ASH Image Bank (2001); doi:10.1182/ashimagebank-2001-100170
Copyright © 2001 by the American Society of Hematology.
Amyloidosis: Acquired Factor X Deficiency
John Lazarchick, MD
Medical University of South Carolina
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Figure 1. Skin demonstrating "pinch purpura" pattern secondary to amyloid deposition in blood vessels of the dermis. (Courtesy of Dr. Joi Lenczowski, Medical University of South Carolina.)
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Figure 2. Resolving purpuric area over the lower extremity. Cutaneous hemorrhage is common in this disorder even with mild trauma.
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Figure 3. Peripheral smear showing mild rouleaux formation and plasmacytoid-appearing lymphocytes with basophilic cytoplasm and condensed nuclear chromatin.
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Figure 4. Bone marrow aspirate showing a small aggregate of mature plasma cells (arrows). Marrow differential count showed 22% plasma cells.
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Figure 5. Bone marrow biopsy illustrating diffuse infiltrate of amyloid protein with only scattered residual hematopoietic cells identifiable.
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Figure 6. Bone marrow biopsy showing amorphous infiltrate of amyloid protein (arrows). Congo Red stain showed apple-green fluorescence.
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Figure 8. Bone marrow biopsy showing infiltration of a blood vessel with amyloid protein and similar appearing infiltrate in the marrow interstitial areas.
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Figure 9. Core biopsy of the liver showing disruption of the liver parenchyma by an amorphous infiltrate of amyloid protein (arrow). Despite the extensive involvement, hepatic function is usually normal.
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Figure 10. Immunofixation electrophoresis of the patient's urine showing a Lambda restricted immunoglobulin light chain band. A monoclonal band was not detected in the serum.
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Clinical Summary
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The patient is a 42-year-old white woman who complained of increasing abdominal girth over the past year and had noted easy bruising with "black and blue" areas on her arms and legs. There is no personal or family history of a bleeding disorder.
She is a chronically ill-appearing woman who has ecchymoses on her forearms and legs. Linear purpuric lesions are also evident. Hepatosplenomegaly is present but no significant adenopathy is noted. There is 2+ pitting edema of the lower extremities.
Lab: Hemoglobin (Hgb) 10.3 g/dL, white blood cells (WBC) 6100/uL, platelets 318,000/uL; Albumin 1.9 and globulin 3.2 g/dL; SPEP - normal pattern; liver function tests were normal; urine analysis -proteinuria; 24-hour urine collection - 1.8 grams of protein. EKG - low voltage noted.
Prothrombin (PT) and activated partial thromboplastin (aPTT) times were prolonged. Fibrinogen and D-Dimer were normal. Mixing study showed correction, consistent with a factor deficiency. Factor X level was 12%.
The patient was given FFP and the PT, aPTT, and factor X level were repeated 30 minutes after infusion. The PT and aPTT remained abnormal and repeat factor X measurement was 11%.
Sex
Female
Age
42
Ethnicity
White
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Diagnosis
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The clinical picture was consistent with amyloidosis with nephrotic syndrome and an acquired coagulation factor inhibitor. Appropriate biopsies were obtained to confirm this diagnosis and define the type of amyloid present. In this case it was AL secondary to underlying myeloma.
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Discussion
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Amyloidosis is a disorder in which amyloid protein complexes form insoluble fibrillar tissue deposits in various organs, leading to organ dysfunction. Classification of the amyloidoses is based on the chemical composition of the fibrillar component of these deposits. Nineteen different fibrillar proteins have been identified thus far. In AL amyloidosis, associated with plasma cell dyscrasias, the protein component is composed of immunoglobulin light chains (usually lambda) or light chain fragments. These deposits have a predilection for packing around/in small blood vessels. Clinically, signs and symptoms vary widely and are reflective of specific organs that are infiltrated and whose functions are compromised. Renal involvement is characterized by proteinuria and eventuates in chronic renal failure requiring dialysis.
Cardiac deposition leads to congestive heart failure and arrythmias. Hepatic and splenic involvement cause organomegaly but little functional impairment.
Hemorrhagic manifestations are primarily due to subendothelial deposition of amyloid leading to capillary fragility and impaired vascular contractility resulting in ucocutaneous hemorrhage. Periorbital purpuric lesions are a characteristic finding. The bleeding time is typically prolonged but platelet aggregation and von Willebrand functional activity are normal. A rare complication is an acquired factor X deficiency state resulting from factor X adsorption to the amyloid fibrils in the vasculature. Residual factor X levels range from 2% to 50%. As a result, both the PT and aPTT are prolonged but the thrombin time and fibrinogen concentration are normal. Mixing studies of the patient's plasma and normal plasma correct the abnormal PT and aPTT, suggesting a factor deficiency state; however, infusion of factor X results in a rapid loss of factor X activity. A similar mechanism can occur with isolated factor IX deficiency. Therapy of either deficiency is difficult since adequate levels can not be readily achieved with standard coagulation factor replacement products.
Splenectomy has been suggested to be of benefit by removing a large amyloid pool. Therapy directed at the underlying plasma cell dyscrasia may improve hemostasis but not acutely. Additional causes of a hemorrhagic diathesis in this disorder include an acquired fibrin monomer polymerization defect and hyperfibrinolysis due to plasminogen activator inhibitor-1 deficiency (PAI-1).
This defect will respond to antifibrinolytic therapy. Other laboratory abnormalities include apple-green fluorescent staining using Congo Red of tissue containing amyloid; monoclonal Ig, usually light chains only, can be seen in the serum or urine in 80% to 90% of patients; bone marrow plasmacytosis (more than 10% of cells) in 40% of patients.
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Differential Diagnosis
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AL secondary to underlying myeloma.
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Chapter 13: Plasma cell dyscrasias
Copyright © 2001 by the American Society of Hematology.
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