Serum Fibrinogen Degradation Products Research Articles

Identification of parameters in routine blood and coagulation tests related to the severity of COVID-19.

Objective: This study aimed to identify the predictive value of simple markers in routine blood and coagulation tests for the severity of coronavirus disease 2019 (COVID-19).Methods: A total of 311 consecutive COVID-19 patients, including 281 patients with mild/moderate COVID-19 and 30 patients with severe/life-threatening COVID-19, were retrospectively enrolled. Logistic modeling and ROC curve analyses were used to assess the indexes for identifying disease severity.Results: Lymphocyte and eosinophil counts of COVID-19 patients in the severe/life-threatening group were significantly lower than those of patients in the mild/moderate group (P < 0.001). Coagulation parameters, high-sensitivity C-reactive protein (hsCRP) levels and procalcitonin levels were higher in the severe/life-threatening group compared with the mild/moderate group (all P < 0.05). Univariate and multivariate logistic models revealed that hsCRP and fibrinogen degradation products (FDPs) were predictors of severe COVID-19 (OR = 1.072, P = 0.036; and OR = 1.831, P = 0.036, respectively). The AUROCs of hsCRP and FDP for predicting severe/life-threatening COVID-19 were 0.850 and 0.766, respectively. The optimal cutoffs of hsCRP and FDP for the severe/life-threatening type of COVID-19 were 22.41 mg/L and 0.95 µg/ml, respectively.Conclusion: Serum CRP and FDP levels are positively related to the severity of COVID-19. This finding indicates that CRP and FDP levels may potentially be used as early predictors for severe illness and help physicians triage numerous patients in a short time.

Elevated Serum Fibrinogen Degradation Products on Admission Is a Novel Predictive Factor for Recurrence of Chronic Subdural Hematoma

Previous studies reported an association of hematologic parameters, including white blood cells, neutrophil, eosinophils, or coagulation-related factors, with prognosis in cerebrovascular disorders. However, an association of recurrence rate with serum coagulation-related factors (e.g., D-dimer or fibrinogen degradation products [FDP]) in chronic subdural hematoma (CSDH) is unclear. Ninety-two patients who experienced first-time CSDH treated with burr-hole hematoma evacuation were included in this study. Laboratory data on admission were used to divide patients into 2 groups: serum FDP >5 μg/mL or FDP ≤5 μg/mL (within normal range), based on the reference range of our institute. We retrospectively compared the recurrence rate of CSDH within 90 days after the first operation between these groups. Statistical significance was accepted at P < 0.05. Patients with an FDP greater than 5 μg/mL showed a significantly increased recurrence rate compared with those with a normal FDP (≤5 μg/mL; 27.3% vs. 10.2%, respectively; P= 0.03). Patients with an FDP greater than 5 μg/mL also showed a significantly higher recurrence rate within 30 days after the operation (15.2% vs. 3.4%, respectively; P= 0.04), but no difference in the recurrence rate at 31-90 days after the operation (12.1% vs. 6.8%, respectively; P= 0.38). In multivariable analysis, monolayer hematoma (odds ratio, 7.61; P= 0.003) and an FDP >5 μg/mL (odds ratio, 5.04; P= 0.01) were independent predictive factors for recurrence within 90 days. Elevated serum FDP on admission is a novel predictive factor for the recurrence of CSDH. These patients require careful follow-up, and recurrence within 30 days after the first operation should be considered.

