Understanding Fibrinogen: Key Insights into Blood Coagulation
Fibrinogen (Factor I), a crucial protein in regulating blood coagulation, plays a pivotal role in our body's hemostasis process, especially in scenarios like wound healing. Synthesized in the liver, fibrinogen transforms into fibrin under the influence of thrombin, forming clots that staunch bleeding.
This process, essential for preventing excessive blood loss, involves various proteins and factors.
However, fibrinogen imbalance can lead to clotting disorders with severe health implications. High fibrinogen levels, for instance, elevate the risk of clot formation, potentially causing cardiovascular complications or strokes. Conversely, low levels might result in prolonged bleeding.
Monitoring fibrinogen levels through a simple blood test helps clinicians assess clotting mechanisms and diagnose related conditions. Normal values typically range between 200 to 400 mg/dl in adults, varying slightly across age groups.
Several factors can influence fibrinogen levels. Stress, pregnancy, tobacco use, and certain medications like oral contraceptives or anticoagulants can elevate them. Conversely, genetic mutations, ageing, cold temperatures, dietary factors, and obesity may contribute to fluctuations.
Understanding fibrinogen's role and maintaining balance is crucial for overall health, emphasizing the significance of proactive measures and medical monitoring.
Fibrinogen and its proteolytic cleavage product, ?brin, are critical plasma proteins with multiple functions in blood clotting. Although the primary function of fibrinogen is in fibrin clot formation, it has a multitude of other functions which include factor XIIIa–mediated ?brin crosslinking, non-substrate thrombin binding, a ligand for platelet glycoprotein IIb/IIIa, platelet aggregation, and ?brinolysis.
A variety of structural abnormalities can occur in ?brinogen and can interfere with one or more of its haemostatic roles. Structurally abnormal ?brinogens are collectively termed dys?brinogenemia (Acharya, 2018; Lewis, Bain and Bates, 2006).
Managing fibrinogen levels is essential for preventing adverse health outcomes. Lifestyle modifications, including a balanced diet, regular exercise, stress reduction, and smoking cessation, can help maintain optimal levels. Additionally, prompt medical intervention may be necessary to address imbalances, utilizing therapies like antiplatelet or anticoagulants.
Laboratory testing Insights:
Fibrinogen assays are an important screening tool for blood coagulation disorders or an unexplained prolongation of the activated partial thromboplastin time (APTT) or prothrombin time (PT).
The Clauss and PT-derived methods are both coagulable protein methods for the quantification of fibrinogen concentrations. Although numerous methods are available, no consensus has been reached as to which method is preferable.
In the laboratory, PT measures the activity of the extrinsic pathways; hence, it is sensitive to abnormalities in factor VII, X, V, II (prothrombin) and fibrinogen. A PT test is performed by adding calcium and thromboplastin, an activator of the extrinsic pathway, to the blood sample then measuring the time (in seconds) required for fibrin clot formation. While APTT measures the activity of the intrinsic pathways, thereby is sensitive to abnormalities in factor XII, XI, IX & VIII.
Principle of Modified Clauss Assay: Dilutions of standard normal plasma with the known fibrinogen content are prepared in glyoxaline buffer. The clotting time is measured after the addition of thrombin, and a graph is constructed. The clotting time is proportional to the concentration of fibrinogen and 1/10 dilution in imidazole buffer is taken to represent the value in standard preparation. The test plasma is diluted 1/10 and the result is read from the standard line.
For manual techniques, the test is done in duplicate. This is not necessary for most coagulometers when the test is automated.
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Plot the mean clotting time v/s Fibrinogen concentration on log/log graph paper taking the 1/10 dilution to represent the standard value.
For most Clauss techniques this relationship is linear over a limited range of clotting times, typically 10 to 25 seconds.
The test is not affected by heparin at the levels used for treatment of Venous thromboembolism.
The higher levels used for Cardiopulmonary bypass can have prolonged clotting times leading to underestimation of fibrinogen unless the reagent contains heparin neutralizers to counter this.
The calibration curve must be established with the reagent in local use
Assays Variabilities: Fibrinogen heterogeneity and sensitivity to environmental factors make it an ideal subject for discussion regarding the evolutionary hypotheses in humans. Variability in fibrinogen concentrations between two given populations is most commonly due to the dynamic heterogeneity of the three different pairs of polypeptide chains and several external factors that affect fibrinogen concentration; including gender, age, body mass index, physical exercise, smoking, stress and alcohol consumption. Variability in fibrinogen concentration between laboratories is much higher because of the major effect of differences in methods and the composition of reagents. These factors can be specific to different areas of the country; further complicated by the lack of an international fibrinogen standard.
Below the comparison for both the assays:
Several studies also supported the fact that the Clauss assay is more favourable in comparison to the PT-derived fibrinogen results; however, it has certain shortcomings. To prevent missed diagnoses, performing both PT-derived and Clauss methods on all Citrate sample requests is the best practice.