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Biomedical subjects

F B Taylor

Publications and source records attributed to F B Taylor.

At least 109 records · Page 6Linked to original sources
PubMed1980

Endogenous anticoagulation during extracorporeal perfusion: generation of a heparinlike inhibitor.

Studies were done to define the coagulation defect that develops in hemodynamically stable anesthetized dogs perfused on our arteriovenous extracorporeal system without added heparin. After 45 min, the dogs developed whole blood clotting times (WBCT) greater than 24 h. There was an associated decrease in ADP-induced platelet aggregation and a drop in factor V, VIII, and X levels of 75.8, 33.5, and 46.8%, respectively. Despite an increase in fibrinogen degradation products, there was no significant change in fibrinogen level or platelet count. An inhibitor of thrombin and factor Xa clotting of plasma appeared that was "heparinlike", because it stimulated the inactivation of factor Xa by antithrombin III (ATIII) but not by O-methyl isoureamodified ATIII. Thrombin inhibition by ATIII was also stimulated. The inhibitor was heat stable, adsorbed by BaSO4, and neutralized by protamine. Infusion of protamine sulfate into two perfused dogs neutralized the inhibitor and brought the WBCT from greater than 24 h to less than control. Six dogs developed inhibitor levels equivalent to 0.98 to 6.15 U/ml heparin. Five eviscerated dogs in which the hepatic artery was ligated developed peak plasma inhibitor levels of 3.2 +/- 1.0 U/ml. Thus, the endogenous heparinlike inhibitor is a major contributor to the anticoagulated state induced with our perfusion system and may have an extrahepatic origin.

Animals↗
PubMed1980

The procoagulant effect of platelets on conversion of prothrombin to thrombin in nonanticoagulated plasma.

The effects of normal platelets and dysfunctional platelets on the activities of prothrombin complex components (fluid-phase factor X, factor V, and prothrombin) and on prothrombin conversion products were studied in nonanticoagulated plasma by both functional and physical methods. Rapid centrifugation of small blood volumes at 24 degrees C yielded PRP and PPP before changes could be detected by functional and physical means. It was shown for the first time in native nonanticoagulated PRP that prothrombin and factor V consumption by functional assays depends on physiologically active platelets, since inhibition by PGE and theophylline or by dibutyryl cyclic AMP and acceleration by ADP was observed. These platelet-dependent phenomena occurred in two stages: (1) a decrease in factor V activity coinciding with platelet clumping and (2) a decrease in prothrombin activity simultaneous with clot appearance. Neither of these stages was clearly separated in recalcified citrated plasma. In studies of patients (Glanzmann's thrombasthenia, Hermansky-Pudlak syndrome, and Gray platelet syndrome) inhibition of the first stage and abnormalities in subsequent clotting events occurred only in Gray platelet syndrome patients, whose platelets carry a defect in alpha-granules. Finally, with [3H]prothrombin and SDS-PAGE, prothrombin conversion was found to be platelet-dependent and to proceed mainly through the factor Xa activation pathway.

Adenosine Diphosphate↗
PubMed1979

Role of platelets in lysis of dilute plasma clots: requirement for metabolically active platelets.

The role of platelets in clot lysis has been investigated functionally with the use of dPRP clots formed at 4 degrees and shifted to 37 degrees. Clots handled in this manner lysed in 6 hr (+/- 1 hr), whereas clots formed at 4 degrees or at 37 degrees and held at those temperatures, or clots formed from dPPP did not lyse in less than 20 hr. dPRP clots having the shorter (6 hr) lysis time released 14C-5-HT at the time of the temperature shift. Preincubation of dPRP with antimycin A and 2-deoxy-D-glucose before addition of thrombin prolonged the clot lysis to 26 hr and inhibited release of 14C-5-HT at the time of the temperature shift. These studies demonstrate that metabolically active platelets are required to mediate the optimal clot lysis seen in the 4 degrees to 37 degrees system and that they continue to function (i.e., take up and release 5-hydroxytryptamine) after they have been incorporated into a clot. Thus the dPRP clot lysis system provides a model by which the timing and sequence of the interaction of metabolically active platelets with the fibrin framework of the formed clot can be studied.

Blood Coagulation↗
PubMed1979

A phenomenologic description of clot lysis in dilute human plasma correlating structure and function of platelets.

Platelets in a dilute platelet-rich plasma clot formed by the addition of thrombin at 4 C do not lose their alpha-granules or develop platelet-fibrin interconnections. These clots do not retract or lyse. If after clot formation for 30 minutes the clots are transferred to 37 C, the alpha-granules then disappear from the platelet, extensive platelet-fibrin interconnections develop, and the clots retract and lyse. When the dilute plasma clots, however, are formed at 37 C, alpha-granules are quickly lost, few platelet-fibrin interconnections develop, and the clots do not retract or lyse. Deoxyglucose and antimycin, when added before thrombin at 4 C, prevent the loss of alpha-granules and development of platelet-fibrin interconnections after transfer of the clot to 37 C. These inhibited platelets did not retract or lyse. From the results reported here we conclude that the development of platelet-fibrin interconnections as well as the retraction and lysis of the clot occur in conjunction with the release of alpha-granules from the platelet. It may be necessary for this release to occur after the fibrin network is completed, since release of the alpha-granules in the 37 C clot before clot formation did not result in formation of many platelet-fibrin interconnections or in clot retraction or lysis.

Blood Coagulation↗
PubMed1979

The dilute whole blood clot lysis assay: a screening method for identifying postoperative patients with a high incidence of deep venous thrombosis.

