Protein S and protein C gene mutations in Japanese deep vein thrombosis patients

AbstractThrombophilia may be anticipated by single or combined hereditary defects in encoding genes factor V, Prothrombin, and MTHFR. The aim of this study was to determine the prevalence and associated risks of V Leiden (G1691A), Prothrombin (G20210A), and MTHFR (C677T) mutations in Saudi women with Deep Vein Thrombosis (DVT) and women with recurrent pregnancy loss (RPL). Protein C and protein S activity were measured to determine combined effects, if any. We examined 60 women with a history of DVT and 60 with RPL, extracted DNA from EDTA blood and determined three mutations by using multiplex PCR reactions followed by Strip Assay KIT. Pro C Global assay was used to determine the cutoff value [PCATNR = 0.80]. Protein C/S chromogenic assay was used to estimate protein C and S percentages. Frequency of Factor V Leiden G/A genotype in patients with DVT 7 (11.6%) had a significant association for DVT χ2 (OR = 5.1, P = 0.03). In women with RPL the three mutations did not show any significant association, levels of Protein C, protein S and PCAT-NR in patient groups not different from controls (P > 0.05). In conclusion, we recommend expanding on these data to provide larger-scale studies.

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Protein C Inhibitor and Other Components of the Protein C Pathway in Patients with Acute Deep Vein Thrombosis during Heparin Treatment

Thrombosis and Haemostasis ◽

10.1055/s-0038-1645051 ◽

1990 ◽

Vol 63 (03) ◽

pp. 380-382 ◽

Cited By ~ 18

Author(s):

D Tabernero ◽

F España ◽

V Vicente ◽

A Estellés ◽

J Gilabert ◽

...

Keyword(s):

Deep Vein Thrombosis ◽

Protein C ◽

Normal Values ◽

Protein S ◽

Mean Value ◽

Vein Thrombosis ◽

Heparin Treatment ◽

Protein C Inhibitor ◽

Acute Deep Vein Thrombosis ◽

Deep Vein

SummaryThe protein C inhibitor (PCI) concentration and other parameters of the protein C pathway were studied in 19 patients with symptomatic acute deep vein thrombosis before and during the first 5 days of heparin treatment. The mean levels of PCI antigen and activity decreased rapidly and significantly during the first day of heparin therapy from 83 and 81% to 60 and 59% of the pooled normal human plasma (p <0.01), respectively, and to 56 and 54% after 5 days of treatment (p <0.01). In contrast, antithrom-bin III decreased progressively 25% during 5 days of heparin treatment. Protein C antigen and activity and total protein S remained unchanged during heparin treatment. Free protein S was decreased before heparin treatment (83%, p <0.05) and increased to normal values after 5 days of treatment. C4b-binding protein was significantly increased before and during heparin treatment (p <0.01). Activated protein C (APC) complexed to its two major plasma inhibitors, PCI and α1-antitrypsin (α1AT) were measured by specific ELISA’s. Before treatment, 18 of the 19 patients studied had increased levels of APC: α1AT complexes with a mean value of 27 ± 22 ng/ml (range, 6−86 ng/ml) compared to normal values (8 ± 2 ng/ml) and 12 of the patients also had detectable APC:PCI complex levels with a mean value of 11 ±17 ng/ml (range, 5−68 ng/ml). Both APC:inhibitor complexes decreased significantly during heparin treatment.

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High Frequency of Thrombogenic Markers in Polytransfused HbE-Thalassemia.

