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Biomedical subjects

G F Savidge

Publications and source records attributed to G F Savidge.

86 records · Page 5Linked to original sources
PubMed1984

Inhibitor to factor VIII in mild haemophilia.

Factor VIII inhibitors in mild haemophilia are uncommon and the management of such patients is controversial. The development of a persistently high responding F VIII inhibitor in a mild haemophiliac is reported and the behaviour of the inhibitor discussed in the context of the various therapeutic regimes employed for symptomatic management. When inhibitor titres were low, endogenous F VIII stimulation, by DDAVP, was less immunogenic than the administration of exogenous F VIII concentrates. This inhibitor displayed characteristics of an autoantibody, and was characterised as an immunoglobulin of IgG subtype.

Adult↗
PubMed1984

A double-blind trial of ticlopidine in sickle cell disease.

Baseline studies of 111Indium oxine labelled platelet life-span, platelet alpha-granule release products, beta-thromboglobulin (beta TG) and platelet factor 4 (PF4), and factor VIII related activities were performed on 9 asymptomatic patients with sickle cell disease, who were subsequently randomised in a prospective double-blind trial of ticlopidine (250 mg. b. d.) or placebo for one month and the investigations repeated. Control studies indicated that 5 of the 9 patients had shortened platelet survivals: mean beta TG (50.8 ng/ml) and PF4 (19.5 ng/ml), factor VIII:C (283.4 i.u./dl) and factor VIIIR:AG (168.7 u/dl) levels were raised. Ticlopidine treatment did not significantly improve platelet life-span or factor VIII levels, though it was associated with reduced values of beta TG and PF4. One patient taking ticlopidine developed an infarctive sickle crisis. Although ticlopidine blocked platelet activation, this alone did not improve platelet survival or prevent sickle crisis: in view of evidence of platelet activation in sickle cell disease, however, a longer trial of prophylactic antiplatelet drugs might be warranted.

Adult↗
PubMed1984

Von Willebrand factor has more than one binding site for platelets.

By the use of a series of monoclonal antibodies against platelet membrane glycoproteins (GP) and the von Willebrand factor (vWF), it is shown that thrombin-induced binding to GP IIb/IIIa involves a different site on vWF from ristocetin-induced binding to GP Ib.

Antibodies, Monoclonal↗
PubMed1984

The effects of amrinone on platelet count, survival and function in patients with congestive cardiac failure.

In a prospective trial, the immediate and long-term haematological effects of amrinone were studied in sixteen patients with refractory cardiac failure. The platelet count was significantly and variably reduced in all patients and the reduction was related to log plasma amrinone concentration. Platelet survival was significantly reduced in those cases studied. No evidence of disseminated intravascular coagulation or intravascular platelet deposition was observed and the reduced platelet survival was not considered to be the result of an immunological process. Evidence of a marrow response to the reduced platelet count and survival was seen. Although no haemorrhagic symptoms were observed in the patients, the haematological side-effects were considered to be of such severity as to limit the use of this drug in clinical practice.

Adult↗
PubMed1983

Rapid quantitation of plasma heparin and antithrombin III levels for cardiopulmonary bypass monitoring, using fluorometric substrate assays.

Plasma heparin and ATIII levels were determined using recently developed fluorometric substrate techniques on serial samples taken from 9 unselected patients undergoing open-heart surgery on cardiopulmonary bypass. The fluorometric assay for ATIII and established clotting and immunological methods showed a highly significant correlation (p less than 0.001). Heparin recovery was reduced in all cases, and plasma levels (fluorometric assay) demonstrated poor correlation to Whole Blood Activated Clotting Time (Hemochron) estimations. ATIII levels were dramatically reduced during bypass, and in 3 cases reached levels below 0.08 iu/ml. Heparin reversal schedules based upon empirical dosage led to excessive protamine administration by a mean factor of 3.3, as assessed by in vitro neutralization of standardized heparin concentrations.

Antithrombin III↗
PubMed1983

Interposition arthroplasty in the management of advanced haemophilic arthropathy of the elbow.

Six patients with severe haemophilic arthropathy of the elbow have been treated by limited excision arthroplasty using a sheet of silicone rubber as an interposition membrane. There were no complications. The symptoms and signs before and after operation have been assessed using the grading system advocated recently by the World Federation of Haemophilia. In all cases there was relief of pain and increased movement. Moreover, the subsequent incidence of spontaneous haemorrhage into the elbow has been reduced with considerable cost benefit.

Adolescent↗
PubMed1982

An acquired coagulation inhibitor to factor II.

An elderly woman with a bleeding problem associated with prolonged PTT, PT and thrombin time but with normal snake venom time was found to have very high levels of plasma antithrombin. The antithrombin activity was isolated and characterized and found to be an IgG which directly inhibited thrombin and also precipitated prothrombin. The concentration in plasma of the gamma-globulin inhibitory activity was equivalent per ml to 80 NIH units of thrombin. Corticosteroid and immunosuppressive treatment reduced the level of the inhibitor with remission of bleeding symptoms.

Aged↗
PubMed1981

The surgical management of varus deformity in haemophilic arthropathy of the knee.

