Fibrin/fibrinogen Degradation Products Research Articles

High-Altitude Pulmonary Edema Is Associated With Coagulation and Fibrinolytic Abnormalities

ObjectivesHigh-altitude pulmonary edema (HAPE) can develop in unacclimatized persons after acute ascent to high altitude and is associated with fibrinolytic and coagulation abnormalities. The authors investigated whether fibrinolytic and coagulation abnormalities were associated with the severity of HAPE. MethodsSixty-one patients who developed HAPE after acute ascent to altitudes above 3600m were recruited. Twenty unacclimatized controls who acutely ascended to the same altitude and 20 acclimatized inhabitants served as controls. Tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) levels were measured using chromogenic substrate assays. Plasma fibrinogen concentration was determined by the sodium sulphite fractionation method. The concentrations of fibrin/fibrinogen degradation products (FDP) and D-dimer were measured by enzyme linked immunosorbent assay. ResultsThe plasma concentrations of D-dimer, fibrinogen, FDP and t-PA and PAI-1 were significantly higher in patients with HAPE than controls. In addition, these abnormalities were correlated with the severity of HAPE. The plasma concentrations of D-dimer and fibrinogen recovered to normal upon recovery from HAPE while t-PA, PAI-1 and FDP levels in HAPE patients still remained significantly increased over those of unacclimatized controls. ConclusionThe development of HAPE is associated with abnormalities in the fibrinolysis and coagulation system, and these abnormalities correlate with the severity of HAPE.

Diagnostic values of urine CYFRA21-1, NMP22, UBC, and FDP for the detection of bladder cancer

BackgroundWe compared the diagnostic utilities of CYFRA 21‐1, nuclear matrix protein-22 (NMP22), urinary bladder cancer antigen (UBC), and fibrin/fibrinogen degradation products (FDP) for detecting urinary bladder cancer. MethodsWe assayed CYFRA 21‐1, NMP22, UBC and FDP from urine samples for 250 subjects. Among them, 54 were diagnosed as bladder cancer, and the remaining 196, which consisted of healthy individuals and patients with hematuria, inflammation/infection, or benign prostate hyperplasia, were assigned to the control group. ResultsUrinary levels of all 4 markers were higher in the bladder cancer group than the control group. The areas under the receiver operating characteristic curves (ROC-AUCs) of CYFRA 21‐1, NMP22, UBC and FDP, corrected with urine creatinine concentrations, were 0.90, 0.89, 0.80 and 0.77, respectively, for discriminating bladder cancer from controls. The ROC-AUCs for the combinations of the markers were not significantly higher than those with CYFRA 21‐1 or NMP22. NMP22 was the only independent variable for predicting bladder cancer among the four markers in the multivariate analysis. ConclusionsAll 4 tumor biomarkers exhibited diagnostic utility for predicting bladder cancer. Among them, CYFRA 21‐1 and NMP22 were the most effective at predicting bladder cancer.

Haemostatic and inflammatory responses to blood flow‐restricted exercise in patients with ischaemic heart disease: a pilot study

Low-intensity resistance exercise can effectively induce muscle hypertrophy and increases in strength when combined with moderate blood flow restriction (BFR). As this type of exercise does not require lifting heavy weights, it might be a feasible method of cardiac rehabilitation, in which resistance exercise has been recommended to be included. Although previous studies with healthy subjects showed relative safety of BFR exercise, we cannot exclude the possibility of unfavourable effects in patients with cardiovascular disease. We therefore aimed to investigate haemostatic and inflammatory responses to BFR exercise in patients with ischaemic heart disease (IHD). Nine stable patients with IHD who were not taking anticoagulant drugs performed four sets of knee extension exercise at an intensity of 20% one-repetition maximum (1RM) either with or without BFR. Blood samples were taken before, immediately after and 1 h after the exercise session and analysed for noradrenaline, D-dimer, fibrinogen/fibrin degradation products (FDP) and high-sensitive C-reactive protein (hsCRP). Plasma noradrenaline concentration increased after the exercise, and the increase was significantly larger after the exercise with BFR than without BFR. On the other hand, increases in concentrations of plasma D-dimer and serum hsCRP were independent of the condition. However, increases in D-dimer and hsCRP were no longer observed after plasma volume correction, suggesting that hemoconcentration was responsible for these increases. Plasma FDP concentration did not change after the exercise. These results suggest that applying BFR during low-intensity resistance exercise does not affect exercise-induced haemostatic and inflammatory responses in stable IHD patients.

