scholarly journals Clinical profile, common thrombophilia markers and risk factors in 85 young Indian patients with arterial thrombosis

2013 ◽  
Vol 131 (6) ◽  
pp. 384-388 ◽  
Author(s):  
Mahendra Narain Mishra ◽  
Ravi Kalra ◽  
Shalesh Rohatgi
Keyword(s):  
Myocardial Infarction ◽  
Family History ◽  
Arterial Thrombosis ◽  
Protein C ◽  
Positive Family History ◽  
Protein S ◽  
Factor V ◽  
C Protein ◽  
Indian Patients ◽  
Low Levels

CONTEXT AND OBJECTIVE: Arterial thrombosis may occur consequent to hereditary thrombophilia and increased lipoprotein(a) [Lp(a)] and fibrinogen. Our aim was to study the prevalence of common thrombophilia markers in 85 consecutive cases of arterial thrombosis. DESIGN AND SETTING: A retrospective study was conducted from 85 consecutive young patients treated as outpatients or admitted due to stroke or myocardial infarction at a tertiary care hospital. METHODS: Eighty-five Indian patients (age < 45 years) presenting ischemic stroke (n = 48) or myocardial infarction (n = 37) and 50 controls were studied for seven thrombophilia markers including antithrombin (AT), factor V, protein C, protein S, activated protein C resistance (APC-R), fibrinogen and Lp(a). Functional assays for protein C, protein S, factor V and APC-R were performed using clotting-based methods. Semi-quantitative estimation of fibrinogen was done using Clauss's method and Lp(a) using immunoturbidimetry. Statistical analysis was done using the Epi Info 6 software. RESULTS: Thirty-three samples (38.8%) tested positive for one or more thrombophilia markers. The three commonest abnormalities were elevated Lp(a) (20%), fibrinogen (17.6%) and low APC-R (14.2%). Low levels of protein C, protein S and AT were present in 4.7, 9.4 and 7% of the patients, respectively. Overall, the risk factor profile was: smoking (33%), positive family history (15.3%), hyperlipidemia (7%), hypertension, diabetes mellitus and obesity (2.3% each). CONCLUSIONS: An association was found between low levels of protein C, protein S and AT and arterial thrombosis, but only elevated fibrinogen levels, smoking, positive family history and hyperlipidemia showed statistical significance.

scholarly journals Thrombophilia And Arterial Ischemic Stroke

2017 ◽  
pp. 45
Author(s):  
A.A. Abrishamizadeh
Keyword(s):  
Ischemic Stroke ◽  
Vitamin K ◽  
Arterial Thrombosis ◽  
Protein C ◽  
Antithrombin Iii ◽  
Factor V Leiden ◽  
Protein S ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
C Protein