A dilute whole blood clot lysis assay was used to identify patients with a high incidence of DVT. Of 191 orthopedic and urologic patients who underwent surgery, the over-all incidence of DVT as determined by 125I-fibrinogen leg scan was 35% in the 92 individuals with abnormal assays and 1% in the 99 patients with normal assays. The likelihood that an individual patient might have developed DVT increased progressively with the number of abnormal assays (p less than 0.001). The incidence of DVT increased from 28% in patients who had one abnormal assay, to 35% in patients with two abnormal assays, to 56% in patients with three abnormal assays. These studies establish the clot lysis assay as a simple means to screen for patients with a high incidence of DVT. A normal assay can eliminate patients from consideration for more extensive studies (venography, fibrinogen scan, impedance plethysmography), whereas those patients with one or more abnormal assays should be seriously considered for these additional studies.

Adult↗
PubMed1978

Prolonged shock in the baboon subjected to infusion of E. coli endotoxin.

This study was designed to examine the response of the baboon during a 24-hour period following Escherichia coli endotoxin infusion. Experiments were conducted on young adult baboons, unrestrained and maintained at a light plane of anesthesia induced with pentobarbital sodium. Light and electron microscopic studies on lung, heart, liver, and kidney were conducted; hematologic changes and physiologic responses were measured. The efficacy of heparin to prevent the coagulopathy and increase survivability was assayed. Hepatic sinusoidal fibrin thrombi with underlying hepatocyte cellular damage was seen in the endotoxin-treated group. In contrast, the experimental group receiving heparin showed no sinusoidal fibrin thrombi but demonstrated hepatocellular damage. Liver dysfunction was indicated by elevation of blood levels of enzymes. Glomerular fibrin thrombi were not present. Although heparin prevented the formation of hepatic thrombi in endotoxin-treated baboons, it did not increase survival. Platelet and complement levels decreased in both experimental groups, while wide variations in white blood cell and fibrinogen levels were observed. Polymorphonuclear leukocyte-platelet aggregations previously reported in the pulmonary vasculature during acute shock were not observed in the present study, and their absence may have been related to the longer time of survival.

Animals↗
PubMed1971

The streptokinase-human plasminogen activator complex. Composition and identity of a subcomponent with activator activity.

Reactions between purified plasminogen and streptokinase, labelled with (131)I and (125)I respectively, were investigated by polyacrylamide-gel discontinuous electrophoresis. A molecular complex consisting of both (131)I-labelled plasminogen and (125)I-labelled streptokinase migrated between plasminogen and streptokinase. This complex contained bovine plasminogen activator activity. The relative quantities of (131)I-labelled plasminogen and (125)I-labelled streptokinase in this complex were markedly affected by reaction conditions. A fragment that retained 50% or more of the parent activator activity was released from the complex after exposure to mercaptoethanol. This subcomponent had an estimated molecular weight of 70000, and contained both (131)I-labelled plasminogen and (125)I-labelled streptokinase.

Aminocaproates↗
PubMed1970

Qualitative description of factors involved in the retraction and lysis of dilute whole blood clots and in the aggregation and retraction of platelets.

Dilute whole blood clots were prepared by addition of thrombin to blood diluted 1:10 in phosphate buffer. The pH of this buffer was 7.4 and the ionic strength was 0.084. Though the ionic strength was low, there was no hemolysis of red corpuscles due to the contribution to the osmotic gradient by plasma salts and proteins. In the standard assay the clot was formed by addition of thrombin at 4 degrees C then incubated at 37 degrees C. Retraction and lysis of these clots were inhibited by removal of platelets and by increasing concentrations of purified thrombin. Retraction and lysis were also inhibited by inactivation of any one of the following factors: gammaM globulin, complement components C4 and 3, and (in the case of lysis) plasminogen. Evidence that some of the above serum factors were adsorbed to the platelet membrane was obtained by aggregation of washed platelets by antisera to these factors (i.e. fibrinogen, gammaM, and C4 or C3). These platelets were not aggregated by antisera to other serum proteins (by albumin, transferrin, gammaG globulin). These and other studies suggested that platelets, thrombin, fibrinogen, gammaM globulin (cold agglutinin), complement components, and plasminogen influenced and facilitated retraction and lysis of clots. These studies also suggested that platelets and some of these factors were physically associated. Because of this physical association, and because of the fact that clot retraction is associated with aggregation and retraction of platelets, we extended the above observations to include a study of the effect of these same serum factors on serum-induced aggregation and retraction of washed platelets. (Other terms which have been in use in the past to describe serum-induced platelet aggregation and retraction have included those such as platelet "fusion" and "viscous metamorphosis," neither of which fully described the phenomena.)Platelet aggregation and retraction induced by serum was markedly accelerated by addition of increasing concentrations of thrombin and (or) cold agglutinin. Hirudin and antisera to gammaM globulin inhibited seruminduced aggregation and retraction of platelets. Reconstitution of inactivated serum with purified C4, 3, and 5 and thrombin restored its capacity to induce aggregation and retraction of platelets.Therefore, we postulated that platelet aggregation and retraction were necessary for clot retraction and that platelet aggregation and clot retraction facilitated clot lysis. More specifically we postulated that thrombin, in addition to catalyzing clot formation, also modified the platelet membrane such that gammaM globulin (cold agglutinin) and complement components can act on the platelet membrane leading to (a) aggregation and retraction of the platelets, (b) retraction of the clot, and (c) to the activation of plasminogen either on the surface of the platelet by C8i and (or) by release of platelet activators of plasminogen.

Antibodies↗