Five Challenging Cases of Hereditary Antithrombin Deficiency Characterized by Thrombosis or Complicated Pregnancy

Abstract

Hereditary antithrombin deficiency (ATD) is a rare autosomal dominant condition (estimated prevalence 1:500–1:5000). Most ATD patients have AT activity levels 40–60% of normal. We present treatments for venous thromboembolism (VTE) in five cases of hereditary ATD. Four patients had a family history of ATD, and one had a de novo mutation. The majority of patients had a VTE while on prophylactic anticoagulation. AT concentrate augmentation was added in these cases to treat the VTE and for prophylaxis against further episodes. Two patients had significant bleeding events, one had permanent physical sequelae. Two of the patients were pregnant. VTE is a common cause of morbidity and mortality during pregnancy. Although low molecular weight heparins are the drugs of choice during pregnancy, this treatment was inadequate in one patient (developed VTE on therapy). These cases emphasize the need to screen for ATD in young patients (<55 years) presenting with VTE. AT augmentation therapy may be necessary in patients inadequately treated with conventional anticoagulants. Careful monitoring and individualized care are needed in ATD patients, especially those with demonstrated bleeding tendencies.

Keywords:

• clotting disorders
• venous thromboembolism
• anticoagulation
• bleeding tendencies

Abbreviations

AT, antithrombin; ATD, antithrombin deficiency; DVT, deep vein thrombosis; HCG, human chorionic gonadotropin; INR, international normalized ratio; IVC, inferior vena cava; PE, pulmonary embolism; VTE, venous thromboembolism.

Data Sharing Statement

All the relevant data for this study are available within the article. Complementary data can be made available by the corresponding author upon reasonable request.

Ethics Approval and Informed Consent

Ethics committee approval was not sought for this study because the institutions involved do not require approval for reporting individual cases. This study was completed in accordance with the Helsinki Declaration as revised in 2013. Written informed consent was obtained from the patients described below or their authorized representatives for their anonymized information to be published in this article.

Consent for Publication

There are no images, videos, recordings, or other materials requiring consent to be published other than the informed consent described above.

Acknowledgments

Michael K. James, Ph.D. is acknowledged for medical writing and Jordi Bozzo, Ph.D., CMPP, for editorial assistance.

Author Contributions

All authors made significant contributions to the work including conception, execution, acquisition of data, and analysis. All authors participated in the drafting and revision of the manuscript and have agreed to submission to this journal. All authors have agreed to revisions and final form of the manuscript for submission and take responsibility and accountability for the contents therein.

Disclosure

Dr Annette von Drygalski reports that the manuscript was developed by a medical writer with funding support from Grifols. Dr Michael Tarantino is an Advisory Board Consultant and member of Speaker Bureau for Amgen, BioMarin, Dova, Genentech, Grifols, Octapharma, Principia, Sobi, Takeda, and UCB; in addition Grant Reviewer, Clinical Trial PI for Pfizer and Spark Therapeutics outside the submitted work. The authors report no other conflicts of interest in this work.

Additional information

Funding

This study was supported by Grifols (Barcelona, Spain).