J Koutts

Monash University (Australia), Melbourne, Victoria, Australia

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Publications (25)238.49 Total impact

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    ABSTRACT: 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.
    British Journal of Haematology 04/1985; 59(3):485-96. · 4.94 Impact Factor
  • T E Gan, R J Sawers, J Koutts
    Blood 02/1983; 61(1):210. · 9.78 Impact Factor
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    ABSTRACT: 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.
    British Journal of Haematology 06/1982; 51(1):47-57. · 4.94 Impact Factor
  • British Journal of Haematology 02/1982; 50(2):379-380. · 4.94 Impact Factor
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    ABSTRACT: 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.
    American Journal of Hematology 10/1981; 11(2):153-7. · 4.00 Impact Factor
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    ABSTRACT: 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.
    British medical journal (Clinical research ed.) 07/1981; 282(6282):2083-5.
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    ABSTRACT: 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.
    British Journal of Haematology 05/1981; 47(4):607-15. · 4.94 Impact Factor
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    ABSTRACT: 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.
    JAMA The Journal of the American Medical Association 10/1980; 244(10):1122-3. · 29.98 Impact Factor
  • M A Howard, Jean Perkin, J Koutts
    The Lancet 04/1980; 1(8170):715. · 39.21 Impact Factor
  • H H Salem, J Koutts, B G Firkin
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    ABSTRACT: The platelet survival time and the presence of circulating platelet aggregates have been studied in patients with ischaemic heart disease (IHD). Platelet aggregates were detected in patients with recent myocardial infarcts and not in patients with asymptomatic ischaemic heart disease. A highly significant correlation was found between the presence of circulating platelet aggregates and the shortening in platelet survival.The significance of these findings on the overall prognosis is as yet uncertain but the recognition of two groups of patients with or without aggregates could influence the choice and effectiveness of antiplatelet therapy.
    Thrombosis Research 04/1980; 17(5):707-11. · 3.13 Impact Factor
  • T E Gan, R J Sawers, J Koutts
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    ABSTRACT: A patient with clinical and laboratory evidence of von Willebrand syndrome is described in association with an IgG-kappa immunoglobulin and Bence-Jones proteinuria due to a probable lymphoproliferative disorder. He had a persistently prolonged bleeding time of greater than 20 minutes, factor VIII related antigen (VIII:R.Ag), factor VIII procoagulant activity (VIII:C) and factor VIII ristocetin co-factor (VIIIR:Rcof) below 10%. Following cryoprecipitate or high purity factor VIII concentrate infusion, he had the expected immediate rise in VIII:C, VIII:R.Ag, and VIIIR:Rcof, but there was a rapid decline in all three components within two hours. The larger forms of VIII:R.Ag were preferentially removed from the plasma, and this paralleled the fall in plasma VIIIR:Rcof level. However, no inhibitory activity could be demonstrated in vitro using the patient's plasma or IgG. Using protein A it was possible to demonstrate that his plasma or IgG bound factor VIII and that this complex retained its biological activity in vitro. It is postulated that the monoclonal IgG forms complexes with factor VIII in vivo and these are rapidly removed by the reticuloendothelial system (RES).
    American Journal of Hematology 02/1980; 9(4):363-71. · 4.00 Impact Factor
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    ABSTRACT: Previous authors have noted that discrepancies occur for factor VIII-related antigen (VIII-Ag) levels when different techniques are used for its measurement. However no systematic study has been undertaken to identify the causes for these discrepancies. Factor VIII-related antigen (VIII-Ag) has been quantitated by either electroimmunoassay (EIA), solid or liquid phase radioimmunometric assay (S-IRMA or L-IRMA respectively). In general a close correlation existed between levels of VIII-Ag measured by these techniques. Values for VIII-Ag in serum, cryosupernatant and the plasma of haemophiliacs who have developed antibodies to factor VIII(FVIII) were found to be lower when measured by S-IRMA than by EIA; the L-IRMA gave intermediate values. Wherever a lack of correlation existed between the assays the VIII-Ag was found to have an increased electrophoretic mobility on radio 2-dimensional immunoelectrophoresis (radio 2-DIEP). Measurement of VIII-Ag of column fractions from a purification of FVIII concentrate confirmed that the S-IRMA failed to detect small VIII-Ag forms. It could be demonstrated that the antibody used for IRMA showed selection of the antibody towards large VIII-Ag forms. This selection together with the ‘two antibody sandwich’ technique used in S-IRMA may explain loss of reactivity towards the small VIII-Ag forms of FVIII.
