Calibrated automated thrombogram

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The calibrated automated thrombogram (CAT or CT) is a thrombin generation assay (TGA) and global coagulation assay (GCA) which can be used as a coagulation test to assess thrombotic risk. [1] [2] It is the most widely used TGA. [3] The CAT is a semi-automated test performed in a 96-well plate and requires specialized technologists to be performed. [3] As a result, it has seen low implementation in routine laboratories and has been more limited to research settings. [3] [4] Lack of standardization with the CAT has also led to difficulties in study-to-study comparisons in research. [3] [5] However, efforts have recently been made towards standardization of the assay. [5] [6] [7] [8] An example of a specific commercial CAT is the Thrombinoscope by Thrombinoscope BV (now owned by Diagnostica Stago). [9]

The CAT can be used to measure thrombogram parameters such as the endogenous thrombin potential (ETP) [2] [10] and to assess activated protein C resistance (APCR). [5] The CAT ETP-based APC resistance test is especially sensitive to estrogen-induced procoagulation, such as with combined oral contraceptives. [2] [5] [11]

In 2018, a commercial fully-automated TGA system and alternative to the CAT called the ST Genesia debuted. [3] It has been said that this system should allow for more widespread adoption of TGAs in clinical laboratories. [3] [12] The ST Genesia system also shows improved reproducibility compared to the CAT. [3]

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<span class="mw-page-title-main">Activated protein C resistance</span> Medical condition

Activated protein C resistance (APCR) is a hypercoagulability characterized by a lack of a response to activated protein C (APC), which normally helps prevent blood from clotting excessively. This results in an increased risk of venous thrombosis, which resulting in medical conditions such as deep vein thrombosis and pulmonary embolism. The most common cause of hereditary APC resistance is factor V Leiden mutation.

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<span class="mw-page-title-main">Carboxypeptidase B2</span>

Carboxypeptidase B2 (CPB2), also known as carboxypeptidase U (CPU), plasma carboxypeptidase B (pCPB) or thrombin-activatable fibrinolysis inhibitor (TAFI), is an enzyme that, in humans, is encoded by the gene CPB2.

Thrombodynamics test is a method for blood coagulation monitoring and anticoagulant control. This test is based on imitation of coagulation processes occurring in vivo, is sensitive both to pro- and anticoagulant changes in the hemostatic balance. Highly sensitive to thrombosis.

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Thrombin–antithrombin complex (TAT) is a protein complex of thrombin and antithrombin. It is a marker of net activation of coagulation.

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.

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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.

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

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.

Activated protein C–protein C inhibitor (APC-PCI) is a complex of activated protein C (APC) and protein C inhibitor (PCI). It has been measured in coagulation testing to evaluate coagulation, thrombosis, and other cardiovascular complications. It is a marker of thrombin generation and indicates hypercoagulability. The half-life of APC-PCI is either 40 minutes or 140 minutes.

References

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