Plasma Fibrinogen Levels and Protein C Activity in Patients with Chronic Kidney Disease in a Nigerian Tertiary Hospital
DOI:
https://doi.org/10.4314/ajtmbr.v6i2.8Keywords:
Protein C activity, plasma fibrinogen, chronic kidney disease, renal replacement therapyAbstract
INTRODUCTION
Haemostatic abnormalities have been observed in patients with chronic kidney disease (CKD). Hypercoagulability and thrombotic complications may contribute to the increased morbidity and mortality associated with CKD. Thrombotic tendency has not been fully evaluated in CKD subjects in our environment. This research was to assess the plasma fibrinogen and protein C activity levels in patients with CKD in a Nigerian tertiary hospital, with the view of deducing their associations with thromboembolic manifestations and providing possible therapeutic interventions.
MATERIAL AND METHODS
A hospital based; cross-sectional survey conducted amongst CKD patients on renal replacement therapy (RRT), who were managed in the renal unit of the University of Benin Teaching Hospital (UBTH). Participants were appropriately matched with apparently healthy control subjects and these were interviewed with a structured questionnaire to obtain data on their clinical details as well as hospital records. Citrated plasma was obtained and analysed to determine the functional protein C activity as well as the fibrinogen levels of both subjects on RRT and apparently healthy control. Haematologic and biochemical parameters were also determined including complete blood count, urea and creatinine and liver function tests. Descriptive and Inferential statistics were performed using Statistical Package for Social Sciences (SPSS) version 20. Results were presented in tables and charts
RESULTS
A total of 222 subjects participated in this study, comprising 74 patients with CKD on conservative management, 74 subjects with CKD on RRT, and 74 apparently healthy control subjects. The mean age across the groups including subjects on conservative management, RRT, and controls were 54.70±14.42, 49.5±15.73, and 49.3±12.5 years respectively; with the median age of 56-, 52-, and 48.5-years f across the groups respectively.
The mean plasma fibrinogen levels across the groups were 240.4±57.76, 241.8±54.87, 360.9±69.5mg/dl
respectively. This was statistically significant. The mean protein C activity for the respective groups was 59.6
± 24.20, 63.6 ± 28.89, 86.7.±2.6%. Protein C activity was significantly depleted in the CKD subjects (p =
0.002).
CONCLUSION
The study showed a low protein C activity amongst patients with CKD and those with cardiovascular or
thromboembolic events, suggestive of thromboembolic risk in these individuals.
Contrary to existing literature, plasma fibrinogen levels were not significantly elevated in patients with CKD,
and there was no association with thromboembolic events.
References
George C, Mogueo A, Okpechi I, et al. chronic kidney disease in low-income to middle-income countries: the case for increased screening. BMJ Glob Health 2017;2: e000256. doi:10.1136/bmjgh-2016-000256
Josef Coresh. Update on the Burden of CKD. J Am Soc Nephrol 2017; 28: 1020–1022: doi: 10.1681/ASN.2016121374
Kovesdy CP. Epidemiology of chronic kidney disease: an update 2022. Kidney Int Suppl (2011). 2022 Apr;12(1):7-11. doi:10.1016/j.kisu.2021.11.003. Epub 2022 Mar1 8 . P M I D : 3 5 5 2 9 0 8 6 ; P M C I D : PMC9073222.
Jager K.J., Kovesdy C., Langham R., et al. A s ingle number for advocacy and communication-worldwide more than 850 million individuals have kidney diseases. Kidney Int. 2019; 96:1048–1050.
Olanrewaju, T.O., Aderibigbe, A., Popoola, A. et al. Prevalence of chronic kidney disease and risk factors in North-Central Nigeria: a population-based survey. BMC Nephrol 2020; 21, 467.
Jalal, Diana & Chonchol, Michel & Targher, Giovanni. Disorders of Hemostasis Associated with Chronic Kidney Disease. Seminars in thrombosis and hemostasis. 2010. 36. 34-40. 10.1055/s-0030-1248722.
