Thrombosis Tendency After Splenectomy in a Danish Family With Hemoglobin Volga, and a Literature Review

Abstract

Hemoglobin (Hb) Volga is a rare, unstable β-chain hemoglobin variant (β27 Ala→Asp), causing chronic hemolytic anemia. This study presents two members of a Danish family, splenectomized due to Hb Volga at and with multiple thrombotic events. The proband was diagnosed with Hb Volga 9 years old and splenectomy was performed as a part of treatment. Throughout his life, he experienced multiple superficial thrombophlebitis, two episodes of distal deep venous thrombosis (DVT) on lower extremities (age 32 and 33) and a transient ischemic attack (TIA) presented as amaurosis fugax (age 51). Thrombophilia investigation was normal. The proband’s son was diagnosed with Hb Volga and underwent splenectomy at the age of 6. Despite anticoagulation therapy, he suffered from multiple venous thromboembolic events in his youth and died of chronic pulmonary embolism (PE)/pulmonary hypertension combined with infection. Given the observed propensity for multiple thromboses in these two patients, a literature review was conducted investigating reported occurrence of thrombotic events in individuals with Hb Volga.

Currently 25 cases of Hb Volga are reported worldwide. The clinical symptoms primarily described are related to hemolytic anemia. Splenectomy is reported in 15 patients. Thromboses have previously been reported in only three patients who were also splenectomized. These cases involved DVT and PE, myocardial infarction, and an unspecified thrombotic event. The proband represents the first reported Hb Volga case with both venous and arterial thrombotic disorders. The exact mechanism underlying thrombotic tendency in patients with Hb Volga remains unknown, but it is probably associated with splenectomy.

Keywords:

• Thrombosis
• hb volga
• hemoglobin variant
• hemolytic anemia
• splenectomy

Acknowledgement

We would like to thank the Danish Red Blood Center at Copenhagen University Hospital – Rigshospitalet for carrying out the analyses, and librarian Peter Everfelt for sourcing any literature, no matter how well hidden it is.

Ethical approval

Ethical approval is not required for this study in accordance with local or Danish national guidelines.

Declaration of generative AI and AI-assisted technologies in the writing process

During the preparation of this work, the authors used OpenAI's language model, GPT-3.5 in order to improve language and readability. After using this tool/service, the authors reviewed and edited the content as needed and take full responsibility for the content of the publication.

Patient consent

The patient is aware that his and his son’s clinical details are used in this paper, and he and his wife have read the manuscript prior to submission. Written informed consent was obtained from the patient and the wife/mother of the son for the publication of this case report.

Authors’ contributions

Johanne Kodal Breinholt conducted the literature review, interpreted the data, wrote the initial draft of the manuscript, and approved the final manuscript.

Andreas Glenthøj supervised the osmotic gradient ektacytometry, high-performance liquid chromatography, and an isopronol stability test, interpreted the data, and approved the final manuscript.

M. Vakur Bor planned the study, supervised the subject recruitment, interpreted the data, supervised the manuscript writing, and approved the final manuscript.

Disclosure statement

A. Glenthøj (Consultancy: Agios, bluebird bio, Novo Nordisk, Bristol Myers Squibb, Novartis, Pharmacosmos; Research support: Novo Nordisk, Saniona, Sanofi).

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Data availability statement

All data generated during this study are included in this article. Further enquiries can be directed to the corresponding author.

Additional information

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.