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Biomedical subjects

G F Savidge

Publications and source records attributed to G F Savidge.

At least 55 records · Page 3Linked to original sources
PubMed1993

Heparin-induced skin reaction due to two different preparations of low molecular weight heparin (LMWH)

Heparin-induced skin reaction is a recognized complication of subcutaneously administered, unfractionated heparin, and has recently been described in association with the use of two LMWH preparations, Fragmin and Fraxiparin. We describe the case of a 25-year-old woman in whom characteristic skin lesions were induced on separate occasions by unfractionated heparin, Fragmin and a third preparation of LMWH, Clexane. This case demonstrates that substitution of one preparation of heparin for another does not prevent recurrence of skin reaction in susceptible patients. Alternative anticoagulants should be considered in these cases.

Adult↗
PubMed1993

Recombinant factor VIIa for intracranial haemorrhage in a Jehovah's Witness with severe haemophilia A and factor VIII inhibitors.

A Jehovah's Witness with severe haemophilia A and a high titre, high responding inhibitor to both human and porcine factor VIII (FVIII) was treated with recombinant activated factor VII (rVIIa) during an episode of intracranial bleeding. He recovered completely without any adverse effects or neurological sequelae. Treatment with rVIIa in this case was safe and effective. This therapeutic agent should be considered in haemophilia patients with inhibitors who refuse management with blood products on religious grounds and when recombinant factor VIII is not a cost-effective option.

Adult↗
PubMed1993

Acquired haemophilia in association with type III von Willebrand's disease: successful treatment with high purity von Willebrand's factor and recombinant factor VIIa.

A patient with autosomal dominant (Type III) von Willebrand's disease (vWd) developed acquired haemophilia post-operatively, possibly due to exposure to amoxycillin. She refused porcine factor VIII (pFVIII) on religious grounds and was managed successfully with recombinant activated factor VII (rFVIIa) together with highly purified von Willebrand factor concentrate (vWf-VHP). In patients with acquired haemophilia rFVIIa appears to be a suitable agent for symptomatic management.

Factor VIIa↗
PubMed1992

Disseminated intravascular coagulation and hepatocellular necrosis due to clove oil.

We describe the case of a 2-year-old child who suffered from disseminated intravascular coagulation (DIC) and hepatocellular necrosis, following ingestion of clove oil. The patient was treated with heparin and fresh frozen plasma, and, following specific haemostasis assays, with appropriate coagulation factor and inhibitor concentrates. The case demonstrates how this approach can be successfully used in the management of DIC with coexisting liver failure.

Child, Preschool↗
PubMed1992

The influence of therapeutic blocking of Gp IIb/IIIa on platelet alpha-granular fibrinogen.

Recent evidence suggests that platelet alpha-granule fibrinogen (fg) is derived from the plasma pool. Since platelets from patients with Type I Glanzmann's thrombasthenia (GT) are deficient in intracellular fibrinogen (fg) it was hypothesized that Gp IIb/IIIa could mediate the uptake of fg. To study the potential role of Gp IIb/IIIa in intracellular fg trafficking, the influence of therapeutic blocking of Gp IIb/IIIa on platelet fg was studied in 12 patients with stable ischaemic heart disease. Patients were either given a single intravenous dose of the monoclonal antibody 7E3 Fab (n = 4) or a combination of bolus and continuous infusion up to 24 (n = 3), 36 (n = 3) or 96 h (n = 2). All patients showed grossly prolonged bleeding times with a significant reduction of ex-vivo ADP induced aggregation. Although, surface Gp IIb/IIIa binding sites were consistently reduced in all patients, there was a variable but delayed decrease in platelet fg relative to vWf:Ag in only six out of the 12 patients studied. The reduction in fg appeared dependent upon both dosage and duration of Gp IIb/IIIa blockade. The study provides further evidence for the novel role of Gp IIb/IIIa in the intracellular trafficking of fg to platelet and megakaryocytic alpha-granules.

Adult↗
PubMed1991

Hepatitis C antibody profile and viraemia prevalence in adults with severe haemophilia.

Sera from 21 patients who had received large amounts of unheated factor VIII concentrate were tested for antibodies to the hepatitis C virus (HCV) by both commercial (Ortho C100) and 'in house' ELISAs. 'In house' assays utilized recombinant structural (core) or non-structural (replicase) HCV proteins generated by a baculovirus expression system. Antibodies to HCV were detected in 100% of the sera by the core protein based ELISA but in only 62% and 19% by the C100 and replicase based ELISAs, respectively. Hepatitis C viraemia was demonstrated in 90% of the patients by in vitro amplification of the 5' non-coding region of the HCV genome. Amplification with primer sets from two other regions of the genome proved less efficient at detecting viraemia. We conclude that the prevalence of hepatitis C infection in haemophiliacs may have been underestimated previously and that almost all HCV-infected patients have evidence of on-going viral replication.

Adult↗
PubMed1991

Folic acid absorption in patients infected with the human immunodeficiency virus.

To determine the folic acid absorption characteristics of patients with human immunodeficiency virus (HIV) infection, a prospective, controlled, result-blind single-dose oral absorption study was conducted. A total of 25 subjects were fasted and given 5 mg oral folic acid; blood samples were taken at time zero and after 30, 60, 90 and 180 min. Absorption of folic acid appears to be significantly impaired in HIV disease, irrespective of the stage of the disease and notwithstanding gastro-intestinal complaints, pathogen-negative diarrhoea or drug treatment. We here present functional data, complementary to previously reported structural and biochemical findings, to support the hypothesis that the virus can cause an enteropathy in the absence of opportunist infection. Folinic acid is absorbed by the same gut mechanism as folic acid, so caution may be needed when employing oral folinic acid rescue procedures in these patients, even when resting serum and red cell folate levels appear to be normal.

