Levels Of Fibrinogen Degradation Products Research Articles

Good or poor responses of hemostatic molecular markers in patients with hematopoietic disorders after treatment of disseminated intravascular coagulation.

Changes of hemostatic markers in 226 patients with disseminated intravascular coagulation (DIC) and hematopoietic disorders were examined after treatment of DIC. The changes in prothrombin time (PT) ratio, fibrinogen, fibrin and fibrinogen degradation products (FDP), antithrombin, and protein C, thrombin-antithrombin complex (TAT), plasmin-plasmin inhibitor complex (PPIC), and soluble fibrin monomer complex (SFMC) in all patients with DIC were significant during the clinical course of DIC, but those of D-dimer, thrombomodulin (TM), tissue factor (TF), and tissue factor pathway inhibitor (TFPI) were not. Activated partial thromboplastin time (aPTT) and PT were significantly longer in the poor response group than in good response group. Plasma levels of FDP, TAT, PPIC, SFMC, TM, and DIC score were significantly higher in poor response group than in good response. Protein C and antithrombin levels were significantly lower in poor response group than in good response group. The changes of PT ratio, fibrinogen, FDP, DIC score, antithrombin, plasmin inhibitor, and protein C were significant in the good response group, but these levels were not significant in the poor response group. The changes in plasma TAT and SFMC levels were significant in the good response group but were not in poor response group. The changes in D-dimer, TM, TF, or TFPI were not significant in both groups. These findings suggest that anticoagulant agents should be administered at levels below TAT 40 ng/mL or SFMC 300 microgram/mL in patients with DIC and hematopoietic disorders.

Coagulation/fibrinolysis abnormality and vascular endothelial damage in the pathogenesis of thrombocytopenic multiple organ failure.

Until recently, attention has been directed to disseminated intravascular coagulation as a cause of multiple organ failure (MOF). On the other hand, it has now become clear that humoral mediators play important roles in the pathogenesis of MOF. Therefore, we performed the present study in patients with thrombocytopenic MOF to investigate the relationship between various humoral mediators and vascular endothelial damage reported to be triggered by such humoral mediators in the pathogenesis of MOF. A retrospective clinical study. Intensive care unit of a university hospital. The study included 18 thrombocytopenic patients whose conditions progressed to septic MOF (MOF group) and 20 others who did not progress to MOF (non-MOF group). The MOF group and non-MOF group were also presented with infection and with platelet counts of <100,000/mm3. The MOF group had fibrinolysis abnormality, as indicated by increased plasminogen activator inhibitor-1 level. On the other hand, the MOF group had increased polymorphonuclear elastase and polymorphonuclear-mediated fibrinogen degradation product levels with consequent prolonged elevation of thrombomodulin. In addition, both polymorphonuclear elastase and polymorphonuclear-fibrinogen degradation products were significantly positively correlated with thrombomodulin in the MOF group, but no such positive correlation was observed between interleukin-6 or plasminogen activator inhibitor-1 and thrombomodulin. In the non-MOF group, on the other hand, thrombomodulin exhibited no significant positive correlation with polymorphonuclear elastase, polymorphonuclear-fibrinogen degradation products, interleukin-6, or plasminogen activator inhibitor-1. Our study provided evidence that vascular endothelial damage was the primary cause of organ failures in patients with thrombocytopenic MOF and that humoral mediators played a major role in the development of vascular endothelial damage in such patients. These results suggest that it is important to treat thrombocytopenic MOF as a condition of vascular endothelial damage, with weight placed on countermeasures against disorders of humoral mediators.

Acute chest pain 16 days after coronary artery bypass surgery: An unusual cause

J Thorac Cardiovasc Surg 2002;124:182-4

Biochemical and morphological alterations in lungs induced by experimental inhibition of fibrinolytic activity.

