A case-report of two patients with hereditary protein S deficiency treated by rivaroxaban

Lou, Jianyao; Yin, Li; Ke, Xueying; Zhang, Liang; Xu, Fangfang; Liu, Zhenjie

doi:10.1097/mbc.0000000000000929

Cited by 6 publications

(5 citation statements)

References 14 publications

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“…To date, there is no consensus regarding the anticoagulant choice of hereditary thrombophilia. Several recent reports have demonstrated good clinical outcomes of rivaroxaban in patients with hereditary protein S deficiency [16,17] . In line with this, our patient received rivaroxaban as a long-term therapy choice and achieved a good prognosis.…”

Section: Discussionsupporting

confidence: 82%

Rapid identification of a pathogenic variant of PROS1 in a thrombophilic family by whole exome sequencing

2021

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Rationale: Venous thrombosis remains a significant problem in modern days. Genetic factors contribute to a subset of patients with venous thrombosis. It is sometimes challenging to identify the underlying culprit in thrombophilic individuals based on traditional laboratory testing and Sanger sequencing. Patient concerns: A thrombophilic family presented with multiple venous thrombosis was examined. Diagnoses: Molecular genetic analysis revealed a pathogenic missense variant of the PROS1 gene. Based on this finding and clinical manifestations, a final diagnosis of protein S deficiency was made. Interventions: Whole exome sequencing (WES) of the proband was performed to identify disease-causing variants. Subsequently, Sanger sequencing was performed to validate the variant in the affected members. Outcomes: Using WES, we rapidly identified a proven pathogenic missense variant (c.1543C > T, p.Arg515Cys) in the sex hormone-binding globulin domain of PROS1, which was confirmed by Sanger sequencing. The decreased level and activity of protein S caused by the variant explained the phenotypes of the family. Patients received rivaroxaban as a long-term anticoagulation therapy and achieved a good prognosis. Lessons: Our study suggests WES as a rapid search strategy to identify the genetic factors underlying thrombophilic disorders. Patients with venous thrombosis caused by PROS1 mutations could receive rivaroxaban as the first choice of anticoagulation therapy.

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Section: Discussionsupporting

confidence: 82%

Rapid identification of a pathogenic variant of PROS1 in a thrombophilic family by whole exome sequencing

2021

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“…Several case reports have described patients who presented with VTE in the context of severe thrombophilia, such as PS deficiency, and were successfully treated with edoxaban [68,69] or rivaroxaban [70][71][72][73][74]; PC deficiency successfully treated with rivaroxaban [75,76] or edoxaban [77,78]; AT deficiency successfully treated with apixaban [79] or rivaroxaban [80]; homozygous FVL mutation successfully treated with rivaroxaban [81]; or double heterozygous FVL and F2 c.*97G>A mutations successfully treated with apixaban [82]. One case of a patient with severe hypofibrinogenemia successfully treated with rivaroxaban shows how challenging therapeutic management can become during the perioperative period [83].…”

Section: Place Of Doac For the Treatment Of Vtd In Patients With Inhe...mentioning

confidence: 99%

Inherited Thrombophilia in the Era of Direct Oral Anticoagulants

Khider

Gendron

Mauge

2022

IJMS

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Severe inherited thrombophilia includes rare deficiencies of natural anticoagulants (antithrombin and proteins C and S) and homozygous or combined factor V Leiden and FII G20210A variants. They are associated with a high thrombosis risk and can impact the duration of anticoagulation therapy for patients with a venous thromboembolism (VTE) event. Therefore, it is important to diagnose thrombophilia and to use adapted anticoagulant therapy. The widespread use of direct anticoagulants (DOACs) for VTE has raised new issues concerning inherited thrombophilia. Concerning inherited thrombophilia diagnosis, DOACs are directed toward either FIIa or FXa and can therefore interfere with coagulation assays. This paper reports DOAC interference in several thrombophilia tests, including the assessment of antithrombin, protein S, and protein C activities. Antithrombin activity and clot-based assays used for proteins C and S can be overestimated, with a risk of missing a deficiency. The use of a device to remove DOACs should be considered to minimize the risk of false-negative results. The place of DOACs in the treatment of VTE in thrombophilia patients is also discussed. Available data are encouraging, but given the variability in thrombosis risk within natural anticoagulant deficiencies, evidence in patients with well-characterized thrombophilia would be useful.

