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Hypercoagulability State in Celiac Disease and Hepatitis C Association

Cornel Aldea, Daniel Sur, Ciprian Silaghi
International Journal of Celiac Disease. 2018, 6(3), 74-75. DOI: 10.12691/ijcd-6-3-3
Received September 17, 2018; Revised October 28, 2018; Accepted January 04, 2019

Abstract

A concerning pathological and serological aspect that is found in both HCV and celiac disease is the hypercoagulability state which can lead to various complications.

1. Introduction

Is there any connection between celiac disease and hepatitis C? 1. Celiac disease (CD) is characterized by heterogeneous clinical manifestations of variable severity that can occurat any age 2. It is worth paying attention to one warning sign that occurs in advanced cases of CD and liver complications in HCV patients, namely the hypercoagulant state.

2. Hipercoagulabity State in CD Patients

In CD patients, the pathogenesis of hypercoagulant state is the result of various interplay between genetic factors (methylenetetrahydrofolate reductase mutations), autoimmunity (thrombophilic autoantibodies), haematological factors (abnormality of platelets and endothelial dysfunction) and vitamin deficiencies (folate, vitamin B12 or vitamin K) 3. It is well known that vitamin K is necessary for the carboxylation of coagulation factors (II, VII, IX, X), anticoagulation factors (protein C and S), but also for the carboxylation of extrahepatic vitamin K dependent proteins, such as osteocalcin in bone 4, growth arrest specific protein 6 (Gas6) 5 and matrix Gla protein (Mgp) in arterial wall 6, 7. In a case report was noticed that low vitamin K supplies, due to malabsorption or poorly dietary intake of vitamin K, were assigned to a defectively controlled CD 8. Furthermore, Berthoux et al have identified risk factors for thrombosis, such as deficiency of protein C and S due to vitamin K insufficiency, which could be associated to CD 9.

3. Hipercoagulabity State in HCV Patients

On the contrary,in HCV patients with liver fibrosis, there is an apparent paradox: a manifest decline in procoagulant factorsactivity leading to prolonged common coagulation tests 10, 11 coexist with theevidence of hypercoagulabilitycaused by an impaired synthesis of anticoagulant factors, such as protein C and antithrombin III 12, 13. Moreover, it has been assessed that in patients with progressive HCV liver disease the promotion of thrombin formation will lead to the activation of hepatic stellate cells therefore via PAR-1 cleavage, promoting liver fibrosis 14, 15. Other findings strengthen the link between liver fibrosis in HCV patients, activated protein C resistance and acquired protein C deficiency 16, 17, these patients being prone to thrombotic events.A study on 3686 patients with newly diagnosed HCV compared the incidence ofvenous thromboembolism in the HCV group and a 14,744 healthy control group, the risk of venous thromboembolism was significantly higher in the HCV group than in the control group 18. Following the idea of assessing the carboxylating status, the most sensitive marker for vitamin K deficiency is the prothrombin induced by vitamin K absence-II (PIVKA-II), which is a functional marker of coagulation 19. Kamel et al have found elevated PIVKA-II serum levels in patients with hepatocellular carcinoma, the most significant complication of viral hepatitis, concluding that PIVKA-II could be a sensitive and specific marker for its early detection 20.

4. Conclusion

Accordingly, to ascertain whether hypercoagulant state is actually (and to what extent) established in CD or HCV patients with liver complications, laboratory analyses should go beyond the common coagulation tests. In this regard, vitamin K deficiency has to be assessed by using non-invasive serum markers, e.g. PIVKA-II for liver, different carboxylated / uncarboxylated conformations of osteocalcin for bones and Mgp for vasculature.

References

[1]  Samaşca G, Burac L, Farcău D, Dejica D. Celiac disease screening in viral hepatitis C. Romanian Journal of Pediatrics 2010; 59(1): 49-50.
In article      
 
[2]  Sur ML, Colceriu M, Aldea C, Sur G, Floca E. Celiac Disease a Road Paved with Many Obstacles. Differential Diagnosis in Children. International Journal of Celiac Disease 2018; 6(1): 7-10.
In article      View Article
 
[3]  Lerner A, Blank M. Hypercoagulability in celiac disease - an update. Autoimmun Rev. 2014; 13(11): 1138-41.
In article      View Article  PubMed
 
[4]  Lacombe J, Ferron M. Gamma-carboxylation regulates osteocalcin function. Oncotarget. 2015; 6(24): 19924-5.
In article      View Article  PubMed
 
[5]  Bellido-Martin L, de Frutos PG. Vitamin K-dependent actions of Gas6. Vitam Horm 2008; 78: 185-209.
In article      View Article
 
[6]  Silaghi CN, Fodor D, Crăciun AM. Circulating matrix Gla protein: a potential tool to identify minor carotid stenosis with calcification in a risk population. Clin Chem Lab Med 2013; 51: 1115-1123.
In article      View Article  PubMed
 
[7]  Silaghi CN, Gheorghe SR, Fodor D, Crăciun AM. Circulating matrix Gla protein in patients with vascular pathology. Human and Veterinary Medicine 2016; 8: 187-191.
In article      
 
