Inherited thrombophilia in pediatric ischemic stroke: an Egyptian study

Pediatric stroke is relatively uncommon, with often subtle clinical presentations. Numerous predisposing risk factors can be both inherited and acquired, including cardiac disease, vascular abnormalities, infectious diseases, collagen tissue diseases, inborn errors of metabolism, anticardiolipin antibody, lupus anticoagulant, deficiencies of protein C, protein S, antithrombin, or plasminogen, and prothrombotic mutations. We explored risk factors, clinical features, and neuroimaging among Egyptian children with ischemic stroke, and estimated the prevalence of inherited thrombophilia. We included 20 children with ischemic stroke, recruited from the Pediatric Neurology Outpatient Clinic (Ain Shams University). Basic clinical evaluations for stroke and genotyping for factor V 1691 G-A (factor V Leiden), prothrombin 20210 G-A mutations, and methylenetetrahydrofolate reductase 677 C-T polymorphisms were performed using real-time polymerase chain reaction, with fluorescent melting curve detection analysis. Ten patients (50%) manifested methylenetetrahydrofolate reductase polymorphisms (six homozygotes and four heterozygotes). Heterozygous factor V Leiden was present in five (25%), whereas prothrombin mutation was present in only one (5%). Five patients (25%) manifested combined prothrombotic abnormalities. Thirteen demonstrated evidence of inherited thrombophilic disorder; 25% manifested more than one mutation. For appropriate risk assessment, even in the presence of overt acquired thrombotic risk factors, physicians should request complete thrombophilia screening for patients with stroke.     

Inherited thrombophilia in childhood arterial stroke: data from Lebanon

Pediatric ischemic stroke still represents a burden, and more than half of the survivors will experience cognitive or motor disabilities. The objective of this study was to investigate the role of thrombophilia in a cohort of children with arterial ischemic stroke. The records of infants and children with clinically and radiologically confirmed stroke were reviewed. Patients with venous or perinatal stroke were not included. Thirty-three patients were diagnosed with arterial ischemic stroke. The male/female ratio was 1.75:1. The median age was 4 years. The most frequent clinical manifestations were hemiparesis (54.5%) and seizures (33.3%). Genetic thrombophilia testing was available on 24 patients. Nine of the 24 patients (37.5%) were heterozygous for factor V Leiden. None of the patients carried the factor II G20210A variant. Ten patients (41.7%) were heterozygous and 3 (12.5%) were homozygous for methylenetetrahydrofolate reductase (MTHFR) C677T variant. Fifteen patients (62.5%) had one or more genetic polymorphism. Factor V Leiden was significantly associated with arterial ischemic stroke (P < 0.001). Stroke recurred in 2 children with multiple risk factors and MTHFR C677T mutation. Factor V Leiden is one of the major genetic risk factors for pediatric arterial ischemic stroke in Lebanon. MTHFR C677T was prevalent among patients with recurrent stroke.     

Inherited and acquired risk factors and their combined effects in pediatric stroke

The aim of this study was to identify hereditary and acquired risk-factors as they are related to the occurrence of stroke in children. We identified 21 children with stroke. A search of the Factor V Leiden mutation, the Factor II G20210A variant, and the thermolabile variant of methylenetetrahydrofolate reductase was performed in patients and in a control group (n = 115).We identified risk factors of acquired and/or hereditary nature for stroke in 19 of 21 children. Eleven children had three or more risk factors, seven had two risk factors, and one child had only one risk factor. We found three carriers (14.3%) of the Factor V Leiden mutation, two carriers (9.5%) of the Factor II G20210A variant, eleven (52.4%) thermolabile variant of methylenetetrahydrofolate reductase heterozygote carriers, and one (4.8%) homozygotes for this variant.Frequencies of the Factor V Leiden mutation and the Factor II variant were higher in patients than in controls, suggesting that these variants are associated with an increased risk of stroke in childhood. Homozygosity for the thermolabile variant of methylenetetrahydrofolate reductase was equally frequent amongst patients and controls.Our study confirms that stroke in children is commonly associated with a combination of multiple risk factors, both genetic and acquired, and that the Factor V Leiden mutation and the Factor II G20210A variant are predisposing factors for this situation.     