Blood ◽

10.1182/blood.v110.11.3983.3983 ◽

2007 ◽

Vol 110 (11) ◽

pp. 3983-3983

Author(s):

Vineeta Sharma ◽

Bijender Kumar ◽

Rajesh Ahuja ◽

Renu Saxena

Keyword(s):

Deep Vein Thrombosis ◽

Portal Vein ◽

Iron Overload ◽

Portal Vein Thrombosis ◽

Protein C ◽

Hepatic Dysfunction ◽

Protein S ◽

C Protein ◽

Vein Thrombosis ◽

Deep Vein

Abstract Thromboembolic complications have been well documented in HbE thalassemia Patients. Thrombophelic complications may be either due to genetic factors, hemostatic abnormality or due to hepatic dysfunction. The main objective of this study was to search for the actual cause of thrombophelic complication and to estimate the overall frequency of Protein C, Protein S, APCR, ATIII and MTHFR (677 C-T and 1298A-C) polymorphism in HbE-thalassemia patients. Protein C, protein S, APCR and ATIII were measured in 50 HbE thalassemia patients and 35 controls while MTHFR polymorphisms were studied in 40 HbE thalassemia patients and 35 controls. Levels of Protein C, Protein S, APCR and ATIII were reduced in 14%, 32%, 8% and 46% of HbE-Thal patients respectively and 677het*(CT), 677hom**(TT), 1298het(AC), 1298hom(CC) were 7.5%, 2.5%, 22.5% and 10% respectively. These were more frequent in older Splenectomized patients in comparison to non spelenectomized patients When the values were compared with those of controls Protein C, Protein S and ATIII showed the significant difference(P=0.001) while APCR, 677CT, 677TT, 1298AC, 1298CC showed nonsignificant difference (P= >0.05). However APCR showed significant difference when splenectomoized patients were compared with controls(P=0.01) and non splenectomized patients(P=0.03). Hepatic dysfunction as evidenced by Serum transaminase level of more than 55 IU/L and Serum albumin level less than 3g% were present in 7(14%) patients. Serum Ferritin >1000 ng/ml was observed in 7(14%) patients. Protein C and Protein S showed no correlation with Iron overload and Hepatic dysfunction, however ATIII showed significant correlation with hepatic dysfunction and APCR showed significant correlation with Iron overload. Clinically evident thrombosis was detected in 8(16%) patients. One Patient had recurrent pulmonary thromboembolism, one had developed Portal vein thrombosis Two had Cerebral vascular thrombosis and four had Deep Vein Thrombosis. Six of them were splenectomized. Although APCR and MTHFR Polymorphisms were not significant when compared with controls, two patients developed Deep vein thrombosis due to APCR while one patient having portal vein thrombosis was found to be homozygous for 677C-T. It is evident from this study that genetic factors and haemostatic alterations along with hepatic dysfunction and iron overload play a role in the development of thrombotic complications in HbE-thalassemia patients. * het = heterozygous, **homo =homozygous. Features of Thrombotic Patients Siteof thrombosis Ferritin(ng/ml) SGPT/Alb (IU/l/g %) Pro.C (%) Pro.S (%) APCR(%) ATIII(%) MTHFR polymorphism *= Low level, **= Normal level, DVT=Deep Vein Thrombosis, PVT=Portal Vein Thrombosis, PTE=Pulmonary Thromboembolism, CVT=Cerebral vascular Thrombosis PVT 690 48/3.8 78** 60** 140** 98** 677TT(homo) DVT 1200 50/4.4 75** 58** 80* 110** Negative CVT 754 26/3.6 50* 45* 160** 40* Negative DVT 1000 60/2.1 39* 64** 110* 92** Negative DVT 490 45/4.8 38* 40* 200** 89** Negative DVT 1400 35/3.4 78** 49* 129** 60* Negative CVT 489 29/3.7 80** 40* 130** 70* Negative PTE 645 58/2.8 46* 39* 130** 82* Negative

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Patients with APC Resistance Compared with Those with Other Clotting Inhibitor Deficiencies Show Later Onset of Venous Thrombosis During Oral Contraception

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/107602969500100405 ◽

1995 ◽

Vol 1 (4) ◽

pp. 274-276 ◽

Cited By ~ 7

Author(s):

Antonio Girolami ◽

Paolo Simioni ◽

Sandra Zanardi ◽

Luigi Scarano ◽

Bruno Girolami

Keyword(s):

