Fibrin-related Antigen Research Articles

Angiotensin II Receptor Blockade Ameliorates Mesangioproliferative Glomerulonephritis in Rats through Suppression of CTGF and PAI-1, Independently of the Coagulation System

Background: Previously we observed that the coagulation system promotes matrix protein accumulation through transforming growth factor (TGF)-β and connective tissue growth factor (CTGF) expression in rat mesangioproliferative glomerulonephritis (MsPGN). Angiotensin II receptor blockers (ARBs) are known to suppress matrix accumulation in experimental MsPGN. In the present study, we investigated whether ARB suppresses MsPGN through inhibition of these profibrotic cytokines, and in relation to coagulation and fibrinolytic systems. Methods: MsPGN was induced in Wistar rats by intravenous injection of anti-Thy-1.1 monoclonal antibody, OX-7. As an ARB, olmesartan was orally administered in rat feed from the day of OX-7 injection (day 0) to day 8, when rats were sacrificed and kidney specimens were collected. The degrees of cellular proliferation, matrix production, coagulation factors, and inhibitory factor of fibrinolysis were evaluated. Results: Although blood pressure did not change in the normal, disease control, or treatment groups, the amount of urinary protein was significantly decreased in the ARB-treated groups, compared with the disease control group (p < 0.05). α-Smooth muscle actin expression was suppressed significantly in the treatment groups (p < 0.001). Blue-staining areas of trichrome, the number of proliferating cell nuclear antigen (PCNA)- or ED-1-positive cells, fibronectin and plasminogen activator inhibitor type 1 in glomeruli significantly decreased in the treatment groups (p < 0.05, respectively); however, fibrin-related antigen and factor V depositions were not suppressed in the treatment groups. Conclusions: These results suggest that the ARB drug would ameliorate MsPGN in vivo, at least partly through CTGF and plasminogen activator inhibitor type 1 suppression, and independently of the local coagulation system in glomeruli.

Coagulation in the mesangial area promotes ECM accumulation through factor V expression in MsPGN in rats.

It is well known that tissue factor starts the extrinsic coagulation pathway, which activates factor X to Xa, and factor V is a membrane-bound potent cofactor for the terminating stage of prothrombin activation by factor Xa. In a previous in vitro study, factor V was induced in cultured mesangial cells by inflammatory stimulation and increased expression of factor V promoted fibrin generation on the cultured mesangial cell surface. We report that extracellular matrix (ECM) accumulation is increased in association with coagulation in the mesangial area through factor V expression in mesangioproliferative glomerulonephritis (MsPGN). Wistar rats were intravenously injected with rabbit anti-rat thymocyte serum accompanied with or without simultaneous injection of rabbit anti-factor V antibody. Time course study in immunohistochemistry revealed that factor V expression was prominent on day 3 and fibrin-related antigen (FRA) deposition, then ECM accumulation, followed from day 3 to day 8. Massive fibronectin depositions and transforming growth factor (TGF)-beta expression were also noted in glomeruli from the disease control group, markedly higher than those in the normal group, and these depositions and expressions were significantly decreased in the anti-factor V neutralizing antibody-injected group. Northern blot analysis revealed that factor V mRNA expression was prominent on day 3 and was weak on day 8. Double-labeling experiments revealed the frequent colocalization of alpha-smooth muscle actin with factor V, FRA, and fibronectin in the same mesangial areas of glomeruli. TGF-beta, connective tissue growth factor (CTGF), collagen type IV, and fibronectin mRNA were upregulated in the disease control group, and anti-factor V-neutralizing antibody injection suppressed these mRNA expressions in glomeruli. The present results suggest that ECM components accumulation may progress in accordance with coagulation in the mesangial area through mesangial factor V expression and upregulated expression of TGF-beta and CTGF in MsPGN.

