Search PubMed⌕ Search

Biomedical subjects

B G Firkin

Publications and source records attributed to B G Firkin.

At least 37 records · Page 2Linked to original sources
PubMed1987

Lupus anticoagulant in women with multiple spontaneous miscarriage.

A link between the presence of the lupus anticoagulant (LA) and recurrent spontaneous miscarriage exists; however, the incidence of the LA in patients with unexplained recurrent miscarriage is unknown. We have therefore investigated the incidence of the LA in women with recurrent miscarriage but without evidence of systemic lupus erythematosus or other syndromes known to predispose towards spontaneous abortion. Plasma from 29 such women was obtained and tested in the activated partial thromboplastin time (APTT), testing for correction with normal plasma if prolonged and in the dilute simplastin time test (DSTT), again mixing with normal plasma if prolonged. Using a prolongation in either/or both tests which was not corrected by mixing with normal plasma as criteria for the presence of the LA, 14 (48%) patients showed evidence for the presence of the LA. Substitution of platelet-rich plasma for phospholipid and plasma in the APTT corrected the prolonged clotting time in every patient (9/29) in which it was prolonged, further substantiating the presence of the LA. We suggest that the presence of the LA should be investigated in any patient with unexplained recurrent miscarriage.

Abortion, Habitual↗
PubMed1987

High dose intravenous gammaglobulin in Coombs positive hemolytic anemia.

Four patients with warm type autoimmune hemolytic anemia who failed to respond to steroid therapy received high dose intravenous gammaglobulin (0.2-0.4 g/kg daily) for five days. In one patient hemolysis occurred in association with non-Hodgkin's lymphoma and in the others the cause of the hemolysis was not established; two patients had prior splenectomy. A response to gammaglobulin therapy, demonstrable by a rise in or stabilisation of hemoglobin levels, a decrease in elevated serum bilirubin and lactate dehydrogenase levels, or prolongation of a shortened red cell (51Cr) survival, was observed in three patients. In two of these patients the effect of gammaglobulin therapy was temporary but allowed for splenectomy to proceed in one patient, without blood transfusion. The third patient continued to improve after cessation of gammaglobulin treatment. These findings suggest that high dose intravenous gammaglobulin may temporarily ameliorate hemolysis in some individuals with warm type immune hemolytic anemia, and may be a useful adjunct to steroids immediately before splenectomy.

Adult↗
PubMed1987

Lupoid thrombocytopenia.

Lupoid thrombocytopenia is herein defined as a disorder in which patients with thrombocytopenia have a positive Hep 2 antinuclear antibody. Although these patients may have other clinical or laboratory findings consistent with systemic lupus erythematosus, they do not satisfy the revised diagnostic criteria set down by the American Rheumatism Association (1982). In all other respects they have similar findings to patients with idiopathic thrombocytopenic purpura. Six patients are described with their clinical and laboratory features. It is proposed that this disorder should be distinguished from other forms of autoimmune thrombocytopenia including that associated with systemic lupus erythematosus.

Adult↗
PubMed1987

Further investigations on the significance of a plasma coagulation-accelerating factor in glomerular disease.

The prevalence of the coagulation acceleration factor (CAF) in patients with renal disease (predominantly glomerulonephritis) has been investigated. The relationship between the activated partial thromboplastin time, F.VIII:C/vWf, prekallikrein, plasminogen and the pathogenesis of glomerulonephritis was also investigated. One hundred and seventeen patients were entered into the study on the basis of admission for renal biopsy. Thirteen percent of the patients showed evidence for CAF and 15% of patients were found to have reduced levels of plasma prekallikrein; however, no correlation was found between any of the variables measured and the type, activity or progression of glomerular disease in these patients.

Adolescent↗
PubMed1987

Analysis of platelet von Willebrand factor antigen.

Platelet lysates were obtained from suspensions of normal washed platelets by freeze-thawing or Triton X-100 lysis. The resultant platelet lysates contained 0.34 +/- 0.15 U/10(9) platelets (n = 8) of von Willebrand factor antigen (vWf:Ag) as determined by radioelectroimmunoassay using a monospecific antibody to vWf:Ag. The vWf:Ag level was higher in platelet lysates prepared from freshly drawn blood than from outdated platelet packs. Platelet lysates from patients with severe von Willebrand's disease type I (n = 2) did not contain detectable vWf:Ag. When normal platelet lysates were analyzed by radiocrossed immunoelectrophoresis in agarose using a monospecific polyclonal antibody to plasma vWf:Ag, two immunochemically identical precipitin peaks were seen. One of the platelet vWf:Ag peaks corresponded in its electrophoretic mobility to plasma vWf:Ag, while the other peak, i.e. platelet vWf:Ag-peak II, migrated to a more anodal position. The presence of the platelet vWf:Ag-peak II suggests structural differences between plasma and platelet vWf:Ag and illustrates previously unrecognized heterogeneity of platelet vWf:Ag.

