Prothrombin G20210A mutation and oral contraceptive use increase upper-extremity deep vein thrombotic risk

2003 ◽  
Vol 89 (03) ◽  
pp. 452-457 ◽  
Author(s):  
Yolanda Mira ◽  
Jose Mateo ◽  
Cristina Falco ◽  
Piedad Villa ◽  
Amparo Estelles ◽  
...  
Keyword(s):  
Oral Contraceptive ◽  
Upper Extremity ◽  
Protein C ◽  
Protein S ◽  
Prothrombin G20210a ◽  
Protein S Deficiency ◽  
Factor V Leiden Mutation ◽  
G20210a Mutation ◽  
S Deficiency ◽  
Deep Vein

SummaryThe role played by a hypercoagulable state, either inherited or acquired, in the pathogenesis of upper-extremity deep vein thrombosis (UEDVT) remains a question of debate. We performed a case-control study including 79 patients with a first objectively confirmed episode of UEDVT, 31 secondary and 48 primary, and 165 healthy controls. Nine patients (11.4%) with UEDVT were carriers of the prothrombin G20210A mutation vs. six (3.7%) in controls; P = 0.025, OR: 3.39 (95% CI 1.16 to 9.88). No statistical difference was observed between cases and controls for the factor V Leiden mutation, AT, protein C or protein S deficiency and anticardiolipin antibodies (ACAs). Thirteen (35.1%) UEDVT patients were oral contraceptive (OC) users vs. 12 (16%) controls; P = 0.020, OR: 2.89 (95% CI 1.16-7.21). When secondary UEDVT patients were compared with controls, no differences were observed in any of the risk factors analysed. On the other hand, when primary UEDVT was considered, six (12.5%) patients were carriers of the prothrombin G20210A mutation vs. six (3.7%) controls; P = 0.031, OR: 3.76 (95% CI 1.15-12.26). Regarding ACAs, a borderline statistical significance was observed when primary UEDVT was compared with controls, P = 0.048; OR: 4.88 (95% CI 1.05-22.61). In primary UEDVT, 52% of the fertile women were OC users vs. 16% of controls; P = 0.001, OR:5.78 (95% CI 2.13-15.67). When the interaction of both factors, i.e. prothrombin G20210A mutation and OC intake, were considered, the risk increased markedly, indicating a synergistic effect as observed with other thrombotic locations. In patients with primary UEDVT screening for antithrombin, protein C and protein S deficiency and APC resistance would not be justified, although it might be reasonable to determine the carrier status of the prothrombin G20210A mutation only in OC users.

The Risk of Thromboembolism in Asymptomatic Patients with Protein C and Protein S Deficiency: A Prospective Cohort Study

1994 ◽  
Vol 71 (04) ◽  
pp. 441-445 ◽  
Author(s):  
Ingrid Pabinger ◽  
Paul A Kyrle ◽  
Max Heistinger ◽  
Sabine Eichinger ◽  
Eva Wittmann ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
High Risk ◽  
Protein C ◽  
Protein S ◽  
Thromboembolic Events ◽  
Protein S Deficiency ◽  
Vein Thrombosis ◽  
S Deficiency ◽  
Superficial Vein Thrombosis ◽  
Deep Vein

SummaryBackground: Prospective studies on the incidence of thrombosis in asymptomatic individuals with hereditary protein C- or protein S deficiency have not been performed so far.Objective: We have carried out a prospective cohort study in 44 asymptomatic protein C- and protein S deficient subjects and in 49 asymptomatic non-deficient relatives (age at study entry > 14 years) of symptomatic deficient patients.Methods: 20 asymptomatic protein C deficient (median age 20 years) and 24 asymptomatic protein S deficient patients (median age 21.5 years) were prospectively followed and compared with 20 asymptomatic non-deficient relatives (median age 25 years) of protein C- and 29 (median age 27 years) of protein S deficient patients. The total observation period was 118.8 patient years for protein C deficient and 92.8 for protein S deficient patients. Patients were not on anticoagulants except for short duration in case of high risk situations.Results: Eight thromboembolic events (1 pulmonary embolism, 1 deep vein thrombosis + pulmonary embolism, 3 deep vein thrombosis, 1 caval vein thrombosis and 2 superficial vein thrombosis) occurred in 6 deficient patients. The incidence of thromboembolism was 2.5% per patient year for protein C deficient and 3.5% per patient year for protein S deficient patients. 4 events occurred spontaneously, in 2 patients thromboembolic events were triggered by high risk situations (caesarean section, minor trauma). In the controls no thromboembolic events occurred. The probability for thromboembolism was significantly higher in protein C and protein S deficient patients compared to the control group (Wilcoxon test, p = 0.002, log rank test, p = 0.001). One major and 5 minor uneventful surgeries were carried out in the deficient patients using heparin prophylaxis. 1/8 pregnancies was complicated by superficial vein thrombosis during the second trimester despite prophylactic heparin administration. The same pregnancy was complicated by pulmonary embolism 5 weeks after delivery after discontinuation of heparin.Conclusions: Asymptomatic deficient relatives of symptomatic patients with protein C or protein S deficiency are at an increased risk of thrombosis compared to nondeficient individuals. Prophylactic treatment seems to be highly effective in high risk situations.

