Fibrinogen Tests Research Articles

Pre-diagnostic trajectory of pediatric hemophagocytic lymphohistiocytosis: observations from hematological and hepatic parameters.

Understanding the early features and characteristics of hemophagocytic lymphohistiocytosis (HLH) is essential for identifying high-risk individuals and also providing valuable pathological insights. This study aims to investigate the characteristics and trends of blood and hepatic parameters before an HLH diagnosis was established. Longitudinal hematological and hepatic test results from pediatric patients with HLH and an age- and sex-matched control group were analyzed. According to the length of time between hospital admission and the establishment of the HLH diagnosis, the HLH cases were divided into early-onset (≤ 7 days) and late-onset (> 7days) groups. Among the 229 pediatric HLH patients, the length of time between hospital admission and the establishment of an HLH diagnosis ranged from 0 to 41 days (median = 4 days). Over 80% of pediatric HLH patients presented abnormal laboratory results for aspartate aminotransferase (AST), triglycerides, lactate dehydrogenase (LDH), and hemoglobin at admission. The abnormal rates in the initial platelet count, neutrophil count, and fibrinogen tests were 67.3%, 48.3%, and 52.2%, respectively. The initial test results for AST, alanine aminotransferase (ALT), LDH, serum sodium, and albumin showed AUCs > 80% for discriminating early-onset HLH. For the discrimination of late-onset HLH, the performance of initial test results was poor. To conclude, abnormalities in AST, triglycerides, LDH, and hemoglobin are early presentations of pediatric HLH; platelet, neutrophil, and fibrinogen levels may become abnormal at a relatively late stage of the HLH disease trajectory; and the initial test results for AST, ALT, LDH, serum sodium, and albumin can be used to identify suspected early-onset HLH.

A-150 Extended Pre-Analytical Stability Validation for Coagulation Tests in Brazilian Clinical Laboratory

Abstract Background The transport of samples for coagulation tests is a challenge for clinical laboratories, due to their limited stability and short time for processing according to the manufacturer's recommendations. The objective of this study was to evaluate the possibility of extending the stability of samples collected for Prothrombin Time and Activity (PTA), activated Partial Thromboplastin Time (aPTT) and Fibrinogen tests for up to 10 hours at room temperature, in comparison with the stability described in the literature and by the manufacturer of the reagents (4 hours for aPTT, 8 hours for PTA and Fibrinogen). We verified the acceptability of the samples with a longer period between collection and analysis, including its impact on the clinical management Methods Four tubes of 3.2% sodium citrate from 40 volunteers were analyzed at times of up to 4 h, 6 h, 8 h and 10 h. The results obtained were compared with the dosage performed within 4 hours (recommended by manufacturer) and the Total Error obtained in the analysis of the samples was evaluated. The tubes remained at controlled room temperature of 15 to 25°C and were centrifuged at 1500 g for 15 minutes. Then, the analyses were performed by coagulometric method. Results The results showed safety in the analysis of samples for coagulation tests even within 10 hours after collection at ambient temperature and were within the Maximum Allowable Total Error (Carmen Ricós): 95% of the PTA results (TE 5,3%); 92.2% of aPTT results (TE 4,5%) and 98% of Fibrinogen analyses (TE 13,6%) (Figures 1, 2 and 3). In addition, even the results that exceeded the specified Total Error showed no impact on the clinical decision. Conclusions The study demonstrated that there was no significant loss of stability for the analyses of PTA, aPTT and Fibrinogen performed on samples kept at room temperature within 10 hours after collection. Most of the results showed variation within the specified Total Error and all results showed acceptability from a medical point of view

Coagulation Testing in Real-World Setting: Insights From a Comprehensive Survey.

