Immunotherapy

A recent medical report published in “The Japanese Journal of Clinical Hematology” (Rinsho Ketsueki) has brought into focus a rare yet critical hemostatic disorder: acquired autoimmune coagulation factor XIII deficiency. The case study addresses the complex diagnosis and management of an 88-year-old patient who developed severe anemia and extensive bleeding due to anti-factor XIII (FXIII) autoantibodies. We delve into the details of the published case and assess the broader implications for clinical practice.

Introduction

On January 16, 2024, clinicians were confronted with an alarming case at a renowned hospital in Japan: an 88-year-old man was rushed into the emergency department in an unconscious state due to severe anemia – a deprivation of red blood cells which diminishes the body’s ability to carry sufficient oxygen. The patient’s conditions were graver as he exhibited extensive subcutaneous bleeding across his chest and back and was harboring a significant hematoma within his pectoralis major muscle. This clinical picture posed an urgent diagnostic challenge to the attending hematologists.

Diagnosis

Preliminary coagulation screening tests revealed a compromising reduction in coagulation factor XIII (FXIII) activity, an enzyme critical for the final steps in the blood clotting process. FXIII deficiency commonly leads to a delayed wound healing and a propensity for bleeding since it is essential for stabilizing the blood clot. During his hospitalization, the patient endured repeated bleeding instances within the gastrointestinal tract and muscles, precipitating into hemorrhagic shock, a life-threatening condition.

The clinical team suspected the existence of FXIII inhibitors causing the deficiency and performed an infusion test with FXIII concentrates. Results from the cross-mixing test to examine the cross-linking of fibrin (a protein involved in blood clotting) revealed an inhibition of polymerization of the α-chain, indicating the presence of an anti-FXIII-A autoantibody. These findings, corroborated by the clinical manifestations, formed the basis for diagnosing autoimmune acquired coagulation factor XIII deficiency.

Treatment and Management

The presence of anti-FXIII-A autoantibodies poses a rare immunological response where the body mistakenly targets its own coagulation factor, leading to a disruption in typical hemostasis. The therapeutic approach to this condition, according to experts in cases documented in literature and reflective in the treatment of the patient in question, often involves high-dose steroids or immunosuppressive drugs to curb the autoantibody production.

In this instance, management commenced with administration of FXIII concentrates to temporarily restore the coagulation factor levels and control bleeding. Concomitantly, measures were taken to suppress the autoimmune reaction through immunosuppressive therapy. However, this strategy is fraught with complexity and risk, necessitating a fine balance between controlling the autoimmune response and preserving the patient’s immune function.

Implications for Clinical Practice

Autoimmune acquired factor XIII deficiency remains a poorly understood and underdiagnosed condition. This case study reaffirms the necessity for a high level of vigilance and a comprehensive coagulation assessment in patients presenting with unexplained bleeding phenomena, particularly when bleeding is recurrent or atypical.

Moreover, it emphasizes the critical role of specialized laboratory testing, such as the FXIII infusion test and the cross-mixing test, for the confirmation of FXIII inhibitor presence. Standard coagulation tests like Prothrombin Time (PT) and Activated Partial Thromboplastin Time (aPTT) may not detect this deficiency, rendering diagnosis a challenge without a high index of suspicion.

Keywords

1. Acquired coagulation factor deficiency
2. Autoimmune Factor XIII deficiency
3. Factor XIII autoantibodies
4. Hemorrhagic shock management
5. Immunotherapy in hematology

Conclusion

The publication of this rare case marks an important addition to medical literature, offering clinicians critical insights into the identification and treatment of autoimmune acquired factor XIII deficiency. While the occurrence is uncommon, the significant morbidity attached to such a disorder warrants a concerted effort towards early recognition and individualized patient care.

References

1. Kadono M., Souri M., Shimomura T., Kuroda Y., Munemasa S., Ozaki T., Ichinose A. (2024). Autoimmune acquired coagulation factor XIII/13 deficiency caused by type Ab anti-FXIII-A autoantibody. Rinsho Ketsueki, 64(12), 1508-1513. DOI: 10.11406/rinketsu.64.1508.

2. Muszbek L., Bereczky Z., Bagoly Z., Komáromi I., Katona É. (2011). Diagnosis and management of congenital and acquired FXIII deficiencies. Semin Thromb Hemost, 37(4), 430-439. DOI: 10.1055/s-0031-1276585.

3. Franchini M., Lippi G. (2011). Acquired factor XIII deficiency: An overview. Ann Hematol, 90(9), 971-977. DOI: 10.1007/s00277-011-1192-y.

4. Ivaskevicius V., Seitz R., Kohler H. P., Schroeder V., Muszbek L., Ariëns R. A., Seifried E. (2014). International Society on Thrombosis and Haemostasis. Diagnosis and treatment of factor XIII deficiency: A guideline from the ISTH. J Thromb Haemost, 12(6), 827-839. DOI: 10.1111/jth.12572.

5. Ananyeva N.M., Rivkin M., Liang Y., Pechik I., Kayode O., Haq N.A., Saenko E.L. (2002). Hemorrhagic disorders caused by circulating anticoagulant antibodies. Hemophilia, 8(3), 322-331. DOI: 10.1046/j.1365-2516.2002.00605.x.

The present case study has successfully demonstrated the importance of specialized assays and customized therapeutic approaches in the management of hematologic autoimmune disorders, ensuring better patient outcomes and forwarding the collective understanding of rare bleeding disorders.