Activated protein C–protein C inhibitor

Activated protein C–protein C inhibitor (APC-PCI) is a complex of activated protein C (APC) and protein C inhibitor (PCI).[1][2][3] It has been measured in coagulation testing to evaluate coagulation, thrombosis, and other cardiovascular complications.[2][3][4] It is a marker of thrombin generation and indicates hypercoagulability or presence of thrombosis.[1][5]

Biochemistry

Main articles: Protein C and Protein C inhibitor

Activated Protein C is a vitamin K-dependent serine protease that cleaves and inactivates Factor Va and Factor VIIIa, thus acting as an anticoagulant. Protein C Inhibitor is a 54-kilodalton glycoprotein of the serpin superfamily. Like other serpins, upon cleavage by PC, PCI undergoes a dramatic conformational rearrangement resulting in a stable covalent bond between the two proteins. The resulting PC-PCI protein dimer lacks enzyme activity and is permanently inactivated, an example of suicide inhibition.[6] Formation of this complex is one of the major means of regulation of protein C activity, so that pro-coagulation and anticoagulant activities are kept in balance.[7]

Clinical Significance

Marker of Coagulation Activation

The APC–PCI complex serves as a sensitive and specific biomarker for activated coagulation. Elevated levels of the complex are observed in a range of thrombosis conditions such as deep vein thrombosis, pulmonary embolism, and disseminated intravascular coagulation.[2][4]

Diagnostic applications

In conjunction with other markers like thrombin-antithrombin (TAT) complexes, D-dimer, and prothrombin fragment 1+2 (F1+2), APC–PCI levels can provide information about vascular endothelial function.[8] APC-PCI levels also can be used to monitor for thrombophilia post-surgery or during pregnancy.[2][3] Notably, third-generation combined oral contraceptives cause significantly elevated levels of APC–PCI compared to those using second-generation formulations, suggesting elevated thrombotic risk.[5]

References

  1. ^ a b Merlini PA, Ardissino D (1995). "Laboratory Measurement of Thrombin Activity--What Every Clinician Scientist Needs to Know". Journal of Thrombosis and Thrombolysis. 2 (2): 85–92. doi:10.1007/BF01064374. PMID 10608009. S2CID 28203940.
  2. ^ a b c d Lippi G, Cervellin G, Franchini M, Favaloro EJ (November 2010). "Biochemical markers for the diagnosis of venous thromboembolism: the past, present and future". Journal of Thrombosis and Thrombolysis. 30 (4): 459–71. doi:10.1007/s11239-010-0460-x. PMID 20213258. S2CID 23806848.
  3. ^ a b c Davies RS, Abdelhamid M, Wall ML, Vohra RK, Bradbury AW, Adam DJ (September 2011). "Coagulation, fibrinolysis, and platelet activation in patients undergoing open and endovascular repair of abdominal aortic aneurysm". Journal of Vascular Surgery. 54 (3): 865–78. doi:10.1016/j.jvs.2011.04.010. PMID 21684711.
  4. ^ a b Misra S, Kumar A, Kumar P, Yadav AK, Mohania D, Pandit AK, Prasad K, Vibha D (September 2017). "Blood-based protein biomarkers for stroke differentiation: A systematic review". Proteomics – Clinical Applications. 11 (9–10) 1700007. doi:10.1002/prca.201700007. PMID 28452132. S2CID 13676815.
  5. ^ a b Bremme K, Hamad RR, Berg E, Strandberg K, Stenflo J (October 2012). "The APC-PCI concentration as an early marker of activation of blood coagulation". Thrombosis Research. 130 (4): 636–9. doi:10.1016/j.thromres.2011.11.006. PMID 22154243.
  6. ^ Suzuki K (December 2008). "The multi-functional serpin, protein C inhibitor: Beyond thrombosis and hemostasis". Journal of Thrombosis and Haemostasis. 6 (12): P2017-2026. doi:10.1111/j.1538-7836.2008.03181.x. PMID 18983517.
  7. ^ Canfield, W M; Kisiel, W (1982-12-01). "Evidence of normal functional levels of activated protein C inhibitor in combined Factor V/VIII deficiency disease". Journal of Clinical Investigation. 70 (6): 1260–1272. doi:10.1172/JCI110725. ISSN 0021-9738. PMC 370343. PMID 6294139.
  8. ^ Huntington, J. A.; Li, W. (January 2009). "Structural insights into the multiple functions of protein C inhibitor". Cellular and Molecular Life Sciences. 66 (1): 113–121. doi:10.1007/s00018-008-8371-0. ISSN 1420-682X. PMC 11131510. PMID 18818878.
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