Fibrin monomer

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Fibrin monomers are monomers of fibrin which are formed by the cleavage of fibrinogen by thrombin. [1] Levels of fibrin monomers can be measured using blood tests and can serve as a marker of in vivo fibrinogenesis and coagulation activation. [1] [2] [3] They may be useful in the evaluation hypercoagulability. [1]

Levels of fibrin monomers may be increased with pregnancy [1] and by estrogen-containing combined birth control pills. [2]

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Prothrombin fragment 1+2 (F1+2), also written as prothrombin fragment 1.2 (F1.2), is a polypeptide fragment of prothrombin generated by the in vivo cleavage of prothrombin into thrombin by the enzyme prothrombinase. It is released from the N-terminus of prothrombin. F1+2 is a marker of thrombin generation and hence of coagulation activation. It is considered the best marker of in vivo thrombin generation.

The calibrated automated thrombogram is a thrombin generation assay (TGA) and global coagulation assay (GCA) which can be used as a coagulation test to assess thrombotic risk. It is the most widely used TGA. The CAT is a semi-automated test performed in a 96-well plate and requires specialized technologists to be performed. As a result, it has seen low implementation in routine laboratories and has been more limited to research settings. Lack of standardization with the CAT has also led to difficulties in study-to-study comparisons in research. However, efforts have recently been made towards standardization of the assay. An example of a specific commercial CAT is the Thrombinoscope by Thrombinoscope BV.

A thrombin generation assay (TGA) or thrombin generation test (TGT) is a global coagulation assay (GCA) and type of coagulation test which can be used to assess coagulation and thrombotic risk. It is based on the potential of a plasma to generate thrombin over time, following activation of coagulation via addition of phospholipids, tissue factor, and calcium. The results of the TGA can be output as a thrombogram or thrombin generation curve using computer software with calculation of thrombogram parameters.

The activated protein C resistance (APCR) test is a coagulation test used in the evaluation and diagnosis of activated protein C (APC) resistance, a form of hypercoagulability. Hereditary APC resistance is usually caused by the factor V Leiden mutation, whereas acquired APC resistance has been linked to antiphospholipid antibodies, pregnancy, and estrogen therapy. APC resistance can be measured using either an activated partial thromboplastin time (aPTT)-based test or an endogenous thrombin potential (ETP)-based test.

<span class="mw-page-title-main">Fibrinopeptide</span> Chemical compound

The fibrinopeptides, fibrinopeptide A (FpA) and fibrinopeptide B (FpB), are peptides which are located in the central region of the fibrous glycoprotein fibrinogen and are cleaved by the enzyme thrombin to convert fibrinogen into covalently-linked fibrin monomers. The N-terminal FpA is cleaved from the Aα chains of fibrinogen and FpB from the Bβ chains of fibrinogen, with FpA released before FpB. Subsequent to their formation, fibrin monomers are converted to cross-linked fibrin polymers by the action of thrombin-activated factor XIII, and these fibrin polymers form the backbone of a thrombus. Hence, the fibrinopeptides are sensitive markers of fibrinogenesis, thrombin activity, and coagulation.

Plasmin-α2-antiplasmin complex (PAP) is a 1:1 irreversibly formed inactive complex of the enzyme plasmin and its inhibitor α2-antiplasmin. It is a marker of the activity of the fibrinolytic system and a marker of net activation of fibrinolysis.

The ST Genesia is a fully automated commercial analyzer system for performing thrombin generation assays (TGAs) and hence for coagulation testing. It was developed by Diagnostica Stago and was introduced by the company in 2018.

β-Thromboglobulin (β-TG), or beta-thromboglobulin, is a chemokine protein secreted by platelets. It is a type of chemokine ligand 7. Along with platelet factor 4 (PF4), β-TG is one of the best-characterized platelet-specific proteins. β-TG and PF4 are stored in platelet alpha granules and are released during platelet activation. As a result, they are useful markers of platelet activation. β-TG also has multiple biological activities, for instance being involved in maturation of megakaryocytes.

The overall hemostatic potential (OHP) test is a global coagulation assay which can be used to measure coagulation. The OHP assay measures total fibrin generation in the presence of thrombin or tissue factor and tissue plasminogen activator (t-PA). It generates a fibrin time curve through the use of optical density measurement. This curve represents the balance between fibrin formation induced by thrombin or tissue factor and fibrinolysis induced by t-PA. The assay provides three parameters: overall coagulation potential (OCP), overall hemostatic potential (OHP), and overall fibrinolytic potential (OFP). OHP is the main parameter, while OCP and OFP are supplementary parameters to assess coagulation and fibrinolysis. One further parameter, clot lysis time (CLT), can also be determined. The OHP assay measures the integrated effect of procoagulant, anticoagulant, and fibrinolytic factors.

Coagulation activation markers are biomarkers of net activation of coagulation and fibrinolysis. Examples include prothrombin fragment 1+2 (F1+2), thrombin–antithrombin complex (TAT), fibrinopeptide A (FpA), fibrin monomers (FMs), plasmin-α2-antiplasmin complex (PAP), activated protein C–protein C inhibitor (APC-PCI), and D-dimer (DD). These compounds are markers of thrombin generation, fibrin generation, and fibrinolysis. Coagulation activation markers, particularly D-dimer, are useful in the diagnosis of acute venous thromboembolism. They may also be useful in the assessment of hypercoagulability and venous thromboembolism risk.

References

  1. 1 2 3 4 Refaai MA, Riley P, Mardovina T, Bell PD (November 2018). "The Clinical Significance of Fibrin Monomers". Thromb Haemost. 118 (11): 1856–1866. doi: 10.1055/s-0038-1673684 . PMID   30312978.
  2. 1 2 Douxfils J, Morimont L, Bouvy C (November 2020). "Oral Contraceptives and Venous Thromboembolism: Focus on Testing that May Enable Prediction and Assessment of the Risk". Semin Thromb Hemost. 46 (8): 872–886. doi:10.1055/s-0040-1714140. PMID   33080636. S2CID   224821517.
  3. Farris M, Bastianelli C, Rosato E, Brosens I, Benagiano G (October 2017). "Pharmacodynamics of combined estrogen-progestin oral contraceptives: 2. effects on hemostasis". Expert Rev Clin Pharmacol. 10 (10): 1129–1144. doi:10.1080/17512433.2017.1356718. PMID   28712325. S2CID   205931204.