    Thrombosis Research 01/1980; 19(1-2):63-72. · 3.13 Impact Factor
  • J Koutts, M A Howard, B G Firkin
    Progress in hematology 02/1979; 11:115-45.
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    ABSTRACT: It has been claimed that human anti-VIII:C antibodies do not form stable complexes with factor VIII and this fact has hampered in the past the isolation of such antibodies. In this study the purification of human anti-VIII:C antibodies appearing in haemophiliac patients following replacment therapy has been achieved using two different systems. In a liquid phase system, purified human factor VIII was mixed with IgG from a haemophilic patient with a high titre antibody. Specific anti-VIII:C antibodies were recovered following filtration of the antigen-antibody complexes on Biogel A-5m, dissociation of complexes at pH 3.5 and final isolation by filtration on Sephadex G-200. In a solid phase system, the same IgG fraction was specifically bound to insolubilized human factor VIII. Purified anti-VIII:C antibodies were subsequently recovered by elution of antigen-antibody complexes with magnesium chloride. The results demonstrated that stable complexes from between anti-VIII:C antibodies and either the whole factor VIII molecule, or VIII:C dissociated by previous interaction with the antibodies. It is postulated that, in vivo, similar antigen-antibody complexes may form following replacement therapy in haemophilic patients with antibody.
    British Journal of Haematology 01/1979; 40(4):631-41. · 4.94 Impact Factor
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    ABSTRACT: Platelet Factor VIII-related antigen (VIIIR:Ag) represents a significant proportion of the total circulating VIIIR:Ag pool. However, its participation in the events of primary hemostasis has not been shown. We now report that platelet-contained VIIIR:Ag is released from platelets by collagen, ADP and thrombin. The concentrations of these agonists, required for VIIIR:Ag release, are the same or lower than those required for release of serotonin, lysosomal enzymes, or fibrinogen. This release has the features of an energy-dependent secretory response because it is blocked by the metabolic inhibitors, antimycin A and 2-deoxy-D-glucose. The electrophoretic characteristics of the VIIIR:Ag released by collagen and ADP are similar to those of plasma VIIIR:Ag. However, thrombin-released platelet VIIIR:Ag differs from that of plasma in that the less anodal forms are relatively depleted. These differences do not appear to be the result of proteolytic degradation of platelet-derived VIIIR:Ag, but may reflect interactions between specific molecular forms of VIIIR:Ag and the platelet membrane. These studies suggest mechanisms by which platelet-contained VIIIR:Ag may contribute to the primary events of hemostasis.
    Journal of Clinical Investigation 01/1979; 62(6):1255-63. · 12.81 Impact Factor
  • J Koutts, J M Lavergne, D Meyer
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    ABSTRACT: The relationship between the three measurable components of the factor VIII complex, procoagulant activity (VIII:C), Ristocetin cofactor (VIIIR:WF) and factor VIII related antigen (VIIR:AG), has been investigated using a solid phase immunoadsorption system in which homologous antibodies specific for VIII:C are insolubilized onto Sepharose beads. The VIII:C component of partially purified factor VIII can be completely separated from the Willebrand factor (VIIIR:WF/VIIIR:AG) by this technique. The loss of VIII:C has no detectable effect on the molecular size, antigenicity or electrophoretic mobility of the original molecule. The Willebrand factor (WF) recovered from these immunoadsorption columns was used to absorb heterologous antisera to factor VIII. A specific heterologous antiserum to VIII:C, which no longer neutralized VIIIR:WF nor precipitated VIIIR:AG, was obtained. Heterologous antisera to WF were prepared which potently neutralized VIIR:WF and precipitated with VIIIR:AG, but also weakly neutralized VIII:C (titre I u/ml). This study is compatible with the theory that VIII:C and VIIIR:WF/VIIIR:AG are two different but linked entities.