C4d and C4bp deposition along the glomerular capillarywalls in a patient with preeclampsia

Complement (C) 4d and cofactor C4b binding protein (C4bp) are detected in the glomerular capillary walls of a patient with preeclampsia. A 32-year-old nullipara had proteinuria of 1.2 g/d and edema at the 33rd week of pregnancy. Gradually the urinary protein excretion increased, reaching 5.1 g/d at the 37th week. The patient also showed hypertension at this stage. After normal mature delivery, the level of the urinary protein excretion remained at 3 to 4 g/d. Renal biopsy performed by means of light and electron microscopy, 15 days after delivery, showed almost normal glomeruli and modest subendothelial widening. Immunohistochemistry indicated that immunoglobulin (Ig) A, IgG, C1q, C3c, and C4c were not deposited in the glomeruli, whereas weakly positive IgM and fibrin-related antigen (FRA) were observed. Conversely, C4d, C3d, and C4bp were strongly deposited. Protein S (PS) also was observed, with a similar distribution pattern to that of C4bp. Immunoelectron microscopy showed the deposition of C4d along the capillary walls and of C4bp in the subendothelium. These findings suggest that the C4 activation process as well as the regulation process of C system and of the inflammatory coagulation axis by C4bp and PS may play an important role in the pathophysiology of preeclampsia, so-called glomerular capillary endotheliosis (GCE).

Tissue factor pathway inhibitor expression in human crescentic glomerulonephritis

Tissue factor (TF) pathway inhibitor (TFPI), the major endogenous inhibitor of extrinsic coagulation pathway activation, protects renal function in experimental crescentic glomerulonephritis (GN). Its glomerular expression and relationship to TF expression and fibrin deposition in human crescentic GN have not been reported. Glomerular TFPI, TF, and fibrin-related antigen (FRA) expression were correlated in renal biopsies from 11 patients with crescentic GN. Biopsies from 11 patients with thin basement membrane disease and two normal kidneys were used as controls. TFPI was undetectable in control glomeruli but was detectable in interstitial microvessels. In crescentic biopsies, TFPI was detected in cellular crescents and was more prominent in fibrous/fibrocellular crescents, indicating a correlation with the chronicity of crescentic lesions. TFPI appeared to be associated with macrophages but not endothelial or epithelial cells. TFPI was generally undetectable in regions of the glomerular tuft with minimal damage. In contrast, TF and FRA were strongly expressed in regions of minimal injury, as well as in more advanced proliferative and necrotizing lesions. Despite prominent TF expression, FRA was less prominent in fibrous/fibrocellular crescents in which TFPI expression was maximal. These data suggest that TFPI is strongly expressed in the later stages of crescent formation and is inversely correlated with the presence of FRA in human crescentic GN. This late induction of TFPI may inhibit TF activity and favor reduced fibrin deposition in the chronic stages of crescent formation.

Mechanism of infiltration and activation of glomerular monocytes/macrophages in IgA nephropathy.

