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: 693 relevant articles (5 outcomes, 36 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Thrombosis (Thrombus)
2.	Necrosis
3.	Thrombophilia
4.	Antithrombin III Deficiency
5.	Protein C Deficiency

Experts

1.	Nowak-Göttl, Ulrike: 6 articles (01/2013 - 01/2002)
2.	Martinelli, Ida: 5 articles (11/2013 - 05/2002)
3.	Rosing, Jan: 5 articles (09/2010 - 07/2002)
4.	Hackeng, Tilman M: 5 articles (09/2010 - 12/2004)
5.	van der Meer, Jan: 5 articles (05/2009 - 07/2002)
6.	Bucciarelli, Paolo: 4 articles (11/2013 - 08/2004)
7.	Junker, Ralf: 4 articles (08/2012 - 01/2002)
8.	Pabinger, I: 4 articles (02/2012 - 03/2005)
9.	Rosendaal, F R: 4 articles (02/2012 - 01/2000)
10.	Borrell, Montserrat: 4 articles (01/2011 - 04/2002)

Drugs and Biologics

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

1.	Protein CIBA 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. " 12/01/2013 - "To determine the frequency of FII G20210A and FVL polymorphisms as well as protein C and protein S deficiency in a series of patients with RPL compared with control group. " 07/01/2013 - "Protein C and protein S deficiency - practical diagnostic issues." 01/01/2013 - "The concentrations of sTM and sEPCR in 19 CVST patients without protein C and protein S deficiency were measured by ELISA and compared with 53 healthy controls. " 08/16/2012 - "The risk for VTE was significantly increased among family members with, versus without, IT (hazard ratio = 7.6; 95% confidence interval [CI], 4.0-14.5; P < .001) and highest among carriers of antithrombin, protein C, or protein S deficiency (hazard ratio = 25.7; 95% CI, 12.2-54.2; P < .001). "
2.	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. " 12/01/1998 - "This functional protein S assay can be used for the laboratory diagnosis of protein S deficiency, and to study the mechanism of the APC-independent anticoagulant activity in plasma." 05/01/1995 - "Studies performed in six families (totalling 43 subjects) showed cosegregation of the genetic abnormality with reduced plasma protein S levels, and provided genetic evidence for a heterozygous protein S deficiency in 25 of them. " 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. " 06/01/1992 - "Study of the protein S system in HIV-infected patients: acquired protein S deficiency or unsuitable assays?"
3.	Antithrombin IIIIBA 12/01/1996 - "Protein S deficiency was found in eight cases (6.1%), AT-III deficiency was established in five cases (3.8%) and a fibrinolytic defect in 33 cases (25.4%). " 01/01/1993 - "Acquired antithrombin III deficiency: replacement with antithrombin III concentrates in a patient with protein S deficiency accelerates response to therapy." 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. " 09/01/2005 - "They were screened for protein C, antithrombin III, and protein S deficiencies; and gene analysis was performed using the polymerase chain reaction. " 01/01/2004 - "There were several thrombophilic risk factors detectable (heterozygous factor V Leiden, low levels of antithrombin III, protein S deficiency), whose possible impact in this rare but severe clinical condition is discussed."
4.	Warfarin (Coumadin)FDA LinkGeneric 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. " 10/01/2014 - "Skin necrosis complicated by warfarin-induced protein S deficiency." 01/01/2014 - "We describe herein a patient with protein S deficiency who developed significant skin necrosis without being exposed to warfarin. " 12/01/2010 - "A 50-year-old man with a history of protein S deficiency treated by long-term warfarin presented with right non-arteritic optic neuropathy. "
5.	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%. " 02/01/1996 - "Our results agree with the hypothesis that individuals with APC-resistance or protein S deficiency have an imbalance between pro- and anti-coagulant forces leading to increased thrombin generation and a hypercoagulable state." 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." 09/01/2008 - "In this review, the regulation of thrombin generation by protein S and the pathophysiological implications of protein S deficiency are discussed in the light of recent findings on the anticoagulant function(s) of protein S. "
6.	Heparin (Liquaemin)FDA LinkGeneric 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. " 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." 05/01/1997 - "A patient with heterozygous protein S deficiency experienced cutaneous necrosis following subcutaneous heparin administration. " 05/01/1997 - "Cutaneous heparin necrosis in a patient with heterozygous protein S deficiency."
7.	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. " 02/01/2003 - "Protein S is a vitamin K-dependent plasma protein that inhibits the process of blood coagulation via activation of protein C, another vitamin K-dependent plasma protein A 58-year-old man with hereditary protein S deficiency had repeated attacks of acute myocardial infarction at age 52 and 58 years."
8.	Tissue Plasminogen Activator (Alteplase)FDA Link 01/01/2013 - "[Intravenous recombinant tissue plasminogen activator therapy in a 14-week pregnant woman with embolic stroke due to protein S deficiency]." 07/01/1994 - "Successful delayed thrombolysis with tissue plasminogen activator for recurrent arterial thrombosis secondary 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. "
9.	Complement C4b-Binding ProteinIBA 07/01/1993 - "In this patient, transient functional protein S deficiency during the infectious process was demonstrated with a marked decrease of free protein S and elevated C4b-binding protein levels. " 10/01/1992 - "As C4b-binding protein partial deficiency is associated with high free protein S and protein S activity, this may have protected against acquired protein S deficiency during meningococcaemia." 06/15/1995 - "Evaluation of the relationship between protein S and C4b-binding protein isoforms in hereditary protein S deficiency demonstrating type I and type III deficiencies to be phenotypic variants of the same genetic disease." 06/15/1992 - "Failure of warfarin to prevent new thrombotic processes was observed in three patients with very low free protein S concentrations and high C4b-binding protein (C4bBP) concentrations, and in one patient with hereditary protein S deficiency. "
10.	Proteins (Proteins, Gene)IBA 02/26/1999 - "Genetic mutations that cause amino acid changes within these proteins have been linked to the Marfan syndrome (MFS), CADASIL, protein S deficiency, haemophilia B and familial hypercholesterolaemia, respectively. " 02/01/1989 - "Six patients had one or more abnormalities of regulatory proteins (protein S deficiency, four; protein C deficiency, three; presence of lupus-like anticoagulant, three; plasminogen deficiency, two). " 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. " 11/01/2013 - "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. "