The involvement of ginseng berry extract in blood flow via regulation of blood coagulation in rats fed a high-fat diet

BackgroundThe present study investigated the effect of ginseng berry hot water extract (GBx) on blood flow via the regulation of lipid metabolites and blood coagulation in rats fed a high-fat diet (HFD). MethodsSixty rats were divided into five groups in descending order of body weight. Except for the control group, the other four groups were fed a HFD containing 45% kcal from fat for 11 wk without GBx. GBx groups were then additionally treated by gastric gavage with GBx dissolved in distilled water at 50 (GBx 50) mg/kg, 100 (GBx 100) mg/kg, or 150 (GBx 150) mg/kg body weight for 6 wk along with the HFD. To investigate the effects of GBx on rats fed a HFD, biochemical metabolite, blood coagulation assay, and histological analysis were performed. ResultsIn the experiments to measure the serum levels of leptin and apolipoprotein B/A, GBx treatment attenuated the HFD-induced increases in these metabolites (p < 0.05). Adiponectin and apolipoprotein E levels in GBx-treated groups were significantly higher than the HFD group. Prothrombin time and activated partial thromboplastin time were increased in all GBx-treated groups. In the GBx-treated groups, the serum levels of thromboxane A2 and serotonin were decreased and concentrations of serum fibrinogen degradation products were increased (p < 0.05). Moreover, histomorphometric dyslipidemia-related atherosclerotic changes were significantly improved by treatment with GBx. ConclusionThese results suggest the possibility that GBx can ameliorate blood flow by decreasing intima-media thickness via the regulation of blood coagulation factors related to lipid metabolites in rats fed a HFD.

The efficacy of recombinant human soluble thrombomodulin for the treatment of shiga toxin-associated hemolytic uremic syndrome model mice.

Recombinant human soluble thrombomodulin (rhTM) is a promising therapeutic natural anticoagulant that is comparable to antithrombin, tissue factor pathway inhibitor and activated protein C. In order to clarify the efficacy of rhTM for the treatment of typical hemolytic uremic syndrome (t-HUS), we examined changes in renal damage in t-HUS mice treated with rhTM or vehicle alone. We used severe and moderate t-HUS mice injected with shiga toxin (Stx) and lipopolysaccharide (LPS). The severe t-HUS mice were divided into two subgroups [an rhTM subgroup (Group A) and a saline subgroup (Group B)] along with the moderate t-HUS mice [an rhTM subgroup (Group C) and a saline subgroup (Group D)]. Groups E and F were healthy mice treated with rhTM or saline, respectively. All mice in Group B died at 80-90 h post-administration of Stx2 and LPS whereas all mice in Group A remained alive. Loss of body weight, serum creatinine level, endothelial injury and mesangiolysis scores at 24 h after administration in the t-HUS mice treated with rhTM were lower than those in t-HUS mice treated with saline. The levels of hemoglobin at 6 h and platelet counts at 24 h after administration in Group A were higher than those in Group B. Serum interleukin (IL)-6, IL-1β and tumor necrotic factor (TNF)-α levels at 24 h after administration in Group A were lower than those in Group B. Serum C5b-9 levels at 24 h after the administration and serum fibrinogen degradation product (FDP) at 72 h after the administration of Stx2 and LPS were lower in Group A than in Group B. These results indicate that rhTM might afford an efficacious treatment for t-HUS model mice via the inhibition of further thrombin formation and amelioration of hypercoagulant status.

Incidence and index of severity of hemolytic uremic syndrome in a 26 year period in Fukushima Prefecture, Japan

There have been a number of reports on large outbreaks of hemolytic uremic syndrome (HUS), but there have been no long-term studies of sporadic HUS in Japan. This study therefore investigated the epidemiology and prognosis of HUS in Fukushima Prefecture over a 26 year period. The medical records of 26 patients with HUS between 1987 and 2012 were collected. These children were divided into two groups: those with HUS following an episode of gastroenteritis, often with bloody diarrhea (D + HUS; n = 24) and those with HUS not associated with prodromal diarrhea (D-HUS; n = 2). The D + HUS group was further subdivided into group A (11 patients requiring dialysis) and group B (13 patients not requiring dialysis). The epidemiological and clinical data, as well as prognosis, were retrospectively investigated for each group. Approximately 90% of HUS patients belonged to the D + HUS group. In this group, the mean number of patients per year from 1987 to 1999, and from 2000 to 2012 was 0.92 ± 0.95, and 1.08 ± 0.86, respectively. On admission, lactate dehydrogenase (LDH), alanine aminotransferase (ALT), blood urea nitrogen (BUN), serum creatinine and serum fibrinogen degradation product (FDP) levels in group A were all higher than in group B. Serum albumin level and estimated glomerular filtration rate (eGFR) in group A were lower than in group B. At 6 months after the onset of HUS in the D + HUS group, renal function was normal. The frequency of HUS was constant from 1987 to 2012 in Fukushima. and serum LDH, ALT, BUN, creatinine, and FDP levels as well as eGFR might be risk factors for dialysis in D + HUS children.

