Fibrin/fibrinogen Degradation Products Levels Research Articles

The clinical significance of TAT, PIC, TM, and t-PAIC in vascular events of BCR/ABL-negative myeloproliferative neoplasms

Predicting the likelihood vascular events in patients with BCR/ABL1-negative myeloproliferative neoplasms (MPN) is essential for the treatment of the disease. However, effective assessment methods are lacking. Thrombin-antithrombin complex (TAT), plasmin-α2- plasmininhibitor complex (PIC), thrombomodulin (TM), and tissue plasminogen activator-inhibitor complex (t-PAIC) are the new direct indicators for coagulation and fibrinolysis. The aim of this study was to investigate the changes of these four new indicators in thrombotic and hemorrhagic events in BCR/ABL1-negative MPN. The study cohort of 74 patients with BCR/ABL negative myeloproliferative disorders included essential thrombocythemia, polycythemia vera, and primary myelofibrosis (PMF). A panel of 4 biomarkers, including TAT, PIC, TM, and t-PAIC were determined using Sysmex HISCL5000 automated analyzers, whereas fibrin/fibrinogen degradation products (FDP), D-dimer and Antithrombin III (ATIII) were analyzed using Sysmex CS5100 coagulation analyzer. A total of 24 (32.4%) patients experienced thrombotic events and hemorrhagic events occurred in 8 patients (10.8%). Compared to patients without hemorrhagic-thrombotic events, patients with thrombotic events had higher fibrinogen (FIB) level, FDP level and lower ATIII activity, while patients with hemorrhagic events had lower white blood cell count and hemoglobin level, higher FDP level (P < 0.05). Patients with a JAK2V617F mutation were more likely to experience thrombotic events (P < 0.05). In addtion, patients with thrombotic events had higher TAT, PIC, TM, and t-PAIC levels than patients without hemorrhagic-thrombotic events (P < 0.05), whereas patients with hemorrhagic events had a lower median value in TAT and TM (no statistical difference, P > 0.05). Patients with higher TAT, TM and t-PAIC were more likely to experience thrombotic events (P < 0.05), and only TAT was positively correlated with thrombotic events (Spearman r =0.287, P = 0.019). TAT, PIC, TM, and t-PAIC combined with ATIII and FDP have a certain value for predicting thrombosis in patients with BCR/ABL1-negative MPN. These 6 parameters are worth further exploration as predictive factors and prognostic markers for early thrombotic events.

Evaluation of preoperative coagulation function changes and deep vein thrombosis incidence in elderly patients with hip fractures.

This study involved an analysis of preoperative deep vein thrombosis (DVT) incidence and changes in coagulation function among elderly patients suffering from hip fractures. The objective was to offer guidance on the prevention and management of preoperative DVT in the lower extremities of elderly individuals with hip fractures. A total of 282 elderly individuals with a hip fracture were enrolled and divided into two groups based on the location of the fracture: femoral intertrochanteric fracture (FIF, 161 individuals) and femoral neck fracture (FNF, 121 individuals). The two groups were compared with respect to baseline characteristics, including gender, age, and comorbid chronic diseases. Furthermore, the analysis encompassed the incidence of preoperative DVT in both lower extremities, along with seven coagulation parameters and platelet count before the surgical procedure. There was no significant difference in baseline information between the two groups. The incidence of preoperative DVT in the FIF group was higher than that in the FNF group, along with a significantly higher percentage of patients exhibiting increased levels of D-dimer and fibrinogen/fibrin degradation products (FDPs). Preoperative hypercoagulability and a greater prevalence of DVT were observed in elderly individuals with FIF compared to individuals with FNF. This indicates that clinicians should pay attention to elderly patients with FIFs, especially those with increased D-dimer and FDP levels.

Early prediction for massive fresh frozen plasma transfusion based on fibrinogen/fibrin degradation products and D-dimer in patients with blunt trauma: a single-center, retrospective cohort study.

