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PubMed1999

Antiphospholipid-thrombosis syndromes.

Antiphospholipid antibodies are strongly associated with thrombosis and appear to be the most common of the acquired blood protein defects causing thrombosis. Based upon our experience, approximately 25% of patients with unexplained venous thrombosis, approximately 60% of patients with cerebrovascular thrombosis, approximately 37% of patients with transient ischemic attacks, approximately 18% with premature coronary artery thrombosis and approximately 60% of patients with recurrent fetal loss (recurrent miscarriage syndrome) harbor antiphospholipid antibodies. Although the precise mechanism(s) whereby antiphospholipid antibodies alter hemostasis to induce a hypercoagulable state remain unclear, several theories have been advanced. Since the aPTT is unreliable in patients with lupus anticoagulant and is not usually prolonged in patients with anticardiolipin antibodies, definitive tests, ELISA for IgG, IgA and IgM anticardiolipin antibodies and the dilute Russel's viper venom time (followed by cephalin correction for confirmation) for lupus anticoagulant should be immediately ordered when suspecting the antiphospholipid syndrome in individuals with otherwise unexplained thrombotic or thromboembolic events or recurrent fetal loss. However, if one strongly suspects antiphospholipid thrombosis syndrome clinically and assays for lupus anticoagulants and anticardiolipin antibodies are negative, specific assays for all three idiotypes of phosphatidylserine, phosphatidylethanolamine, phosphatidylcholine, phosphatidylinositol and phosphatidylglycerol are available and should be considered. These may clearly be indicated for difficult diagnostic cases of fetal wastage syndrome, and cerebrovascular events, but their significance in other types of thrombosis, particularly venous, remains unclear at present. Since about 65% of patients with antiphospholipid antibodies will fail warfarin therapy (rethrombose), it is important to define this common defect and institute appropriate antithrombotic therapy for appropriate time periods.

Antiphospholipid Syndrome↗

PubMed1976

Factor X Friuli coagulation disorder. Report of a newly recognized patient and some considerations on the frequency of the disease in the Friuli area.

A newly recognized patient with the factor X Friuli coagulation disorder is presented. The propositus is a 10-year-old boy who presented excessive bleeding after a tooth extraction. This is the 11th patient with this peculiar coagulation disorder discovered in Friuli and the 12th so far described. His parents are consanguineous and heterozygotes together with other family members. The main laboratory features, typical of the disease were prolonged prothrombin time, a prolonged partial thromboplastin time, and a normal Stypven-cephalin clotting time. The incidence of the homozygotes in the Friuli area appear to be 0.000005 (11 cases in a population of 2,000,000). The probable frequency of the abnormal f gene is 0.0033, whereas that of the normal gene F is 0.9967. The theoretical frequency of the heterozygote, Ff condition is 0.007, namely 7 heterozygotes every 1,000 persons. However, only about 70 ascertained heterozygotes have been discovered so far.

Adolescent↗

PubMed1982

Factor VII Padua 1. Another case.

A patient with a peculiar factor VII is described. The propositus is a 70-year-old man without any bleeding tendency. The coagulation pattern is characterized by a prolonged rabbit brain prothrombin time, a normal Stypven cephalin clotting time and a normal thrombotest. Factor VII activity is low when assayed using rabbit brain the thromboplastin but is normal when assayed using ox brain thromboplastin. The neutralization test performed with an antifactor VII antiserum revealed a normal factor VII antigen level. A pedigree study has not been possible, the patient having no living relatives. No differences were observed between the biological results of our patient and those described by Girolami as factor VII + Padua.

Aged↗

PubMed1977

The effect of different regimens of oestrogens on the clotting and fibrinolytic system of the post-menopausal woman.

The effects of six different regimens of hormone replacement therapy on coagulation, fibrinolysis and platelet aggregation were sudied in 33 symptomatic, post-menopausal women. Studies were performed before and after 3 months of therapy in the six treatment groups, Premarin, Progynova, Harmogen, Serial 28, ethynodiol diacetate and a testosterone and oestradiol implant. No changes in any parameter were detected following administration of Premarin, Progynova or an implant of testosterone and oestradiol. Serial 28 produced a significant increase in plasminogen concentration and increased the extent of platelet aggregation in 0.5 micron adrenalin solution. Harmogen produced an increase in the extent of platelet aggregation in 1.0 micron adrenalin solution, but a decrease in the rate of platelet aggregation in 1.0 micron solution. Ethynodiol diacetate caused a significant decrease in the kaolin-cephalin clotting time but decreased the extent of platelet aggregation in 0.5 and 1.0 micron solutions of adrenalin. FDPs developed following therapy in 9 of the 33 patients. These were evenly distributed between the groups. No patients had any change in anti-Xa concentration, platelet count or platelet aggregation in thrombin.

