Why is my patient with systemic amyloidosis at higher risk of bleeding?

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%).

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
Why is my patient with systemic amyloidosis at higher risk of bleeding?

Should my patient with suspected alcoholic hepatitis undergo liver biopsy?

Although a characteristic clinical history and biochemical pattern of liver injury can strongly suggest the diagnosis of alcoholic hepatitis (AH), a definitive diagnosis is confirmed with liver biopsy only. In fact, in 30% of patients clinically diagnosed as having AH, a liver biopsy may lead to an alternative diagnosis.1Understandably, many physicians are reluctant to proceed with biopsy in this fragile patient population given the associated risks, notably bleeding. For this reason, most patients with AH are clinically diagnosed without a liver biopsy. However, there are certain instances in which a biopsy can be helpful, including when:2

  • Diagnosis of AH is in doubt
  • Suspicion for another disease process that may be contributing in parallel to AH is high
  • Obtaining prognostic data or identification of advanced hepatic fibrosis or cirrhosis in AH is desired

Thus, liver biopsy findings may influence short- and long-term management in AH. For these reasons, the European Association for the Study of the Liver recommends consideration of a liver biopsy in patients with AH.3 To minimize the bleeding risk, the transjugular approach is preferred.

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References

  1. Mookerjee RP, Lackner C, Stauber R, et al. The role of liver biopsy in the diagnosis and prognosis of patients with acute deterioration of alcoholic cirrhosis. J Hepatol 2011; 55:1103-1111 Link
  2. Altamirano J, Miquel R, Katoonizadeh A, et al. A histologic scoring system for prognosis of patients with alcoholic hepatitis. Gastroenterology 2014;146: 1231-1239. PDF
  3. European Association for the Study of Liver. EASL clinical practical guidelines: management of alcoholic liver disease. J Hepatol 2012; 57:399-420. PDF

Contributed by Jay Luther, MD, Gastrointestinal Unit, Mass General Hospital, Boston, MA.

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Massachusetts General Hospital, Harvard Catalyst, Harvard University, its affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

 

Should my patient with suspected alcoholic hepatitis undergo liver biopsy?