Pseudo-thrombotic thrombocytopenic purpura: A rare presentation of pernicious anemia

Schistocytes are fragmented red blood cells due to the flow of blood through damaged capillaries and indicate endothelial injury. They are typical of microangiopathic hemolytic anemia seen in life threatening conditions like disseminated intravascular coagulation or thrombotic thrombocytopenic purpura/hemolytic uremic syndrome .We report a rare sub-acute presentation of pernicious anemia with hemolysis, thrombocytopenia and numerous schistocytes that was initially diagnosed as a more serious thrombotic thrombocytopenic purpura.A 31-year-old Caucasian woman presented with fatigue and paresthesia of both feet for 1 week. Past medical history included hypertension and gastro-esophageal reflux disease. Examination revealed scleral icterus and pallor. Examination of the abdomen did not show hepatosplenomegaly. Initial laboratory tests showed severe anemia, and low platelets. Indirect bilirubin and serum Lactate De Hydrogenase were elevated. Prothrombin time, partial thromboplastin time, serum fibrinogen, and serum fibrin degradation product levels were normal. Peripheral smear revealed numerous schistocytes, anisocytosis and macro-ovalocytes. Thrombotic thrombocytopenic purpura (TTP) was suspected due to the constellation of sub-acute onset of fatigue and paresthesia along with thrombocytopenia, schistocytes and an elevated LDH. Plasmapheresis was initiated for possible TTP. However, platelet count worsened despite plasmapheresis for 4 days. On re-evaluation, vitamin B(12) was found to be low. Treatment with intra-muscular vitamin B(12) led to symptomatic and hematologic improvement. Pernicious anemia was confirmed by the presence of anti-intrinsic factor antibodies, elevated serum gastrin level and atrophic gastritis.Clinicians must be aware of unusual clinical presentation of vitamin B(12) deficiency with schistocytes as the management is simple and effective.

Extrahepatic Portal Venous Obstruction due to a Giant Hepatic Hemangioma Associated with Kasabach-Merritt Syndrome

We describe a patient with extrahepatic portal venous obstruction due to a giant hepatic hemangioma associated with Kasabach-Merritt syndrome. A 67-year-old woman presented with upper abdominal distension and appetite loss. The medical history was not relevant to the current disorder. Initial laboratory tests revealed the following: serum platelet count, 9.9 × 10⁴/µL; serum fibrinogen degradation products, 12 µg/mL; prothrombin time, 1.26; and serum fibrinogen, 111 mg/dL. Computed tomography demonstrated homogenous low-density areas, 15 cm in diameter, in the left lobe of the liver. Common hepatic arteriography revealed a hypervascular tumor with pooling of contrast medium in the delayed phase. The portal venous phase of supramesenteric arteriography revealed obstruction and cavernous transformation of the portal vein. We diagnosed extrahepatic portal venous obstruction due to a giant hepatic hemangioma associated with Kasabach-Merritt syndrome. Laparotomy was performed, and the liver was found to be markedly enlarged. After mobilization of the left lobe, left hepatectomy was performed with intermittent clamping. After resection, Doppler ultrasonography revealed recovery of the portal venous flow. The cavernous transformation shrank. Pathologic examination of the surgical specimen confirmed the presence of a giant benign hepatic cavernous hemangioma. The patient was discharged 16 days after operation. Laboratory data and complications improved after 2 months.