[8]  Janeczko CE, Sweeney K, Connaghan G. Supplemental vitamin K improves the stability of anticoagulation in a patient with low tissue stores of vitamin K secondary to coeliac disease. BMJ Case Rep. 2009; 2009. pii: bcr10.2008.1067.
In article      
 
[9]  Berthoux E, Fabien N, Chayvialle JA, Ninet J, Durieu I. Adult celiac disease with thrombosis: a case series of seven patients. Role of thrombophilic factors. Rev Med Interne. 2011; 32: 600-4.
In article      View Article  PubMed
 
[10]  Senzolo M, Burra P, Cholongitas E, Burroughs AK. New insights into the coagulopathy of liver disease and liver transplantation. World J Gastroenterol. 2006; 12(48): 7725-36.
In article      View Article  PubMed
 
[11]  Tripodi A, Mannucci PM. Abnormalities of hemostasis in chronic liver disease: reappraisal of their clinical significance and need for clinical and laboratory research. J Hepatol. 2007; 46(4): 727-33.
In article      View Article  PubMed
 
[12]  Al Ghumlas AK, Abdel Gader AG, Al Faleh FZ. Haemostatic abnormalities in liver disease: could some haemostatic tests be useful as liver function tests? Blood Coagul Fibrinolysis. 2005; 16(5): 329-35.
In article      View Article  PubMed
 
[13]  Saray A, Mesihovic R, Vanis N, Gornjakovic S, Prohic D. Clinical significance of haemostatic tests in chronic liver disease. Med Arch. 2012; 66(4): 231-5.
In article      View Article  PubMed
 
[14]  Gonzalez-Reimers E, Quintero-Platt G, Martin-Gonzalez C, Perez-Hernandez O, Romero-Acevedo L, Santolaria-Fernandez F. Thrombin activation and liver inflammation in advanced hepatitis C virus infection. World J Gastroenterol. 2016; 22(18): 4427-37.
In article      View Article  PubMed
 
[15]  Poujol-Robert A, Boëlle PY, Poupon R, Robert A. Factor V Leiden as a risk factor for cirrhosis in chronic hepatitis C. Hepatology. 2004; 39(4): 1174-5.
In article      View Article  PubMed
 
[16]  Poujol-Robert A, Rosmorduc O, Serfaty L, Coulet F, Poupon R, Robert A. Genetic and acquired thrombotic factors in chronic hepatitis C. Am J Gastroenterol. 2004; 99(3): 527-31.
In article      View Article  PubMed
 
[17]  Wang C-C, Chang C-T, Lin C-L, Lin I-C, Kao C-H. Hepatitis C Virus Infection Associated With an Increased Risk of Deep Vein Thrombosis: A Population-Based Cohort Study. Medicine (Baltimore). 2015; 94(38): e1585.
In article      View Article  PubMed
 
[18]  Liebman HA, Furie BC, Tong MJ, Blanchard RA, Lo KJ, Lee SD, et al. Des-gamma-carboxy (abnormal) prothrombin as a serum marker of primary hepatocellular carcinoma. N Engl J Med. 1984; 310(22): 1427-31.
In article      View Article  PubMed
 
[19]  Kamel MM, Saad MF, Mahmoud AA, Edries AA, Abdel-Moneim AS. Evaluation of serum PIVKA-II and MIF as diagnostic markers for HCV/HBV induced hepatocellular carcinoma. Microb Pathog. 2014; 77: 31-5.
In article      View Article  PubMed
 
[20]  Anstee QM, Dhar A, Thursz MR. The role of hypercoagulability in liver fibrogenesis. Clin Res Hepatol Gastroenterol. 2011; 35(8-9): 526-33.
In article      View Article  PubMed
 

Published with license by Science and Education Publishing, Copyright © 2018 Cornel Aldea, Daniel Sur and Ciprian Silaghi

Creative CommonsThis work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

Cite this article:

Normal Style
Cornel Aldea, Daniel Sur, Ciprian Silaghi. Hypercoagulability State in Celiac Disease and Hepatitis C Association. International Journal of Celiac Disease. Vol. 6, No. 3, 2018, pp 74-75. http://pubs.sciepub.com/ijcd/6/3/3
MLA Style
Aldea, Cornel, Daniel Sur, and Ciprian Silaghi. "Hypercoagulability State in Celiac Disease and Hepatitis C Association." International Journal of Celiac Disease 6.3 (2018): 74-75.
APA Style
Aldea, C. , Sur, D. , & Silaghi, C. (2018). Hypercoagulability State in Celiac Disease and Hepatitis C Association. International Journal of Celiac Disease, 6(3), 74-75.
Chicago Style
Aldea, Cornel, Daniel Sur, and Ciprian Silaghi. "Hypercoagulability State in Celiac Disease and Hepatitis C Association." International Journal of Celiac Disease 6, no. 3 (2018): 74-75.
Share
[1]  Samaşca G, Burac L, Farcău D, Dejica D. Celiac disease screening in viral hepatitis C. Romanian Journal of Pediatrics 2010; 59(1): 49-50.
In article      
 