Deep Vein Thrombosis ◽

Protein C ◽

Antithrombin Iii ◽

Activated Protein C ◽

Protein S ◽

Oral Contraception ◽

Vein Thrombosis ◽

Apc Resistance ◽

At Iii ◽

Deep Vein

The prevalence of deep vein thrombosis in female patients with antithrombin III (AT III), protein C, or protein S deficiency who are on oral contraception has been compared with that of patients with activated protein C (APC) resistance. In the latter case the prevalence was lower (36.4%) than in the AT III deficiency group (71.4%) but similar to that seen in the protein C and protein S group (25%).' Furthermore, venous thrombosis occurred with APC resistance much later than with AT III, protein C, or protein S defects. The time lag between onset of oral contraception and thrombosis (~16 cycles) was not statistically different from that seen in a group of women who were known to have no antithrombin III, protein C, or protein S defects. It appears that as far as the interaction with oral contraception is concerned APC resistance is a much less severe condition compared with other clotting inhibitor defects. Key Words: Oral contraceptive—Activated protein C resistance—Deep vein thrombosis.

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Prevalence of genetic mutations in protein S, protein C and antithrombin genes in Japanese patients with deep vein thrombosis

Thrombosis Research ◽

10.1016/j.thromres.2008.08.020 ◽

2009 ◽

Vol 124 (1) ◽

pp. 14-18 ◽

Cited By ~ 71

Author(s):

Toshiyuki Miyata ◽

Yukiko Sato ◽

Junko Ishikawa ◽

Hiromi Okada ◽

Satoshi Takeshita ◽

...

Keyword(s):

Deep Vein Thrombosis ◽

Protein C ◽

Protein S ◽

Japanese Patients ◽

Genetic Mutations ◽

S Protein ◽

Vein Thrombosis ◽

Deep Vein

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Frequency of natural coagulation inhibitor (antithrombin III, protein C and protein S) deficiencies in Japanese patients with spontaneous deep vein thrombosis

Blood Coagulation & Fibrinolysis ◽

10.1097/00001721-200103000-00002 ◽

2001 ◽

Vol 12 (2) ◽

pp. 95-99 ◽

Cited By ~ 34

Author(s):

E. Suehisa ◽

T. Nomura ◽

T. Kawasaki ◽

Y. Kanakura

Keyword(s):

Deep Vein Thrombosis ◽

Protein C ◽

Antithrombin Iii ◽

Protein S ◽

Japanese Patients ◽

Vein Thrombosis ◽

Coagulation Inhibitor ◽

Deep Vein

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MULTICENTRIC SPANISH STUDY OF BIOLOGICAL CAUSES OF DEEP VEIN THROMBOSIS

10.1055/s-0038-1643044 ◽

1987 ◽

Cited By ~ 1

Author(s):

J Felez ◽

R Rodriguez-Pinto ◽

A Oliver ◽

F Velasco ◽

I de Diego ◽

...

Keyword(s):

Deep Vein Thrombosis ◽

Protein C ◽

Protein S ◽

Point Of View ◽

Control Group ◽

Heparin Cofactor Ii ◽

Vein Thrombosis ◽

Spanish Study ◽

Biological Studies ◽

Deep Vein

305 unselected patients under long-term oral anticoagulation treatment for having presented one o more ep^L sodes of deep vein thrombosis and/or pulmonary embolism, have been studied for the following anomalies: Dysfibrinogenemia, Lupus anticoagulant, Antithrombin-III deficiency, Protein C, Protein S, Heparin Cofactor II, and anomalies in the fibrinolytic components t-PA PAI and Plasminogen. Protein C antigen and activity as well as free Protein S antigen levels have been related to those found in a control group at different intensities of oral anticoagulantAs shown in the table this study, performed on unselected patients from the clinical point of view, has not only confirmed the presence of a previously known congenital defect in 16 patients (5%) but also has per miteed the identification of a previously unkown de- -feet in 45 patients (15%)Since the identification of a congenital abnormality permits to prevention of new thrombotic episodes and the identification of the afected members, these re- -suits support the convenience of performing such syste matic biological studies in patients suffering from thrombosis

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Seasonal Variation in the Incidence of Deep Vein Thrombosis in Patients With Deficiency of Protein C or Protein S

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/107602960200800306 ◽

2002 ◽

Vol 8 (3) ◽

pp. 231-237 ◽

Cited By ~ 14

Author(s):

F. Bilora ◽

V. Boccioletti ◽

E. Manfredini ◽

F. Petrobelli ◽

D. Tormene, ◽

...