The objective of this survey was to gain a real-world perspective on coagulation testing by evaluating the availability of various coagulation laboratory tests, assessing specific analytic and postanalytic steps in clinical laboratories in Korea.Participants were surveyed using a 65-question questionnaire specifically focused on their coagulation testing practices related to prothrombin time (PT), activated partial thromboplastin time (aPTT), plasma-mixing studies, lupus anticoagulant (LA) tests, platelet function tests, coagulation factor assays, and the composition of hemostasis and thrombosis test panels. The survey was performed between July and September 2022.The survey achieved a 77.9% (81 of 104) response rate. PT or aPTT tests were performed directly at all participating institutions, followed by D-dimer and fibrinogen tests, platelet function test, and plasma-mixing studies in order of frequency. Variations existed in the performance of mixing test and LA assessment. Patterns of coagulating testing differed depending on the size of the hospital. The survey revealed that most laboratories conducted coagulation tests following the international guidelines such as Clinical Laboratory Standards Institute guidelines and the Korean Laboratory Certification system. However, some coagulation tests, including mixing test and LA tests, are yet to be standardized in Korea.Continuous education on coagulation test methods and internal and external quality control are required to encourage laboratories to enhance the performance of coagulation testing.

Are tube fill volumes below 90% a rejection criterion for all coagulation tests?

Rejected samples lead to prolonged turnaround time and delayed diagnosis and treatment of patients. This study was conducted to determine minimum acceptable sample volume in Sarstedt brand coagulation tubes to reduce high sample rejection rate. Blood samples were drawn from 20 participants (10 healthy volunteers and 10 patients receiving oral anticoagulant) into coagulation tubes. Six samples were taken from each participant, with tube fill volumes of 100%, 90%, 80%, 70%, 60%, and 50%. Prothrombin time (PT), active partial thromboplastin time (aPTT), and fibrinogen tests were analyzed. According to quality performance specifications, the tube fill volume must be at least 70% for PT and aPTT and 50% for fibrinogen. There was no statistical difference in samples from healthy volunteers for PT, aPTT, and fibrinogen tests when the minimum tube fill volume was at least 80%, 90%, and 50%, respectively. These percentages were 50%, 70%, and 60%, respectively, in patients receiving oral anticoagulant. Sarstedt tubes meet quality standard specifications at a 70% fill rate for PT and aPTT and a 50% fill rate for fibrinogen. Comprehensive studies with larger populations are needed to accept these values as sample acceptance criteria for the laboratory.

Assessment of coagulation assays on Roche Cobas t711 analyzer: performance and clinical implications.

We performed an analytical assessment of five coagulation tests [i.e. prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, thrombin time (TT) and D-dimer] on the Roche Cobas t711 analyzer and a comparison study with the methodology in use at our laboratory (i.e. Werfen ACL Top 750 analyzer), expanding the analysis to the clinical implications of Cobas t711 implementation. Imprecision studies were performed following the Clinical and Laboratory Standards Institute (CLSI) H57 A:2008 guideline. Linearity of D-dimer and fibrinogen tests was analysed according to the CLSI EP06-A: 2003 recommendations. For method comparison, the results were analyzed using the Bland-Altman plot and Passing-Bablok regression. Imprecision met manufacturer claims for PT, aPTT and TT. D-dimer and fibrinogen tests showed a coefficient of variation (CV)% over manufacturer claims at certain concentration levels. Linearity ranges could not be verified. Comparison study revealed that results are not interchangeable for any test, a lower correlation for aPTT test and lower D-dimer results from Roche Cobas t711. The strength of this study relies on the analysis of the clinical implications of reporting Cobas t711 results compared to those obtained with the methodology in use at our laboratory. Different sensibility to factor deficiency, anticoagulant therapy and interferences might explain lower correlation rates obtained for the aPTT test. Different monoclonal antibodies used for D-dimer determination might explain the lower results obtained with the Cobas t711 analyzer. This aspect needs further studies given the relevance of D-dimer test to exclude thrombotic events and reinforces the need of harmonization in the haemostasis laboratory.