Antithrombin reduces reperfusion-induced hepatic metastasis of colon cancer cells

To examine whether antithrombin (AT) could prevent hepatic ischemia/reperfusion (I/R)-induced hepatic metastasis by inhibiting tumor necrosis factor (TNF)-alpha-induced expression of E-selectin in rats. Hepatic I/R was induced in rats and mice by clamping the left branches of the portal vein and the hepatic artery. Cancer cells were injected intrasplenically. The number of metastatic nodules was counted on day 7 after I/R. TNF-alpha and E-selectin mRNA in hepatic tissue, serum fibrinogen degradation products and hepatic tissue levels of 6-keto-PGF(1alpha), a stable metabolite of PGI2, were measured. AT inhibited increases in hepatic metastasis of tumor cells and hepatic tissue mRNA levels of TNF-alpha and E-selectin in animals subjected to hepatic I/R. Argatroban, a thrombin inhibitor, did not suppress any of these changes. Both AT and argatroban inhibited I/R-induced coagulation abnormalities. I/R-induced increases of hepatic tissue levels of 6-keto-PGF(1alpha) were significantly enhanced by AT. Pretreatment with indomethacin completely reversed the effects of AT. Administration of OP-2507, a stable PGI2 analog, showed effects similar to those of AT in this model. Hepatic metastasis in congenital AT-deficient mice subjected to hepatic I/R was significantly increased compared to that observed in wild-type mice. Administration of AT significantly reduced the number of hepatic metastases in congenital AT-deficient mice. AT might reduce I/R-induced hepatic metastasis of colon cancer cells by inhibiting TNF-alpha-induced expression of E-selectin through an increase in the endothelial production of PGI2. These findings also raise the possibility that AT might prevent hepatic metastasis of tumor cells if administered during the resection of liver tumors.

The effects of danaparoid, dalteparin and heparin on tissue factor-induced experimental disseminated intravascular coagulation and bleeding time in the rat

Danaparoid and heparin, on the basis of anti-activated factor X (anti-FXa) activity, were equipotent in accelerating the rate of interaction of FXa and antithrombin III. In rat tissue factor-induced disseminated intravascular coagulation (DIC) models, an intravenous administration of danaparoid inhibited the decrease in plasma fibrinogen and platelet counts and the increase in serum fibrinogen degradation products. Expressed on the basis of anti-FXa activity, these effects were comparable with those of dalteparin and heparin. In rat mesenteric small artery and vein, less bleeding was observed after intravenous administration of danaparoid than after dalteparin or heparin. Danaparoid did not affect adenosine diphosphate- or collagen-induced platelet aggregation, and showed weaker inhibitory effects on aggregation induced by thrombin, or collagen + thrombin, than did dalteparin or heparin. These findings suggest that danaparoid may be useful for the prevention of DIC and has less tendency to cause bleeding than dalteparin or heparin, probably as a result of its weaker ability to inhibit platelet aggregation.

DOS SANTOS PAPER: Fibrinogen and fibrinolysis in blood and in the arterial wall: its role in advanced atherosclerotic disease

High plasma fibrinogen appears to be an important risk factor for the development of atherosclerosis. The aim of our study was to measure fibrinogen and fibrin degradation products (D-dimer), interleukin-6 tissue plasminogen activator, plasminogen activator inhibitor-1 and urokinase-type plasminogen activator in the plasma and arterial walls of 45 patients who had arterial surgery between April 1993 and November 1995. The arterial specimens were also examined by immunohistochemists for these same factors. The serum fibrinogen and fibrin degradation products were high in all patients, and fibrinolysis was depressed. Few leukocytes were seen in the arterial walls, which had poor fibrinolytic activity. Plasminogen-activator inhibitor activity in the wall was also reduced in the affected arterial walls. The abdominal aorta appeared to have the highest levels of fibrinogen and this may be related to its ability to form aneurysms. Fibrinogen may play an important role in the progression of atherosclerotic disease.