This study aimed to examine the association of fibrinogen/fibrin degradation product (FDP) values in comparison with D-dimer and fibrinogen (Fib) values and the need for massive fresh frozen plasma (FFP) transfusion in patients with blunt trauma. This retrospective study included patients with blunt trauma aged ≥ 18years who were transported directly to the tertiary care hospital between April, 2012, and March, 2021. Massive FFP transfusion was defined as a composite outcome of at least 10 units of FFP or death for any cause except for cerebral herniation, within 24h after hospital arrival. We evaluated the diagnostic accuracy of predicting the need for massive FFP transfusions using FDP, D-dimer, and Fib levels at the time of hospital arrival. A total of 2160 patients were eligible for the analysis, of which 167 fulfilled the criteria for the composite outcome. The area under the curve and 95% confidence interval for FDP, D-dimer, and Fib levels were 0.886 (0.865-0.906), 0.885 (0.865-0.906), and 0.771 (0.731-0.810), respectively. When the cutoff values of FDP and D-dimer were set at 90μg/mL and 45μg/mL, the sensitivity values were 77% and 78%, the positive predictive values were 28% and 27%, and the negative predictive values were both 98%, respectively. In contrast, the sensitivity of Fib was low regardless of the cutoff value. FDP and D-dimer levels at the time of hospital arrival showed a higher predictive accuracy for the need for massive FFP transfusion than Fib.

Maternal fibrinogen/fibrin degradation products to high density lipoprotein cholesterol ratio for predicting delivery of small and large for gestational age infants: a pilot study

BackgroundThe purpose of this pilot study was to investigate associations between fibrinogen/fibrin degradation products (FDP) to high density lipoprotein-cholesterol (HDL-C) ratio (FHR) of mothers and the risk of delivering large/small for gestational age (LGA/SGA) infants and to evaluate the predictive power of FHR on LGA/SGA.MethodsThis study retrospectively reviewed 11,657 consecutive women whose lipid profiles and FDP levels were investigated at the time of admission for delivery at a specialized hospital. The FHR was calculated, and perinatal outcomes, including clinical parameters, were analyzed.ResultsThe prevalence of SGA was 9% (n = 1034), and that of LGA was 15% (n = 1806) in this cohort study. FHR was significantly lower in women who delivered SGA infants (4.0 ± 3.2 vs. 4.7 ± 3.3 mg/mmol, P < 0.01) and higher in women who delivered LGA infants (5.7 ± 3.8 vs. 4.7 ± 3.3 mg/mmol, P < 0.01) compared with those who delivered infants of normal size for their gestational age. Women in the top quartile for FHR (> 5.9 mg/mmol) had a 2.9-fold higher risk of delivering LGA infants [adjusted odds ratio (OR) = 2.9, P < 0.01] and a 47% lower risk of delivering SGA infants (adjusted OR = 0.47, P < 0.01) than those in the bottom quartile (< 2.7 mg/mmol). In addition, adding FHR to the conventional models significantly improved the area under the curve for the prediction of delivering LGA (0.725 vs. 0.739, P < 0.01) and SGA (0.717 vs. 0.727, P < 0.01) infants.ConclusionThese findings suggest that the FHR calculated in late pregnancy is an innovative predictor of delivering LGA and SGA infants. Combining FHR with perinatal parameters could thus enhance the predictive ability for predicting the delivery of LGA/SGA infants.

High Plasma tPAPAI-1C Levels May Be Related to a Poor Prognosis in Patients with Severe or Critical COVID-19: A Single-Center Retrospective Study

Severe novel coronavirus disease 2019 (COVID-19) patients have a high incidence of thrombotic complications and mortality. The pathophysiology of coagulopathy involves fibrinolytic system impairment and vascular endothelial damage. This study examined coagulation and fibrinolytic markers as outcome predictors. In an observational study of 164 COVID-19 patients admitted to our emergency intensive care unit, hematological parameters on days 1, 3, 5, and 7 were retrospectively compared between survivors and nonsurvivors. Nonsurvivors had a higher APACHE II score, SOFA score, and age than survivors. Nonsurvivors also had a significantly lower platelet count and significantly higher plasmin/α2plasmin inhibitor complex (PIC), tissue plasminogen activator/plasminogen activator inhibitor-1 complex (tPAPAI-1C), D-dimer, and fibrin/fibrinogen degradation product (FDP) levels than survivors throughout the measurement period. The 7-day maximum or minimum values of the tPAPAI-1C, FDP, and D-dimer levels were significantly higher in nonsurvivors. A multivariate logistic regression analysis showed that the maximum tPAPAI-1C (OR = 1.034; 95% CI,1.014-1.061; p = 0.0041) was an independent factor affecting mortality, with an area under the curve (AUC) of 0.713 (optimum cut-off of 51 ng/mL; sensitivity, 69.2%; and specificity, 68.4%). COVID-19 patients with poor outcomes exhibit exacerbated coagulopathy with fibrinolysis inhibition and endothelial damage. Consequently, plasma tPAPAI-1C might be a useful predictor of the prognosis in patients with severe or critical COVID-19.

