Plasmin Inhibitor Complex Research Articles

Clinical analyses of 379 Japanese and 2 non-Japanese patients with venous or arterial vascular diseases: combined B cell anomalies, gastric cancer, and aggravated ectopic splenosis

To investigate the increased expression of activation-induced cytidine deaminase (AID) in vascular diseases, 379 Japanese and 2 non-Japanese composed of 87 varix, 81 arteriosclerosis obliterans (ASO), 206 aortic aneurysm (AA), and 7 venous thrombosis (VT) patients, whose ages were ranged from 60.7 ± 13.3 to 74.5 ± 8.8 years old, were analyzed clinically. Their coagulation anomalies were described well using their levels of thrombin antithrombin III complex (TAT), α2-plasmin inhibitor-plasmin complex (PIC), and fibrin/fibrinogen degradation products-D dimer (FDP-DD) in all the 4 diseases. VT showed the most severe coagulopathy with the highest levels of TAT, PIC, and FDP-DD, followed by AA. Among the seven VT cases, a lympho-plasmacytic hypophysitis (IgG4-related hypophysitis) case and a retroperitoneal fibrosis case combined with malignant lymphoma (ML) were found. Another VT case involving portal vein thrombosis (PVT) demonstrated a low level (59%) of protein C antigen (Ag) together with ulcerative colitis. In the 81 ASO, two showed ML combined with gastric cancer (GC). Cancers were examined in 87 varix, 81 ASO, and 199 AA cases. The frequency of cancer was 9% (33/367), in which five cases showed double cancer. The most common cancer was gut cancers which were found in 5% cases (20/367). GC was found in 14 cases, and intestinal cancers were found in six cases. The AA onset of ten GC cases seemed to occur at the same time as the onset of GC, 60–70% of which showed postoperative serum amylase elevation. Ectopic splenosis aggravated the clinical symptoms in three AA patients who had undergone gastrectomy, cholecystectomy, or hepatectomy. Bleeding (hemolysis) and thrombosis were main trigger signs in the three AA patients. One of the three developed PVT. Existing high levels of activation-induced cytidine deaminase (AID) were judged from severe coagulopathy, combined B cell malignancy, accompanied autoimmunity, the highest frequency of GC, and aggravated splenosis. AID downregulation was concluded to be an important factor in order to stop vascular disease progressions.

Clinical significance of the ratio between the alpha 2 plasmin inhibitor–plasmin complex and the thrombin–antithrombin complex in advanced non-small cell lung cancer

The aims of this study are to: (a) confirm the prognostic significance of the procoagulant molecules D dimer, thrombin-antithrombin complex (TAT), and plasmin-α2-plasmin inhibitor complex (PIC); (b) to evaluate hemostatic activation in patients with advanced non-small cell lung cancer (NSCLC); and (c) to delineate the relationships between markers of hemostasis and other clinical characteristics. In this study, a low PIC/TAT ratio and poor PS were significant independent negative prognostic factors for survival in patients with advanced NSCLC. The PIC/TAT ratio may become a surrogate marker for treatment with anticoagulants in the future.

Coagulation-Fibrinolysis Changes During Off-Pump Bypass: Effect of Two Heparin Doses

To date, no study has tested the effect of different heparin dosages on the hemostatic changes during off-pump coronary artery bypass graft (OPCABG) surgery, and a wide variety of empirical anticoagulation protocols are being applied. We tested the effect of two different heparin dosages on the activation of the hemostatic system in patients undergoing OPCABG procedures. Forty-two patients eligible for OPCABG procedures were assigned in a randomized fashion to low-dose heparin (150 IU/kg) or high-dose heparin (300 IU/kg). Prothrombin fragment 1+2, plasmin/alpha(2)-plasmin inhibitor complex, D-dimer, soluble tissue factor, tissue factor pathway inhibitor, total thrombin activatable fibrinolysis inhibitor (TAFI), and activated TAFIa were assayed by specific enzyme-linked immunosorbent assays at six different timepoints, before, during, and after surgery. Platelet function was evaluated by means of an in vitro bleeding time test, platelet function analyzer-100. The OPCABG surgery was accompanied by significant changes of all plasma biomarkers, indicative of systemic activation of coagulation and fibrinolysis. A significant increase in circulating TAFIa was detected perioperatively and postoperatively, and multiple regression analysis indicated that prothrombin F1+2 but not plasmin/alpha(2)-antiplasmin complex was independently associated with TAFIa level. Platelet function analyzer-100 values did not change significantly after OPCABG. All hemostatic changes were similar in the two heparin groups, even perioperatively, when the difference in anticoagulation was maximal. Both early and late hemostatic changes, including TAFI activation, are similarly affected in the low-dose and high-dose heparin groups, suggesting that the increase in heparin dosage is not accompanied by a better control of clotting activation during OPCABG surgery.