Coagulopathy in Patients with Plasmacellular Dyscrasia

Disorders of fibrinogen (Fg) are usually the result of genetic mutations that hesitate in reduced levels of protein (hypofibrinogenemia) or in an abnormal molecule (dysfibrinogenemia). However, plasma factors or microenvironment can determine an acquired defect: reduced concentration or altered function. For example, antibodies may bind fibrinogen and/or fibrin by interfering with the polymerization and inhibiting the coagulation.Our goal is to identify the cause of dysfibrinogenemia in a man of 65 years, diagnosed because of a discrepancy between values of immunological Fg and values of coagulative Fg; despite a reduced concentration of functional fibrinogen and an elongation of the thrombin time (TT), activated partial thromboplastin time (aPTT) and of the prothrombin time (PT) we could not put the diagnosis of hereditary deficit, because of normal values of coagulation tests performed by the patient about 12 months before.The identification of a band on plasma immunofixation (western blot), referable to the light chain k, near to the band of fibrinogen, led us to investigate for a possible plasmacellular dyscrasia. Bone marrow plasma cells percentage was within normal range (4-5%). However the cytofluorimetric assay showed a k monoclonality in 80% of the patient's bone marrow plasma cells.FLC-MGUS (monoclonal gammopatia of uncertain significance with the presence of monoclonal protein consisting of only light chain) diagnosis was made.Treatment with dexametasone resulted in an almost complete correction of hemocoagulation parameters (with the only exception of TT elongation).Despite serious altered coagulation tests, patient have never had haemorrhagic manifestations and/or thrombotic diseases.This case is particularly unusual because the inhibitory effect on fibrinogen molecules was induced by a single light chain rather than by a complete antibody molecule. MGUS diagnosis was made on plasma immunofixation: no clonality was identified on serum immunofixation maybe because k chains were binded to fibrinogen molecules, absent in serum assay. In agreement with this hypothesis, after steroid treatment, FLC k (free light chain) values rose as if k light chains were released from fibrinogen molecules.No coagulation tests correction was observed after PNP (pooled normal plasma) addition, (1:1 ratio) or after addition of Fg (obtained from PNP) to patient's plasma: patient's k light chain could inhibit Fg in normal plasma pool as well. Purified Fg from patient plasma was added to purified Fg from PNP: by increasing the patient's Fg share in relation to normal Fg share, we observed an initial decline in functional Fg value until 5:1 ratio was reached. No further functional Fg decline was observed increasing Fg share in dilution: functional fg reached a plateau as if saturation of the interfering capacity of light chains was achieved .There were no differences between coagulation test at 4°C or at 37°C so we could rule out an interaction between k light chain and glucose part of fibrinogen molecule. No alterations in platelet aggregation test were observed, so an interaction in the fibrinogen's binding site for platelets IIb/IIIa glycoprotein, was excluded. As no hemorrhagic events were reported by the patient, an interaction in the fibrinogen's binding site for fXIII (coagulation factor XIII) or a FpA (fibrinopeptide A) impaired release were unlikely. However reptilase time test wasn't available at our laboratoty to assess FpA release.It is known that pathological immunoglobulins (Ig) multiple myeloma (MM) patients interfere with coagulation test, so we screened 20 MM patients control group for dysfibrinogenemia, like patient's one. In 4 MM patients we found TT elongation but normal functional Fg values. In plasma immunofixation light chain bands didn't run at the same level of fibrinogen molecules.We could rule out an interference between Fg and monoclonal light chain in MM patients: we speculated that pathological Ig interefered with fibrin polimerization. However only a comparison between functional and immunological fibrinogen tests should surely exclude dysfibrinogenemia in these patients, despite normal functional fibrinogen values.A specific test to assay interaction between monoclonal light chain (obtained from patient's plasma) and Fg from PNP will be necessary to surely prove dysfibrinogenemia related to monoclonal FLCs. DisclosuresNo relevant conflicts of interest to declare.

