Plasmin-alpha 2-plasmin Inhibitor Complex Research Articles

Inflammation as an exacerbation marker and target for prophylaxis against Coronavirus Disease 2019-related thrombosis

Objectives: There are currently no appropriate markers and target for prophylaxis against COVID-19-related thrombosis, especially in the not-severe cases. We tested the hypothesis that inflammation is a suitable marker and target for prophylaxis against COVID-19-related thrombosis. Methods: Data of all 32 COVID-19 patients admitted to Saitama Medical Center between January 1 and March 30, 2021, were analyzed. Patients were divided into severe (requiring oxygen, n=12) and non-severe (no requirement for oxygen, n=20), and also those with high C-reactive protein (CRP) level (cutoff value: 30 mg/L, n=21) and low-CRP (n=11). We also compared the clinical and laboratory data of a 46-year-old post-liver transplant male patient, who was treated with a combination of immunosuppressants (methylprednisolone, fludrocortisone, cyclosporine, and everolimus) with those of other COVID-19 patients, using the Smirnoff-Grubbs and Box plots tests. Results: The levels of CRP, ferritin, lactate dehydrogenase, aspartate aminotransferase, and thrombin-antithrombin complex (TAT) were significantly higher in the high-severity group than the low-severity group; while other coagulation parameters were comparable. The time between onset of illness and blood levels of lactate dehydrogenase, fibrinogen, D-dimer, TAT, and plasmin alpha2-plasmin inhibitor complex (PIC) were significantly higher whereas lymphocyte count was significantly lower in the high-CRP group. Extremely low levels of TAT, PIC, and plasminogen activator inhibitor-1 (PAI-1) were recorded in the liver transplant patient treated with immunosuppressants. The TAT, PIC, and PAI-1 levels were deemed outliers. Conclusions: Inflammation is a potentially suitable marker and target for prophylaxis against COVID-19-related thrombosis.

Association of Histones With Coagulofibrinolytic Responses and Organ Dysfunction in Adult Post-cardiac Arrest Syndrome.

BackgroundPatients successfully resuscitated from cardiac arrest often develop organ dysfunction caused by systemic inflammation and increased coagulation, leading to disseminated intravascular coagulation (DIC). The involvement of histones in DIC and organ dysfunction in patients with sepsis and trauma has been previously reported, raising the probability that histones may also be associated with pathophysiology in patients after cardiac arrest and resuscitation. This study evaluated the relationship between histones and organ dysfunction related to coagulofibrinolytic changes in patients with post-cardiac arrest syndrome (PCAS).MethodsThis prospective single-center observational study assessed 35 adult patients with PCAS who were divided into two groups, i.e., 15 patients with multiple organ dysfunction syndrome (MODS) and 20 patients without MODS. MODS was defined as a sequential organ failure assessment score of ≥12. The plasma levels of histones and coagulofibrinolytic markers, including soluble fibrin, tissue-type plasminogen activator, plasminogen activator inhibitor-1, plasmin-alpha 2-plasmin inhibitor complex (PIC), and soluble thrombomodulin, were measured in patients with PCAS immediately after admission to the emergency department, and 3 and 24 h after arriving at the hospital.ResultsPCAS patients with MODS had higher DIC scores [4 (3.0–5.0) vs. 1 (0.0–3.0), p = 0.012] and higher mortality rates (66.7% vs. 20.0%, p = 0.013) than those without MODS. Moreover, patients with MODS exhibited higher histone levels than those without MODS during the early phase of the post-resuscitation period. Severe endothelial injury and higher thrombin and plasmin generation were observed in the MODS group. Plasma levels of histones were positively correlated with those of soluble fibrin immediately after resuscitation (rho = 0.367, p = 0.030) and PIC 3 h after arriving at the hospital (rho = 0.480, p = 0.005). This correlation was prominent in the patient population with MODS (soluble fibrin: rho = 0.681, p = 0.005, PIC: rho = 0.742, p = 0.002).ConclusionsThis study demonstrated that elevated histone levels were associated with increased levels of thrombin, and subsequent plasmin generation in PCAS patients, especially those with MODS. Further studies are required to elucidate the causal relationship between histones and organ dysfunction related to DIC in PCAS.

