Concentrations Of Fibrinogen Degradation Products Research Articles

Impact of prolonged clamping of the portal vein during liver transplantation in infants with biliary atresia: renewed interest in a long-standing issue.

Various approaches to portal vein (PV) reconstruction have been described; however, there is still scope to improve the safety and efficiency of how PV anastomosis is performed in infants. We analyzed, retrospectively, the predictive factors for PV reanastomosis during living donor liver transplantation (LDLT) in 117 infants (< 1year old) with biliary atresia (BA). Twenty-six infants required PV reanastomosis because of intraoperative PV thrombosis in 21 and insufficient PV flow in 5. Univariate analysis identified multiple previous laparotomies and a prolonged anhepatic phase (AHP) as significant risk factors for repeated PV anastomosis. The AHP cutoff value for identifying patients requiring PV reanastomosis was 134min. Multivariate analysis revealed prolonged AHP > 134min (odds ratio, 15.98; 95% confidence interval, 5.05-50.6; P < 0.001) as an independent risk factor for repeated PV anastomosis. The plasma D-dimer and fibrinogen degradation product concentration just after reperfusion were significantly higher in patients requiring PV reanastomosis (P < 0.001). Patients requiring reanastomosis of the PV had a higher incidence of PV complications after LDLT than those who did not need PV reanastomosis (P = 0.01). Attempting to minimize the AHP is indispensable for successful LDLT in infants with BA.

Plasmatic coagulation and fibrinolysis in healthy and Otostrongylus-affected Northern elephant seals (Mirounga angustirostris).

Prepatent Otostrongylus arteritis results in hemorrhagic diathesis in free-ranging Northern elephant seals (Mirounga angustirostris) attributed to aberrant larval migration of the lungworm, Otostrongylus circumlitus. Clinical signs are often nonspecific, including lethargy, anorexia, and blepharospasm, but can progress to spontaneous frank hemorrhage and death within 72hours of onset. Previously published case reports describe coagulopathy with prolonged PT and APTT, normal to elevated platelet counts, normal antithrombin concentrations, and low concentrations of fibrinogen degradation products. Disseminated intravascular coagulation was proposed as the cause of hemorrhage, but is inconsistent with some of the reported clinicopathologic changes. The purpose of this study was to compare plasmatic coagulation and fibrinolysis in healthy and Otostrongylus-affected elephant seals, in order to identify potential therapy. We hypothesized that hyperfibrinolysis contributed to hemorrhage in these cases. Citrated plasma samples were collected from 3- to 4-month-old Northern elephant seals in a wildlife rehabilitation hospital. The sampled population included 25 healthy, prerelease seals and 32 clinically ill seals diagnosed with presumptive Otostrongylus arteritis. Twenty-one of the included seals had Otostrongylus infestation confirmed at necropsy. Standard coagulation tests and plasma thromboelastography were performed for a complete assessment of coagulation and fibrinolysis. Northern elephant seals with definitive Otostrongylus infestation were hypocoagulable and hypofibrinolytic compared to healthy controls. Results were most consistent with disseminated intravascular coagulation. Treatment with antifibrinolytic drugs to control hemorrhage may be unrewarding; alternative therapies such as plasma transfusions or coagulation factor concentrates should be investigated.

High fibrinogen in peripheral blood correlates with poorer hearing recovery in idiopathic sudden sensorineural hearing loss.

ObjectivesWe used hearing tests and peripheral blood sample analyses to characterize the pathology of idiopathic sudden sensorineural hearing loss (ISSNHL) and to identify possible prognostic factors for predicting recovery of hearing loss.Study DesignA retrospective, multicenter trial was conducted.MethodsTwo hundred three patients examined within 7 days after the onset of ISSNHL received prednisone with lipo-prostaglandin E1. Pure-tone auditory tests were performed before and after treatment with these drugs. Blood tests were performed on blood samples collected during the patients’ initial visit to our clinic.ResultsIn all patients, elevated white blood cell (WBC) counts, fasting blood sugar levels, HgbA1c, and erythrocyte sedimentation rate (ESR) significantly correlated with high hearing threshold measurements obtained on the initial visit. High fibrinogen levels, WBC counts, ESR, and low concentrations of fibrinogen degradation products (FDP) were associated with lower hearing recovery rates. Additionally, different audiogram shapes correlated with different blood test factors, indicating that different pathologies were involved.ConclusionsHigh fibrinogen levels measured within seven days after ISSNHL onset correlated with poorer hearing recovery. This may be a consequence of ischemia or infections in the inner ear. The high WBC counts also observed may therefore reflect an immune response to inner ear damage induced by ischemic changes or infections. Our data indicate that therapeutic strategies should be selected based on the timing of initial treatment relative to ISSNHL onset.

