Lviv clinical bulletin 2022, 3(39)-4(40): 26-32

https://orcid.org/10.25040/lkv2022.03-04.026

Soluble Fibrin-monomeric Complexes and D-dimers as Indicators of Acute Pancreatitis Severity

S. Chooklin1, B. Pidhirnyi2, R. Barylyak2

1Danylo Halytsky Lviv National Medical University

 

Introduction. Local and systemic inflammation, disorders in the hemostatic system are among the key components of acute pancreatitis (AP) pathogenesis already in its early stages, and in future development of thrombohemorrhagic complications. The degree of systemic hemostatic disorders in AP varies from subclinical activation of coagulation, which can only be detected using sensitive markers of activation of coagulation factors, to fulminant disseminated intravascular coagulation syndrome, characterized by multiple systemic microvascular thrombosis and profuse bleeding from different sites. It has been proven that D-dimers and soluble fibrin-monomeric complexes (SFMK) are valuable markers of coagulation and fibrinolysis activation.

The aim of the study. To study the dynamics of D-dimers, soluble fibrin-monomeric complexes in the blood of patients with acute pancreatitis, depending on the severity of the disease.

Materials and methods. A prospective examination of 206 patients with AP was carried out. According to the criteria of the International Classification, mild pancreatitis was verified in 51 patients, moderate – in 98, severe – in 57. The concentration of SFMK, D-dimers was determined in 66 patients with AP on the first, third, seventh and fourteenth days of conservative treatment. The reference values ​​were estimated in 11 healthy individuals.

Results. The enhansed concentration of SFMK and D-dimers were detected in the blood of all patients under examination. Their content directly correlated with the severity of AP course as determined by the Ranson and BISAP score, the severity of the patient’s condition by the APACHE II score and organ dysfunction by the SOFA score, and the degree of damage to the pancreas by the Balthazar criteria. The concentration of SFMK and D-dimers significantly increased with the occurrence of respiratory, cardiovascular, renal, and metabolic dysfunction. A reliable direct correlation was determined between the amount of SFMK and the concentration of creatinine and glucose in the blood of patients with AP. The increase in the level of D-dimers significantly directly correlated with the concentration of creatinine in the blood serum. The sensitivity of SFMK determination (cut-of value 137.50 ng/L) for predicting pulmonary dysfunction was 86.20 %, and the specificity was 83.80 %, with positive and negative predictive values ​​of 80.65 and 88.57 % respectively.

Conclusions. The course of acute pancreatitis is accompanied by local or systemic inflammation, changes in the hemostatic system, severity of which  correlating with the severity of the disease. Characteristic feature for patients with severe acute pancreatitis is the combination of systemic inflammation with procoagulant changes. The severity of acute pancreatitis, the severity of patient’s condition and organ dysfunction, the severity of pancreatic lesions are associated with an increase of fibrin degradation products. The concentration of soluble fibrin-monomeric complexes can be used to predict pulmonary dysfunction in patients with acute pancreatitis.