[2]  Sur ML, Colceriu M, Aldea C, Sur G, Floca E. Celiac Disease a Road Paved with Many Obstacles. Differential Diagnosis in Children. International Journal of Celiac Disease 2018; 6(1): 7-10.
In article      View Article
 
[3]  Lerner A, Blank M. Hypercoagulability in celiac disease - an update. Autoimmun Rev. 2014; 13(11): 1138-41.
In article      View Article  PubMed
 
[4]  Lacombe J, Ferron M. Gamma-carboxylation regulates osteocalcin function. Oncotarget. 2015; 6(24): 19924-5.
In article      View Article  PubMed
 
[5]  Bellido-Martin L, de Frutos PG. Vitamin K-dependent actions of Gas6. Vitam Horm 2008; 78: 185-209.
In article      View Article
 
[6]  Silaghi CN, Fodor D, Crăciun AM. Circulating matrix Gla protein: a potential tool to identify minor carotid stenosis with calcification in a risk population. Clin Chem Lab Med 2013; 51: 1115-1123.
In article      View Article  PubMed
 
[7]  Silaghi CN, Gheorghe SR, Fodor D, Crăciun AM. Circulating matrix Gla protein in patients with vascular pathology. Human and Veterinary Medicine 2016; 8: 187-191.
In article      
 
[8]  Janeczko CE, Sweeney K, Connaghan G. Supplemental vitamin K improves the stability of anticoagulation in a patient with low tissue stores of vitamin K secondary to coeliac disease. BMJ Case Rep. 2009; 2009. pii: bcr10.2008.1067.
In article      
 
[9]  Berthoux E, Fabien N, Chayvialle JA, Ninet J, Durieu I. Adult celiac disease with thrombosis: a case series of seven patients. Role of thrombophilic factors. Rev Med Interne. 2011; 32: 600-4.
In article      View Article  PubMed
 
[10]  Senzolo M, Burra P, Cholongitas E, Burroughs AK. New insights into the coagulopathy of liver disease and liver transplantation. World J Gastroenterol. 2006; 12(48): 7725-36.
In article      View Article  PubMed
 
[11]  Tripodi A, Mannucci PM. Abnormalities of hemostasis in chronic liver disease: reappraisal of their clinical significance and need for clinical and laboratory research. J Hepatol. 2007; 46(4): 727-33.
In article      View Article  PubMed
 
[12]  Al Ghumlas AK, Abdel Gader AG, Al Faleh FZ. Haemostatic abnormalities in liver disease: could some haemostatic tests be useful as liver function tests? Blood Coagul Fibrinolysis. 2005; 16(5): 329-35.
In article      View Article  PubMed
 
[13]  Saray A, Mesihovic R, Vanis N, Gornjakovic S, Prohic D. Clinical significance of haemostatic tests in chronic liver disease. Med Arch. 2012; 66(4): 231-5.
In article      View Article  PubMed
 
[14]  Gonzalez-Reimers E, Quintero-Platt G, Martin-Gonzalez C, Perez-Hernandez O, Romero-Acevedo L, Santolaria-Fernandez F. Thrombin activation and liver inflammation in advanced hepatitis C virus infection. World J Gastroenterol. 2016; 22(18): 4427-37.
In article      View Article  PubMed
 
[15]  Poujol-Robert A, Boëlle PY, Poupon R, Robert A. Factor V Leiden as a risk factor for cirrhosis in chronic hepatitis C. Hepatology. 2004; 39(4): 1174-5.
In article      View Article  PubMed
 
[16]  Poujol-Robert A, Rosmorduc O, Serfaty L, Coulet F, Poupon R, Robert A. Genetic and acquired thrombotic factors in chronic hepatitis C. Am J Gastroenterol. 2004; 99(3): 527-31.
In article      View Article  PubMed
 
[17]  Wang C-C, Chang C-T, Lin C-L, Lin I-C, Kao C-H. Hepatitis C Virus Infection Associated With an Increased Risk of Deep Vein Thrombosis: A Population-Based Cohort Study. Medicine (Baltimore). 2015; 94(38): e1585.
In article      View Article  PubMed
 
[18]  Liebman HA, Furie BC, Tong MJ, Blanchard RA, Lo KJ, Lee SD, et al. Des-gamma-carboxy (abnormal) prothrombin as a serum marker of primary hepatocellular carcinoma. N Engl J Med. 1984; 310(22): 1427-31.
In article      View Article  PubMed
 
[19]  Kamel MM, Saad MF, Mahmoud AA, Edries AA, Abdel-Moneim AS. Evaluation of serum PIVKA-II and MIF as diagnostic markers for HCV/HBV induced hepatocellular carcinoma. Microb Pathog. 2014; 77: 31-5.
In article      View Article  PubMed
 
[20]  Anstee QM, Dhar A, Thursz MR. The role of hypercoagulability in liver fibrogenesis. Clin Res Hepatol Gastroenterol. 2011; 35(8-9): 526-33.
In article      View Article  PubMed