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Biomedical subjects

J Koutts

Publications and source records attributed to J Koutts.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1985

Clinching the diagnosis: assessment of hemostatic function.

The key to an adequate assessment of the hemostatic status of an individual patient is a full and adequate medical history and proper physical examination, and no set of screening tests can replace this. The vast majority of patients thus assessed will require no tests and the coagulation laboratory staff can concentrate on the full assessment of the small number of patients who will be identified as being at risk. The assessment of disturbances of hemostasis is a logical, and basically quite simple, sequence of tests.

Bleeding Time↗
PubMed1984

Characterization of calcium-dependent binding of endogenous factor VIII/von Willebrand factor to surface activated platelets.

Activation of washed platelets in the presence of EDTA with either 1 U/ml of alpha-thrombin or 2 microM calcium ionophore (A23187) caused the release of one-third to one-half of the platelet factor VIII/von Willebrand factor (FVIII/vWF) into the supernatant. When calcium was present in excess, only 10% of the platelet FVIII/vWF was detected free in the supernatant, regardless of whether calcium was present before stimulation or added to the platelets after thrombin activation. Release of [14C]serotonin and beta-thromboglobulin were not affected by divalent cations indicating that reduced supernatant levels of FVIII/vWF in the presence of calcium were not due to differential release, but were probably due to a calcium-dependent association of released FVIII/vWF with the platelet surface. The presence or absence of intact glycoprotein Ib on the platelet surface made no significant difference to the observed FVIII/vWF partition. Platelets from a patient with Glanzmann's thrombasthenia, however, failed to show a calcium effect with respect to released FVIII/vWF. The combined results suggest that as well as the ristocetin-dependent, divalent cation-independent binding of FVIII/vWF to glycoprotein Ib, there is a divalent cation-dependent binding of FVIII/vWF to the activated platelet surface which is mediated via the glycoprotein IIb/IIIa complex.

Blood Coagulation Factors↗
PubMed1983

Incidence of post-operative deep vein thrombosis in gynaecological oncology.

Using 125I-fibrinogen scanning the incidence of post-operative DVT amongst patients with gynaecological malignancy was shown to be 37.9% which is substantially higher than the 10% to 15% expected in a general gynaecological population. Twenty per cent of the total group studied had isotopic evidence of bilateral venous thrombosis post-operatively. The inaccuracy of clinical diagnosis was demonstrated, and also the need to investigate both limbs if thrombosis was suspected. The incidence of post-operative DVT was found to be significantly lower in smokers (11.5%) compared with non-smokers (68.4%) (p less than 0.00025).

Female↗
PubMed1983

Quinidine-induced thrombocytopenia and leukopenia: demonstration and characterization of distinct antiplatelet and antileukocyte antibodies.

A patient with the rare syndrome of simultaneous quinidine-induced thrombocytopenia and leukopenia was studied. A quinidine-dependent antiplatelet antibody was detected in her serum by platelet aggregometry and by indirect platelet-suspension immunofluorescence. A drug-dependent antileukocyte antibody was demonstrated by leukoagglutination and by granulocyte immunofluorescence. Both antibodies were found to belong to the IgG class by immunofluorescence using monospecific antisera. There appeared to be two distinct antibodies, since the antibody eluted off sensitized platelets reacted only with platelets and that eluted off sensitized granulocytes reacted only with granulocytes. In addition, the patient's serum and quinidine gave a negative reaction on immunofluorescence with platelets from a patient with Bernard-Soulier syndrome (BSS), which lack glycoprotein lb (GPlb) complex, but gave a positive reaction with BSS granulocytes. The quinidine-dependent antiplatelet antibody immunoprecipitated GPlb and a glycoprotein of molecular weight 22,000 (GPlb complex) from Triton-solubilized, periodate-labeled platelets. Similar attempts to identify the granulocyte surface receptor/antigen were unsuccessful. Factor VIII/von Willebrand factor was not required for binding of the drug-dependent antibody to platelets.

Antibody Specificity↗
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↗
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↗
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

Pathogenesis of antibody-induced acquired von Willebrand Syndrome.

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).

Antigen-Antibody Complex↗
PubMed1978

Isolation of human antibodies to factor VIII.

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.

Antibodies↗