Antigens↗
PubMed1986

Effects of EACA on thrombin generation as measured by the chromagen S2238.

In the presence of epsilon aminocaproic acid (EACA) thrombin generation in recalcified platelet rich plasma (PRP) was markedly stimulated, as measured by the cleavage of the synthetic substrate S2238. However, thrombin activity remaining after 30 minutes incubation was reduced when compared with control values. The residual activity was shown to be hirudin insensitive and to be associated with a species of higher molecular weight than free thrombin. These results suggested an inhibition of thrombin binding to the antithrombin, alpha 2-macroglobulin (alpha 2M). Preincubation of PRP with EACA reduced the concentration at which EACA elicited its dual effects. Similar results were obtained with the alpha 2M inhibitor, hydrazine. These experiments indicated that alpha 2M may play a more important role in regulating thrombin generation than has been previously recognized.

Aminocaproates↗
PubMed1986

Binding of human thrombin to human factor VIII:RAg.

The binding capacity of radiolabelled human alpha-thrombin (alpha-thrombin), inactivated with phenyl-methyl sulphonyl fluoride (PMSF), to factor VIII related antigen (VIII:RAg) multimers isolated by immune precipitation and resolved by sodium dodecyl sulphate (SDS) agarose gel electrophoresis has been examined. 125I-PMSF alpha-thrombin bound predominantly to four low molecular weight multimers (LMW) of VIII:RAg prepared from either normal or haemophilia A plasma. Two of these VIII:RAg multimers present in serum had lost the capacity to bind thrombin. No bands were observed when either plasma or serum from three patients with severe von Willebrand's disease (vWd) was processed in an identical manner. This binding was not dependent on the presence of an intact catalytic site on the thrombin molecule. A similar pattern of binding to VIII:RAg multimers was observed with 125I-labelled human anti-FVIII antibodies as 125I-alpha-thrombin and appears to involve the same multimers.

Antigens↗
PubMed1985

Investigation of a coagulation accelerating factor (CAF) in glomerulonephritis.

A coagulation accelerating factor was purified from the plasma of two patients with glomerulonephritis (GN) who suffered from thrombotic complications. The factor co-purified with factor VIII/von Willebrand factor complex (FVIII/vWf) and under dissociating conditions remained associated with the factor VIII coagulant activity (FVIII). Control purified FVIII/vWf showed no coagulation accelerating activity under the experimental conditions used. The levels of coagulation accelerating factor, FVIII and von Willebrand factor (vWf) were reduced by incubation with rabbit anti-human FVIII/vWf or human anti-FVIII serum indicating a close association of these three activities. Multimeric analysis of the plasma FVIII/vWf complex from the two patients demonstrated a reduction in the high molecular weight multimers and the presence of an additional band not present on analysis of normal FVIII/vWf. It is suggested that the coagulation accelerating factor represents an active form of FVIII which has different in vitro properties to thrombin activated FVIII.

Adult↗
PubMed1984

The agglutination of human platelets by botrocetin: evidence that botrocetin and ristocetin act at different sites on the factor VIII molecule and platelet membrane.

Botrocetin caused a factor VIII (FVIII) dependent platelet agglutination which was associated with a reduction in the plasma levels of all FVIII parameters as a result of specific binding of FVIII to the platelets. The site of binding of FVIII to the platelet in response to ristocetin or botrocetin involves the glycoprotein I complex. This is suggested by the inability of chymotrypsin treated platelets or platelets from patients with the Bernard-Soulier syndrome to agglutinate in response to ristocetin. These platelets responded to botrocetin , but this was greatly reduced compared to normal. Crossed immunoelectrophoretic analysis indicated that in the presence of botrocetin most multimetric forms of FVIII bound to the platelet, whereas ristocetin caused binding of high and intermediate molecular weight forms. The antibiotic vancomycin inhibited platelet agglutination by ristocetin but had no effect on that caused by botrocetin . Assays of FVIII von Willebrand factor (VIII:vWf) using botrocetin compared well with those obtained using ristocetin in plasmas from normal individuals and from patients with classical von Willebrand disease (vWd). However, a patient with variant vWd demonstrated 100% botrocetin cofactor activity and 0% ristocetin cofactor activity. This suggested that the site of interaction on the FVIII molecule for botrocetin and ristocetin are different. Therefore the diagnosis of some von Willebrand variants cannot be excluded on the basis of a normal botrocetin cofactor assay.

Blood Platelets↗
PubMed1984

Retraction.

Explore the source record for details and available documents.

Retraction Notice↗
PubMed1983

Investigations of the lupus-like inhibitor by-passing activity of platelets.

