scholarly journals High Mortality and Risk of Severe Sepsis in in-Hospital Cardiac Arrest Patients with Antithrombin Deficiency: Analysis of National Inpatient Sample Database

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4995-4995
Author(s):  
Tien-Chan Hsieh ◽  
Guangchen Zou ◽  
Gin Yi Lee ◽  
Pramuditha Rajapakse ◽  
Yee Hui Yeo
Keyword(s):  
Cardiac Arrest ◽  
Severe Sepsis ◽  
Protein C ◽  
Antithrombin Iii ◽  
Factor V Leiden ◽  
P Value ◽  
Factor V ◽  
Inherited Thrombophilia ◽  
At Iii ◽  
Hospital Cardiac Arrest

Abstract Background: Previous studies found the association between hereditary thrombophilia (HT) and increased risk of inpatient arterial thromboembolism, such as myocardial infarction and ischemic stroke. Nevertheless, the outcomes of hospitalized HT patients with cardiac arrest remains unclear. We aim to investigate the outcomes of inherited thrombophilia after in-hospital cardiac arrest (IHCA). Methods: This is a retrospective analysis of National Inpatient Sample database with 2016-2018 data years. We included adult (age above 18 years old) who had IHCA. IHCA, various types of HT (Factor V Leiden/activated protein C resistance, prothrombin mutation, deficiencies of antithrombin [AT] III, protein C or S deficiencies, other inherited thrombophilia), and other comorbidities were identified with International Classification of Diseases, 10th Revision, Clinical Modification Procedure Codes and Diagnosis Codes. Charlson Comorbidity Index (CCI) was used to adjust for comorbidities. Age distribution was analyzed with unpaired two-samples t-test. Gender and racial group distribution were compared with Chi-square test. Primary outcome was mortality. All independent factors associated with IHCA in inherited thrombophilia were determined by weighted multivariable logistic regression. SAS and R were used for statistical analysis. Results: Among 67,351 adult patients with IHCA, 620 patients had at least one diagnosis of HT (Factor V Leiden: 86; antithrombin III deficiency: 235; protein C/S deficiencies: 301; prothrombin gene mutation: 6; 5 cases have both factor V Leiden and protein C/S deficiencies; 3 cases have both antithrombin III and protein C/S deficiencies). Patients with HT were significant younger (mean age: 60.6 vs 65.9, p value < 0.0001) with fewer comorbidities (mean CCI: 5.32 vs 5.81, p value <0.0005). There was no significant difference in gender and racial groups distribution. HT was not associated with risk of mortality after IHCA (adjusted odds ratio (aOR): 0.98, Confidence interval (CI): 0.82 - 1.16, p value = 0.75). Nevertheless, subgroup analysis with different types of HT revealed increased mortality in AT III deficiency group (aOR: 1.40, CI: 1.02 - 1.91 p value < 0.05). On the contrary, factor V Leiden and protein C/S deficiencies had a weak association of lower mortality (aOR: 0.70, p value < 0.1; aOR: 0.80, p value = 0.06). AT III deficiency was also associated with higher risk of developing severe sepsis (aOR: 1.56, p < 0.005). Myocardial infarction, ischemic stroke, pulmonary embolism, and deep venous thrombosis were not significantly associated with HT after adjusted for other potential confounders. Conclusion: HT patients who developed IHCA were younger with fewer underlying comorbidities. Only AT III deficiency subgroup was associated with higher odds of mortality and severe sepsis. Factor V Leiden and protein C/S deficiencies had a tendency of favorable outcomes. The unfavorable outcome of AT III deficiency subgroup couldn't be attributed to either arterial or venous thromboembolism. Disclosures No relevant conflicts of interest to declare.

A Heparin Cofactor II Mutation (HCII Rimini) Combined with Factor V Leiden or Type I Protein C Deficiency in Two Unrelated Thrombophilic Subjects

1996 ◽  
Vol 76 (04) ◽  
pp. 505-509 ◽  
Author(s):  
F Bernardi ◽  
C Legnani ◽  
F Micheletti ◽  
B Lunghi ◽  
P Ferraresi ◽  
...  
Keyword(s):  
Protein C ◽  
Antithrombin Iii ◽  
Factor V Leiden ◽  
Type I ◽  
Factor V ◽  
Protein C Deficiency ◽  
Heparin Cofactor Ii ◽  
Factor V Leiden Mutation ◽  
Heterozygous Condition ◽  
Inherited Thrombophilia

