Thrombophilia Testing in Hospitalized Children: Waste Not, Want Not?
Authors: Mahajerin Arash , Vik Terry , Mehta Rakesh P , Heiny Mark 
Published: October 2019

Abstract
Abstract 1150

Introduction
The incidence of venous thromboembolism (VTE) in children is rising. Our institutional experience has shown VTE incidence in hospitalized children rose from 0.3 to 71/10,000 admissions over a 13 year span. Many of these children had multiple acquired risk factors, e.g. central venous line (CVL), and many of these children underwent extensive thrombophilia testing. Hypothesis: Thrombophilia testing in hospitalized children with VTE is unnecessary and adds cost burden to patient (pt) care.

Methods
We evaluated thrombophilia testing performed in children aged 0–20 admitted to Riley Hospital for Children from Jan 2005-Apr 2012. Eligibility criteria included admission for > 48 hours with no clinical suspicion of VTE on admit and subsequent VTE confirmed by ultrasound, CT or MRI. We evaluated for presence of 8 acquired risk factors identified a priori and known to be significant at our hospital: BMI > 85th %ile for age/gender, length of stay > 7 days, mechanical ventilation, direct ICU admit, bacteremia, immobilization > 72 hours, estrogen therapy, and CVL presence (Sharathkumar et al J Thromb Haemost 2012). Thrombophilia testing included Protein C, Protein S, and Antithrombin activities, antiphospholipid antibody panel (APLA, including anti-phosphatidylserine, anti-cardiolipin and lupus anticoagulant), β2 glycoprotein 1 (β2GP1) Ab, presence of Factor V Leiden (FVL) and prothrombin 20210A gene (PTm) mutations, PAI-1 and MTHFR gene (A1298C & C677T) polymorphisms. A thrombophilic condition was diagnosed if a low Protein C, Protein S, or Antithrombin activity was found initially and confirmed after VTE resolution, if APLA or β2GP1 Ab was positive at diagnosis and again after > 12 weeks, hetero- or homozygosity for FVL or PTm, 4G/5G or 4G/4G PAI-1 status with elevated PAI-1 serum level, or MTHFR mutation with elevated fasting AM homocysteinelevel. Cost of thrombophilia testing was evaluated with hospital charges and Medicaid reimbursement rates.

Results
VTE was diagnosed in 239 patients. At least 1 risk factor was found in 232 (97%) patients and 7 (3%) had no risk factors. These 7 patients with no risk factors had thrombophilia tests done and none had a positive test. Presence of a CVL was significantly associated with nothaving any tests done (p<0.0022).
At least 1 thrombophilia test was ordered on 157/239 patients (66%). There were 940 total tests ordered (6 tests/pt) and only 16 positive results (1.7%). Eleven patients were FVL heterozygous and 1 patient was FVL homozygous yielding FVL prevalence of 7.6%. Four patients were PTm heterozygous yielding PTm prevalence of 2.5%. This is similar to prevalence of FVL (5–7%) and PTm (3%) in healthy populations (Martinelli J Thromb Haemost2001).
Table 1 shows thrombophilia testing distribution. Cost analysis shows average Medicaid reimbursement of 32.7% of charges billed. Medicaid cost savings of up to $365.25/ptcan be attained by eliminating routine thrombophilia testing in hospitalized children who develop VTE.

Discussion
The incidence of VTE in hospitalized children is increasing. Many hospitalized children who develop VTE undergo thrombophilia testing. With increased survival of children with chronic diseases and increased prevalence of acquired VTE risk factors, thrombophilia testing in hospitalized children is not necessary and adds cost burden. Thrombophilia testing in children may best be limited to spontaneous VTE. This evaluation is somewhat limited by the low number of subjects with APLA, PAI-1 serum activity or homocysteine labs. Also, we did not include other risk factors, e.g. family history. However, recent ACCP guidelines recommend anticoagulation duration not be adjusted for presence of thrombophilia. There is also concern Medicaid may not reimburse for inpatient VTE in children in the future. Considering we found no difference between hospitalized children with VTE and healthy populations along with current and future financial concerns, we support not testing for thrombophilia in hospitalized children who develop VTE.

Disclosures:
No relevant conflicts of interest to declare.