Elevated TAT in COVID-19 Patients with Normal D-Dimer as a Predictor of Severe Respiratory Failure: A Retrospective Analysis of 797 Patients.

Although previous studies have revealed that elevated D-dimer in the early stage of coronavirus 2019 (COVID-19) indicates pulmonary intravascular coagulation, the state of coagulation/fibrinolysis disorder with normal D-dimer is unknown. The study aimed to investigate how coagulation/fibrinolysis markers affect severe respiratory failure in the early stage of COVID-19. Among 1043 patients with COVID-19, 797 patients were included in our single-center retrospective study. These 797 patients were divided into two groups, the normal D-dimer and elevated D-dimer groups and analyzed for each group. A logistic regression model was fitted for age, sex, body mass index (BMI) ≥ 30 kg/m2, fibrinogen ≥ 617 mg/dL, thrombin-antithrombin complex (TAT) ≥ 4.0 ng/mL, and plasmin-alpha2-plasmin inhibitor-complex (PIC) > 0.8 µg/mL. A multivariate analysis of the normal D-dimer group demonstrated that being male and TAT ≥ 4.0 ng/mL significantly affected severe respiratory failure. In a multivariate analysis of the elevated D-dimer group, BMI ≥ 30 kg/m2 and fibrinogen ≥ 617 mg/dL significantly affected severe respiratory failure. The elevated PIC did not affect severe respiratory failure in any group. Our study demonstrated that hypercoagulation due to SARS-CoV-2 infection may occur even during a normal D-dimer level, causing severe respiratory failure in COVID-19.

Coagulation and Fibrinolysis Biomarkers as Potential Indicators for the Diagnosis and Classification of Ovarian Hyperstimulation Syndrome

Background: Accurate diagnosis and classification of ovarian hyperstimulation syndrome (OHSS) is important for its management. We employed a new high-sensitivity chemiluminescence immunoassay to detect the thrombin-antithrombin complex (TAT), plasmin alpha2-plasmin inhibitor complex (PIC), soluble thrombomodulin (sTM), and tissue plasminogen activator-inhibitor complex (TPAI-C), and evaluated their diagnostic and classification performance for OHSS.Methods: A total of 106 women were enrolled, including 51 patients with OHSS (25 mild or moderate OHSS, 26 severe OHSS), and 55 without OHSS (control group). TAT, PIC, sTM, and TPAI-C levels were measured using the Sysmex HISCL5000 automated analyzer.Results: Compared to the control group, TAT, PIC, and TPAI-C levels were significantly higher (P < 0.001, P < 0.001, P < 0.001, respectively), whereas the sTM level was significantly lower (P < 0.001) in the patients with OHSS. The receiver operating characteristic was used to evaluate the diagnostic efficiency. For the diagnosis of OHSS, the area under the curves (AUCs) for TAT, PIC, sTM, and TPAI-C were 0.991, 0.973, 0.809, and 0.722, respectively. In particular, the sensitivity, specificity, positive predictive value, and negative predictive value for TAT and PIC were all above 90%. For the differential diagnosis of mild–moderate and severe OHSS, the AUCs for TAT, PIC, and TPAI-C were 0.736, 0.735, and 0.818, respectively. The cutoff values of TAT, PIC, and TPAI-C for the differential diagnosis of mild–moderate and severe OHSS were 11.5 ng/mL, 2.4 μg/mL, and 5.8 ng/mL, respectively. Based on these cutoff values, eight cases of mild–moderate OHSS exceeded the cutoff values, two of which developed to severe OHSS in the following days. However, of the remaining 17 cases of mild–moderate OHSS patients with negative biomarkers, none subsequently developed severe OHSS.Conclusions: TAT, PIC, sTM, and TPAI-C can be used as sensitive biomarkers in the diagnosis of OHSS. Meanwhile, TAT, PIC, and TPAI-C also displayed remarkable potential in the classification of OHSS. In addition, the levels of TAT, PIC, and TPAI-C above the cutoff values in patients with mild–moderate OHSS might predict a high risk of developing severe OHSS.