The fibrinolytic system is known to play an important role in the protection of lung architecture and function. This study investigated the effects on lungs of inhibiting the fibrinolytic system using tranexamic acid (TXA). Thirty cats were used, 15 experimental and 15 control. TXA was administered intravenously to the experimental animals for 3 h at 200 mg/kg (acute) and 7 days at 100 mg/kg (chronic). Blood samples were obtained from the carotid artery. The acute dose cats were sacrificed at 3 h and 24 h and the chronic dose cats at 8 days. Samples of inflated and fixed lung were examined morphologically and their collagen contents were determined. Fibrinolytic activity in blood samples was determined by fibrinogen degradation products levels, fibrin plate lytic area diameter, and the euglobulin lysis time. Hyperemia, lung interstitial oedema, haemorrhaging, inflammatory cell infiltration, pneumocyte type II cell proliferation, thrombosis and emphysema-related changes, characterized by enlargement of air spaces accompanied by destruction of alveolar walls, were observed in experimental cats group. None of these alterations except hyperemia and lung interstitial oedema were observed in two control animals. Electron microscopy results revealed oedema fluid in the interstitium, proliferation of pneumocyte type II cells, thickening of the alveolar septa and presence of marked amounts of collagen. Vacuoles were seen in the capillary endothelial cells. Elastic tissue was observed as elastic masses and partly disrupted, although elastic fibers were not prominent in all parts of the interstitium. Collagen content in the chronic dose experimental group was significantly higher than in all control and acute dose experimental groups. The inhibition of fibrinolytic system appears to have caused the emphysematous alterations, alveolar wall destruction and collagen accumulation possibly by causing microthromboses leading to mechanical blockage-ischemic changes, or by causing secondary fibrinolysis as a result of fibrin degradation products affecting local plasminogen activators and proteases. An injury-repair process also appears to have occurred.

Coagulation profile and platelet function in patients with extrahepatic portal vein obstruction and non-cirrhotic portal fibrosis.

Coagulation disorders commonly develop in patients with cirrhosis of the liver. They have also been reported in patients with non-cirrhotic portal fibrosis (NCPF) and extra-hepatic portal venous obstruction (EHPVO); the two conditions with portal hypertension and near-normal liver functions. The spectrum and prevalence of coagulation abnormalities and their association with the pathogenesis of these diseases and with hypersplenism was prospectively studied. Eighteen EHPVO patients that included an equal number of NCPF patients and 20 healthy controls were prospectively studied. The coagulation parameters assessed included: international normalized ratio, partial thromboplastin time, and fibrinogen and fibrinogen degradation products. Platelet aggregation and malondialdehyde levels were measured. Both EHPVO (83%) and NCPF (78%) patients had a significantly prolonged international normalized ratio and a decrease in fibrinogen and platelet aggregation. The EHPVO patients had a significant prolongation in partial thromboplastin time (67% patients), with increased levels of fibrinogen degradation product levels occurring in all patients; these were normal in NCPF patients. Platelet malondialdehyde levels were normal in both groups. Hypersplenism was present in four EHPVO and seven NCPF patients. It did not significantly influence the coagulation profile in either NCPF or EHPVO patients. Coagulation anomalies are common and significant in both NCPF and EHPVO patients, suggestive of a mild disseminated intravascular coagulation disorder. These imbalances could be caused by chronic subclinical endotoxemia and cytokine activation after the initial portal thromboembolic event. The persistence of these abnormalities in adolescent patients indicates an ongoing coagulation derangement.

Treatment of Acute Cerebral Infarction with Arginine Esterase: A Controlled Study with Heparin