Five patients severely affected by haemophilia, in whom six knees showed advanced haemophilic arthropathy, have been studied. The patients presented with painful limitation of movement and increasingly frequent episodes of spontaneous bleeding in the affected knees. These all showed secondary degenerative changes and varus deformity. A Corrective osteotomy of the proximal tibia was performed under full haematological cover without complications. Follow-up ranged from 6 to 36 months, with a mean of 18 months. At follow-up all patients were free of pain and had retained their range of movement. In the three patients with a longer follow-up there was radiological improvement. The most significant feature was that there was almost complete cessation of bleeding episodes into the knee in all patients and no progression of the arthropathy. The cost benefit implications of this corrective procedure are discussed.

Adult↗
PubMed1980

Influence of age, sex and blood groups on 15 blood coagulation laboratory variables in a reference material composed of 80 blood donors.

15 blood coagulation and fibrinolysis variables were determined in 80 healthy blood donors. Males were shown to have significantly higher levels of factor VII and factor X, and in subjects with blood group O significantly lower levels of VIIIR:AG were observed. In individuals with blood group O a skewed distribution of VIIIR:AG suggested a mixed population of this antigenic determinant. No significant correlation (r less than 0.36) was found between age and any of the laboratory variables.

Adult↗
PubMed1980

Late thrombotic malfunction of the Björk-Shiley tilting disc valve in the tricuspid position. Principles for recognition and management.

Among 52 consecutive patients surviving tricuspid valve replacement with the Björk-Shiley tilting disc valve, follow-up extends between 1/2-9 years, mean 4.9 years. Four patients suffered thrombotic obstruction of their tricuspid prosthesis on 8 occasions, an incidence of 3.2%/year. Ebstein's anomaly and deficient anticoagulation were identified as likely contributory factors, but the complication remained unexplained in 2/8 instances. Thrombotic malfunction of the tricuspid prosthesis seems to constitute a relatively benign clinical entity with mild manifestations and diagnostic possibilities by non-invasive methods. Relief by means of thrombolytic treatment in the form of streptokinase (Kabikinase) (4) or replacement of the clotted prosthesis (4) involved neither disabling complications nor mortality. Our clinical observations and experimental studies suggest that thrombolytic therapy is effective, provided that prosthetic malfunction is due to a recent red clot, whereas encapsulation of the prosthetic disc by organized white-grey pannus necessitates re-operation. Streptokinase treatment should be attempted before surgery, but it is hardly meaningful to proceed for more than 24 hours. Restored prosthetic function within this time limit indicates the likely resolution of a red clot.

Angiocardiography↗
PubMed1979

Rapid thrombolysis and preservation of valvular venous function in high deep vein thrombosis. A comparative study between streptokinase and heparin therapy.

The results of streptokinase and heparin treatment are compared in a 4-year prospective study with special reference to preservation of high valvular venous function. An objective assessment was based upon phlebographic examinations before, during and 1-2 months after therapy. Complete lysis was demonstrated in 44% of high thromboses treated with streptokinase and in 6% treated with heparin. Retrograde phlebography revealed normal function of the proximal femoral valves in 92% of streptokinase-treated high thromboses, compared with 13% of those treated with heparin. These phlebographic results were considered to be a valid prognostic indicator of the eventual development of the postthrombotic syndrome. Allergic reactions were seen in 39% and minor haemorrhagic complications in 18% of the streptokinase-treated cases. The therapeutic benefit of streptokinase therapy in this study was found to outweigh any disadvantages incurred by observed complications.

Drug Evaluation↗
PubMedDate not supplied

Protamine sulphate and heparin rebound following open-heart surgery.

The efficacy of heparin reversal was investigated in 35 patients undergoing open-heart surgery. A total protamine sulphate dose of 3.0 mgs/kg was administered in divided doses and given as a continuous infusion. On this regime complete heparin neutralisation was observed 10 min after decannulation, but heparin levels were again detectable in 29% of cases 2 hours later. This phenomenon was found to correlate with the total circulating load of heparin to be neutralised. All cases with detectable postoperative heparin levels had in-vivo protamine sulphate: heparin ratios of less than 1.6. These data suggest that in-vitro assays of protamine sulphate neutralisation of heparin may seriously underestimate the required dose of protamine sulphate following open-heart surgery.

Adult↗
PubMedDate not supplied

Significance of the whole blood activated clotting time in cardiopulmonary bypass.

Recent publications have described a poor correlation between whole blood activated clotting time (WBACT) values and plasma heparin levels during cardiopulmonary bypass (CPB). A prospective, controlled study was undertaken to investigate the variables which may influence the WBACT in this situation. Antithrombin III levels over a range of 35-93 u/dl did not influence either the WBACT value or plasma heparin level. However, reduced platelet function following infusion of prostacyclin (10 ng/kg/min prior to CPB and 20 ng/kg/min thereafter); platelet number (range 63-287 X 10(9)/l) and packed cell volume (range 16-30%) were found to correlate with the WBACT. It is concluded that in addition to the circulating plasma heparin level, the wide variations in platelet number, platelet function and packed cell volume which are frequently observed during cardiopulmonary bypass may also influence the WBACT value.

Adult↗