Fibrinogen ''Leuven'', Another Genetic Variant

S ummary . An in vitro coagulation defect, shown by a prolongation of the thrombin time and a discrepancy between fibrinogen determinations with different methods, is described in a young healthy female. The disturbance in the fibrinogen-fibrin conversion, using different enzymes, persisted after purification of fibrinogen from plasma and was shown to be caused by a delayed aggregation of the patient's fibrin monomers. The presence of a delayed fibrinogen-fibrin conversion in several members of the family indicates an inherited variant.     

A Red Cell Membrane Protein Abnormality in Hereditary Elliptocytosis

S ummary . Membrane protein was extracted with acetic acid from the red cells of patients with hereditary elliptocytosis and subjected to electrophoresis on urea-starch gel. Four different families were studied. Three patients from three families showed elliptocytosis in the absence of significant haemolysis. The membrane protein in these patients failed to demonstrate any alteration in electrophoretic pattern from the normal. Cases of elliptocytosis associated with severe haemolysis demonstrated an abnormal membrane protein electrophoretic pattern. This pattern differed within the same family varying with the severity of haemolysis. Thus one sibling with severe haemolysis demonstrated a grossly abnormal pattern while a less severely affected member showed an electrophoretic pattern similar to that of hereditary spherocytic red cells.     

A New Variant of Hereditary Hemolytic Anemia With Stomatocytosis and Erythrocyte Cation Abnormality

A new variant of congenital hemolyticanemia associated with stomatocytosis,reticulocytosis, decreased osmotic fragility, type I autohemolysis and shortened erythrocyte survival without specific splenic sequestration was discoveredin three siblings of Swiss-German ancestry. Increased intracellular sodium(two to three times normal) and slightlydecreased intracellular potassium weredetected. Total sodium efflux was eight-fold greater than normal but total potassium influx was normal and ouabain-sensitive potassium influx was decreased.The ouabain-sensitive sodium efflux:potassium influx ratio was 26:1 ratherthan the 3:2 ratio noted in normal cells.The consanguineous parents, four othersiblings, and 44 other family membershad mild stomatocytosis, reticulocytosis,and, when studied, decreased osmoticfragility, increased autohemolysis, intermediate abnormalities of cation content,cation flux, and moderate shortening oferythrocyte survival. Autosomal dominant inheritance was suggested. Noabnormalities of RBC enzymes, hemoglobin or lipids were observed. No abnormalities of membrane protein weredetected on acrylamide gel. Substratedepletion of these hypermetabolic cellsresulted in intracellular dehydrationwith potassium loss in excess of sodiumgain and decreased deformability. Although the exact nature of the defectresponsible for hemolysis is unknown,this syndrome differs from other hereditary hemolytic anemias associated withstomatocytosis.

Submitted on December 21, 1970 Revised on March 16, 1971 Accepted on March 29, 1971     

Quantitative Abnormality of an Aα Chain Molecular Weight Form in the Fibrinogen of Cirrhotic Patients

Summary . The molecular weight heterogeneity of fibrinogen from the whole plasma of 12 normal and seven cirrhotic individuals was examined by means of a novel two-dimensional sodium dodecyl sulphate (SDS) gel electrophoretic technique. Fibrinogen was first separated from other plasma proteins on a large pore gel, cut out of the gel, reduced, and separated into its component Aα, Bβ and γ chains on a second gel. Fibrinogen was resolved into two major bands, I and II, on the first gel. The ratio of fibrinogen II to fibrinogens I plus II was approximately 0.3 (range 0.2-0.35) for both normals and cirrhotic patients. Two major molecular weight (mol wt) forms of Aα chain were present in normal fibrinogen I: Aα/I and/or Aα/2, mol wt 7 × 10⁴ and 6.7 × 10⁴ respectively. Normal fibrinogen II contained either one of these Aα chains plus one of the smaller Aα chains, Aα/6-10, accounting for the 3–4 × 10⁴ mol wt difference between bands I and II. Aα/2 comprised 33% of the total Aα chains (range 27–41%) in normal fibrinogen I and approximately 25% of the Aα chains in normal fibrinogen II. In contrast, fibrinogen I from six out of the seven patients contained a lower percentage of Aα/2 (range 10–25%). Similarly fibrinogen II from these patients was deficient in Aα/2, although the protein contained normal levels of lower mol wt Aα derivatives. No correlation was found between per cent fibrinogen II and per cent Aα/2 in either normal or cirrhotic subjects. These results suggest that at least two independent processes are responsible for the observed levels of Aα heterogeneity in normals and cirrhotics and that the process controlling Aα/2 production is abnormal in cirrhotic individuals. This decrease in Aα/2 does not affect the coagulability of fibrinogen. Fibrin monomer aggregation studies indicate that a serum component is, in part, responsible for the abnormally transparent clot formed from the plasma of cirrhotics.     

„Fibrinogen Hannover“, ein weiteres atypisches Fibrinogen

Zusammenfassung Es wird über eine weitere Fibrinogenvariante — Fibrinogen Hannover — berichtet.Es handelt sich um eine fakultative hämorrhagische Diathese mit der von anderen Dysfibrinogenämien her bekannten Verminderung des gerinnbaren Fibrinogens bei normaler Fibrinogenkonzentration in den immunologischen Testen, bei Hitzefällung und im Staphylokokken-Klumpungstest. Auch hier waren bei Verwendung von Thrombin und thrombinähnlichen Enzymen die Gerinnungszeiten verlängert und ein Hemmeffekt auf die Fibrinbildungsgeschwindigkeit eines normalen Plasmas nachweisbar. Eine Störung der Plasminwirkung in vitro fand sich nicht.