Dysfunctional coagulation and fibrinolysis systems due to adenomyosis is a possible cause of thrombosis and menorrhagia

ObjectiveTo study the effects of adenomyosis on the coagulation and fibrinolysis system during menstruation and the relationship between dysfunction of the coagulation and fibrinolysis system and the symptoms and complications of adenomyosis. Study designConcentrations of thrombin–antithrombin complex (TAT) and soluble fibrin (SF) as markers of coagulation, D-dimer (DD) as a marker of both coagulation and fibrinolysis, and plasmin-alpha 2-plasmin inhibitor complex (PIC) as a marker of fibrinolysis in the peripheral blood of eight patients with adenomyosis were measured daily from the first to fifth day of menstruation. Associations between levels of these markers during menstruation and patient characteristics, history of thrombotic disorder, and hemoglobin loss during menstruation were investigated. ResultsTAT, SF, DD and PIC increased in 5, 2, 3 and 1 of the 8 patients, respectively. TAT increased in 5 of the 6 patients with an adenomyotic uterus ≥100 cubic centimeters. Patients with elevated DD, SF and/or PIC were among patients with elevated TAT. DD was only increased in 3 patients with a past history of small cerebral infarction or pulmonary thromboembolism and/or hemoglobin loss >2.0g/dl during menstruation. SF was increased only in 2 patients with a past history of cerebral infarction or pulmonary thromboembolism. PIC increased in 1 of the 2 patients with hemoglobin loss >2.0g/dl during menstruation. ConclusionAdenomyosis patients with a uterus volume ≥100 cubic centimeters are at risk of having an activated coagulation system. These patients, particularly those with elevated SF and DD, may be at risk of thrombotic disorders. Fibrinolysis is activated in a portion of patients with activated coagulation during menstruation. Activated fibrinolysis during menstruation may contribute to menorrhagia in patients with adenomyosis, as only patients with activated fibrinolysis suffered menorrhagia, even though patients with an adenomyotic uterus ≥100 cubic centimeters without activated fibrinolysis did not. These results suggest extensive adenomyosis confers a potential risk of infarction and thrombosis and exacerbates menorrhagia via activation of coagulation and fibrinolysis during menstruation.

Predicting Perioperative Venous Thromboembolism in Japanese Gynecological Patients

ObjectiveTo develop a convenient screening method that can predict perioperative venous thromboembolism (VTE) and identify patients at risk of fatal perioperative pulmonary embolism (PE).MethodsPatients hospitalized for gynecological abdominal surgery (n = 183) underwent hematology tests and multidetector computed tomography (MDCT) to detect VTE. All statistical analyses were carried out using the SPSS software program (PASWV19.0J)ResultsThe following risk factors for VTE were identified by univariate analysis: plasmin-alpha2-plasmin inhibitor complex (PIC), thrombin-antithrombin III complex (TAT), and prolonged immobility (all p<0.001); age, neoadjuvant chemotherapy (NAC), malignancy, hypertension, past history of VTE, and hormone therapy (all p<0.01); and hemoglobin, transverse tumor diameter, ovarian disease, and menopause (all p<0.05). Multivariate analysis using these factors revealed that PIC, age, and transverse tumor diameter were significant independent determinants of the risk of VTE. We then calculated the incidence rate of perioperative VTE using PIC and transverse tumor diameter in patient groups stratified by age. In patients aged≦40 years, PIC ≧1.3 µg/mL and a transverse tumor diameter ≧10 cm identified the high-risk group for VTE with an accuracy of 93.6%. For patients in their 50 s, PIC ≧1.3 µg/mL identified a high risk of VTE with an accuracy of 78.2%. In patients aged ≧60 years, a transverse tumor diameter ≧15 cm (irrespective of PIC) or PIC ≧1.3 µg/mL identified the high-risk group with an accuracy of 82.4%.ConclusionsWe propose new screening criteria for VTE risk that are based on PIC, transverse tumor diameter, and age. Our findings suggest the usefulness of these criteria for predicting the risk of perioperative VTE and for identifying patients with a high risk of fatal perioperative PE.