Study of Hemostatic Biomarkers in Acute Ischemic Stroke by Clinical Subtype

We studied the usefulness of hemostatic biomarkers in assessing the pathology of thrombus formation, subtype diagnosis, prognosis in the acute phase of cerebral infarction, and differences between various hemostatic biomarkers. Our study included 69 patients with acute cerebral infarction who had been hospitalized within 2 days of stroke onset. Fibrin monomer complex (FMC), soluble fibrin (SF), D-dimer, thrombin-antithrombin III complex, fibrinogen, antithrombin III, and fibrin/fibrinogen degradation products (FDPs) were assayed as hemostatic biomarkers on days 1, 2, 3, and 7 of hospitalization. In the cardioembolic (CE) stroke group, FMC and SF levels were significantly higher on days 1 and 2 of hospitalization, and D-dimer levels were significantly higher on day 1 of hospitalization, compared to the noncardioembolic (non-CE) stroke group. FDP levels were significantly higher at all times in the CE group compared to the non-CE group. Neither the National Institute of Health Stroke Scale (NIHSS) used during hospitalization nor the modified Rankin Scale (mRS) used at discharge found any significant correlations to hemostatic biomarkers, but the NIHSS score during hospitalization was significantly higher in the CE group than in the non-CE group. Measurements of hemostatic biomarkers, such as FMC, SF, and D-dimer on the early stage of cerebral infarction are useful for distinguishing between CE and non-CE stroke.

Effects of Two Tetrahydroisoquinolines (YS-49 and YS-51) on Experimental Disseminated Intravascular Coagulation Induced by Lipopolysaccharide in Rats

Disseminated intravascular coagulation (DIC) is a pathological syndrome, which occurs following the uncontrolled widespread activation of blood coagulation, resulting in the intravascular formation of fibrin, which may lead to thrombotic occlusion of small and midsize vessels. The effects of 1-(alpha-naphthylmethyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (YS-49, CAS 132836-42-1) and 1-(beta-naphthylmethyl)-6,7-dihydroxy-1,2,3,4-tetra-hydroisoquinoline (YS-51, CAS 213179-96-5) on the experimental DIC induced by lipopolysaccharide (LPS) in rats, were investigated. The oral administration of YS-49 and YS-51 (10 or 50 mg/kg) attenuated the dramatic increase of serum fibrinogen/fibrin degradation product (FDP) level, the decrease of plasma fibrinogen concentration and the number of platelets in blood and the prolongation of prothrombin time (PT) and activated partial thromboplastin time (aPTT) induced by LPS. The liver and kidney function parameters, aspartate amino-transferase (AST) and blood urea nitrogen (BUN), were also improved with YS-49 and YS-51. The above results suggest that YS-49 and YS-51 have therapeutic potential for DIC and/or accompanying multiple organ failure.

Evaluation of latex agglutination tests for fibrin–fibrinogen degradation products in the forensic identification of menstrual blood

The identification of menstrual blood is important when discriminating menstruation from vaginal trauma in sexual assault cases. The aim of this study was to evaluate two fibrin–fibrinogen degradation product (FDP)-latex agglutination test kits, FDPL® Test (FDP-L) and FDP Plasma “RD” (FDP-P), for their ability to forensically identify menstrual blood. Sensitivity and specificity of the two kits were compared for menstrual blood and various body fluids, and the sensitivity of the FDP-latex agglutination test kit was also compared with that of an immunochromatographic test for human hemoglobin. The robustness of the FDP-latex agglutination test was compared with that of gene expression analysis of menstrual blood specific markers. The FDP-L kit was more sensitive than the FDP-P kit, but it cross-reacted with peripheral bloodstains from healthy volunteers. The FDP-P kit was specific for menstrual blood, with the exception of postmortem blood samples, and was not affected by other body fluids. In an FDP-negative menstrual blood sample, the sensitivity of human hemoglobin detection was lower than for FDP-positive samples and peripheral blood stains, suggesting that determination of human hemoglobin could be useful in interpreting negative results in the FDP-latex agglutination test. In menstrual blood samples incubated in wet conditions, FDP was found to be a robust marker in the identification of menstrual blood compared with mRNA markers. FDP-P testing was shown to be a suitable and highly efficient rapid screening test for the laboratory identification of menstrual blood.