Hereditary and acquired thrombophilia in patients with upper extremity deep-vein thrombosis

2008 ◽  
Vol 100 (09) ◽  
pp. 440-446 ◽  
Author(s):  
Florian Meister ◽  
Jan Schwonberg ◽  
Marc Schindewolf ◽  
Dimitrios Zgouras ◽  
Edelgard Lindhoff-Last ◽  
...  
Keyword(s):  
Deep Vein Thrombosis ◽  
Upper Extremity ◽  
Factor V Leiden ◽  
Common Finding ◽  
Prothrombin G20210a ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
Vein Thrombosis ◽  
G20210a Mutation ◽  
Deep Vein

SummaryThe prevalence of coagulation disorders in patients with upper extremity deep-vein thrombosis (UE-DVT) is unknown due to only a few observational studies of limited size reporting varying results. Therefore, we aimed to evaluate the prevalence of thrombophilia in patients with UE-DVT compared to patients with lower extremity deep vein thrombosis (LE-DVT). One hundred fifty consecutive patients (15 to 91 years of age) with UE-DVT were recruited from the MAISTHRO (MAin-ISar-THROmbosis) registry. Three hundred LE-DVT patients matched for gender and age served as controls. Thrombophilia screening included tests for the factor V Leiden mutation, the prothrombin G20210A mutation, antiphospholipid antibodies and factor VIII (FVIII), protein C, protein S and antithrombin activities. At least one thrombophilia was present in 34.2% of UE-DVT and 39.2% in UE-DVT that was unrelated to venous catheters relative to 55.3% in LE-DVT patients (p<0.001). In particular, a persistently elevated FVIII is less likely to be found in UE-DVT patients than in those with LE-DVT and is the only thrombophilia that is differentially expressed after controlling for established VTE risk factors [OR 0.46, (95% CI 0.25–0.83)]. Although less prevalent than in LE-DVT patients, thrombophilia is a common finding in patients with UE-DVT, especially in those with thrombosis that is unrelated to venous catheters.

scholarly journals A Case of Deep Vein thrombosis due to Protein C, Protein S Deficiency and Hyper-Homocystinaemia, A Rare Genetic Abnormalities

2013 ◽  
Vol 22 (1) ◽  
pp. 27-29
Author(s):  
Ahmed Hossain ◽  
Quazi Tarikul Islam ◽  
Umme Kulsum Mitu ◽  
Jayanta Banik ◽  
HM Mostafisur Rahman ◽  
...  
Keyword(s):  
Protein C ◽  
Signs And Symptoms ◽  
Protein S ◽  
Protein S Deficiency ◽  
C Protein ◽  
Vein Thrombosis ◽  
S Deficiency ◽  
Genetic Abnormalities ◽  
Left Lower Limb ◽  
Deep Vein

Approximately 80% of Deep Vein Thromboses (DVTs) are clinically asymptomatic, 20% of those that actually demonstrate signs and symptoms. DVT associated with protein C and protein S deficiencies are rare genetic abnormalities that cause thrombophilia and lead to thrombosis. Here we describe a case of 55-year old male who presented with recurrent DVT of left lower limb and eventually diagnosed as a case of DVT due to protein C and protein S deficiency with hyperhomocystinaemia.. The particular interest in this case report is that it is important to consider sceening for thrombophilia incase of DVT with uncertain aetiology. DOI: http://dx.doi.org/10.3329/bjmed.v22i1.13598 Bangladesh J Medicine 2011; 22: 27-29