Hemostasis Disorders in Patients with De Novo Acute Leukemias

Aim. To study hemostasis disorders in patients with de novo acute leukemias (AL) prior to chemotherapy. Materials & Methods. The study enrolled 107 patients with newly diagnosed AL, aged 18-80 years and treated at the National Research Center for Hematology. Acute lymphoblastic leukemia (ALL) was identified in 37 patients, acute myeloid leukemia (AML) was diagnosed in 46 patients, and acute promyelocytic leukemia (APL) was reported in 24 patients. Hemorrhagic and thrombotic complications were analyzed; platelet count, APPT, prothrombin and fibrinogen concentration were determined; thromboelastography (TEG; native tests, functional fibrinogen tests) and rotation thromboelastometry (ROTEM; EXTEM, INTEM, FIBTEM, APTEM) were performed. The data were statistically processed using SAS 9.4 software. Results. At AL onset hemorrhagic syndrome was detected in 34 (32 %) out of 107 patients. It was manifested by petechia (n = 16), subcutaneous hematomas (n = 12), gingival (n = 10) and nose (n = 6) bleeding, uterine bleeding (n = 2), hematuria (n = 2), gastrointestinal bleeding (n = 1), brain hemorrhage (n = 6), and periorbital hematoma (n = 1). According to TEG and ROTEM hypocoagulation was more common in APL patients. Hyperfibrinolysis could be detected using only ROTEM in 54 % of APL patients, in 8 % of ALL and 4 % of AML patients. Compared to other AL patients those with APL showed different parameters of fibrinogen concentration of < 1.75 g/L (sensitivity 83.3 %, specificity 83.13 %), D-dimer concentration of > 2686 pg/L (sensitivity 72.73 %, specificity 64.79 %), MCF<sub>FIBTEM</sub> < 12.5 mm (sensitivity 80 %, specificity 80 %), and MA<sub>FF</sub> < 9.7 mm (sensitivity 86.96 %, specificity 90.12 %). Conclusion. The parameters that distinguish APL from other categories of AL patients are hypofibrinogenemia, higher D-dimer concentration, ROTEM changes, and hyperfibrinolysis.

Thromboelastography clot strength profiles and effect of systemic anticoagulation in COVID-19 acute respiratory distress syndrome: a prospective, observational study.

Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) infection may yield a hypercoagulable state with fibrinolysis impairment. We conducted a single-center observational study with the aim of analyzing the coagulation patterns of intensive care unit (ICU) COVID-19 patients with both standard laboratory and viscoelastic tests. The presence of coagulopathy at the onset of the infection and after seven days of systemic anticoagulant therapy was investigated. Forty consecutive SARS-CoV-2 patients, admitted to the ICU of a University hospital in Italy between 29th February and 30th March 2020 were enrolled in the study, providing they fulfilled the acute respiratory distress syndrome criteria. They received full-dose anticoagulation, including Enoxaparin 0.5 mg·kg-1 subcutaneously twice a day, unfractionated Heparin 7500 units subcutaneously three times daily, or low-intensity Heparin infusion. Thromboelastographic (TEG) and laboratory parameters were measured at admission and after seven days. At baseline, patients showed elevated fibrinogen activity [rTEG-Ang 80.5° (78.7 to 81.5); TEG-ACT 78.5 sec (69.2 to 87.9)] and an increase in the maximum amplitude of clot strength [FF-MA 42.2 mm (30.9 to 49.2)]. No alterations in time of the enzymatic phase of coagulation [CKH-K and CKH-R, 1.1 min (0.85 to 1.3) and 6.6 min (5.2 to 7.5), respectively] were observed. Absent lysis of the clot at 30 minutes (LY30) was observed in all the studied population. Standard coagulation parameters were within the physiological range: [INR 1.09 (1.01 to 1.20), aPTT 34.5 sec (29.7 to 42.2), antithrombin 97.5% (89.5 to 115)]. However, plasma fibrinogen [512.5 mg·dl-1 (303.5 to 605)], and D-dimer levels [1752.5 ng·ml-1 (698.5 to 4434.5)], were persistently increased above the reference range. After seven days of full-dose anticoagulation, average TEG parameters were not different from baseline (rTEG-Ang p = 0.13, TEG-ACT p = 0.58, FF-MA p = 0.24, CK-R p = 0.19, CKH-R p = 0.35), and a persistent increase in white blood cell count, platelet count and D-dimer was observed (white blood cell count p < 0.01, neutrophil count p = 0.02, lymphocyte count p < 0.01, platelet count p = 0.13 < 0.01, D-dimer levels p= 0.02). SARS-CoV-2 patients with acute respiratory distress syndrome show elevated fibrinogen activity, high D-dimer levels and maximum amplitude of clot strength. Platelet count, fibrinogen, and standard coagulation tests do not indicate a disseminated intravascular coagulation. At seven days, thromboelastographic abnormalities persist despite full-dose anticoagulation.

Trials and Tribulations of Viscoelastic-Based Determination of Fibrinogen Concentration.