Plasma Prekallikrein as a Risk Factor for Diabetic Retinopathy

The aim of the study was to verify the hypothesis that in diabetes there is an increased activation of coagulation system leading in consequence to diabetic retinopathy. Thirty three healthy subjects (controls, 16 males and 17 females) and 35 patients with diabetes type 1 (15 males and 20 females) were examined. We monitored plasma prekallikrein (PPK), glycemia, fructosamine, glycosylated hemoglobin, activated partial thromboplastin time (PTT), INR, fibrinolysis in euglobulins time (FET), level of antithrombin III (AT III), fibrinogen (Fb) and fibrinogen degradation products (FDP). In diabetic patients without retinopathy, PKK concentration was 16% higher (p <0.005), in patients with background retinopathy 33% higher (p <0.001), and in patients with proliferative retinopathy PKK concentration was 50% higher (p <0.001) than in controls. In the subgroup of patients with proliferative retinopathy PTT was significantly shorter (p <0.001), and FET was significantly longer (p <0.001) than in control. In patients with diabetes higher FDP concentrations were found than in controls (p <0.05). Significant correlations were found between PPK and fructosamine levels in all diabetic patients (R(S)=+0.57 p <0.001), in diabetic patients without retinopathy (R(S)=+0.61, p <0.05), and in diabetic patients with retinopathy (R(S)=+0.62, p <0.005). We found negative correlation between PPK concentration and PTT (R(S)=-0.43, p <0.001) and positive correlation between PPK concentration and FET (R(S)=+0.59, p <0.00001) in the entire study group. The occurrence of diabetic retinopathy is connected with higher levels of plasma prekallikrein.

The Role of Intrinsic Fibrinolytic System Activation in Pathogenesis of Hemostasis Disturbances in Hemodialized Patients with Chronic Renal Failure

In the hemodialysis patient, hemostasis changes may occur. The contribution of fibrinolysis in pathogenesis of these disorders is unclear. The aim of the study was to estimate intrinsic fibrinolysis pathway in patients treated with hemodialysis (HD) because of chronic renal failure caused by chronic glomerulonephritis. The study was performed with 43 patients; the control group consisted of 51 healthy volunteers chosen by sex and age. The following parameters were determined: concentration of the urokinase plasminogen activator antigen (uPA:Ag), plasmin–antiplasmin complexes (PAP), fibrin and fibrinogen degradation products (FDP), activity of prekallikrein (PK) and C1‐inhibitor (C1‐INH) and also euglobulin clot lysis time (ELT). The above parameters were assessed in the patients before and after HD and were compared with the control group. In the HD patients, in comparison with the control group, prolonged statistically ELT [153 (125;215) vs. 105 (75;142) min.; p < 0.001], with increase of PAP (508.6 ± 274.7 vs. 184.7 ± 69.4. µg/L; p < 0.001) and FDP concentrations [5 (5;15) vs. 2.5 (0;0.3), µg/mL; p < 0.05] before the procedure were determined. It suggests increased plasmin production and fibrin digestion despite determination of decreased general fibrinolytic activity. The C1‐INH activity before HD was also significantly increased as compared with the control group [157 (136;171) vs. 107 (100;124), %; p < 0.001], and its significant decreased after the HD is [157.7 ± 23.9 vs. 122.3 ± 20.3, %; p < 0.001], as it seems to be a nondirect proof of intrinsic pathway contribution in fibrinolysis activation in the HD patients. The remaining examined parameters did not change significantly after the dialysis procedure.

Detection of anticoagulant activities of isolated canine fibrinogen degradation products X, Y, D and E using resonance thrombography.

The objective of the study was to examine the influence of fibrinogen degradation products (FDPs) on the resonance thrombogram (RTG). Different concentrations (up to 5 g/l plasma) of purified canine FDP X, FDP Y, FDP D and FDP E were added to the blood of healthy dogs and the RTG was measured. Of the examined RTG parameters [reaction time, fibrin formation time (RTG-f), and fibrin amplitude], FDP X, FDP Y, and FDP D showed the clearest effects on RTG-f. RTG-f was on the average prolonged by addition of 0.06 g/l FDP Y, 0.15 g/l FDP X, and 0.17 g/l FDP D to the upper limit of the reference range. Based on the gram amounts of the added FDP, fragment Y also showed in other RTG parameters the most marked effect, followed by FDP X and FDP D. FDP E showed no substantial effect rS [Spearmans rank correlation coefficient (< 0.3, P > or = 0.5)] in any of the examined RTG parameters. The closest correlation between FDP concentration and the result of the different RTG parameters was found for the RTG-f (FDP X, rS = 0.819; FDP Y, rS = 0.795; FDP D, rS = 0.764). The results indicate that RTG is a useful screening test for the detection of increased FDP concentrations.