Fibrinogen degradation products in patients with the Quebec platelet disorder.

The Quebec platelet disorder is a serious bleeding disorder associated with proteolysis of alpha-granular proteins, including fibrinogen. We evaluated fibrinogen degradation product (FDP) assays as screening tests for this disorder. Patients with the Quebec platelet disorder (13/13) had elevated serum FDPs (P < 0.01) due to secreted degraded platelet fibrinogen, but normal plasma FDPs and D-dimers. Unrelated controls with bleeding disorders (32/34) had undetectable FDPs, and controls with FDPs due to disseminated intravascular coagulation (DIC) and other illnesses (11/11) had elevated FDPs in all assays (P < 0.01). Immunoblot analyses indicated plasma fibrinogen was normal in the Quebec patients and platelet FDPs were found in their platelet lysates, releasates and serum samples. Their platelet FDPs were not altered by treatment with fibrinolytic inhibitors and were different from the FDPs in DIC and in plasmin-digested fibrinogen. Tests for serum FDPs may provide a simple rapid way to screen for the Quebec platelet disorder.

New quantitative enzyme immunoassays for degradation products of fibrin and fibrinogen in plasma: A comparison with other laboratory methods

Summary The traditional assays for measuring fibrin/ogen degradation products (FDP) have limitations due to the use of serum, and do not discriminate between FDPs deriving from fibrin or fibrinogen. The crosslinked fibrin derivatives may be detected by means of monoclonal based assays in plasma (D-dimer tests, both ELISA or latex). More recently, new quantitative immunoassays have been proposed and are now available for clinical and laboratory use. The Fibrinostika System kits allow separate and specific determination on plasma samples of degradation products derived from fibrin (FbDP), from fibrinogen (FgDP) and the total amount of FbDP plus FgDP (TDP). The within- and between-assays reproducibility showed acceptable CV% values. The FbDP and FgDP sums correlated well with TDP test values; evaluation of the total degradation products can thus be achieved by either the two separate tests or the global one. The FbDP test showed more frequently higher than normal results in appropriate clinical conditions than the D-dimer test (both ELISA or latex). Furthermore, we observed important discrepancies between the levels of plasma TDP and serum FDP, as the latter often failed to detect fibrin/ogen derivatives measurable with the plasma method. This finding confirms that the serum FDP assays may be affected by technical problems and may therefore lead to unreliable results. The Fibrinostika System tests are reproducible and easy to perform and have a short time-to-result; they seem, therefore, to be useful tools in the clinical coagulation laboratory.

Role of D Dimer in Patients with Elevated Fibrinogen Degradation Products in Serum: Further Study in Chronic Myelogenous Leukemia

We quantitatively assayed the levels of cross-linked fibrin degradation products (D dimer) in plasma at 73 points in time in 32 patients with elevated fibrin/fibrinogen degradation products (FDP) in serum. The assay of FDP was performed on serum samples prepared in test tubes containing 5 U/ml thrombin (final concentration) by a method based on latex agglutination using antifibrinogen antibodies, and the levels of D dimer in plasma were determined by a newly developed latex immunoassay using monoclonal antibodies which do not cross-react with fibrinogen. 5 patients with chronic myelogenous leukemia (CML) had highly elevated FDP levels with normal levels of D dimer. Plasma samples from such patients with CML were treated with various concentrations of thrombin (2-10 U/ml) and after the removal of fibrin clots the levels of FDP in supernatants were assayed by the FDP assay procedure described above. The levels of FDP were normalized when plasma were treated with 10 U/ml thrombin. In 2 patients with CML who had elevated levels of FDP in serum, it was impossible to remove fibrinogen completely by addition of 5 U/ml thrombin. However, FDP levels in the sera treated with 5 U/ml thrombin were almost normal in normal controls and patients with other diseases than CML. From these results it is concluded that residual fibrinogen reacted in the assay procedure as markedly increased FDP in supernatants and elevated FDP levels in serum reflected fibrinogen-related materials, which may not completely polymerize in the presence of lower concentrations of thrombin in some patients with CML. The assay of D dimer in plasma using monoclonal antibodies is recommended in cases of CML to rule out disseminated intravascular coagulation.

