Unreliability of Serum- or Plasma-based Assays of D-dimer or Fibrin (Fibrinogen) Degradation Product for Diagnosing Periprosthetic Joint Infection: A Prospective Parallel Study.

OBJECTIVE: The ability of D-dimer to diagnose periprosthetic joint infection (PJI) before revision hip or knee arthroplasty is still controversial, and the differences in diagnostic ability between serum- or plasma-based assays of D-dimer and fibrin (fibrinogen) degradation product (FDP) are uncertain. The prospective parallel study was performed to determine the ability of D-dimer to diagnose PJI before revision hip or knee arthroplasty, and the differences in diagnostic ability between serum- or plasma-based assays of D-dimer and FDP. METHODS: Patients undergoing knee or hip arthroplasty at our institution were prospectively enrolled into the following groups: those without inflammatory diseases who were undergoing primary arthroplasty ("Prim" group), those with inflammatory arthritis who were undergoing primary arthroplasty ("Prim/Inflam"), those undergoing revision arthroplasty because of aseptic failure ("Rev/Asept"), or those undergoing revision arthroplasty because of PJI ("Rev/PJI"). The ability of preoperative levels of D-dimer or FDP in serum or plasma to diagnose PJI in each group was assessed using areas under receiver operating characteristic curves (AUCs) and other diagnostic performance indicators. The diagnostic performance of these assays was compared with that of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). RESULTS: In the final analysis, Prim included 42 patients; Prim/Inflam, 40; Rev./Asept, 62; and Rev./PJI, 47. D-dimer assays led to AUCs of 0.635 in serum and 0.573 in plasma, compared to 0.593 and 0.607 for FDP. Even in combination with CRP or ESR, these assays failed to perform as well as the combination of CRP and ESR for diagnosing PJI. CONCLUSION: Levels of D-dimer or FDP in serum or plasma, whether used alone or together with CRP or ESR, are unreliable for diagnosing PJI before revision arthroplasty.

Efficacy of Coagulofibrinolytic Markers for Postoperative Prediction of Venous Thromboembolism in Colorectal Surgery Patients: A Retrospective Observational Study.

Objectives: A low rate of the incidence of venous thromboembolism (VTE) after surgeries that are preoperatively classified as having high risk of VTE has been reported in recent years. We seek to identify the optimal cases to receive perioperative pharmacologic thromboprophylaxis. In this study, we evaluated the incidence rate of VTE among patients undergoing colorectal surgery who did not receive perioperative pharmacologic thromboprophylaxis, and the ability of coagulofibrinolytic markers to predict the postoperative development of VTE. Methods: We retrospectively analyzed the rate of postoperative development of VTE in 70 patients undergoing elective colorectal surgery without perioperative pharmacologic thromboprophylaxis and the ability of coagulofibrinolytic markers to predict the development of VTE. Results: The incidence of VTE was observed in 11 patients (15.7%); all cases were asymptomatic and distal-type deep vein thrombosis (DVT). Comparisons of time course changes in perioperative coagulofibrinolytic markers between patients with and without DVT revealed significant differences in soluble fibrin (SF), thrombin-antithrombin complex (TAT), fibrin/fibrinogen degradation product (FDP) and D-dimer. Dynamic postoperative physiological coagulofibrinolytic responses were shown, but all four markers at each postoperative point demonstrated moderate accuracy (median area under the curve [AUC]: 0.788, median sensitivity: 0.865, median specificity: 0.644) for predicting the development of DVT. Conclusions: The incidence of postoperative VTE was low in patients with colorectal surgery even in those who did not receive perioperative pharmacologic thromboprophylaxis. SF, TAT, FDP and D-dimer were useful for predicting the development of DVT when we set cut-off values taking the physiological perioperative coagulofibrinolytic responses into consideration.

Predictive value of D-dimer and fibrinogen degradation product for splanchnic vein thrombosis in patients with severe acute pancreatitis: a single-center retrospective study.