Coagulofibrinolytic changes in patients with disseminated intravascular coagulation associated with post-cardiac arrest syndrome― Fibrinolytic shutdown and insufficient activation of fibrinolysis lead to organ dysfunction

IntroductionPost-cardiac arrest syndrome (PCAS) is often associated with disseminated intravascular coagulation (DIC), thus leading to the development of multiple organ dysfunction syndrome (MODS). The aim of this study was to examine the pathophysiological relationships between coagulation, fibrinolysis and fibrinolytic shutdown by evaluating the levels of coagulofibrinolytic markers, including soluble fibrin, thrombin-activatable fibrinolysis inhibitor (TAFI), tissue plasminogen activator-plasminogen activator inhibitor-1 complex (tPAIC), plasmin-alpha2 plasmin inhibitor complex (PPIC), neutrophil elastase and fibrin degradation product by neutrophil elastase (EXDP). Materials and MethodsFifty-two resuscitated patients were divided into two groups: 22 DIC and 30 non-DIC patients. ResultsThe levels of soluble fibrin, PPIC, tPAIC, EXDP and neutrophil elastase in the DIC patients with PCAS were significantly higher than those observed in the non-DIC patients. The values of the tPAIC and JAAM DIC scores were found to be independent predictors of increased SOFA scores in the DIC patients. The MODS patients demonstrated significantly higher levels of soluble fibrin and tPAIC; however, the levels of TAFI and EXDP were identical between the patients with and without MODS. In addition, positive correlations were observed between the levels of tPAIC and EXDP in the patients with non-MODS; however, no correlations were observed between these markers in the MODS patients. ConclusionsThrombin activation and fibrinolytic shutdown play important roles in the development of organ dysfunction in PCAS patients. Neutrophil elastase-mediated fibrinolysis cannot overcome the fibrinolytic shutdown that occurs in DIC patients with PCAS, thus resulting in the development of MODS.

A low TAFI activity and insufficient activation of fibrinolysis by both plasmin and neutrophil elastase promote organ dysfunction in disseminated intravascular coagulation associated with sepsis

IntroductionWe hypothesized that thrombin activatable fibrinolysis inhibitor (TAFI) and the activation of fibrinolysis by both plasmin and neutrophil elastase is insufficient to overcome fibrinolytic shutdown, contributing to multiple organ dysfunction syndrome (MODS) in sepsis-induced disseminated intravascular coagulation (DIC). Materials and MethodsFifty patients with sepsis were prospectively enrolled. The DIC was diagnosed based on the Japanese Association for Acute Medicine (JAAM) DIC and the International Society on Thrombosis and Haemostasis (ISTH) overt DIC criteria. ResultsThe JAAM DIC scores were independent predictors of patient death and MODS. The JAAM DIC patients, especially those who met the ISTH overt DIC criteria, showed lower TAFI activity, and higher levels of soluble fibrin, neutrophil elastase, fibrin degradation product by neutrophil elastase (EXDP), plasmin-alpha2 plasmin inhibitor complex (PPIC), tissue plasminogen activator-plasminogen activator inhibitor-1 complex (tPAIC) and D-dimer in comparison with non-DIC patients. There were differences in the levels of soluble fibrin, tPAIC, TAFI activity, and neutrophil elastase between the patients with and without MODS. However, no differences were observed in the levels of PPIC, D-dimer, or EXDP. Soluble fibrin negatively correlated with the TAFI activity. High neutrophil elastase, low TAFI activity and PPIC are independent predictors of patient death and MODS. tPAIC is an independent predictor of elevation of EXDP in DIC patients. ConclusionsActivation of fibrinolysis both by plasmin and neutrophil elastase cannot overcome fibrinolytic shutdown, leading to MODS and a poor outcome in sepsis-induced DIC. The systemic activation of neutrophils and a low TAFI activity are also involved in the pathogenesis of MODS.