Keyword(s):

Deep Vein Thrombosis ◽

Seasonal Variation ◽

Anticoagulant Therapy ◽

Protein C ◽

Total Population ◽

Protein S ◽

Circannual Rhythm ◽

Vein Thrombosis ◽

Deep Vein

An attempt was made to identify circaseptanal or seasonal variation of deep vein thrombosis (DVT) in a population with protein C or protein S deficit. Forty-four patients with DVT and protein C or protein S deficit were studied for 1 year. A significant circannual rhythm was found for the total population that peaked during winter. There was also a significant falling circaseptanal rhythm on Fridays. These observations may optimize an adequate and precise anticoagulant therapy in patients witi protein C or protein S deficits.

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Prevalence of Antiphospholipid Antibodies and Lupus Anticoagulant in Juvenile Patients with Objectively Documented Deep-vein Thrombosis

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/107602969600200114 ◽

1996 ◽

Vol 2 (1) ◽

pp. 69-73 ◽

Cited By ~ 5

Author(s):

E. Zanon ◽

M.A. Saracino ◽

Paolo Simioni ◽

Alberto Cogo ◽

M.A. Fadin ◽

...

Keyword(s):

Deep Vein Thrombosis ◽

Antiphospholipid Antibodies ◽

Lupus Anticoagulant ◽

Protein C ◽

Young Patients ◽

Protein S ◽

Control Group ◽

Heparin Cofactor Ii ◽

Vein Thrombosis ◽

Deep Vein

The prevalence of lupus anticoagulant (LA) and antiphospholipid antibodies (APA) in young patients (<45 years) with deep-vein thrombosis (DVT) is not clearly defined yet. We studied 93 consecutive patients (36 males, 57 females; aged 15 to 45) with objectively documented DVT. A control group consisting of 100 nor mal, sex- and age-matched individuals was also investi gated. In all subjects, we evaluated prothrombin time (PT), partial thromboplastin time (PTT), AT III antigen and activity, protein C antigen and activity, free and total protein S antigen and protein S activity, fibrinogen, plas minogen, heparin cofactor II, plasminogen activator in hibitor (PAI), lupus anticoagulant (LA), and APA. For the assessment of LA, we used the PTT-LA kit (Boeh ringer Mannheim, Milan, Italy) as a screening test, with mixing studies with the Staclot-PNP kit and the Staclot- LA kit (Boehringer Mannheim, Milan, Italy) as confirma tory procedures. For the detection of APA, we used a commercially available enzyme-linked immunoassay (ELISA) (Asserachrom APA, Boehringer Mannheim, Mi lan, Italy). History was elicited in all patients to deter mine if the thrombotic episode was idiopathic or the re sult of a well-identified risk factor. LA was found in 11 (11.8%) patients. APA were positive in 13 (14%) and bor derline in 19 (20.4%) patients. In the control group, no patients were positive for LA or APA, but five exhibited borderline APA levels. LA was significantly more fre quent (p = 0.05) in patients with idiopathic DVT than in patients with secondary DVT; no difference was found for APA (p > 0.5). An inherited coagulation defect was found in seven (7.5%) patients. Our data suggest that the presence of LA or APA is associated with an increased incidence of thrombotic manifestation in young patients. Moreover LA is more frequent in patients with idiopathic DVT. Because the incidence of recurrent thrombotic manifestations in patients with LA or APA is estimated to be ∼50% within 2 years from the first thrombotic episode, the tests should be performed in all patients with juvenile thrombosis.

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