Two cousins with neonatal stroke, PAI-1 4G variant and MTHFR A1298C mutation

The authors describe 2 female cousins with neonatal stroke. One was heterozygous for the plasminogen activator inhibitor-1 4G variant and compound heterozygous for the A1298C and C677T methylenetetrahydrofolate reductase mutations. Her cousin was homozygous for the plasminogen activator inhibitor-1 4G variant and heterozygous for the methylenetetrahydrofolate reductase A1298C and factor V Leiden mutations.     

Factor V Leiden and hemophilia

Several inherited prothrombotic risk factors have been identified so far. Among them, the factor V (FV) Leiden mutation causes a reduced ability of activated protein C to inactivate activated FV and is the most frequent genetic predisposing factor for venous thromboembolism. However, the high prevalence of FV Leiden (up to 15%) in the Caucasian population suggests that this mutation might confer an evolutionary survival advantage. Indeed, there is mounting evidence about the role of FV Leiden in modulating the clinical phenotype of some physiological and pathological conditions, including hemophilia. The existing literature on the interaction between FV Leiden and hemophilia-related factor VIII or IX mutations is analyzed in this review focusing on the clinical effects and possible pathogenic mechanisms. In summary, current evidence suggests that this prothrombotic mutation may compensate for the low factor VIII or IX levels, resulting in more efficient thrombin generation and ensuing attenuation of clinical symptoms. On the other hand, the association of this prothrombotic mutation with other acquired or inherited thrombophilic factors might overcome the congenital bleeding tendency in hemophiliacs, thereby increasing the risk of thrombotic complications.     

Profile of prothrombotic factors in Indian children with ischemic stroke

This study was undertaken in view of paucity of data regarding the profile of prothrombotic factors in children with ischemic stroke. Sixty-four children with ischemic stroke were prospectively evaluated for prothrombotic factors over a 2 year period. The blood samples were analyzed for protein C (PC), protein S (PS), activated protein C resistance (APCR), factor V Leiden (FVL), anti-thrombin-III (AT-III), lipoprotein (a) [Lp(a)], lupus anticoagulant (LA), anti-cardiolipin antibodies (aCL) immunoglobulin (Ig) M and IgG, homocysteine, and methylenetetrahydrofolate reductase (MTHFR) at least 3 months after the onset of stroke. At least one prothrombotic factor was identified in 45.3% children (29/64). These included hyperhomocysteinemia (11/64), PC deficiency (9/64), aCL (8/64), PS deficiency (5/64), APCR (3/64), AT-III deficiency (2/64) and LA (1/64). Multiple factors were coexistent in 17.2% (11/64). The prevalence of PC deficiency, PS deficiency and co-existence of multiple abnormalities observed were similar to the published literature. Elevated Lp(a) and APCR were less prevalent. FVL and MTHFR were not seen in any of the study children. Forty-five percent of children had at least one prothrombotic abnormality. Hyperhomocysteinemia, PC deficiency, aCL and PS deficiency were the most frequent prothrombotic abnormalities.     