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“…Recall that hypoxia can induce PS deficiency [51]; thus, hypoxia secondary to intense exercise may be a factor in the negative correlation between lifestyle change and PS level. As for pharmaceutical management of PS deficiency, direct oral anticoagulants (DOAC) have been found to be efficient in the treatment and prevention of VTE in patients with mutations in the PROS1 gene [56,57]. Traditionally, heparin or vitamin K antagonists, such as warfarin, have been used to prevent VTE; however, the DOACs described in these studies, rivaroxaban and apixaban, may offer more predictable outcomes in the case of PS deficiency.…”

Section: Management Of Protein S Deficiencymentioning

confidence: 99%

Section: Management Of Protein S Deficiencymentioning

confidence: 99%

“…Further, Lou et al described two patients with hereditary PS deficiency who had deep vein thrombosis even after warfarin therapy for two years [56]. However, after the patients were treated with 20 mg/ day rivaroxaban, they did not have any thromboembolic events even after one year follow-up [56]. A consensus should be reached for moving toward new oral anticoagulants such as rivaroxaban and enoxaparin-VKA, which can preserve PS level during clotting events.…”

Section: Management Of Protein S Deficiencymentioning

confidence: 99%

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Protein S: function, regulation, and clinical perspectives

Majumder

Nguyen

2021

Current Opinion in Hematology

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Purpose of review Protein S (PS) is an essential natural anticoagulant. PS deficiency is a major contributor to acquired hypercoagulability. Acquired hypercoagulability causes myocardial infarction, stroke, and deep vein thrombosis in millions of individuals. Yet, despite its importance in hemostasis, PS is the least understood anticoagulant. Even after 40 years since PS was first described, we are still uncovering information about how PS functions. The purpose of this review is to highlight recent findings that advance our understanding of the functions of PS and explain hypercoagulability caused by severe PS deficiency. Recent findings PS has long been described as a cofactor for Activated Protein C (APC) and Tissue Factor Pathway Inhibitor (TFPI). However, a recent report describes direct inhibition of Factor IXa (FIXa) by PS, an activity of PS that had been completely overlooked. Thrombophilia is becoming a more frequently reported disorder. Hereditary PS deficiency is an anticoagulant deficiency that results eventually in thrombophilia. In addition, PS deficiency is a predisposing factor for venous thromboembolism (VTE), but an effect of PS deficiency in arterial thrombosis, such as arterial ischemic stroke, is uncertain. Plasma PS concentration decreases in pregnant women. Inherited thrombophilias are important etiologies for recurrent pregnancy loss, and anticoagulation therapy is of benefit to women with recurrent pregnancy loss who had documented only PS deficiency. Hypoxia is a risk factor for VTE, and hypoxia downregulates plasma PS level. Importantly, COVID-19 can lead to hypoxemia because of lung damage from IL6-driven inflammatory responses to the viral infection. Because hypoxia decreases the abundance of the key anticoagulant PS, we surmise that the IL6-induced cytokine explosion combined with hypoxemia causes a drop in PS level that exacerbates the thrombotic risk in COVID-19 patients. Summary This review is intended to advance understanding of the anticoagulant function of an important plasma protein, PS. Despite 40+ years of research, we have not had a complete description of PS biology as it pertains to control of blood coagulation. However, the picture of PS function has become sharper with the recent discovery of FIXa inhibition by PS. Hemostasis mediated by PS now includes regulation of FIXa activity alongside the cofactor activities of PS in the TFPI/APC pathways. In addition, the direct inhibition of FIXa by PS suggests that PS, particularly a small derivative of PS, could be used to treat individuals with PS deficiencies or abnormalities that cause thrombotic complications.

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A case-report of two patients with hereditary protein S deficiency treated by rivaroxaban

Cited by 6 publications

References 14 publications

Rapid identification of a pathogenic variant of PROS1 in a thrombophilic family by whole exome sequencing

Rapid identification of a pathogenic variant of PROS1 in a thrombophilic family by whole exome sequencing

Inherited Thrombophilia in the Era of Direct Oral Anticoagulants

Protein S: function, regulation, and clinical perspectives

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