Acquired bleeding disorders


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PubMed Search: Amyloidosis [title] coagulation

Kendall Crookston, M.D., Ph.D.
Julie Kim Harrington, M.D.
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Cite this page: Crookston K, Rosenbaum LS, Gober-Wilcox J. Amyloidosis. website. Accessed June 2nd, 2023.
Definition / general
  • Amyloidosis is a generic term for multiple disorders with extracellular tissue deposition of insoluble low molecular weight fibrils
  • May be inherited or acquired
  • May cause acquired Factor X deficiency due to Factor X binding to amyloid, causing a shortened half time
  • Bleeding usually does not occur unless Factor X levels fall below 10% (Am J Hematol 2010;85:171)
  • Some patients have normal levels of coagulation factors, but severe hemorrhage can result from amyloid deposition in small to medium sized vessel walls, leading to wall damage
  • For example, cerebral amyloid angiopathy is usually asymptomatic, but can cause primary lobar intracerebral hemorrhage in the elderly
  • Amyloidosis is rare, but is found in 15% with multiple myeloma
  • Amyloid deposits between the endothelium and the basement membrane of vessel walls
  • Generally involves the microvasculature of any organ but can involve the great vessels of the brain
  • Amyloid deposits in spleen can cause splenic rupture and severe hemorrhage (Amyloid 2009;16:47)
  • Deposition in the liver can cause decreased synthesis of coagulation factors in patients with advanced liver disease
  • Factor X deficiency is due to:
    • Binding to amyloid fibrils primarily in the liver and spleen
    • Decreased synthesis of coagulation factors in patients with advanced liver disease
  • AL ("amyloid light chain") amyloidosis (primary):
    • AL amyloidosis is caused by deposition of immunoglobulin light chain fragments
    • Usually due to a plasma cell dyscrasia; most patients have monoclonal immunoglobulin light chains detectable in the serum or urine
    • 9% have Factor X levels that are ← 50% of normal (Blood 2001;97:1885)
  • AA ("amyloid associated") amyloidosis (secondary):
    • Composed of fragments of amyloid A
    • Seen with chronic diseases associated with ongoing inflammation: rheumatoid arthritis, chronic infection, inflammatory bowel disease
  • Beta-2 microglobulin amyloid:
    • Amyloid composed of fibrils from beta-2-microglobulin
    • Seen with long term hemodialysis
  • Transthyretin (prealbumin) amyloid:
    • Amyloid composed of a mutant form of transthyretin (prealbumin)
    • This type of amyloid is deposited in familial amyloid polyneuropathies and in the heart in senile systemic amyloidosis
  • Beta amyloid:
    • Found in Alzheimer disease brain lesions
  • Amylin (islet amyloid polypeptide) amyloid:
    • Found in pancreas of patients with type 2 diabetes
Clinical features
  • Factor X levels in amyloidosis typically range from 2% to 50%
  • Bleeding symptoms usually do not arise unless Factor X levels fall below 10%
  • Frequently presents as purpuric bleeding, typically occurs at pressure points
  • Purpura may occur in periorbital regions (raccoon eyes) after minor trauma or valsalva maneuver
  • Some patients with abnormal bleeding have no abnormality in any coagulation test (JAMA 1983;249:1322)
    • Amyloid infiltration of blood vessels may contribute to the bleeding diathesis
  • Bleeding due to acquired von Willebrand disease has been described in AL amyloidosis (Am J Hematol 2007;82:363)
  • An interaction between amyloid beta-peptide and tissue-type plasminogen activator also may contribute to the tendency to hemorrhage in cerebral amyloid angiopathy, as in vitro studies have shown that amyloid beta-peptide analogues markedly stimulate plasminogen activation by tissue-type plasminogen activator
  • Diagnosis of amyloidosis requires confirmation by tissue biopsy
  • Fat pad aspiration biopsy has a low sensitivity for amyloidosis in patients with single organ involvement, but higher sensitivity in those with multiorgan involvement
  • Because fat pad aspiration biopsy is less likely than liver, renal, or rectal biopsy to be complicated by serious bleeding, it is suggested for initial biopsy in patients with other than single organ involvement
Prognostic factors
  • Prognosis varies by etiology
Case reports
  • Treatment is directed toward the underlying condition
  • For dialysis related amyloidosis, altering the mode of dialysis or considering renal transplantation is recommended
  • For the hereditary amyloidoses in which the mutant amyloid precursor protein is produced by the liver (eg: transthyretin, apolipoprotein A-I, and fibrinogen Aa), liver transplantation may prevent further deposition of amyloid and lead to regression of established deposits
Differential diagnosis
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