Bilateral Cerebellar Infarcts in a Patient with Type II Protein S Deficiency and Crohn's Disease: Case Report.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 5067-5067
Author(s):  
Elizabeth Befekadu ◽  
Thaslim Ahamed Kassim ◽  
Zuhair Ghanem ◽  
Anita Aggarwal
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Arterial Thrombosis ◽  
Factor V Leiden ◽  
Protein S ◽  
Prothrombin G20210a ◽  
Type Ii ◽  
Protein S Deficiency ◽  
Factor V Leiden Mutation ◽  
S Deficiency

Abstract Abstract 5067 Background Protein S deficiency as a risk factor for arterial thrombosis is still debatable. We report a young adult male with known protein S deficiency who presented with stroke. Case report A 39 -year-old African American male with history of Crohn's disease in remission and recurrent deep venous thrombosis (DVT) diagnosed 3 years ago presented with unsteady gait and vertigo. Neurological exam revealed dysmetria, dysdiadochokinesia, and ataxic gait. His International Normalized Ratio (INR) on admission was 1.2 while he was on warfarin. Magnetic Resonance Imaging (MRI) of the brain revealed acute bilateral cerebellar ischemic infarcts. Transthoracic and transesophageal echocardiography did not reveal any septal defects or clots. Carotid doppler studies ruled out possible embolic source. Vasculitic profile revealed normal results. Thrombophilia work up including factor V Leiden mutation, prothrombin G20210A mutation, protein S and protein C level and activity, antithrombin III, homocysteine and the antiphospholipid syndrome was done. The only positive finding was type II protein S deficiency with a solely functional activity deficiency: 37% (Normal range 65%-140%). Three years ago, at the time of initial diagnosis of DVT, thrombophilia work up was done and it revealed similar results. As a result of recurrent DVT and pulmonary embolism, the patient had been on warfarin for 3 years. During this hospitalization, warfarin was continued and the patient attained therapeutic INR upon discharge. Discussion Thrombosis is a common complication of inflammatory bowel disease (IBD) and most commonly present as recurrent DVT with or with out pulmonary embolism. Factor V Leiden mutation, antithrombin deficiency, prothrombin (G20210A) gene mutation, protein C and S deficiency and hyperhomocysteinemia have been documented in IBD. The association between protein S deficiency and IBD has been established mainly based on free protein S level (Saibeni S et al, 2001). However, larger data, other than case reports described in the literature, have failed to prove that such association entails thrombotic events. The incidence of arterial thrombosis is even less in patients with IBD although this has been described in few case reports (Deepak Joshi et al, 2008). In general, existing literature on protein S deficiency and arterial thrombosis exhibits conflicting data. Few cases are reported demonstrating protein S deficiency patients presenting with cerebrovascular accident (Girolami A. et al, 1989; Hector R Martinez et al, 1993). Bilateral cerebellar infarcts in a patient with type II protein S deficiency without history of IBD has been reported in the literature (Verma R, 2007). Our patient with IBD and type II protein S presented with bilateral cerebellar infarcts is an anecdote unprecedented in medical literature. Even if we cannot confirm the causal relationship, the lack of any other risk factors makes protein S deficiency the only possible explanation for the occurrence of cerebrovascular accident in our patient. Conclusion Although the importance of protein S deficiency as stimulus to arterial thrombosis was disregarded in few studies, such cases continue to appear revealing coexistence thus indicating a role. To the best of our knowledge, an arterial thrombosis in a Crohn's disease patient with an exclusive type II protein S deficiency has not been reported before. Our case is unique. The pathogenesis and causality remain challenges necessitating large-scale study addressing young patients to elucidate protein S levels and activity for those who lack any other obvious triggers. Disclosures No relevant conflicts of interest to declare.

Abstract 3371: Inherited Thrombophilias In Cryptogenic Stroke Patients Under 55 Years Old

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Patricia Martinez-Sanchez ◽  
Marta Martinez-Martinez ◽  
Blanca Fuentes ◽  
Maria Vicenta Cuesta ◽  
Gerardo Ruiz-Ares ◽  
...  
Keyword(s):  
Brain Ischemia ◽  
Protein C ◽  
Brain Infarction ◽  
Cryptogenic Stroke ◽  
Factor V Leiden ◽  
Protein S ◽  
Prothrombin G20210a ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
G20210a Mutation

