Use of recombinant human antithrombin concentrate in pregnancy

Patient 3 is a 27-year-old female with a history of pulmonary embolism 4 days after cesarean delivery of her first child. She was treated with weight-based enoxaparin without monitoring of anti-Xa levels. The patient sought hematology evaluation when she was 8 weeks pregnant with her second child. A hypercoagulable work-up was notable for an antithrombin level of 63%. Repeat testing showed antithrombin activity levels of 64%–73% with normal antigen levels. The patient had no family history of thrombosis. Due to the discrepancy between the amount of clinical heparin resistance and her antithrombin activity, sequencing of the SERPINC1 gene was completed. She was found to have a heterozygous mutation in the heparin binding site (c.218C > T, p.Pro73Leu) which is associated with type II antithrombin deficiency. To achieve therapeutic anticoagulation, the patient was treated with 1.8 mg/kg of enoxaparin. She did not require further increase in her enoxaparin dose after therapeutic levels were obtained ( Figure 1 ). She underwent elective induction at 37 weeks 3 days after rhAT infusion was initiated. Her last dose of enoxaparin was 24 hours prior to induction. Patient 3 required a cesarean delivery on HD2 due to intrapartum spontaneous conversion to breech presentation. A healthy male infant was delivered with an estimated blood loss of 1,200 mL due to uterine atony. Eight hours postpartum the patient was started on heparin infusion and warfarin. She achieved therapeutic anticoagulation within 4 hours. Her AT activity remained in the normal range without adjustments of her rhAT infusion ( Figure 2 ). On HD3, the patient developed right arm pain and was noted to have an occlusive superficial thrombus of the right basilic vein and a nonocclusive deep thrombosis of the distal right axillary vein associated with the peripherally inserted central catheter (PICC). The PICC was removed as it was considered the etiology of the thrombosis, and the patient continued the rhAT via a peripheral intravenous infusion. The patient’s right arm pain resolved and she was discharged on HD8 after therapeutic anticoagulation with warfarin was achieved.

In contrast to the Phase III trial of rhAT at delivery, the presented three patients did not require dose modifications to maintain therapeutic levels. 4 The continuous infusion also avoids peak and trough levels that occur with intermittent dosing of the pdAT concentrate. 1 Use of a recombinant product also removes the risk of blood-borne pathogen transmission, although no reported infectious transmissions with the pdAT have occurred. 1 The rhAT is more expensive than pdAT and carries a theoretic risk of immunogenicity. Our patients’ antibody testing per the US Food and Drug Administration’s post-marketing surveillance is pending, and no neutralizing antibodies were detected in other reported cases. 2 One of our patients experienced a catheter-associated thrombosis, and recurrent thrombosis has also been reported in patients treated with plasma-derived AT concentrates. 5 – 7 Even when AT replacement is given, physicians should remain vigilant about thrombosis and avoid other provoking factors if possible. Overall, the availability of two products to treat women with AT deficiency at delivery allows providers to select the management strategy best suited for their patient and institution.