Severe Arterial Forearm Thrombosis in an 11-year-old Girl with Homozygous Antithrombin Deficiency typ IIb Budapest 3 and Mild Factor VII Deficiency Due to Homozygous Polymorphisms in the Factor 7 Gene and Antithrombotic Treatment

Background: Inherited antithrombin (AT) type IIb Budapest 3 (AT Bp3) deficiency is a rare disorder affecting the heparin binding site of AT. Homozygosity for ATBp3 deficiency in contrast to a homozygous AT type I deficiency may not be fatal.

We report on a girl out of a family with homozygous AT Bp3 deficient members and concomitant mild factor VII deficiency (57-66%) related to polymorphisms in the factor 7 gene. She developed severe arterial thrombosis of the radial and ulnar arteries of the right forearm after a three weeks influenza period. A first thrombectomy in an external hospital was in vain despite the substitution of AT concentrate, argatroban anticoagulation and aspirin therapy.

Aim: To stabilise the anticoagulation and antithrombotic therapy before anew thrombectomy and during the surgical procedure, then to maintain a permanent patency of the occluded vessels.

Methods: Patient: 11 years, 140 cm, 45 kg b.w.; AT was monitored by factor Xa-based (AT-Xa) chromogenic, enoxaparin by chromogenic anti-factor Xa assay (AXa). D-dimers were measured by automated LIA, prothrombin fragments F1+2 by ELISA, apixaban was determined by an AXa-based chromogenic assay using an apixaban calibrator. Antiplatelet therapy with clopidogrel was monitored by multiplate whole blood impedance aggregometry. Preoperative treatment after admission: supplementation of AT i.v., anticoagulation with enoxaparin 2 mg/kg bw. x 24 h, intraoperatively standard heparin i.v.; after thrombectomy intraoperative thrombolysis with alteplase was performed. Also i.v. prostaglandin E1 (alprostadil) was given for 3 days, then clopidogrel was started with 150 mg, continued with 75 mg/d for 5 days, then reduced to 37.5 mg/d. Enoxaparin anticoagulation and AT substitution were continued. 4 days after surgery it was exchanged to apixaban starting with 5 mg b.i.d.; AT application ended 24 h later.

Findings: Previous data of the girl showed AT-Xa 11-14%, increased D-dimers between 0.55 and 0.65 mg/l (ref. < 0.5) over 12 months and borderline F1+2 of 0.344 nM (ref < 0.34) indicating a preexisting prethrombotic state. After admission to our hospital D-Dimers between 7.9 and 11 mg/l were seen. By high dose antithrombin and enoxaparin i.v. AT-Xa levels of 89 to 102% were achieved for 2 d, enoxaparin AXa levels were between 0.67 to 0.88 IU/ml. After thrombectomy D-dimers declined < 5 mg/l within 7 d. Clopidogrel induced a sufficient antiplatelet effect in multiplate assay. The apixaban dose induced sufficient apixaban trough of 78 and peak levels upto 261 ng/ml. Thereunder the D-dimers rapidly declined to 1.1 mg/ml within 10 days.

Conclusions: Patients with homozygous antithrombin Budapest 3 deficiency are at an increased risk of arterial and venous thromboembolic complications already during childhood. Anticoagulation with apixaban in combination with antiplatelet therapie with clopidogrel is efficient for secondary thromboprophylaxis after recurrent brachial and forearm arterial thrombosis.

 

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No conflict of interest has been declared by the author(s).