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.

The dynamics and clinical significance of alpha 2 plasmin inhibitor-plasmin complex and thrombin-antithrombin complex in postoperative pleural effusion following a pulmonary lobectomy

The overall incidence of postoperative alveolar air leakage (AAL) remains high; however, the mechanism regarding how to adequately heal such postoperative AAL remains to be elucidated. The aim of this study was to determine any correlations between the activity of the fibrinolytic and coagulation system in the postoperative pleural effusion and appearance or disappearance of postoperative AAL. This study prospectively investigated 25 patients who underwent a pulmonary lobectomy from July 2005 to March 2006. Pleural effusion was collected through the chest tube. Alpha 2 plasmin inhibitor-plasmin complex (PIC), as a fibrinolytic marker, and thrombin-antithrombin complex (TAT), as a coagulation marker, were measured. The activity of the coagulation system was higher than that of the fibrinolytic system. The concentration of TAT tended to increase (3rd vs 4th postoperative day [POD], P = 0.0907). The mean time of appearance and disappearance of postoperative AAL was 1.4 days and 3.2 days, respectively. The patients with postoperative AAL had a TAT level significantly below the average on the 3rd POD in comparison to the patients without postoperative AAL (P = 0.0163). Moreover, the concentration of TAT in patients with postoperative AAL was significantly lower than that in patients without postoperative AAL (1824.0 +/- 137.3 ng/ml vs 3444.0 +/- 287.6 ng/ml, P = 0.0113) on the 3rd POD. On the 4th POD, the concentration of TAT was almost same and there was no significance (P = 0.6759). This study demonstrated for the first time the course of the fibrinolytic and coagulation activity in the pleural effusion after a pulmonary lobectomy, and showed that the delayed activity of the coagulation system is associated with the appearance of the postoperative AAL.

QS16. The Dynamics and Clinical Significance of Alpha 2 Plasmin Inhibitor-Plasmin Complex and Thrombin-Anti Thrombin Complex in Postoperative Pleural Effusion Following Pulmonary Lobectomy

QS16. The Dynamics and Clinical Significance of Alpha 2 Plasmin Inhibitor-Plasmin Complex and Thrombin-Anti Thrombin Complex in Postoperative Pleural Effusion Following Pulmonary Lobectomy

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.

Comparison of a transdermal contraceptive patch vs. oral contraceptives on hemostasis variables

Purpose The aim of this study was to compare effects of the transdermal contraceptive patch, a desogestrel/ethinyl estradiol (EE)-containing, monophasic combination oral contraceptive (COC) and a levonorgestrel/EE-containing, triphasic COC on hemostasis variables. Study Design This was a randomized, open-label study of 104 young women who received six cycles of treatment. Blood was collected at baseline and on treatment; changes by Day 20/Cycle 6 in baseline hemostasis markers [prothrombin fragment 1+2 (F 1+2), plasmin–plasmin inhibitor complex (PAP) and fibrin degradation products ( d-dimer)] were assessed. Results All contraceptives induced similar increases in F 1+2 and d-dimer. Patch-induced PAP increases were less than with the monophasic and similar to the triphasic COC. Decreases in protein S and increases in sex hormone-binding globulin were greater with the patch than with either COC. Patch-induced increases in activated protein C resistance were greater than with the triphasic and similar to the monophasic COC. Conclusion These contraceptives appeared to accelerate baseline procoagulation processes to a similar extent and to change coagulation potency variables differently.