Adams MJ, Irish AB, Watts GF, Oostryck R, Dogra GK. Hypercoagulability in chronic kidney disease is associated with coagulation activation but not endothelial function. Thromb Res. 2008; 123(2):374–380.
Mohapatra A, Valson AT, Gopal B, Singh S, Nair SC, Viswabandya A, Varughese S, Tamilarasi V, John GT. Hemostatic Abnormalities in Severe Renal Failure: Do They Bark or Bite? Indian J Nephrol. 2018 Mar-Apr;28(2):135-142.
Suzuki, Hiromichi. Bleeding Diathesis in Hemodialysis Patients. Haemodialysis. 2013. 10.5772/45929(Chapter 4), –. doi:10.5772/52926
Ga¨ckler A, Rohn H, Lisman T, Benko¨ T, Witzke O, Kribben A, et al. Evaluation of hemostasis in patients with end-stage renal disease. PLoS ONE 2019; 14(2): e0212237.
Wu T, Tang LV, Hu Y. Venous Thromboembolism in Kidney Diseases and Genetic Predisposition. Kidney Dis. 2022;8:181–189
Nikolova‐Vlahova M, Baleva MP, Nikolov PK. Thromboembolism in Renal Diseases [Internet]. Embolic Diseases - Unusual Therapies and Challenges. InTech; 2017. Available from: http://dx.doi.org/10.5772/ intechopen.68486
Kattula S, Byrnes JR, and Wolberg AS. Fibrinogen and Fibrin in Hemostasis and Thrombosis. Arteriosclerosis, Thrombosis, and Vascular Biology. 2017. Volume 37, Issue 3, Pages e13-e21
Luyendyk JP, Schoenecker JG, Flick MJ. The multifaceted role of fibrinogen in tissue injury and inflammation. Blood (2019) 133 (6):511–520.
Tamayo-Velasco Á, Cebeira MJ, Bombín- Canal C, Acevedo-García RM, Peñarrubia- Ponce MJ. Fibrinogen Deficiency with Thrombotic Manifestations. Eur J Case Rep Intern Med. 2022 Jun 28;9(6):003400.
Rui Vilar, Richard J. Fish, Alessandro Casini, Marguerite Neerman-Arbez. Fibrin(ogen) in human disease: both friend and foe. Haematologica 2020;105(2):284-296
Simurda T, Asselta R, Zolkova J, Brunclikova M, Dobrotova M, Kolkova Z, Loderer D, Skornova I, Hudecek J, Lasabova Z, Stasko J, Kubisz P. Congenital Afibrinogenemia and Hypofibrinogenemia: Laboratory and Genetic Testing in Rare Bleeding Disorders w i t h L i f e - T h r e a t e n i n g C l i n i c a l M a n i f e s t a t i o n s a n d C h a l l e n g i n g Management. Diagnostics (Basel). 2021 Nov 19;11(11):2140. doi: 10.3390/diagnostics11112140. PMID: 34829490; PMCID: PMC8622093.
Susan E. Shapiro. Diagnosis and Management of Dysfibrinogenemia. Clinical Advances in Hematology & Oncology. September 2018 - Volume 16, Issue 919. Henri H. Versteeg, Johan W. M. Heemskerk, Marcel Levi, and Pieter H. Reitsma. Physiol Rev2013 93:1, 327-358
Dahlbäck B and Villoutreix BO. Regulation of Blood Coagulation by the Protein C Anticoagulant Pathway: Novel Insights into Structure-Function Relationships and Molecular Recognition. Arteriosclerosis, Thrombosis, and Vascular Biology. 2005; 25:1311–1320
Dahblӓck B, Stenflo J. The protein c a n t i c o a g u l a n t s y s t e m . I n : Stamatoyannopoulos G, Nienbuis AW, Majerus PW, Varmus H (eds). The molecular basis of blood diseases. 2nd ed. Philadelphia: W. B. Saunders, 1994: 599 -627.