Ischemic stroke (IS) is a common cause of morbidity and mortality with significant socioeconomic impact especially when it affects young patients. Compared to the older adults, the incidence, risk factors, and etiology are distinctly different in younger IS. Hypercoagulable states are relatively more commonly detected in younger IS patients.Thrombophilic states are disorders of hemostatic mechanisms that result in a predisposition to thrombosis .Thrombophilia is an established cause of venous thrombosis. Therefore, it is tempting to assume that these disorders might have a similar relationship with arterial thrombosis. Despite this fact that 1-4 % of ischemic strokes are attributed to Thrombophillia, this   alone rarely causes arterial occlusions .Even in individuals with a positive thrombophilia screen and arterial thrombosis, the former might not be the primary etiological factor.Thrombophilic   disorders can be broadly divided into inherited or acquired conditions. Inherited thrombophilic states include deficiencies of natural anticoagulants such as protein C, protein S, and antithrombin III (AT III) deficiency, polymorphisms causing resistance to activated protein C(Factor V Leiden mutation), and disturbance in the clotting balance (prothrombin gene 20210G/A variant). Of all the inherited  thrombophilic disorders, Factor V Leiden mutation is perhaps the commonest cause. On the contrary, acquired thrombophilic disorders are more common and include conditions such as the antiphospholipid syndrome, associated with lupus anticoagulant and anticardiolipin antibodies.The more useful and practical approach of ordering various diagnostic tests for the uncommon thrombophilic states tests should be determined by a detailed clinical history, physical examination, imaging studies and evaluating whether an underlying hypercoagulable state appears more likely.The laboratory thrombophilia   screening should be comprehensive and avoid missing the coexisting defect and It is important that a diagnostic search protocol includes tests for both inherited and acquired thrombophilic disorders.Since the therapeutic approach (anticoagulation and thrombolytic therapy) determines the clinical outcomes, early diagnosis of the thrombophilic  disorders plays an important role. Furthermore, the timing of test performance of some of the  thrombophilic  defects (like protein C, protein S, antithrombin III and fibrinogen levels) is often critical since these proteins can behave as acute phase reactants and erroneously elevated levels of these factors may be observed in patients with acute thrombotic events. On the other hand, the plasma levels of vitamin K-dependent proteins (protein C, protein S and APC resistance) may not be reliable in patients taking vitamin K antagonists. Therefore, it is suggested that plasma-based assays for these disorders should be repeated3 to 6 months after the initial thrombotic episode to avoid false-positive results and avoid unnecessary prolonged   anticoagulation therapy. The assays for these disorders are recommended after discontinuation of oral anticoagulant treatment or heparin for at least 2 weeks.    

Myocardial infarction under the age of 36: prevalence of thrombophilic disorders

2003 ◽  
Vol 90 (08) ◽  
pp. 272-279 ◽  
Author(s):  
Chrusula Belesi ◽  
Helen Manioudaki ◽  
Vassilis Chatziioakimidis ◽  
Vassiliki Fakitsa ◽  
Loukas Sinos ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Protein C ◽  
Antithrombin Iii ◽  
Protein S ◽  
Factor V ◽  
C Protein ◽  
G20210a Mutation ◽  
Factor V Gene ◽  
Prothrombin Gene ◽  
V Gene

SummaryIt has been suggested that thrombotic tendency increases the risk of myocardial infarction (MI). To investigate the association between the risk of MI at a young age and genetic thrombogenic disorders (G20210A mutation in the prothrombin gene, G1691A mutation in the factor V gene and deficiencies of protein C, protein S and antithrombin III) we conducted a case-control study among 70 survivors of MI who had experienced the event before the age of 36 and 260 healthy subjects. The G20210A mutation in the prothrombin gene was found more often in young patients with MI than among controls (11.4 versus 3.1%). The odds ratio (OR) for MI for carriers versus non-carriers was 4 (95% confidence interval [CI], 1.5 to 11.3). The adjusted OR for major cardiovascular risk factors (smoking, hypecholesterolaemia, diabetes mellitus, hypertension and obesity) was 4.3 (95% CI,1.3 to 14). The simultaneous presence of both G20210A mutation in the prothrombin gene and smoking further increased the risk of MI compared with nonsmokers and non-carriers (OR, 58; 95% CI, 11.4-294). The G1691A mutation in factor V gene was not associated with an increased relative risk for MI (OR, 0.87; 95% CI, 0.26 to 2.5). Finally, there was no significant difference in the prevalence of deficiencies of protein C, protein S and antithrombin III between cases and controls. In conclusion, our data indicate that the G20210A mutation in the prothrombin gene was the only genetic prothrombotic risk factor associated with the risk of developing MI under the age of 36 years.

