Protein S Deficiency (Deficiency, Protein S)

An autosomal dominant disorder showing decreased levels of plasma protein S antigen or activity, associated with venous thrombosis and pulmonary embolism. PROTEIN S is a vitamin K-dependent plasma protein that inhibits blood clotting by serving as a cofactor for activated PROTEIN C (also a vitamin K-dependent protein), and the clinical manifestations of its deficiency are virtually identical to those of protein C deficiency. Treatment with heparin for acute thrombotic processes is usually followed by maintenance administration of coumarin drugs for the prevention of recurrent thrombosis. (From Harrison's Principles of Internal Medicine, 12th ed, p1511; Wintrobe's Clinical Hematology, 9th ed, p1523)

Also Known As:

Networked: 874 relevant articles (9 outcomes, 44 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Thrombophilia
2.	Thrombosis (Thrombus)
3.	Ischemic Stroke
4.	Necrosis
5.	Factor XII Deficiency

Experts

1.	Nowak-Göttl, Ulrike: 7 articles (01/2021 - 01/2002)
2.	Undas, Anetta: 7 articles (01/2021 - 07/2013)
3.	Martinelli, Ida: 7 articles (10/2017 - 05/2002)
4.	Wypasek, Ewa: 6 articles (01/2021 - 07/2013)
5.	van der Meer, Jan: 6 articles (05/2009 - 07/2002)
6.	Simioni, Paolo: 5 articles (02/2022 - 01/2008)
7.	Van Cott, Elizabeth M: 5 articles (11/2020 - 05/2005)
8.	Bucciarelli, Paolo: 5 articles (10/2017 - 08/2004)
9.	Hackeng, Tilman M: 5 articles (09/2010 - 12/2004)
10.	Rosing, Jan: 5 articles (09/2010 - 07/2002)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Protein S Deficiency:

