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PubMed1983

Human factor IX inhibitors: immunochemical characteristics and treatment with activated concentrate.

Plasma was obtained from two patients with severe factor IX deficiency who had developed specific inhibitors of factor IX. Immunochemical characterization of the inhibitors by coagulation inhibitor neutralization assays and by immunoelectrophoretic methods demonstrated that both were IgG antibodies. One of the antibodies appeared to be monoclonal in origin with IgG subclass 4 heavy chains and lambda light chains. The other appeared to be oligoclonal and contained IgG subclass 1 and subclass 4 heavy chains and kappa and lambda light chains. One of the patients was treated with conventional, non-activated factor IX concentrate and with activated factor IX concentrate (Feiba) for repeated bleeding episodes. Administration of Feiba resulted in a progressive shortening of the kaolin cephalin clotting time and was followed by a good clinical response. Infusion of non-activated factor IX concentrate failed to induce clinical resolution of haemarthroses and had minimal effect on laboratory tests. The presence of circulating immune complexes could not be demonstrated in this patient.

Adult↗

PubMed1988

Lupus anticoagulant: a clinical and laboratory study of 100 cases.

The clinical and laboratory features of 100 patients with lupus anticoagulant (LA) are reviewed. Subjects were divided into three groups according to their age (1-5, 15-35, 45-89 years). Female prevalence was observed in each group and overall F/M ratio was 3/1. An underlying autoimmune disease (principally lupus erythematosus) was found in 47 cases (10% of the children, 80% of the 15-35-year-old patients and 37% of the elderly patients). Biological criteria for the LA diagnosis were prolonged activated partial thromboplastin time and diluted thromboplastin time (1.3 x control), not corrected after addition of control to patient's plasma. Thromboplastin time was normal in 77 patients. Other types of coagulation inhibitors were eliminated by specific factor assays (with a 10-fold increase of cephalin concentration when necessary). Twenty-three thrombotic episodes were observed. No significant difference was found in the incidence of thrombosis between the autoimmune and non-autoimmune disease group, but the age when first thrombosis occurred was clearly lower in the former. Fourteen obstetrical accidents were noted in eight women but 13 pregnancies terminated without accident. Four patients experienced haemorrhagic complications; they all presented with a severe thrombocytopenia associated with the LA. In our experience, LA is a frequent coagulation abnormality, associated in about half of the cases with a clearly defined autoimmune disease. Clinical presentation appears as notably different according to the patient's age; it is particularly noteworthy that in nine out of 10 children, LA disappeared spontaneously within 6 months.

Adolescent↗

PubMed1976

The effect of intravenous injection of purified human tissue thromboplastin in rats.

As a background for the development and testing of phospholipase C in the therapy of post-traumatic and post-surgical intravascular coagulation, highly purified tissue thromboplastin was injected i.v. into rats. The levels of factor V, VII, VIII and blood platelets and the activity of the intrinsic coagulation pathway in general (the cephalin test) were followed. Histological examination of pulmonary, kidney and liver tissue was carried. The dose-response was highly dependent on the injection rate. A marked activation of factor VII and a fall in the activities of factors V and VIII as well as in thrombocyte counts were observed. Very few or no thrombi were seen beyond the pulmonary circulation. The main changes (fibrin-containing thrombi and platelet aggregates) were observed in the lungs during the first 15 min after injection. Atter 15 min virtually no thrombi or platelet aggregates could be detected. The effect of tissue thromboplastin was counteracted by large doses of antithrombin III.

Animals↗

PubMed1983

Hereditary factor VII deficiency in a Chinese family.

Hereditary deficiency of factor VII is demonstrated in a Chinese family. The proposita was a 32-year-old female with bleeding diathesis consisting of spontaneous ecchymosis, menorrhagia and recurrent haemarthrosis. The prothrombin time was prolonged and the prothrombin and proconvertin test was 10% of normal. The activated partial thromboplastin time and the Stypven-cephalin clotting time were normal. The prolonged prothrombin time could be corrected by the addition of normal serum, but not by adsorbed normal or coumadin plasma. The factor VII level was 3.6% of normal. One of her brothers had bleeding symptoms and died at age 25, suggesting that factor VII deficiency might have been present. 13 of her family members had partial deficiency of factor VII with plasma levels ranging from 24 to 50%. These results suggest an autosomal recessive inheritance with a homozygous state occurring in the proposita and possibly in her brother, and a heterozygous state occurring in 13 of her family members. Our study marks an extensive survey of factor VII deficiency in an Oriental family.

Adult↗

PubMed1986

Prothrombin Segovia: a new congenital abnormality of prothrombin.