BACKGROUND AND AIM: Early diagnosis of splanchnic vein thrombosis (SVT) after severe acute pancreatitis (SAP) remains difficult because of its insidious onset. Common serum markers for thrombosis such as D-dimer (D-D) have lost their diagnostic value due to their elevation in non-thrombotic patients with SAP. The aim of this study is to predict SVT after SAP using common serum indicators of thrombosis by establishing a new cut-off value. METHODS: 177 SAP patients were included in a retrospective cohort study from September 2019 to September 2021. Patient demographics, dynamic changes of coagulation and fibrinolysis indicators were collected. Univariate analyses and binary logistic regression analyses were applied to assess potential risk factors for the development of SVT in SAP patients. A receiver operating characteristic (ROC) curve was generated to assess the predictive value of independent risk factors. Moreover, clinical complications and outcomes were compared between two groups. RESULTS: Among 177 SAP patients, 32 (18.1%) developed SVT. The most common cause of SAP was biliary (49.8%), followed by hypertriglyceridemia (21.5%). Multivariate logistic regression analyses showed that D-D (OR, 1.135; 95%CI, 1.043-1.236; p = 0.003) and fibrinogen degradation product (FDP) (OR, 1.037; 95%CI, 1.015-1.060; p = 0.001) were independent risk factors for SVT development in patients with SAP. The area under ROC curve for D-D was 0.891 (p = 0.003, sensitivity= 95.3%, specificity = 74.1%) at a cut-off value of 6.475, and the area under ROC curve for FDP was 0.858 (p = 0.001, sensitivity = 89.4%, specificity = 72.4%) at a cut-off value of 23.155. CONCLUSION: D-D and FDP are significant independent risk factors with high predictive value for SVT in patients with SAP.

Comparative Evaluation of Plasma Fibrinogen Degradation Product and Salivary Fibrin Precipitating Factor in Oral Submucous Fibrosis Patients and Betel Quid Chewers.

Aim and Objectives: Estimation and correlation of plasma fibrinogen degradation product (FDP) and salivary fibrin precipitating factor (FPF) in oral sub mucous fibrosis (OSMF) patients, betel quid chewers without OSMF and healthy individuals. The study aims to evaluate whether FDP and FPF can be used as a marker for development and progression of OSMF and whether there is any correlation between the two. Methodology: The study included 163 subjects grouped into three categories, Group 1, which included 54 control patients, Group 2, which included 55 betel quid chewers, and Group 3, which included 54 clinically confirmed OSMF patients. All of them were subjected to the estimation of plasma FDP and salivary FPF. Results: FDP was present in 52 (96.3%) patients in Group 3, 2 (3.6%) patients in Group 2, and 1 patient in Group 1 (1.9%). FPF was positive in eight patients. The correlation of FDP and FPF was done by Fisher's exact test and was found to be statistically nonsignificant. Conclusion: In the present study, FDP was positive in 52 (96.3%) OSMF patients; hence, FDP may be used as an early indicator of OSMF. FDP was found to be positive in two patients with a habit of chewing betel quid without OSMF. It may be hypothesized that these patients are more likely to develop OSMF. Hence, the estimation of FDP may be used as a diagnostic test to predict an impending OSMF before it could manifest itself clinically. FPF was negative in some OSMF patients, may be because it is below the detectable range.

Study on influencing factors of plasma FDP and D-dimer levels of newborns in NICU / 国际儿科学杂志

