Portal-Splenic-Mesenteric Venous Thrombosis in a Patients with Protein S Deficiency due to NovelPROS1Gene Mutation

Abstract

Protein S (PS), a vitamin K-dependent glycoprotein, performs an important role in the anticoagulation cascade as a cofactor of protein C. Because of the presence of a pseudogene and two different forms of PS in the plasma, protein S deficiency (PSD) is one of the most difficult thrombophilias to study and a rare blood disorder associated with an increased risk of thrombosis. We describe a unusual case of previously healthy 37-year-old man diagnosed with portal-splenic-mesenteric vein thrombosis secondary to PSD. The patient was admitted to the hospital due to continuous nonspecific abdominal pain and nausea. Abdominal computed tomography revealed acute venous thrombosis from inferior mesenteric vein to left portal vein via splenic vein, and laboratory test revealed decreased PS antigen level and PS functional activity. Conventional polymerase chain reaction and direct DNA sequencing analysis of the PROS1 gene demonstrated duplication of the 166th base in exon 2 resulting in frame-shift mutation (p.Arg56Lysfs*10) which is the first description of the new PROS1 gene mutation to our knowledge. Results from other studies suggest that the inherited PSD due to a PROS1 gene mutation may cause venous thrombosis in a healthy young man without any known predisposing factor.

Analysis of PROC and PROS1 single nucleotide polymorphisms in a thrombophilia family

“…10 The protein C pathway is known to play a major role in regulating coagulation. 11 Protein S, encoded by the PROS1 gene, is a vitamin K-dependent glycoprotein, performing an important role in the anticoagulation cascade as a cofactor of protein C. 12 Individuals with inherited protein C deficiency may be susceptible to venous thrombosis. 13 Protein S deficiency is also an inherited or acquired disorder that contributes to an increased risk of thrombosis.…”

Thrombosis Associated with Protein S Deficiency: A Case Report and Literature Review

“…Acquired forms can occur as a result of a number of factors such as low vitamin-K levels, liver disease, HIV infection, sickle-cell anemia, and in warfarin therapy [13][14][15] . Inheritable forms are rare, with an incidence of about 0.03% [4] and usually due to large deletions in the PS gene, PROS1 [16] , although other defects such a frameshift [17] , and nonsense mutations have been described [18] . Since PS deficiency is autosomal-dominant (AD), even one allele may still be wild type, heterozygous individuals have an increased risk of thrombophilic events and their PS levels are diminished [16] .…”