Background: Hereditary Protein S (PS) deficiency is an autosomal dominant disorder with increased risk of venous thromboembolism (VTE), prevalent in 0.5% of the general population. The PS Heerlen polymorphism is a rare mutation at codon 501 of the PS gene that was initially considered a variant of uncertain significance but has since been shown to have a reduced levels of free PS.

Aims: Description of PS Heerlen polymorphism in an adolescent with deep venous thrombosis.

Methods: Collection of clinical data from Hamilton Health Sciences Medical record.

Results: A female patient, 14-year-old, presented with history of left lower leg fullness was diagnosed with deep vein thrombosis. The patient recently had prolonged airline travel and was using combined oral contraceptives. Anticoagulation with low molecular weight heparin was initiated. MRI venogram showed a narrowed left common iliac vein with mild compression of the proximal left common iliac vein by right common iliac artery, consistent with May Thurner syndrome. After 9 months of anticoagulation, a pro-thrombotic work up was initiated, including antithrombin III, protein C, Factor V Leiden, anticardiolipin antibodies, prothrombin gene mutation, which were normal. Free PS was decreased, 0.60 U/mL (some pediatric ranges reported, but not established). Peripheral blood was sent for DNA sequencing of Protein S, positive for heterozygous missense mutation variant, c.1501T>C, p.(Ser501Pro), (Heerlen polymorphism) in exon 13. The patient has continued on prolonged anticoagulation.

Conclusions: The association between PS Heerlen and VTE is controversial. In the pediatric population, PS deficiency alone generally increases risk of VTE 3x. This patient case indicates that Heerlen polymorphism is a potential contributing risk factor for VTE, in combination with other prothrombotic states, such as oral contraceptives and anatomical variants (May Thurner). Pediatric patients with this polymorphism should be considered to have a genetic basis of PS deficiency and managed accordingly, including genetic counseling and consideration of secondary thromboprophylaxis.

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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/a-case-of-a-pediatric-patient-with-protein-s-heerlen-polymorphism-and-deep-venous-thrombosis/