Prognostic Factors in Acute Subdural Hematoma and the Significance of Serum FDP Measurement

Sixty-two cases of acute subdural hematoma were clinically analyzed with special reference to such prognostic factors as age, Glasgow Coma Scale (GCS) score on admission, pupillary signs, decerebration, and initial computed tomography (CT) findings. Intraparenchymal lesions demonstrated by CT were evaluated according to Yamaura's classification. In 19 cases, serum fibrin and fibrinogen degradation products (FDP) were measured at the time of admission. Emergency surgery was performed in 46 cases, and the remaining 16 patients were treated conservatively. The final outcome was judged according to the Glasgow Outcome Scale, and patients were divided into a "good outcome" group (good recovery or moderate disability) and a "poor outcome" group (severe disability, vegetative state, or death). In general, the outcomes proved to be unsatisfactory. Forty-four patients (71%) had a poor outcome, with 32/62 (52%) mortality, and only 18 (29%) had a good outcome. The clinical factors associated with a poor outcome were age over 64 years, a GCS score on admission of less than 7, decerebration, and absence of pupillary reaction to light. Initial CT scans showed brain damage in 46 patients (74%), 39 (85%) of whom had a poor outcome. This indicates that the outcome was significantly related to brain injury complicating the acute subdural hematoma. A high serum FDP level was similarly related to a poor outcome, which suggests that the serum FDP level reflects the degree of both primary and secondary brain injury. Thus, measurement of serum FDP may be valuable both in assessing clinical status and in evaluating the extent of brain injury in acute subdural hematoma.

In Vivo Measurements of Fibrin Formation and Fibrinolysis in Operable Breast Cancer

Fibrin formation and fibrinolysis were estimated in 89 breast cancer patients by measurement in plasma of Fibrin Fragment B beta 15-42 and Fibrinopeptide A (FPA), serum Fibrin(ogen) Degradation Products (FDPs) and plasminogen activator by Fibrin Plate Lysis Assay. Results were compared with (a) 26 patients with benign breast diseases; and (b) 45 healthy factory workers. FPA, FDP and B beta 15-42 levels were elevated in both breast cancer patients and benign disease patients, but there were no significant differences between these two groups. Cancer stage, patient age and smoking habits did not affect these results, but Oestrogen Receptor (ER) positive patients had higher B beta 15-42 values than ER negative patients (p = 0.017). These results show that fibrin formation is enhanced preoperatively in patients with either benign or malignant breast disease. The fibrinolytic response to activated coagulation may be relatively deficient in breast cancer. The roles of malignancy, stress and other factors in the causation of these abnormalities require further assessment.

81 Prognostic value of serum and plasma fibrinogen degradation products in patients with acute upper gastrointestinal bleeding

81 Prognostic value of serum and plasma fibrinogen degradation products in patients with acute upper gastrointestinal bleeding

Effects of the new glycopeptide antibiotic teicoplanin on platelet function and blood coagulation.