Objective:To investigate the influencing factors of physiological and pathological conditions at birth of newborn and gestational conditions of pregnant mothers on plasma fibrin/fibrinogen degradation products(FDP)and D-dimer levels.Methods:From May 1, 2018 to October 31, 2018, 222 newborns admitted to NICU of the Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology were enrolled in this study.Newborns were sent to NICU within 2 hours after birth and venous blood was collected immediately.The levels of FDP and D-dimer were detected by immunoturbidimetry.Groups were divided according to different gender, gestational age, birth weight, relationship between gestational age and birth weight, mode of delivery, asphyxia at birth, acidosis, antenatal hormone use, anticoagulant drugs, and perinatal risk factors(gestational hypertension, premature rupture of membranes, abnormal placenta, gestational diabetes). The levels of plasma FDP and D-dimer were compared among the groups.Mann Whitney U test, Kruskal Wallis H test, Spearman rank correlation and generalized linear model were used for statistical analysis. Results:The plasma FDP and D-dimer values of 222 NICU neonates were skewed at birth, with median values of 6.00 mg/L and 1.74 mg/L, and quartile distances of 10.40 mg/L and 2.55 mg/L, respectively.The concentrations of FDP in neonates born to natural labour and cesarean section were 11.70 mg/L and 5.30 mg/L, respectively, and D-dimer concentrations were 2.92 mg/L and 1.52 mg/L, respectively.The FDP and D-dimer levels were significantly higher in the former(Z values were -4.006 and -4.198, respectively, P<0.05). The levels of FDP and D-dimer in newborns with different gestational age, different birth weight and different blood pH values were compared respectively, and the differences were statistically significant( χ2 values were 15.322, 18.394, 9.677, 11.492, 7.023 and 8.345, respectively, P<0.05). Further analysis showed that the levels of FDP and D-dimer in neonates with gestational age < 34 weeks were significantly higher than those in~<37 weeks group and ≥37 weeks group( P<0.05). The FDP and D-dimer levels in the birth weight<1 500 g group were significantly higher than those in~<2 500 g group and ≥2 500 g group( P<0.05). Higher FDP and D-dimer levels were found in the pH<7.20 group than in the pH ≥7.35 group( P<0.05). A generalized linear model was established for multifactor analysis.The results showed that the concentration of FDP and D-dimer in plasma was related to gestational age, birth weight and arterial pH value. Conclusion:The levels of plasma FDP and D-dimer in NICU newborns at birth were influenced by gestational age, birth weight and acid-base balance.

Increase in Fibrinogen Degradation Product Levels 5 Days after a Traumatic Insult.

CONTEXT: Few reports have investigated the time course of fibrinogen (or fibrin) degradation product (FDP) levels for trauma patients in the subacute phase. AIMS: This study aimed to investigate the time course of the FDP levels among patients with moderate and severe trauma in the subacute phase. SETTINGS AND DESIGN: A retrospective medical chart review in a single hospital. SUBJECTS AND METHODS: From September 2017 to March 2018, a medical chart review was retrospectively performed for all patients with trauma who were admitted to our department, and these patients were included as participants in the present study. We collected the data on each patient's sex, age, presence of head injury, mechanism of injury, Glasgow Coma Scale on arrival, systolic blood pressure, heart rate, type of injury (blunt versus penetrating), injury severity score, complication of infection, surgical procedure, duration of admission, survival rate, and FDP level from the 1st to 7th hospital day. The average level of FDP on each hospital day was compared with that on the previous day. STATISTICAL ANALYSIS USED: The statistical analyses were performed using a paired Student's t-test. P < 0.05 was considered to indicate a statistically significant difference. RESULTS: From the 1st to 4th hospital day, the average level of FDP significantly diminished day by day. However, from the 5th hospital day, the average level significantly increased. This trend persisted even after excluding the complications of infection and surgical procedures performed between the 2nd and 7th hospital day. CONCLUSIONS: Among trauma patients, the average level of FDP significantly diminished day by day from the admission to the 4th hospital day; however, from the 5th hospital day, the average level significantly increased. Further studies are needed to determine the time course of FDP or D-dimer levels in the long term and when FDP levels return to normal limits.

New method for determining fibrinogen and FDP threshold criteria by artificial intelligence in cases of massive hemorrhage during delivery.

AIM: To investigate the feasibility of a novel method using artificial intelligence (AI), in which the fibrinogen criterion was determined by the quantitative relation between the distributions of fibrin/fibrinogen degradation products (FDPs) and fibrinogen. METHODS: A dataset of 154 deliveries comprising more than 2000 g of blood lost due to hemorrhage, excluding disseminated intravascular coagulation (DIC), among patients from eight national perinatal centers in Japan from 2011 to 2015 were obtained. The fibrinogen threshold criterion was identified by using the function that best fit the distributions of FDP as determined by AI. FDP production was described by differential equations using a dataset containing fibrinogen levels less than the fibrinogen criterion and solved numerically. RESULTS: A fibrinogen level of 237 mg/dL as the threshold criterion was obtained. The FDP threshold criteria were 2.0 and 8.5 mg/dL for no coagulopathy and a failed coagulation system, respectively. CONCLUSION: The fibrinogen threshold criterion for patients with massive hemorrhage excluding DIC at delivery were obtained by selecting the functions that best fit the distributions of FDP data by using AI.