Background: inherited thrombophilias cause venous thrombotic events, however, their association with brain ischemia in adult patients is controversial. Our objective was to study the association between thrombophilia and cryptogenic stroke in patients under 55 years of age. Methods: prospective observational study of consecutive patients under 55 years of age who had had a brain ischemia (transient ischemic attack of brain infarction). The patients with cryptogenic brain ischemia were compared with the controls patients with brain ischemia of known cause. We examined the presence of thrombophilia (Factor V Leiden and prothrombin G20210A gene mutations; deficiencies in protein S, protein C and antithrombin levels; resistance to activated protein C) and patent foramen ovale (PFO) in all patients. Results: Two hundred fifty-four patients were included, 108 with cryptogenic brain ischemia and 146 controls patients with brain ischemia of known cause. Patients with cryptogenic brain ischemia were younger (mean age 42.4 vs. 45.6 years old, P=0.002). The frequency of thrombophilia was significantly higher among patients with cryptogenic brain ischemia than those with brain ischemia of known cause (22.2% vs. 6.8%, P<0.001). Taking into account each thrombophilic disorder separately, prothrombin G20210A mutation and protein C or S deficiency were significantly higher in the cryptogenic brain ischemia group than in the known cause group (10.2% vs. 2.7% and 8.3% vs. 2.1%, respectively, P<0.05) while Factor V Leiden mutation was similar in both groups (4.6% vs. 2.7%, P NS). The frequency of PFO and PFO plus thrombophilia were higher among patients with cryptogenic brain ischemia (35.2% vs. 12.3% and 8.4% vs. 0%, respectively, P<0.001). The PFO (+) cryptogenic brain ischemia patients showed higher frequency of thrombophilia than the other patients (23.7% vs. 11.6%, P=0.043), in particular prothrombin G20210A mutation (15.8% vs. 4.2%, P=0.014). Multivariate analysis adjusted confounding factors showed than the presence of thrombophilia was independently associated with cryptogenic brain ischemia (OR 3.9; 95% CI, 1.69 - 8.97; P=0.001). Conclusion: there is an association between thrombophilia and cryptogenic brain ichemia in patients under 55 years old. These data suggest that systemic thrombophilic disorders are cause of thromboembolic phenomena in brain arteries

Deep vein thrombosis associated with protein C and protein S deficiency: An unusual cause of acute abdomen

2010 ◽  
Vol 39 (5) ◽  
pp. 287-289
Author(s):  
Selim Doganay ◽  
Fitnet Sonmezgoz ◽  
Yasar Sen ◽  
Ercan Kocakoc
Keyword(s):  
Deep Vein Thrombosis ◽  
Acute Abdomen ◽  
Protein C ◽  
Protein S ◽  
Protein S Deficiency ◽  
Vein Thrombosis ◽  
S Deficiency ◽  
Deep Vein

The Frequency of Type I Heterozygous Protein S and Protein C Deficiency in 141 Unrelated Young Patients with Venous Thrombosis

1988 ◽  
Vol 59 (01) ◽  
pp. 018-022 ◽  
Author(s):  
C L Gladson ◽  
I Scharrer ◽  
V Hach ◽  
K H Beck ◽  
J H Griffin
Keyword(s):  
Venous Thrombosis ◽  
Protein C ◽  
Antithrombin Iii ◽  
Young Patients ◽  
Protein S ◽  
Type I ◽  
Protein S Deficiency ◽  
Protein C Deficiency ◽  
Low Protein ◽  
S Deficiency

SummaryThe frequency of heterozygous protein C and protein S deficiency, detected by measuring total plasma antigen, in a group (n = 141) of young unrelated patients (<45 years old) with venous thrombotic disease was studied and compared to that of antithrombin III, fibrinogen, and plasminogen deficiencies. Among 91 patients not receiving oral anticoagulants, six had low protein S antigen levels and one had a low protein C antigen level. Among 50 patients receiving oral anticoagulant therapy, abnormally low ratios of protein S or C to other vitamin K-dependent factors were presented by one patient for protein S and five for protein C. Thus, heterozygous Type I protein S deficiency appeared in seven of 141 patients (5%) and heterozygous Type I protein C deficiency in six of 141 patients (4%). Eleven of thirteen deficient patients had recurrent venous thrombosis. In this group of 141 patients, 1% had an identifiable fibrinogen abnormality, 2% a plasminogen abnormality, and 3% an antithrombin III deficiency. Thus, among the known plasma protein deficiencies associated with venous thrombosis, protein S and protein C. deficiencies (9%) emerge as the leading identifiable associated abnormalities.

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