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J Lazarchick

Publications and source records attributed to J Lazarchick.

69 records · Page 4Linked to original sources
PubMedDate not supplied

Mechanism of factor VIII inactivation by human antibodies. IV. Antibody binding prevents factor VIII proteolysis by thrombin.

Factor VIII activation by thrombin is the result of a proteolytic cleavage of the procoagulant component. These studies examine the effect of human antibody on this activation step in a solid phase immunoadsorbent assay system. Radiolabeled factor VIII antibody: factor VIII protein immune complexes were bound to agarose beads by mouse monoclonal antifactor VIII R:Ag antibody. The incubation of these bound labeled immune complexes with high ionic strength buffers (1 M NaCl, 0.24 M CaCl2), or with acidic buffers (0.01 M glycine-0.1 M NaCl, pH 3.0 or 3.5), or with trypsin (1, 5, and 20 mg per ml) dissociated 14 to 62 percent of the bound radiolabel. Thrombin at a concentration of 0.05 U per ml, however, only dissociated 2.9 percent of the label, an amount not significantly different than borate buffered saline control. It is concluded that inactivation of factor VIII is the result of human antibody inhibition of thrombin-induced proteolysis of factor VIII procoagulant protein.

Antigen-Antibody Complex↗
PubMedDate not supplied

Lupus anticoagulants in children.

Although a great deal of information is available in the literature on the frequency, clinical/laboratory findings and significance of lupus anticoagulants in adults, little is known about such acquired inhibitors in children. Clinical and laboratory findings are presented on seven non-hemophiliac children, four females and three males, ranging in ages from three to 14 years, who developed such inhibitors. In most, the inhibitor is a transient phenomena and is not associated with a bleeding or thrombotic diathesis.

Adolescent↗
PubMedDate not supplied

Platelet-directed antibody in the serum of patients with primary thrombotic thrombocytopenic purpura.

Utilizing two platelet antibody assay systems, flow cytometric analysis and a microcytotoxicity assay, it was possible to demonstrate for the first time platelet-directed antibody in the sera of three of six patients with primary thrombotic thrombocytopenic purpura. These results lend support for an immune-mediated pathologic process in some patients with this disorder.

Adult↗
PubMedDate not supplied

The mechanism of factor VIII inactivation by human antibodies. II. The effect of factor VIII R: antigen on the rate of interaction.

Factor VIII R:Ag by binding to the procoagulant component (VIII:C) inhibits the extent and rate of interaction of human antifactor VIII antibodies with VIII:C. When this reaction is examined under ionic strength conditions (0.24M CaCl) which dissociate the two factor VIII components, the extent of the reaction is increased approximately two fold and the initial rate of interaction is increased three to four fold for both intact IgG antibody and its Fab' derivative. With isolated procoagulant component, increased ionic strength conditions only influence the rate of interaction. These studies further explain the peculiar time-dependence of this interaction.

Antigens↗
PubMedDate not supplied

Common variable immune deficiency syndrome associated with lupus anticoagulant.

A patient with an acquired immune deficiency syndrome developed a lupus anticoagulant in which the inhibitory activity was manifested only as a prolongation of the partial thromboplastin time. Contrary to previous reports, the substitution of platelets or platelet sonicates for phospholipid in this coagulant assay failed to correct the abnormality and the inhibitor did not exhibit immunoreactivity against phospholipids. The possible mechanisms of action of these inhibitors are discussed.

Adult↗
PubMedDate not supplied

Mechanism of factor VIII inactivation by human antibodies. III. Proteolytic cleavage of factor VIII:C and C antigen by thrombin.

Thrombin activation of factor VIII results in a marked, but transient, increase in factor VIII procoagulant activity. This proteolytic process has been examined by immobilizing factor VIII in a solid phase system using mouse monoclonal antibody specific for the factor VIII related antigen. These studies demonstrate that thrombin activation is the result of proteolytic cleavage from the factor VIII:C protein of a peptide fragment which contains both the factor VIII:C procoagulant and VIII:C antigen sites recognized by human antibodies.

Animals↗
PubMedDate not supplied

The effect of the physicochemical state of factor VIII on its interaction with human antibodies.

To assess the effect of the physicochemical state of factor VIII on its interaction with human antibodies, this interaction was examined using buffer conditions which would insure dissociation of the factor VIII complex. Anti-factor VIII titers were increased 2 to 2.5 fold under such conditions. When isolated factor VIII procoagulant material was used as the antigen source, the antibody titers were increased but no difference was noted in the presence or absence of the high ionic strength buffers. These studies indicate that factor VIII-related antigen in some manner retards the interaction of the procoagulant portion of factor VIII with human antibodies and may explain the peculiar time-dependence of factor VIII inactivation by these antibodies.

Antigen-Antibody Reactions↗
PubMedDate not supplied

Hairy cell leukemia and vasculitis.

A patient with hairy cell leukemia, systemic vasculitis, and HB8 antigenemia is reported. The patient presented with polyarthralgia before the diagnosis of the leukemia and had documented polyarthritis before the subsequent recognition of the vasculitis. The association of systemic vasculitis and hairy cell leukemia in the setting of HB8 antigenemia is discussed. The therapeutic challenge of treating coincident hairy cell leukemia and vasculitis is presented.

Adult↗
PubMedDate not supplied

The effect of 6% hydroxyethyl starch and desmopressin infusion on von Willebrand factor: ristocetin cofactor activity.

