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.

ProC® Global Assay in the Evaluation of Women with History of Severe Preeclampsia or HELLP Syndrome

2002 ◽  
Vol 8 (4) ◽  
pp. 319-324 ◽  
Author(s):  
Lothar Heilmann ◽  
Georg-Friedrich v. Tempelhoff ◽  
Kuhnhart Pollow
Keyword(s):  
Hellp Syndrome ◽  
Protein C ◽  
Activated Protein C ◽  
Factor V Leiden ◽  
Protein S ◽  
Anticardiolipin Antibodies ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
Lupus Anticoagulants ◽  
Apc Resistance

Preeclampsia/HELLP syndrome has been associated with a high incidence of defects in the protein C pathway and increased anticardiolipin-antibodies/lupus anticoagulants. It is also apparent that thrombophilia is responsible for other pregnancy complications, such as recurrent spontaneous abortion, fetal growth restriction, intrauterine fetal death, and abruptio placentae. ProC® Global is a new global clotting assay designed to evaluate the abnormalities in the protein C anticoagulant pathway. It is based on the ability of endogenous activated protein C, generated by activation of protein C by Protac®, to prolong an activated partial thromboplastin time. A total of 61 patients with a history of severe preeclampsia or HELLP syndrome and 61 normal pregnant women (controls) were evaluated, 15 of whom had factor V Leiden mutation, 12 had protein C/S deficiency, 30 had a repeated lupus anticoagulants, and 27 increased anticardiolipin antibodies (ACA). All carriers of factor V Leiden mutation (N= 15) as well as all the patients with low activated protein C (APC) resistance ratio (N= 15) had a ProC® Global normalized ratio (NR) less than 0.80 (sensitivity 100%). Twenty-four patients positive for the lupus anticoagulants (LA) and 19 patients positive for ACA (> 5.0 IgG U/mL) had a ProC® Global NR less than 0.8, while six and eight, respectively, had a ProC® Global NR greater than 0.8 (sensitivity, 70%-80%). The detection of a reduced protein C/protein S activity (<70%) was low (sensitivity, 33%-44%). In 25 cases with pathologic ProC® Global results, a thrombophilic defect (protein S/LA/ACA without APC resistance) was diagnosed in 18 women; but in 7 cases, no known thrombophilic defect was present. ProC® Global is a new screening test to identify patients with defects of the protein C system and an activated clotting system in preeclampsia but cannot correctly cover each thrombophilic component.

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.    

Fundamentals and Patient Evaluation

2006 ◽  
Author(s):  
Richard C. Becker ◽  
Frederick A. Spencer
Keyword(s):  
General Population ◽  
Venous Thrombosis ◽  
Protein C ◽  
Factor V Leiden ◽  
Protein S ◽  
Incidence Rates ◽  
Factor V ◽  
Inherited Thrombophilia ◽  
Occult Malignancy ◽  
History Of

Thrombophilia is the term used to describe a tendency toward developing thrombosis. This tendency may be inherited, involving polymorphism in gene coding for platelet or clotting factor proteins, or acquired due to alterations in the constituents of blood and/or blood vessels. An inherited thrombophilia is likely if there is a history of repeated episodes of thrombosis or a family history of thromboembolism. One should also consider an inherited thrombophilia when there are no obvious predisposing factors for thrombosis or when clots occur in a patient under the age of 45. Repeated episodes of thromboembolism occurring in patients over the age of 45 raise suspicion for an occult malignancy. A summary of inherited thrombophilias are summarized in Table 24.1. This list continues to grow, as new genetic polymorphisms and combined mutations are being detected. The prevalence of common thrombophilias is shown in Figure 24.1. Factor V Leiden (FVL) mutation and hyperhomocysteinemia are present in nearly 5% of the general population and are often found in patients with venous thrombosis, while deficiencies of antithrombin (AT), protein C, and protein S are relatively uncommon. Elevated levels of factor VIII (FVIII) are uncovered frequently in the general population and in patients with thrombosis. This is not surprising as FVIII is an acute-phase reactant that increases rapidly after surgery or trauma; however, prospective studies have shown that FVIII elevation in some patients cannot be attributed to a stress reaction and probably represents mutations in the genes regulating FVIII synthesis or release (Kyrle et al., 2000). The same may be true for factors IX and XI. The relative risks for thrombosis among patients with inherited thrombophilias have been determined. While AT mutations are the least common, they are associated with a substantial risk of venous thrombosis; similar risk is seen with protein C and S deficiency. In contrast, the lifetime risk of having a thromboembolic event in an individual heterozygous for FVL is comparatively low (Martinelli et al., 1998). Incidence rates markedly increase with age, and are highest among those with AT deficiency, followed by protein C and protein S, and least with FVL.

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.

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.

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

1996 ◽  
Vol 75 (03) ◽  
pp. 393-394 ◽  
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.

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.

Resistance to activated protein C, the FV: Q506 allele, and venous thrombosis

1998 ◽  
Vol 18 (01) ◽  
pp. 1-10
Author(s):  
A. Hillarp ◽  
S. Rosen ◽  
B. Zöller ◽  
B. Dahlbäck
Keyword(s):  
Venous Thrombosis ◽  
Protein C ◽  
Antithrombin Iii ◽  
Single Point ◽  
Activated Protein C ◽  
Factor Xa ◽  
Protein S ◽  
Single Point Mutation ◽  
Factor V ◽  
Endothelial Cell Surface

SummaryVitamin K-dependent protein C is an important regulator of blood coagulation. After its activation on the endothelial cell surface by thrombin bound to thrombomodulin, it cleaves and inactivates procoagulant cofactors Va and Villa, protein S and intact factor V working as cofactors. Until recently, genetic defects of protein C or protein S were, together with antithrombin III deficiency, the established major causes of familial venous thromboembolism, but they were found in fewer than 5-10% of patients with thrombosis. In 1993, inherited resistance to activated protein C (APC) was described as a major risk factor for venous thrombosis. It is found in up to 60% of patients with venous thrombosis. In more than 90% of cases, the molecular background for the APC resistance is a single point mutation in the factor V gene, which predicts substitution of an arginine (R) at position 506 by a glutamine (Q). Mutated factor V (FV: Q506) is activated by thrombin or factor Xa in normal way, but impaired inactivation of mutated factor Va by APC results in life-long hypercoagulability. The prevalence of the FV:Q506 allele in the general population of Western countries varies between 2 and 15%, whereas it is not found in several other populations with different ethnic backgrounds. Owing to the high prevalence of FV:Q506 in Western populations, it occasionally occurs in patients with deficiency of protein S, protein C, or antithrombin III. Individuals with combined defects suffer more severely from thrombosis, and often at a younger age, than those with single defects, suggesting severe thrombophilia to be a multigenetic disease.

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.

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