Preoperative elevated FDP may predict severe intraoperative hypotension after dural opening during decompressive craniectomy of traumatic brain injury.

PURPOSE: Coagulation disorder and intraoperative hypotension are representative complications of traumatic brain injury which cause worse perioperative outcome. The aim of this study was to survey the relation of coagulation disorder and intraoperative hypotension (IH) during decompressive craniectomy. METHOD: Patients who underwent emergency decompressive craniectomy due to traumatic brain injury were retrospectively surveyed. The relation between preoperative coagulation date and intraoperative hypotension (systolic blood pressure < 60 mmHg after dural opening) was analyzed. RESULTS: Of 41 patients screened, 12 patients (27.9%) developed IH. Fibrinogen degradation products (314 vs 64.4 µg/mL; p = 0.01) were significantly higher in the IH group. In contrast, fibrinogen (181 vs 239 mg/dL; p = 0.01) was significantly lower in the IH group. Reduction rate of sBRP before and after dural opening (%) was higher in IH group than in non-IH group (49.1 vs 27.6%: p = 0.001). CONCLUSIONS: Preoperative elevated FDP may predict IH after dural opening during traumatic decompressive craniectomy.

Correlation study of serum homocysteine with renal function and coagulation indexes in hypertensive patients / 中华检验医学杂志

Objective The purpose of this study was to investigate the correlation of serum homocysteine with renal function and coagulation indexes in hypertensive patients .Methods Through retrospective design , 224 hypertensive patients and 212 healthy subjects who sought medical service in Henan Province Hospital of TCM during 2017 to 2018, were divided into four groups according to hypertension and homocysteine level, that was normotensive normal Hcy group (103 patients), normotensive high Hcy group (109 patients), hypertensive normal Hcy group (115 patients), and hypertensive high Hcy group ( 109 patients ) .Serum homocysteine , serum lipid and renal function indexes were detected by automatic biochemical analyzer .The level of coagulation indexes were detected by automatic coagulation analyzer and platelet was tested by automatic blood cell analyzer .Comparisons of variables between four groups were evaluated by one way ANOVA .The correlation was expressed by the Pearson′s correlation coefficient analysis.Multivariate linear regression analysis was performed to identify variables and influence factor associated with Hcy.Results The concentration of Urea in hypertensive high Hcy group (5.73 ± 1.67)mmol/L was significantly increased compared to normotensive normal Hcy group (4.79 ±1.05)mmol/L (t=3.508, P=0.001).The leve of Urea in hypertensive high Hcy group (5.73 ±1.67) mmol/L was significantly increased compared to normotensive high Hcy group (5.21 ±1.21) mmol/L ( t=1.983, P=0.049) and hypertensive normal Hcy group (4.81 ±1.21)mmol/L (t=3.600, P=0.000).The level of Crea in hypertensive high Hcy group ( 79.52 ±25.92 )μmol/L was significantly increased compared to normotensive normal Hcy group (58.39 ±12.83)μmol/L (t=6.121, P=0.000) and hypertensive normal Hcy group (60.93 ±13.74)μmol/L (t=5.526, P=0.000).The level of UA in hypertensive high Hcy group (389.96 ±96.03)μmol/L were significantly higher than normotensive normal Hcy group (293.65 ± 89.94)μmol/L (t=5.722, P=0.000),normotensive high Hcy group (327.02 ±66.55)μmol/L (t=3.837, P=0.000 ) and hypertensive normal Hcy group ( 291.50 ±73.42 )μmol/L ( t=6.128, P=0.000).The level of BMG,CysC in hypertensive high Hcy group and normotensive high Hcy group were higher than normotensive normal Hcy group and hypertensive normal Hcy group .The level of RBP ,D-Dimer, FDP in hypertensive high Hcy group were significantly higher than that of the other three groups .Serum homocysteine correlated positively with Urea (r=0.276,P=0.000),Crea(r=0.389,P=0.000),UA(r=0.339,P=0.000),BMG(r=0.221,P=0.002),RBP(r=0.396,P=0.000),CysC(r=0.200,P=0.006).Multivariate regression analysis showed that the Hcy level was the influencing factors of Urea , Crea and RBP, and hypertension was the influencing factor of Crea , UA, BMG RBP and CysC. Conclusions Hypertensive patients with hyperhomocysteinemia caused renal injury easily . Serum homocysteine may play an important role in renal injury and further affect the occurrence and development of hypertension by impairing the function of platelet , coagulation and fibrinolysis system .