A clustering of unfavourable common genetic mutations in stroke cases

OBJECTIVES: The aetiological role of common genetic mutations was analysed in a subgroup of stroke patients. MATERIAL AND METHODS: A total of 406 patients were examined because of ischaemic stroke. After a detailed clinical scrutiny, 5 were found who did not exhibit any of the classical clinical risk factors. In this clinically homogeneous subgroup of stroke patients, the prothrombin A20210G, Hong Kong, Cambridge and methylenetetrahydrofolate reductase C677T (MTHFR C677T) mutations, angiotensin-converting enzyme polymorphism (ACE polymorphism) and apolipoprotein E (APO E) genotype were examined. RESULTS: In all 5 patients, the same type of clustering of three mutations was manifested. A heterozygous Leiden V mutation was observed in all 5 subjects, while a heterozygous MTHFR C677T mutation and an I/D genotype for ACE polymorphism were detected in 4 of them, and a homozygous D/D genotype and a homozygous MTHFR C677T mutation in 1. This type of clustering of the mutations was not observed in the remaining 401 stroke patients. CONCLUSION: These results suggest that the Leiden mutation might possibly be an aetiological factor for stroke in a rare subgroup of patients who do not display any of the classical risk factors. The roles of ACE D polymorphism and the MTHFR C677T mutation in stroke, should also be taken into consideration in this subgroup of stroke patients. These unfavourable genetic factors might be aetiological factors if they are clustered together in a stroke patient not presenting any of the standard clinical risk factors.     

Cerebrovascular disorders in children with the factor V Leiden mutation.

Since 1995, at least 128 children with a cerebrovascular disorder, cerebral palsy, or both and the factor V Leiden mutation have been reported. The majority of these strokes were in the first year of life, many of them in the perinatal period. Two thirds had an additional exogenous risk factor for thrombosis, and 42% had another recognized endogenous prothrombotic risk factor in combination with the mutation. We review the association of the factor V Leiden mutation and a cerebrovascular disorder in children younger than 16 years of age and describe the clinical features of 8 children with cerebral palsy and the Leiden mutation. This mutation should be considered in the evaluation of children with a stroke or its sequelae, including infants with perinatal stroke.     

Evaluation of the modifying effects of unfavourable genotypes on classical clinical risk factors for ischaemic stroke

OBJECTIVES: Ischaemic stroke is a frequent heterogeneous multifactorial disease that is affected by a number of genetic mutations and environmental factors. We hypothesised the clinical importance of the interactions between common, unfavourable genetic mutations and clinical risk factors in the development of ischaemic stroke. METHODS: The Factor V Leiden G1691A (Leiden V), the prothrombin G20210A, the methylenetetrahydrofolate reductase C677T (MTHFR C677T) mutations, the angiotensin converting enzyme I/D (ACE I/D), and apolipoprotein allele e4 (APO e4) genotypes were examined by the polymerase chain reaction (PCR) technique in 867 ischaemic stroke patients and 743 healthy controls. Logistic regression models were used to estimate the roles of the co-occurrences of the clinical risk factors and common genetic mutations in ischaemic stroke. RESULTS: The Leiden V mutation in combination with hypertension or diabetes mellitus increased the risk of ischaemic stroke. We found synergistic effects between the ACE D/D and MTHFR 677TT genotypes and drinking or smoking. The presence of the APO e4 greatly facilitated the unfavourable effects of hypertension, diabetes mellitus, smoking, or drinking on the incidence of ischaemic stroke. CONCLUSION: In certain combinations, pairing of common unfavourable genetic factors, which alone confer only minor or non-significant risk, with clinical risk factors can greatly increase the susceptibility to ischaemic stroke.     

Risk factors for perinatal arterial stroke: a study of 60 mother-child pairs

The objective of the present study was to examine demographic, historical, and prothrombotic risk factors in infants with perinatal arterial stroke and their mothers. Risk factors were evaluated in 60 mother-child pairs with perinatal arterial stroke. Prothrombotic factors analyzed included the DNA mutations factor V Leiden, prothrombin 20210, MTHFR C677T and A1298C; serum activity levels for protein C, protein S, and antithrombin III; serum levels of lipoprotein(a); and, in the mothers, antiphospholipid antibodies. Boys predominated, 36:24. There were four twin sets. Sixty percent were term and 22% were post-date. Ten were large for gestational age. Five mothers had abdominal trauma. Nine mothers (15%) had preeclampsia. Emergency caesarean section was performed in 17 cases (28%). Eight placental exams revealed seven with abnormalities. Seizures were the presenting sign in 70%, and 30% presented with early handedness or cerebral palsy. Prothrombotic risk factors were found in 28 of 51 mothers (55%) and 30 of 60 children (50%). Forty-one pairs (68%) had at least one abnormality in mother, child, or both. Long-term sequelae included cerebral palsy (40 of 51; 78%), cognitive impairment (35 of 51; 68%), seizures (23 of 51; 45%), and microcephaly (26 of 51; 51%). Perinatal arterial stroke is the result of multifactorial, synergistic fetal and maternal factors among which the prothrombotic factors, both fetal and maternal, appear significant.     