Hemoperfusion With a Polymyxin B Fiber Column Decreases Clotting Activity

We investigated whether hemoperfusion with a polymyxin B column (DHP-PMX) was able to improve coagulation abnormalities in patients with sepsis. Sixteen patients with sepsis were enrolled in the study. They all had signs of systemic inflammatory response syndrome due to infection and a mean arterial blood pressure > or =65mm Hg (irrespective of the use of catecholamines). A thermodilution catheter was inserted prior to DHP-PMX for intravenous infusion, and DHP-PMX was performed twice within 24 h for 3 h each time. Circulating levels of thrombin-antithrombin complex (TAT), plasmin-alpha2 plasmin inhibitor complex (PIC), the TAT/PIC ratio, and plasminogen activator inhibitor-1 (PAI-1) were measured six times. Before DHP-PMX, the TAT level was 24.5 +/- 8.3 ng/mL, the PIC level was 2.5 +/- 1.1 microg/mL, the TAT/PIC ratio was 13.9 +/- 3.5, and the PAI-1 level was 143.0 +/- 24.4 ng/L. The TAT level, TAT/PIC ratio, and PAI-1 were all significantly lower (P < 0.05) after 48 hr compared with before DHP-PMX, but no significant change of PIC was observed. In these patients with sepsis, fibrinolysis was inhibited by PAI-1, whereas clotting activity was significantly increased. This coagulation/fibrinolysis imbalance was improved by DHP-PMX. The present results suggest that indirect inhibition of clotting activity can be achieved in patients with sepsis through adsorption of lipopolysaccharide by DHP-PMX.

Antithrombin effect on coagulation and fibrinolytic profiles after living donor liver transplantation: a pilot study

Early after liver transplantation, patients are in a hypercoagulable state because of an imbalance between coagulation and fibrinolysis because of the slow recovery of depleted anticoagulant proteins. Antithrombin (AT) is used in anticoagulant protocols to prevent thrombosis. The subjects of the present study were 17 men and eight women that underwent living donor liver transplantation. The initial 15 cases were administered AT concentrate (1500 U/day) on postoperative days (POD) 1 through 3 (AT group) and the following 10 consecutive cases were not administered AT (control). AT, thrombin-AT complex, plasmin-alpha2 plasmin inhibitor complex, thrombomodulin, fibrin degradation product D-dimer (FDP-DD) level, prothrombin time international normalized ratio, activated partial thromboplastin time, and platelet counts were measured. In the AT group, AT activity was maintained at levels >80% for 5 days after transplantation. In the control group, AT activity did not return to normal during the first 2 weeks after the operation. FDP-DD levels were significantly higher in the control group than in the AT group (P < 0.05). Six patients in the control group and three patients in the AT group required transfusions with platelet concentrate (P < 0.05). AT supplementation might reduce FDP-DD levels and prevent decreased platelet counts in the early stages after liver transplantation.

Coagulation Activity is Increased in the Left Atria of Patients With Paroxysmal Atrial Fibrillation During the Non-Paroxysmal Period Comparison With Chronic Atrial Fibrillation

Evaluation of plasma markers of thrombin activity (thrombin-antithrombin III complex: TAT), active fibrinolysis (plasmin-alpha 2-plasmin inhibitor complex: PIC), and platelet activity (platelet factor 4: PF4) is useful for identifying patients with various cardiovascular disorders who are at high risk of thromboembolism. In this study, these markers were investigated in the left atria (LA) of patients with paroxysmal atrial fibrillation (pAF) in the non-paroxysmal period. Patients with pAF (n=10) and chronic AF (cAF) (n=10) were enrolled. TAT, PIC, and PF4 levels were determined in blood samples obtained from the LA of AF patients before radiofrequency catheter ablation. TAT levels were high in both pAF and cAF patients. PF4 levels were slightly elevated in both groups, but there was no significant difference between the groups. On the other hand, PIC levels in both groups were almost within normal limits, again with no significant difference between groups. Coagulation activity is elevated in the LA of patients with pAF, even in the non-paroxysmal period, so these patients are at high risk of thromboembolism and anticoagulant therapy is indicated.

Abstract 1940: Coagulation Activity is Increased in the Left Atrium of Patients with Paroxysmal Atrial Fibrillation

