A splanchnic venous thrombosis revealing Biermer's disease: A case report.

doi:10.21203/rs.3.rs-3954514/v1

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Case Report

A splanchnic venous thrombosis revealing Biermer's disease: A case report.

https://doi.org/10.21203/rs.3.rs-3954514/v1

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Background

The relationship between Biermer's disease and increased thrombotic risk, while uncommon, represents a critical clinical concern necessitating heightened diagnostic awareness for patients presenting with unexplained thrombotic symptoms.

Case presentation:

This report details the case of a 57-year-old male, with a prior diagnosis of Graves' disease, who developed splanchnic venous thrombosis. An extensive etiological investigation revealed mild hyperhomocysteinemia, associated with an undiagnosed Biermer's disease.

Conclusions

Our case underscores a critical association between Biermer's disease, hyperhomocysteinemia, and venous thrombosis, emphasizing the imperative for further research elucidating their interconnected pathogenesis.

Internal Medicine

Biermer's Disease

Splanchnic Venous Thrombosis

Hyperhomocysteinemia

Thrombotic Risk

Thrombotic events are rarely reported as a manifestation of Biermer's disease. The pathophysiological explanation is often attributed to hyperhomocysteinemia secondary to vitamin B12 deficiency [1]. However, this explanation remains a subject of debate: Is it a risk factor or simply a risk marker? We present the case of a 57-year-old patient who developed splanchnic venous thrombosis, with an exhaustive etiological investigation proving negative, except for mild hyperhomocysteinemia associated with previously unrecognized Biermer's disease.

A 57-year-old man, a smoker, with no family history of thrombosis, with a medical history of tonsillectomy, appendectomy, and Graves' disease complicated by hypothyroidism following IRA therapy, presented urgently due to acute abdominal pain resembling a surgical condition. Conventional paraclinical investigations yielded negative results. An abdominal-pelvic CT scan was requested one week later, revealing thrombosis in a proximal jejunal branch of the superior mesenteric vein.

The temperature was 37.2°C, blood pressure 130/80 mmHg, heart rate 80 bpm, and respiratory rate 20 cycles/min. The patient mentioned a history of recurrent oral aphthosis. Clinical examination revealed tenderness upon palpation of the epigastrium and right hypochondrium, along with Hunter's glossitis aspect, although no oral ulcers were observed upon examination of the oral cavity. Genital examination did not reveal genital aphthae or scars from aphthous ulcers. Ophthalmologic examination showed no signs of uveitis or vasculitis. The Pathergy test was negative.

Biological investigations revealed macrocytosis at 114 fl without anemia and without anomalies in other blood cell lines. The vitamin B12 assay, performed five days after the initiation of substitute therapy, was within normal limits, with an associated iron deficiency and hyperhomocysteinemia at 46 µmol/L (Normal value < 15). Other explorations, including hemostasis assessment, tumor markers, electrophoretic profile of serum proteins, antinuclear antibodies, and anti-cardiolipin/anti β2-glycoproteine-1 antibodies, as well as lupus anticoagulant, were negative. Constitutional thrombophilia screening did not reveal deficiencies in proteins C/S, antithrombin III, or mutations in factor V Leiden or II G20210. Genetic study did not show a JAK-2 mutation, and the search for the HLA B-51 allele was negative.

The upper gastrointestinal endoscopy suggested an atrophic fundic gastritis. Histological examination of the fundic mucosa biopsy confirmed the diagnosis of Biermer's disease. Abdominopelvic computed tomography did not reveal any other anomalies, notably no signs indicative of an underlying neoplasm.

The patient was initially treated with heparin therapy, followed by antivitamin K therapy for three months. Substitutive treatment with vitamin B12, along with iron supplementation, was continued in accordance with recommendations. Clinical progression was positive, with improvement in digestive symptoms and the absence of other thromboembolic incidents. Post-treatment biological analyses showed normalization of mean corpuscular volume and iron reserves, while the homocysteine level remained unchanged.

The clinical case we presented underscores an uncommonly reported initial manifestation of Biermer's disease [1–4]: splanchnic venous thrombosis. This unique manifestation, observed in our case, was discovered through a thorough etiological evaluation, revealing mild hyperhomocysteinemia. Our observation raises fundamental questions about the role ascribed to hyperhomocysteinemia in the pathogenesis of thrombotic events, particularly within the pathological context of Biermer's disease.

The scientific literature provides diverse perspectives on this association [5]. Several previous studies have suggested that hyperhomocysteinemia, as a consequence of vitamin B12 deficiency, could play a crucial role in promoting venous thromboses [6–10]. Hyperhomocysteinemia is known to induce endothelial dysfunction [11], promote oxidation of lipoproteins, and stimulate the proliferation of vascular smooth muscle cells [12], all factors contributing to a prothrombotic state.