Background and Purpose: There is no treatment proven to be of definitive benefit for ischemic stroke. Arginine esterase, a natural product from a snake venom, has been shown to reduce the serum fibrinogen level in human beings and may be useful in the treatment of ischemic stroke. In the present study, we compared the therapeutic effect of arginine esterase with that of heparin. Subjects and Methods: We studied 50 consecutive patients with acute ischemic stroke who were admitted to the Asan Medical Center. We randomly administered either arginine esterase 0.005 unit/kg × 2 times/day or heparin (activated partial thromboplastin time 2–3 times of baseline value) intravenously for 7 days. Antiplatelets were administered afterwards in both groups. Blood fibrinogen, fibrinogen degradation product (FDP) and D-dimer levels were measured at 0, 6, 12, 18 h and 1, 2, 3, 7 and 30 days after the onset of stroke. NIH stroke scale was measured daily by 2 neurologists while Barthel index and Rankin scale were assessed at 7 days and 1 month after the onset of stroke by a research nurse. All these investigators were blinded to the therapeutic regimen each patient received. Results: There were no significant differences in the mean age, gender proportion, stroke subtypes and baseline neurological severity between the two groups. One patient in the arginine esterase group died in an acute stage due to massive herniation and 1 in the heparin group underwent surgery for herniation. One (arginine esterase group) died of massive gastrointestinal bleeding due to previously unrecognized stomach cancer. Otherwise, no significant clinical and laboratory side effects were observed in both groups. In the arginine-esterase treated group, D-dimer and FDP levels were significantly (p < 0.05) elevated, and fibrinogen level significantly (p < 0.05) decreased at 2–7 days after the onset of stroke compared to the heparin-treated group. However, there was no significant difference in the neurological improvement reflected by NIH stroke scale, Barthel index and Rankin scale. Conclusion: Arginine esterase seems to be safe and has significant fibrinolytic effects when administered in the patients with acute ischemic stroke. However, in this preliminary study, it was not superior to heparin in terms of the improvement of neurological deficits. Further studies with larger doses and a larger number of subjects are required.

Coagulation and fibrinolysis disorder in muscular dystrophy

To investigate whether there are any basic abnormalities of coagulation and fibrinolysis in muscular dystrophy, we measured serum levels of the MM isozyme of creatine kinase (CK-MM), fibrin and fibrinogen degradation products (FDP), plasma levels of fibrinogen, antithrombin (AT), and D-dimer in 36 patients with Duchenne muscular dystrophy (DMD), 11 with Becker muscular dystrophy (BMD), 5 with Fukuyama congenital muscular dystrophy (FCMD), 5 with myotonic dystrophy (MyD), and 5 with spinal muscular atrophy (SMA) type 2. FDP levels were elevated in the patients with DMD, BMD, and FCMD (1.0 to 84.9 μg/ml), but not in the patients with MyD and SMA type 2. In DMD, BMD, and FCMD, FDP levels significantly correlated with CK-MM, but not with age, fibrinogen, AT, D-dimer, and type of dystrophy (multiple regression analysis; r2 = 0.814, P < 0.0001). These findings suggested that enhanced coagulation and fibrinolysis are associated with muscle degeneration in patients with DMD, BMD, and FCMD. © 2001 John Wiley & Sons, Inc. Muscle Nerve 24: 399–402, 2001

Coagulation and fibrinolysis disorder in muscular dystrophy

To investigate whether there are any basic abnormalities of coagulation and fibrinolysis in muscular dystrophy, we measured serum levels of the MM isozyme of creatine kinase (CK-MM), fibrin and fibrinogen degradation products (FDP), plasma levels of fibrinogen, antithrombin (AT), and D-dimer in 36 patients with Duchenne muscular dystrophy (DMD), 11 with Becker muscular dystrophy (BMD), 5 with Fukuyama congenital muscular dystrophy (FCMD), 5 with myotonic dystrophy (MyD), and 5 with spinal muscular atrophy (SMA) type 2. FDP levels were elevated in the patients with DMD, BMD, and FCMD (1.0 to 84.9 microg/ml), but not in the patients with MyD and SMA type 2. In DMD, BMD, and FCMD, FDP levels significantly correlated with CK-MM, but not with age, fibrinogen, AT, D-dimer, and type of dystrophy (multiple regression analysis; r(2) = 0.814, P < 0.0001). These findings suggested that enhanced coagulation and fibrinolysis are associated with muscle degeneration in patients with DMD, BMD, and FCMD.