Glomerular deposits of fibrin-related antigens (FRA), C3c, membrane attack complex (MAC) were examined by the immunoperoxidase method on 176 renal biopsy specimens from 120 cases with IgA nephropathy including 56 cases with sequential biopsies. On 47 sets of repeated renal biopsy specimens, the glomerular infiltration of the following immune cells was examined by the indirect immunoperoxidase method; immune cells positive for C3bi receptor (C3biR; CR3/CD11b, CR4/CD11c), HLADR antigen and several leukocyte surface markers (CD45R, CD3, CD15 and CD68). Twenty-four-hour urine protein (UP) at the renal biopsy was also evaluated. The glomerular deposition of FRA was inversely correlated with C3c/MAC deposition (p < 0.00001). Most cases (163 of 176) were classified into the following two types; type C with dominant deposition of C3c (97 cases) and type F with dominant deposition of FRA (66 cases), except for 13 cases with equivalent deposits of C3c and FRA (7 cases, type B) and without C3 or FRA deposits (6 cases, type O). In 56 rebiopsied cases, apparent conversion from type F or C into the other was observed only in one case though a few cases in type C lost or reduced C3c deposition to an equivocal type at the follow-up biopsy, which were included in type C', an expanded category of type C. In the whole cases, the glomerular infiltration of immune cells was significantly correlated with FRA deposition (p < 0.0002) but not with C3c. Glomerular CD11c+ cells were significantly correlated with C3c deposition in type C' (p < 0.0001), but not in type F. Glomerular HLADR positive immune cells were significantly correlated with glomerular CD3+ T cells in type F (p < 0.001), but not in type C'. In type C', UP was significantly correlated with glomerular CD11c+ cells (p < 0.0001) but not with CD 15+ or HLADR+ cells. On the other hand, in type F, UP was significantly correlated with CD 15+ and HLADR+ cells (p < 0.001) but not with CD11c+ cells. These results suggested that there are multiple pathways in inducing glomerular infiltration of immune cells in IgA nephropathy. In type C, local activation of complements might primarily induce immune cell infiltration through C3biR and these C3biR+ cells are involved in inducing proteinuria. On the other hand, in type F, in which complement activation is weak, immune cells might infiltrate directly through their Fc receptor or MHC class II antigens, and might be activated by T-cell/macrophage interaction to induce proteinuria.

Pathological improvement of IgA nephropathy and Henoch-Schönlein purpura nephritis with urokinase therapy.

The pathological findings of 13 patients with immunoglobulin A (IgA) nephropathy or Henoch-Schönlein purpura nephritis before and after urokinase (UK) administration were investigated retrospectively. The mean activity index value decreased significantly at the time of the second biopsy compared with that of the biopsy before UK treatment. The mean chronicity index value, which was considered to reflect the renal outcome, before and after UK treatment did not change significantly, although it improved significantly in six patients. Immunofluorescence microscopy showed that the immune deposition of C3 decreased, but that of IgA and fibrin-related antigen were unchanged, by UK therapy. These results suggest that UK may prevent the mesangial proliferation associated with IgA nephropathy and Henoch-Schönlein purpura nephritis not only by its fibrinolytic action, but also by other mechanisms, such as digestion of the mesangial matrices.

Intraglomerular deposition of intact cross-linked fibrin in IgA nephropathy and Henoch-Schönlein purpura nephritis.

To investigate the significance of intraglomerular coagulation and fibrinolysis in IgA nephropathy (IgA-N) and Henoch-Schönlein purpura nephritis (HSPN), the distribution of intact cross-linked fibrin (XFb) modulated by plasmin activity was examined in 25 patients with IgA-N and in 12 with HSPN. In addition to the conventional method detecting fibrin-related antigen (FRA) with an antibody against fibrinogen, the enhanced intensity of immunoreactivity of cross-linked FRA (KL-FRA) using the monoclonal antibody DD3B6/22 after plasmin exposure was evaluated to assess intraglomerular deposition of intact XFb. Also, intraglomerular invasion of macrophages was detected using the monoclonal antibody KP1 against CD68. Sixteen of a total of 37 specimens (43%) showed increased intensity of XL-FRA staining after plasmin treatment which is considered to reflect the distribution of intact XFb. Increases in the intensity of XL-FRA staining were observed mainly in mesangium and partially along glomerular capillary loops and also in a few cases in the crescents. The incidence (67%) of increases in XL-FRA staining after plasmin exposure in HSPN specimens was significantly higher than that in IgA-N specimens (32%; p < 0.05). In the group positive for XL-FRA after plasmin exposure, the numbers of macrophages per glomerulus were significantly higher (n = 15; mean +/- SD = 1.6 +/- 0.9) than in the negative group (n = 6; 0.5 +/- 0.6; p < 0.01). In HSPN, the number of macrophages per glomerulus (n = 8; 1.9 +/- 1.0) was higher than that in IgA-N (n = 13; 0.9 +/- 0.9; p < 0.05). Based on these results, we conclude that XFb is often produced and distributed in intact form in the glomeruli both in IgA-N and HSPN, associated with a relatively low intraglomerular plasmin activity, and that intraglomerular coagulation may progress in accordance with macrophage infiltration, especially in HSPN.