Acquired fibrinogen deficiency is a major determinant of severe bleeding in different clinical conditions, including cardiac surgery, trauma, postpartum hemorrhage, liver surgery, and transplantation. The existing guidelines recommend to supplement fibrinogen in patients with severe bleeding when the fibrinogen concentration is <1.5 g/L. Viscoelastic tests (VETs) provide a fast determination of the fibrinogen contribution to clot firmness and allow prompt treatment of acquired fibrinogen deficiency. However, different VET devices are presently available on the market, based on different technologies and different activators and platelet inhibitors. The available tests are the functional fibrinogen (FF, thromboelastography), the fibrinogen contribution to clot firmness (fibrinogen determination [FIBTEM], thromboelastometry), and the fibrinogen contribution to clot strength (FCS, sonorheometry). All these tests have a moderate to very good correlation with the Clauss fibrinogen assays; however, when comparing VET-based fibrinogen contribution to clot firmness with Clauss fibrinogen concentration, strong differences occur within the same test under different conditions and between different tests. The most widely studied test is the thromboelastometric FIBTEM; the best predictor of a Clauss fibrinogen <1.5 g/L is placed at a maximum clot firmness around 8 mm of amplitude. Fewer data are available for thromboelastographic FF, but the correspondent value is in the range of 12 mm. Overall, due to an incomplete inhibition of platelet contribution, FF overestimates the fibrinogen contribution with respect to FIBTEM. Data on sonorheometry FCS are limited and conflicting. When addressing the correlation between different tests, it is good in general, but no fixed conversion factors can be proposed, due to a considerable dispersion of the experimental points. In conclusion, VET-based fibrinogen tests are certainly powerful tools that are presently suggested by the existing guidelines; however, when using them for clinical decision-making, users should consider the possible sources of bias, which include the different level of platelet inhibition, the role of platelet count and function, the possible different degrees of blood activation with tissue factor, the important role of factor XIII in stabilizing the fibrin clot, and others.

English

Plasma prothrombin time (PPT) and activated partial thromboplastin time (aPTT) are coagulation tests routinely performed in laboratories to evaluate the function of the coagulation system. Generally, samples with haemolysis, icterus and lipaemia are rejected in different laboratories which delays medical care and cause discomfort to patients. This was a cross sectional study conducted to determine the effect of haemolysis, icterus and lipaemia on PT, aPTT and fibrinogen as measured by Sysmex CA-50. Included samples were those that were showing one or more of the following characteristics: hemolysis, icterus, or lipemia. A purposive sampling technique was used to select the study participants. Venous blood were collected from the participants using Tri-Sodium Citrate anticoagulated tubes, centrifuged and visually inspected for hemolysis, icterus and lipemia. aPTT, PT and fibrinogen of the selected specimen were determined by Sysmex CA-50 at La Croix du Sud Hospital. An independent 𝑡-test was used for comparison of quantitative measurements between the two groups (normal and icteric, normal and hemolyzed, normal and lipemic), and the level of statistical significance was set as 0.05 (5%) in all tests. This study reports that while PT and fibrinogen are not statistically (P&gt;0.05) significantly affected by hemolysis, Icterus, and lipemia among the participants; aPTT was affected by hemolysis (results of non-hemolyzed decreased from 32.5 &plusmn; 1.89 to 31.5 &plusmn; 2.87 for hemolyzed sample, P value=0.002) but it remains almost constant for both icteric and lipemic samples. After a careful visual inspection of blood specimen for coagulation tests, only aPPT test should cause rejection patient&rsquo;s samples with hemolysis while icteric and lipemic should not be rejected at all when aPTT, PT, and fibrinogen tests are to be performed. There is a need for further study to be done on effects of icterus, hemolysis, and lipemia on other clotting factors. There is a need for further studies to be done on effects of icterus, hemolysis, and lipemia on other clotting factors. Key words: Hemolyis, icterus, lipemia, partial thromboplastin (PT), activated partial thromboplastin time (aPTT), fibrinogen. &nbsp