Thrombophilic risk factors and homocysteine levels in Behçet's disease in eastern Spain and their association with thrombotic events

Beh?et's disease (BD) is a chronic inflammatory disorder in which thrombosis occurs in about 30% of patients. The prothrombotic mechanisms are unknown. Thrombophilic defects and hyperhomocysteinaemia may be involved in the pathogenesis of thrombotic events, although results have been controversial. Moreover, no information is available on this issue for eastern Spain. We studied the prevalence of inherited and acquired thrombophilic risk factors in 79 patients with BD (43 men, 36 women) who had (n = 23) or did not have (n = 56) thrombosis, and in 84 healthy control subjects (42 men, 42 women). Risk factors examined were antithrombin, protein C and protein S levels, factor V Leiden, the prothrombin G20210A mutation, the methylenetetrahydrofolate reductase C677T polymorphism, and acquired thrombophilic risk factors, including anticardiolipin antibodies, lupus anticoagulant, and serum homocysteine levels. There were no differences between patients and controls in any of the parameters studied. When we studied BD patients with and without thrombotic events, the only thrombophilic defect that differed was the prothrombin G20210A mutation: Three out of 23 patients with thrombosis were carriers, compared with none of 56 patients without thrombosis (p = 0.022). Two of the three carriers developed catastrophic or recurrent thrombotic episodes; one was a homozygous carrier of the G20210A prothrombin mutation and the other was doubly heterozygous for the G20210A prothrombin mutation and factor V Leiden. A meta-analysis demonstrated an association of factor V Leiden and prothrombin mutation with thrombosis in BD. When studies from Turkey were excluded from the meta-analysis, only the prothrombin G20210A mutation was associated with thrombosis.     

Evaluation of the interactions of common genetic mutations in stroke subtypes

Objective: Ischemic stroke is a frequent heterogeneous multifactorial disease that is affected by several genetic mutations and environmental factors. We hypothesised the clinical importance of the co-occurrence of common, unfavorable genetic mutations in the development of different stroke subtypes. Method and material: The Factor V Leiden G1691A (Leiden V), the prothrombin G20210A and the methylenetetrahydrofolate reductase C677T (MTHFR C677T) mutations and the angiotensin-converting enzyme I/D (ACE I/D) and apolipoprotein E (APOE) genotypes were examined by the PCR technique in 689 ischemic stroke patients and 652 stroke-free controls. Logistic regression models were used to estimate the relative risks of different stroke subtypes for different genotype combination patterns. Results: The ACE D/D genotype alone or in combination with the MTHFR 677T or the APOE 4 allele or with both was highly specific for small-vessel infarction. The Leiden V mutation alone or in different combination patterns with the ACE D, APOE 4 and MTHFR 677T alleles was specifically predisposed to large-vessel infarction. The APOE 4 allele alone was calculated to be a general, minor genetic risk factor for ischemic stroke. The MTHFR 677T allele alone was not a risk factor for any stroke subtype. In the different specific predisposition gene combinations, however, both the APOE 4 and MTHFR 677T alleles could increase the relative risk of the given stroke subgroup. Conclusions: Common mutations which alone are minor or non-significant risk factors for ischemic stroke can yield, in specific combination patterns, a highly significant, moderate genetic risk of specific stroke subtypes. Received: 5 February 2002, Received in revised form: 17 April 2002, Accepted: 22 April 2002 Correspondence to Dr. Z. Szolnoki, M. D.     