1.	RivaroxabanIBA 09/01/2020 - "A case-report of two patients with hereditary protein S deficiency treated by rivaroxaban." 07/01/2014 - "PROS1 mutations associated with protein S deficiency in Polish patients with residual vein obstruction on rivaroxaban therapy." 09/01/2020 - "However, it is unknown whether rivaroxaban is effective for the treatment of VTE in patients with thrombophilia, including protein S deficiency, due to lack of evidence. " 06/01/2021 - "Protein S deficiency may be a predisposing factor in recurrent ischemic stroke, and rivaroxaban can be a safe and effective treatment option. " 10/01/2022 - "deep vein thrombosis; protein S deficiency; rivaroxaban."
2.	Protein CIBA 12/01/2004 - "Of the control group, no protein C or AT-III deficiency was ever found, whereas 2 (4.0%) volunteers were presented with protein S deficiency and 3 (6.0%) with positive results of APC-R. " 06/01/2019 - "This study aimed to determine the prevalence and genetic basis of protein C and protein S deficiencies in Thai population. " 08/01/2019 - "Most importantly, congenital or acquired Protein C or Protein S deficiencies are associated with severe recurrent thrombotic events. " 05/01/2017 - "Out of the 28 tested patients protein C and protein S deficiencies were detected in 22 (78.6%) and 17 (60.7%) patients, respectively. " 06/01/2014 - "Protein C and protein S deficiency were detected in 6/140 (4.3%) women with > 3 PL and in 2/175 (1.1%) women with ≤ 3 PL. "
3.	AnticoagulantsIBA 07/01/2014 - "Protein S deficiency and novel oral anticoagulants: an intriguing case." 08/01/2010 - "Deficiency of natural anticoagulants occurred in 10 patients, with protein S deficiency being the most frequent one. " 04/01/2008 - "Functional characterization of twelve natural PROS1 mutations associated with anticoagulant protein S deficiency." 10/01/1992 - "Complement activation, abnormalities of natural anticoagulants such as protein S deficiency, and genetic association with DR4, DR7, and DRw53 have also been studied." 01/31/1990 - "Results obtained with both ELISA's in plasma's of healthy volunteers, patients with hereditary protein S deficiency type I and patients using oral anticoagulant treatment correlate very well with those of the IRMA: r = 0.974 (n = 57) for ELISA-p and r = 0.966 (n = 57) for ELISA-m. "
4.	Heparin (Liquaemin)FDA LinkGeneric 01/01/2004 - "An intravenously administered regimen of heparin was begun, because of a protein S deficiency. " 07/01/2001 - "To our knowledge this is the first reported case of a dialysis patient presenting with skin ulceration induced by heparin and protein S deficiency. " 01/01/2018 - "We herein report a case of on-pump coronary artery bypass grafting in a patient with protein S deficiency who received fresh frozen plasma targeting the two heparin cessation periods. " 03/01/2006 - "[Successful delivery following subcutaneous heparin administration in a 7-weeks pregnant patient suffering from cerebral venous thrombosis due to secondary protein S deficiency]." 05/01/1997 - "The putative association of protein S deficiency with cutaneous heparin necrosis could not be proven, however, since attempts to reproduce the heparin necrosis were unsuccessful."
5.	Protein SIBA 01/01/2007 - "With this as background, we evaluated the association of p.Pro667Pro dimorphism with free and total protein S centrally measured in a panel of 119 normal controls, 222 individuals with low protein S and 137 individuals with normal PS levels belonging to 76 families with protein S deficiency enrolled in the ProSIT study. " 01/01/1995 - "To screen for point mutations causing protein S deficiency, we used a sequence of techniques specifically for the study of the protein S active gene, PS alpha. " 02/01/1992 - "The hereditary nature of protein S deficiency was documented by family studies, since nine additional family members deficient in protein S were identified. " 06/01/2022 - "Protein S Erlangen: a novel PROS1 gene mutation associated with quantitative protein S deficiency." 02/02/2022 - "If protein S activity is less than 10%, protein S deficiency caused by homozygous or complex heterozygous variants should be considered. "
6.	Proteins (Proteins, Gene)FDA Link 04/01/1993 - "This study shows that protein S deficiency is common in long-term HIV-infected patients and is caused by a decrease in the free protein, rather than by changes in the bound complex. " 07/01/2004 - "Identification of protein Salpha gene mutations including four novel mutations in eight unrelated patients with protein S deficiency." 07/01/2023 - "A case of ischemic stroke associated with protein-losing gastroenteropathy and protein S deficiency." 03/13/2021 - "A deficiency in this protein or decreased activity, as seen in hereditary protein S deficiency, can lead to life-threatening thrombosis. " 12/01/1996 - "Three patients had low levels of these proteins; two had protein C deficiency, and one protein S deficiency. "
7.	Warfarin (Coumadin)FDA LinkGeneric 05/01/2023 - "Based on our observations, warfarin was the better long-term prophylactic management method for our patient's protein S deficiency. " 09/01/2013 - "In addition, warfarin was used to improve his protein S deficiency. " 05/01/1994 - "Blood investigations later confirmed the diagnosis of protein S deficiency and he was started on warfarin therapy for life. " 07/01/2018 - "Warfarin-induced skin necrosis in a patient with protein S deficiency." 10/01/2014 - "Skin necrosis complicated by warfarin-induced protein S deficiency."
8.	ThrombinFDA Link 04/01/2006 - "In addition, protein S deficiency may be excluded when the percentage of APC-induced endogenous thrombin potential inhibition is >63%. " 01/01/2020 - "Protein S deficiency is also associated with an increased risk of thromboembolism from reduced thrombin generation. " 04/01/1995 - "In order to determine whether there is a relationship between acquired free protein S deficiency and increased thrombin generation, we performed a cross-sectional study of patients with systemic lupus erythematosus (SLE). " 09/01/1997 - "Efficacy of danazol in a patient with congenital protein-S deficiency: paradoxical evidence for decreased platelet activation with increased thrombin generation." 02/01/2016 - "Thrombin generation and other coagulation parameters in a patient with homozygous congenital protein S deficiency on treatment with rivaroxaban."
9.	Vitamin KFDA Link 08/01/2003 - "We postulate that the accepted strong thrombogenicity of antiphosphospholipid syndrome was further increased by protein S deficiency and a possibly procoagulatory effect of the abnormal monocytes explaining the severe thrombophilia resistant to standard therapeutic anticoagulation with a vitamin K antagonist and usual therapeutic doses of low molecular weight heparin, respectively." 10/15/2002 - "We have identified 2 PROS1 missense mutations in the exon that encodes the vitamin K-dependent Gla domain of protein S (Gly11Asp and Thr37Met) in kindred with phenotypic protein S deficiency and thrombosis. " 01/01/2001 - "In patients experiencing necrosis with a vitamin K antagonist, concomitant protein C deficiency, protein S deficiency or lupus anticoagulant has been described, whereas the precise mechanism of the other reactions is unknown. " 09/01/2008 - "Protein S has been one of the least mechanistically understood amongst the vitamin K-dependent coagulation proteins, and diagnosis of protein S deficiency and quantification of the associated thrombotic risk are not straightforward. " 12/31/2020 - "The thrombophilia screen performed six weeks after the suspension of vitamin K antagonists (VKAs) revealed severe deficiencies of protein C and protein S. In this report, we present the first case of recurrence of fatal thromboembolic events under well-conducted oral anticoagulation in a patient with PPCM associated with severe protein C and protein S deficiencies."
10.	Tissue Plasminogen Activator (Alteplase)FDA Link 07/01/1994 - "Successful delayed thrombolysis with tissue plasminogen activator for recurrent arterial thrombosis secondary to protein S deficiency." 01/01/2013 - "[Intravenous recombinant tissue plasminogen activator therapy in a 14-week pregnant woman with embolic stroke due to protein S deficiency]." 01/01/2002 - "Protein S deficiency should be considered in a neonate with aortic thrombosis, and it can be treated successfully with a combination of high-dose tissue plasminogen activator and heparin followed by long-term heparin use." 04/01/1994 - "In eight patients with Legg-Perthes disease, we assessed the etiologic roles of thrombophilia caused by protein C and protein S deficiency and hypofibrinolysis mediated by low levels of tissue plasminogen activator activity. " 05/09/2012 - "Both primary factors of hyper-coagulability, such as resistance to activated protein C, protein C and protein S deficiency, low levels of tissue plasminogen activator, high levels of plasminogen activator inhibitor, von Willebrand factor, lipoprotein (a), and secondary factors of hypercoagulability with factors potentially activating intravascular coagulation, such as pregnancy, antiphospholipid antibodies, systemic lupus erythematosus, hemoglobinopathies and sickle cell disease, and hemato-oncologic diseases are discussed in this article. "