Broekmans AW, Conard J. Hereditary protein c deficiency. In: Bertina RM (ed). Protein C and related proteins. Harlow Essex, United Kingdom: Churchill Livingstone, Longman, 1988: 160 –168.
Nunns GR, Moore EE, Chapman MP, Moore HB, Stettler GR, Peltz E, Burlew CC, Silliman CC, Banerjee A, Sauaia A. The hypercoagulability paradox of chronic kidney disease: The role of fibrinogen. Am J Surg. 2017 ec;214(6):1215-1218. doi: 10.1016/j.amjsurg.2017.08.039.
Khurshid S, Tariq R, Qureshi J, Mazher R. Prevalence of Abnormal Thrombophilia Profile in
Chronic Kidney Disease. Int.j. pathol.2021;19(1): 2-5.
Odubanjo MO, Oluwasola AO, Kadiri S. The epidemiology of end-stage renal disease in Nigeria:
the way forward. Int Urol Nephrol. 2011 Sep;43(3):785-92.
Monagle, Paul. Methods in Molecular Biology. Haemostasis. 2013. Volume 992 || Fibrinogen.,
1007/978-1-62703-339- 8(Chapter 14), 181–192.
Levey AS, Eckardt KU, Tsukamoto Y, Levin A, Coresh J, Rossert J, De Zeeuw D, Hostetter TH,
Lameire N, Eknoyan G. Definition and classification of chronic kidney disease: a position statement
from kidney disease: Improving Global Outcomes (KDIGO). Kidney Int. 2005 Jun;67(6):2089- 100.
Wang V, Vilme H, Maciejewski ML, Boulware LE. The Economic Burden of Chronic Kidney Disease and
End-Stage Renal Disease. Semin Nephrol. 2016 Jul;36(4):319-30.
Jha V, Al-Ghamdi SMG, Li G, Wu MS, Stafylas P, Retat L, Card-Gowers J, Barone S, Cabrera C, Garcia Sanchez JJ. Global Economic Burden Associated with Chronic Kidney Disease: A Pragmatic Review of Medical Costs for the Inside CKD Research Programme. Adv Ther. 2023 Jul 26. doi: 10.1007/s12325-023-02608-9.
Chukwuonye II, Oviasu E. The plight of chronic kidney disease patients in Nigeria. J Dental Med Sci. 2012;2(2):52–55.
Chukwuonye II, Ogah OS, Anyabolu EN, Ohagwu KA, Nwabuko OC, Onwuchekwa U, Chukwuonye ME, Obi
EC, Oviasu E. Prevalence of chronic kidney disease in Nigeria: systematic review of population- based studies. Int J Nephrol Renovasc Dis. 2018 May 22; 11:165-172.
Ulasi, Ifeoma I.; Ijoma, Chinwuba K. The Enormity of Chronic Kidney Disease in Nigeria: The Situation in a Teaching Hospital in South-East Nigeria. Journal of Tropical Medicine, 2010, 1–6. doi:10.1155/2010/501957
Huang M, Wei R, Wang Y, et al. Blood coagulation system in patients with chronic kidney disease: a prospective observational study. BMJ Open 2017;7: e014294.
Martinez M, Vaya A, Alvarino J, Barbera JL, Ramos D, et al. Hemorheological alterations in patients with chronic renal failure. Effect of hemodialysis. Clin. Hemorheol. Microcirc. 1999; 21(1):1-6
Ramaprabha P, Bhuvaneswari T, Aravind KR. Coagulation profiles an indicator of vascular haemostatic function in chronic renal failure patients who are on renal dialysis. Sch. J. App.Med. Sci. 2014; 2(2B):592-59.
Rattan R, Swain M, Srikrushnamahapatra. Plasma fibrinogen level, homeostatic alterations and
nitric oxide levels in chronic renal disease. IOSR-JDMS. 2017; 16(4): 35-37.
