thromboplastin and Paraproteinemias

Factor VIII-related antigen (FVIII-RA)-positive microvessel areas were measured by both immunohistochemistry and computerized image analysis in patients with active multiple myeloma (MM), nonactive MM, and monoclonal gammopathies of undetermined significance (MGUS). A five-to sixfold larger area was found in patients with active MM compared to the other two groups. Aquaporin 1 (AQP1)-positive microvessel areas, measured with the same techniques on adjacent tissue sections, were also increased in active MM, and tended to be larger than and closely correlated with the FVIII-RA areas. Numerous mast cells were found in the bone marrow of active MM patients, and counts were strictly correlated with the microvessel density. The conditioned medium (CM) of bone marrow plasma cells from active MM patients stimulated endothelial cell proliferation and chemotaxis, monocyte chemotaxis, and angiogenesis in vivo (assessed by the chick embryo chorioallantoic membrane [CAM] system) more strongly and frequently than the CM of patients with nonactive MM and MGUS. Immunoassay of plasma cell lysates gave significantly higher levels of fibroblast growth factor-2 (FGF-2) in patients with active MM than in the other two groups, and a neutralizing anti-FGF-2 antibody inhibited by 46% to 68% the biological activity exerted by the CM in vitro and in the CAM. In situ hybridization of bone marrow plasma cells and zymography of CM showed that patients with active MM express higher levels of matrix metalloproteinase-2 (MMP-2) mRNA and protein than those with nonactive MM and MGUS, whereas MMP-9 expression and secretion overlapped in all groups. Overall data indicate that patients with active MM represent the vascular phase of plasma cell tumors that is induced, at least partly, through FGF-2 and MMP-2. Mast cells possibly contribute to the vascular phase via angiogenic factors in their secretory granules. Both angiogenesis and MMP-2 secretion can account for intramedullary and extramedullary spreading of plasma cells in patients with active MM.

Topics: Angiogenesis Inducing Agents; Aquaporin 1; Aquaporins; Blood Group Antigens; Bone Marrow; Fibroblast Growth Factor 2; Humans; Immunoenzyme Techniques; Mast Cells; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Multiple Myeloma; Neovascularization, Pathologic; Paraproteinemias; Prognosis; Thromboplastin

The clinical and laboratory findings in seven female patients with primary autoimmune diseases, one female patient with lymphoplasmacytoid (LP) immunocytoma and IgM paraproteinemia, and two male patients with multiple myeloma are described. The common denominator in all patients was a lupus anticoagulant or a closely related coagulation disorder. Recurrent thrombosis was observed in six patients with autoimmune diseases and in two patients with malignant monoclonal gammopathies. Other clinical manifestations included cerebral disorders (four patients with autoimmune disease/two patients with monoclonal gammopathy), repeated obstetric complications (6/1), asymptomatic valvular heart disease (6/1), renal dysfunction (6/2), hepatic involvement (2/2), and arthropathy (2/0). Laboratory investigations revealed a biologic false-positive serological test for syphilis in six patients with autoimmune disease and one with monoclonal gammopathy, antinuclear antibodies (4/0), antibodies against DNA (4/1), and a positive direct Coombs test (3/1) which was accompanied by hemolytic anemia in two patients (1/1). Additionally slight leukocytopenia (2/1) and thrombocytopenia (6/2) were observed; abnormal bleeding was only seen in one patient with severe thrombocytopenia. Other complications characteristic of LP immunocytoma or multiple myeloma were missing. The obvious similarities between the patients with autoimmune diseases and the patients with malignant monoclonal gammopathies suggest analogous pathogenetic mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Abortion, Spontaneous; Autoantibodies; Autoimmune Diseases; Blood Coagulation Factors; Blood Coagulation Tests; Brain Diseases; Female; Humans; Immunoglobulins; Lupus Coagulation Inhibitor; Lupus Erythematosus, Systemic; Lymphoma; Multiple Myeloma; Paraproteinemias; Pregnancy; Thromboplastin; Thrombosis

Hémorrhagic manifestations are relatively common in dysproteinemias (7 à 15% in myeloma, 36% in macroglobulinemia) but they are not often related to a qualitative platelet defect. In the present work we have studied the influence of some monoclonal immunoglobulins on the function of isolated normal platelets. The results show that platelet aggregations to collagen and ADP are impaired in presence of high concentration of paraproteins (about 50 gm/l). The molecular size of the protein is also important. This is in agreement with most studies and support the hypothesis that paraproteins interfere with platelet activity.

Topics: Blood Platelet Disorders; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin kappa-Chains; Immunoglobulin lambda-Chains; Multiple Myeloma; Paraproteinemias; Platelet Adhesiveness; Platelet Aggregation; Surface Properties; Thromboplastin; Waldenstrom Macroglobulinemia