Influence of Fibrinogen Degradation Products on Thrombin Time, Activated Partial Thromboplastin Time and Prothrombin Time of Canine Plasma

To investigate how thrombin time, activated partial thromboplastin time (APTT) and prothrombin time are influenced by fibrinogen degradation products (FDP), different concentrations (0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.8 and 1.0 mg/ml) of the purified FDP X, Y, D and E were added to the plasma of healthy dogs. If fragment Y was added to the plasma a considerable inhibitory effect could be demonstrated for all three test systems. A significant prolongation (p < 0.05) was found for concentrations of ≥0.1 mg/ml (thrombin time, APTT) and ≥0.2 mg/ml (prothrombin time). With FDP Y concentrations from >0.185 mg/ml (prothrombin time) to >0.24 mg/ml (APTT) coagulation time was prolonged beyond the respective reference range. As regards the other fragments, a comparable inhibitory effect could only be shown for fragment X added to the thrombin time test system. This effect can most probably be explained by the competition of the FDP X and fibrinogen for the fibrinogen binding sites of thrombin, rather than by a fibrin polymerization disorder. The results demonstrate that for plasma with normal fibrinogen concentration the group tests are only prolonged beyond the reference range at FDP concentrations very rarely found in spontaneous hyperfibrinolysis.

Use of tranexamic acid for an effective blood conservation strategy after total knee arthroplasty

We have investigated the effect of treatment with tranexamic acid, an inhibitor of fibrinolysis, on blood loss, blood transfusion requirements and blood coagulation in a randomized, double-blind, placebo-controlled study of 42 patients after total knee arthroplasty. Tranexamic acid 15 mg kg-1 (n = 21) or an equivalent volume of normal saline (n = 21) was given 30 min before surgery and subsequently every 8 h for 3 days. Coagulation and fibrinolysis values, blood loss and blood units administered were measured before administration of tranexamic acid, 8 h after the end of surgery and at 24 and 72 h after operation. Coagulation profile was examined (bleeding time, platelet count, prothrombin time (PT), activated partial thromboplastin time (aPTT), plasminogen, beta-thromboglobulin and fibrinogen). Fibrinolysis was evaluated by measurement of concentrations of D-dimer and fibrinogen degradation products (FDP). Total blood loss in the tranexamic acid group was 678 (SD 352) ml compared with 1419 (607) ml in the control group (P < 0.001), and occurred primarily during the first 24 h after surgery. Thirteen patients received 1-5 u. of packed red blood cells in the control group compared with two patients in the tranexamic acid group, who received 3 u. (P < 0.001). Postoperative packed cell volume values were higher in the tranexamic acid group despite fewer blood transfusions. Postoperative concentrations of plasminogen were decreased significantly in the tranexamic acid group (P < 0.001). Platelet count, PT, aPTT, bleeding time, beta-thromboglobulin, fibrinogen and FDP concentrations did not differ between groups, but D-dimer concentrations were increased in the control group. Thromboembolic complications occurred in two patients in the control group compared with none in the tranexamic acid group.

Increased tissue-type plasminogen activator antigen release is not accompanied by increased systemic fibrinolytic activity in severe neonatal respiratory distress syndrome.

Intravascular and intraalveolar fibrin depositions in preterm infants with severe respiratory distress syndrome (RDS) have been attributed to activation of clotting. We questioned whether in the face of activated clotting, fibrinolysis is sufficient in these infants. We found, in infants with severe RDS within 6 to 12 h of birth, increased median thrombin-antithrombin III complex formation (11.1 versus 1.3 ng/mL in the group with mild-to-moderate RDS, p < 0.001), indicating activation of clotting. Simultaneously, we found increased tissue-type plasminogen activator antigen (t-PA) release in plasma of these infants represented by increased median t-PA plasma concentrations (8.3 versus 2.5 ng/mL in the group with mild-to-moderate RDS, p < 0.01). This increased t-PA release was not accompanied with more plasminogen and antiplasmin consumption and with more fibrin and fibrinogen degradation than in the infants with mild-to-moderate RDS because plasma plasminogen and antiplasmin activity and total fibrin and fibrinogen degradation product concentrations were similar in both groups. We have found that activated clotting and t-PA plasma concentrations are positively correlated with arterial-to-alveolar oxygen tension ratio and ventilator efficiency index values. Plasminogen and antiplasmin activity, and total fibrin and fibrinogen degradation product concentrations were not correlated with these continuous measures of RDS severity. In neonatal RDS, clotting activity contributes to disease severity. Insufficient fibrinolysis likely facilitates the deleterious effects of activated clotting.