However, contradictory studies have also been reported, where hyperhomocysteinemia was not significantly correlated with an increased risk of thrombosis [13, 14]. This discordance raises the question of whether hyperhomocysteinemia is a true causal factor or simply a risk marker associated with other underlying mechanisms.

In the case of our patient, there was no family history of thrombosis or other obvious risk factors, except for Biermer's disease and hyperhomocysteinemia. It is pertinent to note that, despite vitamin supplementation, the homocysteine level remained elevated. This observation might suggest that, in some cases, hyperhomocysteinemia may persist as an independent risk factor even after correcting vitamin B12 deficiency.

While our case confirms the association between Biermer's disease, hyperhomocysteinemia, and venous thrombosis, it also underscores the complexity and multifactorial nature of thrombotic pathogenesis in this autoimmune condition. More scientific research is essential to fully elucidate the mechanisms by which hyperhomocysteinemia contributes to thrombogenesis.

Not applicable

- Ethics approval and consent to participate : Not applicable

- Consent for publication : We obtained verbal consent from the patient. Our patient is illiterate.

- Availability of data and material : Not applicable (all the data of the reported case are available from the corresponding author).

- Competing interests : The authors declare that they have no competing interests

- Funding : The authors have not received funding in any form.

- Authors' contributions : B.C.A contributed to the writing of the article, its correction and the management of the patient. B.S, D.Y, and T.A contributed to the care of the patient in the department. All authors read and approved the final manuscript.

- Acknowledgements : Not applicable

Barrios, M., & Alliot, C. (2006). Venous thrombosis associated with pernicious anaemia. A report of two cases and review. Hematology (Amsterdam, Netherlands), 11(2), 135–138.
Ammouri, W., Tazi, Z.M., Harmouche, H. et al. Venous thromboembolism and hyperhomocysteinemia as first manifestation of pernicious anemia: a case series. J Med Case Reports 11, 250 (2017).
Venkatesh, P., Shaikh, N., Malmstrom, M.F. et al. Portal, superior mesenteric and splenic vein thrombosis secondary to hyperhomocysteinemia with pernicious anemia: a case report. J Med Case Reports 8, 286 (2014).
Karchafi A, Oualim Z, Amezyane T, Mahassin F, Ghafir D, Ohayon V, Archane MI. Maladie de Biermer et thrombose veineuse. A propos de deux observations. Rev Med Int 2002;23:563–566.
Eldibany, M. M., & Caprini, J. A. (2007). Hyperhomocysteinemia and thrombosis: an overview. Archives of pathology & laboratory medicine, 131(6), 872–884.
Falcon C, Cattaneo M, Panzeri D, Martinelli I, Mannucci P. High prevalence of hyperhomocysteinemia with juvenile venous thrombosis. Arterioscler Thromb.1994;14:1080–1083.
Den Heijer M, Koster T, Blom HJ, et al. Hyperhomocysteinemia as a risk factor for deep-vein thrombosis. NEngl JMed.1996;334:759–762.
Eichinger S, Stumpfen A, Hirschl M, et al. Hyperhomocysteinemia is a risk factor of recurrent venous thromboembolism. Thromb Haemost.1998;80: 566–569.
den Heijer M, Brouwer I, Bos G, et al. Vitamin supplementation reduces blood homocysteine levels. A controlled trial in patients with venous thrombosis and healthy volunteers. Arterioscler Thromb Vasc Biol.1998;18:356–361.
Simioni P, Prandoni P, Burlina A, et al. Hyperhomocysteinemia and deep veinthrombosis: a case control study. Thromb Haemost.1996;76:883–886.
Durand P, Prost M, Loreau N, Lussier-Cacan S, Blache D. Impaired homocysteine metabolism and atherothrombotic disease .Lab Invest. 2001;81:645672.
Welch G, Upchurch G, Loscalzo J. Homocysteine, oxidative stress and vascular disease. Hosp Pract.1997;32:81–92.
Martinelli I, Cattaneo M, Panzeri D, Taioli E, Mannucci PM. Risk factors for primary deep vein thrombosis of the upper extremities. Ann InternMed.1997; 126:707–711.
De Stefano V, Casorelli I, Rossi E, et al. Interaction between hyperhomocysteinemia and inherited thrombophilic factors in venous thromboembolism. Semin Thromb Hemost. 2000;26:305–311.

The authors declare no competing interests.

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A splanchnic venous thrombosis revealing Biermer's disease: A case report.

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Abstract

Background

Case presentation

Discussion

Conclusions

List of abbreviations

Declarations

References

Additional Declarations

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