Prevalence and risk factors of preoperative deep venous thromboembolism in spinal fracture

To investigate the incidence of lower extremity deep vein thrombosis (DVT) before surgery in patients with spinal fracture and analyze its risk factors. The clinical data of 1 046 patients with spinal fracture who underwent surgery from October 2017 to December 2020 were retrospectively analyzed, including patient's age, gender, body mass index (BMI), smoking history, complications, the time from injury to diagnosis of DVT, blood index results on admission. The complications included hypertension, osteoporosis, diabetes, coronary heart disease, chronic obstructive pulmonary disease (COPD), anemia, obesity, hypokalemia, hyponatremia, hypoproteinemia, renal insufficiency, spinal cord injury;blood index results on admission included hematocrit (HCT), creatinine (Cre), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein(LDL), D-dimer(D-D), fibrin/fibrinogen degradation products(FDP), and C-reactive protein(CRP). The patients were divided into group according to whether DVT was diagnosed by the lower extremity venous ultrasonography after admission to pre-operation. The patients with DVT were set as the DVT group, and the patients without DVT were set as the non-DVT group. First, the above-mentioned possible risk factors were analyzed by univariate analysis, and then the risk factors of DVT before spinal fracture surgery were analyzed by multivariate Logistic regression. Among 1 046 patients with spinal fracture, 137 had DVT before operation and 909 had no DVT. There were significant differences in age, the incidence of preoperative osteoporosis, diabetes, anemia, hypoalbuminemia, the levels of LDL, plasma D-D, FDP, and CRP between the two groups (P<0.05). Multivariate Logistic regression analysis showed that osteoporosis (OR=3.116, 95%CI:1.816-5.346, P<0.001), hypoproteinemia (OR=2.508, 95%CI:1.583-3.974, P<0.001), preoperative serum LDL>4.645 mmol/L(OR=2.586, 95%CI:1.394-4.798, P<0.001), plasma D-D>558.00 ng/ml (OR=23.916, 95%CI:15.108-37.860, P<0.001), FDP>13.81 µg/ml(OR=3.873, 95%CI:2.614-5.739, P<0.001) and age were independent risk factors for the occurrence of DVT before spinal fracture surgery, and the incidence of DVT in patients aged 36-50, 51-65 and over 65 years was 2.49, 2.59 and 4.02 times of those aged 18-35 years, respectively. The incidence of preoperative DVT in patients with spinal fracture is 13.10%(137/1 046). Preoperative complicating osteoporosis, hypoalbuminemia, serum LDL>4.645 mmol/L, plasma D-D> 558.00 ng/ml, FDP> 13.81 µg/ml and age are risk factors for DVT. And the older the patient, the higher the risk of DVT.

Decreased low-density lipoprotein and the presence of pulmonary arterial hypertension among newly diagnosed drug-naïve patients with systemic lupus erythematosus: D-dimer as a mediator.

