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Biomedical subjects

B G Firkin

Publications and source records attributed to B G Firkin.

At least 55 records · Page 3Linked to original sources
PubMed1982

Simplified immunoradiometric assay for factor VIII coagulant antigen.

A simplified, non-competitive, solid phase immunoradiometric assay has been developed for the quantitation of factor VIII coagulant antigen (VIII:CAg)--the antigenic counterpart of FVIII coagulant activity (VIII:C). Both homologous and heterologous antibodies to human factor VIII (FVIII) were used in this assay. Initially, FVIII in a test sample was attached to immobilized, human IgG obtained from a polytransfused haemophilia A patient with a high titre antibody to VIII:C. The bound FVIII was then detected using rabbit 125I-IgG specific for human FVIII. The concentration of VIII:CAg correlated well with VIII:C levels in the plasma from normal donors (r = 0.84, n - 15). Homozygote von Willebrand's disease patients had undetectable levels of VIII:CAg in their plasma. Patients with severe haemophilia A (VIII:C less than 0.01 u/ml) could be divided into groups on the basis of the VIII:CAg levels, i.e. those having undetectable VIII:CAg and other with measurable VIII:CAg. VIII:CAg detected in normal serum was less than 0.002 u/ml. In this assay the use of human antibody to FVIII is considerably decreased compared to other methods for VIII:CAg, and the time-consuming steps to immunopurify human anti-FVIII antibody are eliminated.

Antigens↗
PubMed1982

Aggregation of human platelets by amniotic fluid.

Twenty-four amniotic fluid samples were examined for their effects on human platelets. All samples caused irreversible platelet aggregation. The active material precipitated with high-speed ultracentrifugation and was completely inhibited by prior incubation with purified collagenase. The presence of free collagen in amniotic fluid was further confirmed by polyacrylamide-gel electrophoresis and hydroxyproline assays. Beside platelet-aggregating activity, amniotic fluid samples were also shown to significantly shorten the recalcification time of normal plasma. This procoagulant activity appears to be related to the presence of thromboplastin, collagen and other as yet unidentified procoagulant material in amniotic fluid. The presence of activators of platelets and clotting factors in amniotic fluid would account for the strong clot-promoting activity of this fluid. These studies suggest that the ideal management of the coagulopathy of pregnancy should include a combination of anticoagulant and antiplatelet drugs.

Amniotic Fluid↗
PubMed1982

Variant von Willebrand's disease type B--revisited.

Results of investigations of the factor VIII (FVIII) of a patient with an unusual variant form of von Willebrand's disease (vWD) are presented. A two-peak crossed-immunoelectrophoresis (CIE) pattern was seen when fresh plasma was electrophoresed, but the CIE pattern became normal by incubating the plasma at 37 degree C for more than 72 hr. The two peaks on CIE were separated by cryoprecipitation: the slow-moving peak precipitating and the fast-moving forms of FVIII remaining in the cryosupernate. An additional protein band was seen on multimeric analysis of FVIII. The platelet-rich plasma (PRP) from this patient did not respond to ristocetin, but agglutinated normally in response to botrocetin. Multimeric and CIE analysis of the FVIII post agglutination and 125I-FVIII binding studies to normal formalin-fixed platelets indicated that this patient's FVIII interacted normally with botrocetin but failed to interact with ristocetin. These data strongly suggest that the sites on the FVIII molecule or the multimeric forms involved for ristocetin and botrocetin are different and that the ristocetin reaction is more closely aligned to the physiologic function of FVIII.

Animals↗
PubMed1981

Hypercoagulation in glomerulonephritis.

The clotting values of 50 patients with glomerulonephritis were examined. Three different coagulation groups were recognised: those with normal clotting values (group 1); those with high concentrations of factor VIII but otherwise normal clotting results (group 2); and patients who showed the presence of an activator of the intrinsic coagulation pathway, indicated by the presence of a short activated partial thromboplastin time or the ability of patients' plasma to shorten control clotting time in mixing studies (group 3). Patients in group 2 either had a uniform rise in all three components of the factor VIII molecule or a disproportionately higher concentration of factor-VIII-related antigen. In contrast, the level of VIII clotting activity in patients in group 3 was always higher than concentrations of either VIIIAg or VIIIWF. A significantly high incidence of thrombotic complications was observed in patients with group 3 but in none of the patients in either group 1 or group 2. Impaired renal function was more common in patients in groups 2 and 3, with higher mean serum creatinine concentrations in those with group 3. Patients with glomerulonephritis who have a short partial thromboplastin time with kaolin or who shorten control clotting time form a subgroup in whom hypercoagulation could adversely affect the course of their disease. The value of antiplatelet or anticoagulant treatment in these patients needs to be explored.

Adolescent↗
PubMed1981

The aggregation of human platelets by ascitic fluid: a possible mechanism for disseminated intravascular coagulation complicating LeVeen shunts.