A family with a new congenital dysprothrombinemia is presented. The propositus is a 21-yr-old man who presented simultaneously with hemartrosis of the left knee and an extensive hematoma following a minor trauma. Prothrombin time and activated partial thromboplastin time were prolonged. Prothrombin activity was very low when measured by biological assay using physiological activators (7% by one-stage method and 20% by two-stage method) or a Russel's viper venom-cephalin mixture (23%), Notechis scutatus scutatus venom (15%) and Echis carinatus venom (17%); in contrast, the level was found to be borderline to normal using Taipan viper venom (64%) and normal by both staphylocoagulase and immunologic methods. Family studies revealed consanguinity between the propositus' mother and father and both presented a 50% reduced prothrombin level when physiological activators or Echis carinatus viper venom were used. A line of identity between normal and abnormal prothrombin was observed on immunodiffusion. The migration of the abnormal prothrombin was less anodic and was not changed by the addition of calcium. The patient's serum showed 3 bands in the bidimensional immunoelectrophoresis system, whereas normal serum showed only 2 bands. The term prothrombin Segovia is proposed to define this new prothrombin abnormality.

Adult↗

PubMed1963

LIPID COMPOSITION AND SYNTHESIS IN THE PLEUROPNEUMONIA-LIKE ORGANISM MYCOPLASMA GALLISEPTICUM.

Tourtellotte, Mark E. (University of Connecticut, Storrs), Robert G. Jensen, George W. Gander, and Harold J. Morowitz. Lipid composition and synthesis in the pleuropneumonia-like organism Mycoplasma gallisepticum. J. Bacteriol. 86:370-379. 1963.-A simple method of extracting lipids from cells of Mycoplasma gallisepticum by use of silicic acid columns is described. Proteolipids (peptides) extracted with chloroform-methanol (2:1) by other methods were not extracted with the lipid by this method, nor were proteins and nucleic acids. Fractionation of lipids of M. gallisepticum demonstrated the presence of saturated hydrocarbons, free fatty acids, cholesterol, cholesterol esters, di- and triglycerides, phosphatidic acids, cephalins, inositides, phosphatidyl choline, and sphingomyelin. The fatty acid composition of the various fractions was also determined. The positive identification of cholesterol and cholesterol esters in this organism by chromatography, melting point, and infrared spectroscopy confirms reports by others that cholesterol is present in the pleuropneumonia group of microorganisms. The incorporation of P(32) orthophosphate into four phospholipid fractions, of oleic acid-1-C(14) into neutral and phospholipids, and cholesterol-4-C(14) into cholesterol esters clearly demonstrated the ability of M. gallisepticum to synthesize these lipids from simpler compounds. Between 70 and 80% of the lipid of this organism was found in the membrane.

Biological Products↗

PubMed1966

Variation in Lipid Content of Strains of Histoplasma capsulatum Exhibiting Different Virulence Properties for Mice.

Nielsen, H. S., Jr. (Duke University Medical Center, Durham, N.C.). Variation in lipid content of strains of Histoplasma capsulatum exhibiting different virulence properties for mice. J. Bacteriol. 91:273-277. 1966.-Lipid content and virulence were studied in six isolates of Histoplasma capsulatum in an attempt to determine whether or not the two factors could be correlated in this fungus. Virulence was evaluated by injecting dba line 1 male mice intracerebrally with 2.8 x 10(4) infective yeast-phase units and recording organ involvement and spontaneous deaths occurring in a 20-day period. Yeast cells were extracted with mixtures of ethyl alcohol-diethyl ether (3:1, v/v), and the total extractable lipid, as determined by solubility in petroleum ether, was separated into acetone-soluble and phospholipid fractions by acetone precipitation. Neutral lipids were measured directly by weighing, whereas total phospholipids were calculated after the colorimetric determination of phosphorus. The mixed phosphatides of two isolates, differing in virulence, were separated into five fractions by use of a column of silicic acid and Hyflo Super-Cel. In the six isolates studied, neither total extractable lipid, acetone-soluble lipid, nor phospholipid showed a quantitative correlation with virulence. Phosphatidylserine, cephalin, phosphoinositides, and sphingolipids were present in essentially the same amounts in the two strains investigated; however, a lecithin fraction was absent in the less virulent form. These data suggest that the quantity of phosphatidylcholine demonstrated for a given isolate of H. capsulatum may provide some insight as to its virulence, although such a relationship is lacking for total lipid, the acetone-soluble fraction, and the combined phospholipids of yeast-phase growth.

Journal Article↗

PubMed1989

Ehlers-Danlos syndrome, clotting disorders and muscular dystrophy.

