Thrombotic thrombocytopenic purpura with colitis in an elderly woman.
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Aged↗
Biomedical subjects
L E Silberstein
Publications and source records attributed to L E Silberstein.
Effect of plasma exchange on phenytoin plasma concentration.
The effect of plasma exchange on the concentrations of total and unbound phenytoin (DPH) was determined in one normal subject and four patients undergoing therapeutic plasma exchange (PE). The average percentage of plasma exchanged ranged from 57 to 70% among the five patients studied. The reduction in DPH concentration was more variable and ranged from 10 to 16%. However, the extent of reduction within each patient for both total DPH and "free" DPH serum concentrations was minimal; in addition, the ratio of free to total DPH remained virtually unchanged by plasma exchange. Thus, the replacement of endogenous albumin with exogenous albumin, which is an integral part of therapeutic plasma exchange, does not appear to alter DPH binding. Our findings indicate that rapid equilibration of DPH occurs between the intra- and extravascular compartments and that for the occasional plasma exchange procedure, dose adjustment does not appear indicated.
Blood Component Removal↗
Etiologic aspects of cold agglutinin disease: evidence for cytogenetically defined clones of lymphoid cells and the demonstration that an anti-Pr cold autoantibody is derived from a chromosomally aberrant B cell clone.
This study investigated the clonal nature of cold agglutinin disease in a series of nine patients, which included the benign or idiopathic form as well as cases with an underlying lymphoma. Surface marker phenotyping and karyotypic analysis were performed on peripheral blood lymphocytes. An increased proportion of B cells was found in four cases and in three of these patients a monoclonal B cell population was identified with a mu, kappa phenotype. In the same three cases, as well as an additional patient, an aberrant karyotype was demonstrated. The cytogenetic abnormality present in all four cases included trisomy 3; two patients also had a trisomy 12. One of these four patients had a well-differentiated lymphoma and underwent a splenectomy. Splenic lymphocytes were transformed with Epstein-Barr virus and cultured en masse. Eight clones were established producing the same cold agglutinin with identical specificity as that present in the patient's plasma. Five of these clones were studied cytogenetically, and all had the same abnormal karyotype (51,XX,+3,+9,+12,+13,+18) found in peripheral blood and splenic lymphocytes. Thus, in this case, the cold reactive autoantibody was produced by the chromosomally abnormal, neoplastic clone of lymphocytes. Our findings support the view that cold agglutinin disease represents a spectrum of clonal disorders.
Adult↗
Quality control in the blood bank.
In discussing quality assurance in the blood bank, where many of the standard statistical techniques of measuring accuracy simply do not apply, three questions come to mind: How much? How often? Who says? Because of severe changes in the prospective payment plan and a new interest in cost effectiveness, many transfusion services are re-examining blood banking methodologies and their relative usefulness in promoting patient well-being. Many serologists are beginning to say that "less is better." This concern for simplification and reduction of workload is reflected in the quality control.
Blood Banks↗
Therapeutic trial of plasma exchange in osteosclerotic myeloma associated with the POEMS syndrome.
A patient with osteosclerotic myeloma and POEMS syndrome, unresponsive to pulse prednisone and melphalan therapy, was admitted to the hospital for a trial of plasma exchange therapy. The presentation included IgG lambda monoclonal gammopathy, peripheral neuropathy, hepatosplenomegaly, hyperpigmentation and thickening of the skin, edema, and tense ascites. Laboratory tests confirmed hypothyroidism, hypogonadism, and adrenal insufficiency. Six exchange procedures failed to affect the clinical course, and the patient died. Greater-than-one-plasma-volume exchanges (patient's measured plasma volume, 2,703 cc) were performed. When IgG and cholesterol removal were compared to the predicted removal, based on the volume of plasma removed, significantly less reduction in concentration than predicted was measured. IgG concentrations increased postapheresis and, at 2 weeks, three-fourths of the removed IgG had reaccumulated. A reduced efficiency of removal of both IgG and cholesterol can be explained by postulating increased vascular permeability with free exchange of soluble substances from one compartment to another. If an abnormal product is produced by the disease and is responsible for the clinical syndrome, a more intensive schedule of plasma exchange therapy may be needed to achieve a sustained depletion of the responsible soluble substance. Alternatively, neither increased vascular permeability or the clinical manifestations are responsive to removal of a soluble substance or are caused by a soluble substance produced by the malignancy.