Basilar artery thrombosis in a child heterozygous for factor V Leiden mutation

Activated protein C resistance, usually because of factor V Leiden mutation, is considered to be the most common hereditary prothrombotic condition. A 9-year-old male with a basilar artery stroke and activated protein C resistance is described. The patient, found to be heterozygous for factor V Leiden mutation, is one of several recent reports that suggest that activated protein C resistance is an important risk factor for spontaneous arterial thrombosis in infancy and childhood.     

Different additional risk factors for cerebral infarctions associated with the factor V Leiden mutation in a family

Several cases with cerebral infarctions associated with the factor V Leiden mutation have been reported. However, bearing in mind the large number of asymptomatic individuals with the factor V Leiden mutation, additional risk factors for cerebral infarctions should be considered. In this report, two siblings with cerebral infarctions associated with a combination of heterozygous factor V Leiden mutation and different additional exogenous and endogenous thrombogenic risk factors are described. Respiratory problems in the perinatal period and increased lipoprotein (a) concentrations in the first patient and an episode of gastroenteritis from Shigella infection and persistent high titers of serum anticardiolipin and beta(2)-glycoprotein I antibodies in the second patient were recorded as additional thrombogenic risk factors. Furthermore, both patients were found to be heterozygous for the methylenetetrahydrofolate reductase gene C677T mutation. These findings suggest that even in the same family, different additional thrombogenic risk factors can be present in infants with cerebral infarctions associated with the factor V Leiden mutation. An extensive search of additional circumstantial and genetic thrombogenic risk factors should be useful for prophylaxis and prognosis of these infants with cerebral infarctions associated with the factor V Leiden mutation and of their related family members. To our knowledge, the second patient in this study is the first patient reported to have cerebral infarctions associated with the combination of the factor V Leiden mutation and persistent high titers of serum beta(2)-glycoprotein I antibodies.     

Genetic Risk Factors for Perinatal Arterial Ischemic Stroke

The cause of perinatal arterial ischemic stroke is unknown in most cases. We explored whether genetic polymorphisms modify the risk of perinatal arterial ischemic stroke. In a population-based case-control study of 1997-2002 births at Kaiser Permanente Northern California, we identified 13 white infants with perinatal arterial ischemic stroke. Control subjects included 86 randomly selected white infants. We genotyped polymorphisms in nine genes involved in inflammation, thrombosis, or lipid metabolism previously linked with stroke, and compared genotype frequencies in case and control individuals. We tested several polymorphisms: tumor necrosis factor-α ?308, interleukin-6, lymphotoxin A, factor V Leiden, methyltetrahydrofolate reductase 1298 and 667, prothrombin 20210, and apolipoprotein E ε2 and ε4 alleles. Patients with perinatal arterial ischemic stroke were more likely than control subjects to demonstrate at least one apolipoprotein E ε4 allele (54% vs 25%, P = 0.03). More patients with perinatal arterial ischemic stroke carried two ε4 alleles than did control subjects (15% vs 2%, P = 0.09), although this finding lacked statistical significance. Proinflammatory and prothrombotic polymorphisms were not associated with perinatal arterial ischemic stroke. The apolipoprotein E polymorphism may confer genetic susceptibility for perinatal arterial ischemic stroke. Larger population-based studies are required to confirm this finding.     

Arterial ischemic stroke in childhood: risk factors and outcome in old versus new era

Risk factors of children with arterial ischemic stroke were retrospectively evaluated. The children were grouped according to values on developing diagnostic tools: 13 in the old era (1987-1994) and 18 in the new era (1995-2004). The old era battery included 5 tests: protein C, protein S, antithrombin, lupus anticoagulants, and anticardiolipin antibodies. The new era battery added 5 more tests: homocystine level, factor VIII level, mutations for factor V Leiden and prothrombin G20210A, and lipoprotein (a) level. At least 1 risk factor was found in 5 of 13 children (38.5%) in the old era and in 8 of 18 (44.4%) in the new era. The extended battery for prothrombotic disorders revealed 7 risk factors in 4 children (22.2%) in the new era, whereas the limited battery identified a single risk factor in 1 child (7.7%) in the old era. For the correct etiologic identification, prothrombotic risk factors should be extensively evaluated in patients with arterial ischemic stroke.     