Summary305 patients with juvenile thromboembolic episodes were screened for the presence of heparin cofactor II deficiency. The heterozygous deletion of two bases was found in the exon 5 of the heparin cofactor II gene in two unrelated patients, very likely due to a founder effect. This molecular lesion, causing a frameshift and elongated translation, affects the core of the molecule and should cause the complete unfolding of the protein, which is in accordance with the observed type I deficiency. The corresponding region of antithrombin III gene is affected by a cluster of frameshift mutations suggesting that heparin cofactor II and antithrombin III could share similar mutational patterns.The heparin cofactor II gene alteration was associated with, in one patient, the factor V Leiden mutation and, in the other, type I protein C deficiency. The tracing of the single defects in several family members indicated that the mutations became clinically manifest only when present in the doubly heterozygous condition. This study provides two examples, based on molecular findings, of the interplay of risk factors which is potentially useful to define a role for heparin cofactor II deficiency in inherited thrombophilia.

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.

Hereditary Thrombophilia as a Model for Multigenic Disease

1999 ◽  
Vol 82 (08) ◽  
pp. 662-666 ◽  
Author(s):  
Sandra J. Hasstedt ◽  
Mark F. Leppert ◽  
George L. Long ◽  
Edwin G. Bovill
Keyword(s):  
Risk Factors ◽  
Protein C ◽  
Antithrombin Iii ◽  
Factor V Leiden ◽  
Protein S ◽  
Factor V ◽  
Antithrombin Deficiency ◽  
Factor V Leiden Mutation ◽  
The Past ◽  
S Deficiency

IntroductionNearly 150 years ago, Virchow postulated that thrombosis was caused by changes in the flow of blood, the vessel wall, or the composition of blood. This concept created the foundation for subsequent investigation of hereditary and acquired hypercoagulable states. This review will focus on an example of the use of modern genetic epidemiologic analysis to evaluate the multigenic pathogenesis of the syndrome of juvenile thrombophilia.Juvenile thrombophilia has been observed clinically since the time of Virchow and is characterized by venous thrombosis onset at a young age, recurrent thrombosis, and a positive family history for thrombosis. The pathogenesis of juvenile thrombophilia remained obscure until the Egeberg observation, in 1965, of a four generation family with juvenile thrombophilia associated with a heterozygous antithrombin deficiency subsequently identified as antithrombin Oslo (G to A in the triplet coding for Ala 404).1,2 The association of a hereditary deficiency of antithrombin III with thrombosis appeared to support the hypothesis, first put forward by Astrup in 1958, of a thrombohemorrhagic balance.3 He postulated that there is a carefully controlled balance between clot formation and dissolution and that changes in conditions, such as Virchow’s widely encompassing triad, could tip the balance toward thrombus formation.The importance of the thrombohemorrhagic balance in hypercoagulable states has been born out of two lines of investigation: evidence supporting the tonic activation of the hemostatic mechanism and the subsequent description of additional families with antithrombin deficiency and other genetically abnormal hemostatic proteins associated with inherited thrombophilia. Assessing the activation of the hemostatic mechanism in vivo is achieved by a variety of measures, including assays for activation peptides generated by coagulation enzyme activity. Activation peptides, such as prothrombin fragment1+2, are measurable in normal individuals, due to tonic hemostatic activity and appear elevated in certain families with juvenile thrombophilia.4 In the past 25 years since Egeberg’s description of antithrombin deficiency, a number of seemingly monogenic, autosomal dominant, variably penetrant hereditary disorders have been well established as risk factors for venous thromboembolic disease. These disorders include protein C deficiency, protein S deficiency, antithrombin III deficiency, the presence of the factor V Leiden mutation, and the recently reported G20210A prothrombin polymorphism.5,6 These hereditary thrombophilic syndromes exhibit considerable variability in the severity of their clinical manifestations. A severe, life-threatening risk for thrombosis is conferred by homozygous protein C or protein S deficiency, which if left untreated, leads to death.7,8 Homozygous antithrombin III deficiency has not been reported but is also likely to be a lethal condition. Only a moderate risk for thrombosis is conferred by the homozygous state for factor V Leiden or the G20210A polymorphism.9,10 In contrast to homozygotes, the assessment of risk in heterozygotes, with these single gene disorders, has been complicated by variable clinical expression in family members with identical genotypes.11 Consideration of environmental interactions has not elucidated the variability of clinical expression. Consequently, it has been postulated that more than one genetic risk factor may co-segregate with a consequent cumulative or synergistic effect on thrombotic risk.12 A number of co-segregating risk factors have been described in the past few years. Probably the best characterized interactions are between the common factor V Leiden mutation, present in 3% to 6% of the Caucasian population,13,14 and the less common deficiencies of protein C, protein S, and antithrombin III. The factor V Leiden mutation does not, by itself, confer increased risk of thrombosis. The high prevalence of the mutation, however, creates ample opportunity for interaction with other risk factors when present.The G20210A prothrombin polymorphism has a prevalence of 1% to 2% in the Caucasian population and, thus, may play a similar role to factor V Leiden. A number of small studies have documented an interaction of G20210A with other risk factors.15-17 A limited evaluation of individuals with antithrombin III, protein C, or protein S deficiency revealed a frequency of 7.9% for the G20210A polymorphism, as compared to a frequency of 0.7% for controls.18 The G20210A polymorphism was observed in only 1 of the 6 protein C-deficient patients.18 In the present state, the elucidation of risk factors for venous thromboembolic disease attests to the effectiveness of the analytical framework constructed from the molecular components of Virchow’s triad, analyzed in the context of the thrombohemorrhagic balance hypothesis. Two investigative strategies have been used to study thromobophilia: clinical case-control studies and genetic epidemiologic studies. The latter strategy has gained considerable utility, based on the remarkable advances in molecular biology over the past two decades. Modern techniques of genetic analysis of families offer important opportunities to identify cosegregation of risk factors with disease.19 The essence of the genetic epidemiologic strategy is the association of clinical disease with alleles of specific genes. It is achieved either by the direct sequencing of candidate genes or by demonstration of linkage to genetic markers.