The relationship among the D-dimer,C-reactive protein and left tatrial diameter in the patients with atrial fibrillation

Objective To investigate the relationship among the D-dimer,C-reactive protein and left atrial diameter in the patients with atrial fibrillation(AF). Methods 53 AF patients were selected,the control group consisted of 32 cases of sinus rhythm(SR). The levels of D-dimer, CRP and LAD in AF group were compared with each other, and with those in the control group. Correlation analysis between D-dimer, CRP and LAD were made.Results D-dimer,CUP and LAD in AF group were significantly different from those in SR group. D-dimer and CRP in persistent AF and permanent AF differed significantly from that in SR and paraxymal AF. LAD in the group of persistent AF differed from that in SR group. LAD in permanent AF was significantly different from that in paraxymal AF and SR. Positive linear correlations were found between D-dimer, CRP and LAD in AF (r=0.376; 0.33).Conclusion Hypercoagulable state existsed in AF; the elevation of CRP should be the result and related to persistence time of AF. Positive correlation existsed between LAD and hypercoagulable state and inflammatory reaction. Key words: Atrial fibrillation; Fibrin fibrinogen degradation products; C-reactive protein; Atrial function,left

新しいモノクローナル抗体(D-DE72)を用いたELISA法による高感度の尿中FDPD-dimer定量の意義

In order to clarify the abnormalities of the coagulation and fibrinolysis system in patients with various renal diseases, we produced a new monoclonal antibody for FDP (fibrin/fibrinogen degradation product) D-dimer (D-D E72). We also established a new highly sensitive method of enzyme-linked immunosorbent assay (ELISA) for urinary FDP D-dimer using this monoclonal antibody. The urine from 110, patients with various renal diseases was investigated for the FDP D-dimer. The results are summarized as follows: 1) Urinary FDP D-dimer in normal subjects was 0.69 +/- 0.60 ng/ml. 2) The level of urinary FDP D-dimer in patients with primary nephrotic syndrome and in patients with chronic renal failure was significantly higher than that of normal subjects, whereas the urinary FDP D-dimer levels in patients with diabetes mellitus were higher than those of normal subjects. 3) In the CGN and NS groups there was a tendency for an increase in the level of urinary FDP D-dimer in more active forms of the disease. 4) A significant correlation between urinary FDP D-dimer and urinary protein in the CGN and NS groups was demonstrated. 5) In all of the renal diseases investigated in this study, the ratio of urinary FDP D-dimer to total FDP was less than 4%.

Endogenous plasma activated protein C levels and the effect of enoxaparin and drotrecogin alfa (activated) on markers of coagulation activation and fibrinolysis in pulmonary embolism

IntroductionThere are no published data on the status of endogenous activated protein C (APC) in pulmonary embolism (PE), and no data on the effect of drotrecogin alfa (activated) (DAA) given in addition to therapeutic dose enoxaparin.MethodsIn this double-blind clinical trial, 47 patients with computed tomography (CT)-confirmed acute submassive PE treated with 1 mg/kg body weight of enoxaparin twice daily were randomized to groups receiving a 12-hour intravenous infusion of 6, 12, 18, or 24 μg/kg/hour of DAA or a placebo. Blood samples were drawn before starting DAA infusion, after 4, 8 and 12 hours (at the end of the infusion period), and on treatment days 2, 3, 4, 5 and 6.ResultsInitial endogenous plasma activated protein C (APC) levels were 0.36 ± 0.48 ng/ml (<0.10 to 1.72 ng/ml) and remained in the same range in the placebo group. APC levels in patients treated with DAA were 13.67 ± 3.57 ng/ml, 32.71 ± 8.76 ng/ml, 36.13 ± 7.60 ng/ml, and 51.79 ± 15.84 ng/ml in patients treated with 6, 12, 18, and 24 μg/kg/hour DAA, respectively. In patients with a D-dimer level >4 mg/L indicating a high level of acute fibrin formation and dissolution, DAA infusion resulted in a more rapid drop in soluble fibrin, D-dimer, and fibrinogen/fibrin degradation products (FDP) levels, compared to enoxaparin alone. There was a parallel decline of soluble fibrin, D-dimer, FDP, and plasmin-plasmin inhibitor complex (PPIC) in response to treatment with enoxaparin ± DAA, with no evidence of a systemic profibrinolytic effect of the treatment.ConclusionsIn patients with acute submassive PE endogenous APC levels are low. DAA infusion enhances the inhibition of fibrin formation.Trial registrationClinicalTrials.gov: NCT00191724

