fibrin and Hypertension--Malignant

Electrophoretic profiles of the molecular weight distributions of fibrinogen derivatives in blood provide a tool for combined assessment of coagulation and fibrinolysis in the course of vascular disease. Profiles obtained in studies on an experimental model of hypertension and in humans with occlusive vascular disease are discussed. In the experimental studies elevations in the level of cross-linked dimers provided a more reliable means for predicting development of malignant hypertension than did many other criteria, especially near the outset when blood pressure changed to similar degrees in rats with malignant and benign hypertension. Similarly, we find that levels of dimeric and occasionally trimeric forms of fibrinogen are more prominently elevated than degraded forms of fibrinogen in patients with occlusive vascular disease.

Topics: Animals; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Humans; Hypertension, Malignant; Immunoelectrophoresis; Molecular Weight; Rats

Topics: Abruptio Placentae; Adrenal Glands; Aminocaproates; Animals; Basement Membrane; Biopsy; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Platelets; Brain; Female; Fibrin; Fibrinogen; Fibrinolysis; Fluorescent Antibody Technique; Hemorrhage; Hemorrhagic Disorders; Heparin; Humans; Hypertension, Malignant; Kidney Cortex Necrosis; Kidney Failure, Chronic; Kidney Glomerulus; Liver; Maternal Mortality; Microscopy, Electron; Myocardium; Placental Extracts; Pre-Eclampsia; Pregnancy; Rabbits; Shwartzman Phenomenon; Thromboplastin; Thrombosis

We have previously shown abnormalities of haemostasis suggestive of intravascular coagulation in patients with malignant hypertension, a condition associated with retinopathy and renal fibrin deposition. To determine whether such abnormalities are specific to malignant hypertension, we have measured several haemostatic and haemorheological variables in 18 patients with malignant hypertension (Group 1), 18 matched healthy controls (Group 2), and 18 patients with non-malignant hypertension (Group 3) matched for renal pathology, blood pressure and serum creatinine with Group 1. Both Groups 1 and 3 had increased mean levels of fibrinogen, factor VIIIc, beta-thromboglobulin, plasma viscosity and blood viscosity (corrected for haematocrit); and decreased mean levels of haematocrit, antithrombin III and platelet count. Mean levels of fast antiplasmin and alpha2-macroglobulin were elevated in Group 1 but not in Group 3. We conclude that most blood abnormalities are not specific to malignant hypertension; are also present in patients with non-malignant hypertension who have similar levels of blood pressure and renal damage; and might result from renal damage as well as promoting further renal damage by enhancing fibrin deposition. However increased levels of fibrinolytic inhibitors in malignant hypertension merit further investigation in relation to removal of renal fibrin.

Topics: Adult; beta-Thromboglobulin; Blood Viscosity; Factor VIII; Female; Fibrin; Fibrinogen; Hemostasis; Humans; Hypertension; Hypertension, Malignant; Male

Topics: Animals; Aorta, Abdominal; Arteries; Basement Membrane; Coronary Vessels; Fibrin; Hypertension, Malignant; Male; Mesenteric Arteries; Pancreas; Rats

The urinary concentration of fibrin-fibrinogen degradation products (F.D.P.) was measured in 90 patients with proteinuria above 2 g/1 and correlated with proteinuria, differential protein clearances, serum urea and creatinine, and renal biopsy findings. There was a linear correlation (r equals 0-7; P less than 0-001) between the urinary F.D.P. excretion and the selectivity of the proteinuria such that patients with highly selective proteinuria excreted only small amounts of F.D.P. whereas those with non-selective proteinuria excreted much higher levels. There was a significant correlation between the urinary F.D.P. excretion and the urine:serum (U:S) ratio of IgG excretion but not with the U:S ratio or urinary excretion of albumin or transferrin. Sephadex G200 column chromatography of the concentrated urine in 26 cases showed that patients with highly selective proteinuria excreted predominantly F.D.P. of low molecular weight in the urine whereas those with non-selective proteinuria excreted mainly fibrinogen and products of high molecular weight. Hence the type and quantity of F.D.P. in the urine are determined primarily by the differential filtration of fibrinogen and the various degradation products from the plasma through the glomerular basement membrane, which in turn is determined by the "pore size" of the basement membrane. In clinical nephrology measurement of the urinary F.D.P. level provides a rapid and convenient means of estimating the differential protein clearance.