Ehlers-Danlos syndrome includes 11 distinct entities. The diversity of this collagen dysplasia and its combination with other abnormalities make it difficult to understand physiopathologically. A case of Ehlers-Danlos syndrome is reported, which is novel owing to its combination with clotting abnormalities and especially with muscular dystrophy. To our knowledge this has not previously been reported. The patient was a young man aged 16 years who presented with Ehlers-Danlos syndrome satisfying Perelman's diagnostic criteria. His father and two brothers had comparable clinical symptoms, but his mother and sister were healthy. The four male subjects had an increased cephalin-kaolin time, reduced levels of factor VIII and Willebrand's factor (but without haemophilia A or Willebrand's disease), and, especially, an abnormal platelet ATP secretion. The proband alone had muscular disease with bilateral quadriceps fatigability and amyotrophy. The muscle enzyme levels were greatly increased, the electromyographic trace was myogenic, and the biopsy showed severe muscular dystrophy. This new observation poses the problem of the relation between clotting abnormalities and collagen abnormalities in the Ehlers-Danlos syndrome. It is difficult to classify this case within any of the 11 known types because of its muscular manifestations. It may perhaps be a fortuitous combination or an extension of the nosological framework of this syndrome.

Adenosine Triphosphate↗

PubMed1989

Antibody to phosphatidylethanolamine in a patient with lupus anticoagulant and thrombosis.

Most patients with lupus anticoagulant (LA) activity have coincident antibodies to a group of negatively charged phospholipids, and its is suggested that LA and anticardiolipin tests detect antibodies with overlapping specificities. Some discordance between the two assays has been described, however. One patient presenting with severe thrombotic disease (recurrent deep vein thrombosis, pulmonary embolism, inferior venocaval obstruction, myocardial infarction, and digital gangrene) showed strong LA activity in February 1987. An enzyme linked immunosorbent assay (ELISA) showed no binding to the negatively charged phospholipids cardiolipin, phosphatidylserine, and phosphatidic acid, but binding to zwitterionic phosphatidylethanolamine (PE) was demonstrated. Inhibition studies and affinity purification confirmed this finding. Interestingly, the serum did not bind to the kaolin cephalin clotting time reagent when used as antigen in an ELISA. The pathogenic significance of anti-PE antibodies and their relation to LA remains to be clarified. Further studies of the occurrence of anti-PE antibodies in patients with LA activity who have negative anticardiolipin tests are suggested.

Autoantibodies↗

PubMed1991

Lupus anticoagulant: clinical significance in anticardiolipin positive patients with systemic lupus erythematosus.

The significance of anticardiolipin antibodies and the lupus anticoagulant was studied in 58 consecutive patients with systemic lupus erythematosus. On 85 occasions serum IgG and IgM anticardiolipin antibodies were measured by an enzyme linked immunosorbent assay (ELISA), and simultaneous plasma samples tested for lupus anticoagulant activity. The most significant association with clinical events (previous thrombosis or thrombocytopenia occurring in 11/58 patients) was with prolonged tissue thromboplastin inhibition time (TTIT) followed by prolonged kaolin cephalin clotting time (KCCT) then raised IgG anticardiolipin antibody concentrations and dilute Russell's viper venom time. Although IgG anticardiolipin antibodies or KCCT were the most sensitive tests in identifying this group, the TTIT was the most specific (98%). Nine patients were IgG anticardiolipin antibody positive and lupus anticoagulant negative, of whom one had thrombocytopenia but none had thrombosis. The presence of a lupus anticoagulant in anticardiolipin antibody positive patients increases specificity for certain adverse clinical events.

Antibodies↗

PubMed1986

Guidelines to control heparin treatment.

With new guidelines for the control of heparin infusion rates the proportion of kaolin cephalin clotting time ratios was significantly improved compared with ratios achieved without their use. Further improvement might result from careful preparation and delivery of the infusion.

Heparin↗

PubMed1987

Subcutaneous calcium heparin versus intravenous sodium heparin in treatment of established acute deep vein thrombosis of the legs: a multicentre prospective randomised trial.

One hundred patients with phlebographically proved acute deep vein thrombosis of the legs were prospectively randomised into two treatment groups to compare the safety and efficacy of subcutaneous calcium heparin versus intravenous sodium heparin administered by constant infusion pump. The dose of heparin was determined by daily measurement of the kaolin cephalin clotting time. Treatment was maintained for up to 14 days, after which phlebography was repeated. Of 49 patients who received subcutaneous calcium heparin, two showed an increase in thrombus size, while eight showed complete lysis. In the 47 patients who received intravenous sodium heparin thrombus increased in size in 13 while only one showed evidence of complete lysis. These differences were significant. There were no significant differences between the two groups in the incidence of serious complications, although almost half of those receiving intravenous heparin had some minor problem with the constant infusion pump and just over half of those receiving subcutaneous heparin had some bruising at the injection site. This study showed that subcutaneous calcium heparin was more effective in helping lyse existing thrombus and preventing its propagation than intravenous sodium heparin.