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.

Relationship between Hemostatic Markers and Platelet Indices in Patients with Aortic Aneurysm

The purpose of this study was to investigate whether platelet indices [platelet count, mean platelet volume (MPV), platelet-large cell ratio (P-LCR) and platelet distribution width (PDW)] could serve as diagnostic tools to evaluate the potential significance of platelet heterogeneity on thrombus formation in patients with aortic aneurysm (AA). Blood samples were obtained from 54 patients with AA (mean age 73 years; 40 males and 14 females), and from 120 age-matched controls (AC; mean age 74 years; 61 males and 59 females). Blood platelet indices were measured using an automated counter for all AC (n = 120) and AA (n = 54). Plasma thrombin-antithrombin III complex (TAT), α₂-plasmin inhibitor-plasmin complex (PIC), D-dimer, von Willebrand factor antigen (vWF:Ag) and interleukin-6 (IL-6) were also measured in part of AC and AA. In AA patients, TAT, PIC, D-dimer, vWF:Ag and IL-6 levels were significantly (p ≤0.0005) higher than in AC. In the patients, TAT was significantly inversely correlated with platelet count (ρ = –0.302, p = 0.038, n = 48), and significantly positively correlated with MPV (ρ = 0.329, p = 0.0373, n = 48), P-LCR (ρ = 0.361, p = 0.0134, n = 48) and PDW (ρ = 0.315, p = 0.0466, n = 48). PIC was negatively correlated with platelet count and inversely correlated with MPV, P-LCR and PDW. vWF:Ag was not correlated with platelet count, and inversely correlated with MPV, P-LCR and PDW in the patients. IL-6 was positively correlated with platelet count, and significantly inversely correlated with MPV, P-LCR and PDW in the patients. In AC, vWF:Ag was inversely correlated with platelet count and significantly positively correlated with MPV, P-LCR and PDW. However, PIC, TAT and IL-6 were not correlated with platelet indices in AC. D-dimer was not at all correlated with platelet indices both in AA and AC. In conclusion, the correlation between platelet indices and plasma hemostatic factor levels, e.g. TAT, PIC, D-dimer, vWF:Ag and IL-6, will be important factors for the understanding of platelet heterogeneity in patients with AA.

Effects of a protease inhibitor, ulinastatin, on coagulation and fibrinolysis in abdominal surgery

Ulinastatin is well known to inhibit the activity of polymorphonuclear leukocyte elastase (PMNE). The PMNE concentration correlates with the activities of coagulation and fibrinolysis. The purpose of the present study was to investigate the effects of ulinastatin, a protease inhibitor, on coagulation and fibrinolysis in abdominal surgery. Thirty patients, aged 40 to 70 years, with American Society of Anesthesiologists (ASA) physical status I or II, scheduled for major abdominal surgery, were enrolled. Anesthesia was induced with midazolam and thiopental, and was maintained with sevoflurane, nitrous oxide in oxygen, and an epidural block. An infusion of ulinastatin, 6000 units x kg(-1) in 30 min, was started 1 h after the start of surgery in the ulinastatin group (15 patients). In the control group (15 patients), no protease inhibitors were infused. White blood cell count; platelet count; prothrombin time; activated partial thromboplastin time; and plasma concentrations of PMNE, antithrombin (AT), fibrin/fibrinogen degradation product (FDP), fibrinogen, plasminogen, plasmin-(alpha2) plasmin inhibitor complex (PIC), and thrombin-antithrombin complex (TAT) were measured before, at the end of, and 12 h after surgery. TAT, PIC, and FDP after surgery were significantly lower in the ulinastatin group than in the control group. AT was decreased in the control group but not in the ulinastatin group, with significant differences between the two groups. Ulinastatin could inhibit coagulation and fibrinolysis in abdominal surgery.

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.