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Summary Another abnormal fibrinogen — fibrinogen Hannover — is reported.As known from most dysfibrinogenemias the clottability is poor, while immunologic tests, heat precipitating test and the staphylococcal clumping test give normal fibrinogen concentrations. The clotting time when using thrombin or thrombin like enzymes is prolonged, it can be corrected with high thrombin concentrations or thrombin combined with calcium ions, but not with thrombin like enzymes combined with calcium ions. The mild bleeding diathesis was first noted when the patient underwent an operation.

     

Fibrinogen, a cardiovascular risk factor

Fibrinogen level is an independent predisposing factor for coronary heart disease and has a prognostic significance comparable with that of cigarette smoking, serum cholesterol level and hypertension. In our study fibrinogen levels were measured in 45 patients with cardiovascular disease of which 25 (55%) had a high fibrinogen level and in 45 persons healty, of which only 3 (6.6%) increased fibrinogen. The impact of fibrinogen level on the risk of cardiovascular disease was more consistent in men of all ages considered. The authors note that the independent contribution of fibrinogen to the cardiovascular risk may reflect hypercoagulability, hyperviscosity and increased platelet aggregation. Therefore they consider, the dosing of fibrinogen level important in the research of cardiovascular risk factors.     

Erythrocyte Abnormality Induced, by Protein Malnutrition

Red cell survival studies using ⁵¹ Cr-labelled erythrocytes were carried out on 14 subjects with protein malnutrition (12 kwashiorkor and two marasmus). The T ½ varied from 3 to 20 days with a mean of 12.4 days. There was significant accumulation of radioactivity demonstrable on scanning over the liver and spleen in three kwashiorkor patients.
Erythrocytes of three kwashiorkor patients showed shortened T ½ both when auto-transfused and when injected into three normal controls. The T ½ of erythrocytes from two normal donors injected into four subjects with kwashiorkor was also considerably reduced.
After protein repletion, auto-transfusion in nine cases showed a T ½ which varied from 20 to 29 days with a mean of 23.7 days.
This investigation has shown considerably reduced erythrocyte survival in patients with protein malnutrition (kwashiorkor and marasmus); this shortened survival time appears to be due to both corpuscular and extra-corpuscular factors. Following protein feeding considerable improvement in the erythrocyte survival took place. Since improvement in erythrocyte survival occurred on a low iron-containing protein diet without haematinics or vitamin supplements it is considered that protein depletion is principally responsible for this shortened survival.     

Immunological Homogeneity of Membrane Proteins from Hereditary Spherocytic, Hereditary Elliptocytic, and Normal Red Cells

S ummary . Haemagglutination inhibition and immunodiffusion techniques were applied to the study of red-cell membrane protein obtained from normal human subjects, patients with hereditary spherocytosis, patients with hereditary elliptocytosis, and also from calves and monkeys.
These techniques failed to detect differences between the normal and abnormal human red cells but did show differences between the red cells of the human and the two other mammalian species.     

Hereditary xerocytosis,a misleading anemia

Annals of Hematology -     

Hereditary macrothrombocytopathia, nephritis and deafness

Two unrelated families were studied in which two members of each have a syndrome of macrothrombocytopathia, nephritis and deafness. A third member of one family, a young child, has the platelet disorder and a mild hearing loss. The mode of inheritance of the syndrome appears to be dominant. Except for its severity in affected females, the renal disease is indistinguishable from the classic type of hereditary nephritis. Likewise, the high frequency sensorineural hearing loss is similar to that seen in Alport's syndrome. The platelet disorder is characterized by thrombocytopenia, giant platelets with an abnormal ultrastructure, prolonged bleeding time and defective adherence of platelets to glass. Aggregation in response to collagen and epinephrine, and release of platelet factor 3 are impaired, and the release of nucleotide after exposure to collagen is abnormally low.     

Another really, really big virus

Viruses with genomes larger than 300 kb and up to 1.2 Mb, which encode hundreds of proteins, are being discovered and characterized with increasing frequency. Most, but not all, of these large viruses (often referred to as giruses) infect protists that live in aqueous environments. Bioinformatic analyses of metagenomes of aqueous samples indicate that large DNA viruses are quite common in nature and await discovery. One issue that is perhaps not appreciated by the virology community is that large viruses, even those classified in the same family, can differ significantly in morphology, lifestyle, and gene complement. This brief commentary, which will mention some of these unique properties, was stimulated by the characterization of the newest member of this club, virus CroV (Fischer, M.G.; Allen, M.J.; Wilson, W.H.; Suttle, C.A. Giant virus with a remarkable complement of genes infects marine zooplankton. Proc. Natl. Acad. Sci. USA 2010, 107, 19508-19513). CroV has a 730 kb genome (with ～544 protein-encoding genes) and infects the marine microzooplankton Cafeteria roenbergensis producing a lytic infection.     

Another Kell-Related Antibody, Anti-K19

Abstract. A new high-frequency antigen related to the Kell system was defined by the serum of a patient, Mrs. Sub. The antigen was lacking from her cells and those of one of her three siblings. All random cells tested were incompatible with her serum as were bloods of other various 'null' phenotypes, but K_o bloods were compatible suggesting that the antibody, subsequently called anti-K19, was related to the Kell blood group system.