Plasmas from ten patients with a lupus or lupus-like inhibitor were investigated. In each case the partial thromboplastin time with kaolin (PTTK) was prolonged and failed to correct on the addition of an equal volume of normal plasma. Activated control platelets corrected the inhibitory effect in the PTTK or thrombin generation time (TGT) in every instance. Activated autologous platelets were as effective as control platelets and may thus explain why bleeding is rarely associated with the lupus inhibitor. Experiments using platelets or plasma from patients congenitally deficient in a single clotting factor or normal washed platelets resuspended in deficient plasma indicated that the inhibitor by-passing activity is platelet and not plasma derived. Platelet fractionation studies suggested that this activity is localised at the platelet membrane.

Blood Coagulation Disorders↗
PubMed1983

Fast migrating protein, immunochemically related to human factor VIII, studied by crossed immunoelectrophoresis in agarose.

A fast migrating protein (FMP) was detected by agarose radio-crossed immunoelectrophoresis, in addition to factor VIII antigen (VIII:RAg), using antiserum to human factor VIII (FVIII). FMP had partial immunochemical identity with FVIII, migrated as an alpha-protein, and was distinct from alpha-2 macroglobulin, fibronectin or IgM. FMP was precipitated by concanavalin A and was separable from the bulk of VIII:RAg by ammonium sulphate fractionation. A significant amount of FMP was seen in normal serum (n = 12), plasma from patients with: (a) disseminated intravascular coagulation (n = 12) and (b) severe haemophilia A (n = 6). Trace amounts of FMP were observed in plasma from normal donors (n = 12), but neither VIII:ARg nor FMP was detectable in the plasma or serum from patients with severe von Willebrand's disease (n = 3). Freshly prepared cryoprecipitate contained trace amounts of FMP, similar to normal plasma, but increased levels were observed in antihaemophilic factor concentrates prepared for patient use. Significant levels of FMP were also seen in cryoprecipitate after storage at 4 degrees C for 7 d and this generation of FMP was diminished by the addition of protease inhibitors. The presence of significant levels of FMP in situations where proteolytic enzymes may be activated and inhibition of its generation by protease inhibitors, suggest that this protein is produced by proteolytic action of enzyme(s) on the FVIII molecule.

Antigens↗
PubMed1983

Coagulopathy of peritoneovenous shunts: studies on the pathogenic role of ascitic fluid collagen and value of antiplatelet therapy.

The role of ascitic fluid collagen in the pathogenesis of the coagulopathy that follows peritoneovenous shunting was examined. Collagen was partially purified from ascitic fluid and infused into rabbits. All animals developed changes in their haemostatic profile consistent with intravascular coagulation. Aspirin therapy, for five days before the collagen infusion, prevented these changes. Seven patients undergoing a total of eight peritoneovenous shunts for intractable ascites received antiplatelet therapy (aspirin and dipyridamole) in the immediate pre- and postoperative period. After six shunts no thrombocytopenia or prolongation of clotting times developed to suggest decompensated consumptive coagulopathy. Complicating factors may have contributed to the deterioration in haemostasis in the other two patients. There was no early shunt occlusion. The results support the hypothesis that ascitic fluid collagen is important in the pathogenesis of intravascular coagulation postascitic fluid infusion and indicate that antiplatelet drugs may be of value in preventing this complication.

Adult↗
PubMed1983

Association of increased immune complexes, platelet IgG and serum IgG in chronic active hepatitis.

Platelet associated IgG (PA-IgG), serum IgG and immune complexes (IC) were measured and correlated with the degree of thrombocytopenia in 32 patients with chronic active hepatitis (CAH), classified as of autoimmune type in 24 and cryptogenic in eight. Of the 32 patients, 24 had raised PA-IgG and 18 of these were thrombocytopenic (greater than 150 X 10(9) platelets/1); in only two thrombocytopenic patients was the level of PA-IgG not increased. Platelet counts showed a significant inverse logarithmic correlation with PA-IgG levels (r = 0.456, P less than 0.01). Twelve patients had raised levels in serum of ICs, 11 of these also had raised PA-IgG and 10 of these 11 were thrombocytopenic. Serum IgG was raised in 10 patients and correlated with PA-IgG (r = 0.489, P less than 0.01). Of the 24 patients with autoimmune CAH, 13 had low platelet counts and 10 had raised levels of PA-IgG whereas of the eight patients with cryptogenic CAH, seven had raised PA-IgG and all were thrombocytopenic. These results for patients with CAH show that raised levels of circulating ICs are associated both with thrombocytopenia and with raised PA-IgG, and support the hypothesis that serum IgG and/or ICs may influence amounts of PA-IgG.

Antigen-Antibody Complex↗