PLATSAK, a Potent Antithrombotic and Fibrinolytic protein, Inhibits Arterial and Venous Thrombosis in a Baboon Model

Antiplatelet-antithrombin-staphylokinase (PLATSAK) is a chimeric protein that was recombinantly produced in Escherichia coli cells. The protein was designed to target haemostasis at three different levels. It consists of staphylokinase for activation of fibrinolyis, the Arg-Gly-Asp sequence for the prevention of platelet aggregation, and an antithrombotic peptide for the inhibition of thrombin. The in vivo activity of PLATSAK was evaluated by assessing its effect on platelet deposition in a baboon model of arterial and venous thrombosis. Dacron vascular graft segments and expansion chambers, inserted as extensions into permanent femoral arteriovenous shunts, were used to simulate arterial and venous thrombosis, respectively. PLATSAK (3.68 mg/kg) was administered as a bolus 10 minutes before placement of the thrombogenic devices. Platelet deposition onto the graft surface and in the expansion chamber was imaged in real time with a scintillation camera as the deposition of 111In-labeled platelets. After 2 hours, platelet deposition in the graft segments and expansion chambers was inhibited by 50% and 85%, respectively, when compared to control studies. The activated partial thromboplastin time was lengthened to greater than 120 seconds. Interestingly, the level of fibrinogen degradation products in plasma did not increase after administration of PLATSAK. These results demonstrate that PLATSAK effectively inhibited platelet deposition in both arterial- and venous-type thrombosis in an animal model.

Decreased tissue factor and tissue-plasminogen activator antigen in relapsed acute promyelocytic leukemia.

This study evaluated hemostatic data in 28 patients with newly diagnosed acute promyelocytic leukemia (APL) and 15 patients with relapsed APL. Activated partial thromboplastin time and prothrombin time were prolonged at initial onset of APL. Plasma level of fibrinogen was significantly decreased in patients with initial disease of APL, but it was not decreased significantly during the relapse of APL. Plasma fibrin and fibrinogen degradation products levels were significantly increased and platelet counts significantly decreased in both groups. Plasma levels of antiplasmin significantly decreased at initial onset but not during relapse. Plasma levels of antithrombin were within normal range in patients with initial disease but significantly decreased in those with relapse. Plasma levels of D-dimer, soluble fibrin monomer (sFM), plasmin-plasmin inhibitor complex (PPIC), and thrombin antithrombin complex (TAT) levels were significantly high in both groups. Plasma levels of PPIC, sFM, and D-dimer were significantly higher at initial onset of APL than during relapse. However, there was no significant difference in DIC score between patients with initial onset and those with relapse; plasma levels of tissue factor (TF) significantly increased in both groups, but they were significantly higher at initial onset of APL than during relapse. TF and tissue type plasminogen activator (t-PA) antigen levels in leukemic cell lysate were significantly increased in both groups, and they were significantly lower during relapse than at initial onset. Hemostatic abnormalities occurring in patients with relapsed APL might be the result of the decrease of TF and t-PA in leukemic cells. These findings suggest that DIC in APL patients with relapse might not be caused only by TF and t-PA and thus should be treated with different therapy from patients with initial onset of APL.

Effect of reteplase on hemostasis variables: analysis of fibrin specifity, relation to bleeding complications and coronary patency

The first aim of the present study was to characterize the systemic and fibrin-specific lytic effect of reteplase in the treatment of patients with acute myocardial infarction. The second aim was to investigate the relation of hemostasis variables to risk of bleeding complications and to coronary patency. The present study is a hemostatic substudy of the German Recombinant Activator Study. Forty two patients have been treated with 10 MU of reteplase (Group A) and 100 patients with 15 MU of reteplase (Group B), given as a single bolus. Blood samples for assessment of fibrinogen, plasminogen, alpha-2-antiplasmin, fibrinogen degradation products (FDP) and D-dimers were obtained before and at 2, 4, 8, and 24 h after thrombolytic therapy. The median fibrinogen concentration was decreased from 279 to 169 mg/dl in Group A and from 254 to 92 mg/dl in Group B four hours after administration of reteplase. The decrease in fibrinogen was significantly more pronounced in Group B ( P=0.0004). The median plasminogen concentration was decreased to 53% in Group A and to 33% in Group B two hours after administration of reteplase ( P=0.0001). Alpha-2-antiplasmin was reduced to 27% and 17,5%, respectively ( P=0.0007). D-Dimer levels were increased to 5.2 μg/ml in Group A and 11,6 μg/ml in Group B ( P=0.02) and FDP levels to 3.0 μg/ml in Group A and 12,6 μg/ml in Group B ( P=0.04). Patients with bleeding complications revealed significant lower nadir levels of fibrinogen than patients without bleeding complications (54 mg/dl versus 125.5 mg/dl, P=0.02). There was no significant difference in any hemostatic parameter between patients with patent and nonpatent infarct related arteries. Conclusions: Reteplase causes a moderate systemic lytic effect comparable with other relative fibrin specific thrombolytic agents. An increase in the dose from 10 to 15 MU is associated with a marked increase in both fibrin specific and systemic lytic effect. Patients with bleeding complications reveal significant lower nadir levels of fibrinogen than patients without bleeding complications. Determination of any hemostatic parameter seems to be no useful method to predict efficacy of thrombolysis in terms of coronary patency in the individual patient.