Factor V Leiden mutation enhances fibrin formation and dissolution in vivo in a human endotoxemia model

Disseminated intravascular coagulation in sepsis is associated with microvascular thrombosis and organ dysfunction. It was expected that prothrombotic disposition such as factor V Leiden (FVL) mutation would worsen clinical outcome. Astonishingly, clinical trial and animal experimental data indicate that FVL can be associated with improved survival. This study investigated the effect of FVL on the response to endotoxin of the coagulation and fibrinolytic system in humans. Fourteen healthy male subjects without FVL and 15 healthy males with heterozygous FVL received an intravenous bolus dose of endotoxin, 2 ng/kg of body weight. Blood samples were drawn before and 1, 2, 4, 6, and 24 hours after administration of the endotoxin. Injection of endotoxin led to a more pronounced increase in soluble fibrin in patients with FVL than in controls. Patients with FVL displayed a more sustained increase in plasmin-plasmin inhibitor complex after 4, 6, and 24 hours. Patients with FVL mutation also displayed higher levels of D-dimer and fibrinogen-fibrin degradation products in plasma after 24 hours. Patients with FVL generate higher levels of soluble fibrin, which may serve as cofactor in tissue plasminogen activator-induced plasminogen activation, leading to a more sustained activation of fibrinolysis with production of more fibrinogen- and fibrin-degradation products.

Measurement of urinary fibrin/fibrinogen degradation products by latex photometric immunoassay.

Intraglomerular coagulation and fibrinolysis could be involved in the exacerbation of renal diseases, and urinary fibrin/fibrinogen degradation products (FDP) may be applicable as an index. Although the urinary FDP can be estimated by the latex agglutination method, this technique has disadvantages such as a poor sensitivity and is of the semiassay type. Recently, a new method of measurement which improves on these disadvantages, termed the latex photometric immunoassay (LPIA) method, has been developed. However, since FDP measurement by LPIA was designed for the purpose of serum FDP estimation, a measurement technique for urinary FDP has not yet been established. The purpose of the present study was to devise a measurement procedure for urinary FDP employing the LPIA method, and to obtain data on the normal levels of urinary FDP in healthy subjects. The results obtained may be summarized as follows. (1) The urinary pH and coexistent substances such as bovine serum albumin, glucose, urea, bilirubin, ascorbic acid, and hemoglobin, did not influence the urinary FDP measurement. (2) No changes in urinary FDP were observed after 28-day storage at -20 degrees C or -80 degrees C in the presence or absence of tranexamic acid. (3) The coefficient of variation was 5.3%. (4) The normal level of FDP excretion was 3.33 +/- 7.95 micrograms/day. The present data demonstrated that the LPIA method enables the urinary FDP to be measured quantitatively with a good sensitivity.