Hydroxyethyl starch is commonly used as a plasma volume expander in the surgical patient. Although it is generally considered a safe plasma substitution, some reports of an acquired von Willebrand's disease-like syndrome have been documented. To examine this further, von Willebrand factor: ristocetin cofactor activity (RCoF) was measured in two groups of patients perioperatively, following hydroxyethyl starch infusion and at 30, 60, and 240 minutes following either deamino-8-D-arginine vasopressin (DDAVP) (group I, n = 12) or saline (group II, n = 11). Following hydroxyethyl starch infusion, ristocetin cofactor activity decreased to 58 percent (group I) and 55 percent (group II) of their respective baseline values. After infusion of DDAVP, mean ristocetin cofactor activity in group I increased significantly to 95 percent at 30 minutes and 100 percent of baseline at 60 minutes. Mean ristocetin cofactor activity levels in group II, however, remained decreased, 69 percent and 57 percent of baseline at the same time points. There was no statistical difference between groups before or immediately after hydroxyethyl starch administration or at 240 minutes post-DDAVP or saline infusion. It is our conclusion that DDAVP is a safe therapy for the mild coagulapathy infrequently associated with hydroxyethyl starch administration.

Blood Coagulation Disorders↗
PubMedDate not supplied

Acquired von Willebrand's disease following bone marrow transplantation.

A 41-year-old male underwent allogeneic bone marrow transplantation for the treatment of acute myelogenous leukemia. Six months later, he was admitted to a hospital with signs and symptoms consistent with worsening chronic graft-vs-host disease. Despite a negative past history for a bleeding diathesis, the patient was found to have absent factor VIII procoagulant and ristocetin cofactor activities with markedly reduced von Willebrand factor antigen, all consistent with a diagnosis of acquired von Willebrand's disease. Successful treatment of this disorder with aggressive apheresis and von Willebrand factor replacement therapy is noted.

Adult↗
PubMedDate not supplied

Alterations in von Willebrand factor antigen in premature infants with respiratory distress syndrome and chronic lung disease.

Elevated levels of von Willebrand Factor Antigen (vWF:Ag) may occur in the presence of endothelial injury, a component in the pathology of acute pulmonary insufficiency. The vWF:Ag levels were examined in 13 well infants (controls) and 20 infants with respiratory distress syndrome (RDS), nine of whom developed bronchopulmonary dysplasia (BPD). All infants were very low birth weight (730 to 1500 g) and premature (25 to 34 weeks estimated gestational age). Plasma samples were obtained at birth and weekly through 28 days of age and frozen at -70 degrees C. The vWF:Ag was quantified by the enzyme linked immunosorbent assay (ELISA) method for 138 plasma specimens; in addition, 77 samples were analyzed for multimer pattern by SDS-agarose (1.7 percent) electrophoresis and densitometric scanning. All groups had elevated mean levels of vWF:Ag, compared to adults. Although levels remained stable over the four week period, the group of infants with BPD had a significantly high mean level of vWF:Ag at 21 days than those groups without BPD (p < 0.05). Visual examination of vWF multimer patterns revealed absence of unusually large vWF multimers and triplet patterns suggestive of increased proteolytic degradation of von Willebrand factor. However, densitometer scanning revealed that samples with higher vWF:Ag levels (> 200 percent) had increased amounts of moderate to smaller sized multimers, regardless of presence or absence of BPD. It is our conclusion that von Willebrand factor antigen levels are nonspecifically elevated in premature infants and that chronic lung disease is associated with even higher plasma values, possibly owing to pulmonary endothelial injury.

Antigens↗
PubMedDate not supplied

Acquired free protein S deficiency in children with steroid resistant nephrosis.

Plasma and urine concentrations of protein S were measured in five children with steroid-resistant nephrotic syndrome. It was found that plasma free protein S was reduced in three out of the five patients studied. Thus, acquired free protein S deficiency does occur in children with nephrotic syndrome and is one of many factors which may place them at risk for a thromboembolic event.

Child↗
PubMedDate not supplied

HLA-Dr negative acute non-lymphocytic leukemia.

Absent or diminished HLA-Dr antigen representation on the cell surface of both normal and leukemic promyelocytes is a hallmark of this stage of myeloid maturation. In order to document the specificity of this finding for acute promyelocytic leukemia, flow cytometric analysis of leukemic blasts was utilized on 36 cases of acute non-lymphocytic leukemia. All 15 of the promyelocytic leukemias (FAB-M3) studied showed absent or markedly decreased HLA-Dr antigen on their cell surface. However, the majority of cases (21) in which this finding was noted were other than promyelocytic leukemias and included all FAB subtypes, most particularly FAB-M2, i.e., myeloblastic leukemia with maturation. It is concluded that absent to decreased HLA-Dr antigen representation on leukemic blasts lacks specificity and can be seen in all acute myeloid/monocytic leukemic subtypes.

Adolescent↗
PubMedDate not supplied

Factor V inhibitor in a liver transplant patient associated with porcine xenoperfusion.

The development of a high-titer factor V inhibitor is described in a patient who underwent orthotopic liver transplantation followed by porcine xenoperfusion after an acute rejection episode. The inhibitor showed no cross-reactivity to either porcine or bovine factor V, nor was it accessible to human platelet factor V. The limitations of treatment modalities including intravenous immunoglobulin, steroids, cytotoxic therapy, intense plasmapheresis and platelet transfusions are discussed.

Adult↗