Tissue-type plasminogen activator and fibrin monomers synergistically cause platelet dysfunction during retransfusion of shed blood after cardiopulmonary bypass

Reduced hemostasis and bleeding tendency after cardiopulmonary bypass results from platelet dysfunction induced by the bypass procedure. The causes of this acquired platelet dysfunction are still subject to discussion, although, recently, greater emphasis has been placed on an overstimulated fibrinolytic system as a probable cause. In the first part of this study we assessed the effects of postoperative retransfusion of shed blood on blood loss to patients undergoing cardiopulmonary bypass. We observed that increasing concentrations of fibrinogen degradation products and tissue-type plasminogen activator stimulating activity in shed blood correlated significantly with a higher postoperative bleeding tendency (p < 0.05 for both). We further noted that retransfusion of shed blood increased the total postoperative blood loss by 43% (925 versus 1320 ml, p < 0.05). On the basis of these clinical observations, we hypothesized that the increased bleeding tendency was caused by fibrinolysis. In the second part of this study we collected evidence in support of this hypothesis by an in vitro study, in which we introduced similar (pro)fibrinolytic activity to platelet-rich plasma and measured the influence of this treatment on platelet function indicated by ristocetin agglutination. Tissue-type plasminogen activator and fibrin monomers (tissue-type plasminogen activator stimulator) together induced severe platelet damage, resulting in a decreased ristocetin agglutination response. Therefore, we propose a fibrinolysis-related mechanism for platelet dysfunction during cardiopulmonary bypass, dependent on fibrinolytic factors such as fibrin monomers, D-dimers, and tissue-type plasminogen activator.

The Change of Plasma Concentrations of Fibrinogen Degradation Products and Fibrin Degradation Products During the Open Heart Surgery

The Change of Plasma Concentrations of Fibrinogen Degradation Products and Fibrin Degradation Products During the Open Heart Surgery

Changes in the fibrinolytic system associated with physical conditioning.

The effects of physical conditioning on plasma fibrinolytic activity were studied in two groups of subjects. Volunteers not engaged in any sport were compared with individuals having been subjected to aerobic conditioning (middle-distance runners, defined as men running more than 80 km per week). Plasma concentrations of the different components of the fibrinolytic system were evaluated before and immediately after a maximal effort treadmill protocol. Comparison of the resting parameters revealed that under basal conditions for plasma concentrations of plasminogen, fibrinogen, alpha 2-antiplasmin, protein C and protein S there were no differences between the two groups. Concentrations of the fibrin degradation products (FbDP) and fibrinogen degradation products (FgDP) were significantly higher in the runners than in the control group, indicating an increased fibrinolytic potential that seemed to be a consequence of the reduced formation of tissue plasminogen activator-plasminogen activator inhibitor (t-PA-PAI) complexes. Acute maximal exercise resulted in pronounced fibrinolysis, evidenced by the elevation of FbDP and FgDP concentrations, in both groups of subjects. The acceleration of the fibrinolytic activity was larger in conditioned individuals, which could be accounted for by a higher t-PA release and reduced formation of t-PA-PAI complexes when compared to the untrained subjects.

Kringle domains and plasmin denaturation

The rate of plasmin denaturation was in the order of Lys-plasmin > miniplasmin > microplasmin. Fibrinogen degradation products (FDP) dose dependently increased the denaturation rate of Lys-plasmin and miniplasmin with a maximal rate constant at the FDP/plasmin ratio of about 0.5. The denaturation rate constant of microplasmin was not affected. FDP increased the rate of plasmin denaturation was in parallel with its effect on the interaction among kringle domains. Without FDP only trace amounts of plasminogen dimer could be detected by cross-linking with bis-(sulfosuccinimidyl)-suberate followed by SDS gel electrophoresis. In the low concentration of FDP significant amounts of oligomers of Glu-, miniplasminogens, kringle 1–3 and kringle 1–5 were observed. High concentration of FDP, however, decreased plasminogen oligomer.

