Laboratory Fibrinogen Research Articles

An audit of the diagnostic accuracy of the ROTEM®sigma for the identification of hypofibrinogenaemia in cardiac surgical patients.

The ROTEM®delta (TEM Innovations GmbH, Munich, Germany) has been used extensively worldwide for the assessment of coagulation in cardiac surgical patients. Recently, a new cartridge-based ROTEM device (ROTEM®sigma, TEM Innovations GmbH, Munich, Germany) has become available. In this paper we report an audit of the diagnostic accuracy of the ROTEM sigma for the identification of hypofibrinogenaemia in cardiac surgical patients. We hypothesised that the diagnostic accuracy of the ROTEMsigma for the identification of hypofibrinogenaemia would be in a similar range to that previously reported for the ROTEMdelta. Simultaneous blood samples for Clauss laboratory fibrinogen and ROTEMsigma FIBTEM measurements were obtained immediately after heparin reversal post-cardiopulmonary bypass in 200 adult cardiac surgical patients. The sensitivity, specificity, and positive and negative predictive values for FIBTEM A5 and A10 for the identification of hypofibrinogenaemia (Clauss fibrinogen <1.5 g/l) were calculated. The prevalence of hypofibrinogenaemia across the 200 patients was 8%. The mean sensitivity and specificity of FIBTEM A10 ≤8 mm for the identification of hypofibrinogenaemia were 0.75 and 0.90 respectively, which are in a similar range to that reported in several previous studies using the ROTEMdelta. For FIBTEM A5 ≤6 mm the values were 0.63 and 0.98 respectively. The predictive values were also in a similar range to those previously reported for the ROTEMdelta, with low false negative rates (2% for A10 ≤8 mm; 3% for A5 ≤6 mm). These findings support the use of the ROTEMsigma as an alternative to the ROTEMdelta for the identification of hypofibrinogenaemia post-cardiopulmonary bypass in cardiac surgical patients. However, further studies are required in other settings.

The sensitivity and specificity of rotational thromboelastometry (ROTEM) to detect coagulopathy during moderate and severe postpartum haemorrhage: a prospective observational study

IntroductionPoint-of-care viscoelastic haemostatic assays such as rotational thromboelastometry (including ROTEM and TEG) have been used in the management of postpartum haemorrhage (PPH). This study compared results obtained from the automated ROTEM Sigma with laboratory tests of coagulation and platelet count during PPH. MethodsA prospective observational cohort study recruited women with PPH ≥1000 mL (or clinical concern of bleeding). The Fibtem A5, Extem CT and Pltem (Extem A5 – Fibtem A5) results were compared with laboratory tests of fibrinogen, prothrombin time (PT), activated partial thromboplastin time (APTT) and platelet count. Results521 women were recruited, including 274/277 (98.9%) of women with PPH ≥1500 mL. Fibtem A5 results were matched with laboratory fibrinogen in 552/644 (85.7%) samples. The incidence of abnormal laboratory results was low: fibrinogen ≤2 g/L 23/464 (5.0%), PT or APTT >1.5 × midpoint of reference range 4/464 (0.9%), and platelet count <75 × 109/L 11/477 (2.3%). Area-under-the-receiver operator characteristic curve for Fibtem A5 to detect fibrinogen ≤2 g/L was 0.96 (95% Confidence Interval (CI) 0.94 to 0.98, P<0.001), with sensitivity and specificity of Fibtem A5 ≤11 mm to detect fibrinogen ≤2 g/L of 0.76 and 0.96. Prolonged Extem CT results improved after treatment of hypofibrinogenaemia alone. Intervention points for platelet and fresh frozen plasma (FFP) transfusion based on ROTEM Sigma parameters could not be established. ConclusionDuring PPH (≥1000 mL or cases of clinical concern about bleeding), ROTEM Sigma Fibtem A5 can detect fibrinogen ≤2 g/L and guide targeted fibrinogen replacement. Laboratory results should continue to be used to guide platelet and FFP transfusion.

Point‐of‐care blood clotting test and its correlation with fibrinogen level: Potential in goal‐directed transfusion in postpartum hemorrhage

To study the correlation of conventional point-of-care clotting test (POCCT) of whole blood with laboratory fibrinogen levels in women with primary major postpartum hemorrhage (PPH) to generate evidence regarding its potential in rationalizing transfusion of blood components for supplementing fibrinogen. A total of 68 samples were studied: 40 from women with primary major PPH, 20 from women without PPH, and eight samples of Fresh Frozen Plasma (FFP). POCCT was performed in the PPH and non-PPH groups and at the same time, sample for laboratory fibrinogen was sent. Values were correlated using Pearson's correlation coefficient (r). Depending upon the laboratory fibrinogen values, POCCT in the PPH group was divided into three subgroups of less than 7, 7-11, and more than >11min as subgroups 1, 2, and 3, respectively. Women in the PPH group (n=40) had a mean fibrinogen level of 346.15±143.37mg% with a significant negative correlation with POCCT (r=-0.69, P<0.001). Mean fibrinogen levels of non-PPH group and FFP samples were 602.1±169.72 and 286.75±103.42mg%, respectively. PPH subgroups 1, 2, and 3 had mean fibrinogen of 452.2±141.8, 332.58±138.51, and 158.71±145mg%, respectively. These values may potentially guide FFP transfusions. POCCT is easy, costs nothing and has a potential role in rationalizing FFP transfusion in low- and middle-income countries.