The Prevalence of Factor XII Deficiency in 103 Orally Anticoagulated Outpatients Suffering from Recurrent Venous and/or Arterial Thromboembolism

1992 ◽  
Vol 68 (03) ◽  
pp. 285-290 ◽  
Author(s):  
Walter-Michael Halbmayer ◽  
Christine Mannhalter ◽  
Christine Feichtinger ◽  
Karl Rubi ◽  
Michael Fischer
Keyword(s):  
Myocardial Infarction ◽  
Family History ◽  
Protein C ◽  
Positive Family History ◽  
Protein S ◽  
Thrombotic Complication ◽  
Factor Xii ◽  
Protein C Deficiency ◽  
Arterial Thromboembolism ◽  
Recurrent Venous Thrombosis

SummaryOne hundred and three patients suffering from recurrent venous thrombosis, recurrent arterial thromboembolism and/or recurrent myocardial infarction and 50 healthy subjects were tested for Hageman factor (FXII) coagulant activity and antigen. Among the 103 patients we identified 15 subjects with FXII deficiency (15%), 3 with protein C deficiency (3%) and 3 with protein S deficiency (3%). Combined FXII and protein C, protein S or antithrombin III deficiency was not observed. The 103 patients were devided into subgroups according to the type of thrombotic complication. Among patients with exclusively recurrent venous thromboembolism 8% (p = 0.153) were deficient in FXII. Among patients suffering from recurrent arterial thromboembolism and/or myocardial infarction, the incidence of FXII deficiency was significantly higher (20%, p < 0.003). In 67% of the patients with FXII deficiency a positive family history of thrombosis could be established. In contrast, only 32% of all venous and 28% of all arterial thrombosis patients had a positive family history. We believe that reduced levels of FXII should be considered as a risk factor in the development of thromboembolism. Consequently, more attention should be payed to the measurement of FXII when evaluating thromboembolic risk factors especially in cases of recurrent arterial thromboembolism and/or myocardial infarction.

Clinical Features in 36 Patients Homozygous for the ARG 506 → GLN Factor V Mutation

1997 ◽  
Vol 77 (04) ◽  
pp. 620-623 ◽  
Author(s):  
Joseph Emmerich ◽  
Martine Alhenc-Gelas ◽  
Marie-Françoise Aillaud ◽  
Irène Juhan-Vague ◽  
Brigitte Jude ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Clinical Features ◽  
Oral Contraceptives ◽  
Arterial Thrombosis ◽  
Protein C ◽  
Post Partum ◽  
Protein S ◽  
Factor V ◽  
Thrombotic Complications ◽  
Risk For Thrombosis

SummaryWe analyzed the clinical features of 36 patients homozygous for the Arg 506 to Gin factor V mutation and found a circumstantial event at risk for thrombosis in 29 of the 31 patients with thrombosis. The most frequent predisposing factors were the post-partum period and the use of oral contraceptives in women, and surgery in both sexes. Venous thrombosis recurred in 48% of the patients. One patient had a myocardial infarction at age 33 years, and also had an antiphospholipid syndrome. Homozygous Gin 506 mutation leads to far less severe thrombotic complications than homozygous protein C and protein S deficiencies and does not seem to predispose patients to arterial thrombosis.

Selective testing for thrombophilia in patients with first venous thrombosis: results from a retrospective family cohort study on absolute thrombotic risk for currently known thrombophilic defects in 2479 relatives

Blood ◽  
2009 ◽  
Vol 113 (21) ◽  
pp. 5314-5322 ◽  
Author(s):  
Willem M. Lijfering ◽  
Jan-Leendert P. Brouwer ◽  
Nic J. G. M. Veeger ◽  
Ivan Bank ◽  
Michiel Coppens ◽  
...  
Keyword(s):  
Family History ◽  
Venous Thrombosis ◽  
Protein C ◽  
Positive Family History ◽  
Protein S ◽  
Factor V ◽  
Recurrence Rates ◽  
Thrombotic Risk ◽  
History Of ◽  
Fv Leiden