Clinical significance of coagulation factors in operable colorectal cancer.

Abnormal hemostasis in cancer patients has prev iously been studied. The primary objective of the present study was to evaluate the association between preoperative hemostasis markers and clinicopathological parameters, and to identify a hemostasis marker affecting survival in patients following curative resection for colorectal cancer. A total of 170 patients who underwent curative surgery for colorectal carcinoma were evaluated. Preoperative coagulation tests included platelet, prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, D-dimer and fibrinogen degradation product (FDP). The clinicopathological variables, including age, gender, tumor location (rectum/colon), tumor size (≥5 cm vs. <5 cm), depth of tumor invasion, lymph node metastasis, stage, lymphovascular invasion, margin involvement and histological differentiation were analyzed. The median age of analyzed patients was 63 years (range, 28-84). The male to female ratio was 62:38. Increased levels of plasma fibrinogen, PT and platelet count (PLT) were associated with larger tumor size (P<0.001, P=0.015 and P=0.002, respectively). Increased plasma fibrinogen levels were significantly associated with depth of tumor invasion and stage (P=0.014 and P=0.048, respectively). Increased plasma D-dimer and FDP levels were significantly associated with tumor node metastasis stage (P=0.031 and P=0.002, respectively). Prolonged PT level (≥11.7 sec), hyper-fibrinogenemia (≥327 mg/dl), high D-dimer level (≥1.3 µg/ml) and increased FDP level (≥2.7 µg/ml) were the prognostic factors associated with shorter survival. Preoperative plasma fibrinogen level was significantly associated with tumor size and depth of tumor invasion. Preoperative plasma prolonged PT level, hyperfibrinogenemia, high D-dimer level and increased FDP level may function as hemostasis markers that predict overall survival in operable patients with colorectal cancer.

Fibrinogen degradation product levels on arrival for trauma patients requiring a transfusion even without head injury.

BACKGROUND: There have been few reports on the clinical significance of the fibrinogen degradation product (FDP) level in trauma patients with and without head injury. We retrospectively analyzed trauma patients with or without head injury to investigate the clinical significance of the FDP level. METHODS: From April 2013 to June 2015, a medical chart review was retrospectively performed for all patients with trauma. The exclusion criteria included patients who did not receive a transfusion. The patients were divided into two groups: a FDP>100 group, which included patients who had an FDP level on arrival over 100 ng/mL, and a FDP≤100 group. RESULTS: The ratio of open fractures and the prothrombin ratio in the FDP>100 group were significantly smaller than those observed in the FDP≤100 group. The average age, ratio of blunt injury, Injury Severity Score (ISS), volume of transfusion and mortality ratio in the FDP>100 group were significantly greater than those in the FDP≤100 group. There was a weakly positive correlation between the FDP level and ISS (R=0.35, P=0.002), but it was not associated with the transfusion volume. The results of an analysis excluding patients with head injury showed a similar tendency. CONCLUSION: The FDP levels may be a useful biochemical parameter for the initial evaluation of the severity of trauma and mortality even in blunt traumatized patients without head injury or with stable vital signs.

Fibrinogen degradation product levels on arrival for trauma patients requiring a transfusion even without head injury / 世界急诊医学杂志（英文）

