scholarly journals Risk of Venous Thromboembolism and Clinical Manifestations in Carriers of Antithrombin, Protein C, Protein S Deficiency, or Activated Protein C Resistance

1999 ◽  
Vol 19 (4) ◽  
pp. 1026-1033 ◽  
Author(s):  
Paolo Bucciarelli ◽  
Frits R. Rosendaal ◽  
Armando Tripodi ◽  
Pier Mannuccio Mannucci ◽  
Valerio De Stefano ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Protein C ◽  
Activated Protein C ◽  
Clinical Manifestations ◽  
Protein S ◽  
Protein S Deficiency ◽  
Activated Protein C Resistance ◽  
C Protein ◽  
S Deficiency

scholarly journals Exacerbated venous thromboembolism in mice carrying a protein S K196E mutation

Blood ◽  
2015 ◽  
Vol 126 (19) ◽  
pp. 2247-2253 ◽  
Author(s):  
Fumiaki Banno ◽  
Toshiyuki Kita ◽  
José A. Fernández ◽  
Hiroji Yanamoto ◽  
Yuko Tashima ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Venous Thrombosis ◽  
Protein C ◽  
Activated Protein C ◽  
Protein S ◽  
Protein S Deficiency ◽  
Wild Type ◽  
S Deficiency ◽  
Key Points ◽  
Cofactor Activity

Key Points A protein S-K196E mutation reduced its activated protein C cofactor activity in recombinant murine protein S-K196E and in K196E mutant mice. Mice carrying a protein S-K196E mutation or heterozygous protein S deficiency were more vulnerable to venous thrombosis than wild-type mice.

scholarly journals Inherited thrombophilia in children with venous thromboembolism and the familial risk of thromboembolism: an observational study

Blood ◽  
2012 ◽  
Vol 120 (7) ◽  
pp. 1510-1515 ◽  
Author(s):  
Susanne Holzhauer ◽  
Neil A. Goldenberg ◽  
Ralf Junker ◽  
Christine Heller ◽  
Monika Stoll ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Protein C ◽  
Protein S ◽  
Factor V ◽  
Protein S Deficiency ◽  
C Protein ◽  
Inherited Thrombophilia ◽  
S Deficiency ◽  
Factor Ii ◽  
Factor V G1691a

Abstract Screening for inherited thrombophilia (IT) is controversial; persons at high risk for venous thromboembolism (VTE) who benefit from screening need to be identified. We tested 533 first- and second-degree relatives of 206 pediatric VTE patients for IT (antithrombin, protein C, protein S, factor V G1691A, factor II G20210A) and determined the incidence of symptomatic VTE relative to their IT status. 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). Annual incidences of VTE were 2.82% (95% CI, 1.63%-4.80%) among family members found to be carriers of antithrombin, protein C, or protein S deficiency, 0.42% (0.12%-0.53%) for factor II G202010A, 0.25% (0.12%-0.53%) for factor V G1691A, and 0.10% (0.06%-0.17%) in relatives with no IT. Given the high absolute risk of VTE in relatives with protein C, protein S, and antithrombin deficiency, we suggest screening for these forms of hereditary thrombophilia in children with VTE and their relatives. Interventional studies are required to assess whether thromboembolism can be prevented in this high-risk population.

scholarly journals Rivaroxaban Causes Missed Diagnosis of Protein S Deficiency but Not of Activated Protein C Resistance (Factor V Leiden)

2017 ◽  
Vol 142 (1) ◽  
pp. 70-74 ◽  
Author(s):  
Elena Maryamchik ◽  
Matthew W. Rosenbaum ◽  
Elizabeth M. Van Cott
Keyword(s):  
Protein C ◽  
Activated Protein C ◽  
Factor V Leiden ◽  
Protein S ◽  
Factor V ◽  
Protein S Deficiency ◽  
Activated Protein C Resistance ◽  
Functional Protein ◽  
S Deficiency ◽  
Protein S Activity

