An unusual circulating anticoagulant in an asymptomatic child.
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Blood Coagulation↗
Biomedical subjects
J Lazarchick
Publications and source records attributed to J Lazarchick.
Plasma fibronectin levels in preeclampsia: a possible biochemical marker for vascular endothelial damage.
Fibronectin is a plasma glycoprotein which is involved in coagulation, platelet function, tissue repair, and the vascular endothelial basement membrane. We have found plasma fibronectin concentrations to be elevated in a group of preeclamptic patients. This finding is consistent with other evidence for a role of the vascular endothelium in preeclampsia.
Blood Vessels↗
Detection of platelet antibodies by flow cytometric analysis.
A rapid, sensitive indirect immunofluorescence assay utilizing flow cytometry to detect immune-mediated thrombocytopenia is described. Fluorescein-conjugated F(ab')2 antihuman IgG or IgGAM is reacted with donor platelets after their incubation with test sera and the resulting immune complex is measured using flow cytometric analysis. With this technique excess of Ig on the platelet, expressed as a ratio of fluorescence of test sera/autologous control sera, was noted in 24 of 30 patients (80%) with immune thrombocytopenias caused by auto- or allo-antiplatelet antibodies. Twenty-four sera from nonimmune thrombocytopenic patients were consistently negative. This technique has the advantage of being highly reproducible and avoids the subjective interpretation inherent with manual immunofluorescence assays.
Antibodies↗
Elevated glucose concentrations increase factor VIIIR:Ag levels in human umbilical vein endothelial cells.
To determine if endothelial cell metabolism is affected by the elevated glucose concentrations known to occur in diabetes mellitus, we measured cellular Factor VIIIR:Ag in endothelial cells grown under conditions of increased glucose concentration. The results of this study illustrate that, under cell culture conditions, an increase in glucose concentration results in increased cellular levels of Factor VIIIR:Ag. Specifically, a glucose concentration of 300 mg/dl resulted in a 23% increase in Factor VIIIR:Ag levels while a glucose concentration of 600 mg/dl resulted in a 54% increase in Factor VIIIR:Ag levels. These in vitro findings may relate to the increase in plasma Factor VIIIR:Ag levels known to occur in diabetic patients.
Antigens↗
Normal range of plasma fibrinogen.
The automated thrombin time procedure was used to establish the normal range of fibrinogen concentration. Our results indicate a non-Gaussian distribution of this plasma protein and suggest this distribution is both age- and sex-dependent. The 95% confidence interval for the normal range of fibrinogen was 145-348 mg/dl.
Adult↗
Synthesis and release of factor VIII by cultured human endothelial cells.
Endothelial cells (ECs) derived from human umbilical veins were cultured in order to study the physiological control of factor VIII synthesis and release. The culture media were studied from multiple replicate cultures at confluence. Factor VIII related antigen (VIIIR:Ag) and factor VIII coagulant antigen (VIII:CAg) were measured by sensitive immunoradiometric assays. De novo synthesis of factor VIII related protein (VIII:R) was quantitated by incorporation of labelled amino acids into specific protein subunits. The following agents were added to the culture medium in a range of concentrations from physiological to pharmacological: adrenaline, 5 hydroxytryptamine, 2,3-DPG, cyclic AMP, thyroxine, hydrocortisone, and human growth hormone. None of them had any effect at any concentration on the rate of accumulation of VIIIR:Ag in the culture medium. Addition of exogenous factor VIII had no effect on do novo synthesis of VIII:R. VIII:CAg was found to be stable under the conditions of culture but none was released from the ECs. Long-term monocyte cultures also failed to release VIII:CAg. It appears that VIII:R is a constitutive gene product of umbilical vein endothelial cells and that VIII:CAg is not made by these cells.
Antigens↗
Mixed mononuclear cell cultures do not elaborate factor VIII.
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Cells, Cultured↗
Prenatal diagnosis of classic hemophilia.
Prenatal diagnosis of classic hemophilia (hemophilia A) in mid-trimester was achieved by means of immunoradiometric assays for factor VIII on fetal plasma and amniotic-fluid mixtures obtained by fetoscopy. Samples were analyzed from six male fetuses at risk for severe hemophilia and from nine control fetuses for which fetoscopy was carried out to attempt prenatal diagnosis of other genetic disorders. The factor VIII coagulant-antigen values for the control (non-hemophilic) samples were 17 to 94, and the factor VIII related-antigen concentrations were 50 to 155 U per deciliter. Three of the fetuses at risk for hemophilia had factor VIII values in the control range, and these infants were normal at birth. The other three fetuses had low concentrations of factor VIII coagulant antigen but normal concentrations of factor VIII related antigen. These values and the diagnoses of severe hemophilia were confirmed with blood from the abortuses.
Amniotic Fluid↗
Immunoradiometric measurement of the factor VIII procoagulant antigen.
A fluid-phase immunoradiometric assay has been developed which identifies an antigen on the Factor VIII (antihemophilic factor) procoagulant protein. This sensitive and quantitative assay is not influenced by levels of Favor VIII-related antigen (von Willebrand factor) or other plasma proteins. There is a close correlation of procoagulant activity and immunologically detectable protein in normal and von Willebrand's disease plasmas. In contrast, several different patterns have been identified in hemophilic plasmas. Neither procoagulant activity nor procoagulant antigen is detectable in plasmas from patients with severe classic hemophilia. Patients with mild and moderate hemophilia have either comparable plasma concentrations of procoagulant activity and procoagulant antigen or relatively greater levels of immunologically detectable protein.
Antigens↗
The properties of immune complexes formed by human antibodies to factor VIII.
