 74% of patients had at least a 50% increase in PTT ratios from baseline [5]. The average increase in PTT ratios was over 88%. Another analysis of 52 HD patients who received heparin 5000 unit/mL total lumen volume HD locking solution was compared to 91 patients who received citrate or heparin 1000 unit/mL HD total catheter volume locking solution [6]. Patients who received the heparin 5000 unit/mL HD catheter locking solution had significantly more major and minor bleeding events OR 11.9; 95% CI 1.10–128.9; p = 0.04. A multicenter, double blind, trial of 291 HD patients randomized to citrate lock or heparin 5000 unit/mL total lumen volume observed a significant increase in major bleeding in the 143 patients in the heparin lock arm (p = 0.01) [9].

Clinically and statistically significant elevations in PTT assays were observed in our study in therapeutically anticoagulated patients receiving heparin infusions after administration of heparin 1000 unit/mL HD catheter lock solution. PTTs were capped at 150 s if the laboratory result was reported as greater than 150 s. The elevated average reported PTT assay would have been even higher, given that 14% of patients had PTTs exceeding 150 s. Given the half‐life of heparin is approximately 60 min with therapeutic heparin dosing and greater than 100 min with supratherapeutic levels, it is likely that most of the patients PTTs would have exceeded 100 s within minutes of heparin locking [10]. Supratherapeutic levels of heparin have been associated with increased risk of major bleeding. One major trial involving heparin anticoagulation reported for every 10 s increase in PTT, the probability of major bleeding increased by 7% (p = 0.0004) [11]. In another large trial involving intravenous heparin anticoagulation, PTT ratios greater than 2.75 were associated with a significant increase in major/minor bleeding OR 2.11; 95% CI 1.27–3.53; p = 0.004 [12]. Major bleeding occurred after the administration heparin HD lock in 55% of applicable surgical patients in our study with 23% requiring blood transfusions. The occurrence of supratherapeutic PTTs and bleeding in this study of patients receiving therapeutic intravenous heparin anticoagulation and heparin 1000 unit/mL HD lock is consistent with studies of heparin 5000 unit/mL HD lock in nonanticoagulated patients.

Several guidelines suggest or recommend the use of heparin or citrate lock to maintain patency of central venous HD catheters [7, 8]. Normal saline lock has successfully been used as HD catheter lock solution as well [13, 14]. Citrate lock has been shown to have potential benefit over saline lock in a randomized‐controlled trial in maintaining nontunneled HD catheter patency [15]. Based off this information and guidance, our inpatient electronic medical record order for HD catheter lock has been modified with provider information to use citrate lock instead of heparin 1000 unit/mL lock if patients are on intravenous therapeutic heparin infusions or have known or suspected heparin‐induced thrombocytopenia.

5. Conclusion

The use of heparin 1000 unit/mL HD catheter lock for patients on therapeutic intravenous heparin anticoagulation can lead to significant supratherapeutic increases in PTT assays that can be seen for up to 6 h after administration of the heparin lock. This supratherapeutic anticoagulation may be associated with a higher bleed risk in surgical patients. In patients receiving therapeutic heparin requiring HD catheter lock, citrate or saline lock may be preferable to heparin lock to avoid undesired supratherapeutic anticoagulation in high‐bleed‐risk patients.

Conflicts of Interest

The authors declare no conflicts of interest.

Tuggle T., Noureddine L., and Hobbs R., “Impact of Heparin Hemodialysis Catheter Lock on Partial Thromboplastin Time Assays in Inpatients on Therapeutic Intravenous Heparin,” Seminars in Dialysis 38, no. 4 (2025): 282–285, 10.1111/sdi.13260.

Data Availability Statement

Research data are not shared.