Context.— Rivaroxaban causes a false increase in activated protein C resistance (APCR) ratios and protein S activity. Objective.— To investigate whether this increase masks a diagnosis of factor V Leiden (FVL) or protein S deficiency in a “real-world” population of patients undergoing rivaroxaban treatment and hypercoagulation testing. Design.— During a 2.5-year period, we compared 4 groups of patients (n = 60): FVL heterozygous (FVL-HET)/taking rivaroxaban, wild-type/taking rivaroxaban, FVL-HET/no rivaroxaban, and normal APCR/no rivaroxaban. Patients taking rivaroxaban were tested for protein S functional activity and free antigen (n = 32). Results.— The FVL-HET patients taking rivaroxaban had lower APCR ratios than wild-type patients (P &lt; .001). For FVL-HET patients taking rivaroxaban, mean APCR was 1.75 ± 0.12, versus 1.64 ± 0.3 in FVL-HET patients not taking rivaroxaban (P = .005). Activated protein C resistance in FVL-HET patients fell more than 3 SDs below the cutoff of 2.2 at which the laboratory reflexes FVL DNA testing. No cases of FVL were missed despite rivaroxaban. In contrast, rivaroxaban falsely elevated functional protein S activity, regardless of the presence or absence of FVL (P &lt; .001). A total of 4 of 32 patients (12.5%) had low free protein S antigen (range, 58%–67%), whereas their functional protein S activity appeared normal (range 75%–130%). Rivaroxaban would have caused a missed diagnosis of all cases of protein S deficiency during the study if testing relied on the protein S activity assay alone. Conclusions.— Despite rivaroxaban treatment, APCR testing can distinguish FVL-HET from normal patients, rendering indiscriminate FVL DNA testing of all patients on rivaroxaban unnecessary. Free protein S should be tested in patients taking rivaroxaban to exclude hereditary protein S deficiency.

scholarly journals Deficiency of the natural anticoagulant proteins in women with pregnancy related venous thromboembolism

2009 ◽  
Vol 62 (1-2) ◽  
pp. 53-62 ◽  
Author(s):  
Gorana Mitic ◽  
Ljubica Povazan ◽  
Radmila Lazic ◽  
Dragan Spasic ◽  
Milana Maticki-Sekulic
Keyword(s):  
Venous Thromboembolism ◽  
Protein C ◽  
Protein S ◽  
Single Woman ◽  
Control Group ◽  
Protein S Deficiency ◽  
Clotting Factors ◽  
Protein C Deficiency ◽  
S Deficiency ◽  
Increased Risk

Inherited thrombophilia can be defined as a predisposition to thrombosis caused by heritable defects, such as mutations in genes encoding the natural anticoagulants or clotting factors. Pregnancy related risk of VTE is sixfold increased comparing to non pregnant age matched women. Pregnancy is an independent risk factor for the development of venous thromboembolism and this risk is further increased by the presence of thrombophilia. Aim of the study: The aim of the study was to evaluate the association between deficiency of natural anticoagulants: antithrombin, protein C and protein S and pregnancy related thromboembolism. We have determined the activities of antithrombin, proten C and protein S in 74 women with pregnancy related thrombosis and in 45 healthy women who had at least two uncomplicated pregnancies. Among the women with the history of venous thromboembolism antithrombin deficiency was found in 4 (5.4%), protein C deficiency in 2 (2.7%) and protein S deficiency in 5 (6.76%). The total of 11 (14.6%) women was found to be deficient. Not a single woman in the control group was found to be deficient in natural anticoagulants. Deficiencies of coagulation inhibitors are associated with an increased risk of venous thrombosis during pregnancy and puerperium (p= 0.006). Antithrombin, protein C and protein S deficient women are at higher risk of developing venous thromboembolism during antepartal period (p= 0.0097). Prophylactic treatment with heparin should be recommended from the very beginning of the following pregnancy in women with antithrombin, protein C or protein S deficiency.

scholarly journals Increased Thrombophilic Tendency in Pediatric Cystic Fibrosis Patients

2009 ◽  
Vol 16 (1) ◽  
pp. 71-76 ◽  
Author(s):  
Vaughan Williams ◽  
Adrian B. M. Griffiths ◽  
Zen L. Yap ◽  
James Martin ◽  
Gregory Smith ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
General Population ◽  
Protein C ◽  
Activated Protein C ◽  
Protein S ◽  
Activated Protein C Resistance ◽  
Antithrombin Deficiency ◽  
Indwelling Catheters ◽  
C Protein ◽  
Lupus Anticoagulants

Thrombophilia has recently been reported to be increased in patients with cystic fibrosis (CF). We wanted to determine whether this was applicable to our population with CF and how our patients compared to the previously reported groups. Seventy one pediatric CF patients were assessed for a thrombophilic tendency, using a lupus anticoagulant screen, protein C, protein S, antithrombin assay, and activated protein C resistance (APCR) screen. The incidence of activate protein C resistance (4.2%) was within expected limits for the general population as was the incidence of antithrombin deficiency. However there was a marked increase in the incidence of lupus anticoagulants (18%) and 14% and 19.7% of the patients showed a reduced protein C and protein S, respectively, far in excess of the general population. This increased incidence of thrombophilia was not related to any specific CF phenotype and while perturbed liver function cannot be entirely ruled out, it appeared unlikely to be responsible for all the abnormal coagulation findings. Despite the apparent thrombophilic tendency, no clinically evident thrombotic episodes were noted during the study period. Thrombophilia is of concern because of the increasingly frequent placement of indwelling catheters in CF patients. The precise cause for the thrombophilic tendency in CF patients is unknown at this stage.

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