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

Liked this post? Download the app on your smart phone and sign up below to catch future pearls right into your inbox, all for free!

Subscribe to Blog via Email

Enter your email address to subscribe to this blog and receive notifications of new posts by email.

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?

Does hypertension cause epistaxis?

Although traditionally we think of epistaxis as a potential sign of hypertension, particularly when severe, whether hypertension causes epistaxis is unclear and even the association of these 2 conditions has been challenged in recent years.

A 2014 systematic review found that although the majority of studies reported an association between these 2 conditions, many did not include a control group, were of poor methodological quality and did not adjust for confounding variables such as age, sex, and anticoagulation1.  Indeed, a larger study that controlled for many potential confounding factors failed to confirm such an association2.  A small prospective study also found no correlation between the severity of hypertension and epistaxis3.

Even when an association between hypertension and epistaxis has been found, it is unclear how much of the stress of bleeding itself and white coat syndrome may affect the readings1. However, an interesting 2017 study found masked hypertension (normal blood pressure in office, abnormal on ambulatory measurements) in 33.3% of patients with epistaxis with night time blood pressures that were significantly higher among patients with epistaxis4.

So the data is all over the place! It makes sense that long standing hypertension through its effects on blood vessels such as atherosclerosis and endothelium dysfunction may set the stage for epistaxis1,5, particularly in our ever-aging population on anticoagulants.  But whether hypertension by itself is enough to cause epistaxis is likely to be debated for years to come.  

 

References

  1. Kikidis D, Tsioufis K, Papanikolaou V, et al. Is epistaxis associated with arterial hypertension? A systematic review of the literature 2014;271:237-243. https://www.ncbi.nlm.nih.gov/pubmed/23539411
  2. Fuchs FD, Moreira LB, Pires CP, et al. Absence of association between hypertension and epistaxis: a population-based study. Blood Press 12:145-48. http://www.tandfonline.com/doi/abs/10.1080/08037050310001750
  3. Knopfholz J, Lima-Junior E, Précoma-Neto D, et al. Association between epistaxis and hypertension: A one year follow-up after an index episode of nose bleeding in hypertensive patients. Internat J Cardiol 2009;134:e107-e109. https://www.ncbi.nlm.nih.gov/pubmed/18499285
  4. Acar B, Yavuz B, Yildiz E, et al. A possible cause of epistaxis: increased masked hypertension prevalence in patients with epistaxis. Braz J Otorhinolaryngol 2017;83:45-49. http://www.scielo.br/pdf/bjorl/v83n1/1808-8694-bjorl-83-01-0045.pdf
  5. Celik T, Iyisoy A, Yuksel UC, et al. A new evidence of end-organ damage in the patients with arterial hypertension: epistaxis? Internat J Cardiol 2008;141:105-107. https://www.ncbi.nlm.nih.gov/pubmed/19138805
Does hypertension cause epistaxis?