Adrenal Insufficiency↗
A combination of IgG and IgM autoantibodies in chronic cold agglutinin disease: immunologic studies and response to splenectomy.
A patient with chronic cold agglutinin disease and anti-I antibody was studied. The titer of the patient's serum at 4 degrees C was 700 with adult I RBC, 256 with cord RBC, 256 with adult i RBC. At room temperature the titers were decreased and the serum also reacted at a titer of 4,000 with enzyme treated adult I RBC. Dithiothreitol treatment of the serum and purified antibody decreased reactivity only slightly, indicating that the antibody was IgG. The heat eluate contained 1.2 mg/ml IgG kappa, but only 80 micrograms/ml IgM kappa. A hybridoma made by fusing the patient's peripheral blood lymphocytes with a human myeloma cell line contained only IgM kappa (30 micrograms/ml) anti-I activity. The IgM fraction of the heat eluate reacted similarly to the hybridoma supernatant. The IgG fraction resembled the serum and heat eluate. In this case study, IgG kappa and IgM kappa immunoglobulins, both possessing cold agglutinin activity, were present in the patient's serum. This finding is unusual in idiopathic cold agglutinin disease and in view of the predominance of an IgG cold agglutinin, splenectomy was recommended for treatment.
Adult↗
Plasma exchange in autoimmune hemolytic anemia (AIHA).
Plasma exchange therapy in autoimmune hemolytic anemia (AIHA) was used in four patients (two with warm hemolytic anemia and two with cold hemolytic anemia). The size of each plasma exchange approximated 1 plasma volume; three consecutive daily exchanges removed 80-90% of the immunoglobulins--immunoglobulin G (IgG) and immunoglobulin M (IgM)-, complement (C3, C4), and reduced antibody titers. Transfusion requirements dramatically decreased after plasma exchange in each case. In two patients, red blood cell (RBC) survival studies were performed to more accurately assess the effect of plasma exchange therapy, since steroid and/or immunosuppressive therapy was given concomitantly. In one case of cold AIHA, homologous 51Cr-RBC were injected 4 days prior to plasma exchange and repeat injection (same donor) following completion of plasma exchange. The survival curve prior to plasma exchange therapy had a T 1/2 = 7.8 days (r = -0.988) and after plasma exchange therapy had a T 1/2 = 20.4 days (r = 0.925). RBC survival studies using homologous 51Cr-RBC were also performed in a patient with warm AIHA. The survival curve before plasma exchange had a T 1/2 = 2 days (r = -0.95), and postplasma exchange a T 1/2 = 1.8 days (r = -0.91). Plasma exchange therapy seems to have a beneficial effect in cold rather than warm autoimmune hemolytic anemia.
Adult↗
Angiotensin-1-converting enzyme (ACE) activity in human serum following plasma exchange.
Although angiotensin-1-converting enzyme (ACE), which catalyzes both the conversion of angiotensin 1 to angiotensin 2 and the hydrolysis of bradykinin, is known to be present in serum, little information is available about its source or turnover characteristics. We determined the removal and recovery characteristics of serum ACE for two normal subjects and 16 patients, with various diseases, who were undergoing partial plasma exchange. Cholesterol was removed as predicted, but the average actual removal of ACE, 70% of that originally present, was 28% greater than predicted. Recovery of serum levels of ACE after plasma exchange was 34% on Day 1, 62% on Day 3, 94% on Day 5, and 104% on Day 8, and the level remained relatively constant thereafter up to 28 days of study. The pattern of recovery of serum ACE is more compatible with a system of synthesis and release of ACE than with a simple exchange mechanism from sites on the plasma membrane of the endothelial cell or a shift of the enzyme from one space to another.
Cholesterol↗
Production of autoantibodies by human-human hybridomas.