Adult↗

PubMed1993

Cerebral blood flow alterations in a rat model of cerebral sinus thrombosis.

BACKGROUND AND PURPOSE: Outcome from sinus vein thrombosis is very variable, with symptoms from headache to coma. Experimental findings suggest that an involvement of cortical veins is necessary to affect the cerebral microcirculation. Laser Doppler flowmetry was used to investigate the regional and temporal changes in local cortical blood flow after experimental occlusion and thrombosis of the superior sagittal sinus and tributary cortical veins in rats. METHODS: Thrombosis was induced by slow injection of kaolin-cephalin suspension after frontal and caudal ligation of the sagittal sinus in rats. Local cerebral blood flow was measured by laser Doppler flowmetry and correlated with parenchymal damage found 24 hours after induction of thrombosis. RESULTS: Local cerebral blood flow 1 hour after sinus occlusion and induction of thrombosis had decreased to 60.92 +/- 29.05% (p < 0.01); however, there was a large variability among individual animals. Only five of 12 rats showed histological damage and intracerebral hemorrhages 24 hours after induction of thrombosis. A subgroup analysis revealed that parenchymal damage occurred in concurrence with reduced blood flow values after sinus ligation and injection of the thrombogenic material. Sinus thrombosis alone, without alteration of blood flow, did not cause tissue necrosis. CONCLUSIONS: The data support the contention that sinus vein thrombosis evolves gradually, with major symptoms occurring only if the thrombus expands from the sinus into bridging and cortical veins. Collateral venous outflow pathways are thereby occluded, and local blood flow may become reduced to and below the ischemic threshold.

Animals↗

PubMed1996

Alterations of regional cerebral blood flow and oxygen saturation in a rat sinus-vein thrombosis model.

BACKGROUND AND PURPOSE: The pathophysiology of sinus-vein thrombosis (SVT) in patients and experimental animals is still poorly understood. This study was designed to examine and further elucidate the pathophysiological sequence of events, especially the relationship between local and regional blood flow and hemoglobin oxygen saturation (HbSO2) detected at identical locations. The use of both parameters as outcome indicators should be compared. METHODS: SVT was induced by ligation of the superior sagittal sinus (SSS) and slow injection of kaolin-cephalin suspension into the SSS in rats. Regional cerebral blood flow (rCBF) was assessed by laser-Doppler flowmetry together with regional HbSO2, which was measured by a microspectrophotometric technique at 48 identical locations for 90 minutes after SVT using a scanning technique. Fluorescence angiography was performed before and 30 and 90 minutes after SVT induction. After 48 hours the animals were killed for histology. RESULTS: The fluorescence angiographic findings could divide animals into three groups: (1) group A, with a solitary SSS thrombus (n=8); (2) group B, with a thrombosis of SSS and cortical veins (n=10); (3) group C, animals that had undergone sham operation (n=5). Decreases of rCBF and HbSO2 and brain damage were seen in group B but not in group A. The reduction of local HbSO2 preceded the flow decrease after sagittal sinus ligation but before thrombosis. Blood pressure in group A was found to be significantly higher after SVT than in groups B and C. CONCLUSIONS: The brain with acute extension of thrombus from the SSS into cortical veins experiences a critically reduced supply of blood and oxygen. CBF, local HbSO2, and repeated angiography can be helpful monitors for the early detection of critical conditions after SVT. Local HbSO2 has a greater sensitivity to predict outcome than lCBF. Moreover, therapies directed to improve perfusion pressure or reduce vascular resistance may open further therapeutic windows during SVT progression.

Animals↗

PubMed1979

Human plasma protein C: isolation, characterization, and mechanism of activation by alpha-thrombin.