Coagulation studies: achieving the right mix in a large laboratory network

Basic coagulation tests, activated partial thromboplastin time (APTT), prothrombin time (PT) and the related international normalised ratio (INR), are performed frequently in hospital settings. From a laboratory perspective, unexpected abnormal results require further action; either informing the ordering clinician, or second line testing to determine the underlying cause. To streamline laboratory workflow, a new system of expert laboratory rules was implemented. The medical implications of this new laboratory system are evaluated here. The electronic ordering system was updated to mandate clinical information regarding the presence of an anticoagulant, or 'no anticoagulant'. When the PT or APTT were abnormal, and no anticoagulant was reported, second line testing was automatically performed. The second line tests performed were: mixing studies, fibrinogen and thrombin time. Any sample with a mixing study that did not completely correct, or fibrinogen <1.0 g/L, or INR >7.0, was flagged for clinical review by the laboratory haematology registrar. In a 17-month period there were 362,692 APTT, PT/INR and fibrinogen tests performed. Of these, 14,160 (3.9%) were abnormal with either no reported anticoagulant, or an unknown anticoagulant status. A total of 934 (0.3%) were referred for review by the haematology registrar. Three (<0.001%) cases received altered medical management as a result of the haematology registrar review. In hospital settings, most abnormal coagulation studies are anticipated by the ordering clinician. Unexpected abnormal coagulation results of clinical significance are rare. Automated second line coagulation testing and medical review improves laboratory workflow without compromising patient safety.

Nitric oxide releasing lipid bilayer tethered on titanium and its effects on vascular cells

The aim of this study was to investigate the feasibility and potential use of tethered lipid bilayer (tLB) membranes with a lipophilic nitric oxide (NO) donor (10-nitrooleate) incorporated into the bilayer to achieve the controlled release of NO from tLB membrane-anchored on a metal surface. NO releasing tLB membranes were prepared via two steps: (1) tethering phospholipids on a metal surface and (2) fusing NO donor containing liposomes with the lipids pre-tethered on the surface. Surface analyses using Fourier transform infrared (FTIR), fluorescent and confocal and atomic force microscopy (AFM) were utilized to prove the successful tLB formation on titanium surface. Bovine serum albumin and fibrinogen tests showed minimum adsorption on the tLB samples when compared with bare titanium plates. After the incorporation of 10-nitrooleate into the bilayer, the samples exhibited sustained NO release profiles up to 24h. In vitro cell study demonstrated that NO releasing tLB has pleiotropic effects on endothelial cells and smooth muscle cells. Finally, these results open up a door for the potential use of bioactive gas releasing tLB for biomedical devices.

Thromboelastography and Thromboelastometry in Assessment of Fibrinogen Deficiency and Prediction for Transfusion Requirement: A Descriptive Review.

Fibrinogen is crucial for the formation of blood clot and clinical outcomes in major bleeding. Both Thromboelastography (TEG) and Rotational Thromboelastometry (ROTEM) have been increasingly used to diagnose fibrinogen deficiency and guide fibrinogen transfusion in trauma and surgical bleeding patients. We conducted a comprehensive and comparative review on the technologies and clinical applications of two typical functional fibrinogen assays using TEG (FF TEG) and ROTEM (FIBTEM) for assessment of fibrinogen level and deficiency, and prediction of transfusion requirement. Clot strength and firmness of FF TEG and ROTEM FIBTEM were the most used parameters, and their associations with fibrinogen levels as measured by Clauss method ranged from 0 to 0.9 for FF TEG and 0.27 to 0.94 for FIBTEM. A comparison of the interchangeability and clinical performance of the functional fibrinogen assays using the two systems showed that the results were correlated, but are not interchangeable between the two systems. It appears that ROTEM FIBTEM showed better associations with the Clauss method and more clinical use for monitoring fibrinogen deficiency and predicting transfusion requirements including fibrinogen replacement than FF TEG. TEG and ROTEM functional fibrinogen tests play important roles in the diagnosis of fibrinogen-related coagulopathy and guidance of transfusion requirements. Despite the fact that high-quality evidence is still needed, the two systems are likely to remain popular for the hemostatic management of bleeding patients.