Peripheral blood lymphocytes and splenocytes of patients with autoimmune disease were used to prepare human-human hybridomas that produce autoantibodies. Because exogenous immunization was not used, the hybridoma antibodies were derived from B cells that spontaneously produced autoantibodies. 108 hybrids grew from 4,254 wells (2.5%). Optimal conditions for obtaining hybridomas with the GM 4672 myeloma line included initial growth in 2-ml wells, the use of 44% polyethylene glycol, a mononuclear cell/GM 4672 cell ratio 5:1, and prior stimulation of the B lymphocytes with pokeweed mitogen. Hybridoma supernatants had activity against ssDNA, platelets, and erythrocytes. The results demonstrate the feasibility of producing human-human hybridomas from lymphocytes of patients with various autoimmune diseases.
Anemia, Hemolytic, Autoimmune↗
Altered blood group expression in a patient with congenital rubella infection.
An infant with probable congenital rubella infection developed altered blood group expression. This was noted at 4 months of age. The child's blood was typed on seven separate occasions during the first 8 weeks of life as type A, but on repeat testing, her cells failed to agglutinate with anti-A and anti-A,B typing serum. The A antigen was present, however, because an eluate made after incubating her red cells with anti-A contained anti-A, and A antigen was demonstrated on buccal mucosa cells. Altered expression of blood group A (loss of agglutinability) has occurred previously only in association with hematologic malignancy.
ABO Blood-Group System↗
Calcium homeostasis during therapeutic plasma exchange.
Because the removal of substantial quantities of plasma calcium during plasma exchange is rarely attended by clinically significant hypocalcemia, we evaluated calcium homeostasis during this procedure. Twenty-one procedures were performed on 10 patients with various neurological disorders. The reduction by plasma exchange in the serum concentrations of total calcium, ionized calcium, magnesium, and phosphate was significantly less than predicted (p less than 0.001) based on plasma volume of the patient and size of the exchange. However, N-terminal parathomone (PTH) levels increased to 242 +/- 120 percent midway into the procedure and were 207 +/- 84 percent after plasma exchange; urinary cyclic adenosine monophosphate (cAMP) levels rose by 165 +/- 35 percent. These data demonstrate a rapid compensatory response in N-terminal PTH and urinary cAMP to the reduction by plasma exchange of serum concentrations of total calcium, ionized calcium, and phosphate. The routine administration of supplemental calcium during plasma exchange may therefore be unnecessary in patients with normal parathyroid function.
Adrenal Cortex Hormones↗
The efficacy of intensive plasma exchange in acquired von Willebrand's disease.
This study describes the response to therapeutic plasma exchange in a 60-year-old man with Waldenström's macroglobulinemia who developed a clinically severe bleeding disorder with laboratory features characteristic of acquired von Willebrand's disease. The patient's plasma levels of factor VIII coagulant activity, von Willebrand's factor antigen, and ristocetin cofactor activity were all less than 15 percent of normal, and the bleeding time was more than 20 minutes. In vitro studies did not demonstrate an inhibitor to factor VIII/von Willebrand factor, nor was a precipitating antibody to von Willebrand's factor antigen found in the patient's plasma. Neither infusions of cryoprecipitate nor combination chemotherapy corrected the clinical or laboratory abnormalities. In contrast, plasma exchange corrected the in vitro coagulation abnormalities and was effective in preventing surgical hemorrhage and controlling severe mucosal bleeding on 11 separate occasions. The current case demonstrates that the clinical and laboratory abnormalities in a patient with acquired von Willebrand's disease can be corrected completely by plasma exchange; it is recommended therefore that plasma exchange be considered as a mode of therapy in symptomatic patients with this disorder.
Bleeding Time↗
An autologous fibrinogen-based adhesive for use in otologic surgery.
Successful middle ear surgery requires the availability of a safe, effective bonding material. Side effects caused by synthetic materials have led to the use of biologic adhesives; however, they carry the risk of transmission of infectious disease if they are prepared from pooled human blood. A procedure for the production of an autologous fibrinogen-based adhesive using polyethylene glycol to precipitate the fibrinogen-factor XIII component from plasma is described. This procedure requires 40 ml of whole blood and approximately 3 hours' preparation time, and it can be performed in any blood bank with the facilities for sterile techniques. This adhesive has been used successfully for otologic surgery in 12 patients, and further study of the use of this biologic adhesive for other microsurgical techniques should be undertaken.