A.G. Stack and others, Plasma fibrinogen associates independently with total and cardiovascular mortality among subjects with normal and reduced kidney function in the general population, QJM: An International Journal of Medicine, Volume 107, Issue 9, September 2014, Pages 701–713,
Irish A. Cardiovascular disease, fibrinogen and the acute phase response: associations with lipids and blood pressure in patients with chronic renal disease. Atherosclerosis. 1998; 137:133–139.
Stenvinkel P, Heimburger O, Paultre F, Diczfalusy U, Wang T, et al. Strong association
between malnutrition, inflammation, and atherosclerosis in chronic renal failure. Kidney
Int.1999; 55(5):1899–1911.
Lee AJ, Lowe GD, Woodward M et al. Fibrinogen in relation to personal history of prevalent hypertension, diabetes, stroke, intermittent claudication, coronary heart disease, and family history: the Scottish Heart Health Study. Br Heart J .1993; 69: 338–342.
Ridker PM. Inflammation, atherosclerosis, and cardiovascular risk: an epidemiologic view. Blood Coagul Fibrinolysis. 1999; 10(Suppl 1): S9–S12.
Lai KN, Yin JA, Yuen PM, Li PK. Effect of hemodialysis on protein C, protein S, and antithrombin III levels. Am J Kidney Dis. 1991;17(1):38-42.
Faioni EM, Franchi F, Krachmalnicoff A, Valsecchi C, Vigano GL, et al. Low levels of the anticoagulant activity of protein C in patients with chronic renal insufficiency: an inhibitor of protein C is present in uremic plasma.
Thromb Haemost. 1991; 66:420–425.
Nosseir, N. M., Tawfik, M. S., Bakheet, O., El- Maghraby, D. F. Procoagulant FVIII and Anticoagulant Protein C in Renal Failure Patients on Hemodialysis. Egyptian Journal of Radiation Sciences and Applications, 2022; 35(1):
-18.
Kant KS, Glueck HI, Coots MC, Tonne VA, Brubaker R, et al. Protein S deficiency and skin necrosis associated with continuous ambulatory peritoneal dialysis. Am J Kidney Dis., 1992;19(3):264-71
Mohamad NM, Alsiddig B. Estimation and assessment of protein c/s among Sudanese patients in Aljazeera state with chronic renal failure. IJIRR. 2015; 2(12):1447-1449.
Folsom, AR. Protein C, Antithrombin, and Venous Thromboembolism Incidence: A Prospective Population-Based Study. Arteriosclerosis, Thrombosis, and Vascular Biology.2002; 22(6), 1018–1022
Downloads
Published
Issue
Section
License
Copyright (c) 2024 African Journal of Tropical Medicine and Biomedical Research
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
The data collected from registered and non-registered users of this journal falls within the scope of the standard functioning of peer-reviewed journals. It includes information that makes communication possible for the editorial process; it is used to informs readers about the authorship and editing of content; it enables collecting aggregated data on readership behaviors, as well as tracking geopolitical and social elements of scholarly communication.
This journal’s editorial team uses this data to guide its work in publishing and improving this journal. Data that will assist in developing this publishing platform may be shared with its developer Public Knowledge Project in an anonymized and aggregated form, with appropriate exceptions such as article metrics. The data will not be sold by this journal or PKP nor will it be used for purposes other than those stated here. The authors published in this journal are responsible for the human subject data that figures in the research reported here.
Those involved in editing this journal seek to be compliant with industry standards for data privacy, including the European Union’s General Data Protection Regulation (GDPR) provision for “data subject rights” that include (a) breach notification; (b) right of access; (c) the right to be forgotten; (d) data portability; and (e) privacy by design. The GDPR also allows for the recognition of “the public interest in the availability of the data,” which has a particular saliency for those involved in maintaining, with the greatest integrity possible, the public record of scholarly publishing.