Pulmonary arterial hypertension (PAH) is commonly associated with systemic lupus erythematosus (SLE). The present study investigated the relationship between coagulation and changes in lipid parameters in newly-diagnosed patients with SLE in the presence of PAH and whether the coagulation parameters were mediators between lipids and PAH presence. A total of 301 subjects scheduled for new-onset drug-naïve SLE were consecutively enrolled. Baseline data for patients without PAH and with PAH were gathered and compared. Coagulation and lipid parameters were compared across patients without lipid regulating and anticoagulation medications. Multivariable logistic regression model was applied to examine potential predictors of PAH in SLE. The relationships between them were examined using Spearman's correlation analysis. The relationship between coagulation index and lipids with SLE-PAH was evaluated using mediation analysis. Female patients accounted for 88.0% of the 301 subjects, and the average age was 32 years (range, 25-45 years). A total of 40 patients (13.3%) had PAH, and the average pulmonary artery systolic pressure (sPAP) was 55.825±26.67 mmHg. Patients with PAH were older and had higher levels of fibrin/fibrinogen degradation products (FDP), D-dimer, C-reactive protein, lower levels of complement 3, complement 4 and 25-hydroxy vitamin D3 compared with the non-PAH group. Multivariable logistic regression analysis showed that age and D-dimer were independent predictor factors for PAH. Among patients without lipid regulating and anticoagulation medications, patients in the PAH group had higher levels of D-dimer and FDP, and lower low-density lipoprotein (LDL) levels compared with patients without PAH. There was also a positive relationship between sPAP and D-dimer and FDP, and a negative relationship between sPAP and total cholesterol and LDL. Mediation analysis indicated that 25.61% of the effect of low LDL on PAH presence in systemic lupus erythematosus was mediated by D-dimer. Overall, the effect of low LDL on SLE-PAH appeared to be mediated by D-dimer, which mediated 25.61% of this effect.

Exposure to a Postoperative Hypercoagulable State Predicts Poor Prognosis After Transthoracic Esophagectomy in Patients with Esophageal Cancer.

The contribution of postoperative coagulation-fibrinolysis status to prognosis is yet to be fully investigated. Thus, in this study, we aimed to elucidate the relationship between postoperative hypercoagulable state (PHS) after transthoracic esophagectomy and long-term outcome in patients with esophageal cancer. Patients with esophageal cancer who underwent transthoracic esophagectomy were selected from a prospectively maintained database. Based on the trend of postoperative plasma fibrin-fibrinogen degradation product (FDP) levels, patients with PHS were identified. The prognostic significance of PHS was evaluated via multivariate analysis using the Cox regression model. Based on the plasma FDP levels of 172 patients that reached a plateau between POD5 and POD7, we calculated the mean FDP value of POD5, 6, and 7, setting a median value as a cutoff. Consequently, 87 patients were classified as PHS. The overall survival (OS) in the PHS group was determined to be significantly lower than in the non-PHS group (5-year OS; 68% and 80%, p = 0.012). Recurrence-free survival (RFS) in the PHS group was significantly lower than in the non-PHS group (5-year RFS; 60% and 79%, p = 0.017). Using the pathological stage as a covariate in the multivariate analysis, PHS was an independent prognostic factor of OS [hazard ratio (HR) 2.517, p = 0.009] and RFS (HR 1.905, p = 0.041). PHS was found to be an independent negative prognostic factor in patients with esophageal cancer. Possible improvement of the oncological outcome by early postoperative intervention with anticoagulants should be explored in clinical trials.

Fibrin/fibrinogen Degradation Products Are Associated With Tumor Stage and Prognosis in Patients Undergoing Resection of Esophageal Cancer.

To investigate the significance of preoperative fibrin/fibrinogen degradation products (FDP) in patients with esophageal cancer (EC), we examined the association between the preoperative FDP level and clinicopathological features in patients with EC who underwent McKeown esophagectomy with gastric tube reconstruction without neoadjuvant therapy. Ninety patients with EC who underwent surgery between 2006 and 2014 were included in this study. We investigated the association of FDP levels with clinicopathological features and prognosis. Multivariate analysis revealed increased FDP level and pathological tumor depth to be independent prognostic factors for overall survival (OS) (p=0.008 and p=0.002, respectively). In addition, FDP levels were significantly positively associated with more advanced pathological TNM stage as a continuous variable (p for trend=0.002). The preoperative FDP level was associated with a poor prognosis and was an independent prognostic factor for the OS of EC patients who underwent esophagectomy. Furthermore, the tumor stage-related increase in FDP indicated that a high FDP level is associated with tumor progression in patients with EC.

