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Blood Coagulation and Anemia Biomarkers

Blood coagulation can be defined as the process in which blood clots. This important and complex process enables the blood to plug and heal a wound to stop any unwanted bleeding in the body. Coagulation involves the action of platelets and coagulation (clotting) factors. This process is normally under the inhibitory control of several inhibitors to avoid thrombus propagation. The balance may be interrupted by an increase of procoagulant activity or by a decrease of the inhibiting factors. The majority of clotting factors are zymogens that circulate in an inactive form. For example, fibrin is an important insoluble protein that plays a role in blood clotting. This insoluble protein is a product of fibrinogen, and collects around wounds in a mesh-like structure to strengthen platelet plugs. Most of these procoagulants or anticoagulants are produced by the liver, and must undergo a post translational modification to enable them to bind to calcium or other divalent cations to participate in the cascade.

The balance between clotting and bleeding is always maintained in the body, and along with it are its complications that may result in abnormal bleeding or clotting. Over-clotting of blood can result in deep vein thrombosis (DVT), and a lack of clotting is a condition known as hemophilia. Most of these disorders are hereditary; however, there are disorders that can be acquired, such as disseminated intravascular coagulation, consumptive coagulopathies, and fibrinolysis defects.

A lack of the proper amount of red blood cells, or dysfunctional red blood cells, is characterized as anemia. Anemia is the most common blood disorder, affecting more than 3 million Americans according to the National Heart, Lung, and Blood institute. This condition causes a lack of oxygen in the body and causes dizziness, weakness, and many other symptoms. Anemia is most commonly caused by iron deficiency, where a lack of sufficient iron to form normal red blood cells is observed. Approximately 5% and 2% of American women and men, respectively, have iron deficiency anemia (Johnson et al., 2011). Other causes of anemia include malaria, schistosomiasis, chronic kidney disease, and genetic disorders of hemoglobin such as sickle cell disease and thalassemia.

There has recently been an emerging use of utilizing the concept of biomarkers for the clinical diagnosis of anemia and blood coagulation. Biomarkers are measurable cellular, biochemical or molecular alterations that provide a dynamic and powerful approach in evaluating disease prediction, cause, diagnosis, progression, regression, or outcome of treatment disease (Mayeux, 2004). As biomarker research takes the spotlight, the role of immunohistochemistry within that process is increasing. Please see AssaySolution’s catalog of Premier IHC antibodies for your needs.

Listed below are a few of the biomarkers related to anemia and blood coagulation with their descriptions. Here at AssaySolution, we provide high quality ELISA Kits for the detection and quantification of anemia and blood coagulation biomarkers. Please see our catalog for the full list of ELISA kits.

Erythropoietin – Erythropoietin (Epo) is produced primarily in the kidneys upon low blood oxygen availability. This protein stimulates erythropoiesis in the bone marrow and the decrease of plasma volume, resulting in blood hemoglobin content to hematocrit (Lundby et al., 2006). Overexpression of Epo may be associated with certain pathophysiological conditions such as polycythemia and tissue hypoxia. Deficient Epo production is found in conjunction with certain types of anemias. Many anemic conditions are associated with the generation of IL-1 and TNF-a, which are inhibitors of Epo activity. Recombinant human Epo (rHuEpo), first cloned in 1985 by Jacobs et al. (1985) is clinically used for the effective treatment of chronic anemia in patients with end-stage renal disease (ESRD); however, rHuEpo has also been used to increased exercise performance by more than 50% (Thomsen et al., 2007) and continues to be abused by athletes.

Ferritin – Serum ferritin is considered as the most useful biomarker to measure iron status and concentrations. Low iron concentrations in combination with anemia is termed iron-deficiency anemia. Iron deficiency in the absence of anemia suggests that dietary iron intake is metabolically sufficient but insufficient to accumulate any stores. One limitation of this biomarker is due to increased concentrations of ferritin in the presence of inflammation even if iron stores are low; therefore, interpreting true ferritin concentration may be difficult where exposure to inflammation is common (Thurnham et al., 2010). 

Fibrinogen – Fibrinogen is an acute phase soluble plasma glycoprotein that is produced primarily in the liver and converted enzymatically by thrombin into fibrin during blood coagulation. Elevated levels of fibrinogen are associated with inflammation, trauma, surgery, and malignancy. Decreased levels are associated with congenital deficiencies, thrombosis or disseminated intravenous coagulation, which is the most common cause of low plasma fibrinogen. Fibrinogen also plays an important role in mediating inflammation of bacterial infections (Kim et al., 2018).

Folate – Folates are water-soluble vitamins that play an important role in the transfer of one-carbon units in amino acid interconversions, essential for protein synthesis and hematopoiesis. Prolonged folate deficiency leads to megaloblastic anemia, with folate status able to be measured by both serum folate and red blood cell concentrations.

Transferrin – Transferrin saturation tests are used to screen for and monitor conditions of iron overload and iron deficiency. Transferrin transports serum iron, with a saturation that exhibits a daily fluctuation similar to that of serum iron. The total transferrin concentration in blood is characterized as the maximum iron-binding capacity of the plasma. The amount of unbound binding capacity on transferrin in normal humans is thought to provide protection against unbound, free iron in the blood (Bothwell et al., 1979). To approximate the amount of stored iron, the log ratio of serum soluble transferrin receptor (sTfR) to serum ferritin concentrations can be calculated (Cook et al., 2003).

Thrombin activatable fibrinolysis inhibitor (TAFI) – TAFI is a plasma zymogen that can be converted enzymatically into activated TAFI (TAFIa) by thrombin, plasmin, or thrombomodulin. Thrombin-catalyzed conversion of plasma fibrinogen into fibrin and the formation of a fibrin clot, which is protected from lysis by TAFIa. Thus, defects in TAFI activation may contribute to the severity of bleeding disorders, whereas an increased activation of TAFI may be associated with thrombotic disorders. TAFI also plays an important role in the progression of human cerebral hemorrhage, by contributing to the inhibition of inflammation and thrombosis formation (Plug and Meijers, 2016 and Yaoita et al., 2016).

D-dimer – D-dimer is a fibrin degradation product and a well-known indicator of coagulation activation and fibrinolysis. D-dimer is normally present in only negligible amounts (of the order 100-200 ng/mL), and elevated blood concentration of D-dimer may indicate intravascular coagulation and thrombotic disease. Several reports indicate that D-dimer is associated with the risk of venous thromboembolism (VTE) in patients with cancer (Arpaia et al., 2009 and Ferroni et al., 2012).  Furthermore, it was shown that D-dimer may even be a valuable biomarker for predicting recurring VTE in cancer patients after discontinuation of anticoagulation (Cosmi et al., 2005).

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