Protein C is a vitamin K-dependent protein, which exists in bovine plasma as a precursor of a serine protease. In this study, protein C was isolated to homogeneity from human plasma by barium citrate adsorption and elution, ammonium sulfate fractionation, DEAE-Sephadex chromatography, dextran sulfate agarose chromatography, and preparative polyacrylamide gel electrophoresis. Human protein C (M(r) = 62,000) contains 23% carbohydrate and is composed of a light chain (M(r) = 21,000) and a heavy chain (M(r) = 41,000) held together by a disulfide bond(s). The light chain has an amino-terminal sequence of Ala-Asn-Ser-Phe-Leu- and the heavy chain has an aminoterminal sequence of Asp-Pro-Glu-Asp-Gln. The residues that are identical to bovine protein C are underlined. Incubation of human protein C with human alpha-thrombin at an enzyme to substrate weight ratio of 1:50 resulted in the formation of activated protein C, an enzyme with serine amidase activity. In the activation reaction, the apparent molecular weight of the heavy chain decreased from 41,000 to 40,000 as determined by gel electrophoresis in the presence of sodium dodecyl sulfate. No apparent change in the molecular weight of the light chain was observed in the activation process. The heavy chain of human activated protein C also contains the active-site serine residue as evidenced by its ability to react with radiolabeled diisopropyl fluorophosphate. Human activated protein C markedly prolongs the kaolin-cephalin clotting time of human plasma, but not that of bovine plasma. The amidolytic and anticoagulant activities of human activated protein C were completely obviated by prior incubation of the enzyme with diisopropyl fluorophosphate. These results indicate that human protein C, like its bovine counterpart, exists in plasma as a zymogen and is converted to a serine protease by limited proteolysis with attendant anticoagulant activity.

Blood Coagulation↗

PubMed1995

Measurement of superoxide dismutase-like activity of natural antioxidants.

The superoxide dismutase (SOD)-like activity of natural antioxidants was evaluated by measuring the inhibition of pyrogallol autoxidation that is catalyzed by the superoxide radical. Among 22 water-soluble antioxidants tested, L-ascrobic acid, L-ascorbic acid 6-palmitate, glutathione (reduced form), (+)-catechin, and (-)-epicatechin showed effective SOD-like activity. To analyze lipophilic antioxidants, an optically clear organic system composed of diethyl ether, surfactant (dioctyl sulfosuccinate, AOT) and water, called reverse micelles, was developed. The optimum concentrations of AOT, water and pyrogallol for determining SOD-like activity were found to be 50 mM, 1.3 M, and 40 mM, respectively. After proving that pyrogallol autoxidation was mediated by the superoxide anion in that system, the SOD-like activity of 24 lipophilic antioxidants was measured. Cinnamon oil, gamma-oryzanol, extract of rosemary leaf, L-alpha-lecithin, and L-alpha-cephalin exhibited activity, although the activity of some antioxidants could not be measured because of the intense color or low solubility.

Antioxidants↗

PubMed1988

Effect of tamoxifen on oestrogen binding, lipid and lipoprotein concentrations and blood clotting parameters in premenopausal women with breast pain.

As part of a controlled trial of the use of tamoxifen for the treatment of mastalgia, some of the metabolic and haematological effects of this agent were measured. A panel of haemostatic variables including prothrombin time, kaolin cephalin clotting time, fibrinogen, euglobulin lysis time, factor VII, factor VIII, protein C and anti-thrombin III were determined. In addition, levels of sex hormone-binding globulin and both total and free oestradiol were estimated. No alteration in clotting function was found during the administration of tamoxifen, although hepatic function did alter during this period with an increase in concentration of sex hormone-binding globulin. There was a significant increase in total oestradiol and free oestradiol although the percentage of biologically available free oestradiol fell slightly during the course of tamoxifen treatment. There was a slight reduction in low-density lipoprotein cholesterol with an increase in HDL2, a subclass of high-density lipoprotein (HDL) cholesterol, consistent with an oestrogen-agonist effect. These data suggest that tamoxifen administration does not adversely influence haemostatic mechanisms or lipoprotein metabolism in the short term.

Adult↗

PubMed1975

Studies in cholestasis of pregnancy. III. Fatty acid composition of serum phosphoglycerides.

