Rapid paper diagnostic for plasma fibrinogen concentration.

Fibrinogen is a blood protein that is essential for clotting. It is converted into the polymer fibrin by the blood enzymes thrombin and factor XIIIa. Fibrinogen is one of the first proteins to be depleted in heavily bleeding patients. Patients with early hypofibrinogenemia need urgent fibrinogen replenishment to prevent the onset of haemorrhage and death. However, currently there is no rapid, sensitive, cheap and easy-to-use fibrinogen assay that can detect fibrinogen concentrations. In this study, we have developed a new paper-based diagnostic to quantify the fibrinogen concentration in blood at room temperature. This diagnostic is a 2-step process: first, plasma is added onto thrombin-treated paper strips where fibrinogen is converted to fibrin; then the strips are placed into an aqueous dye bath where elution occurs. The test operates by measuring the change in hydrophobicity, which increases with fibrinogen concentration under otherwise constant conditions. The diagnostic can precisely measure fibrinogen concentration within the range of 0-2 g L-1, which is ideal for the clinical diagnosis of hypofibrinogenemia. Furthermore, testing needs only 12 µL of plasma, 60 mU of thrombin and 7.5 minutes of testing. This diagnostic has the potential to revolutionise point of care testing and save many lives.

Fibrinogen Diagnostics in Major Hemorrhage.

Fibrinogen is one of the first factors to fall to critically low levels in the blood in many coagulopathic events. Patients with hypofibrinogenemia are at a significantly greater risk of major hemorrhage and death. The rapid replacement of fibrinogen early on in hypofibrinogenemia may significantly improve outcomes for patients. Fibrinogen is present at concentrations between 2 and 4 g/L in the plasma of healthy people. However, hypofibrinogenemia is diagnosed when the fibrinogen level drops below 1.5-2 g/L. This review analyses different types of fibrinogen assays that can be used for diagnosing hypofibrinogenemia. The scientific mechanisms and limitations behind these tests are then presented. Additionally, the current state of clinical major hemorrhage protocols (MHPs) is presented and the structure, function and physiological role of fibrinogen is summarized.

Paper Diagnostic for Direct Measurement of Fibrinogen Concentration in Whole Blood.

The ability to diagnose and treat critically bleeding patients can save more than 2 million lives a year. Diagnosing hypofibrinogenemia is essential in these patients. Recently, with the development of new handheld diagnostics, fibrinogen concentration can be measured rapidly at the point of care. However, these diagnostics can only work with plasma and hence need blood cells to be separated before use. In this study, we demonstrate a handheld fibrinogen diagnostic that works with whole blood. The test works by (1) forming a premixed droplet of a whole blood sample and thrombin solution on a solid surface, (2) allowing it to clot, and (3) dropping a paper strip on top. The further that blood moves down the strip, the lower the fibrinogen concentration. The diagnostic can easily measure plasma fibrinogen concentrations below 1.6 g/L for blood samples with hematocrits between 40 and 50%. Furthermore, diluting blood samples not only increases the test's sensitivity but also eliminates the effect of hematocrit and thrombin inhibitors. The test can be completed in 3-4 min, making it suitable for diagnosing early hypofibrinogenemia and allowing for fibrinogen replacement therapy in critically bleeding patients.

Rapid, hand-held paper diagnostic for measuring Fibrinogen Concentration in blood.

Critical bleeding causes over 2 million deaths a year. Early hypofibrinogenemia is a strong predictor of mortality in critically bleeding patients. The early replenishment of fibrinogen can significantly improve outcomes. However, over replenishment can also be dangerous. Furthermore, there is no rapid, cheap, hand-held diagnostic that can aid critically bleeding patients in fibrinogen replacement therapy. In this study, we have developed a hand-held paper diagnostic that measures plasma fibrinogen concentrations. The diagnostic has the potential to be used as a point of care device both inside and outside of hospital settings. It can vastly reduce the time to treatment for fibrinogen replacement therapy. The diagnostic is a two-step process. First, thrombin and plasma are added onto horizontially-orientated paper strips where the fibrinogen is converted into fibrin, drastically increasing the plasma's hydrophobicity. Second, an aqueous blue dye is pipetted onto the strips and allowed to wick through the fibrin. The distance the blue dye wicks through the strip correlates precisely to the fibrinogen concentration. The diagnostic can provide results within a minute. It can distinguish low fibrinogen concentrations (ie. <2 g/L) from normal fibrinogen concentrations. It shows remarkable reproducibility between healthy individuals. It is unaffected by common blood conditions such as acidosis, blood alcohol, severe hypertriglyceridemia, severe haemolysis and warfarin administration. Finally, it is unaffected by humidity and can withstand cold temperatures.