Ozone-Induced Airway Hyperresponsiveness in Patients With Asthma: Role of Neutrophil-Derived Serine Proteinases

Proteinase inhibitors may be of potential therapeutic value in the treatment of respiratory diseases such as chronic obstructive pulmonary disease (COPD) or asthma. Our aim was to study the role of neutrophils, and neutrophil-derived serine proteinases in an acute model in patients with asthma. Exposure to ozone induces an acute neutrophilic inflammatory reaction accompanied by an increase in airway hyperresponsiveness. It is thought that these two effects of ozone are linked, and that neutrophil-derived serine proteinases (i.e. elastase) may play a role in the ozone-induced airway hyperresponsiveness. Therefore, we examined the effect of recombinant antileukoprotease (rALP), one of the major serine proteinase inhibitors in the lung, on ozone-induced changes in airway hyperresponsiveness in this model. We observed that 16 h after exposure to ozone, airway hyperresponsiveness to methacholine was increased both following placebo and rALP treatment. There was no significant difference between placebo and rALP treatment (change in area under the dose-response curve to methacholine: 117.3 ± 59.0 vs 193.6 ± 59.6 %fallxDD; p = .12). Moreover, the immediate decrease in FEV 1 after ozone exposure was not significantly different between the two groups (placebo: −29.6 ± 6.7%; rALP: −20.9 ± 3.8%; p = .11). In addition, no significant differences were observed in plasma levels of fibrinogen degradation products generated by neutrophil serine proteinases before and after exposure to ozone. We conclude that neutrophil-derived serine proteinases are not important mediators for ozone-induced hyperresponsiveness.

Coagulopathies in Patients After Transurethral Resection of the Prostate

This prospective, randomized study evaluated the effects of spinal versus general anesthetic technique on perioperative blood loss and the development of postoperative coagulopathies in 50 patients undergoing transurethral resection of the prostate (TURP).Preoperative hematologic measurements included hemoglobin, platelet count, electrolytes, prothrombin time, partial thromboplastin time, fibrinogen, factor V, plasminogen, antithrombin III, and fibrinogen degradation product (FDP) levels. All hematologic blood samples were repeated postoperatively at 1, 6, and 24 h. Intraoperative blood loss was not significantly different between the spinal and general anesthesia groups. The total blood loss after TURP was significantly correlated (r = 0.76; P < 0.0001) with the prostatic tissue weight. When the tissue weight resected exceeded 35 g, blood loss was in excess of the linear correlation shown with the weight of resected prostatic tissue. Platelet count decreased and prothrombin time increased in the spinal group at all postoperative time intervals compared to preoperative value (P < 0.05). There was no significant difference in measured coagulation variables (fibrinogen, factor V, plasminogen, antithrombin III, and FDP) between the spinal and general anesthesia groups, but there were significant decreases in postoperative fibrinogen and Factor V levels compared to preoperative values in both spinal and general anesthesia groups. Three patients (6%) had increased FDP levels 1 h postoperatively. The prostatic tissue weight and the surgical duration was significantly higher in these patients. We conclude that perioperative blood loss in TURP patients is not affected by the anesthetic technique. However, 6% of TURP patients developed subclinical intravascular coagulopathies which correlated with mass of resected prostate tissue. (Anesth Analg 1995;81:680-5)