@#BACKGROUND:There have been few reports on the clinical significance of the fibrinogen degradation product (FDP) level in trauma patients with and without head injury. We retrospectively analyzed trauma patients with or without head injury to investigate the clinical significance of the FDP level. METHODS:From April 2013 to June 2015, a medical chart review was retrospectively performed for all patients with trauma. The exclusion criteria included patients who did not receive a transfusion. The patients were divided into two groups:a FDP>100 group, which included patients who had an FDP level on arrival over 100 ng/mL, and a FDP≤100 group. RESULTS:The ratio of open fractures and the prothrombin ratio in the FDP>100 group were significantly smaller than those observed in the FDP≤100 group. The average age, ratio of blunt injury, Injury Severity Score (ISS), volume of transfusion and mortality ratio in the FDP>100 group were significantly greater than those in the FDP≤100 group. There was a weakly positive correlation between the FDP level and ISS (R=0.35, P=0.002), but it was not associated with the transfusion volume. The results of an analysis excluding patients with head injury showed a similar tendency. CONCLUSION:The FDP levels may be a useful biochemical parameter for the initial evaluation of the severity of trauma and mortality even in blunt traumatized patients without head injury or with stable vital signs.

Co-occurrence of hyperleukocytosis and elevated fibrin-fibrinogen degradation product levels is a risk factor for early intracranial hemorrhage in patients with de novo acute leukemia.

Early intracranial hemorrhage (eICH) is a potentially fatal complication of acute leukemia. We analyzed risk factors for eICH in patients with de novo acute leukemia. Ninety-one de novo acute leukemia patients at our institution between September 2003 and June 2014 were included. Of the 91 patients, eight (8.8 %) and 83 were included in the eICH and non-eICH groups, respectively. Univariate analysis demonstrated that white blood cell (WBC) count (P = 0.018), fibrin-fibrinogen degradation product (FDP) level (P = 0.0075), co-occurrence of WBC ≥50,000/µl and FDP level >40 µg/ml (P < 0.001), and fever (P = 0.248) were all significant predictors of eICH at the 0.25 level. In a subsequent multivariate analysis involving these parameters, only the combination of hyperleukocytosis and elevated FDP levels was found to be significant at the 0.05 level. A significant difference in the duration of the overall survival (OS) period was detected between patients that did and did not exhibit the combination of hyperleukocytosis and elevated FDP levels (P < 0.001). Co-occurrence of hyperleukocytosis and elevated FDP levels is a significant risk factor for eICH in patients with de novo acute leukemia and has a significant adverse affect on OS.

Evaluating the diagnostic value of vWF:Ag, D-D and FDP in patients with acute cerebral infarction using ROC curves.

Cerebral infarction is usually associated with arteriosclerosis, vascular endothelial cell injury and blood flow through the vascular system. The diagnostic value of markers, including von Willebrand factor antigen (vWF:Ag), D-dimer (D-D) and fibrinogen/fibrin degradation product (FDP), have not been studied in patients with acute cerebral infarction. Thus, the aim of the present study was to use receiver operating characteristic (ROC) curves to evaluate the diagnostic significance of vWF:Ag, D-D and FDP in 94 cases of acute cerebral infarction. The results revealed that vWF:Ag and D-D concentrations were significantly higher in acute cerebral infarction patients as compared with the normal controls (P<0.01), whereas no statistically significant difference in FDP was observed between the groups (P>0.01). Plasma vWF:Ag and D-D concentrations significantly correlated with the National Institute of Health Stroke Scale (NIHSS) scores (r=0.625 and 0.582, respectively; P<0.01). In addition, the vWF:Ag concentration significantly correlated with the D-D concentration (r=0.320; P<0.01), whereas FDP concentration did not correlate with D-D or vWF:Ag concentrations or the NIHSS scores (r=0.172, 0.188 and 0.065, respectively; P>0.05). The area under the ROC curve using vWF:Ag as a diagnostic marker in patients with acute cerebral infarction was 0.900, while for D-D the area was 0.795 and for FDP the area was 0.465. Logistic regression analysis revealed that the odds ratios of vWF:Ag and D-D were 16.727 and 2.324, respectively, which were statistically significant (P<0.001 and 0.023, respectively). These results indicated that using vWF:Ag as a diagnostic marker is likely to significantly improve the sensitivity of diagnosing patients with acute cerebral infarction. The diagnostic value of vWF:Ag concentration was significantly higher compared with D-D and FDP levels.

Functional characterization of a slow and tight-binding inhibitor of plasmin isolated from Russell's viper venom.