Immunotactoid Glomerulopathy with Unusually Thick Extracellular Microtubules and Nodular Glotnerulośclerosis in a Diabetic Patient

It has recently been suggested that immunotactoid glomerulopathy be separated from much more common fibrillary glomerulonephritis by ultrastructural features of highly organized immune deposits containing tubules of more than 30 nm in diameter. We report and discuss the results of a light, immunofluorescence and electron microscopic study of a needle renal biopsy from a 75-year-old, non-insulin dependant diabetic female presented with nephrotic syndrome, hypertension and a progressive renal failure. A unique coexistence of nodular glomerulosclerosis, as traditionally ascribed to diabetes with a peculiar type of immunotactoid glomerulopathy was confirmed by the exclusion of amyloidosis, monoclonal gammopathies, systemic autoimmune diseases and cryoglobulinemia. Mesangial, scattered subepithelial and segmentally prominent subendothelial immune deposits were found highly organized in mostly parallel arrays of 40 to 91 nm thick tubules. The average thickness of 67 nm exceeds the average diameter of tubules in all other 11 published cases of immunotactoid glomerulopathy to date. By immunofluorescence, predominantly capillary wall, thick, ribbon-like glomerular deposits contained IgG, IgM, kappa and lambda light chains of equal intensity, C3, C4 and fibrin related antigens. Mild to moderate glomerular cell proliferation associated with nodular sclerosis has been assumed to be causally related to immunotactoid deposits.

Detection of the antigenicity of the d-dimer of cross linked fibrin in the glomerulus by plasmin treatment

Intraglomerular coagulation is thought to be involved in the development of glomerular injury [1, 2]. High levels of fibrinrelated antigen (FRA) are often present in injured glomeruli, and cross linked FRA (XL-FRA) also occurs in the endothelium of these glomeruli [3). XL-FRA is currently detected using the monoclonal antibody DD3B6/22 against the d-dimer. However, XL-FRA staining is usually weaker than that of FRA. We used plasmin to detect the antigemcity of the d-dimer in the glomerulus. After this procedure, FRA staining was virtually unchanged and XL-FRA staining often increased. Sometimes, XL-FRA staining was negative before, and apparently positive after, plasmin treatment. This method is useful for detecting the intraglomerular deposition of cross linked fibrin (XFb).

Mesoglycan treatment restores defective fibrinolytic potential in cutaneous necrotizing venulitis.

Cutaneous necrotizing venulitis (CNV) is a clinical disorder associated with segmental inflammation and fibrinoid necrosis of the dermal venules. It usually presents clinically as palpable purpura, even sometimes as nodules, bullae, ulcers, and urticarial lesions. This form, when showing as leukocytoclastic vasculitis is apparently characterized by the tissue deposition of circulating immune complexes and by reduced cutaneous (CFA) and plasma (PFA) fibrinolytic activity due to reduced release of plasminogen activator (PA) from the venular endotheliocytes. Reduced CFA and PFA cause large amounts of fibrin deposits in both intra- and perivascular areas, which are able to magnify and self perpetuate the inflammatory processes following immune complex deposition. We have studied both the PFA and CFA potential (the maximum amount of PA released in the skin after certain stimuli) and the deposits of immunoglobulins, C3, and fibrin related antigen, before and after intradermal injection of histamine (a substance able to provoke endothelial release of PA), in three subjects affected by CNV before and 20 days after 10 mg/kg/day I.M. treatment with the fibrinolytic agent mesoglycan. Cutaneous fibrinolytic activity and CFA potential, reduced prior to treatment, was normal after treatment, while the deposits of immunoglobulins (IgA, IgG and IgM), C3, and fibrin related antigen, detected with direct immune fluorescence (DIF) showed similar findings before and after treatment. These data suggest that reduced CFA may play a major role in the pathogenesis of the immunologically mediated injury in CNV. The intraperivascular deposition of fibrin is favored. The fibrinolytic agent mesoglycan seems effective in restoring defective fibrinolysis in patients affected by cutaneous necrotizing venulitis, suggesting that in cases with reduced cutaneous fibrinolytic activity (or potential) the use of a fibrinolytic agent should be considered.