Teicoplanin, a new glycopeptide antibiotic, is structurally related to ristocetin, an antibiotic known to induce human platelet agglutination and, thus, thrombocytopenia and thromboembolic side effects. The aim of this study was to evaluate the effects of teicoplanin on platelet function in vitro and ex vivo and on blood coagulation ex vivo. In the in vitro studies, spontaneous platelet aggregation; platelet aggregation induced by ADP, collagen, and ristocetin; and the release of beta-thromboglobulin from platelets were assessed. Platelets from healthy subjects were incubated with teicoplanin at final concentrations of 100, 1,500, 5,000, and 10,000 micrograms/ml. The maximal achievable concentration with therapeutic doses is 100 micrograms/ml. When compared with saline, teicoplanin at concentrations of 100 and 1,500 micrograms/ml had no effect on platelet function, but at concentrations of 5,000 and 10,000 micrograms/ml, it induced greater spontaneous platelet aggregation (P less than 0.01) and inhibited platelet aggregation induced by ADP, collagen, and ristocetin (P less than 0.01). Teicoplanin at concentrations of 100, 1,500, and 5,000 micrograms/ml did not induce the release of beta-thromboglobulin, in contrast to teicoplanin at a concentration of 10,000 micrograms/ml and ristocetin at a concentration of 1.5 mg/ml (P less than 0.01). In the ex vivo studies, platelet count, bleeding time, plasma beta-thromboglobulin, platelet aggregation induced by ADP, ristocetin, and epinephrine, activated partial thromboplastin time, prothrombin time, thrombin clotting time, and serum fibrinogen degradation products were evaluated at days 0, 3, and 6 and at 72 h after the end of therapy. All subjects completed the study without evidence of side effects. When compared with the pretreatment values, none of the values from these assays showed a significant change at any time during and after treatment. We concluded that platelet function and blood coagulation are not affected by therapeutic concentrations of teicoplanin and that in vitro platelet function is affected only by concentrations of teicoplanin far in excess of those that are clinically achievable.

Analysis of fibrinogen degradation product in severe liver disorders by immunoblotting.

Increased serum fibrinogen degradation product (FDP) in liver cirrhosis and hepatic carcinoma as measured by latex agglutination was analyzed by means of SDS-polyacrylamide gel electrophoresis followed by immunoblotting with anti-fibrinogen antibody. The antibody used in this study reacts with fibrinogen, fragment X, Y, D-D, D and E. The validity of this technique was confirmed by the analysis of the serum samples from patients with definite diagnosis of disseminated intravascular coagulation. Serum samples of 14 patients out of 18 with elevated FDP values and severe liver diseases were shown to contain no plasmic digest of fibrin or fibrinogen. By using the SDS-gel electrophoresis after disulfide bond reduction, seven serum samples from these 14 patients, who were shown to have no plasmic digest in serum, were found to contain unclottable fibrinogen retained in sera, while the remaining seven samples were revealed to have fibrin monomer in their sera. Four serum samples from the 18 patients were shown to have plasmic digest of fibrinogen, but these patients had additional diseases leading to 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.

α2antiplasmin and disseminated intravascular coagulation in liver cirrhosis

Subnormal concentrations of α 2 Antiplasmin ( α 2AP) in liver cirrhosis may be due to an impaired hepatic synthesis and/or to a fibrinolysis activation in disseminated intravascular coagulation (DIC).In order to clarify this problem, in 26 cirrhotic patients (15 compensated and 11 decompensated) α 2AP plasma activity and plasma Fibrinopeptide A (FPA) were measured. Serum albumin, p-Cholinesterase (p-CHE), Fibrinogen and Fibrinogen Degradation Products (FDP) were also carried out. Our data show that α 2AP and FPA were equally abnormal in compensated and decompensated cirrhosis.The significant negative correlation obtained between α 2AP and FPA as well as the lack of correlation between α 2AP and albumin, α 2AP and p-CHE in both groups suggests that, in our patients, α 2AP decrease may be due to a fibrinolysis activation induced by a DIC which appears chronic since Fibrinogen and FDP were normal.These findings are in agreement with the results obtained in the four subgroups a posteriori selected on the basis of FPA levels: α 2AP in subgroups with high FPA was significantly different from con trols while it did not differ in subgroups with normal FPA.