BACKGROUND: Snake venoms are rich in Kunitz-type protease inhibitors that may have therapeutic applications. However, apart from trypsin or chymotrypsin inhibition, the functions of most of these inhibitors have not been elucidated. A detailed functional characterization of these inhibitors may lead to valuable drug candidates. METHODS: A Kunitz-type protease inhibitor, named DrKIn-II, was tested for its ability to inhibit plasmin using various approaches such as far western blotting, kinetic analyses, fibrin plate assay and euglobulin clot lysis assay. In addition, the antifibrinolytic activity of DrKIn-II was demonstrated in vivo. RESULTS: DrKIn-II potently decreased the amidolytic activity of plasmin in a dose-dependent manner, with a global inhibition constant of 0.2nM. Inhibition kinetics demonstrated that the initial binding of DrKIn-II causes the enzyme to isomerize, leading to the formation of a much tighter enzyme-inhibitor complex. DrKIn-II also demonstrated antifibrinolytic activity in fibrin plate assay and significantly prolonged the lysis of the euglobulin clot. Screening of DrKIn-II against a panel of serine proteases indicated that plasmin is the preferential target of DrKIn-II. Furthermore, DrKIn-II treatment prevented the increase of FDP in coagulation-stimulated mice and significantly reduced the bleeding time in a murine tail bleeding model. CONCLUSION: DrKIn-II is a potent, slow and tight-binding plasmin inhibitor that demonstrates antifibrinolytic activity both in vitro and in vivo. GENERAL SIGNIFICANCE: This is the first in-depth functional characterization of a plasmin inhibitor from a viperid snake. The potent antifibrinolytic activity of DrKIn-II makes it a potential candidate for the development of novel antifibrinolytic agents.

Clinical significance of plasma D-dimer, fibrinogen and fibrin/fibrinogen degradation product detection in patients with chronic obstructive pulmonary disease / 中国医师进修杂志

Objective To investigate clinical significance of plasma D-dimer (D-D),fibrinogen (FIB) and fibrin/fibrinogen degradation product (FDP) in patients with chronic obstructive pulmonary disease (COPD).Methods The level of plasma D-D,FIB and FDP in 150 patients with COPD and 80 healthy persons were detected,and compared.Results The level of plasma D-D,FIB and FDP in COPD patients were significantly higher than those in healthy persons[(2.16 ± 0.61) mg/L vs.(0.55 ± 0.04) mg/L,(5.88 ± 1.52) g/L vs.(3.12 ± 0.35) g/L,(7.18 ± 1.63) mg/L vs.(3.62 ± 1.55) mg/L],there were significant differences (P ＜ 0.01).Conclusion Monitoring the level of plasma D-D,FIB and FDP in COPD patients can provide reliable basis in hypercoagulable state and primary and secondary hyperfibrinolysis.

Quantitative estimation of Serum Fibrinogen Degradation Product levels in Oral Premalignant and Malignant lesions.

BACKGROUND: A specific association between cancer and the hemostatic system has been recognized for decades. Fibrinogen degradation product (FDP) is one of the factors, which opposes coagulation causing fibrinolysis. The mechanism of fibrinolysis can be used by the malignant cells to facilitate invasion into surrounding tissues and metastases to distant organs by breaking the fibrin barrier. The coagulation cascade also plays an important role in both the formation of tumour stroma and the promotion of hematogenous metastasis. The present study was undertaken to evaluate the serum FDP levels in individuals without any oral lesions and those with oral premalignant and malignant lesions, and determine whether the estimation of the same can be used as an aid in early diagnosis. MATERIALS & METHODS: 25 cases each of Leukoplakia, Oral submucous fibrosis and Oral squamous cell carcinomas (OSCC) and normal control cases were selected. The OSCC cases were staged according to the TNM classification. Diagnosis of all cases was confirmed by histopathological examination. The aspirated serum was then subjected to the Thrombo-Wellco test which was used for the biochemical analysis of FDP. RESULTS: Increased serum FDP levels were seen corresponding to the stage of the OSCC, but no appreciable difference was noted between the histological grades or in cases of premalignant lesions. CONCLUSIONS: The study demonstrates that FDP levels correlate with the cancer stage and progression. Thus, the estimation of serum FDP levels can be used as a reliable prognostic indicator and as a biologic marker of tumour spread How to cite this article: Gharat L, Rathod GP. Quantitative estimation of Serum Fibrinogen Degradation Product levels in Oral Premalignant and Malignant lesions. J Int Oral Health 2013; 5(5):65-72.

