Reduction Of Fibrinogen Research Articles

The Plasma Fibrinogen Level and Vascular Diseases

An increase in the level of plasma fibrinogen is associated with occlusive arterial diseases, venous thrombo-embolism and may precede disseminated intravascular coagulation. In addition fibrinogen levels may be predictive of fatal coronary artery disease and post-operative venous thrombosis. It is possible that fibrinogen may produce its effects by increase in blood and plasma viscosity, by arterial wall infiltration or by its effects on platelet function. Acute reduction in fibrinogen levels by ancrod (Arvin) alters all these parameters and may return them to normal. As yet no study has been carried out with long term reduction of fibrinogen by stanozolol but this is now feasible and such a trial is indicated.

Ellipsometric observations of surface adsorption and molecular interactions of native and modified fibrinogen and factor VIII

The adsorption of native and modified factor VIII and of fibrinogen on gold surfaces has been evaluated by ellipsometiy. Fibrinogen and commercial factor VIII concentrate were adsorbed at similar rates after diffusion in buffered saline at 21°C, and the measured mean thicknesses of the monolayers were 17.3 and 17.4 Å respectively. Treatment of factor VIII with CaCl 2 (0.25 M) reduced the measured film thickness by 4 Å, and reduction of fibrinogen to α,β and γ chains was associated with a 7.7 Å loss of film thickness. Thrombin appeared to bind to fibrinogen and stage 1 plasmin digests, but not to stage 2 or 3 digests.

Subcutaneous ancrod therapy in peripheral arterial disease: improvement in blood viscosity and nutritional blood flow.

Nine patients with extensive peripheral arterial disease were treated with subcutaneous injections of ancrod (Arvin) for 10 to 21 days. Reduction in plasma fibrinogen was associated with a sustained reduction in plasma and blood viscosity, and a sustained increase in nutritional skin blood flow, measured by a Xenon-133 clearance technique (P less than 0.001). These findings may be relevant to the therapeutic effect of ancrod in ischemic rest pain.

Clofibrate and diabetes control in patients treated with oral hypoglycaemic agents.

1. Twenty-two maturity-onset type diabetics treated with oral hypoglycaemic agents entered a single-blind crossover study using placebo (periods A and C, 2 months each) and clofibrate (2 g/day; period B; 2 months). 2. In thirteen patients, under reasonably good control, clofibrate did not reduce fasting or post-prandial blood glucose, nor 24 h glycosuria; no improvement was noted in the M-value, an index of diabetes control. 3. In contrast, in nine patients, with poor diabetes control, clofibrate reduced 24 h glycosuria and significantly improved the M-value. 4. In all patients, clofibrate therapy was associated with a significant 19-23% reduction in plasma fibrinogen. 5. It is suggested that addition of clofibrate may be useful in maturity-onset diabetics not adequately controlled by diet combined with oral hypoglycaemic agents.

A report on the use of Arvin in patients with pre-gangrene of the lower limb.

Sixteen patients with arteriosclerosis and pre-gangrene of a lower limb were treated for 5 days by intravenous injection of Arvin. The effects of the injection on plasma fibrinogen, the viscosity of blood and the patient's symptoms were measured. There was a 90 per cent reduction in plasma fibrinogen and a significant reduction in the viscosity of blood. Five patients experienced some relief of pain during the treatment. In only one patient were the symptoms relieved permanently.

Thrombocytopenia Occurring During the Administration of Heparin

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.

Exchange Transfusions with Frozen Blood

Abstract. On 15 newborn infants, 31 exchange transfusions were performed, 11 with previously frozen red blood cells resuspended in albumin‐electrolyte‐glucose solution, 4 with previously frozen red blood cells resuspended in fresh frozen plasma and 16 with ACD blood.Good clinical effects were obtained in all cases and no untoward clinical reactions were noticed. More pronounced decreases in vB pH and vB standard bicarbonate were noted after exchange transfusions with frozen blood than after ACD blood transfusions. Small and unimportant changes of plasma electrolytes were recorded following exchange transfusions with frozen blood. The P‐haemoglobin concentrations were higher in the frozen blood than in the ACD blood, resulting in an increase of P‐haemoglobin following exchange transfusion with frozen blood.The wash‐out effect of the frozen blood was indicated by a reduction of platelets, fibrinogen and IgG during the exchange transfusions to 20% of the original value. Furthermore, a decrease in coagulation capacity was observed as revealed by considerable changes in TT and APTT values.For newborn infants with suspected or manifest coagulation disorders and for newborn infants needing more than one exchange transfusion, frozen, thawed and washed red blood cells should be resuspended in fresh or fresh frozen plasma when used as transfusion blood.

