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

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.

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Elevated Levels of Prothrombin Activation Fragment 1+2 in Plasma from Patients with Heterozygous Arg506 to Gin Mutation in the Factor V Gene (APC-Resistance) and/or Inherited Protein S Deficiency

Thrombosis and Haemostasis ◽

10.1055/s-0038-1650259 ◽

1996 ◽

Vol 75 (02) ◽

pp. 270-274 ◽

Cited By ~ 57

Author(s):

Benget Zöller ◽

Johan Holm ◽

Peter Svensson ◽

Björn Dahlbäck

Keyword(s):

Plasma Concentration ◽

Protein C ◽

Protein S ◽

Factor V ◽

Protein S Deficiency ◽

Apc Resistance ◽

S Deficiency ◽

Increased Risk ◽

Factor V Gene ◽

V Gene

SummaryInherited resistance to activated protein C (APC-resistance), caused by a point mutation in the factor V gene leading to replacement of Arg(R)506 with a Gin (Q), and inherited protein S deficiency are associated with functional impairment of the protein C anticoagulant system, yielding lifelong hypercoagulability and increased risk of thrombosis. APC-resistance is often an additional genetic risk factor in thrombosis-prone protein S deficient families. The plasma concentration of prothrombin fragment 1+2 (F1+2), which is a marker of hyper-coagulable states, was measured in 205 members of 34 thrombosis-prone families harbouring the Arg506 to Gin mutation (APC-resistance) and/or inherited protein S deficiency. The plasma concentration of F1+2 was significantly higher both in 38 individuals carrying the FV:Q506 mutation in heterozygous state (1.7 ± 0.7 nM; mean ± SD) and in 48 protein S deficient cases (1.9 ± 0.9 nM), than in 100 unaffected relatives (1.3 ±0.5 nM). Warfarin therapy decreased the F1+2 levels, even in those four patients who had combined defects (0.5 ± 0.3 nM). 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.

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Thrombophilia And Arterial Ischemic Stroke

Advances in Bioscience and Clinical Medicine ◽

10.7575/aiac.abcmed.ca1.45 ◽

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.

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Factor V Gene Mutation Is a Risk Factor for Cerebral Venous Thrombosis

Thrombosis and Haemostasis ◽

10.1055/s-0038-1650284 ◽

1996 ◽

Vol 75 (03) ◽

pp. 393-394 ◽

Cited By ~ 95

Author(s):

I Martinelli ◽

G Landi ◽

G Merati ◽

R Cella ◽

A Tosetto ◽

...

Keyword(s):

Venous Thrombosis ◽

Cerebral Venous Thrombosis ◽

Protein C ◽

Dna Analysis ◽

Protein S ◽

Factor V ◽

Antithrombin Deficiency ◽

Apc Resistance ◽

Factor V Gene ◽

V Gene

SummaryTo evaluate the association between coagulation defects and cerebral venous thrombosis, a case-control study was conducted in 25 patients who had no autoimmune, neoplastic or infectious disease and 75 healthy individuals. There were no patients with deficiency of protein C or protein S. Four had resistance to activated protein C (APC) and one had APC resistance associated with antithrombin deficiency. APC resistance was investigated by DNA analysis, and diagnosed by the presence of a point mutation in the factor V gene, which predicts replacement of Arg506 with Gin at one of the two APC cleavage sites in activated factor V. The prevalence of APC resistance was 20% in patients and 2.7% in controls. This difference was statistically significant (p = 0.01) and the odds ratio was 9.1. A circumstantial factor predisposing to cerebral venous thrombosis (such as oral contraceptive intake, pregnancy, puerperium, trauma or prolonged immobilization) was reported in 72% of cases. In conclusion, APC resistance is the most frequent coagulation abnormality associated with cerebral venous thrombosis.