Abstract Thrombophilia screening is controversial. In a retrospective family cohort, where probands had thrombosis and a thrombophilic defect, 2479 relatives were tested for thrombophilia. In antithrombin-, protein C–, and protein S–deficient relatives, annual incidences of venous thrombosis were 1.77% (95% CI, 1.14-2.60), 1.52% (95% CI, 1.06-2.11), and 1.90% (95% CI, 1.32-2.64), respectively, at a median age of 29 years and a positive family history of more than 20% symptomatic relatives. In relatives with factor V (FV) Leiden, prothrombin 20210G>A, or high FVIII levels, these were 0.49% (95% CI, 0.39-0.60), 0.34% (95% CI, 0.22-0.49), and 0.49% (95% CI, 0.41-0.51), respectively. High FIX, FXI, and TAFI, and hyperhomocysteinemia were not independent risk factors. Annual incidence of major bleeding in antithrombin-, protein C–, or protein S–deficient relatives on anticoagulants was 0.29% (95% CI, 0.03-1.04). Cumulative recurrence rates in relatives with antithrombin, protein C, or protein S deficiency were 19% at 2 years, 40% at 5 years, and 55% at 10 years. In relatives with FV Leiden, prothrombin 20210G>A, or high levels FVIII, these were 7%, 11%, and 25%, respectively. Considering its clinical implications, thrombophilia testing should address hereditary deficiencies of antithrombin, protein C, and protein S in patients with first venous thrombosis at young age and/or a strong family history of venous thrombosis.

scholarly journals Prevalence of common thrombophilia markers and risk factors in Indian patients with primary venous thrombosis

2010 ◽  
Vol 128 (5) ◽  
pp. 263-267 ◽  
Author(s):  
Mahendra Narain Mishra ◽  
Varinder Singh Bedi
Keyword(s):  
Venous Thrombosis ◽  
Protein C ◽  
Quantitative Estimation ◽  
Protein S ◽  
Anticardiolipin Antibodies ◽  
Factor V ◽  
Cross Sectional ◽  
C Protein ◽  
Lupus Anticoagulants ◽  
Significant Difference

CONTEXT AND OBJECTIVE: Venous thrombosis occurs as a result of interaction of genetic and acquired factors including activated protein C resistance (APC-R), fibrinogen levels, antithrombin, protein C, protein S, lupus anticoagulants and anticardiolipin antibodies. This study was aimed at determining the prevalence of these common thrombophilia markers in Asian Indians with primary venous thrombosis. DESIGN AND SETTING: This was a cross-sectional study carried out in Mumbai. METHODS: Samples from 78 patients with a confirmed diagnosis of venous thrombosis and 50 controls were tested. Semi-quantitative estimation (functional assays) of protein C, protein S and antithrombin was performed. Quantitative estimation of fibrinogen was done using the Clauss method. Lupus anticoagulants were screened using lupus-sensitive activated partial thromboplastin time and β2-glycoprotein-I dependent anticardiolipin antibodies were estimated by ELISA. APC-R was measured using a clotting-based method with factor V deficient plasma and Crotalus viridis venom. Statistical analysis was performed using Epi-info (version 6). RESULTS: The popliteal vein was the most commonly involved site. Forty-four samples (56%) gave abnormal results. The commonest were elevated fibrinogen and APC-R (17.9% each), followed by low protein S (16.6%). CONCLUSIONS: This study confirms the literature findings that fibrinogen level estimation and screening for APC-R are important for the work-up on venous thrombosis patients since these, singly or in combination, may lead to a primary thrombotic episode. The frequency of the other thrombophilia markers was higher among the patients than among the controls, but without statistically significant difference.

scholarly journals Association between the Prevalence of Antibodies to β2-Glycoprotein I, Prothrombin, Protein C, Protein S, and Annexin V in Patients with Systemic Lupus Erythematosus and Thrombotic and Thrombocytopenic Complications

2001 ◽  
Vol 47 (6) ◽  
pp. 1008-1015 ◽  
Author(s):  
Junzo Nojima ◽  
Hirohiko Kuratsune ◽  
Etsuji Suehisa ◽  
Yoshiaki Futsukaichi ◽  
Hachiro Yamanishi ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Lupus Erythematosus ◽  
Arterial Thrombosis ◽  
Plasma Proteins ◽  
Protein C ◽  
Significant Risk ◽  
Fetal Loss ◽  
Annexin V ◽  
Protein S ◽  
C Protein

