Abstract Number: PB1300
Meeting: ISTH 2020 Congress
Background: Antithrombin (AT) deficiency is the most severe thrombophilia and is caused by various mutations on the SERPINC1 gene. The functional defect affecting the heparin binding site (HBS) of AT in homozygous individuals confers high risk of venous thrombembolism (VTE).
Aims: To evaluate the response to anticoagulant therapy.
Methods: We present a case of a 15-year-old boy with iliofemoral phlebothrombosis with extension to the vena cava inferior. He was diagnosed in early childhood with epilepsy syndrome and cerebral palsy and is on multiple antiepileptic drugs (AEDs). The thrombophilia screening showed only a slight decrease in AT activity. After administration of weight-based therapeutic dose low molecular weight heparin (LMWH), the measured peak anti-Xa level was very low. AT deficiency was suspected and genetic analysis was performed. Because of potential drug interactions of acenocoumarol with AEDs and difficulties in regular laboratory monitoring in this patient, it was decided to start off-label use of DOACs (Apixaban 2 x 2.5 mg or Dabigatran 110 mg once daily).
Results: AT activity was 74 % (Berichrom® AT III, range 79.4% – 112%). Anti-Xa level measured 4 hours after administration of Clexane 30 mg twice daily was < 0.1 U/mL. DNA analysis showed homozygous mutation - p.Leu131Phe at the HBS of AT (Illumina MiSeq platform). We found trough plasma level of Apixaban 16 ng/mL (DiXaI®, range 42 – 140 ng/mL). The plasma level of Dabigatran measured 12 hours after administration was 86 ng/mL (Hemoclot®, trough level 45 – 220 ng/mL). There was neither VTE recurrence nor bleeding events during one year of follow-up.
Conclusions: As previously described, molecular testing identifies mutations that can be missed by traditional activity assays. Therapeutic LMWH doses can´t attain sufficient anticoagulation in patients with homozygous HBS AT deficiency. Dabigatran seems to be an appropriate alternative to conventional anticoagulants in these patients.
To cite this abstract in AMA style:
Doncheva E, Paskaleva I, Dobrev D, Kaneva A, Vazharova R, Balabanski L, Atanasoska M. Heparin Resistence in Pediatric Patient with Homozygous Antithrombin Deficiency, Treated with Dabigatran: A Case Report [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/heparin-resistence-in-pediatric-patient-with-homozygous-antithrombin-deficiency-treated-with-dabigatran-a-case-report/. Accessed March 22, 2024.« Back to ISTH 2020 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/heparin-resistence-in-pediatric-patient-with-homozygous-antithrombin-deficiency-treated-with-dabigatran-a-case-report/