    British Journal of Haematology 12/1977; 37(3):415-28. · 4.94 Impact Factor
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    ABSTRACT: WE report the presence of precipitating antibodies in three patients with von Willebrand's disease (VWD), an inherited deficiency of factor VIII (anti-haemophilic factor, AHF). To our knowledge this is the first description of patients with complete biological and immunological deficiency of a plasma-clotting protein responding to replacement therapy by the production of antibodies with properties indistinguishable from those elicited in animals. AHF is a high molecular weight (> 106) glycoprotein complex1 associated with two biological activities; one necessary for normal clotting (VIII: C) and the other for normal platelet function (Willebrand factor, VIIIR: WF). Specific antigenic determinants (VIIIR: AG) can be reliably quantified using heterologous antisera2,3. Any concept of the structure or the molecular genetics of AHF needs to incorporate the clinical and immunological findings in the two congenital disorders associated with AHF deficiency: haemophilia A and VWD. The former is a sex-linked deficiency of VIII: C alone whereas the latter represents a deficiency of all three parameters of the AHF complex and is inherited as an autosomal trait. Non-precipitating antibodies to AHF, acquired after replacement therapy, are common in haemophilia A (ref. 4) but only one case has been reported in VWD5,6.
    Nature 08/1976; 262(5564):141-2. · 38.60 Impact Factor
  • J Koutts, N Gude, B G Firkin
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    ABSTRACT: A monospecific heterologous antibody which specifically inhibited von Willebrand factor (W.F.) but had no factor VIII procoagulant (VIIIc) neutralising properties was insolubilised by attachement to sepharose beads. When fresh normal plasma was mixed with such beads, VIIIc, W.F. and factor VIII related antigen (VIIIAg) were removed in equal proportions, with the VIIIc lost from the plasma being detectable attached to the sepharose. This VIIIc was removed from the sepharose and largely recovered in the eluate after treatment with 0.2M calcium chloride. Subsequent addition of plasma resulted in a high transfer of VIIIc from the plasma onto the sepharose beads without accompanying W.F. and VIIIAg. Similar experiments, with initial treatment of antibody attached sepharose beads with serum, resulted in no independent segregation of VIIIc on subsequent addition of plasma. It is suggested that VIIIc and W.F. exist in plasma as separate, but attached molecules in a dynamic equilibrium. In serum, W.F. loses its ability to attach VIIIc.
    Thrombosis Research 06/1976; 8(5):533-41. · 3.13 Impact Factor
  • J Koutts, L Stott, B G Firkin
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    ABSTRACT: The absence of ristocetin-induced platelet aggregation appears to correlate with the platelet defect in von Willebrand's disease, suggesting that this reaction mimics a physiological process. The effect of ristocetin on plasma and on the residual levels of the von Willebrand factor (vWF), Factor VIII procoagulant activity, and Factor VIII-related protein in plasma after aggregation of platelet rich plasma by this agent has been studied in order to further elucidate the mechanism and requirements of this reaction. Ristocetin-induced platelet aggregation causes a consumption of vWF, Factor VIII procoagulant activity, and Factor VIII antigen from the supernatant plasma which is proportional to the number of platelets aggregated. Such a consumption of these factors does not appear to occur after aggregation by other agents. Factor VIII procoagulant activity does not appear necessary for ristocetin-induced platelet aggregation, yet is utilized in this process. These findings support the hypothesis that the molecule associated with Factor VIII procoagulant activity is carried by the molecule necessary for ristocetin-induced platelet aggregation.
    American Journal of Hematology 02/1976; 1(3):313-7. · 4.00 Impact Factor
  • J Koutts, N Gude, B Firkin
    Thrombosis et diathesis haemorrhagica 12/1975; 34(2):607.

Publication Stats

238 Citations
238.49 Total Impact Points

Institutions

  • 1974–1985
    • Monash University (Australia)
      • Department of Medicine
      Melbourne, Victoria, Australia
  • 1974–1983
    • Alfred Hospital
      Melbourne, Victoria, Australia
  • 1975
    • University of Melbourne
      Melbourne, Victoria, Australia