Background: Measurements of plasma markers which reflect thrombin activity (thrombin-antithrombin III complex; TAT), active fibrinolysis (plasmin-alpha 2-plasmin inhibitor complex; PIC), and platelet activity (platelet factor 4; PF4) are useful in identifying patients with various cardiovascular disorders at high risk of thromboembolism. In this study, we investigated the hemostatic status of the left atrium in patients with paroxysmal atrial fibrillation (pAF). Methods: Patients with pAF (n=10) and chronic AF (cAF) (n=10), and control subjects without AF (n=10) were enrolled in this study. TAT, PIC, and PF4 levels were determined in specimens of blood obtained from the left atrium of AF patients who were undergoing catheter ablation. The blood specimens were also obtained from the left ventricle of control subjects. Results: Levels of PIC and PF4 did not differ significantly among 3 groups, whereas TAT levels in the left atrium of pAF and cAF patients were significantly higher than those in the left ventricle of control subjects (pAF: 29±19ng/ml, cAF: 28±19ng/ml, control: 3.1±3.0ng/ml, p&lt;0.01). Conclusion: We demonstrated for the first time that coagulation system is activated in the left atrium of pAF patients as well as cAF patients. This result suggests that even in a non-paroxysmal period, pAF patients are at high risk of thromboembolism, and anticoagulation therapy is indicated in those patients.

Association of D-dimer with microalbuminuria in patients with type 2 diabetes mellitus

Microalbuminuria has been reported to be related to incidence of cardiovascular complications in diabetes. No consistent findings have been obtained on the relationships of microalbuminuria with blood coagulation and fibrinolysis. The purpose of this study was to determine whether microalbuminuria is associated with blood markers reflecting coagulation and fibrinolysis activities in patients with type 2 diabetes. The relationships of albumin excretion rate (AER) with atherosclerosis-related variables, including blood coagulation and fibrinolysis markers, were investigated in patients with type 2 diabetes who showed normoalbuminuria (AER: less than 20 microg/min) and microalbuminuria (AER: 20 microg/min or higher and less than 200 microg/min). AER was significantly correlated with body mass index (BMI), maximum intima-media thickness of common carotid arteries, blood HDL cholesterol, uric acid, creatinine and D-dimer. On the other hand, AER showed no significant correlation with blood platelets, fibrinogen, thrombin-antithrombin III complex, plasmin-alpha2 plasmin inhibitor complex and plasminogen activator inhibitor-1. In multiple regression analysis, using age, sex, BMI, pulse pressure, hemoglobin A1c, HDL cholesterol, uric acid, creatinine, D-dimer and history of anti-thrombotic therapy as explanatory variables, only D-dimer showed a significant correlation with AER. The mean level of log-converted D-dimer after adjustment for age and sex was significantly higher in subjects with microalbuminuria than in those with normoalbuminuria. D-dimer is associated with microalbuminuria in patients with diabetes and this suggests that glomerular dysfunction is in part mediated by hypercoagulability.

Thoracic Aortic Plaque Enhances Hypercoagulability in Patients With Nonrheumatic Atrial Fibrillation

Patients with atrial fibrillation (AF) are at risk for thromboembolism, and coexistent cardiovascular diseases could affect their prothrombotic profiles. The relationship between plasma hemostatic markers and aortic atherosclerosis was determined in patients with AF or in sinus rhythm (SR). Sixty patients with nonrheumatic AF and 46 patients in SR who underwent transesophageal echocardiography and did not receive anticoagulant therapy constituted the study group. Markers for platelet activity (platelet factor 4 and beta-thromboglobulin), thrombotic status (thrombin-antithrombin III complex and prothrombin fragment 1+2 (F1+2)) and fibrinolytic status (plasmin-alpha2-plasmin inhibitor complex (PIC) and D-dimer) were determined. Levels of F1+2, PIC and D-dimer were higher in AF patients with severe atheroma than in those without severe atheroma (p<0.05). In patients in SR, hemostatic markers were not significantly increased even if they had severe aortic atherosclerosis. AF (Odds ratio (OR) 4.06, p=0.04) and age>or=75 years (OR 3.98, p=0.02) were independently predictive of elevated D-dimer levels and severe atheroma was predictive of elevated F1+2 levels (OR 5.52, p=0.04). Elderly patients with AF and severe aortic atherosclerosis might be in a prothrombotic state, and could benefit from intensive antithrombotic therapy.