Assessment of Relative Contributions of Fibrinolysis and Fibrinogenolysis to the Abnormalities of Plasma Fibrinogen/Fibrin-Retated D and E Antigens and Their Ratio in Liver Cirrhosis

Many pathogenic mechanisms play a part in hemorrhage in chronic liver disease. This study was done to characterize the alterations of fibrinogen components and dysfibrinogenemia in patients with liver cirrhosis. Plasma from 31 patients with liver cirrhosis was analyzed to determine the fibrinogen/fibrin-related D and E antigens by latex photometric immunoassay; fibrinogen by the Clauss method; fibrinogen degradation product (FgDP), protein C antigen, and tissue plasminogen activator (tPA) by enzyme immunoassay; and antithrombin III by the colorimetric method, respectively. Reptilase, time and fibrin monomer (FM) tests were also done. Fibrinogen/fibrin-related D and E antigens were higher and their ratio (D/E) was lower in liver cirrhosis compared with normal subjects. Fibrinogen levels were inversely correlated with D (p = 0.0001) and E (p = 0.0001) antigenic levels in plasma. FgDP levels were not significantly correlated with D and E levels. However, semiquantitative D-dimer levels had significant association with D and E levels. Reptilase time was abnormally prolonged in all patients with high D and E levels, and FM tests were also positive in most patients with increased levels of D and E. Protein C antigen levels were inversely correlated with D (p = 0.0110) and E (p = 0.0112) concentrations but were well correlated with clottable fibrinogen concentrations (p = 0.0058). Hypercoagulability followed by pathologic activation of fibrinolysis, rather than synthesis of abnormal fibrinogen molecules, may contribute to hemorrhage. Not only true hypofibrinogenemia due to the decreased synthesis of intact fibrinogen but also elevated levels of these antigens may be clinically significant in the treatment of cirrhotic patients at risk of bleeding. Protein C may play an important regulatory role in fibrinolysis.

Measuring plasma fibrinogen levels in patients with liver cirrhosis. The occurrence of proteolytic fibrin(ogen) degradation products and their influence on several fibrinogen assays

In patients with liver cirrhosis the fibrinogen molecule is under constant attack of various proteolytic enzymes, which might affect results of the different assay systems for fibrinogen. We therefore studied the measurement of fibrinogen in the plasma of patients with mild, moderate and severe cirrhosis of the liver. Fibrinogen levels were measured with the Clauss method (functional fibrinogen); an enzyme immuno assay (EIA) for HMW + LMW fibrinogen; and an assay that measures the total clottable fibrinogen. With all three methods we found normal or slightly increased fibrinogen levels in patients with mild or moderate cirrhosis, whereas patients with severe cirrhosis had decreased levels. No evidence was found for increased partial fibrinogen proteolysis, resulting in increases of LMW'-fibrinogen in cirrhotic patients. We further observed that fibrinogen degradation products levels increased slightly with the severity of the disease, but were still in the normal range in patients with severe cirrhosis. This indicates a very low level of primary fibrinolysis. Fibrin degradation products levels increased much stronger, which points to intravascular coagulation. The levels of the fibrin degradation products remained below the level where they are expected to influence the Clauss assay. In patients with liver cirrhosis the measurement of plasma fibrinogen levels with the three studied methods give comparable results. We suggest to apply the Clauss assay in cirrhotic patients because of this and because it has a good reproducibility and because the test is cheap, quick and easy to perform.

Markers of coagulation and fibrinolysis in blood drawn into citrate with and without D-Phe-Pro-Arg-Chloromethylketone (PPACK)

In order to compare levels of Prothrombin Fragment 1+2 (F 1+2), Thrombin-antithrombin III complex (TAT), Fibrinogen Degradation Products (FgDP) and Fibrin Degradation Products (FbDP) in plasma from blood drawn into sodium citrate with and without the protease inhibitor D-Phe-Pro-Arg-Chloromethylketone (PPACK), blood samples were collected from 41 patients on the first day after elective gastric surgery. Levels of F 1+2, TAT and FbDP were not significantly different in plasma with and without PPACK. FgDP levels were significantly higher in plasma with PPACK. Our results did not support previous suggestions that PPACK should be used as a routine anticoagulant for measurement of haemostatic activation products.