scholarly journals Heritable Thrombophilia in Venous Thromboembolism in Northern Pakistan: A Cross-Sectional Study

2021 ◽  
Vol 2021 ◽  
pp. 1-5
Author(s):  
Maria Khan ◽  
Chaudhry Altaf ◽  
Hamid Saeed Malik ◽  
Muhammad Abdul Naeem ◽  
Aamna Latif
Keyword(s):  
Venous Thromboembolism ◽  
Protein C ◽  
Gene Mutations ◽  
Factor V Leiden ◽  
Factor V ◽  
Protein C Deficiency ◽  
Factor V Leiden Mutation ◽  
Inherited Thrombophilia ◽  
At Deficiency ◽  
Prothrombin Gene

Background. Venous thromboembolism (VTE) is referred to as formation of clots in a deep vein or lodging of thrombus towards the lungs which could be fatal yet preventable. The risk of developing VTE can be increased by various factors. Where there are innumerable acquired causes, the possibility of inherited thrombophilia cannot be ignored. In view of this, we have evaluated all patients with venous thromboembolism for inherited thrombophilia. Objective. To evaluate the frequencies of antithrombin (AT) deficiency, protein C and S deficiencies, Factor V Leiden, and prothrombin gene mutations in patients harboring venous thromboembolism. Materials and Methods. A study comprising of 880 patients who were presented with manifestations of venous thromboembolism was conducted from July 2016 to June 2017. A blood sample collected from patients was screened for thrombophilia defects encompassing AT, protein C and S deficiencies, Factor V Leiden, and prothrombin gene mutations. All acquired causes of thrombosis were excluded. Results. Of 880 patients who underwent screening for thrombophilia, 182 patients demonstrated VTE history. Their age ranged from 1 to 58 years. Males constituted a predominant group. About 45 (24.7%) patients had evidence of heritable thrombophilia. Of these, 20 (10.9%) had AT deficiency, 9 (4.9%) had Factor V Leiden mutation, 6 (3.2%) had protein C deficiency, whereas protein S deficiency and prothrombin gene mutation both were found in 5 (2.7%) patients. Conclusion. Our study illustrated the highest frequency of antithrombin deficiency among other investigated thrombophilia defects.

scholarly journals Evaluation of Direct Oral Anticoagulants in the Treatment of Venous Thromboembolism for Inherited Thrombophilia Disorders

