Quality of warfarin anticoagulation in adults with short bowel syndrome on home parenteral nutrition
The prevalence of home parenteral nutrition (HPN) in Europe is 0.65–12.7/1,000,000 adult population [1]. The risk of thromboembolic complications among HPN patients is high with an estimated annualized incidence of approximately 11.4% [2]. Risk factors for thromboembolic events include permanent venous catheters, hyperosmolar nutrition solutions, endothelial damage, and pre-existing prothrombotic diseases.
The prevalent use of long-term anticoagulation among HPN patients ranges between 22% and 66% [3]. Currently, there is no firm evidence on optimal anticoagulation for HPN patients and prescriptions necessarily rely on individual characteristics. Extended parenteral anticoagulation may be associated with poor compliance, risk of heparin-induced thrombocytopenia (HIT), and osteoporosis. Direct oral anticoagulants seem to be a feasible option for the primary and secondary thrombosis prevention, although their bioavailability may vary depending on the degree of their oral absorption [4, 5, 6]. Finally, the quality of vitamin K antagonists (VKA) treatment is influenced by oral absorption, hepatic impairment associated with abnormal INR values, routine vitamin K supplementation, and bacterial overgrowth leading to impaired vitamin K metabolism. Despite this, VKA remains the most widely used drug class in this population and is recommended by the European Society for Clinical Nutrition and Metabolism (ESPEN) guidelines in case of catheter-related venous thrombosis [7, 8].
In light of the substantial paucity of data on the quality of VKA anticoagulation in adults on HPN, we studied this in patients on HPN and matched controls with an indication for VKA.
We retrospectively analyzed a cohort of 12 consecutive patients on HPN and warfarin who have been followed for more than 3 months during follow-up. All patients were managed at the reference HPN center of the University Hospital in Torino, Italy (2004–2015). Patient data were retrieved from their medical records. HPN patients were matched based on sex, age, and the indication for anticoagulation in a 1:8 ratio to 96 patients on VKA enrolled in the Italian START register [9]. The quality of VKA was measured as time in therapeutic range (TTR; INR range: 2–3) calculated according to the interpolated Rosendaal′s formula and expressed as percentual of in-rage days.
Baseline characteristics were analyzed using appropriate descriptive statistics. Thromboembolic complications (i.e., arterial and venous thromboembolism) and major bleeding events (International Society on Thrombosis and Haemostasis criteria) were recorded as reported by the treating medical staff and expressed as absolute number and incidence (number of events/100 patient-years). The time unit of statistical analysis was patient-year and the start of observation was set at onset of the VKA therapy. Individuals were right-censored at the time of event, VKA discontinuation, death or if they were lost to follow-up. Individuals still receiving VKA at the time of data collection were right-censored in accordance with the latest available follow-up visit. The software Jamovi (version 1.6) based on R language was used for the analysis. Ethical approval was obtained at each center participating in the START-registry and at the aforementioned HPN referral center.
The baseline characteristics of the study population are depicted in Table I. The median follow-up time was 48 (Q1–Q3: 23–89) months for HPN patients and 30 (Q1–Q3: 19–43) months for controls. The most frequently used central vein catheter in HPN patients was the Groshong catheter (n=8). Median TTR calculated over the entire follow-up period was 62% (Q1–Q3: 47–73) in HPN patients and 68% (Q1–Q3: 55–78) in controls. During stable anticoagulation, namely excluding the initial 3 months of VKA therapy, TTR was 63% (Q1–Q3: 46–77) and 69% (Q1–Q3: 55-78), respectively. The incidence of a composite of thromboembolic, major bleeding, and anticoagulation-related death events was similar in both groups with an incidence ratio of 0.9 (95% CI: 0.2–3.0). A total of two bleeding and one thromboembolic complications was reported in HPN patients: one patient had a gastrointestinal bleeding and a second had a gastrointestinal bleeding and a catheter-related thrombosis. The latter had a low median TTR of 44.5%. Among controls there were 11 bleedings (6 gastrointestinal, 2 hematuria, 1 cranial and 2 unknown), 1 arterial thromboembolism (transient ischemic attack), and 1 anticoagulation-related death (fatal intracerebral hemorrhage).
Our findings indicate that the quality of VKA anticoagulation in HPN patients appeared similar to that observed in controls (62% vs. 68%), and exceeding the 60% limit from the literature defining adequate anticoagulation [10]. This group of HPN patients seemed to be characterized by similar rate of anticoagulant-related complications than controls and by an overall lower event rates as compared to other HPN cohorts of unselected patients [2, 7]. This study has a number of limitations which include the small sample size and consequently the low precision of the estimates, the retrospective study design, unaccounted differences in the baseline characteristics between groups, and the lack of information concerning HPN cases in whom VKA was discontinued early (i.e., in the first 3 months) possibly due to poor INR control. Moreover, one cannot exclude that the good quality of VKA treatment among HPN patients may have been due, at least in part, to higher intensity of medical care.
In conclusion, we provided initial data on the quality of VKA in selected adult patients on HPN, suggesting that VKA might be adequately managed also in this patient population and associated to an acceptable rate of complications.
References
1 Home parenteral nutrition in adults: a european multicentre survey in 1997. ESPEN-Home Artificial Nutrition Working Group. Clin Nutr. 1999;18(3):135–40.
2 Home parenteral nutrition-associated thromboembolic and bleeding events: results of a cohort study of 236 individuals. J Thromb Haemost. 2016;14(7):1364–73.
3 . Anticoagulants for the prevention and treatment of catheter-related thrombosis in adults and children on parenteral nutrition: a systematic review and critical appraisal. Blood Transfus. 2017;15(4):369–77.
4 . Rivaroxaban as anticoagulant therapy in short bowel syndrome. Report of three cases. Thromb Res. 2015;135(3):568–70.
5 Pharmacokinetics of dabigatran etexilate and rivaroxaban in patients with short bowel syndrome requiring parenteral nutrition: The PDER PAN study. Thromb Res. 2017;160:76–82.
6 . Insufficient anticoagulation with dabigatran in a patient with short bowel syndrome. Thromb Haemost. 2014;112(2):419–20.
7 . Anticoagulants decrease the risk for catheter-related venous thrombosis in patients with chronic intestinal failure: A long-term cohort study. J Parenter Enteral Nutr. 2021.
8 ESPEN practical guideline: Clinical nutrition in chronic intestinal failure. Clin Nutr. 2021;40(9):5196–220.
9 The Italian START-Register on Anticoagulation with Focus on Atrial Fibrillation. PLoS One. 2015;10(5):e0124719.
10 . Benchmark for time in therapeutic range in venous thromboembolism: a systematic review and meta-analysis. PLoS One. 2012;7(9):e42269.