Distinct reactivity of the commercially available monoclonal antibodies of D-dimer and plasma FDP testing to the molecular variants of fibrin degradation products.

Fibrin degradation products (FDP) are an important marker of coagulopathy. We assessed the reactivity of the monoclonal antibodies used in clinical laboratory testing (6 D-dimer reagents, D-dimer-1-6; 4 plasma FDP reagents, plasma FDP-1-4) to quantify FDP using in vitro-generated FDP as well as FDP in clinical samples. The monoclonal antibodies used in D-dimer-1, -2, -5, and -6 reacted poorly to the low molecular weight forms of in vitro-generated FDP. The monoclonal antibodies used in D-dimer-3 and -4 had better reactivity to the low molecular weight forms of in vitro-generated FDP. The monoclonal antibodies used in plasma FDP-2, -3, and -4 reacted well to the high and low molecular weight FDP forms, while the monoclonal antibody in plasma FDP-1 reacted poorly to the low molecular weight FDP forms. Analysis of clinical samples revealed deviations in FDP molecular weight forms in DIC samples. The reactivity of the monoclonal antibodies of laboratory FDP testing to FDP variants in clinical samples was similar to that of in vitro-generated FDP. In conclusion, the monoclonal antibodies used in clinical laboratories to detect FDP have distinct reactivity to the molecular variants of FDP generated in vitro as well as those present in clinical samples. Our findings support the consensus for the standardization of D-dimer and plasma FDP testing.

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.

INTRODUCTION: Post-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 METHODS: Fifty-two resuscitated patients were divided into two groups: 22 DIC and 30 non-DIC patients. RESULTS: The 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. CONCLUSIONS: Thrombin 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.

Macrovascular dysfunction detected by comparison of serum FDP detected by simplified venous occlusion test in patients with NIDDM and CVA / 대한내과학회지

OBJECTIVES: In diabetic patients, the incidence of atherosclerotic disease are increased, which may be due to decreased fibrinolytic activity. The aim of study is to elucidate the relationship between angiopathies and vascular function evaluated by simplified venous occlusion test in patients with non-insulin dependent diabetes mellitus (NIDDM) and cerebrovascular accident (CVA). METHODS: The study was conducted on 63 patients who were hospitalized during the period from March 1, 1994 to May 30, 1997. The serum concentration of fibrinogen degradation products (FDP) was measured before and 5 min after venous occlusion in 31 NIDDM patients, 16 CVA patients and 16 age-matched control subjects. FDP was measured with the anti-fibrinogen- coated latex particle agglutinin assay system. RESULTS: 1) The basal serum FDP level was higher in diabetic patients with macroangiopathy (12.3+/-5.8 ug/ml) and patients with CVA (11.2+/-5.1 ug/ml) than in control subjects (5.7+/-1.8 ug/ml) (p<0.05). 2) The increment of serum FDP level after venous occlusion in diabetic patients with microangiopathy (6.6+/-2.2 to 10.3+/-4.1 ug/ml) and control subjects (5.7+/-1.8 to 11.4+/-4.3 ug/ml) was significantly higher than basal serum FDP level (p<0.05). But the increment of serum FDP level after venous occlusion in diabetic patients with macroangiopathy (12.3+/-5.8 to 15.2+/-5.1 ug/ml) and patients with CVA (11.2+/-5.1 to 13.7+/-4.8 ug/ml) wasn't significantly higher than basal serum FDP level. 3) The increment rate of serum FDP after venous occlusion in diabetic patients with macroangiopathy (24.4+/-29.3%) and patients with CVA (29.4+/-34.5%) was significantly lower than diabetic patients with microangiopathy (66.3+/-71.7%) and control subjects (84.1+/-69.3%) (p<0.05). CONCLUSION: The responsiveness of fibrinolytic activity to venous occlusion was significantly lower in diabetic patients with macroangiopathy, as in patients with CVA, compared with that in control subjects. We conclude that measurement of the increase in serum FDP concentration 5 min after venous occlusion may be useful to detect vascular dysfunction in patients with macrovascular disease caused by atherosclerosis.