Absorption↗
PubMed1991

Bleeding diathesis coincident with chronic myelomonocytic leukaemia.

Two important haematological problems were found in an otherwise healthy 78 year old man: chronic myelomonocytic leukaemia; and a complex, acquired, hyperfibrinolytic bleeding disorder characterized by prolonged coagulation times, deficiency of coagulation factors V, X, and XI, anti-thrombin III and proteins C and S, with high concentrations of circulating tissue plasminogen activator, and low concentrations of plasminogen activator inhibitor. There may be a causal relation between the two conditions, with the peripheral blood monocytes mediating the hyperfibrinolytic process by the abnormal production of tissue plasminogen activator, though no previous description of a similar association has been reported.

Aged↗
PubMed1991

The interaction of the factor VIII/von Willebrand factor complex (VIII/vWf), with guanidinium-derivatized matrices.

Five different guanidinium (Gu)-derivatized agarose matrices were investigated for their potential in chromatographically resolving the Factor VIII/von Willebrand complex, VIII/vWf, fibrinogen, Fg, and fibronectin, Fn, from cryoprecipitate. Using conventional NaCl gradient methodology it was found that the order of elution of specific plasma proteins, and the yield of VIII/vWf, varied with the methods used to derivatize the agarose beads. Good yields of VIII:C (generally 30-45%) were obtained with Gu-matrices prepared by bis-oxirane coupling procedures. Cryoprecipitate binding studies showed that the capacity of Gu-Sepharose 4B, prepared by isourea modification of amino-Sepharose 4B, was 36 units VIII/vWf per ml matrix. The product, depleted of both Fg and Fn, had a specific activity of 2 units VIII:C per mg total protein, (yield 100% vWf:Ag and 47% VIII:C).

Chromatography, Affinity↗
PubMed1990

Alpha-granule pool of glycoprotein IIb-IIIa in normal and pathologic platelets and megakaryocytes.

Using an immunogold staining technique and electron microscopy, we investigated the localization of the alpha-granule pool of glycoprotein (GP) IIb-IIIa in normal platelets and maturing megakaryocytes (MK), in pathologic platelets from a patient with type I Glanzmann's thrombasthenia (GT), and from three patients with the gray platelet syndrome (GPS). In normal resting platelets, GPIIb-IIIa was observed on the plasmatic side of the plasma membrane, the open canicular system (OCS) membranes, and along the internal face of the alpha-granule membrane. This location was found with three monospecific polyclonal antibodies: one anti-GPIIb-IIIa antibody, the second specific for GPIIb, and the third specific for GPIIIa. After thrombin stimulation, the alpha-granule labeling disappeared whereas membrane labeling increased. Platelets from GT did not display labeling on plasma membranes, OCS membranes, or alpha-granule membranes. Platelets from the three patients with GPS displayed intense labeling of the plasma membrane and the OCS membrane, as well as the abnormal small alpha-granules and along the inside of large vacuoles (which contain the granule membrane protein [GMP]-140). In cultured immature MK from normal progenitors, both peptide components of GPIIb-IIIa appeared in the Golgi saccules and vesicles, and in the small precursors of alpha-granules, labeling both their membranes and their matrix. It was then observed only on the membrane of the mature MK alpha-granules, although labeling was less consistent than on the platelet granules. The MK plasma membrane and demarcation membrane system also displayed GPIIb-IIIa labeling. In conclusion, this study demonstrates that GPIIb-IIIa is present on the internal face of the alpha-granule membranes of platelets (where it appears early during MK maturation) as well as in the abnormal alpha-granules of gray platelets; it is absent from GT type I platelets.

Antibody Specificity↗
PubMed1990

Silastic interposition for haemophilic arthropathy of the elbow.

Thirteen elbows affected by severe haemophilic arthropathy and treated by silastic interposition arthroplasty were followed up for at least five years. The severity of pain, the frequency and severity of spontaneous haemorrhage and the range of movement were assessed before operation and at review. All patients were much improved and needed less factor replacement. Three elbows were revised, one for infection and two because of fragmentation of the silastic sheet. They regained good function following revision.

Adult↗
PubMed1989

Comparison of the in vitro characteristics of von Willebrand factor in British and commercial factor VIII concentrates.

Qualitative/quantitative analysis of von Willebrand factor antigen (vWf:Ag) in either heat or solvent/detergent treated factor VIII concentrates, used for haemophilia replacement therapy, was undertaken to assess their suitability for the treatment of vWD. For the first time immunoaffinity purified vWf:Ag (Monoclate by-product) was also evaluated by in vitro assessment. Potencies of vWf:Ag varied considerably but were consistently higher (28.9-420.5 iu/ml) than factor VIII:C (one-stage) activity (8.13-42.44 iu/ml). The functional activity of vWf was assessed by either Ristocetin Cofactor (vWf:RCo) or collagen binding methods (vWf:CBA) with typical vWf:RCo/vWf:Ag ratios ranging from 0.08 to 0.94. Multimeric analysis confirmed that in vitro biological activity was dependent on the presence of the high molecular weight forms of vWf:Ag. A significant correlation (r = 0.95) between vWf:RCo activity and collagen binding was observed in all of the concentrates with the exception of the immunopurified product. The data suggest that either NHS 8Y (mean vWfRCo/vWf:Ag = 0.94), Haemate P (mean vWf:RCo/vWf:Ag = 0.69) and high purity Octapharma V.I (vWf:RCo/vWf:Ag = 0.82) which contain medium/high MW vWf:Ag multimers are likely to be most cost-effective in the treatment of symptomatic severe vWD patients than other currently available concentrates.

Chemical Phenomena↗