Factor V1691 G-A, prothrombin 20210 G-A, and methylenetetrahydrofolate reductase 677 C-T variants in Turkish children with cerebral infarct

Inherited gene defects related to the coagulation system have been reported as risk factors for ischemic stroke. These gene defects include a G-A transition at nucleotide 1691 in exon 10 of the Factor V gene causing activated protein C resistance; a G-A transition in the 3' untranslated region of the prothrombin gene at nucleotide position 20210 (G-A), which is associated with increased levels of prothrombin activity; and a C-T polymorphism at nucleotide 677 in the methylenetetrahydrofolate reductase gene responsible for an alanine to valine substitution, resulting in the synthesis of a thermolabile form of methylenetetrahydrofolate reductase that causes increased levels of homocysteine. The case-control study included 28 patients with cerebral infarction; all were 18 years of age or younger (range, 10 months to 18 years). Seven (25%) of the 28 patients were heterozygous for the FV1691 mutation. Five (17.8%) of the patients carried the PT20210A mutation. Two (7.1%) of the patients carried both mutations. When compared to controls, the difference was significant for both mutations (P = .007; .04). The frequency of allele T of methylenetetrahydrofolate reductase 677 was 0.3214, which was not significant when compared to controls (0.231; P = .3). A total of 12 (42.8%) patients carried one or both of the mutations FV1691 G-A and PT20210 G-A. From our data, it appears that FV1691 G-A and PT20210 G-A are associated with cerebral infarct risk independently. Risk assessment of double prothrombotic gene alterations did not reveal synergy between these mutations. In conclusion, the presence of FV1691 A and PT20210 A mutations but not the methylenetetrahydrofolate reductase 677 TT mutation correlate with the occurrence of cerebral infarction in children.     

Inherited thrombophilia as a risk factor for the development of ischemic stroke in young adults

INTRODUCTION: Several recent studies have analyzed a possible effect of thrombophilia risk factors such as factor V Leiden, the prothrombin variant (allele 20210 A), and homozygosity for thermolabile methylenetetrahydrofolate reductase (MTHFR-T) on the development of ischemic stroke (IS). In the present study, we determined the role of these prothrombotic polymorphisms in the early onset of arterial IS or cerebral venous thrombosis (CVT) in a group of young Brazilian adults of Caucasian and African descent. MATERIALS AND METHODS: We conducted a cross-sectional study of 167 survivors of IS (153 patients with arterial IS and 14 cases of CVT; 66 men: 101 women; 124 of Caucasian and 43 of African origin; median age: 32.6 years; range: 15 to 45 years) and compared the prevalence of inherited thrombophilia risk factors with a control group of 225 sex and age matched individuals of the same ethnic background. To determine the interaction with atherogenic risk factors, the following diagnoses were considered: hypertension, hyperlipoproteinemia, diabetes mellitus, smoking status and use of oral contraceptives. RESULTS: In the arterial IS group, no significant variation was found between patients and controls of Caucasian origin regarding the prevalence of factor V Leiden (P = 0.92), the prothrombin variant (P = 0.13) or homozygosity for MTHFR-T (P = 0.61). Among Brazilians of African descent, 10.3% were homozygous for MTHFR-T, which was significantly elevated, odds ratio of 5.9 (95% CI: 0.88 to 49.15). In the CVT group, two Caucasian patients (20%) were heterozygous for the prothrombin variant, odds ratio of 9.7 (95% CI: 0.95 to 89.71) and one patient was carrier of factor V Leiden (P = 0.49). No prothrombotic polymorphism was identified in patients with CVT of African descent. All women in the CVT group were in use of oral contraceptives or in the post-partum state. DISCUSSION: Inherited thrombophilia risk factors were not found to increase the risk of arterial IS among young patients of Caucasian descent. However, a potential role of homozygosity for MTHFR-T was observed in a small group of patients of African origin. The analysis of patients with CVT revealed an increased risk due to the prothrombin gene variant or oral contraceptive use. Further studies including all incoming patients with IS are necessary to evaluate the impact of inherited thrombophilia risk factors on early mortality.     

