sodium-dodecyl-sulfate and Vascular-Diseases

Six patients with thrombotic microangiopathy associated with drug therapy had serial analyses of von Willebrand factor (vWF) multimeric patterns in their EDTA-plasma samples by sodium dodecyl sulfate-1% agarose gel electrophoresis and autoradiography. In the plasma of five patients (one with chronic myelogenous leukemia, two with prostatic cancer, and two with lymphoma), vWF abnormalities were observed during evolution of the thrombotic microangiopathy. These abnormalities were either the presence of unusually large (UL)vWF multimers of the type similar to those found within, and released or secreted by, endothelial cells (three patients) or a relative decrease in the largest plasma vWF multimers of the type that can be induced to attach to platelets (one patient) or both vWF abnormalities in different serial samples (one patient). In the one cardiac transplant patient who did not develop vWF multimeric abnormalities associated with thrombotic microangiopathy, vWF antigen levels were elevated more than threefold. This later individual received therapy with cyclosporin A alone. The other five thrombotic microangiopathy patients received cyclosporin A in combination with other chemotherapeutic agents (two patients); mitomycin-C, along with other chemotherapy (two patients); or multiple chemotherapeutic drugs, but not cyclosporin A or mitomycin C (one patient). The finding of vWF multimeric abnormalities during serial analysis of plasma samples from five of six patients with drug-associated thrombotic microangiopathy suggests the possibility that ULvWF forms derived from damaged or stimulated endothelial cells, along with the largest plasma vWF multimers, may be involved in the intravascular platelet clumping that is an essential part of the pathophysiology of this disorder.

Topics: Adolescent; Adult; Aged; Antigens; Cyclosporine; Electrophoresis, Agar Gel; Female; Humans; Male; Microcirculation; Polymers; Sodium Dodecyl Sulfate; Thrombosis; Vascular Diseases; von Willebrand Factor

A patient, CAL, with gamma heavy chain disease is presented who has had a complete remission lasting over 2 yr with combination chemotherapy consisting of pulsatile cyclophosphamide and prednisone. The patient exhibited many features of an atuoimmune process including a vasculitis, low serum complement levels, a positive antiglobulin (Coombs) test, Raynaud's phenomenon, and keratoconjunctivitis sicca. The CAL paraprotein was found to have several previously undescribed characteristics. It reacted with antisera to Fd, Fab, and Fab', suggesting that most of the Fd portion of the molecule was intace. CAL protein consists of two polypeptide chains of molecular weight 49,000 covalently linked to form a dimer of 95,000 molecular weight. The covalent linkage suggests that the hinge region of this gamma heavy chain is intact.

Topics: Bone Marrow Examination; Chromatography, Gel; Complement C3; Coombs Test; Cyclophosphamide; Drug Therapy, Combination; Electrophoresis, Polyacrylamide Gel; Electrophoresis, Starch Gel; Heavy Chain Disease; Humans; Immune Sera; Immunoelectrophoresis; Immunoglobulin Fragments; Lymph Nodes; Male; Microscopy, Electron; Middle Aged; Prednisone; Remission, Spontaneous; Skin; Sodium Dodecyl Sulfate; Vascular Diseases