Tranexamic acid attenuates early post-operative systemic inflammatory response and nutritional loss and avoids reduction of fibrinogen in total hip arthroplasty within an enhanced recovery after surgery pathway

Total hip arthroplasty (THA) is an intervention with significant inflammatory response. The impact of additional doses of tranexamic acid (TXA) on inflammatory response, trauma and nutrition parameters, and coagulation and fibrinolysis changes has rarely been reported. A prospective double-blind randomized trial was performed on elective primary THA. Ninety-nine adult patients were recruited consecutively from 2019 to 2020. They were randomized to receive single-dose of TXA before incision, another dose of TXA at three hours post-operatively, or another two doses of TXA at three and six hours post-operatively. The primary outcomes included changes in white blood cell (WBC) counts, creatine kinase (CK), haemoglobin(Hb), and albumin(Alb); the secondary outcomes included coagulation and fibrinolysis parameters. Compared with single-dose TXA, patients received threedose TXA had significantly reduced WBC counts and fibrinogen/fibrin degradation product (FDP) levels, increased albumin and fibrinogen levels, and prolonged PT on post-operative day (POD) three. Though patients received threedose TXA had a tendency that increased Hb, decreased CK, reduced D-D, and prolonged APTT on POD3, it is not statistically significant. And the other measured outcomes on POD1 and POD2W shared a similar statistical result, except PT. The PT is significantly prolonged on POD2W in threedose group compared with single dose. Three-dose TXA contribute to attenuate early post-operative systemic inflammatory response and nutritional loss, increase fibrinogen, reduce FDP levels, and prolong PT in THA patients within an ERAS pathway, which may associate with reduced early post-operative haemorrhagic tendency, thrombosis risks, and hypercoagulability.

Alterations of coagulation and fibrinolysis in patients with blunt splenic injury after splenic artery embolization.

BackgroundThrombotic complications following splenectomy have been documented. However, there has been sparse literature regarding thrombotic complications following splenic artery embolization (SAE).The objective of this study was to determine changes in coagulation and fibrinolysis and assess the thrombotic risk after SAE in patients with blunt splenic injury (BSI).MethodsThis study included 38 BSI patients who were hemodynamically stable on admission. SAE was performed if the splenic injury was classed as grade III or greater and had no requirement of immediate surgery. Platelet (PLT), fibrinogen (FIB), D‐dimers (D‐D), fibrinogen/fibrin degradation products (FDP), antithrombin III (AT III), prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), hemoglobin (Hb), and hematocrit (Hct) were measured before SAE procedures and then 1d, 3d, and 7d after SAE.ResultsThe technical success rate of SAE and the splenic salvage rate were 100%. There was no mortality. Compared with pre‐SAE values, the levels of PLT, FIB, D‐D, and FDP increased significantly at 3 days and 7 days after SAE (p < 0.05). However, AT III, PT, APTT, TT, Hb, and Hct showed no statistically significant difference at 1d, 3d, and 7d after SAE (p > 0.05).ConclusionAlterations in PLT and hemostatic parameters might contribute to the increased risk of thrombotic complications in BSI patients undergoing SAE. Thromboembolism following SAE should be considered and thrombotic prophylaxis should be recommended.

Coagulation phenotypes in sepsis and effects of recombinant human thrombomodulin: an analysis of three multicentre observational studies

BackgroundA recent randomised trial showed that recombinant thrombomodulin did not benefit patients who had sepsis with coagulopathy and organ dysfunction. Several recent studies suggested presence of clinical phenotypes in patients with sepsis and heterogenous treatment effects across different sepsis phenotypes. We examined the latent phenotypes of sepsis with coagulopathy and the associations between thrombomodulin treatment and the 28-day and in-hospital mortality for each phenotype.MethodsThis was a secondary analysis of multicentre registries containing data on patients (aged ≥ 16 years) who were admitted to intensive care units for severe sepsis or septic shock in Japan. Three multicentre registries were divided into derivation (two registries) and validation (one registry) cohorts. Phenotypes were derived using k-means with coagulation markers, platelet counts, prothrombin time/international normalised ratios, fibrinogen, fibrinogen/fibrin-degradation-products (FDP), D-dimer, and antithrombin activities. Associations between thrombomodulin treatment and survival outcomes (28-day and in-hospital mortality) were assessed in the derived clusters using a generalised estimating equation.ResultsFour sepsis phenotypes were derived from 3694 patients in the derivation cohort. Cluster dA (n = 323) had severe coagulopathy with high FDP and D-dimer levels, severe organ dysfunction, and high mortality. Cluster dB had severe disease with moderate coagulopathy. Clusters dC and dD had moderate and mild disease with and without coagulopathy, respectively. Thrombomodulin was associated with a lower 28-day (adjusted risk difference [RD]: − 17.8% [95% CI − 28.7 to − 6.9%]) and in-hospital (adjusted RD: − 17.7% [95% CI − 27.6 to − 7.8%]) mortality only in cluster dA. Sepsis phenotypes were similar in the validation cohort, and thrombomodulin treatment was also associated with lower 28-day (RD: − 24.9% [95% CI − 49.1 to − 0.7%]) and in-hospital mortality (RD: − 30.9% [95% CI − 55.3 to − 6.6%]).ConclusionsWe identified four coagulation marker-based sepsis phenotypes. The treatment effects of thrombomodulin varied across sepsis phenotypes. This finding will facilitate future trials of thrombomodulin, in which a sepsis phenotype with high FDP and D-dimer can be targeted.