Topics: Albuminuria; Amyloidosis; Chromatography; Fibrin; Fibrinogen; Filtration; Glomerular Filtration Rate; Glomerulonephritis; Humans; Hypersensitivity; Hypertension, Malignant; Immunodiffusion; Immunoglobulin G; Lupus Erythematosus, Systemic; Molecular Weight; Nephrotic Syndrome; Proteinuria; Purpura; Thrombosis; Transferrin

Retinal changes in accelerated hypertension were studied in seventeen monkeys with experimental hypertension by means of ophthalmoscopy and colour and flourescence photography during life, and by injection and digest preparations and light and electron microscopy after the animals had been killed. Cotton-wool spots developed in all but three monkeys. The arteries became tortuous and dilated and the light reflex decreased in those animals that became hypertensive. The earliest abnormality was a development of many points of fluorescein leakage on terminal arterioles or small arteries. Such leaking points were always present in relation to cotton-wool spots but were not confined to such areas. Focal narrowing of arteries was not observed but arteriolar occlusion and retrograde filling of the distal segment was present in three animals. Superficial linear haemorrhages were noted in five animals. Light microscopy revealed cotton-wool spots which were identical to those observed in man with a collection of swollen axons containing densely staining pseudonuclei. Study of the arterioles by electron microscopy showed findings ranging from normality to extensive necrosis. Many precapillary arteries were constricted and some were virtually occluded. Degenerative changes were present in smooth muscle cells in the wall of many of the constricted arterioles. Many arteries also showed insudation into their wall of plasma which had seeped into the muscular coat displacing and sometimes entirely replacing the smooth muscle cells. Except for arterioles with advanced necrosis, there was no indication of how plasma insudation occurred. Two arterioles with extensive necrosis showed a break within the endothelial cell cytoplasm through which penetration of plasma proteins had probably occurred. The extravascular tissues showed collections of amorphous material, sone of it with the typical banded configuration of fibrin. The sequence of events proposed to explain these features is as follows: (1) The arterioles constrict as the pressure rises, most likely as a result of vascular autoregulation. This may head to occlusion of the precapillary arterioles and is associated with necrosis of vascular smooth muscle. (2) Dilatation then occurs with insudation of plasma into the unsupported wall through a damaged endothelium. This stage probably corresponds to the autoregulatory break-point and is evidenced clinically by focal leakage of fluorescein. (3) Progressive plasma insudation

Topics: Animals; Arterial Occlusive Diseases; Basement Membrane; Blood Flow Velocity; Blood Pressure; Capillaries; Dilatation; Fibrin; Fluorescein Angiography; Haplorhini; Hypertension, Malignant; Muscle, Smooth; Necrosis; Ophthalmoscopy; Reflex, Pupillary; Retina; Retinal Artery; Retinal Diseases; Urea

Topics: Adult; Arteries; Biopsy; Child; Disseminated Intravascular Coagulation; Female; Fibrin; Graft Rejection; Humans; Hypertension, Malignant; Kidney; Kidney Diseases; Kidney Glomerulus; Kidney Tubular Necrosis, Acute; Pre-Eclampsia; Pregnancy; Scleroderma, Systemic; Transplantation, Homologous; Vascular Diseases

Topics: Aged; Arthritis, Rheumatoid; Blood Cell Count; Blood Platelets; Carbon Radioisotopes; Collagen Diseases; Factor XIII; Female; Fibrin; Fibrinolysis; Heart Failure; Humans; Hypertension, Malignant; Infections; Leukemia; Liver Diseases; Neoplasms; Pulmonary Embolism; Sepsis; Streptokinase

Topics: Antigens; Electrophoresis, Polyacrylamide Gel; Factor XIII; Female; Fibrin; Fibrinogen; Heparin; Humans; Hypertension, Malignant; Immunodiffusion; Kidney Failure, Chronic; Kidneys, Artificial; Male; Middle Aged; Platelet Adhesiveness; Renal Dialysis; Time Factors