Enhanced Effective Fibrinolysis following the Neutralization of Heparin in Open Heart Surgery Increases the Risk of Post-Surgical Bleeding

The tissue-type plasminogen activator related fibrinolytic system was studied in 24 patients undergoing cardiopulmonary bypass surgery. The degradation of fibrinogen and fibrin was followed during and after surgery by means of new sensitive and specific assays and the changes were related to the blood loss measured in the chest tube drain during the first 24 postoperative hours. Although tissue-type plasminogen activator was significantly released into the circulation during the period of extracorporeal circulation (p less than 0.01), constantly low levels of fibrinogen degradation products indicated that a systemic generation of plasmin could be controlled by the naturally occurring inhibitors. Following extracorporeal circulation heparin was neutralized by protamine chloride, and in relation to the subsequent generation of fibrin, there was a short period with increased concentrations of fibrinogen degradation products (p less than 0.01) and a prolonged period of degradation of cross-linked fibrin, as detected by increased concentrations of D-Dimer until 24 h after surgery (p less than 0.01). Patients with a higher than the median blood loss (520 ml) in the chest tube drain had a significantly higher increase of D-Dimer than patients with a lower than the median blood loss (p less than 0.05). We conclude that the incorporation of tissue-type plasminogen activator into fibrin and the in situ activation of plasminogen enhance local fibrinolysis, thereby increasing the risk of bleeding in patients undergoing open heart surgery.

Relation of Intraperitoneal and Intravascular Coagulation and Fibrinolysis Related Antigens in Peritoneal Dialysis

Patients received 2,000 ml of dialysate intraperitoneally with five exchanges per day during continuous peritoneal dialysis (CAPD) for the treatment of terminal renal insufficiency. During a dwell time of 4 h the dialysate reached a total protein concentration up to 100 mg/dl by mass transfer of intravascular proteins. The composition is dependent on the molecular weight of the proteins. This results in an intraperitoneal hemostatic system of low concentration and different composition. We found an intraperitoneal fibrinogen cleavage and thrombin-antithrombin III-complex formation leading to increased levels of fibrinopeptide A (FPA: 33.3 +/- 7.0 ng/ml) and thrombin-antithrombin III-complex (TAT: 4.7 +/- 0.4 ng/ml) in plasma by mass transfer from dialysate to plasma. t-PA (tissue plasminogen activator) and PAI-1 (plasminogen activator inhibitor type 1) concentrations in plasma were within the normal range. The dialysate concentrations indicated a low local secretion. The fibrinolytic fibrin fragment D-dimer and the fibrinogen degradation product concentrations in plasma were greater than in dialysate. But the relations of the proteins between plasma and dialysate refer to a local intraperitoneal production as well. The results show that intraperitoneal coagulation predominates over fibrinolysis which is accompanied by an intravascular fibrinolysis in patients undergoing CAPD. Neoantigens produced in dialysate and diffused to plasma are comparable to changes seen in disseminated intravascular coagulation.

Biological study of intravenous anisoylated plasminogen streptokinase activator complex in acute myocardial infarction.

An anisoylated plasminogen streptokinase activator complex (APSAC) has been administered as a bolus intravenous injection of 30U to 14 patients with acute myocardial infarction. Systemic effects on coagulation and fibrinolysis were studied. In 1 patient, the treatment produced no biological modification, which could be explained by an increased streptokinase resistance in this patient, apparent from the sample collected before treatment. In the other patients, as expected, fibrinogen, plasminogen, alpha 2-antiplasmin and factors V and VIIIc fell dramatically, while there was an increase in serum fibrinogen degradation product concentrations. In addition, plasma fibrin derivatives increased during APSAC therapy, both in patients who had occluded or patent coronary arteries. Discrepancies were found between methods used to measure fibrinogen: with the Ellis and Stransky method, concentrations were higher than with the Clauss method; and for plasminogen, automated methods using different analysers may give higher results in some patients.

Coronary thrombolysis with recombinant single-chain urokinase-type plasminogen activator in patients with acute myocardial infarction.