Characterization of fibrin/fibrinogen degradation products reagents and their utility in critical care patients with enhanced fibrinolysis.

Fibrin/fibrinogen degradation products (FDP) values reflect coagulation and fibrinolysis status, and FDP levels are helpful for diagnosis and classification of disseminated intravascular coagulation (DIC). FDP measurement has always played a key role in diagnosing DIC, a phenomenon that has recently gained renewed attention because of its occurrence in coronavirus disease 2019 (COVID-19) patients. Although the evaluation of FDP is crucial for the management of critical care, the variability among FDP reagents is unclear. In this study, we aimed to compare LIASAUTO P-FDP with three FDP reagents and investigate their characteristics. In total, 172 plasmas samples were used in the correlation. The sample data were divided into three groups including negative, no and positive discrepancy based on the discrepancy percentages calculated from each correlation between LIASAUTO P-FDP and other three reagents. D-dimer, plasmin-α2 plasmin inhibitor complex (PIC), fibrin monomer complex (FMC), fibrinogen (Fbg) and Plasmin-α2 Plasmin Inhibitor (α2 PI) were measured and included in data analysis. The positive discrepancy groups showed higher D-dimer, PIC and FMC values than the negative discrepancy groups. The data indicated that LIASAUTO P-FDP had higher reactivity to D-dimer than other reagents and the values were elevated in the fibrinolysis-enhanced samples with various FDP fragments. LIASAUTO P-FDP displayed the reactivity towards various fibrin/fibrinogen degradation products, and it might be useful for DIC diagnosis because the fibrinolytic status differed in the DIC types and stages.

High fibrin/fibrinogen degradation product value as a risk factor for progressive remote traumatic intracranial haemorrhage following neurosurgery

Introduction Remote traumatic intracranial haemorrhage (RTIH) may develop after neurosurgery. Recognition of the risk factors for RTIH before surgery might be of great value. The purpose of this study was to verify if the fibrin/fibrinogen degradation product (FDP) value may be a risk factor for RTIH. Methods This was a retrospective study of the data of 56 patients with traumatic intracranial hematomas shown on initial computed tomography (CT) who were treated with craniotomy or decompressive craniectomy and underwent a follow-up CT at a single centre over a period of approximately 10.5 years. We divided the patients into 2 groups: those who developed RTIH (Positive: P-group) and those who did not (Negative: N-group). We compared the 2 groups in terms of not only the laboratory data before surgery, but also patient age, sex, antiplatelet/antithrombotic medications received, cause of injury, and GCS score on arrival. Results RTIH was observed in 22 patients (P-group, 39.3%). The FDP value was the only significant risk factor identified in this study (p = 0.00076). The cut-off value was estimated on the basis of the area under the receiver operating characteristic (ROC) curve. The cut-off FDP value was 120 µg/mL (63.6% sensitivity and 85.3% specificity). Conclusions FDP levels over 120 µg/mL were determined to be a risk factor for progressive RTIH after neurosurgery. We suggest the FDP level be checked before surgery for traumatic intracranial haemorrhage and follow-up CT be done as soon as possible after the surgery if the serum FDP level is over 120 µg/mL.