References

  1. Zheng Z, Ding Y-X, Qu Y-X, Cao F, Li F. A narrative review of acute pancreatitis and its diagnosis, pathogenetic mechanism, and management. Ann Transl Med. 2021;9(1):69.
  2. Zhou J, Ke L, Yang D, Chen Y, Li G, Tong Z et al. Predicting the clinical manifestations in necrotizing acutepancreatitis patients with splanchnic vein thrombosis. Pancreatology. 2016;16(6):973-978.
  3. Yano T, Taniguchi M, Shirasaka T, Tsuneyoshi I. Effectiveness of soluble recombinant human thrombomodulin in patients with severe acute pancreatitis complicated by disseminated intravascular coagulation. Turk J Anaesthesiol Reanim. 2019;47(4):320-326.
  4. Tomkötter L, Erbes J, Trepte C, Hinsch A, Dupree A, Bockhorn M et al. The effects of pancreatic microcirculatory disturbances on histopathologic tissue damage and the outcome in severe acute pancreatitis. Pancreas. 2016;45(2):248-253.
  5. Weitz JI, Fredenburgh JC, Eikelboom JW. A test in context: D-dimer. J Am Coll Cardiol. 2017;70(19):2411-2420.
  6. Ieko M, Nakabayashi T, Tarumi T, Naito S, Yoshida M, Kanazawa K, Mizukami K, Koike T. Soluble fibrin monomer degradation products as a potentially useful marker for hypercoagulable states with accelerated fibrinolysis. Clin Chim Acta 2007;386:38-45.
  7. Banks PA, Bollen TL, Dervenis C, Gooszen HG, Johnson CD, Sarr MG et al. Classification of acute pancreatitis – 2012: revision of the Atlanta classification and definitions by international consensus. Gut. 2013;62:102-111.
  8. Dellinger EP, Forsmark CE, Layer P, Lévy P, Maraví-Poma E, Petrov MS et al. Determinant-based classification of acute pancreatitis severity: an international multidisciplinary consultation. Ann Surg. 2012;256:875-880.
  9. Ranson JH, Rifkind KM, Roses DF, Fink SD, Eng K, Spencer FC. Prognostic signs and the role of operative management in acute pancreatitis. Surg Gynecol Obstet. 1974;139(1):69-81.
  10. Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Crit Care Med. 1985;13(10):818-829.
  11. Wu BU, Johannes RS, Sun X, Tabak Y, Conwell DL, Banks PA.The early prediction of mortality in acute pancreatitis: a large population-based study. Gut. 2008;57(12):1698-1703.
  12. Vincent JL, Moreno R, Takala J, Willatts S, De Mendonça A, Bruining H et al. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the working group on sepsis-related problems of the European Society of Intensive Care Medicine. Intensive Care Med. 1996;22(7):707-710.
  13. Balthazar E, Robinson D, Megibow A, Ranson J. Acute pancreatitis: value of CT in establishing prognosis. Radiology. 1990;174(2):331-336.
  14. Singh N, Pati HP, Tyagi S, Upadhyay AD, Saxena R. Evaluation of the diagnostic performance of fibrin monomer in comparison to d-dimer in patients with overt and nonovert disseminated intravascular coagulation. Clin Appl Thromb Hemost. 2017;23(5):460-465.
  15. Linkins LA, Takach Lapner S. Review of D-dimer testing: Good, Bad and Ugly. Int J Lab Hematol. 2017;39(Suppl 1):98-103.
  16. Ruan Q, Lu H, Zhu H, Guo Y, Bai Y. A network-regulative pattern in the pathogenesis of kidney injury following severe acute pancreatitis. Biomed Pharmacother. 2020;125:109978.
  17. Akbal E, Demirci S, Koçak E, Köklü S, Başar O, Tuna Y. Alterations of platelet function and coagulation parameters during acute pancreatitis. Blood Coagul Fibrinolysis. 2013;24(3):243-246.
  18. Ke L, Ni HB, Tong ZH, Li WQ, Li N, Li JS. D-dimer as a marker of severity in patients with severe acute pancreatitis. J Hepatobiliary Pancreat Sci. 2012;19(3):259-265.
  19. Liu C, Zhou X, Ling L, Chen S, Zhou J. Prediction of mortality and organ failure based on coagulation and fibrinolysis markers in patients with acute pancreatitis: A retrospective study. Medicine (Baltimore). 2019;98(21):e15648.
  20. Jennewein C, Tran N, Paulus P, Ellinghaus P, Eble JA, Zacharowski K. Novel aspects of fibrin(ogen) fragments during inflammation. Mol Med. 2011;17(5-6):568-573.
  21. Ding N, Guo C, Song K, Li C, Zhou Y, Yang G, Chai X. Nomogram for the prediction of in-hospital incidence of acute respiratory distress syndrome in patients with acute pancreatitis. Am J Med Sci. 2022;363(4):322-332.