Fibrinogen/Fibrin Degradation Products in Acute Aortic Dissection

The elevated D-dimer value is one of the clues used to diagnose acute aortic dissection (AAD), but the rapid D-dimer assay is not used at all emergency hospitals. The fibrinogen/fibrin degradation products (FDP) value is also an indicator of enhanced fibrinolysis and may therefore be a useful marker in patients with AAD. In addition, the association between FDP values and partial thrombosis of the false lumen is not elucidated. The present study enrolled 50 patients (66.5±11.2 years of age; median, 66.5 years of age, male subjects comprised 60.0% of the series) with AAD who were admitted to the hospital between July 2005 and December 2007 and 57 patients with acute myocardial infarction (AMI; 70.8±10.4 years of age; median, 71.0 years of age, male subjects comprised 71.9% of the current series) served as a control group. The FDP values (µg/mL) in patients with AAD were significantly higher than those of AMI patients (40.2±78.6; median, 14.7 vs. 5.2±9.8; median, 1.7, p<0.001). A receiver operating characteristic curves analysis showed that an elevated FDP level (2.05 µg/mL) was predictive of a diagnosis of AAD with a sensitivity and specificity of 98% and 54%, respectively. The FDP levels of patients (n=14) who had partial thrombosis of the false lumen were significantly higher than in discharged patients without a surgical repair (n=21) who had a patent or complete thrombosis of the false lumen (35.8±43.2; median, 18.8 vs. 14.0±21.3; median, 5.5, p=0.01). The measurement of FDP may therefore be useful for the initial assessment of patients with suspected AAD and in the prediction of thrombotic status of the false lumen.

Clinical Use of D-Dimer Measurement for the Diagnosis of Disseminated Intravascular Coagulation in Dogs

We measured the plasma D-dimer (DD) concentration in 205 dogs. Simultaneously, fibrinogen/fibrin degradation products (FDPs) concentration, platelet (PLT) count, prothrombin time (PT), activated partial thromboplastin time (APTT), and plasma concentrations of fibrinogen (Fib) were measured in the same dogs. From these results, we were able to divide the animals into four groups: control (healthy dogs, n=18), pre-disseminated intravascular coagulation (preDIC) (n=20), disseminated intravascular coagulation (DIC) (n=21), and other (n=146). Significant differences in plasma DD concentration were found among the four groups: control, 0.45 ± 0.46 µg/ml (reference range, 0-1.37); preDIC, 5.0 ± 4.8 µg/ml; DIC, 16.3 ± 12.2 µg/ml; and other, 1.5 ± 2.7 µg/ml. A weak positive correlation (r=0.62) was found between FDPs and DD concentrations in the DIC group. As a DIC diagnostic test, the PLT/APTT/FDPs/DD combination had the highest accuracy of 100%, with a sensitivity of 73% and a specificity of 97%. We propose the use of FDPs and DD concentrations as part of the DIC diagnostic test panel, with DD and FDPs to provide accurate diagnosis.

The relationship between high level of FDP (fibrin/fibrinogen degradation products) on the admission and massive bleeding in patients with blunt trauma

背景：鈍的外傷による早期の死亡は大量出血によるものが大半である。その原因として，臓器損傷や血管損傷による直接的な出血と凝固障害を原因とする出血の2つの側面がある。今回，鈍的外傷患者では治療開始前の搬入直後に線溶亢進が認められ，その線溶亢進が凝固障害による大量出血と関係があるとの仮設を立て，受傷現場から直接搬入された鈍的外傷患者を対象に搬入直後の凝固線溶系の検査結果と大量出血の関係を後ろ向きに検討した。方法：2005年1月1日から2006年12月31日の間に，受傷現場から北海道大学病院先進急性期医療センターに直接搬入となったabbreviated injury scaleが3以上の損傷を含む鈍的外傷症例を対象とした。対象患者の診療録から，患者背景，搬入直後の血液検査結果，輸血量などの情報を後ろ向きに収集し，大量出血群と非大量出血群に分類した。結果：83名が参入基準を満たした。大量出血群は17症例，非大量出血群66症例であった。fibrin/fibrinogen degradation products（FDP）とD-dimerに関しては，両群とも著明な高値を示し，大量出血群が非大量出血群と比較して統計学的な有意差を認めていた。ロジスティック回帰分析ではFDPのみが大量出血の独立した予測変数として選択された。大量出血予測に関するreceiver operating characteristic曲線では，FDPが最も大きな曲線下面積を示した。結語：鈍的外傷患者では，搬入直後にフィブリン/フィブリノゲン分解に伴うFDPの異常高値を示しており，FDP>64.1μg/mlをカットオフ値とすることで，外傷早期の線溶亢進を原因とする大量出血を予測しうることを示した。鈍的外傷患者の搬入直後のFDP値に注目することにより，外傷早期の凝固障害に対して速やかに対応できる可能性がある。