Fibrin and fibrinogen-related antigens in systemic sclerosis (scleroderma)

Abnormalities in fibrin deposition are implicated in the pathogenesis of vascular occlusion in systemic sclerosis. We have used a technique that involves electrophoresis and densitometric analysis of captured fibrin- and fibrinogen-related antigens to measure the concentration of the individual fibrin and fibrinogen degradation products in 13 patients with systemic sclerosis and in 15 healthy control subjects. As a group, patients with systemic sclerosis had markedly elevated levels of total fibrin-related antigen (p = 0.0007) and D-dimer (p = 0.0004), the terminal degradation product of cross-linked fibrin. The levels of fibrin monomer, an intermediate product in the conversion of fibrinogen to cross-linked fibrin, and of D-monomer, a terminal breakdown fragment of fibrinogen and fibrin monomer, were also elevated (p less than 0.005). We conclude that patients with systemic sclerosis have evidence of enhanced fibrin formation and degradation.

Relationship of Intraglomerular Coagulation and Platelet Aggregation to Glomerular Sclerosis

In order to investigate the relationship between intraglomerular coagulation and glomerular sclerosis, the distribution of fibrin-related antigen (FRA) in glomeruli without extracapillary lesions was examined by immunoperoxidase microscopy in 80 patients with IgA nephropathy (IgA-N). A total of 302 glomeruli were examined, including 20 with global sclerosis, 31 with segmental sclerosis (SS glomeruli), and 251 nonsclerosed glomeruli. In the nonsclerotic areas of SS glomeruli, the deposition of FRA was significantly greater than in the nonsclerosed glomeruli. In the nonsclerosed glomeruli FRA was mainly found in the mesangium, while in the nonsclerotic areas of SS glomeruli FRA was not only present in the mesangium but also in the endothelium of the glomerular capillary loops. FRA-positive microclots were also often observed attached to the endothelium of the capillaries of the nonsclerotic areas of SS glomeruli. Cross-linked FRA was also observed in the endothelium of the same capillaries using the monoclonal antibody DD3B6/22. Deposition of von Willebrand factor (vWF) was greater in the endothelium than in the mesangium in the same areas. Aggregated platelets adhering to the glomerular capillary walls in these areas were frequently detected using the monoclonal antibody P2. Such distribution of platelets and vWF showed that the endothelium of the nonsclerotic areas of SS glomeruli was more severely damaged than that of nonsclerosed glomeruli. These findings suggest that endothelial cell damage might activate the intraglomerular coagulation, which might be one of the factors in the development of global glomerular sclerosis.

Fibrin- and Fibrinogen-Related Antigens in Patients With Venous Disease and Venous Ulceration

Abnormalities in systemic fibrinolysis have been implicated in the pathogenesis of venous ulceration. Patients with venous disease have a prolonged euglobulin lysis time and elevated plasma fibrinogen levels, yet little is known about the metabolism of fibrinogen and fibrin in such patients. In this study, we have used a technique that involves electrophoresis and densitometric analysis of captured fibrin-related antigens to measure the concentration and proportions of the individual fibrin and fibrinogen degradation products in patients with venous disease of the lower extremity. As a group, patients with venous disease had markedly elevated levels of total fibrin-related antigen and D-dimer, the terminal degradation product of cross-linked fibrin. Levels of D-monomer, the breakdown product of fibrinogen and non-cross-linked fibrin monomer, and a measure of fibrinogenolysis were normal in all patients. In patients with ulcers, the levels of D-dimer were disproportionately higher than expected from fibrin monomer levels. On an individual basis, significant elevations of D-dimer were present in six (55%) of the 11 patients with venous disease with ulcers and in three (43%) of the seven patients with venous disease without ulcers. We conclude that patients with venous disease have uniform evidence for enhanced fibrin formation, as evidenced by elevated levels of total fibrin-related antigen and D-dimer. This is regardless of whether the venous disease is accompanied by ulceration.