To identifiy causative factors responsible for the disseminated intravascular coagulation complicating peritoneovenous (LeVeen) shunts, the ascitic fluid from 12 patients with alcoholic liver disease or peritoneal malignancy was examined for its effects on human platelets. In all patients, concentrated ascitic fluid caused irreversible platelet aggregation. Properties of the aggregating factor suggested that it is collagen, and subsequently, the presence of collagen in ascitic fluid was confirmed. This finding, together with the known effects of collagen on platelets and contact clotting factors, would be sufficient to explain the development of disseminated intravascular coagulation following this procedure. Aspirin by inhibiting collagen-induced aggregation may have a therapeutic role in the management of this problem.

Adenosine↗
PubMed1981

Quantitation of binding of factor VIII antigen to concanavalin A.

This study establishes a convenient method for screening plasma samples for abnormalities of the carbohydrate content of the factor VIII (FVIII) molecule. A radioimmuno-electrophoretic technique has been developed to quantitate the percentage binding of FVIII-related antigen (VIII-Ag) to the lectin concanavalin A (Con A). Plasma samples were electrophoresed through a strip of agarose containing Con A into agarose containing a mixture of unlabelled anti-FVIII and 125I-anti-FVIII where precipitant lines formed, the height of which was dependent upon the degree of VIII-Ag binding to Con A in the first gel. Using this system reduced binding of VIII-Ag to Con A was found in the plasma of 12 patients with moderate classical von Willebrand's disease (vWd), while the Con A binding of six haemophilia A patients fell within the normal range. The VIII-Ag in normal cryoprecipitate showed increased % binding to Con A while the VIII-Ag remaining in the cryo-supernate demonstrated reduced Con A % binding.

Antigens↗
PubMed1981

Relationship of raised platelet IgG in thrombocytopenia to total platelet protein content.

Platelet-associated IgG (PA IgG) of washed platelets of 20 normal controls and 45 thrombocytopenic patients was measured by radioimmunoassay and related to total platelet protein content. Mean values (+/- 2 SD) for 20 normals were 4.4 +/- 3.5 fg IgG per platelet (fg IgG/pl), 2.1 +/= 1.0 pg protein per platelet (pg protein/pl) and a ratio of IgG per g platelet protein of 2.1 +/- 1.8 mg IgG/g protein. Patients could be divided into two groups: Group I (31) with normal IgG/g protein ratios and either normal (16) or raised (15) fg IgG/pl, and Group II (14) with both fg IgG/pl and IgG/g protein raised. Of the 21 patients with idiopathic thrombocytopenia (ITP), 13 were in Group I (seven with raised and six with normal fg IgG/pl), and eight in Group II. There was significant correlation between PA IgG (fg IgG/pl) and platelet protein for the entire Group I (r = 0.95, P less than 0.001). The ITP patients in this group showed a similar correlation (r = 0.77, P less than 0.001), suggesting that raised PA IgG levels in Group I patients may be a result of protein-rich platelets. 60-90% of PA IgG was found in the soluble fraction of lysates of platelets from both normals and patients. Thus, it is either non-specifically associated with platelets or is antibody directed towards easily solubilized platelet antigens. Nine thrombocytopenic patients without immune disorders had raised PA IgG. These results question the assumption that raised PA IgG always indicates specific antiplatelet antibody.

Blood Platelets↗
PubMed1981

Quinine- and quinidine-dependent antiplatelet antibodies. Requirement of factor VIII-related antigen for platelet damage and for in vitro transformation of lymphocytes from patients with drug-induced thrombocytopenia.

The requirement of Factor VIII-related antigen (VIIIR:Ag) for platelet damage by quinine-and quinidine-dependent antibodies was studied in platelet-rich plasma (PRP) of four patients with severe von Willebrand's disease (vWd) (Factor VIII deficiency). Platelet factor 3 availability, platelet aggregation, and release of [(14)C]serotonin from labeled vWd-PRP by drug-dependent antibodies were significantly reduced in comparison with PRP from normal controls. Addition of purified VIIIR:Ag restored levels of platelet damage to that of normal PRP. In vWd-PRP, platelet damage by two human antiplatelet sera, not dependent on drugs, and by a rabbit antiplatelet serum did not differ from that in normal PRP. PRP from patients deficient in Factor VIII coagulant activity, Factor IX, or Factors II, VII, IX, and X behaved like normal PRP. The role of VIIIR:Ag in forming antigen able to transform lymphocytes of patients who had recovered from drug-induced thrombocytopenia was investigated by measuring incorporation of [methyl-(3)H]thymidine into DNA. When lymphocytes were cultured for 7 d, significantly less transformation occurred in response to platelets and the drug in the presence of vWd sera than in normal sera or sera deficient only in Factor VIII coagulant activity or Factor IX. Addition of purified VIIIR:Ag to vWd sera restored transformation to that obtained in normal sera. Nonspecific lymphocyte transformation by pokeweed mitogen was not affected by VIIIR:Ag. Thus VIIIR:Ag is involved both in platelet damage by drug-dependent antibodies and in the interaction between platelet and drug which produces an antigen able to transform sensitized lymphocytes.

