The major mechanism of bleeding tendency in primary systemic amyloidosis (AL) appears to revolve around amyloid deposit infiltration of the vasculature and musculature, leading to amyloid angiopathy, fragility, impaired vasoconstriction, tears and hemorrhage. ^1,2 Other potential mechanisms include:

• Presence of plasma inhibitors of fibrinogen conversion to fibrin
• Deficiencies of factor X, IX and V due to their affinity for amyloid substance
• Presence of circulating heparin-like anticoagulants
• Uremic platelet dysfunction in the presence of renal involvement

In a study involving 36 patients with AL, ~30% had bleeding symptoms with alterations of 1 or more clotting tests found in ~85%: prolonged prothrombin time (PT) ratio (22%), activated partial thromboplastin time (aPTT) (65%) and thrombin time (85%).¹ 

Clinical manifestations of amyloidosis related to its bleeding diathesis include petechiae, ecchymoses, purpura (“raccoon eyes when periorbital), uncontrollable epistaxis, gingival bleeding, and gastrointestinal bleed or submucosal hematomas. ^1-6

Due to its convenience and relative safety, a biopsy of abdominal fat or minor salivary glands is often initially performed for definitive diagnosis of amyloidosis, followed by biopsy of specific organs (eg, kidney, liver), if needed. ^3,6

Due to the potential risk of bleeding complications, transjugular liver biopsy is preferred over percutaneous approach. This is because the liver capsule is not perforated with transjugular liver biopsy and if bleeding occurs, the blood returns directly into the venous system rather than into the peritoneum. ^7-8 

Bonus Pearl: Did you know that AL amyloidosis is the most common type of systemic amyloidosis in western countries? This is because the incidence of the other major type of amyloidosis (AA), often related to chronic infections or inflammatory diseases, has been dropping in these countries.³

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References

1. Gamba G, Montani N, Anesi E, et al. Clotting alterations in primary systemic amyloidosis. Haematologica 2000;85:289-92. https://moh-it.pure.elsevier.com/en/publications/clotting-alterations-in-primary-systemic-amyloidosis
2. Marconcini LAL, Stewart FM, Sonntag L, et al. AL amyloidosis complicated by persistent oral bleeding. Case Reports in Hematology 2015, Article ID 981346. https://www.hindawi.com/journals/crihem/2015/981346/
3. Desport E, Bridoux F, Sirac C, et al. AL Amyloidosis. Orphanet Journal of Rare Diseases 2012, 7:54. https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-7-54
4. Yoshii S, Mabe K, Nosho K, et al. Submucosal hematoma is a highly suggestive finding for amyloid light-chain amyloidosis: Two case reports. W J Gastroenterol 2012;4:434-37. https://www.ncbi.nlm.nih.gov/pubmed/23125904
5. Kon T, Nakagawa N, Yoshikawa F, et al. Systemic immunoglobulin light-chain amyloidosis presenting hematochezia as the initial symptoms. Clin J Gastroenterol 2016;9:243. http://europepmc.org/article/med/27318996
6. Petre S, Shah IA, Gilani N. Review article:gastrointestinal amyloidosis-clinical features, diagnosis and therapy. Alim Pharmacol Ther 2008;27:1006-16. https://www.ncbi.nlm.nih.gov/pubmed/18363891
7. Grant A, Neuberger J. Guidelines on the use of liver biopsy in clinical practice. Gut 1999;45(Suppl IV):IV1-IV11. https://www.ncbi.nlm.nih.gov/pubmed/10485854
8. Dohan A, Guerrache Y, Boudiaf M, et al. Transjugular liver biopsy: Indications, technique and results. Diagnostic and Interventional Imaging 2014;95:11-15. https://www.ncbi.nlm.nih.gov/pubmed/24007769