Atherosclerotic plaque growth

Focal smooth muscle cell proliferation is widely perceived as a key event in the formation of stenosing atherosclerotic lesions, but the stimuli for this remain uncertain. Soluble extracts of human aortic intima from proliferative gelatinous and transitional lesions, as well as surface encrusted thrombi, have been shown by us to be mitogenic for the chick chorioallantoic membrane (CAM). They have also been shown to stimulate increase in vascularity of the CAM. When active samples were passed through anti-albumin and anti-whole-serum affinity columns, mitogenic activity in the unabsorbed, fibrin related antigen fraction remained close to the original whole extract level. In contrast, when the unabsorbed fractions from anti-whole-serum columns were passed through an antifibrinogen affinity columns, the activity was reduced to insignificant levels. Similarly, whole extracts lost activity after passing through an antifibrinogen column. This has been taken one stage further by dividing the unabsorbed fraction from an anti-whole-serum column into two equal volumes and passing one half through an antifibrinogen fragment D affinity column, and the other through an antifibrinogen fragment E affinity column. The activity of the unabsorbed fraction from the fragment D column remained the same, but that from the fragment E column was significantly reduced. Most of the fibrin degradation products (FbDP) in lesion extracts are derived from fibrin, not fibrinogen, and clotting out fibrinogen and fragment X with thrombin did not remove the activity. Whole extracts of atherosclerotic lesions clotted on the CAM surface as has previously been shown with plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

Immunohistochemical Diagnosis of Disseminated Intravascular Coagulation in Newborns

Disseminated intravascular coagulation (DIC) and other clotting abnormalities are common in sick newborn infants who have a variety of conditions. To document evidence of DIC at autopsy, immunoperoxidase staining of fibrin-related antigens (FRA) was used to detect intravascular microthrombi in liver, kidney, and lung from 127 newborns. Patients were selected from seven major disease groups: hyaline membrane disease/bronchopulmonary dysplasia, infection, meconium aspiration, necrotizing enterocolitis, congenital heart disease, other congenital anomalies, and extreme prematurity. Staining for FRA in intravascular microthrombi was seen in 40% of cases studied. The liver showed the highest frequency of intravascular microthrombi, located predominantly in the sinusoids. Unlike the adult kidney, the newborn kidney seldom had evidence of intravascular coagulation. Extravascular staining of FRA was observed in the renal distal tubular epithelium in 48 cases, many of which also had evidence of intravascular FRA staining. No significant differences in FRA staining patterns were seen among the disease groups except for cases of extreme prematurity in which all tissues showed minimal staining. Control tissues from SIDS patients also showed minimal FRA staining. Hepatic sinusoidal staining was the only tissue finding that correlated with thrombocytopenia, a clinical indicator of DIC. Despite the use of this immunohistochemical staining method, discrepancies between the clinical and autopsy diagnosis of DIC remain.

Immunoelectron microscopic localization of fibrin-related antigen in human glomerular diseases.

The distribution of fibrin-related antigen (FRA) in glomeruli was examined by immunoelectron microscopy in 9 patients with idiopathic membranous nephropathy (MN), 8 patients with minimal-change nephrotic syndrome, and 10 patients with IgA nephropathy (IgA-N), using antisera against human gamma--chain, alpha-chain, mu-chain, and fibrinogen. Electron-dense reaction products of FRA were observed in the endothelium, subendothelium, and/or in electron-dense deposits (EDD). Among the three glomerular diseases, the amount of electron-dense reaction products of FRA in the endothelium was highest in MN. This suggests that coagulation occurs on the endothelium in MN. Although the mesangial EDD of IgA-N were intensely stained with reaction products of FRA, the staining was weak in the subepithelial EDD of MN. This suggests that FRA hardly penetrates into the subepithelial EDD in MN.

