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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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.

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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

  1. ↑ Hemker HC, Giesen P, AlDieri R, Regnault V, de Smed E, Wagenvoord R, Lecompte T, Béguin S (2002). "The calibrated automated thrombogram (CAT): a universal routine test for hyper- and hypocoagulability". Pathophysiol Haemost Thromb. 32 (5–6): 249–53. doi: 10.1159/000073575 . PMID   13679651. S2CID   8378673.
  2. 1 2 3 Lim HY, Donnan G, Nandurkar H, Ho P (January 2022). "Global coagulation assays in hypercoagulable states". J Thromb Thrombolysis. 54 (1): 132–144. doi:10.1007/s11239-021-02621-1. PMID   34997471. S2CID   245804095.
  3. 1 2 3 4 5 6 7 Reda S, Morimont L, Douxfils J, Rühl H (August 2020). "Can We Measure the Individual Prothrombotic or Prohemorrhagic Tendency by Global Coagulation Tests?". Hamostaseologie. 40 (3): 364–378. doi: 10.1055/a-1153-5824 . PMID   32726831. S2CID   220878363.
  4. ↑ Lim HY, Leemaqz SY, Torkamani N, Grossmann M, Zajac JD, Nandurkar H, Ho P, Cheung AS (July 2020). "Global Coagulation Assays in Transgender Women on Oral and Transdermal Estradiol Therapy". J Clin Endocrinol Metab. 105 (7): e2369–e2377. doi: 10.1210/clinem/dgaa262 . PMID   32413907. S2CID   218659931.
  5. 1 2 3 4 Morimont L, Haguet H, Dogné JM, Gaspard U, Douxfils J (2021). "Combined Oral Contraceptives and Venous Thromboembolism: Review and Perspective to Mitigate the Risk". Front Endocrinol (Lausanne). 12: 769187. doi: 10.3389/fendo.2021.769187 . PMC   8697849 . PMID   34956081.
  6. ↑ Douxfils J, Morimont L, Delvigne AS, Devel P, Masereel B, Haguet H, Bouvy C, Dogné JM (January 2020). "Validation and standardization of the ETP-based activated protein C resistance test for the clinical investigation of steroid contraceptives in women: an unmet clinical and regulatory need". Clin Chem Lab Med. 58 (2): 294–305. doi:10.1515/cclm-2019-0471. PMID   31444961. S2CID   201644826.
  7. ↑ Morimont L, Bouvy C, Delvigne AS, Dogné JM, Douxfils J (April 2020). "Proof of concept of a new scale for the harmonization and the standardization of the ETP-based APC resistance". J Thromb Haemost. 18 (4): 895–904. doi: 10.1111/jth.14745 . PMID   31984653. S2CID   210922482.
  8. ↑ Morimont L, Didembourg M, Haguet H, Modaffari É, Tillier M, Bouvy C, Lebreton A, Dogné JM, Douxfils J (October 2021). "Interlaboratory variability of activated protein C resistance using the ETP-based APC resistance assay". Res Pract Thromb Haemost. 5 (7): e12612. doi:10.1002/rth2.12612. PMC   8563922 . PMID   34761157.
  9. ↑ Kintigh J, Monagle P, Ignjatovic V (January 2018). "A review of commercially available thrombin generation assays". Res Pract Thromb Haemost. 2 (1): 42–48. doi:10.1002/rth2.12048. PMC   6055498 . PMID   30046705.
  10. ↑ Duarte RC, Ferreira CN, Rios DR, Reis HJ, Carvalho MD (2017). "Thrombin generation assays for global evaluation of the hemostatic system: perspectives and limitations". Rev Bras Hematol Hemoter. 39 (3): 259–265. doi:10.1016/j.bjhh.2017.03.009. PMC   5568585 . PMID   28830606.
  11. ↑ Tchaikovski SN, Rosing J (July 2010). "Mechanisms of estrogen-induced venous thromboembolism". Thromb Res. 126 (1): 5–11. doi:10.1016/j.thromres.2010.01.045. PMID   20163835.
  12. ↑ Favaloro EJ, Lippi G (April 2019). "Recent Advances in Mainstream Hemostasis Diagnostics and Coagulation Testing". Semin Thromb Hemost. 45 (3): 228–246. doi:10.1055/s-0038-1676579. PMID   30912101. S2CID   85517668.


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