Fibrin/fibrinogen degradation products in late pregnancy promote macrosomia prediction in normal uncomplicated pregnancy

ObjectiveThe purpose of this study was to explore the association of fibrin/fibrinogen degradation products (FDP) levels with the risk of macrosomia, and determine whether FDP, either alone or combined with traditional factors in late pregnancy, could be used to predict macrosomia at birth in healthy pregnancies. MethodsA total of 9464 health pregnant women with singleton pregnancy were recruited in this retrospective cohort study. Maternal plasma FDP levels at hospital admission and birth outcomes were obtained from laboratory system and hospital records, respectively. ResultsFDP levels in late pregnancy were significant higher in women who delivered macrosomia than those who delivered infants with normal weight [median (interquartile range, IQR): 8.2 (5.8–11.9) vs. 6.6 (4.7–9.6) mg/L; P < 0.001]. Multivariable logistic regression analysis demonstrated that FDP levels were independently associated with macrosomia risk. Pregnant women in the highest quartile of FDP had a 2.99-fold higher risk of delivering macrosomia compared with those in the lowest (adjusted OR: 2.99; 95% CI: 2.27–3.93). In addition, the incorporation of FDP into the crude prediction model significantly improved the area under curve (AUC) for predicting macrosomia (0.774 vs. 0.787; P < 0.001). ConclusionOur findings suggest that maternal plasma FDP levels in late pregnancy are independently and significantly associated with risk of macrosomia. Combination of FDP levels and traditional risk factors could promote the prediction of macrosomia.

Hypofibrinogenemia Caused by Hemocoagulase Injection: A Retrospective Study on Clinical Laboratory Findings

ObjectiveHemocoagulase injection based on the venom of Agkistrodon halys Pallas is widely used in the treatment of hemorrhagic disorders. This study aimed to characterize the clinical laboratory findings of hemocoagulase-induced hypofibrinogenemia as the associated adverse reaction of hemocoagulase injection. MethodsWe retrospectively enrolled 27 in-patients who were treated with hemocoagulase injection for hemoptysis and developed hypofibrinogenemia during the period of January 1, 2015 to March 31, 2018. Clinical data were collected and investigated, including clinical manifestations, hemostatic and fibrinolytic parameters, dosage of hemocoagulase, the medication time, and the cryoprecipitate blood product infusion. Differences in fibrinogen, D-dimer, and fibrin/fibrinogen degradation products (FDP) before, during, and after the application of hemocoagulase injection were analyzed statistically. ResultsPlasma fibrinogen level during medication of hemocoagulase injection decreased significantly compared to that before the treatment (F= 1.80, P < 0.001), with the average decrease of 2.28 g/L (0.63-3.9 g/L). After withdrawal, fibrinogen level increased significantly compared to that during the medication (F = –1.20, P< 0.001), but was still lower than that before the medication (F = 0.59, P = 0.03). The D-dimer level and the FDP level after withdrawal decreased significantly compared to the levels during the medication (F = 0.83, P = 0.002; Wilcoxon-test, Z = –4.54, P<0.001). Spearman’s correlation analyses did not find either fibrinogen change during-before the administration or FDP change after-during the administration was associated with the dosage of hemocoagulase (r = –0.17, P=0.40; r = –0.28, P = 0.15; respectively) and the time of recovery from hypofibrinogenemia (r = –0.45, P = 0.05; r = 0.13, P = 0.61; respectively). ConclusionMonitoring both clotting and fibrinolysis parameters is essential in the management of hemoptysis patients treated with hemocoagulase injection. Clinicians should be aware of hypofibrinogenemia and consider discontinuation of the administration of hemocoagulase whenever necessary.