Treatment of thrombosis by sequential therapy with ancrod followed by streptokinase. Clinical pharmacology and rheology.

The effects of sequential therapy with ancrod followed by streptokinase are reported in a series of patients with thrombotic disease. Measurements have been made in blood coagulation, fibrinolysis and whole blood and plasma viscosity. Intravenous infusion of ancrod resulted in a significant reduction in plasma fibrinogen which was associated with highly significant reduction in both plasma and whole blood viscosity. Sequential therapy with streptokinase resulted in a gradual rise in fibrinogen and a slight but significant rise in whole blood and plasma viscosity. All patients showed clinical improvement and no haemorrhagic complications resulted.

Exchange Transfusions with Frozen Blood

On 15 newborn infants, 31 exchange transfusions were performed, 11 with previously frozen red blood cells resuspended in albumin-electrolyteglucose solution, 4 with previously frozen red blood cells resuspended in fresh frozen plasma and 16 with ACD blood. Good clinical effects were obtained in all cases and no untoward clinical reactions were noticed. More pronounced decreases in vB pH and vB standard bicarbonate were noted after exchange transfusions with frozen blood than after ACD blood transfusions. Small and unimportant changes of plasma electrolytes were recorded following exchange transfusions with frozen blood. The P-haemoglobin concentrations were higher in the frozen blood than in the ACD blood, resulting in an increase of P-haemoglobin following exchange transfusion with frozen blood. The wash-out effect of the frozen blood was indicated by a reduction of platelets, fibrinogen and IgG during the exchange transfusions to 20% of the original value. Furthermore, a decrease in coagulation capacity was observed as revealed by considerable changes in TT and APTT values. For newborn infants with suspected or manifest coagulation disorders and for newborn infants needing more than one exchange transfusion, frozen, thawed and washed red blood cells should be resuspended in fresh or fresh frozen plasma when used as transfusion blood.

Blood coagulation and immunological changes associated with frostbite at high altitude

In 15 cases of frostbite among soldiers stationed between 3690 and 5540 m altitude in the Himalayas investigations of blood coagulation and immunoglobulins were carried out within 24 hours, after 4 weeks and one year. In frostbite evidences of intravascular coagulation were the presence of increased amounts of FDPs in serum, reduction of plasma fibrinogen, fall in platelet counts and haematocrit, increased platelet adhesiveness, and prolonged euglobulin lysis time. Marked lowering of antithrombin III and protease inhibitors α-1 antitrypsin and α2 macroglobulin indicate their increased consumption in the pathological process. Increased immunolglobulins with relative decrease of albumin and the appearance of cryoglobulins in the form of IgG, IgA and IgM complexes, also seem to promote platelet aggregation and release reaction. Anticoagulant therapy combined with antiplatelet adhesive drugs, if instituted in the early stages of frostbite might be successful in preventing damage resulting from intravascular coagulation.

IgE-Induced Blood Coagulation Alterations in the Rabbit: Consumption of Coagulation Factors XII, XI, and IX in Vivo

Intravenous administration of BSA into 3-month-old rabbits producing detectable anti-BSA antibody only of the IgE class of immunoglobulin induced a variety of intravascular blood coagulation alterations observed in the plasma 15 min after antigen challenge included: a) the intravascular consumption of intrinsic blood coagulation factors XII, XI, and IX and possibly the reduction in clottable fibrinogen; b) a significant prolongation of the activated partial thromboplastin time but not the prothrombin time; and c) the production of an inhibitor affecting the last stage of blood coagulation. The observed blood coagulation alterations were not caused by the manipulative procedures utilized, the presence of anti-BSA, IgG or IgM antibody, histamine-induced alterations in the vascular endothelium or the development of hypotensive shock. It is proposed that specific IgE antibody can induce directly or indirectly the activation of intrinsic blood coagulation in vivo.