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The G1691A Mutation of the Factor V Gene (Factor V Leiden) and the G20210A Mutation of the Prothrombin Gene as Risk Factors in Thrombotic Microangiopathies

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/1076029607311778 ◽

2009 ◽

Vol 15 (3) ◽

pp. 360-363 ◽

Cited By ~ 2

Author(s):

Christoph Sucker ◽

Christine Kurschat ◽

Gerd R. Hetzel ◽

Bernd Grabensee ◽

Beate Maruhn-Debowski ◽

...

Keyword(s):

Risk Factors ◽

Factor V Leiden ◽

Factor V ◽

Thrombotic Microangiopathies ◽

G20210a Mutation ◽

Factor V Gene ◽

Prothrombin Gene ◽

V Gene

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

Sao Paulo Medical Journal ◽

10.1590/1516-3180.2013.1316369 ◽

2013 ◽

Vol 131 (6) ◽

pp. 384-388 ◽

Cited By ~ 5

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.

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Factor V gene G1691A mutation, prothrombin gene G20210A mutation, and MTHFR gene C677T mutation are not risk factors for pulmonary thromboembolism in Chinese population

Thrombosis Research ◽

10.1016/s0049-3848(02)00064-6 ◽

2002 ◽

Vol 106 (1) ◽

pp. 7-12 ◽

Cited By ~ 46

Author(s):

Yanhui Lu ◽

Yanfen Zhao ◽

Guozhang Liu ◽

Xiaoling Wang ◽

Zhihong Liu ◽

...

Keyword(s):

Risk Factors ◽

Chinese Population ◽

Pulmonary Thromboembolism ◽

Mthfr Gene ◽

Factor V ◽

G20210a Mutation ◽

C677t Mutation ◽

Factor V Gene ◽

Prothrombin Gene ◽

V Gene

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Anti-Ige (Omalizumab) Improved Trombotic Emboli by Elevating Activated Protein C, Protein S, and Antithrombin III in a Case of Prothrombin G20210A Mutation: Long Term Follow-Up

Journal of Genetic Disorders & Genetic Reports ◽

10.4172/2327-5790.1000129 ◽

2016 ◽

Vol 05 (01) ◽

Author(s):

Arzu Didem Yalcin ◽

Betul Celik

Keyword(s):

Protein C ◽

Antithrombin Iii ◽

Activated Protein C ◽

Protein S ◽

Prothrombin G20210a ◽

C Protein ◽

G20210a Mutation ◽

Long Term Follow Up

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Heightened Thrombin Generation in Individuals with Resistance to Activated Protein C

Thrombosis and Haemostasis ◽

10.1055/s-0038-1650351 ◽

1996 ◽

Vol 75 (05) ◽

pp. 703-705 ◽

Cited By ~ 32

Author(s):

Ida Martinelli ◽

Bianca Bottasso ◽

Francesca Duca ◽

Elena Faioni ◽

Pier Mannuccio Mannucci

Keyword(s):

Protein C ◽

Thrombin Generation ◽

Significant Positive Correlation ◽

Activated Protein C ◽

Protein S ◽

Factor V ◽

Factor V Gene ◽

V Gene ◽

Previous Occurrence ◽

Thrombotic Tendency

SummaryWe chose to evaluate whether or not a state of biochemical hypercoagulability was present in 74 individuals (69 heterozygotes and 5 homozygotes) resistant to activated protein C (APC) due to the Arg506 -> Gin mutation in the factor V gene. To this end, plasma levels of two markers of thrombin formation, prothrombin fragment 1+2 (F1+2) and thrombin-antithrombin complexes (TAT), were measured. High levels of F1+2 and TAT were found in 32% and 23% of APC-resistant individuals vs 4% in controls. The levels of these markers tended to be particularly elevated in three homozygous subjects. A significant positive correlation between F1+2 and TAT was present in APC-resistant individuals. No relationship between marker values and the previous occurrence of thrombotic episodes was found. Therefore, by measuring F1+2 and TAT a state of biochemical hypercoagulability has been identified in about one-third of APC-resistant individuals. This frequency is similar to that previously observed in comparable individuals with inherited deficiencies of protein C and protein S, which are usually associated with a stronger thrombotic tendency than APC-resistant individuals.

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