Combined therapy with gas gangrene antitoxin and recombinant human soluble thrombomodulin for Clostridium perfringens sepsis in a rat model

Cases of Clostridium perfringens septicemia, such as liver abscess, often develop a rapidly progressive intravascular hemolysis and coagulation; the mortality rate with current standard care including antibiotics and surgery is high. Herein, we firstly investigated the effects of gas gangrene antitoxin (GGA) (antitoxin against C. perfringens) and recombinant human soluble thrombomodulin (rTM) on the hemolysis, coagulation status, inflammatory process, and mortality in α-toxin-treated rats. Male 11-week-old Sprague Dawley rats were randomly divided into five groups: control group, α-toxin group, GGA group, rTM group, and combined GGA and rTM (combination group). After α-toxin injection, mortality and platelet counts, and hemolysis were observed for 6 h. The fibrin/fibrinogen degradation products (FDP), and plasma high-mobility group box 1 (HMGB1) were also measured at 6 h. The combination group demonstrated 100% survival compared with 50% survival in the α-toxin group and demonstrated significantly improved hemolysis, platelet counts, and lactate levels compared with those in the α-toxin group (p < .01). The FDP and HMGB1 levels in the combination therapy group were significantly lower than those in the α-toxin group (p < .05). Combination therapy with GGA and rTM administration is applicable as adjunct therapy for fatal C. perfringens sepsis.

Fibrin/fibrinogen degradation products (FDP) at hospital admission predict neurological outcomes in out-of-hospital cardiac arrest patients

ObjectiveThis study aimed to test the hypothesis that coagulation, fibrinolytic markers and disseminated intravascular coagulation (DIC) score (International Society on Thrombosis and Haemostasis) at hospital admission of out-of-hospital cardiac arrest (OHCA) patients can predict neurological outcomes 1 month after cardiac arrest. MethodsIn this retrospective, observational analysis, data were collected from the Sapporo Utstein Registry and medical records at Hokkaido University Hospital. We included patients who experienced OHCA with successful return of spontaneous circulation (ROSC) between 2006 and 2012 and were transferred to Hokkaido University Hospital. From medical records, we collected information about the following coagulation and fibrinolytic factors at hospital admission: platelet count; prothrombin time; activated partial thromboplastin time; plasma levels of fibrinogen, D-dimer, fibrin/fibrinogen degradation products (FDP), and antithrombin; and calculated DIC score. Favorable neurological outcomes were defined as a cerebral performance category 1–2. ResultsWe analyzed data for 315 patients. Except for fibrinogen level, all coagulation variables, fibrinolytic variables, and DIC score were associated with favorable neurological outcomes. In the receiver operating characteristic curve analysis, FDP level had the largest area under the curve (AUC; 0.795). In addition, the AUC of FDP level was larger than that of lactate level. ConclusionsAll of the coagulation and fibrinolytic markers, except for fibrinogen level, and DIC score at hospital admission, were associated with favorable neurological outcomes. Of all of the variables, FDP level was most closely associated with favorable neurological outcomes in OHCA patients who successfully achieved ROSC.

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>40µg/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.

Persistent Endothelial Damage after Intravenous Immunoglobulin Therapy in Kawasaki Disease

Background: Kawasaki disease (KD) is an acute systemic vasculitis of unknown etiology. Although endothelial cell damage associated with vasculitis might lead to the hypercoagulability that is involved in coronary artery disease, the changes in coagulation after intravenous immunoglobulin therapy (IVIG) have not been well investigated in KD. The aims of this study were to address the changes in coagulation before and after IVIG in KD, and to further elucidate the coagulation-inflammation axis, with special attention to endothelial damage. Methods: We retrospectively collected the laboratory data before and after IVIG in 26 pediatric KD patients treated at the Nara Prefecture Western Medical Center between May 2010 and April 2012. Prothrombin time (PT), activated partial thromboplastin time (APTT) and levels of fibrin/fibrinogen degradation products (FDP) and D-dimer were assessed as coagulation markers. Fibrinogen, ferritin, serum amyloid A, procalcitonin and urine F2 microglobulin were assessed as inflammation markers. Thrombomodulin, antithrombin, factor VIII activity (FVIII:C), and von Willebrand factor antigen (VWF:Ag) were used to assess endothelial damage. Results: Prolonged PT and APTT before IVIG were significantly shortened after IVIG, and elevated levels of FDP and D-dimer were significantly decreased. Elevated levels of inflammation markers had decreased significantly after IVIG, but levels of FVIII:C and VWF:Ag remained high, even after IVIG. Conclusions: Ameliorated inflammation by IVIG might improve the hypercoagulable state. Nevertheless, our results suggest that endothelial damage might be prolonged in IVIG-treated patients. Control of endothelial damage in KD is critical. i 2014 S. Karger AG, Basel