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5007-5007 ◽  
Author(s):  
Ali McBride ◽  
Reem Diri ◽  
Ravitharan Krishnadasan ◽  
Pavani Chalasani ◽  
Ivo Abraham ◽  
...  
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Protein C ◽  
Factor V Leiden ◽  
Secondary Prophylaxis ◽  
Factor V ◽  
Inherited Thrombophilia ◽  
Dvt Prophylaxis ◽  
Prothrombin Gene ◽  
Baseline Characteristics

Abstract Background Venous thromboembolism can be classified according to the presence of either environmental or genetic risk factors. Risk factors for thrombosis can include activated protein C resistance, and heritable including deficiencies of antithrombin, protein C or protein S. Factor V Leiden deficiency and prothrombin gene mutations are some of the more common thrombophilias, with a slight increased risk for venous thromboembolism (VTE). Current guidelines suggest the use of low-molecular weight heparins for secondary prophylaxis in patients with VTE. However, there is a lack of data on the use of Direct Oral Anticoagulant (DOACs) in patients with inherited thrombophilia. We evaluated our use of rivaroxaban in patients with thrombophilia disorders treated for secondary DVT prophylaxis. Method We performed a retrospective evaluation of patients in our institution with inherited thrombophilia with an active VTE diagnosis who received DOACs for secondary prophylaxis from November 2013 until April 2016. Data collected included patient demographics, inherited thrombophilia mutation, previous history of VTE, prior treatments, and efficacy and safety of anticoagulation with DOACs. Results We had 13 patients with inherited thrombophilia mutation and 4 patients diagnosed with concomitant cancer (non-Hodgkin lymphoma, melanoma, and 2 with breast cancer) (Table 1). Out of 13 patients 3 failed warfarin, and one failed fondaparinux prior to switching to a DOAC. Mutation with heterozygous Factor V Leiden deficiency was reported in 7 patients, while mutations with Protein C and/or S deficiency were found in 4 patients. One patient had both Factor V Leiden and Protein C deficiency mutations. The prothrombin gene mutation was identified in one patient. The median of length of therapy was 2 years with 8/13 still on rivaroxaban in April 2016. The shortest treatment duration was 41 days for a patient who failed rivaroxaban with a second clot and was switched to apixaban without subsequent treatment failure. Two patients experienced 4 non-major episodes of gastrointestinal bleeding, nose bleeding and dark stool. One patient developed rash with noted bruising during their rivaroxaban therapy. Conclusion: This is the first report on outcomes for secondary DVT prophylaxis with DOACs in patients with underlying thrombophilia mutations. Safety and efficacy of DOACs for secondary VTE prophylaxis yielded favorable results; however, future prospective studies in the setting of thrombophilia are warranted. Table 1 Summary of baseline characteristics and outcomes. Table 1. Summary of baseline characteristics and outcomes. Disclosures McBride: Sanofi: Research Funding.

4g/5g Prevalence in 223 Patients with Thrombosis and in 162 Healthy Controls, from the Centre Region of Portugal.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4057-4057
Author(s):  
Rosa Maia ◽  
Emilia Cortesao ◽  
Catarina Geraldes ◽  
Luis Simoes ◽  
Carla Simoes ◽  
...  
Keyword(s):  
Protein C ◽  
Antithrombin Iii ◽  
Factor V Leiden ◽  
Protein S ◽  
Mthfr C677t ◽  
Insertion Polymorphism ◽  
Factor V ◽  
Centre Region ◽  
History Of ◽  
Pai 1

Abstract A deletion/insertion polymorphism (4G or 5G) in the promoter of the PAI-1 gene has been suggested to be involved in regulation of the synthesis of the inhibitor, the 4G allele being associated with enhanced gene expression, and therefore related with thrombosis. In the present work we studied the prevalence of 4G/5G polymorphism in 223 unrelated patients with history of objectively confirmed thromboembolism, and in 162 healthy unrelated controls, both groups natural from all centre regions of Portugal. In this normal cohort, the prevalence of 4G/4G is 23%, 4G/5G is 38% and 5G/5G is 39%; in the affected population is, respectively, 47%, 21.5% and 30%, which means that 4G/4G is twice more frequent in the patients with thrombosis. When we relate the age of the first thrombosis episodes in the three groups, we find no significative difference, as the respective media is 36.8; 38.6 and 35.5 years in the 4G/4G, 4G/5G and 5G/5G group, respectively. This data suggest that this polymorphism by itself, even in homozygosity, is not associated with earlier thrombosis. In our patients, we studied the presence of Lupus Anticoagulant, Factor V Leiden, Factor IIG20210A, MTHFR C677T, and also Antithrombin III, Protein S and Protein C levels. We analyse the prevalence of the three mutations in patients with DVP, PTE, ischemic and venous CVA and we only find a significative difference in the 4G/4G group: 46.2% patients with DVP and 48.2% patients with PTE (23% in normal cohort). In conclusion, in the centre region of Portugal, the prevalence of 4G/4G is 23%, 4G/5G is 38% and 5G/5G is 39%; in our cohort of unrelated patients the only significative difference is in the 4G/4G group (47%); this variation maintain in the DVP and PTE group. We did not find difference at the age of the first thrombotic episode, in the three groups.