Therapies and Procedures

1.	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. "
2.	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."
3.	Coronary Artery Bypass (Coronary Artery Bypass Surgery) 07/01/2014 - "Coronary artery bypass grafting in a patient with protein S deficiency: perioperative implications." 04/15/2014 - "Coronary artery bypass grafting in 2 thrombophilic patients with protein s deficiency." 12/01/1996 - "Coronary artery bypass graft surgery in a patient with hereditary protein S deficiency." 12/01/2001 - "An intraoperative coronary artery bypass graft thrombosis in a patient with protein S deficiency." 01/01/1996 - "Early coronary artery bypass graft thrombosis in a patient with protein S deficiency."
4.	Transplants (Transplant) 05/27/1999 - "Acquired protein S deficiency with multiple thrombotic complications after orthotopic liver transplant." 02/01/2012 - "We discuss the prior literature of protein S deficiency acquired via liver transplantation, and we evaluate potential criteria by which the safety of transplants utilizing this pool of donors may be enhanced." 12/01/1996 - "Coronary artery bypass graft surgery in a patient with hereditary protein S deficiency." 12/01/2001 - "An intraoperative coronary artery bypass graft thrombosis in a patient with protein S deficiency." 01/01/1996 - "Early coronary artery bypass graft thrombosis in a patient with protein S deficiency."
5.	Cesarean Section (Caesarean Section) 03/01/1995 - "Caesarean section in a patient with protein S deficiency." 08/01/2014 - "[Anesthetic management of cesarean section in a patient with pulmonary embolism due to protein S deficiency]." 06/01/2008 - "[Anesthetic management of cesarean section in a patient with pulmonary embolism due to protein S deficiency diagnosed postoperatively]." 04/01/1999 - "We describe the case of a 36-year-old woman, with a previous history of recurrent abortion due to protein S deficiency, undergoing an elective Caesarean section at 39-weeks gestation. " 04/01/1999 - "Myocardial infarction and death after caesarean section in a woman with protein S deficiency and undiagnosed phaeochromocytoma."