Prompt prediction of fibrinogen concentration during cardiopulmonary bypass: a pilot study.

ABSTRACTPlatelet Mapping can measure both the degree of platelet inhibition and fibrinogen activation, was not originally designed to measure fibrinogen concentration. Traditional laboratory fibrinogen concentration testing requires around 60 minutes; however, fibrinogen activation only takes 10 minutes, and is indicated as maximum amplitude of activator f. If Platelet Mapping can predict fibrinogen concentration during cardiopulmonary bypass, this could facilitate rapid hemostasis management. The aim of this study was to verify whether fibrinogen concentration could be predicted using Platelet Mapping results. Thus, a pilot study was conducted to evaluate this concept during cardiopulmonary bypass. This prospective, observational pilot study investigated 15- to 90-year-old patients who underwent cardiac or aortic surgery from August 2019 to September 2019. Twenty-one patients enrolled in this study, and 43 blood samples were obtained for both fibrinogen activation measurements using Platelet Mapping and traditional laboratory-based tests, respectively. Correlations between results were analyzed using linear regression and the receiver operating characteristic curve. Correlation by Pearson’s correlation analysis indicates a significant relationship (correlation coefficient of r = 0.91), and a receiver operating characteristic curve indicated that sensitivity, specificity, and receiver operating characteristic area were 100% (95% confidence interval, 75.3–100%), 93.8% (79.2–99.2%), and 0.995 (0.984–1.00), respectively. Our results indicate a strong correlation between fibrinogen activation and serum fibrinogen concentration. The maximum amplitude of activator f can estimate low fibrinogen concentration faster than traditional methods; this method quickly provides important information for anesthesia and hemostatic management in cardiac surgery.

Novel Use of Scanning Electron Microscopy for Detection of Iron‐Induced Morphological Changes in Human Blood

Fibrinogen is key to the maintenance of hemostasis and is an acute phase protein that is part of the coagulation cascade of proteins. It plays a fundamental role in inflammation, particularly as indicator for a proinflammatory state and is a prominent marker for developing vascular inflammatory diseases. The ultrastructure of fibrin nets can be studied using scanning electron microscopy (SEM) with the addition of thrombin to plasma. In inflammatory conditions such as thromboembolic ischemic stroke and diabetes, the fibrin networks are changed to from dense matted fibrin deposits (DMDs) instead of typical netlike appearance. Similar DMDs can also be induced with the addition of FeCl(2) and FeCl(3). Importantly, the iron-induced DMDs look similar to those from patients with prothrombotic conditions. Excessive or misplaced tissue iron now is recognized to pose a substantial health risk. The current research therefore investigates the establishment of a laboratory fibrinogen model to study that might mimic fibrin fiber generation that is achieved using plasma from healthy and diseased individuals. Furthermore, to determine whether the addition of iron to purified fibrinogen will show DMDs and whether hydrophilic agents can prevent them. We conclude that SEM is a very effective tool for the visualization of circulatory consequences of the interaction of iron-induced hydroxyl radicals with human fibrinogen. Furthermore, this novel fibrinogen model provides a convenient method to study the interactions of the intramolecular and intermolecular hydrophobic forces responsible for the maintenance of the tertiary structure of native fibrin(ogen) and the prevention of iron-induced DMDs formation by hydrophilic agents.

Use of purified fibrinogen concentrate for dysfibrinogenemia and importance of laboratory fibrinogen activity measurement

We report a patient with dysfibrinogenemia treated with purified fibrinogen concentrate who had discrepant post-treatment laboratory values. The patient had mild bleeding symptoms and was diagnosed with dysfibrinogenemia based on fibrinogen activity of 51 mg/dl and antigen of 240 mg/dl. He was treated for an adenoidectomy with purified fibrinogen concentrate (RiaSTAP®) at a dose of 70 mg/kg. A discrepancy in post-treatment fibrinogen activity was observed between the hospital and reference laboratories. Investigation revealed differences in laboratory assay and calibration methods. Fibrinogen concentrate may be a treatment option for patients with dysfibrinogenemia, but accurate laboratory technique is critical for fibrinogen measurement.