Prevalence of Activated Protein C Resistance Due To Factor V Leiden Mutation among South Asians (India and Pakistan) with Venous Thromboembolism.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4043-4043
Author(s):  
Sirisha Perumandla ◽  
Yelena Patsiornik ◽  
Neetha Mahajan ◽  
Anju Ohri
Keyword(s):  
Protein C ◽  
Chart Review ◽  
South Asians ◽  
Activated Protein C ◽  
Factor V Leiden ◽  
Factor V ◽  
Inherited Thrombophilia ◽  
Apc Resistance ◽  
Fv Leiden ◽  
Work Up

Abstract Objective: To study the prevalence of Activated Protein C (APC) resistance due to Factor V Leiden (FV Leiden) mutation among the first generation immigrants from India and Pakistan with venous thromboembolism (VTE). Introduction: APC resistance due to the substitution of Arginine 506 by Glutamine in coagulation Factor V is caused by G1691A mutation in exon 10 of Factor V gene. This is the commonest cause of inherited thrombophilia in Caucasians, but the frequency of this mutation is low in non-Caucasians. Among subjects in the Physician Health Study, the frequency of FV Leiden was found to be 5.27% in Caucasian Americans vs. 0.45% in Asian Americans. Another study found no mutation in 191 Asian Americans tested. In non-Caucasians with VTE, it is generally considered not cost effective to screen for this mutation. However Asians are a heterogeneous group and the Leiden gene frequency varies among different ethnic populations. While the frequency of FV Leiden gene has been documented to be low in China, Korea, Japan, Thailand, Indonesia etc, the frequency in India and Pakistan is not well studied. Two studies found a carrier frequency of 2% (Rees et al) and 4.2 % (Gou et al) among the general population from India and Pakistan. This is similar to the frequency found in Middle Eastern and European population. We did not come across any study of FV Leiden gene frequency in patients with VTE from India and Pakistan. Patients and Methods: A retrospective chart review of patients of Indian or Pakistani origin seen at Coney Island Hospital, from July 1996 to June 2003, who had a work up for inherited thrombophilia after an episode of VTE. During the chart review age, sex, first or recurrent episode and any predisposing factors such as immobilization, malignancy, hormonal therapy, surgery, pregnancy, and the presence of SLE or MPD were noted. Thrombophilia work up included functional assays for Protein C, S and Antithrombin III, Lupus anticoagulant, ACA and Homocysteine levels. APC resistance was measured by a clotting assay using Factor V depleted plasma and all patients who were borderline or resistant were tested for the presence of FV Leiden mutation by PCR. Results: A total of 18 patients were studied. All had an episode of VTE documented by a Doppler ultrasonography or a Ventilation Perfusion lung scan or a CT angiogram. 3 out of 18 patients (16.6%) had APC resistance. All the three patients were confirmed to be heterozygous for FV Leiden mutation. Two were male and one was a female with a median age of 36 yrs (27, 36 and 57 yrs). The female patient had a recurrent episode, first one occurred during pregnancy, but the second episode had no precipitating events. One male patient had trauma to the leg and was immobilized at the time of the VTE, another male patient was a cab driver by occupation. None of the patients had any other concurrent inherited thrombophilic state. Conclusions: The prevalence of the FV Leiden mutation is significantly high among South Asians with VTE in our study. If the findings are confirmed by a larger study, screening for this mutation for thrombophilia would be relevant in patients of South Asian origin and screening recommendations for family members would be identical to Caucasian population. The high prevalance as in Caucasians suggests a founder effect and possible spread of the mutation by the migration of Neolithic farmers from the Middle East towards Europe and India, ten thousand years ago. This has been confirmed by haplotype analysis.

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