Abstract Background: Anti-phospholipid (aPL) antibodies (Abs) frequently found in the plasma of patients with systemic lupus erythematosus (SLE) have been associated with thrombotic complications. Our aim was to clarify the roles in thrombosis of aPL Abs that react with complexes of phospholipids and plasma proteins such as β2-glycoprotein I (β2-GPI), prothrombin, protein C, protein S, and annexin V. Methods: We determined the prevalence of aPL Abs to various phospholipid-binding plasma proteins in SLE patients with arterial thrombosis (30 cases), venous thrombosis (19 cases), thrombocytopenia (14 cases), fetal loss (14 cases), and patients without complications (91 cases). The aPL Abs were measured by an ELISA system in which human plasma proteins (β2-GPI, prothrombin, protein C, protein S, and annexin V) were immobilized on γ-irradiated or plain polystyrene plates. Results: All types of aPL Abs were frequently observed in the patients with SLE when γ-irradiated polystyrene plates were used (51 of 168 cases positive for anti-β2-GPI, 94 of 168 cases positive for anti-prothrombin, 36 of 168 cases positive for anti-protein C, 47 of 168 cases positive for anti-protein S, and 50 of 168 cases positive for anti-annexin V), whereas no Abs to these plasma proteins were detected when plain polystyrene plates were used. Multivariate analysis confirmed that both anti-β2-GPI and anti-prothrombin Abs were significant risk factors for arterial thrombosis [odds ratios (ORs), 8.8 and 14.5, respectively; 95% confidence intervals (CIs), 3.2–25 and 1.8–116, respectively] but not for venous thrombosis. The presence of anti-protein S Abs was a significant risk factor for venous thrombosis (OR, 30.4; CI, 3.3–281) but not for arterial thrombosis. The only significant risk factor for fetal loss was the presence of anti-annexin V Abs (OR, 5.9; CI, 1.4–14.8). Conclusions: Patients with SLE frequently have some aPL Abs to β2-GPI, prothrombin, protein C, protein S, and annexin V. Thrombotic complications in SLE may depend on the antigenic specificities of these Abs, alone or in combination.

Trombophylia Prevalence in 444 Patients with Clinical Suspicion of Thrombosis.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4088-4088
Author(s):  
Joao Carlos C. Guerra ◽  
Valdir F. Aranda ◽  
Claudio A. Mendes ◽  
Nelson Hamerschlak ◽  
Nydia S. Bacal ◽  
...  
Keyword(s):  
Laboratory Investigation ◽  
Lupus Anticoagulant ◽  
Protein C ◽  
Retrospective Chart Review ◽  
Protein S ◽  
Clinical Suspicion ◽  
Factor V ◽  
C Protein ◽  
Populations At Risk ◽  
Prothrombin Mutation

Abstract Objetives: to evaluate the prevalence of genetic polymorphism of coagulation factors: Leyden factor V (FVL), prothrombin mutation, deficiency of coagulation inhibitors, protein C, protein S and antithrombin (AT), test for the lupus anticoagulant/anticardiolipin and homocistein levels, during the laboratory investigation of patients with clinical suspicion of thrombosis. Patients and methods: This was done as a retrospective chart review study on 444 patients admitted at our hospital between November 2003 and December 2004 ( males 188, females 256). Medium age was 46 years. Prothrombin mutation and Factor V Leyden were searched by multiplex PCR, Protein C, S and lupus anticoagulant were studied by coagulometric methods, AT by chromogenic method, anticardiolipin by immunoenzymatic assay and homocistein by immunometric assay. Statistical analysis was performed using exact Fischer test or × Pearson test. Results and conclusions: Prevalence of FVL was 32 cases, 7.2 %, 2 homozygotes and 30 heterozygotes. Prothrombyn mutation was found in 25 cases, 5.6 %, 1 homozygote and 24 heterozygotes. On 57 cases with genetic alteration 46 (80%) had thrombosis, 39 venous and 7 arterial. On 183 cases that done anticardiolipin test 27 cases were positive, 14.7 % (18 IgG, 6 IgM and 3 IgA). On those cases 22, 81.4 % had thrombosis, 15 venous and 7 arterial. All 3 cases with lupus anticoagulant had thrombosis. Hyperhomocistein was found in 7 cases, 3.2 %, with 4 cases associated with venous thrombosis and 1 with arterial thrombosis. Deficiencies of Protein C, Protein S and AT were found in 117 cases, l2.8 %, associated with 63 cases of thrombosis, 52 venous and 11 arterial, 56.3 %. Pathogenesis of thrombosis is complex and clearly associated with genetic and environmental factors - risk factors. On populations at risk for thrombosis laboratory investigation is essential.