Natural Remedies Lower Elevated Fibrinogen Levels in the Prevention of Atherosclerosis

Cardiovascular Disease (CVD), which includes heart attack and stroke, is the number one cause of death in the United States. Data gathered from certain lab tests utilized as part of an early detection and prevention strategy can be used to gauge the efficacy of preventative measures in an effort to halt or slow the progression of CVD. Acute phase reactant tests, Erythrocyte Sedimentation Rate (ESR), C-Reactive Protein (CRP), Fibrinogen, and Ferritin are the most clinically relevant to detection. Acute phase reactants are proteins that increase or decrease in the presence of inflammatory stimuli. Of the four tests, the most widely used in conventional medicine are ESR and CRP. Fibrinogen tests are underutilized in conventional medicine. Fibrinogen, which originates in the liver, is a fibrous glycoprotein in vertebrates that helps in the formation of blood clots. Fibrinogen levels rise in the following conditions: Inflammation, tissue damage/trauma, infection, cancer, acute coronary syndrome, strokes, and inflammatory diseases. Fibrinogen tests are often used after a cardiovascular incident has occurred or if symptoms are severe enough to warrant a test. However, there is sufficient evidence which shows that fibrinogen levels slowly begin to rise long before a heart attack or stroke and may even be reflective of the severity of subclinical atherosclerotic conditions. Traditional Chinese Medicine (TCM) and other preventative natural medical systems have treatments which reduce or normalize Fibrinogen levels, thereby, preventing the progression of symptoms that can lead to more serious cardiovascular occurrences in the future. This article will review published studies that show how natural remedies can effectively lower elevated plasma fibrinogen levels.

Determination of Age-Dependent Reference Ranges for Coagulation Tests Performed Using Destiny Plus.

BackgroundIn order to apply the right treatment for hemostatic disorders in pediatric patients, laboratory data should be interpreted with age-appropriate reference ranges.ObjectivesThe purpose of this study was to determining age-dependent reference range values for prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen tests, and D-dimer tests.Materials and MethodsA total of 320 volunteers were included in the study with the following ages: 1 month - 1 year (n = 52), 2 - 5 years (n = 50), 6 - 10 years (n = 48), 11 - 17 years (n = 38), and 18 - 65 years (n = 132). Each volunteer completed a survey to exclude hemostatic system disorder. Using a nonparametric method, the lower and upper limits, including 95% distribution and 90% confidence intervals, were calculated.ResultsNo statistically significant differences were found between PT and aPTT values in the groups consisting of children. Thus, the reference ranges were separated into child and adult age groups. PT and aPTT values were significantly higher in the children than in the adults. Fibrinogen values in the 6 - 10 age group and the adult age group were significantly higher than in the other groups. D-dimer levels were significantly lower in those aged 2 - 17; thus, a separate reference range was established.ConclusionsThese results support other findings related to developmental hemostasis, confirming that adult and pediatric age groups should be evaluated using different reference ranges.

Predictive value of autoantibodies from anti-CCP2, anti-MCV and anti-human citrullinated fibrinogen tests, in early rheumatoid arthritis patients with rapid radiographic progression at 1 year: results from the ESPOIR cohort

ObjectivesWe compared the ability of antibodies against cyclic citrullinated peptides (anti-CCP2), against mutated citrullinated vimentin (anti-MCV) and against citrullinated fibrinogen (AhFibA) to predict 1 year rapid radiographic progression (RRP; total...

Variable Manifestations of Severe Hypoprothrombinemia (Factor II Deficiency): 2 Cases

Case 1 is a 28 months female child, who has been symptomatic from 8 month of age with multiple, painful bruises over legs once in 5 to 6 weeks. Her complete blood picture was normal.PT and APTT were prolonged with normal fibrinogen and liver function. Case 2, became symptomatic from day 2 of life. He was treated for blood stained vomiting and black coloured stool and severe anaemia. Second episode was subdural hemorrhage and seizures. Investigations revealed abnormal PT and APTT with normal fibrinogen and liver function. Hereditary prothrombin deficiency is one of the rare congenital coagulation defect encountered in clinical practice. High index of suspicion is required to diagnose this condition with systematic approach as the facility to check factor 2 levels are not freely available in many centres. Bleeding manifestations are dependent on factor level. Children with severe deficiency are prone for life threatening bleeds. We report couple of children who had severe form of hereditary prothrombin deficiency with variable clinical manifestations. In both the cases, coagulation profile was suggestive of common pathway defect, PT and APTT were prolonged. Fibrinogen and Liver function tests were normal. No evidence of sepsis, no response to vitamin K. Further evaluation revealed low prothrombin activity (<1%). Factor v and x were normal.

