Search PubMed⌕ Search

Biomedical subjects

B M Alving

Publications and source records attributed to B M Alving.

86 records · Page 5Linked to original sources

Effects of lipid A and liposomes containing lipid A on platelet and fibrinogen production in rabbits.

The effect of the lipid A moiety of endotoxin on platelet and fibrinogen production was studied in rabbits. Lipid A was infused intravenously in doses ranging from 1 to 100 micrograms/kg body mass; 18 hr later, selenomethionine-75Se was injected intravenously and its incorporation into fibrinogen and platelets determined. Lipid A in saline stimulated fibrinogen and platelet production, but the dose required was 50--100 times that required for an intact endotoxin. Although lipid A solubilized in triethylamine (TEA) was at least 60 times more active in the Limulus amebocyte lysate assay than was lipid A suspended in saline, the sensitivity of platelet and fibrinogen production to solubilized lipid A was increased only twofold. Incorporation of lipid A into liposomes had no effect on its Limulus activity. Lipid A in liposomes continued to stimulate platelet, but not fibrinogen, production. Leukopenia that was induced by lipid A in TEA did not occur when rabbits received the same dose of lipid A in liposomes. Lipid A, like intact endotoxin, can stimulate platelet and fibrinogen production and induce leukopenia but the doses required are high. The low solubility of lipid A in aqueous solutions may be only one factor that determines its biologic activity.

Animals↗

Platelet and fibrinogen production: relative sensitivities to endotoxin.

The relative sensitivities of platelet and fibrinogen production to endotoxin were determined in male New Zealand rabbits. E. coli endotoxin was administered in single intravenous doses of 0.1 to 50.0 mu/g/kg body mass. 75SeM was injected 5, 12, or 18 hr after endotoxin, and the percent incorporation into platelets and fibrinogen was used to measure thrombopoiesis and fibrinogen synthesis. Leukopenia occurred after the infusion of endotoxin at all dose levels; the lowest dose that caused thrombocytopenia was 0.5 microgram/kg. Endotoxin was detected with the Limulus test in plasma of animals that received 5 to 50 microgram/kg. The stimulation of fibrinogen and platelet production, as well as the postinfusion decrease in platelet count, correlated directly with the log of the dose of endotoxin infused. The lowest dose of endotoxin that stimulated platelet and fibrinogen production was 0.5 microgram/kg. In animals that received this dose of endotoxin, increased fibrinogen production was detected only when 75SeM was injected 5 hr later. In animals injected 5, 12, or 18 hr later. Increased platelet production was detected at these two doses only when 75SeM was injected 18 hr after endotoxin. The data indicate that fibrinogen and platelet production have similar sensitivities to endotoxin, although the time course of stimulation is different for these two blood components.

Animals↗

Hypotension associated with prekallikrein activator (Hageman-factor fragments) in plasma protein fraction.

Thirteen lots of plasma protein fraction made by one manufacturer were implicated in 23 recent reports of hypotension in surgical patients. Four of these patients required resuscitation after rapid administration of the product in the postoperative period. All implicated lots had prekallikrein-activator activity but low levels of bradykinin and kallikrein. The prekallikrein activator was identified as Hageman-factor fragments by molecular weight (35,000 as estimated by gel chromatography), isoelectric point (4.2 to 4.4), and inhibition by antibody to Hageman factor. These data suggest that Hageman-factor fragments are potent hypotensive agents, presumably because they trigger the generation of bradykinin in recipients. Prekallikrein-activator activity, usually at levels lower than those in the initial 13 implicated lots, was frequently detected in plasma protein fraction made by other manufactures. Several of these lots were associated with additional reports of hypotension. Prekallikrein-activator activity rarely occurred in albumin.

Bradykinin↗

Fibrinogen synthesis in rabbits: effects of altered levels of circulating fibrinogen.

The effects of altered fibrinogen concentrations on fibrinogen synthesis in rabbits were evaluated by determining the rate of appearance of [75Se]selenomethionine (75SeM) in circulating fibrinogen. Fibrinogen levels were maintained at twice normal by infusion of homologous fibrinogen for either 1 or 6 days before the intravenous injection of 20 micronCi of 75SeM, and the rate of appearance of labeled fibrinogen was measured during the subsequent 24 h. In both groups, synthesis was unchanged. Five hours after induction of partial defibrinogenation by the infusion of bovine thrombin, fibrinogen synthesis was increased threefold. Stimulation was not attributable to decreased fibrinogen concentrations; synthesis was increased equally when levels were maintained above normal by infusion of fibrinogen before administration of thrombin. Heat-inactivated thrombin and diisopropylfluorophosphate-inactivated thrombin did not stimulate fibrinogen synthesis. Thrombin produced elevated titers of fibrinogen-fibrin degradation products (FDP-fdp). However, fibrinogen synthesis was not increased in rabbits that had received FDP-fdp from thrombin-treated donors. These data suggest that neither the fibrinogen concentration nor FDP-fdp influenced fibrinogen synthesis.

Animals↗

Stimulation of fibrinogen synthesis by thrombin in rabbits with ancrod-induced afibrinogenemia.

The effect of intravenous infusions of thrombin on fibrinogen synthesis was evaluated in rabbits rendered afibrinogenemic by ancrod. Fibrinogen production and catabolism were measured simultaneously with 75Se-labeled selenomethionine (75SeM) and with 125I-labeled fibrinogen injected 5, 12, 18, or 26 h after ancrod. In normal rabbits the infusion of ancrod (2 U/kg body mass during 1 h) did not alter fibrinogen synthesis nor did it affect the rate of fibrinogen catabolism measured during a period of 5-120 h after ancrod administration. Normal rabbits that received purified bovine thrombin (100 U/kg body mass during 1 h) exhibited a twofold stimulation of fibrinogen synthesis as measured by the incorporation of 75SeM injected 5 h after thrombin. Rabbits made afibrinogenemic by infusion of ancrod 5 h before thrombin also showed a twofold increase in fibrinogen synthesis, as did animals that received ancrod immediately after thrombin. These experiments show that ancrod alone has no effect on fibrinogen production, and that thrombin stimulates fibrinogen synthesis in afibrinogenemic rabbits to the same extent as in controls.

Afibrinogenemia↗

Thrombocytopenia occurring during the administration of heparin. A prospective study in 52 patients.

In a group of 52 patients receiving continuous intravenous heparin, 16 developed thrombocytopenia (platelets less than 100 000/mm3). Ten of the 16 patients who had thrombocytopenia had elevated titers of fibrinogen-fibrin degradation products, and five of these 10 patients also had a reduction in plasma fibrinogen. The abnormalities disappeared after the heparin preparation was discontinued. These occurrences could not be attributed to drugs other than heparin, to the dose of heparin administered, or to prior exposure to heparin. The mechanism by which the heparin preparation may induce these changes is not known.

Aged↗

Replacement therapy for congenital Factor X deficiency.

We studied a young woman with severe (less than 1%) congenital factor X deficiency during a 2-year period in order to document the levels of factor X required to provide hemostasis for vaginal bleeding, epistaxis, and hemarthroses, as well as during surgery. Factor X levels of 9 to 17 percent, achieved with fresh-frozen plasma (FFP) were satisfactory for minor bleeding. Hemostasis was achieved during emergency surgery for hemoperitoneum by increasing the factor X level to 35 percent with a Factor IX concentrate, followed with infusions of FFP to maintain levels between 10 and 20 percent for 6 days postoperatively. These data suggest that factor X levels of 10 to 20 percent are sufficient for hemostasis in factor X-deficient patients even in the immediate postoperative period.

Adult↗