Hereditary Protein S Deficiency and Venous Thrombo-Embolism

Broekmans, A.W.; Bertina, R. M.; Reinalda-Poot, J; Engesser, L.; Muller, H P; Leeuw, J A; Michiels, Jan; Brommer, E J P; Briët, E.

doi:10.1055/s-0038-1661292

Cited by 105 publications

(52 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…7 Inherited protein S deficiency is an autosomal dominant disorder associated with an increased risk of venous thromboembolism. 8 The estimated prevalence of heterozygous protein S deficiency, which is associated with plasma levels approximately half of normal, varies from 1 in 1000 to 3 in 10 000 individuals in the general population. 9 Extremely low plasma levels determined by homozygous or compound heterozygous mutations in the protein S gene are rare and associated with the onset of purpura fulminans in the neonatal period.…”

Section: Discussionmentioning

confidence: 99%

Anticoagulant Treatment With Rivaroxaban in Severe Protein S Deficiency

et al. 2013

View full text Add to dashboard Cite

We report a case of a 6-year-old girl with severe protein S deficiency due to a homozygous mutation and recurrent episodes of skin necrosis. She developed purpura fulminans at birth and a catheter-related venous thrombosis complicated by massive pulmonary embolism at the sixth day of life. Long-term oral anticoagulant therapy with a vitamin K-antagonist was started with a therapeutic range of the international normalized ratio of prothrombin time between 2.0 and 3.0. Unfortunately, this common range was not sufficient because recurrent episodes of warfarin-induced skin necrosis developed if the international normalized ratio was ,4.0. Vitamin K antagonists decrease plasma level of vitamin K-dependent coagulation proteins, including the natural anticoagulant protein C. In our patient, the hypercoagulable state due to warfarin-induced reduction of protein C, other than severe protein S deficiency, outweighed the anticoagulant efficacy of the inhibition of procoagulant factors II, VII, IX, and X. The switch of anticoagulant therapy from warfarin to rivaroxaban, a direct inhibitor of activated factor X that does not inhibit other vitamin K-dependent proteins, resulted in the disappearance of skin necrosis at 1 year of follow-up. Rivaroxaban may be considered as a valid anticoagulant alternative in patients with severe inherited protein S deficiency and warfarin-induced skin necrosis.

show abstract

Section: Discussionmentioning

confidence: 99%

Anticoagulant Treatment With Rivaroxaban in Severe Protein S Deficiency

et al. 2013

View full text Add to dashboard Cite

show abstract

“…Similarly, Walker (13) observed a fivefold increase of the Factor Va inactivation by APC. The importance of protein S as an anticoagulant protein has been inferred from the inability of APC to prolong the clotting time of protein S-deficient plasma (15,37) and from the high risk ofthrombosis that results from a protein S deficiency (15,(38)(39)(40). Although APC can inactivate purified Factor VIII in the absence of protein S (Figs.…”

Section: Discussionmentioning

confidence: 99%

Inactivation of human factor VIII by activated protein C. Cofactor activity of protein S and protective effect of von Willebrand factor.

Koedam¹,

Meijers²,

Sixma³

et al. 1988

J. Clin. Invest.

225

136

View full text Add to dashboard Cite

Activated protein C (APC) acts as a potent anticoagulant enzyme by inactivating Factor V and Factor VIII. In this study, protein S was shown to increase the inactivation of purified Factor VIII by APC ninefold. The reaction rate was saturated with respect to the concentration of protein S when protein S was present in a 10-fold molar excess over APC. The heavy chain of Factor VIII was cleaved by APC and protein S did not alter the degradation pattern. Factor VIII circulates in a complex with the adhesive protein von Willebrand factor. When purified Factor VIII was recombined with von Willebrand factor, the inactivation of Factor VIII by APC proceeded at a 10-20-fold slower rate as compared with Factor VIII in the absence of von Willebrand factor. Protein S had no effect on the inactivation of the Factor VIII-von Willebrand factor complex by APC. After treatment of this complex with thrombin, however, the actions of APC and protein S towards Factor VIII were completely restored. In hemophilia A plasma, purified Factor VIII associated with endogenous von Willebrand factor, resulting in a complete protection against APC (4 nM). By mixing hemophilic plasma with plasma from a patient with severe von Willebrand's disease, we could vary the amount of von Willebrand factor. 1 U of von Willebrand factor was needed to provide protection of 1 U Factor VIII. Also in plasma from patients with the IIA-type variant of von Willebrand's disease, Factor VIII was protected. In von Willebrand's disease plasma, which was depleted of protein S., APC did not inactivate Factor VIII. These results indicate that protein S serves as a cofactor in the inactivation of Factor VIII and Factor VIIIa by APC and that von Willebrand factor can regulate the action of these two anticoagulant proteins.

show abstract

“…In vivo evidence for the role ofprotein S in regulating blood coagulation comes from studies of patients with hereditary protein S deficiency who are at higher risk of venous thrombotic disease (14)(15)(16)(17)(18). The clinical manifestations reported in protein S-deficient individuals reported in these studies are very similar to those associated with hereditary protein C deficiency (19).…”

mentioning

confidence: 99%

Cloning and characterization of human liver cDNA encoding a protein S precursor.

Hoskins¹,

Norman²,

Beckmann³

et al. 1987

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Human liver cDNA encoding a protein S precursor was isolated from two cDNA libraries by two different techniques. Based upon the frequency of positive clones, the abundance of mRNA for protein S is =0.01%. Blot hybridization of electrophoretically fractionated poly(A)+ RNA revealed a major mRNA =4 kilobases long and two minor forms of -3.1 and =2.6 kilobases. One of the cDNA clones contains a segment encoding a 676 amino acid protein S precursor, as well as 108 and 1132 nucleotides of 5' and 3' noncoding sequence, respectively, plus a poly(A) region at the 3' end. The cDNAs are adenosine plus thymidine-rich (60%) except for the 5' noncoding region, where 78% of the nucleotides are guanosine or cytosine. The protein precursor consists of a 41 amino acid "leader" peptide followed by 635 amino acids corresponding to mature protein S. Comparison of the mature protein region with homologous vitamin K-dependent plasma proteins shows that it is composed of the following domains: an amino-terminal y-carboxyglutamic acid-rich region of 37 amino acids; a 36 amino acid linker region rich in hydroxy amino acids; four epidermal growth factor-like segments, each -45 amino acids long; and a 387 amino acid carboxyl-terminal domain of unrecognized structure and unknown function.

show abstract

Hereditary Protein S Deficiency and Venous Thrombo-Embolism

Cited by 105 publications

References 21 publications

Anticoagulant Treatment With Rivaroxaban in Severe Protein S Deficiency

Anticoagulant Treatment With Rivaroxaban in Severe Protein S Deficiency

Inactivation of human factor VIII by activated protein C. Cofactor activity of protein S and protective effect of von Willebrand factor.

Cloning and characterization of human liver cDNA encoding a protein S precursor.

Contact Info

Product

Resources

About