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Biomedical subjects

A L Bloom

Publications and source records attributed to A L Bloom.

At least 91 records · Page 5Linked to original sources
PubMed1979

Synthesis of procoagulant factor VIII, factor VIII related antigen and other coagulation factors by the isolated perfused rat liver.

The synthesis of factor VIII and other coagulation factors has been studied using an isolated, perfused rat liver. Synthetic function of the liver was validated by adding [35S]L-methionine to the perfusion medium and performing two-dimensional crossed immunoelectrophoresis and autoradiography on samples obtained during perfusion. Progressive incorporation of radioactivity into plasma proteins was demonstrated. This was inhibited by cycloheximide. Coagulation factor assays demonstrated synthesis of factors II, IX and X and of factor V and procoagulant factor VIII (VIIIC). Synthesis of factor VIII related antigen (VIIIRAg), measured in an immunoradiometric assay, was not significantly demonstrated. Addition of warfarin to the perfusion medium inhibited the synthesis of factors II, IX and X but not of factors V and VIII. Cycloheximide completely inhibited synthesis of all coagulation factors but actinomycin acted only after a latent period. Reticuloendothelial cell blockade was attempted by adding ethionine to the perfusion medium or by administration of Indian ink to the donor animals prior to removal of the livers. In these instances synthesis of factor V and factor VIIIC was inhibited but not that of factors II, IX and X. The results confirmed the functional capacity of the isolated liver for synthesizing proteins and the vitamin K dependent coagulation factors, and suggested similar kinetic features for the synthesis of factors V and VIIIC. Failure to detect significant VIIIRAg synthesis in these experiments is consistent with the hypothesis that this protein is released by vascular endothelial cells throughout the body and is activated or joined to VIIIC or stimulates its production in the liver.

Animals↗
PubMed1978

Immunoradiometric assay of procoagulant factor-VIII antigen in plasma and serum and its reduction in haemophilia. Preliminary studies on adult and fetal blood.

An immunoradiometric assay (I.R.M.A.) for antihaemophilic factor (factor VIII) has been developed which is based on a human inhibitor to procoagulant factor VIII (FVIIIC) which arose in a polytransfused haemophiliac. The assay detected and measured the antigen related to FVIIIC (FVIIICAg) in normal plasma and serum but failed to detect any antigen in samples from five patients with severe haemophilia. In a sixth patient with severe haemophilia a non-parallel dose-response curve was obtained. FVIIICAg was also present in plasma and serum from six samples of cord blood and in two samples of fetal serum obtained after termination of pregnancy. The assay may, therefore, be used to measure FVIIICAg in small serum samples and provides a potential practical method for prenatal diagnosis of haemophilia.

Adult↗
PubMed1978

Platelet-associated coagulation factors: immunological detection and the effect of calcium.

Normal platelets were examined by conventional coagulation methods and specific immunological techniques for the presence of platelet-associated coagulation factors. Platelets washed in buffer containing calcium chloride gave different results form those washed in the absence of calcium. Factor XI was not detected in washed platelets by any technique. Factor II and factor X were removed from platelets by washing in calcium-free buffer but not by calcium-containing buffer. Procoagulant factor VIII was readily removed or inactivated by washing in the presence or absence of calcium, but factor VIII related antigen was consistently demonstrated after multiple washes in either buffer. Factor V activity and antigen was detected in platelet suspensions after multiple washes although the presence of calcium in the washing buffer gave higher factor V assays and stronger immunological reactions than when calcium-free buffer was used. The results are consistent with the presence of calcium dependent binding sites in platelets which may have a role in the enhancement of factor V and phospholipid reactions.

Blood Coagulation↗
PubMed1978

Failure of factor VIII inhibitor bypassing activity (Feiba) to secure haemostasis in haemophilic patients with antibodies.

Factor IX concentrates have been widely advocated in the treatment of haemophilic patients with factor VIII inhibitors. Five such patients were given the 'activated' factor IX concentrate--factor VIII inhibitor bypassing activity (Feiba)--for 14 separate bleeding episodes. In six of the episodes, including two with external blood loss, bleeding progressed in spite of treatment. In none of the other eight episodes was there a prompt response, and it was not possible to ascribe a definite therapeutic effect.

Antibodies↗
PubMed1977

Fibrinolytic, factor VIII and pulse rate responses to repeated adrenaline infusion followed by haemorrhage.

The role of catecholamines in the activation of coagulation and fibrinolysis following surgery remains controversial. In this study 5 dogs were infused with 1,2,3,6,9 and 12 microgram kg-1 min-1 of adrenaline at twice weekly intervals and were then reexposed to 3 microgram kg-1 min-1. Pulse rate and factor VIII increased after infusion of 1,2 and 3 microgram kg-1 min-1 but thereafter there was a diminished response and no response on reexposure to 3 microgram kg-1 min-1 although this was not significant in the case of pulse rate. Euglobulin lysis time shortened after each infusion of adrenaline and showed no development of tolerance. A control series of dogs infused with saline showed no similar changes. Both groups of animals were then bled to a blood pressure of 60 mm Hg for 60 minutes. Pulse rate and factor VIII did not change but euglobulin lysis time shortened in both groups. The results suggest that the activation pathways for changes in factor VIII and euglobulin lysis time induced by adrenaline are separate.

Animals↗
PubMed1977

Immunological studies in combined factor V and factor VIII deficiency.

Plasma samples from patients with inherited combined factor V and factor VIII deficiency were examined by immunological methods for the presence of factor V and Factor VIII-related antigens. A factor V-related antigen was consistently demonstrated in all plasma samples by inhibitor neutralization assay using a non-precipitating rabbit antibody. Factor VIII-related antigens were detected by inhibitor neutralization using human antibody and by electroimmunoassay using a precipitating rabbit antibody. The amounts of factor V and factor VIII-related antigens present in the patient's samples were similar to those found in normal human plasma. The findings confirm the presence of normal levels of factor VIII-related antigen in the plasma of these patients and suggest that inactive antigenic determinants of procoagulant factor V and procoagulant factor VIII are also present. The results are consistent with the possibility that a common precursor of porcoagulant factor V and factor VIII is defective in these patients.

Antigens↗