Therapies and Procedures

1.	Therapeutics 01/01/2018 - "Preliminary Data From the Study of Coagulative Profile of HIV Infected Individuals Suggest a Role For Point Mutations in the Gene in Protein S Deficiency in Individuals Undergoing Highly Antiretroviral Therapy." 01/01/2016 - "Our pilot study in Taiwan, an East Asian population, indicated anti-coagulation therapy is of benefit to women with recurrent pregnancy loss who had documented sole protein S deficiency. " 01/01/2001 - "Further tests revealed an isolated protein S deficiency for which oral anticoagulation therapy was initiated. " 06/01/1994 - "Anticoagulation therapy was instituted in a 45-year-old woman with known protein S deficiency and bilateral total hip arthroplasties." 09/03/2021 - "Cerebral venous sinus thrombosis due to protein S deficiency was diagnosed in this adolescent patient, who underwent successful endovascular therapy (EVT). "
2.	Catheters 12/01/2000 - "A 29-week-gestation white infant with a family history of protein S deficiency lost color and blood flow to the right hand several hours after removal of the umbilical artery catheter. " 04/01/2015 - "We report a case of iliofemoral DVT in a 9-year-old boy with IVC atresia and presumed protein S deficiency that was treated successfully using pharmacomechanical thrombectomy and catheter-directed thrombolysis. " 09/01/2009 - "Acute renal vein thrombosis, oral contraceptives, and protein S deficiency: a successful catheter-directed thrombolysis." 08/01/1995 - "The objective of our study was to evaluate the age, sex, clinical conditions, family history, site, catheter association, means of radiologic evaluation, development of pulmonary involvement, prevalence of antithrombin III, protein C and protein S deficiencies, and lupus anticoagulants in children who suffered a thrombotic event. " 10/30/2021 - "Data on sex, age, risk factors related to blood flow stagnation (obesity, long-term bed rest, cardiopulmonary disease, cast fixation, long-term sitting), risk factors related to vascular endothelial disorder (surgery, trauma/fracture, central venous catheterization, catheter tests/treatments, vasculitis, antiphospholipid antibody syndrome, history of venous thromboembolism (VTE)), and risk factors related to hypercoagulability (malignant tumor, use of oral contraceptives/low-dose estrogen progestin/steroids, infection, inflammatory enteric disease, polycythemia, protein C or protein S deficiency, dehydration) were evaluated. "
3.	Renal Dialysis (Hemodialysis) 06/01/1992 - "Case report: a novel form of free protein S deficiency in an HIV-positive patient on hemodialysis." 03/01/2012 - "Results from the study suggest that the inherited protein S deficiency due to a PROS1 gene mutation may cause vascular access thrombosis in hemodialysis patients. " 01/01/1996 - "Free protein S deficiency in hemodialysis patients due to vascular calcifications?" 01/01/1995 - "Calciphylaxis in a chronic hemodialysis patient with protein S deficiency." 01/01/2019 - "Protein C and protein S deficiencies may be related to survival among hemodialysis patients."
4.	Stents 12/01/2010 - "Protein S deficiency is strongly correlated to the occurrence of stent thrombosis, a fact that has hitherto not been recognized and needs further evaluation." 12/01/2010 - "To study the prevalence of protein C and/or protein S deficiency in patients of stent thrombosis and correlate its association with the event, if any. " 12/01/2010 - "Protein C and/or protein S deficiency and occurrence of stent thrombosis: a hitherto unrecognized association." 01/01/2015 - "Stent thrombosis caused by metal allergy complicated by protein S deficiency and heparin-induced thrombocytopenia: a case report and review of the literature."
5.	Local Anesthesia 12/25/2017 - "In our varicose vein center, on a trial basis, among the patients with asymptomatic calf deep vein thrombosis (CDVT) we carefully selected the patients for varicose vein surgery using the requirements as follows; 1) the patients had varicose veins with incompetent saphenous veins, 2) sequential examination including DUS confirmed stability and clinical insignificance of asymptomatic CDVT, 3) the patients do not have any risk factors for DVT such as a coagulation profile disorder (antithrombin deficiency, protein C deficiency, protein S deficiency, or antiphospholipid syndrome) or malignancies, 4) surgery is possible under local anesthesia alone, and 5) the patients can understand the concept of asymptomatic CDVT and undergo the surgery on their own will and informed consent. "