Blood Transfusion, Autologous↗
Production of human warm-reacting red cell monoclonal autoantibodies by Epstein-Barr virus transformation.
Monoclonal antibody technology has been used in both murine and human systems to produce a variety of antibodies that react with the human red cell (RBC). RBC monoclonal autoantibodies have been obtained from animal models of autoimmune hemolytic anemia (AIHA), but to date no warm-reactive monoclonal autoantibodies have been generated from human B cells. Using the Epstein-Barr virus (EBV) transformation method, clones of RBC autoantibodies were generated from two patients with AIHA. These antibodies reacted preferentially at 37 degrees C, agglutinated or bound to a variety of different RBC phenotypes, and were IgM in nature. The serologic reactivity of one clone showed a relative specificity to e+ RBCs that was similar to that seen in the patient's serum. These results are the first to demonstrate that warm-reactive RBC autoantibodies can be obtained from patients with AIHA using the technique of EBV transformation, and they further substantiate the existence of warm-reactive IgM RBC autoantibodies in the spectrum of warm AIHA.
Adult↗
Anti-idiotypic antibodies specific for a pathologic anti-Pr2 cold agglutinin.
The heterogeneity of human red cell (RBC) autoantibodies may be assessed by using anti-idiotypic antibodies. In this study, mouse monoclonal anti-idiotypic antibodies were produced against a pathologic RBC autoantibody with anti-Pr2 specificity. Epstein-Barr virus-transformed B-cell clones were established from a patient who had splenic lymphoma and associated immune hemolysis due to an anti-Pr2 cold autoantibody. Two of the eight clones producing this autoantibody were used to immunize mice for the establishment of hybridomas, and four monoclonal anti-idiotypic antibodies were isolated (2 IgG1 kappa and 2 IgM kappa). By the use of these anti-idiotypic antibodies, strong crossreactivity was seen on enzyme-linked immunosorbent assay with other anti-Pr2-producing clones from the same patient, but no cross-reactivity was seen with RBC autoantibodies from other individuals having anti-Pr or different specificities. Each of the anti-idiotypic antibodies inhibited hemagglutination (HA) by the patient's anti-Pr2 but failed to inhibit HA by antisera of a different RBC specificity. Cross-competition experiments indicated that all of the anti-idiotypic antibodies may recognize the same or a closely related idiotope on the anti-Pr2 autoantibody. These studies suggested that the four anti-idiotypic antibodies are directed against the same (or closely related) idiotypic determinant(s), unique to this patient's anti-Pr2 and located at or near the antigen-binding site. These anti-idiotypic antibodies may be useful tools for the study of this autoimmune response or for the development of immune therapeutic agents.(ABSTRACT TRUNCATED AT 250 WORDS)
Agglutinins↗
Heterogeneity of human red cell autoantibodies assessed by isoelectric focusing.
Human red cell (RBC) autoantibodies may be the products of a single lymphocyte clone or of a restricted number of clones. For insight into the clonal distribution of human RBC autoantibodies, serum fractions from 28 individuals with various forms of autoimmune hemolytic anemia (AHA) and two nonanemic individuals with positive direct antiglobulin tests were separated by isoelectric focusing (IEF), and RBC binding in each fraction was quantitated with a solid-phase radioimmunoassay. IEF fractions of serum from normal volunteers and patients with nonimmune hemolytic anemia served as controls. These studies indicate that RBC antibodies are found in a restricted number of IEF fractions in sera from some patients with immune hemolytic anemia. IEF fractions containing RBC-binding activity vary among patients with idiopathic AHA, and distinct patterns of binding activity are found in serum from some patients with AHA associated with alphamethyldopa and procainamide or with B-cell immunoproliferative diseases. These findings suggest that the mechanism leading to autoantibody production may differ among patients with the various forms of immune hemolytic anemia.
Anemia, Hemolytic, Autoimmune↗
Indications and guidelines for the use of hematopoietic growth factors.
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Acquired Immunodeficiency Syndrome↗