Thrombin-antithrombin complex and α2-plasmin inhibitor-plasmin complex levels in singleton and twin pregnancies

Thrombin-antithrombin complex (TAT) is a sensitive marker for thrombin formation, and alpha2-plasmin inhibitor-plasmin complex (PIC) is a marker for fibrinolysis. Previous studies have shown that blood coagulation and fibrinolysis are activated in normal pregnancies. Thus, the present study examined changes in TAT and PIC levels during the course of singleton and twin pregnancies and compared these markers between the two pregnant groups. The subjects were 148 pregnant women, of whom 84 were women carrying single fetuses and 64 were women with twin fetuses. Their average gestational age at entry was 10, 20, 30 and 38 weeks of gestation in singleton pregnancies and 10, 20, 30 and 35 weeks in twin pregnancies. Peripheral blood was collected, and plasma was separated after centrifugation and then stored at -20 degrees C. The TAT levels increased significantly with the progression of pregnancy in both pregnant groups, whereas the PIC levels increased significantly only in singleton pregnancies between 30 and 38 weeks of gestation. The TAT levels were significantly higher in twin pregnancies than in singleton pregnancies. The PIC levels were significantly lower in twin pregnancies than in singleton pregnancies at 35-38 weeks. Thrombin formation might be enhanced with the progression of pregnancy in both pregnant groups. This enhancement might be more intensified in twin pregnancies. Fibrinolysis might increase only in singleton pregnancies from 30 to 38 weeks of gestation. Fibrinolysis might be less intensified in twin pregnancies than in singleton pregnancies only at 35-38 weeks.

Increased von Willebrand Factor in Acute Stroke Patients With Atrial Fibrillation

Plasma level of von Willebrand factor (vWF) is a useful marker not only for endothelial dysfunction, but also for left atrial thrombogenesis. We measured plasma levels of vWF antigen and other coagulation and fibrinolysis markers in 183 consecutive patients with acute ischemic stroke and compared these data between patients with and without atrial fibrillation (AF). vWF correlated with severity, outcome, and infarct size and were significantly higher in the AF group than in the non-AF group. The positive correlations of vWF with plasmin-alpha2 plasmin inhibitor complex and soluble fibrin monomer complex, and higher levels of vWF in patients with than without spontaneous echo contrast, indicate thrombogenesis in the left atrium. Plasma levels of vWF may reflect thrombogenesis in patients with AF.

Coagulation and fibrinolytic profiles and appropriate use of heparin after living‐donor liver transplantation

Heparin is widely used to reduce the incidence of vascular thrombosis after liver transplantation. Appropriate use of heparin based on changes in coagulation and fibrinolytic profiles, however, has not yet been discussed in detail. We performed living-donor liver transplantation for 128 adult patients. In this series, dalteparin (25 IU/kg/d) was administered until post-operative day (POD) 2. On POD 3, the anticoagulant drug was changed to heparin (unfractionated heparin sodium, 5000 U/d), the dose of which was changed according to the level of activated clotting time (ACT) targeted between 130 and 160 s. The plasma level of plasmin-alpha2 plasmin inhibitor complex, thrombin-antithrombin III complex (TAT), and fibrin degradation product D-dimer (FDP-DD) were monitored in the 21 patients. Predictors for heparin doses were analyzed among clinical parameters (n = 128). Four patients (3%) were complicated with thrombosis despite the above-mentioned anticoagulation protocol. Transfusion and/or relaparotomy for hemostasis were necessary for bleeding in 19 patients (15%). The TAT level markedly elevated until POD 3 and FDP-DD peaked later. The required heparin dose to maintain adequate ACT levels increased linearly until POD 8, and kept constant thereafter, which correlated with the weight of the liver graft (p = 0.01). Thus, frequent monitoring of the heparin dosage is necessary to keep the ACT level in the target range in the first post-operative week. High hemorrhage complications in our series indicate that the lower target ACT range may be preferable in the second post-operative week.