The influence of cholestasis of pregnancy (CP) on liver lipid synthesis as reflected by the composition of serum phosphoglycerides was studied in 28 pregnant women in the last trimester by means of gas-liquid-chromatography (GLC). All patients complained of pruritus and had immunologically detectable lipoprotein-X (LP-X) in serum. Twenty women with uncomplicated pregnancies served as a control series. In lecithin, low palmitic acid (16:0) and high oleic acid (18:1 (n-9)) were found which appear to be characteristic for CP. The increased oleic acid suggests an enhanced liver lecithin synthesis through the cytidine-diphosphate diglyceride pathway. Measurement of the concentrations of lecithin from the gas-liquid-chromatograms was made possible by the use of an internal standard fatty acid added, which gave a linear relation to direct determination of lecithin. For further studies of influences of cholestasis of pregnancy on the relative fatty acid composition, lecithin was chosen because differences between lecithin (PC) and phosphoglycerides (GPL) were found, evidently due to mutual variations among the three components in GPL (lecithin, cephalin and lysolecithin).

Cholestasis↗

PubMed1977

Studies in cholestasis of pregnancy. VI. Fatty acid composition of glycero-phospholipids before and after delivery.

Eight pregnant women, complaining of generalized pruritus with lipoprotein-X (LP-X) in their serum and diagnosed as cases of cholestasis of pregnancy (CP)--were studied during pregnancy and after delivery. Ten women with uncomplicated normal pregnancy served as controls. LP-X, liver function tests and relative fatty acid composition of serum lecithin (determined by gas-liquid chromatography, GLC) were followed. The fatty acid composition in liver and serum lecithin is determined by the synthesis pathways of lecithin in the liver. The faster and quantitatively dominating cytidine-diphosphate diglyceride pathway, pathway I, causes the appearance of lecithin with palmitic acid (16:0) in 1-position and oleic (18:1) or linoleic (18:2) acid in 2-position, while pathway II, with methylation of phosphatidyl-ethanolamine (cephalin) preferentially cases the appearance of lecithin with stearic acid (18:0) in 1-position and arachidonic acid (20:4) in 2-position. Pathway I is enchanced by oestrogenic and pathway II by cholestatic influence. During pregnancy women with CP were characterized in their serum lecithin fatty acid composition by a high palmitic (16:0) and a high oleic (18:1) acid content, in agreement with earlier studies. After delivery, in women with prior CP a decrease in palmitic (16:0) and linoleic (18:2) acids and an increase in stearic (18:0) acid, was interpreted as decreased influence on the major lecithin synthesis pathway I and an enhancement of pathway II. In addition, after delivery in the lactating mother, serum lecithin fatty acid composition data revealed an essential fatty acid (EFA) "consumption." It was earlier shown, that women with previous CP (when studied 8--21 months after delivery) had as judged from their serum lecithin fatty acid composition, a "basic metabolic defect," expressing presumably as estrogen enhanced pathway II of liver lecithin synthesis. In the present study, soon after delivery (on day 4--8) women with prior CP showed, however, less pathway II influence than women with a prior normal pregnancy. This was interpreted as a presistence of the cholestatic influence on liver lecithin synthesis pathways at this short time after delivery. Serum lecithin fatty acid composition appears to be a sensitive variable for the evaluation of metabolic influences in the liver.

Adult↗

PubMed1990

Differences in lipoprotein composition between heads and tails of human sperm: an infrared spectroscopy study.

Human spermatozoa and their fractions (heads and tails) have been studied by infrared spectroscopy. Protein conformation in isolated human spermatozoa heads, although predominantly of the alpha helix or random coil type, has a significant proportion of antiparallel B structure. Spectra of isolated spermatozoa tails show that proteins exist in this fraction preponderantly in pleated-sheet conformation (parallel and antiparallel). The quantity and type of lipids seem to be drastically different between heads and tails of spermatozoa. Head lipids are scarce and difficult to extract, and they are apparently tightly bound to proteins, highly unsaturated, and rich in free hydroxyl and carboxyl groups. Tail lipids are more abundant and more easily extractable. Head phospholipids are probably phosphatidylcholine, cephalins, and inositols, and tail phospholipids are preponderantly plasmalogen-type lecithins and sphingomyelins. The presence of specific infrared bands points to the existence in tails of important amounts of sulfur compounds, probably sulfolipids or sulfoglycolipids.

Humans↗

PubMed1977

Effects of ascorbic acid and vitamin E on serum lipids of cockerels fed Wesson oil-cholesterol diets.