Role of thrombophilic risk factors in children with non-stroke cerebral palsy

BACKGROUND: Thrombophilic risk factors play an important role in the pathogenesis of perinatal stroke and resultant cerebral palsy (CP). The association between thrombophilia and CP caused by etiologies other than stroke is undetermined. METHODS: We assessed three genetic thrombophilic markers (mutation of Factor V Leiden [FV G1691A], 677T polymorphism of thermolabile methylenetetrahydrofolate reductase [MTHFR] and G20210A mutation of the prothrombin gene) in 49 pediatric patients with non-stroke CP and compared the findings with 118 apparently healthy controls. CP in the study group was due to periventricular leukomalacia (n=27), intraventricular hemorrhage (n=9), hypoxic ischemic encephalopathy (n=4), prematurity with no apparent complication (n=8) and intrauterine growth retardation (n=1). Twenty-five children had spastic diplegia, 20 had spastic quadriplegia and 4 had spastic hemiplegia. CP was graded as being severe in 26 children (53%). RESULTS: No significant difference in the prevalence of thrombophilic risk factors was found between the study and control groups. Twelve study children (24.5%) had at least one of the three thrombophilic mutations compared with 27 controls (23%). There was no significant difference in the prevalence of each thrombophilic risk factor in the various etiologic groups and in the subgroups of mild/severe CP and the control group. CONCLUSION: These findings support the notion that thrombophilia neither contributes to the occurrence nor affects the clinical outcome and severity of non-stroke CP.     

Prothrombotic factors and the risk of acute onset non-cardioembolic stroke in young Asian Indians

Introduction

Several prothrombotic factors - both hereditary and acquired - are known to cause stroke. Commonly investigated causes are activated protein C resistance, factor V Leiden mutation, factor VIII levels, prothrombin 20210 G-to-A mutation, coagulation inhibitors such as proteins C and S, and antiphospholipid antibodies such as β₂-glycoprotein.

Objective

The literature on the prevalence of hematological defects pertaining to these variables in the Asian Indian stroke population is limited to a few isolated reports. In the current study we investigate the above-mentioned variables in 120 stroke patients (non-cardioembolic acute-onset stroke) and compare their status with the hematological profile of an equal number of healthy age- and sex-matched controls.

Material and Methods

Plasma and blood leukocytes were collected from all patients and controls for performing hematological assays and molecular tests respectively. The mutations were detected using standard polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) procedures. Statistical analysis was done using SPSS version 12.0.

Results

Factor V Leiden (prevalence 8.3% in patients) and activated protein C resistance (prevalence 19.6% in patients) both showed a high degree of association (P < 0.01) with the disease condition. However, contrary to common expectations, factor V Leiden was observed much less frequently in patients showing activated protein C resistance (10 out of 23; 43.4%) than is commonly observed in the Caucasian population (almost 90%). Post-acute-phase factor VIII levels were also found to be significantly associated with stroke: 125.6 + 21.1% number of profitable positions (NPP) for controls and 136.2 + 28.8% NPP for patients (P = 0.001).

Conclusion

factor V mutations, such as factor V Leiden, may be important risk factors for stroke in an Asian Indian population. Activated protein C resistance has a stronger association with stroke than factor V Leiden and may be caused by other factors such as elevated factor VIII levels in the Asian Indian population apart from factor V Leiden itself.