A non-immunological phospholipid-dependent coagulation inhibitor associated with IgGlambda-type multiple myeloma.
We investigated the rare case of a patient with IgGlambda multiple myeloma for whom both prothrombin time and APTT were significantly prolonged. The IgG inhibited coagulation reactions upstream from prothrombin when coagulation was initiated by mRVVT, but not by FXa, as indicated by a chromogenic substrate for FXa. The mPT and the mAPTT showed inhibition of FXa generation in both the intrinsic and extrinsic pathways. The IgG inhibited both protein C (indicated by APTT) and FX (indicated by RVV) but not amidolysis for either activated protein C or FXa. The addition of excess phospholipid significantly shortened the prolonged RVVT of the patient. It inhibited the coagulation reactions of normal plasma and was dependent on decreasing the PS concentration in the APTT reagent. It was suggested that the IgG showed lupus anticoagulant (LA)-like activity that inhibited phospholipid-dependent coagulation reactions in the intrinsic, extrinsic, and common pathways. However, the IgG did not bind cardiolipin-beta2GPI complex, beta2GPI, or prothrombin in ELISA assays. The IgG did not bind to either PS or phospholipid complexes in the presence or absence of prothrombin, FX, or FXa. Interestingly, the IgG lost its LA like-activity when it was degraded to F(ab')2 and Fc fragments by pepsin. We suspected that the IgG might inhibit the interaction between coagulation factors and acid phospholipid non-immunologically and that this process requires an intact IgG conformation, although the reaction mode is still not clear.
Takamiya
Osamu
O
Laboratory of Hematology, Department of Biomedical Laboratory Sciences, School of Health Sciences, Shinshu University, Matsumoto Asahi, Japan. itosamu@gipac.shinshu-u.ac.jp
Machida
Shinichiro
S
Okuda
Masahiro
M
Nojima
Junzo
J
Koreeda
Chikako
C
Kubara
Katuhiko
K
D001777:Blood Coagulation; D001780:Blood Coagulation Tests; D015951:Factor Xa / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000096:biosynthesis; D007141:Immunoglobulin Fc Fragments / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000378:metabolism* / Q000502:physiology; D016682:Lupus Coagulation Inhibitor / Q000378:metabolism*; D008875:Middle Aged; D009101:Multiple Myeloma / Q000378:metabolism*; D010434:Pepsin A / Q000494:pharmacology; D010743:Phospholipids / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism / Q000502:physiology; D011971:Receptors, Immunologic / Q000096:biosynthesis
C052643:F(ab')2 receptor; D007140:Immunoglobulin Fab Fragments; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D016682:Lupus Coagulation Inhibitor; D010743:Phospholipids; D020033:Protein Isoforms; D011971:Receptors, Immunologic; D015951:Factor Xa; D010434:Pepsin A