Although human antibodies to Factor VIII inactivate its procoagulant activity, they do not form immunoprecipitates when tested with this antigen. To understand this observation, we have examined the interaction of normal human Factor VIII with four high-titer human anti-Factor VIII, two from transfused hemophiliacs and two "spontaneous" antibodies from nonhemophilic individuals. An estimate of the size of complexes formed by these antibodies has been obtained by agarose gel filtration of mixtures of anti-Factor VIII with cryoprecipitate. Complexed anti-Factor VIII was detected by the method of Allain and Frommel: acid dissociation of complexes at pH 3.5. Complexed anti-Factor VIII was detected in column fractions eluting between the void volume and those which correspond to the elution volume of human IgG. In contrast, Factor VIII procoagulant activity was restricted to void volume fractions when separations were carried out in antigen excess, and free anti-Factor VIII was limited to late-eluting fractions when separations were carried out in antibody excess. A small proportion of the complexed anti-Factor VIII was present in void volume fractions; the quantity was directly related to the ratio of antibody to antigen.Thus, although some complexed anti-Factor VIII is detected in void volume fractions, as would be expected for complexes formed with a very large plasma protein, most immune complexes elute in fractions that indicate interaction with a smaller antigen. These findings suggest that human anti-Factor VIII inactivates procoagulant activity by forming a complex with a small, apparently univalent, component of Factor VIII. This property may prevent immunoprecipitate formation.
Antibodies↗
Subclavian venipuncture: preventable complications; report of two cases.
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Adolescent↗
Hemoglobin C--G-Georgia double heterozygosity: a case report.
A 12-month-old black female with an unremarkable past medical history was admitted to the hospital with respiratory distress and fever without identified sepsis. Despite mechanical ventilation, the patient died as a result of respiratory insufficiency secondary to severe necrotizing bronchitis and bronchiolitis with pneumonia. Electrophoretic and biochemical analyses of the patient's hemoglobin showed the patient to be a double heterozygote for hemoglobin C (a beta chain variant) and hemoglobin G-Georgia (an alpha chain variant). This is the first report of this combination of hemoglobin variants.
Electrophoresis↗
Anti-thymocyte globulin induced thrombocytopenia.
Anti-thymocyte globulin is strongly reactive with platelets as measured by flow cytometric analysis. This reactivity appears to be independent of human leukocyte antigen (HLA) phenotype, is dose-dependent with saturation of platelet binding sites readily achieved with concentrations of horse anti-thymocyte globulin (ATG) at 0.25 mg per ml, and cannot be blocked with human anti-PLA1 antibody nor with heat-aggregated human IgG. Results of immunoblot studies after electrophoresis of platelet membrane proteins are consistent with the proposal that horse ATG contains antibodies specific for platelet glycoproteins V and IIa.
Antibody Specificity↗
Maternal platelet antibody levels in neonatal isoimmune thrombocytopenia.
A case of neonatal isoimmune thrombocytopenia (NIT) is described in which maternal platelet antibody levels decreased during the course of pregnancy. It is suggested that if this disorder is clinically suspected, maternal serum should be assessed for anti-platelet specificity using immunoblot analysis.
Adult↗
Impaired platelet function associated with parenteral nafcillin.
A 44-year-old Caucasian female was admitted with a subarachnoid hemorrhage owing to a multilobular tubular anterior communicating artery aneurysm. Eleven days after the original craniotomy, an epidural hematoma was evacuated. The patient was placed on empiric nafcillin antimicrobial coverage (two g every six hours). Within 24 hours, the onset of epistaxis and oozing of blood from the endotracheal tube and craniotomy site was noted. Recurrent subdural and epidural hematomas necessitated a third emergent craniotomy. The development of an acquired qualitative platelet defect was suggested by the findings of a prolonged template bleeding time and markedly abnormal platelet aggregation/ATP release studies despite a normal platelet count. Nafcillin therapy was immediately discontinued. Clinical bleeding resolved. Subsequent bleeding times and platelet aggregation studies confirmed the nafcillin-induced platelet dysfunction.
Adult↗
Passive neonatal thrombocytopenia. A case study of factors predicting the response to i.v. IgG therapy.
A term male infant was noted at birth to have petechiae over the face and trunk and a platelet count of 3 x 10(9) per L. Maternal immune thrombocytopenia (ITP) was suspected from the clinical data and confirmed by the presence of antiplatelet antibody (both in the mother and infant) detected by recently described flow cytometry method. Initial treatment with exchange transfusions, platelet transfusions, steroids, failed to correct thrombocytopenia and, hence, seven doses of high-dose gamma globulin (IV-IgG) were given intravascularly. Initiation of IV-IgG was followed by stabilization of platelet counts with marked reduction in the need for platelet transfusions. In this case of passive ITP, the therapeutic efficiency of high dose IV-IgG seems to depend upon maintaining a certain critical level of serum IgG (which in turn may depend upon the serum antiplatelet antibody titers).
Autoantibodies↗
Factor VIII procoagulant antigen levels in normal pregnancy and preeclampsia.
It has been suggested that the basis for the marked discordance in factor VIII parameters in preeclampsia is the result of proteolysis of the factor VIII procoagulant component (VIII:C) owing to activation of the coagulation system. To investigate this further, levels were compared of factor VIII:C and VIII:C (Ag), the immunologic equivalent of the procoagulant activity, in a series of preeclamptic patients and patients with uncomplicated pregnancies. No significant difference in the mean (+/- SD) level of factor VIII:C or VIII:C (Ag) could be detected between these groups. Our results do not support proteolysis of factor VIII:C as a mechanism to account for the discordant levels of the factor VIII parameters in preeclampsia.
Antigens↗