Disseminated intravascular coagulation with a fibrinolytic phenotype at an early phase of trauma predicts mortality

Introduction Disseminated intravascular coagulation (DIC) with an antifibrinolytic phenotype is characterized by microvascular thrombosis leading to poor outcome at the late-stage of trauma. To test the hypothesis that DIC with a fibrinolytic phenotype at an early stage of trauma also contributes to a poor outcome due to severe bleeding, we conducted a retrospective, cohort study. Materials and Methods The subjects included 314 consecutive severe trauma patients. A systematic review of medical records of the patients was conducted to provide the base line characteristics and DIC-related variables. The data of these variables were obtained at 4 time points within 24 hr after arrival to the emergency department (ED); Time Point 1, immediately after arrival to the ED to 4 hr after arrival; Time Point 2, 4 to 8 hr after arrival; Time Point 3, 8 to 16 hr after arrival; Time Point 4, 16 to 24 hr after arrival. Results Nonsurvivors (87.3%, 48/55) met the Japanese Association for Acute Medicine (JAAM) DIC criteria showing lower fibrinogen levels, a prolonged prothrombin time, and higher fibrin/fibrinogen degradation products (FDP) and D-dimer levels in comparison to those of the 289 survivors. The FDP/D-dimer ratio and lactate level were significantly higher in the nonsurvivors than those of the survivors. Lower fibrinogen levels and higher FDP/D-dimer ratio suggest fibrinogenolysis in DIC of the nonsurvivors. Furthermore a stepwise logistic regression analysis showed that the JAAM DIC score, levels of fibrinogen, FDP and lactate at Time Point 1 are independent predictors of death. Low levels of fibrinogen and high FDP but not D-dimer predict massive bleeding at an early stage of trauma. The optimal cutoff points for the prediction of death and massive bleeding were fibrinogen (1.90, 1.90 g/L) and FDP (35.2, 68.7 mg/L), respectively. Conclusions DIC with a fibrinolytic phenotype modified through fibrinogenolysis at an early phase of trauma contributes to poor prognosis due to massive bleeding. Tissue hypoperfusion may be involved in the pathogenesis of this type of DIC.

Fibrin-fibrinogen degradation products in cerebrospinal fluid as an indicator of neonatal brain damage.

The occurrence of brain damage in 57 full term neonates was investigated. The infants were submitted to a prospective protocol involving clinical (neurological and electroencephalographical) and biological examinations, including the determination of the fibrin-fibrinogen degradation products in the blood and cerebrospinal fluid on D1, D3, D8 and D15. Psychomotor events were followed up for a year. Traumatic lumbar taps did not disturb the results significantly. Blood samples were not found to contain noticeable amounts of FDP. Conversely, the existence of FDP in CSF was not infrequent near to delivery and was shown to be closely related to brain damage as evaluated by the psychomotor events.

Novel recombinant fibrinogenase of Agkistrodon acutus venom protects against LPS-induced DIC

Introduction Disseminated intravascular coagulation (DIC) is an acquired syndrome characterized by the widespread activation of coagulation. This leads to failure of multiple organs in the body and finally death. Because there is no effective therapy for DIC, the clinical prognosis is poor and the mortality is high. Materials and Methods The animals were intravenously injected with Lipopolysaccharide (LPS) for 6 hours and simultaneously infected three doses of recombinant fibrinogenase II (rFII) for 2 hour. Activated partial thromboplastin time (APTT), prothrombin time (PT), platelets count, fibrinogen and fibrin-fibrinogen degradation products (FDP) were determined. The plasma levels of alanine aminotransferase (ALT), creatinine (Cr) and tumor necrosis factor-α (TNF-α) were detected. Liver and kidney samples were stained with hematoxylin-eosin and kidney sections were stained with phosphotungstic acid-hematoxylin. Results We observed that rFII increased survival rate in LPS-induced DIC rabbits as well as heparin did. Administration of rFII as well as heparin attenuated the increased plasma levels of APTT, PT and FDP and the decreased plasma level of fibrinogen at 6 h. rFII reduced hepatic and renal damages and decreased the levels of ALT and Cr as well as heparin did. rFII also significantly reduced the increased plasma levels of TNF-α. rFII significantly reduced the kidney fibrin deposits with respect to LPS treated animals. Conclusions Our findings suggest that rFII from Agkistrodon acutus venom could have protective effect on DIC via reducing liver and renal damages and direct degradation of microthrombi.