The major lipid changes caused by adding 5% Wesson Oil and 1% cholesterol to cockerel diets were large increases in serum cholesterol, cholesteryl esters, and triglycerides. Lecithin and cephalin were not affected. Ascorbic acid significantly increased serum triglycerides; vitamin E significantly lowered serum cholesterol. Percentages of the saturated acids (palmitic, stearic, and arachidonic) of cockerels on the Wesson Oil-cholesterol diet decreased significantly; unsaturated linolenic and linolenic acids increased, and oleic acid remained the same. Dietary ascorbic acid seemed not to affect fatty acid distribution significantly, but when vitamin E was added to the diet, the stearic acid percentage rose and oleic acid percentage was lower. Acrylamide-gel electrophoresis showed that changes the vitamin E caused in the lipid and protein constituents of cockerel serum differed from changes the Wesson Oil-cholesterol diet caused.

Animals↗

PubMed1976

Effect of insulin on serum lipids in juvenile diabetes.

In diabetic children, the effect on serum lipids of insulin by itself and combined with glucose of with Aminosol + glucose has been studied. The level of serum free fatty acids decreased significantly in every case. The cephalin level decreased under the effect of insulin and insulin + Aminosol, whereas it rose after insulin and glucose infusion. The triglyceride level remained unchanged when insulin was applied by itself, and decreased significantly under the effect of insulin + Aminosol, while it showed a rising tendency after insulin + glucose infusion.

Adolescent↗

PubMed2000

[Effect of composition of reagents for activated partial thromboplastin time on their sensitivity during analysis of blood coagulation factors].

Brain cephaline-based reagents for evaluating activated partial thromboplastin time (APTT) and soybean phosphatides with ellagic acid complex activator with intermediate metal ions have been studied. The sensitivity of these reagents to internal clotting factors (VIII and IX) and heparin is determined by phospholipid nature and type of metal. The results help obtain highly active and sensitive APTT reagents.

Factor IX↗

PubMed1975

One-stage assay of heparin.

A simple and rapid one-stage plasma heparin assay based on the heparin-dependent neutralization of activated factor X (Xa) is described. Factor Xa is prepared in a concentration adjusted to produce a clotting time of 18 to 20 seconds when heparin-free plasma is tested in the system. The assay incubation mixture contains "standard human plasma", the heparinized test plasma, cephalin, and factor Xa. Clotting times are measured automatically after incugation and calcium addition. A linear relationship was found between the log of the clotting time and the heparin concentration for the standard curve from which the heparin level is determined. The lower limit of sensitivity is about 0.05 unit heparin per milliliter. Dilution of test plasma is required to bring the heparin level to between 0.05 and 0.2 unit per milliliter. The standard curve is reproducible with a coefficient of variation of 2 to 4 per cent. Ten different, nonheparinized samples had clotting times of 18.9 plus or minus 1.0 (plus or minus 2 S.D.) seconds. Theoretically calculated and experimentally determined heparin levels after pulse injection of heparin agreed well in 5 volunteer subjects with r values between 0.93 and 0.99. This assay is not affected by normal variation in the plasma levels of fibrinogen, prothrombin, and factor V or by the plasma defects induced by coumadin.

Blood Coagulation↗

PubMed1975

Blood coagulation studies in children with surface hemangiomas.

Thirty patients with surface hemangiomas were investigated for any latent coagulopathy. Whole blood clotting time, kaolin cephalin clotting time, prothrombin time, thrombin time and platelet counts did not differ significantly from the control group values. The values of plasma fibrinogen, euglobulin lysis time and serum levels of fibrinogen degradation products remained within the normal ranges but their mean values were significantly different from those of healthy children. The findings may be attributed to a chronic incipient type of "consumption coagulopathy" occurring locally in the hemangiomas.

Adolescent↗

PubMedDate not supplied

[Sural nerve phospholipids in some genetically determined nervous system diseases].

Phospholipid fraction pattern was determined in sural nerve in cases of suspected storage diseases. The material was obtained by means fo biopsy from 22 patients. In some patients features of polyneuropathy were found. Normal values of phospholipids were determined in 22 dying patients who had to neurological diseases. The most frequently observed change concerning the biochemical composition of the sural nerve in this material was a fall in the total amount of phosphatidyl ethanolamine (cephalin) and appearance of lysolecithins which are normally absent. In attempted correlation of histological and biochemical findings in the sural nerve with clinical signs of polyneuropathy it was observed that biochemical changes were present in cases without clinical evidence of polyneuropathy. Biochemical as well as histological investigations of sural nerve may help in intravital diagnosis of diseases belonging to the group of thesauroses.

Adolescent↗