Amyloidosis Presenting with Platelet Dysfunction and Recurrent Retroperitoneal Hemorrhage (RH).

CASE REPORT: A 59-year-old white female with history of easy bruising for 2 years and 2 episode of RH in the last 6 month admitted to ICU with her 3^rd episode of RH. Her previous w/o included a BM Bx which had shown clonal population of plasma cells kappa chain restrictive (7%) with repeatedly negative SPEP and UPEP. PFA-100 was consistent with severe platelet dysfunction. During the ICU admission platelet transfusion with multiple single donor units did not correct her PFA-100 results, which were confirmed with platelet aggregation results. Both, collagen/epinephrine and collagen/ADP closure times were prolonged (>300 and 128 seconds respectively). The patient however did not receive any medications to explain this apparently intrinsic dysfunction. Coagulation studies including PT, aPTT and factor II, VII, VIII, IX all were within normal limit. Factor X levels were slightly decreased (45%). Patient had selective embolization of the fourth lobar artery of the right kidney. Plasma cells in the marrow showed monoclonal expression for cytoplasmic kappa light chains by both IHC and in situ hybridization. Amorphous pink material was present in the walls of blood vessels. Plasma cells stained positively with CD138. The amyloid material stained positively with Congo red and demonstrated apple green birefringence under polarized light. Skeletal survey demonstrated multiple lytic lesions. Serum free light chain measurement showed high levels of M protein (κ) with κ to λ ration of 4.30. Patient was started on treatment with pulse dose steroid and bortezomib.

DISCUSSION: Amyloidosis can cause hemorrhage with multiple mechanisms including amyloid deposition (amyloid angiopathy), platelet dysfunction, coagulation factor deficiencies, abnormal fibrin polymerization and hyperfibrinolysis. Consumption of factor X by amyloid is often called a culprit for hemorrhage in amyloidosis. The slightly decreased level of factor X in this case provided a valuable clue for diagnosis, but was not likely a cause of bleeding in this patient. Amyloid induced platelet dysfunction along with amyloid angiopathy lead to life threatening hemorrhage in our patient. The mechanism of this platelet dysfunction, which also affected the transfused platelets, is not well explained. This effect on platelets complicates the clinical management. The case also illustrates the value of the free light chain assay, which is more sensitive than SPEP and UPEP. These commonly used tests to diagnose plasma cell dyscrasias are reportedly false negative in 3% of cases.

CONCLUSION: Plasma cell dyscrasia has a wide variety of presentation and should be considered as a part of bleeding work up in complex cases.