Evaluation of haemostatic molecular markers for diagnosis of disseminated intravascular coagulation in patients with infections

Early treatment of disseminated intravascular coagulation (DIC) is recommended but global coagulation tests used in authorized DIC criteria are not sensitive for diagnosis of early-phase DIC. We examined the plasma levels of thrombin-antithrombin complex (TAT), plasmin-plasmin inhibitor complex (PPIC) and D-dimer in patients with suspected DIC to determine the cutoff values for diagnosis of DIC. Plasma levels of D-dimer, TAT and PPIC were significantly elevated in patients with DIC and correlated with DIC score. The cutoff values were determined using the receiver operative curve analysis. The cutoff value represented the point at which the sensitivity curve crossed the specificity curve. The cutoff values of D-dimer, TAT and PPIC for DIC were 12.0 mug/ml, 11.0 ng/ml and 1.8 mug/ml, respectively. These values were moderately to highly sensitive for the diagnosis of DIC but not for poor outcome. The combination of D-dimer, TAT and PPIC showed high sensitivity and low specificity when one or more tests were positive, but showed low sensitivity and high specificity when all three tests were positive. We conclude that hemostatic molecular markers might be useful for the diagnosis of DIC and should be confirmed by several trials.

Tissue plasminogen activator in chronic subdural hematomas as a predictor of recurrence

Chronic subdural hematomas (CSDHs) recur in 7 to 18% of cases. The present study was conducted to determine whether serum or lesion concentrations of coagulofibrinolytic and angiogenic factors, which have been reported to be potential markers of CSDH development, might predict such recurrences. Sixty consecutive patients (mean age 71.5 years) with CSDHs (74 affected sides) were studied. Samples of serum in preoperative peripheral venous blood and of hematomas (obtained during surgery) were collected and analyzed. The CSDH recurred in six (8.1%) of the 74 affected sides in six patients. None of the values of the coagulative factors or tests in serum showed significant variation between cases with and those without recurrence. Among coagulofibrinolytic factors, tissue plasminogen activator (TPA) in hematomas demonstrated significantly greater levels in recurrent than in nonrecurrent cases; a similar tendency was noted for alpha2-plasmin inhibitor-plasmin complex in hematomas. Both factors were greater in the lesions than in the serum. Among the angiogenic factors, levels of hepatic growth factor (HGF) and vascular endothelial growth factor (VEGF) in hematomas were significantly greater than in serum, whereas those of basic fibroblast growth factor were rather lower. Note that comparisons between recurrent and nonrecurrent cases revealed no significant difference. Patients harboring CSDHs with high TPA concentrations on sampling at the initial surgery have a relatively high probability of recurrence and require follow up with computerized tomography scanning. Angiogenic factors, such as HGF and VEGF, might be candidate markers of CSDH enlargement but are not useful as predictors of recurrence.

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.

Elevated Plasma Levels of Fibrin Degradation Productsby Granulocyte-Derived Elastase in Patients with Disseminated Intravascular Coagulation

Plasma levels of granulocyte-derived elastase (GE-XDP), D-dimer, and soluble fibrin (SF) were examined in 177 patients with disseminated intravascular coagulation (DIC) of various etiologies. Plasma levels of GE-XDP and D-dimer, but not SF, were significantly high in patients with sepsis and solid cancer. The ratio of GE-XDP/ D-dimer was significantly high in patients with trauma, burn, and sepsis, suggesting that fibrinolysis due to GE-XDP may be dominant in DIC. Plasma levels of GE-XDP and D-dimer, but not SF, were significantly high in patients with overt DIC and correlated with DIC score. Plasma levels of GE-XDP, but not SF, correlated significantly with D-dimer. Plasma levels of D-dimer, but not SF, correlated significantly with plasmin plasmin inhibitor complex (PPIC). Plasma levels of GE-XDP and D-dimer, but not SF, were significantly high in nonsurvivors. Plasma levels of GE-XDP, but not SF, correlated significantly with sepsis-related organ failure assessment (SOFA) score. These results suggest that GE-XDP is a potentially useful marker for the diagnosis of overt-DIC and as a predictor of organ failure-related outcome.

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.