Significance of intravascular coagulation and fibrinolysis in acute hepatic failure

Twenty-two patients with acute hepatic failure were studied to determine the incidence and magnitude of intravascular coagulation and fibrinolysis and their relation to the severity of bleeding and prognosis. The mean platelet count, Thrombotest, plasminogen activator, and plasminogen were reduced; the reduction in fibrinogen was not statistically significant. Fibrin/fibrinogen degradation products were only moderately increased. Hepatic fibrin deposition was not extensive, being present in 11 of 22 hepatic sections, more in areas of confluent necrosis than in the sinusoids. The combination of increased fibrin/fibrinogen degradation products with decreased plasminogen activator, plasminogen, and thrombocytopenia is consistent with a diagnosis of intravascular coagulation and secondary local fibrinolysis. However, neither of these processes was severe. Severity of bleeding was related only to plasminogen levels and prognosis only to Thrombotest levels. There was no relation between hepatic histological and haematological findings. Heparin therapy is not indicated in the routine management of acute hepatic failure, as intravascular coagulation is not severe and heparin may itself cause massive bleeding.

Partial reduction of bovine fibrinogen by some sulphydryl compounds

Bovine fibrinogen dissolved in 0.3 M NaCl at pH 7.5 was treated with mercaptoethanol, reduced glutathione and dithiothreitol. Determination of the free sulphydryl groups liberated demonstrates that the reduction of disulphide bonds is completed in short time and that both mercaptoethanol and glutathione split up to 4, and dithiothreitol up to 10 disulphide bonds in the fibrinogen molecule. All derivatives of the reduced fibrinogen form clots under the action of thrombin (EC 3.4.4.13). Clotting time of the fibrinogen preparations treated with mercaptoethanol is shorter, but treated with glutathione or dithiothreitol is longer than that of the native fibrinogen. The reduced proteins are completely converted into clot by thrombin. Disruption of some of the disulphide bonds by the reagents studied does not induce essential change of the conformation of the fibrinogen molecule as it can be revealed by starch-gel electrophoresis, viscometry, gel filtration on Sepharose 4B and by ultraviolet differential spectrometry. Proteolysis by plasmin (EC 3.4.4.14) of the reduced proteins results in the formation of degradation product closely resembling the protein core (composed of Fragments D and E) derived from native fibrinogen or fibrin. Hence, it may be inferred that the reduction does not affect the protein core, and the disulphide bonds accessible for the reagents under study are probably located externally in the fibrinogen molecule. The remaining disulphide bonds together with some noncovalent bonds seem to maintain the reduced derivatives in a state enabling formation of a clot network after thrombin action.

Metabolism of Albumin and Fibrinogen in Patients with Tropical Sprue

A detailed study of the factors affecting albumin and fibrinogen metabolism has been made in patients with tropical sprue. The synthesis of both albumin and fibrinogen was measured directly and compared to the catabolic rate and to any gastrointestinal protein loss. It was found that hypoalbuminemia in patients with tropical sprue was largely due to a reduced synthesis of albumin. Although increased gastrointestinal loss was present in half of the patients, it was not severe and was of secondary importance in producing hypoalbuminemia. Fibrinogen metabolism was also altered, with a reduction in plasma fibrinogen and total circulating fibrinogen. This reduction was perhaps the result of an earlier reduction in fibrinogen synthesis. Dilution of a normal total circulating albumin with a large plasma volume and a predominantly extravascular distribution of albumin contributed to hypoalbuminemia in some patients. Nitrogen balance studies showed that these patients had a mild increase in fecal nitrogen excretion and a reduced labile nitrogen pool.

Influence of low molecular weight dextran and thrombin infusions on blood platelets and fibrinogen

Summary (1)Intravenous infusion of low molecular weight dextran to rabbits (2–3 g/kg body weight) caused a significant reduction in fibrinogen and thrombocyte levels further than caused by haemodilution. Histopathological examination revealed that this was not accompanied by the occurrence of multiple thrombi. (2)Intravenous infusion of thrombin caused a severe reduction in fibrinogen and thrombocyte levels as well as a high incidence of pulmonary thrombi. Low molecular weight dextran did not significantly influence these changes.