Seventeen patients with acute transmural myocardial infarction and angiographically confirmed complete coronary occlusion were treated with heparin combined with intravenous single-chain urokinase-type plasminogen activator (scu-PA), obtained by expression of the cDNA encoding mature human scu-PA in Escherichia coli. In eight patients, recombinant scu-PA (rscu-PA) was given as a 10 mg bolus followed by 30 mg over 1 hr. Recanalization was obtained in six patients, but with persistent delayed opacification of the vessel in four of these patients. During infusion, a plateau level of rscu-PA antigen in plasma of 3.4 micrograms/ml (median value, range 1.4 to 5.5) was reached. At the end of the infusion the alpha 2-antiplasmin level had decreased to 54% (median, range 22% to 82%) of the preinfusion level, the fibrinogen level to 89% (median, range 26% to 101%), and fibrinogen degradation products (FDPs) to 20 micrograms/ml (median, range 8 to 387). In nine patients, rscu-PA was administered as a 10 mg bolus followed by 60 mg over 1 hr. This resulted in recanalization with normal distal filling of the vessel in seven patients, within 46 +/- 17 min (mean +/- SD). During infusion the concentration of rscu-PA in plasma increased to a median value of 7.4 micrograms/ml (range 4.0 to 13.3). At the end of the infusion the alpha 2-antiplasmin level was 22% of baseline (range 5% to 47%), the fibrinogen level 45% (range 4% to 94%), and the concentration of FDPs 87 micrograms/ml (range 6 to 1034). No significant bleeding or short-term side effects were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

1436 EFFECT OF POLYCYTHEMIA ON FIBRINOGEN DISAPPEARANCE RATE IN PUPPIES

I have shown in previous work that polycythemia in the newborn dog will cause a disease similar pathologically to necrotizing enterocolitis(NEC) in human infants. To explore the patho-physiology of this disease, the effect of polycythemia on fibrinogen disappearance rate was studied in 38 puppies (3-14d). All pups received an exchange transfusion removing 65cc/kg of blood and transfusing 85cc/kg of either whole blood (control, C, resulting Hct.=37), or packed red blood cells(polycythemia, P, resulting Hct.=68). NEC was found in 15 of 19 P and 4 of 19 C pups(p<.01). The concentration of Fibrinogen degradation products measured by tanned red cells hemagglutination inhibition at 2 & 4hr. post transfusion was 36% higher in the P than the C pups (NS). 1251 Fibrinogen and Evan's blue (an albumin marker) were injected 2hr after transfusion and the concentration of clottable labelled fibrinogen and albumin tracer were measured at ½ hr & 2 hrs after injection. The fraction of the tracer that disappeared over the 1½hr period was calculated. In previous experiments pups have been shown to have stable plasma volumes during this period. In the P group 45±18 SD% of the clottable fibrinogen disappeared vs only 28±15% in the C group (2p<.01). In the P group 36±21% of the albumin tracer disappeared vs 31±12% in the C group(NS). Thus polycythemia in the newborn dog is associated with an increased disappearance of clottable fibrinogen not associated with a general increase in protein disappearance rate. The most sensative currently available test for fibrinogen degredation products was inadequate to demonstrate this event.

Fibrinogen degradation products in urological malignant tumors.

Fibrinogen degradation products (FDP) were determined in a series of 98 patients with malignant urological tumors using a staphylococcal clumping test. The results are compared with the FDP of 61 urological patients without malignant tumors. No difference between the series of radically operated tumor patients and the control group could be found. The FDP in a series of patients with persistent tumors were clearly higher than those of the control group: especially the results for patients with renal cell carcinoma were significantly higher. The highest concentration of FDP was found in patients with metastases. Therefore, FDP in serum could be a possible tumor marker for patients with renal cell carcinoma.

Work related symptoms among sewage workers.

Employees at six sewage treatment plants and three drinking water plants were interviewed for the presence of specific medical symptoms. Serum immunoglobulin concentrations, white blood cell counts and fibrinogen degradation product concentrations (FDP) in urine were determined as were the number and species of airborne Gram negative rods in order to characterise exposure to aerosols of sewage water. The highest number of bacteria was found in areas where the sewage water was agitated. A significantly higher proportion of employees at sewage treatment plants reported skin disorders, diarrhoea, and other gastrointestinal symptoms than the control group. No significant differences were found between the groups for white blood cell count or serum immunoglobulin concentrations, except that IgM concentrations were slightly higher in the sewage workers. Some workers had serum transaminase concentrations in excess of normal; some of these returned to normal after the summer holiday. Among non-smokers a higher proportion of sewage treatment workers had increased amounts of FDP in urine. It is conceivable that the symptoms observed were caused by toxins from Gram negative bacteria.