scholarly journals Inherited Hypercoagulable States

1997 ◽  
Vol 2 (4) ◽  
pp. 313-320 ◽  
Author(s):  
A Koneti Rao ◽  
Sunita Sheth ◽  
Robert Kaplan
Keyword(s):  
Arterial Thrombosis ◽  
Protein C ◽  
Factor V Leiden ◽  
Protein S ◽  
Factor V ◽  
Thromboembolic Events ◽  
Heparin Cofactor Ii ◽  
Predisposing Factor ◽  
Inherited Thrombophilia ◽  
Prothrombin Gene

Hypercoagulable states are a group of conditions associated with increased predisposition to thromboembolic events. Most of the inherited abnormalities recognized to date are associated with venous thromboembolism (VTE) rather than arterial thrombosis. The well-recognized inherited hypercoagulable states are the deficiencies of antithrombin, protein C and protein S, and the resistance to APC (factor V Leiden). These entities represent aberrations in the natural anticoagulant systems that exist in plasma. Other causes of inherited thrombophilia include abnormalities in the proteins of the fibrinolytic system, dysfibrinogenemias, deficiency of heparin cofactor II, abnormal thrombomodulin, elevated levels of histidine-rich glycoprotein, and the recently described variation in the prothrombin gene. One entity that has become firmly established as a predisposing factor for recurrent VTE is hyperhomocysteinemia. About half of VTE episodes in patients with inherited thrombophilias occur in relation to events that are generally recognized as predisposing states, such as surgery, pregnancy (particularly puerperium) and immobilization. In this review, the risks of VTE associated with inherited risk factors are discussed, and guidelines for the diagnosis and management are presented.

Activated Protein C Sensitivity, Protein C, Protein S and Coagulation in Normal Pregnancy

1998 ◽  
Vol 79 (06) ◽  
pp. 1166-1170 ◽  
Author(s):  
J. Brennand ◽  
J. A. Conkie ◽  
F. McCall ◽  
I. A. Greer ◽  
Isobel Walker ◽  
...  
Keyword(s):  
Protein C ◽  
Activated Protein C ◽  
Factor V Leiden ◽  
Protein S ◽  
Coagulation Factors ◽  
Normal Pregnancy ◽  
Factor V ◽  
C Protein ◽  
Sensitivity Ratio ◽  
Protein C Activity

SummaryA prospective study of activated protein C sensitivity, protein C, protein S, and other coagulation factors in 239 women during normal pregnancy was carried out. Protein C activity appeared unaffected by gestation, although an elevation of protein C activity was observed in the early puerperium. A fall in total and free protein S with increasing gestation was observed. Activated protein C sensitivity ratio (APC:SR) showed a progressive fall through pregnancy. This fall correlated with changes in factor VIIIc, factor Vc and protein S. 38% of subjects, with no evidence of Factor V Leiden or anticardiolipin antibodies, showed a low APC:SR (APC:SR <2.6) in the third trimester of pregnancy. Aside from a significant reduction in birth weight, no difference in pregnancy outcome was observed between these subjects and those with a normal APC:SR. Activated protein C sensitivity ratio, modified by pre-dilution of patient samples with factor V depleted plasma, showed no consistent trend with gestation.

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