Fibrin and fibrinogen-related antigens in patients with stable and unstable coronary artery disease.

Coronary-artery thrombosis may be important in the pathogenesis of unstable angina at rest. To study this possibility, we measured the serum concentrations of fibrin-related antigen, D dimer (the principal breakdown fragment of fibrin), and fibrin monomer (an intermediate product of fibrin formation) in the serum of five groups of subjects. These included 10 healthy controls, 10 controls with noncardiac pain, and three groups of 10 patients each with chronic stable angina, unstable angina at rest, or acute myocardial infarction. The concentration of fibrin-related antigen (normal range, 48 to 184 ng per milliliter) was normal in the control patients with noncardiac pain (63 to 202 ng per milliliter) and in patients with chronic stable angina (95 to 186), but it was increased in patients with unstable angina (401 to 2507) or acute myocardial infarction (470 to 1930) (P less than 0.001). D dimer concentrations in patients with unstable angina (178.3 to 310.6 ng per milliliter) or acute myocardial infarction (103.9 to 321.6) were higher than those in patients with chronic stable angina (28.6 to 52.1), in controls with noncardiac pain (44.7 to 53.1), and in healthy controls (40.4 to 50.3) (P less than 0.001). Concentrations of fibrin monomer were highest in patients with acute myocardial infarction (247.5 to 571.3 ng per milliliter) (P less than 0.001), intermediate in those with unstable angina (54.7 to 241.7) (P less than 0.001), and normal (normal range, 14.5 to 19.8 ng per milliliter) in controls with noncardiac pain (12.0 to 18.4). and patients with chronic stable angina (10.7 to 17.6). These findings suggest the presence of an active thrombotic process in patients with unstable angina at rest or acute myocardial infarction. The data do not prove that the coronary arteries were the site of the thrombotic process, but the observations are consistent with the hypothesis that thrombus formation may have an important role in the pathogenesis of these conditions.

Glomerular deposition of Hageman factor in IgA nephropathy.

Glomerular localization of Hageman factor and fibrin-related antigen (FRA) was examined in 31 cases of IgA nephropathy by immunofluorescent techniques. Hageman factor was observed in 21 cases (68%) and FRA in 24 cases (77%). It is suggested that blood coagulation occurs and fibrin is formed in the glomerulus of IgA nephropathy.

Postoperative deep vein thrombosis: identifying high-risk patients.

A prospective study was carried out to confirm the validity of a predictive index for patients at risk of developing deep vein thrombosis. The index, which correctly identified nine out of 10 patients and incorrectly identified seven out of 52 patients as being at risk, is based on five variable--namely, the euglobulin lysis time, serum concentration of fibrin-related antigen, age, percentage overweight for height, and presence of varicose veins. Thus a population of patients at particularly high risk of developing postoperative deep vein thrombosis may be identified preoperatively by means of this index, so that prophylaxis may be used more rationally.

Improved method for detecting hemagglutination by centrifugal analysis.

Centrifugal analysis can be used to detect hepatitis B surface antigen, antibody to rubella virus, and fibrin-related antigen. The procedure is performed with the same reagents used in conventional hemagglutination studies. Positive and negative reactions are distinguished by the rates of erythrocyte clearance in the centrifugal field (delta A/delta time); positive cells move more rapidly than negative cells, and this difference varies directly with the concentration of detectable antigen or antibody. This phenomenon is thought to be a result of the greater adhesion of negative cells to the cuvette's surface. Sensitivity and specificity are greater in the centrifugal analysis technique than in the more conventional hemagglutination tests. False-positive reactions are eliminated and the quantitative data are accurate and reproducible.