Usefulness of Fibrinogen/Fibrin Degradation Product to Predict Poor One-Year Outcome of Medically Treated Patients With Acute Type B Aortic Dissection

Previous studies have indicated that medical therapy provides excellent outcomes for patients with uncomplicated Stanford type B acute aortic dissection. However, affected aortas are often compromised by aneurysmal dilatation and rupture, resulting in poor outcomes. The purpose of this study was to determine predictors of aortic events in patients with Stanford type B acute aortic dissection receiving conservative medical therapy. The study group consisted of 78 consecutive patients with Stanford type B acute aortic dissection who were admitted to the hospital within 48 hours of onset. These patients were treated medically and followed up for 1 year. Aortic events were defined as rupture, recurrent dissection, aortic expansion with diameter>or=60 mm, rapid aortic expansion at a rate of >or=10 mm/yr, and the development of visceral or limb ischemia. Predictors of these events were determined using multivariate analyses. During 1-year follow-up, aortic events were observed in 13 (17%) patients, including aortic rupture in 3 (4%), aortic diameter>or=60 mm in 4 (5%), rapid expansion of the aorta in 3 (4%), and the development of visceral or limb ischemia in 3 (4%). On multivariate analysis, fibrinogen-fibrin degradation product level>or=20 microg/ml (odds ratio 7.802, 95% confidence interval 1.405 to 43.335) on admission was the only independent predictor of aortic events at 1 year. In conclusion, careful monitoring is required for patients with medically treated Stanford type B acute aortic dissection associated with fibrinogen-fibrin degradation product level>or=20 microg/ml on admission.

Fibrinolytic system of the armadillo Chaetophractus villosus (Xenarthra, Dasypodidae)

The fibrinolytic mechanism in the armadillo Chaetophractus villosus (Mammalia, Xenarthra, Dasypodidae) quite unknown until now was studied. Results were compared with those corresponding to healthy adult human beings. Whole blood lysis time and diluted blood lysis time were not detectable in armadillos. Euglobulin clot lysis time and plasminogen activity (Plg) were lower than in healthy humans. We established the presence of the fibrinolytic system in Ch. villosus through the measurement of fibrin fibrinogen degradation products. The activity of the plasminogen activator inhibitor was two to four times greater than in healthy humans. The activity of the alpha 2 anti-plasmin (α2AP) was similar and displaced toward lower values. The Plg/α2AP relation was lower. The results obtained suggest that Ch. villosus has a hypercoagulable and hypofibrinolytic profile. Our findings are not only the first contribution to elucidate the physiology of the fibrinolytic system in Xenarthra but also contribute to develop an animal model for studies in haemostasis and thrombosis.

Antithrombotic effects by oral administration of novel proteinase fraction from earthworm eisenia andrei on venous thrombosis model in rats

A novel proteinase fraction, SPP-501, was purified from the earthworm, Eisenia andrei, and its antithrombotic effects compared with those of urokinase and t-PA (tissue type-plasminogen activator) in a thrombosis model, induced by the insertion of a stainless wire coil into the inferior vena cava. SPP-501, urokinase and t-PA were administrated once a day for 14 days. On the oral administration of SPP-501, as well as urokinase and t-PA, the thrombus weight was dramatically decreased. The euglobulin lysis time (ELT) was also shortened by SPP-501, but urokinase and t-PA failed to dissolve the euglobulin clot. Conversely, urokinase and t-PA produced detectable fibrinogen/fibrin degradation products (FDP), but SPP-501 did not. Thrombin induced platelet aggregation was desensitized in the SPP-501 treatment groups. With a high dose of SPP-501 (45 mg/kg), the APTT (activated partial thromboplastin time) was prolonged. These results suggest that SPP-501 shows both antithrombotic and fibrinolytic activities when orally administered.