To examine the possibility that intravascular haemolysis may lead to intravascular coagulation we have compared the degree of fibrin deposition, as measured by levels of serum fibrinogen-fibrin degradation products (F.D.P.), in two different types of intravascular haemolysis associated with red cell fragmentation. F.D.P. levels in 56 patients with intravascular haemolysis secondary to prosthetic heart valves were compared with those in 18 patients who had microangiopathic haemolytic anaemia (M.H.A.) associated with malignant hypertension or renal disease. F.D.P. levels were raised in almost all the patients with M.H.A., and this group had significantly higher levels than any of the valve replacement groups. In contrast, in the prosthetic valve patients F.D.P. levels were usually normal and bore no relation to the degree of haemolysis. It is suggested that in the absence of other precipitating factors intravascular haemolysis will not initiate intravascular coagulation. In M.H.A., while the intravascular haemolysis appears to be a consequence of an underlying intravascular coagulation, it is likely that persistence of the coagulation disturbance is related more to factors such as small vessel damage than to the release of any thromboplastic substances from fragmented red cells.

Topics: Adult; Anemia, Hemolytic; Aortic Valve; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrinogen; Heart Valve Prosthesis; Humans; Hypertension, Malignant; Kidney Diseases; Male; Middle Aged; Mitral Valve

Topics: Animals; Aortic Coarctation; Basement Membrane; Cell Membrane Permeability; Coronary Vessels; Edema, Cardiac; Endothelium; Ferritins; Fibrin; Fibroblasts; Hypertension, Malignant; Kidney Cortex; Male; Microscopy, Electron; Muscle, Smooth; Myocardium; Peroxidases; Plants; Pressure; Rats

The concentration of serum fibrinogen-fibrin-related antigen (F.R.-antigen) was measured in a group of 142 patients with various renal disorders, in 38 of whom urine F.R.-antigen was also estimated. Raised serum F.R.-antigen levels were present in 48% of the patients, with no particular preponderance in any diagnostic category apart from acute reversible intrinsic renal failure in which high levels were invariably present. Significantly-raised serum levels were also present in the patients with microangiopathic haemolytic anaemia and in those with the more severe degrees of renal impairment. Urine F.R.-antigen was increased in 34 of the 38 patients. The amount of F.R.-antigen in the urine correlated with the degree of proteinuria but not with the serum F.R.-antigen levels. The evidence relating to intravascular coagulation in renal disease is reviewed, and it is suggested that there is a high incidence of localized fibrinogen or fibrin degradation in the kidney, which is related more to factors such as the presence of uraemia and microangiopathic haemolytic anaemia rather than to the diagnostic category.

Topics: Acute Kidney Injury; Adolescent; Adult; Aged; Anemia, Hemolytic; Antigens; Child; Child, Preschool; Female; Fibrin; Fibrinogen; Glomerulonephritis; Hemagglutination Inhibition Tests; Humans; Hypertension, Malignant; Kidney Diseases; Male; Middle Aged; Proteinuria; Uremia

Topics: Animals; Cell Membrane; Fibrin; Histocytochemistry; Hypertension, Malignant; Male; Microscopy, Electron; Mitochondria; Myocardium; Myofibrils; Rats

Topics: Adolescent; Adult; Anemia, Hemolytic; Blood Coagulation Disorders; Blood Pressure; Child, Preschool; Desoxycorticosterone; Erythrocytes; Female; Fibrin; Glomerulonephritis; Humans; Hypertension, Malignant; Kidney Diseases; Male; Middle Aged; Necrosis; Nephrectomy; Urea; Vascular Diseases

Topics: Blood Vessels; Diphtheria; Fibrin; Granulomatosis with Polyangiitis; Humans; Hypertension, Malignant; Lupus Erythematosus, Systemic; Necrosis; Polyarteritis Nodosa; Pyelonephritis; Rheumatic Fever; Sepsis; Splenic Artery; Tuberculosis, Meningeal; Vascular Diseases

Topics: Arteriosclerosis; Collagen; Diabetes Mellitus; Fibrin; Geriatrics; Humans; Hyalin; Hypertension; Hypertension, Malignant; Hypertension, Pulmonary; Mitral Valve Stenosis; Pathology; Pyelonephritis