Measurement of serum growth differentiation factor 15 concentration in children with hemophagocytic lympohistiocytosis and implications in the development of hyperferritinemia

Objective To measure the serum growth differentiation factor (GDF15) levels in children with hemophagocytic lympohistiocytosis (HLH), and to explore its possible implications in the development of hyperferritinemia in HLH. Methods Twenty-eight children with newly-diagnosed HLH and 20 age-and-sex matched healthy children were enrolled in this study as research subjects and controls respectively.Serum GDF15 levels were measured by Quantikine ELISA assay (product of R&D Company, USA) according to manufacturer's instructions.Serum ferritin concentration and other biochemical parameters were determined by conventional methods.Comparison of serum GDF15 levels between HLH group and healthy control group were made by nonparametric Mann-Whitney test.Correlations between serum GDF15 concentration and hemobiochemical parameters (Hb, serum ferritin, fibrinogen, blood lipids, and liver and renal function tests) were made via Spearman correlation analysis. Results Serum GDF15 concentration was significantly higher in HLH group than that in healthy control group, with median concentrations and ranges of 1710 ng/L, 190-2400 ng/L, and 260 ng/L, 104-649 ng/L, respectively (P<0.001). Serum GDF15 concentration was correlated neither to Hb concentration at diagnosis nor to lowest Hb concentration before HLH-directed chemotherapy.Nevertheless it was positively correlated to serum level of total bilirubin at diagnosis and highest concentration of trigly-cerates during disease course(χ2=0.475, 0.465; P=0.011, 0.019, respectively), and negatively correlated to lowest levels of fibrinogen and albumin at diagnosis (χ2=-0.423, -0.399; P=0.031, 0.039, respectively). Serum GDF15 level was not correlated to underlying etiology and mortality rate of children with HLH. Conclusions GDF15 has been documented as an upstream negative regulator of hepcidin, the central iron regulatory hormone produced primarily by hepatocytes, and is massively produced by activated macrophages in an autocrine fashion to suppress further activation of macrophages.This research finding that serum GDF15 level is significantly elevated in children with HLH suggests that GDF 15 is intimately implicated in the modulation of iron homeostasis and the development of hyperferritinemia in HLH. Key words: Hemophagocytic lympohistiocytosis; Growth differentiation factor 15; Hyperferritinemia; Child

Iopiperidol: Nonionic iodinated contrast medium with promising anticoagulant and antiplatelet properties

The purpose of this study was to determine the anticoagulant and antiplatelet characteristics of iopiperidol, a nonionic, triiodinated contrast agent. Anticoagulant effects of iopiperidol were assessed both in vitro and in vivo after single or repeated intravenous administrations to rats. To this aim, results of prothrombin time, activated partial thromboplastin time, thrombin time, and fibrinogen tests were evaluated. To define better the mechanism of action of iopiperidol and of the contrast media used for comparison, in vitro tests to study the effects on thrombin activity and on thrombin generation were performed. In addition, the effect of iopiperidol was studied on adenosine diphosphate- and collagen-induced platelet aggregation both in vitro and in vivo after single or repeated intravenous administrations in the rat. In vitro, iopiperidol showed anticoagulant properties similar or superior to those of the ionic ioxaglate. Iopiperidol also inhibited collagen-induced platelet aggregation statistically significantly more than iodixanol and ioxaglate (P < .05). In vivo, no significant differences between iopiperidol and ioxaglate were observed after single or repeated administrations. The in vitro anticoagulant effect of iopiperidol is similar or even superior to that of ioxaglate; the in vivo effect is similar to that of reference nonionic contrast media.

THE ROSE BENGAL TEST FOR LIVER FUNCTION

In a previous paper we 1 suggested the use of rose bengal as a test for total liver function. Further observations have confirmed our earlier conclusions, and lead us to believe that, in rose bengal, we have a dye that has advantages over other dyes, so far studied, in estimating the gross functional capacity of the liver. The various tests that have been devised for the study of separate functions of the liver have been far from satisfactory. Among these should be included the levulose test for carbohydrate function; urobilinogen tests in the urine; fibrinogen tests of the blood; determinations of the lipolytic and fibrinolytic ferments of the blood; studies of the protein metabolism, and the hemoclastic test. Recent studies on the bile pigment metabolism suggest that estimations of the bile pigments in the blood serum may be of value when used alone or in conjunction with other tests. The