Autoantibodies↗
PubMed1980

Leg pain and platelet aggregates in thrombocythemic myeloproliferative disease.

In three patients with thrombocytosis secondary to myeloproliferative disorders, disabling intermittent lower extremity pain occurred in the absence of peripheral vascular insufficiency. In all patients, circulating platelet aggregates were detected. Antiplatelet therapy resulted in prompt relief of pain and the disappearance of platelet aggregates. These findings suggest that abnormal platelet function with the formation of platelet plugs in the microcirculation could be responsible for the observed symptoms and response to treatment. The value of the determination of circulating platelet aggregates in the management of this syndrome is highlighted.

Aged↗
PubMed1980

Iron overload in congenital erythrocyte pyruvate kinase deficiency.

Severe iron overload developed in two patients with congenital erythrocyte pyruvate kinase deficiency. In one of them this was complicated by hepatic cirrhosis and endocrine dysfunction. In both patients, the institution of intermittent subcutaneous administration of desferrioxamine resulted in significant urinary iron excretion and a reduction in the degree of iron overload.

Adult↗
PubMed1980

Study of the factors that cause specific transformation in cultures of lymphocytes from patients with quinine- and quinidine-induced immune thrombocytopenia.

Quinine- or quinidine-induced thrombocytopenic purpura is caused by synthesis of an immunoglobulin (Ig)G antibody, which caused platelet damage in the presence of the offending drug. The nature of the antigenic stimulus has been examined by measuring incorporation of [3H]thymidine into DNA during lymphocyte transformation to blast cells in the presence of the drug. Although patients' lymphocytes responded normally to the nonspecific mitogen, phytohemagglutinin P, they did not respond to either drug or platelets alone. However, significant transformation occurred when patients' lymphocytes were cultured for 7 d with homologous or autologous platelets in the presence of therapeutic concentrations of the drugs (0.39-39 microM). Platelet membranes were more active than intact platelets on the basis of protein content, whereas platelets from a patient with Bernard-Soulier syndrome were inactive. Washed platelets pretreated with the drugs were inactive when cultured with lymphocytes in the absence of the drugs, whereas platelets pretreated similarly in plasma caused transformation. Control lymphocytes from 20 normal patients and 6 patients with nondrug-induced thrombocytopenia were not transformed by drugs and platelets in the presence of normal serum or serum containing drug-dependent antibody, showing that the observed response was specific for presensitized lymphocytes. Thus lymphocytes of patients with drug-induced thrombocytopenia are transformed by an antigen that forms after interaction of plasma, specific platelet membrane components and the drug.

Antigen-Antibody Complex↗
PubMed1979

Abnormal factor VIII in chronic renal failure.

Factor VIII procoagulant activity (VIII-C), related antigen (VIII-AG), and von Willebrand factor (VIII-vWf) were measured in 38 patients with chronic renal failure (CRF), in 19 patients with normal renal function from a general medical ward, and in 17 normal subjects. Wide variation in the levels of factor VIII (FVIII) functions were found in the group of CRF patients. There was no correlation between the levels of the three individual activities of FVIII in renal disease. The levels of the three functions were elevated in the patient controls and no significant differences were found between the two groups of patients, although both groups were significantly different from the normal subjects. Increased electrophoretic mobility (EM) was detected in 22 of the 38 patients with CRF (58%) compared to seven of the 19 patients controls (37%). These studies suggest caution in interpretation of changes in FVIII status in patients with other clinical disorders, such as liver disease.

Antigens↗
PubMed1979

Plasmapheresis in the treatment of thrombotic thrombocytopenic purpura: a report of five cases.

Thrombotic thrombocytopenic purpura, an acute clinical disorder of uncertain aetiology, has previously been associated with almost 100% mortality. Dramatic response to exchange transfusion has been reported, and there is some evidence that a circulating immune complex may be involved in the pathogenesis. Therefore, it was decided to employ large-volume plasma exchange by means of a continuous-flow cell separator in the management of five patients with this disease. Three patients showed a dramatic response, which was manifested by rapid correction of the neurological deficit and of the abnormalities in laboratory findings. We conclude that the thrombotic thrombocytopenic syndrome should be regarded as an indication for emergency plasma exchange.

Adolescent↗
PubMed1979

Erythroleukemia following drug induced hypoplastic anemia.

Three patients with drug-induced hypoplastic anemia terminating 2 to 6 years after presentation with erythroleukemia are described. All were treated for prolonged periods with androgen and corticosteroid and two of the patients showed apparent dependence on this therapy for optimal hematologic status. The leukemic phase was heralded by loss of this dependence and development of sideroblastic dyserythropoiesis with progression to bizarre erythroid hyperplasia and fatal cytopenia. The exact relationship between androgen and corticosteroid therapy and the erythroleukemia remains speculative.

Adrenal Cortex Hormones↗