Quantitative immunological determination of human fibrin- and fibrinogen-degradation products (FDP) in plasma with an antibody against a synthetic peptide

A new method has been developed for the quantitative determination of fibrin - and fibrinogen degradation products (FDP) in plasma. An epitope on the γ-chain of fibrin(ogen) hidden in intact molecules is exposed in fragments E after cleavage by plasmin. A synthetic peptide of this new carboxy terminus has been used for immunization of rabbits. Antibodies isolated by immunoabsorption against a partial sequence of this peptide did not react with intact fibrinogen or fibrin, but recognized equally well all fragments E liberated from fibrinogen (AABB-E,), cross-linked (E, and E 2) and non cross-linked fibrin (E 2). In a sandwich-type enzyme immunoassay, the antibodies obtained were used for coating of microtitration plates, and polyclonal anti-E antibodies coupled to peroxidase for detection of bound FDP. The validity of the assay was investigated by incubation of normal and α 2-antiplasmin depleted plasma with plasmin. Only in the α 2-antiplasmin depleted plasma a significant and steady increase of FDP levels was detectable, reflecting in vitro generation of FDP. Since fragments E are only liberated by action of plasmin, the assay via quantification of FDP reflects free plasmin activity in vivo.

Fibrinogen and Fibrinogen Degradation Product Levels in Thromboangiitis Obliterans

Fibrinogen and fibrinogen degradation product levels were estimated in 20 patients with thromboangiitis obliterans and compared with those in healthy smokers and patients with other peripheral vascular diseases. The presence of increased fibrinogen levels in patients with thromboangiitis obliterans raises the possibility of its being a risk factor in the pathogenesis of Buerger's disease.

The fibrinogen degradation products (FgDP) levels in liver disease.

We measured plasma levels of fibrinogen degradation products (FgDP) with newly developed enzyme-linked immunosorbent assay based on monoclonal antibody to assess the fibrinogenolytic state in 52 patients with various liver diseases (27 patients with liver cirrhosis, 10 with chronic hepatitis, 7 with acute hepatitis, 6 with hepatocellular carcinoma, 2 with intrahepatic cholestasis). As compared with 20 healthy subjects (upper limit: 580 ng/ml), elevated plasma levels (660-32000 ng/ml) of FgDP were found in 19 (36.5%) patients. When analyzed according to the underlying disease categories, the magnitude of elevations of FgDP were most prominent in patients with chronic hepatitis. No correlation was found between plasma FgDP levels and serum AST or ALT activity. These findings indicate that increased primary fibrinogenolysis is not rare in liver disease, but poorly correlates with liver function.

In vitro studies on PMN-independent endothelial cell damage in trauma: decrease of PMN-endothelial cell adherence by fibrinogen degradation products and disturbance of endothelial cell membrane integrity by trauma serum.

Trauma favors the development of adult respiratory distress syndrome (ARDS). Adherence of polymorphonuclear leukocytes (PMN) to endothelial cells (EC) with subsequent EC damage by the respiratory burst products and proteases of the PMN is thought to be one of the basic mechanisms in the pathogenesis of ARDS. Recent studies have shown that there might also be PMN-independent mechanisms of EC damage. It would speak for PMN-independent EC damage if in the state of risk for this damage factors were found which decrease PMN activity or if EC damage appeared without PMN. Because in trauma and sepsis pathologic coagulation with high levels of fibrinogen degradation products (FDP) is often diagnosed, we investigated whether FDP-D and FDP-E might influence PMN adherence to EC. We also investigated whether serum of traumatized patients might provoke EC damage in a PMN-independent system in vitro. To achieve this we evaluated the viability of EC using a fluorescence staining method. We found that both FDP-D and FDP-E decreased PMN adherence to human EC significantly (p < 0.01) at a concentration of 50 micrograms/ml. Furthermore we found that EC membrane integrity can be disturbed by serum of trauma patients. These results suggest that in trauma also PMN-independent mechanisms are important for EC damage.