Clinical Trials as Topic↗

PubMed1962

Blood clotting factors in cerebrospinal fluid.

The activity of blood clotting factors has been investigated in cerebrospinal fluid. No cephalin-like activity was found in cerebrospinal fluid but prothrombin activity averaged about 0.5% of normal plasma activity. The activity of factor VII was negligible in almost all cases. The activity of antihaemophilic factors showed great variation but in the majority of cases it did not exceed 1% of normal plasma activity. High activity for factor V was found in almost all samples of cerebrospinal fluid.

Blood Coagulation↗

PubMed1980

A new cryopathic syndrome.

One case of a syndrome simulating a systemic disease is reported. An HLA-B, patient presented with apparent toxoplasmosis, retinal vein occlusion, autoantibodies against cephalin, contact factors and lipoproteins, immune complexes, rheumatoid factor, and cryoprecipitate. A representation of the immunological mechanisms involved is proposed.

Antigen-Antibody Complex↗

PubMed1992

Acquired factor XI inhibitor in chronic lymphocytic leukaemia.

A 71 year old man with chronic lymphocytic leukaemia (CLL) experienced excessive bleeding following transurethral resection of the prostate. Investigations showed a prolonged kaolin cephalin clotting time (KCCT) with low concentrations of factor XI. The prolonged KCCT was largely corrected by mixing with normal plasma but this correction was lost on incubation, confirming the presence of an inhibitor. He was treated with pulsed methylprednisolone and chlorambucil which resulted in the resolution of the bleeding problem and the loss of detectable circulating inhibitor.

Aged↗

PubMed1997

Potentially prothrombotic abnormalities of coagulation in benign intracranial hypertension.

OBJECTIVE: Benign intracranial hypertension (BIH) may be caused by intracranial venous sinus thrombosis. Cerebral angiograms may, however, be normal in patients with BIH that are associated with conditions with an increased risk of venous thrombosis. This raises the possibility that unrecognised non-occlusive venous thrombus might impede CSF drainage. This study therefore examined the strength of the association between risk factors for thrombosis and BIH. METHODS: The incidence of prothrombotic abnormalities among a mixed prospectively and retrospectively investigated cohort of 38 patients with BIH, was compared with healthy obese subjects, and patients with other neurological diseases. Prothrombotic abnormalities investigated included anticardiolipin antibodies, lupus anticoagulant, antithrombin III, proteins C and S, plasma fibrinogen, kaolin cephalin clotting time, prothrombin time, and full blood counts. RESULTS: Evidence for the presence of an antiphospholipid antibody was found in 32% of cases. Cases of familial deficiency of antithrombin III, thrombocytosis, and polycythaemia were also noted. Additionally, an increased concentration of plasma fibrinogen was found in 26%. A coagulation abnormality was more often detectable in those subjects with normal or low body mass index and in those tested within six months of onset. CONCLUSION: There is a thrombotic pathogenesis in some cases of BIH.

Adolescent↗

PubMed1977

Haematological abnormalities in acute pancreatitis. A prospective study.

Twenty-five patients with acute pancreatitis were studied prospectively in the first week of their admission using haematological and coagulation tests. Platelet counts initially fell and later returned to admission levels. Rising levels of plasma fibrinogen were recorded. The kaolin cephalin clotting time was shorter than its control in twenty-one patients. Eighteen patients had elevated fibrinogen degradation products and fourteen had a positive ethanol gelation test. It is suggested that by taking into account the results in series of individual patients a degree of intravascular coagulation may be a common feature of acute pancreatitis. In one patient (presented in detail) strong evidence for disseminated intravascular coagulation was found

Acute Disease↗

PubMed1979

Two cases of the nephrotic syndrome with a reversible coagulation defect.

Two cases of the nephrotic syndrome with an apparently identical defect of blood coagulation, discovered during preparation for renal biopsy are described. Plasma from both patients showed prolongation of thrombin and kaolin cephalin times which was probably due to abnormally slow polymerization of fibrin monomer. Corticosteroid therapy reversed the abnormal times in one case. One of the patients showed seasonal relapses which occurred in relation to episodes of hay fever associated with allergy to grass pollen. The other patient showed some similar features, but on renal biopsy was found to have proliferative glomerulonephritis.

Adult↗