Clinical implication of plasma level of soluble fibrin monomer-fibrinogen complex in patients with abdominal aortic aneurysm

We prospectively studied the clinical implication of plasma level of soluble fibrin monomer (FM)-fibrinogen complex, a recently established molecular marker reflecting thrombin activity, in patients with abdominal aortic aneurysm (AAA) undergoing elective aortic repair. The study included 49 patients who underwent elective aneurysm repair using a gelatin-sealed or nonimpregnated Dacron prosthesis. Plasma level of soluble FM-fibrinogen complex was measured before surgery and on days 1, 3, 5, 7, and 10 postoperatively by latex agglutination assay utilizing monoclonal antibody IF-43. Plasma levels of thrombin-antithrombin complex (TAT), D-dimer, alpha2-plasmin inhibitor-plasmin complex (PIC), and fibrinogen were also evaluated. The preoperative level of soluble FM-fibrinogen complex showed variation in the degree of hemostatic activation, with fair correlations with TAT (r = 0.509, P < .001), D-dimer (r = 0.521, P < .001), and PIC (r = 0.579, P < .001). The patients with greater intraoperative blood loss (> or = 800 mL) showed a significantly elevated plasma level of soluble FM-fibrinogen complex preoperatively compared with those with less intraoperative blood loss (P = .009). Its postoperative fluctuation showed a similar pattern to that of TAT, reflecting the time course of coagulation activity. Gelatin impregnation of the Dacron vascular graft did not seem to influence the postoperative systemic coagulation mechanism. The results indicated that soluble FM-fibrinogen complex appears to be a useful diagnostic molecular marker to assess the activity of the coagulation system, and that its preoperative level may serve as a potential risk factor for intraoperative hemorrhagic diathesis in patients undergoing elective AAA repair.

Implications of fibrinogenolysis in patients with closed head injury.

The objective of this study was to determine the clinical significance of fibrinogenolysis in patients with isolated closed head injury. We correlated indices of fibrinolytic activity, fibrinogen degradation products (FgDP), and fibrin degradation products (FbDP) with outcome in order to accomplish this. This study consisted of 40 patients with isolated closed head trauma in whom blood sampling could be initiated within 3 h after injury. Patients were divided into two groups according to Glasgow Outcome Scale status at 3 months after injury, characterized as good recovery or moderate disability (group 1, n = 21); and severe disability, vegetative, or death (group 2, n = 19). The plasma fibrinogen concentration correlated with the Glasgow Coma Scale score on admission (r2 = 0.201, p < 0.01), and plasma fibrinogen concentrations in group 2 were lower than in group 1 (p < 0.05). Plasma concentrations of fibrin/fibrinogen degradation products (FDP) and plasmin-alpha2-plasmin inhibitor complex (PIC), molecular markers of activation of fibrinolysis, were higher in group 2 than in group 1 (p < 0.001), and both FgDP and FbDP concentrations in group 2 also were higher than in group 1 (p < 0.001). Both the FgDP and FbDP concentrations correlated with the PIC concentration. Moreover, the plasma FgDP concentrations correlated inversely with alpha2-plasmin inhibitor activity, a potent inhibitor of the fibrinolytic sysytem, as did the FbDP concentration. This study reveals that both fibrinolysis and fibrinogenolysis are involved in the coagulopathy that develops during the acute phase of head injury and correlate with fibrinolytic activity. Decreased activity of alpha2-plasmin inhibitor may contribute to fibrinogenolysis.

Relation of serum sialic acid to blood coagulation activity in type 2 diabetes.

The level of serum sialic acid, which is known to reflect atherosclerotic progress and to be related to the incidence of cardiovascular diseases, is increased in patients with diabetes. To elucidate the mechanism of the relation of serum sialic acid to fibrinogen, the relationship between serum sialic acid and markers of blood coagulation activity was investigated in type 2 diabetic patients. The concentration of serum sialic acid showed significant positive correlations with blood platelet count and with plasma concentrations of fibrinogen, D-dimer, thrombin-antithrombin III complex and plasmin-alpha2 plasmin inhibitor complex. These relationships were still significant after adjustment for age, sex, smoking history, body mass index, hemoglobin A, mean arterial pressure and low-density lipoprotein cholesterol. The correlation coefficient of blood fibrinogen with serum sialic acid was still significant after adjustment for D-dimer, thrombin-antithrombin III complex or plasmin-alpha2 plasmin inhibitor complex. On the contrary, blood fibrinogen showed no significant correlation with D-dimer, thrombin-antithrombin III complex or plasmin-alpha2 plasmin inhibitor complex, although an increase in blood fibrinogen is known to be an atherosclerotic risk factor. These results suggest that the serum sialic acid level reflects blood coagulation activity in type 2 diabetic patients and is related to blood fibrinogen level independently of blood coagulation activity.