Hematologic effects of Crotalus adamanteus (rattlesnake) venom

1. Crotalus adamanteus venom produces a striking neutrophilic leukocytosis in dogs whether administered intramuscularly or intravenously. 2. Intramuscular administration of a lethal dose (1.28 mg/kg) of crystallineCrotalus adamanteus venom to dogs also produced: a terminal increase in serum nonprotein nitrogen, a hypoproteinemia, a reduction in plasma fibrinogen, and a terminal shortening of coagulation time. 3. It is noteworthy that no effects of this venom were noted on the serum bilirubin concentration. It follows, therefore, that contrary to existing impressions this venom does not produce any significant degree of hemolysis in vivo. 4. In addition, the intramuscular administration ofCrotalus adamanteus venom was found not to significantly affect the: blood glucose concentration, the platelet count, the plasma prothrombin time, the prothrombin time withRussell's viper venom, the prothrombin consumption, the thromboplastin generation, or the fibrinolysin activity. Two of five dogs showed a transient rise in erythrocyte count and hematocrit. 5. By contrast,Naja flava venom did not produce neutrophilic leukocytosis when administered in a subacutely toxic dose (0.2 mg/kg/day). 6. Intravenously administeredCrotalus adamanteus venom did not counteract the neutropenic effects of orally administered Myleran in dogs.

Dextran and prolonged bleeding time; results of a sixty-gram, one-liter infusion given to one hundred sixty-three normal human subjects.

The effect of dextran infusions upon the bleeding time was studied in 22 women and 235 men. In 42 % of the subjects the infusion of one liter of 6 % solution of dextran measurably prolonged the bleeding time; in 8% of the subjects the bleeding time after infusion exceeded 30 minutes. The effect was maximal from three to nine hours after the infusion and was not accounted for by any demonstrable dilution or reduction of fibrinogen or thrombocytes. Comparison of dextran preparations showed that those of highest molecular weight had the most marked effect in prolonging the bleeding time. The use of dextrans as plasma expanders carries a risk of serious failure of the hemostatic mechanism and is contraindicated in patients who are known to have a tendency to bleed or who have received large transfusions of whole blood.

Congenital afibrinogenemia: Report on a newborn infant without fibrinogen

Summary<ul><li>1.A case of congenital afibrinogenemia in a newborn infant is presented.</li><li>2.The finding of a possible reduction in fibrinogen in the father and two brothers of the patient is reported.</li><li>3.The use of clotting techniques as a sensitive means of detecting fibrinogen deficits is discussed.</li></ul>

Interference of abnormal plasma proteins with the clotting mechanism

Abstract 1.1. Two types of precipitable blood proteins, a euglobulin and a cryoprecipitable protein complex occurring in a case of multiple myeloma, and a euglobulin found in a case of cirrhosis of the liver have been studied. 2.2. The cryoprecipitable protein complex appeared to consist of fibrinogen and gamma globulin, neither of which was precipitable alone. The two components under certain conditions migrated electrophoretically as a single component of intermediate mobility. This was associated with a marked reduction in fibrinogen and prothrombin activity of the precipitate. 3.3. Both the euglobulins and the cryoprecipitable protein complex coprecipitated with prothrombin and accessory factors. Neither of these components was a macroglobulin. 4.4. Complexing of unusual plasma proteins with clotting mechanism proteins may occur more generally and lead to interference with the clotting mechanism in a variety of diseases.

Effect of Acetylsalicylic Acid Ingestion on Electrophoretic Patterns of Human Plasma.

Summary1. Blood of normal subjects was examined by electrophoresis before and after ingestion of 4 g of acetylsalicylic acid per day for 7 days. Physical and chemical constants obtained were in good agreement with published values.2. No marked changes were observed in any protein components accessible to electrophoresis. The conclusion is drawn that the effect of salicylates on blood clotting time and sedimentation rates of erythrocytes cannot be due to a reduction of plasma fibrinogen, and that salicylates are probably not hepa-to toxic.