Acquired bleeding disorder in a patient with malignant lymphoma: antibody-mediated prothrombin deficiency.
BACKGROUND
Bleeding manifestations secondary to acquired hemostatic abnormalities in cancer patients have been well described. Bleeding due to the development of hemostatic inhibitors is observed less frequently. In this report, the authors describe a patient with a low grade lymphoma who presented with an acquired bleeding disorder and abnormal hemostatic screening tests.


METHODS
Patient plasma samples were collected initially and during the course of treatment. Mixing studies and specific coagulation factor assays were performed to detect and confirm any deficiencies. Patient immunoglobulin G was isolated from plasma, and binding to prothrombin was demonstrated by immunoblot method and enzyme-linked immunosorbent assay (ELISA) techniques.


RESULTS
Initial prolongations in the prothombin time and the activated partial thromboplastin time suggested a factor deficiency in the common pathway of coagulation. Factor assays confirmed that the coagulation abnormality in this patient was the result of an acquired prothrombin (factor II) deficiency. This was confirmed by an immunoassay for prothrombin antigen. Further studies demonstrated the presence of a noninhibitory antibody to prothrombin that interacted with a calcium dependent epitope.


CONCLUSIONS
Successful treatment of the lymphoma resulted in clearance of the antibody and complete correction of all hemostatic abnormalities and manifestations. An acquired prothrombin deficiency has not been reported previously in association with a malignancy, and this patient represents the first such documented case.
Lee
E S
ES
Division of Hematology, Department of Medicine, University of Southern California School of Medicine, Los Angeles, California, USA.
Hibsman
B K
BK
Liebman
H A
HA
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001323:Autoantibodies / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007020:Hypoprothrombinemias / Q000150:complications* / Q000175:diagnosis / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D008228:Lymphoma, Non-Hodgkin / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy; D008875:Middle Aged; D011516:Prothrombin / Q000276:immunology*
D001323:Autoantibodies; D007074:Immunoglobulin G; D011516:Prothrombin