Patients with sickle cell disease (SCD) are at an increased risk of developing venous thromboembolism (VTE), leading to the use of pharmacologic and mechanical thromboprophylaxis (TP) in high-risk settings such as hospitalization. The use of pharmacologic TP increased between 2010 and 2021 in hospitalized adolescents, according to a retrospective study published in Blood Advances.
Jennifer Davila, MD, of Children’s Hospital at Montefiore in New York, and colleagues sourced data from the Pediatric Health Information Systems (PHIS) managed by the Children’s Hospital Association. They studied more than 7,000 patients with SCD between the ages of 13 and 21 who were admitted to a PHIS hospital between January 1, 2010, and June 30, 2021. Dr. Davila and colleagues observed the use of anticoagulant medications among hospitalized patients, the use of mechanical prophylaxis, and the subspecialty of the attending physician to determine hematology involvement.
Of the 7,202 patients and 34,094 unique admissions studied, 3.6% of admissions (n=1,225) received pharmacologic TP, 4.3% received mechanical TP (n=1,474), and 0.3% received both (n=99). During the study period, the use of both pharmacologic and mechanical TP increased significantly (p<0.0001).
Mechanical TP use increased from 3.3% to 6.2% between 2010 and 2017 but decreased to 3.5% by June 2021, conveying no significant change in the prescription of mechanical prophylaxis. In contrast, pharmacologic TP use steadily increased during the span of the study, the greatest rise being between 2017 (4.2%) and 2021 (14.4%). Researchers attributed this to an increased use of enoxaparin – as opposed to direct oral anticoagulants (DOACs) – which was prescribed in 87% of admissions in which pharmacologic TP was used and remained the primary anticoagulant prescribed during the course of the study.
Researchers noted differences in prophylaxis use depending on patient age and hematology involvement. TP was more likely to be used in patients ages 18 to 21 (10.8% of admissions; p<0.001) versus those ages 15 to 17 (6.1%) or 13 to 14 (5.0%). Although most admissions (n=29,775; 87.3%) had a hematology provider involved as the admitting, attending, or consulting physician, patients who were treated without hematology involvement were more likely to receive pharmacologic (4.6% vs. 3.4%; p<0.001) or mechanical (5.4% vs. 4.2%; p<0.001) prophylaxis compared to admissions on the hematology service. However, DOACs were more likely to be prescribed in admissions that involved a hematology/oncology provider (0.1% vs. 0.6%; p<0.0001).
There was no U.S. Food and Drug Administration (FDA) approval for DOAC use in patients younger than 18 at the time of data collection, which researchers said accounts for the rise in DOAC use mainly in patients ages 16 and older. Despite this, DOACs were still prescribed for TP, with the first documented use in 2018. By 2021, DOACs were used in 25% of all admissions in which pharmacologic TP was administered.
This finding indicates that “pediatric treaters ... despite not having evidence-based data to support [TP] in SCD, are still using anticoagulation with [their] pediatric patients,” Dr. Davila said.
A notable limitation of the study is a “lack of granular data ... when looking at a database retrospectively,” Dr. Davila said. More information regarding a patient’s medical history may indicate the use of mechanical or pharmacologic TP for other purposes.
More research is needed to evaluate the safety and efficacy of TP in adolescent patients with SCD, they wrote.
“The issue with pediatric hematology is that we don’t have a lot of data to guide what we do,” Dr. Davila said, adding that she hopes her study offers “more evidence to support pediatric hematologists who are prescribing [TP] in this population.”
Any conflicts of interest declared by the authors can be found in the original article.
Reference
Davila J, Stanek J, O’Brien S. Venous thromboembolism prophylaxis in sickle cell disease: a multicenter cohort study of adolescent inpatients [published online, 2022 Sept 19]. Blood Adv. doi: 10.1182/bloodadvances.2022007802.
Perspectives
In the past decade, there has been mounting evidence of the high risk of VTE in patients with SCD. Studies have shown that more than 10% of individuals with SCD will develop a VTE by age 40, with incidence of VTE starting around adolescence.1 Hospitalization is undoubtedly a major risk factor for VTE in SCD; however, TP protocols have not been standardized, especially among pediatric and adolescent patients.
Using a large multicenter pediatric administrative database, this study investigated the trends in pharmacologic TP prescribing practices from 2010 to 2021 for adolescents ages 13 to 21. The authors found that pharmacologic prophylaxis use jumped from 1.3% to 14.4% in this time, with increasing use of DOACs over time. This study highlights the increasing recognition of SCD as a hypercoagulable state, even in adolescent patients.
While this study suggests clear trends in pharmacologic prophylaxis use, unanswered questions remain. Prior studies in pediatric patients with SCD have suggested that catheters are a primary underlying risk factor for VTE.2 Given the thrombogenicity of catheters, prophylactic doses of anticoagulation may not be sufficient to prevent these thrombotic complications. In addition, this study did not include compliance data, though it is certainly intriguing to speculate that compliance may be higher among patients prescribed DOACs compared to subcutaneous enoxaparin.
The increasing use of pharmacologic TP in SCD is encouraging as it reflects physician recognition of VTE as a modifiable complication in this high-risk population. DOACs promise to change both patient satisfaction and physician attitudes toward TP given their oral rather than subcutaneous administration. More research is needed to confirm the safety and efficacy of DOACs as VTE prophylaxis in SCD.
Rakhi Naik, MD, MHS
Johns Hopkins University
Baltimore, Maryland
References
- Naik RP, Streiff MB, Haywood Jr C, Segal JB, Lanzkron S. Venous thromboembolism incidence in the Cooperative Study of Sickle Cell Disease. J Thromb Haemost. 2014;12(12):2010-2016.
- Woods GM, Sharma R, Creary S, et al. Venous thromboembolism in children with sickle cell disease: a retrospective cohort study. J Pediatr. 2018;197:186-190.e1.