ABSTRACT
OBJECTIVES: To investigate the risk factors and underlying causes of pregnancy-related cerebral venous thrombosis (PCVT). METHODS: A retrospective cohort of 16 patients diagnosed with CVT during pregnancy and postpartum (within six weeks after delivery) in a comprehensive hospital in China between 2009 and 2022 were carefully reviewed, focusing on demographic, clinical, and etiological characteristics, especially underlying causes. We matched 16 PCVT patients with 64 pregnant and puerperal women without PCVT to explore risk factors and clinical susceptibility to PCVT. RESULTS: PCVT occurred commonly during the first trimester (43.75%) and the puerperium (37.5%). The frequency of anemia, thrombocytosis and thrombocytopenia during pregnancy, dehydration, and pre-pregnancy anemia was significantly higher in women with PCVT than in those without PCVT (P < 0.05). Among the 16 patients, five were diagnosed with antiphospholipid syndrome and one was diagnosed with systemic lupus erythematosus. Three patients had distinct protein S deficiency and one had protein C deficiency. Whole Exome Sequencing (WES) was performed for five patients and revealed likely pathogenic mutations associated with CVT, including heterozygous PROC c.1218G > A (p. Met406Ile), heterozygous PROS1 c.301C > T (p. Arg101Cys), composite heterozygous mutation in the F8 gene (c.144-1259C > T; c.6724G > A (p. Val2242Met)) and homozygous MTHFR c.677C > T (p. Ala222Val). CONCLUSIONS: The occurrence of anemia, thrombocytopenia and thrombocytosis during pregnancy, dehydration and pre-pregnancy anemia suggested a greater susceptibility to PCVT. For confirmed PCVT patients, autoimmune diseases, hereditary thrombophilia, and hematological disorders were common causes. Screening for potential etiologies should be paid more attention, as it has implications for treatment and long-term management.
Subject(s)
Intracranial Thrombosis , Venous Thrombosis , Humans , Female , Pregnancy , Retrospective Studies , Adult , Intracranial Thrombosis/epidemiology , Risk Factors , Venous Thrombosis/epidemiology , China/epidemiology , Young Adult , Pregnancy Complications, Hematologic/epidemiology , Pregnancy Complications, Hematologic/diagnosis , Protein S Deficiency/epidemiology , Protein S Deficiency/complications , Protein S Deficiency/diagnosis , Protein S Deficiency/geneticsABSTRACT
Background Recent literature reports a strong thrombotic tendency in patients hospitalized for a coronavirus disease 2019 (COVID-19) infection. This characteristic is unusual and seems specific to COVID-19 infections, especially in their severe form. Viral infections can trigger acquired thrombophilia, which can then lead to thrombotic complications. We investigate for the presence of acquired thrombophilia, which could participate in this phenomenon, and report its prevalence. We also wonder if these thrombophilias participate in the bad prognosis of severe COVID-19 infections. Methods and Results In 89 consecutive patients hospitalized for COVID-19 infection, we found a 20% prevalence of PS (protein S) deficiency and a high (ie, 72%) prevalence of antiphospholipid antibodies: mainly lupus anticoagulant. The presence of PS deficiency or antiphospholipid antibodies was not linked with a prolonged activated partial thromboplastin time nor with D-dimer, fibrinogen, or CRP (C-reactive protein) concentrations. These coagulation abnormalities are also not linked with thrombotic clinical events occurring during hospitalization nor with mortality. Conclusions We assess a high prevalence of positive tests detecting thrombophilia in COVID-19 infections. However, in our series, these acquired thrombophilias are not correlated with the severity of the disease nor with the occurrence of thrombotic events. Albeit the strong thrombotic tendency in COVID-19 infections, the presence of frequent acquired thrombophilia may be part of the inflammation storm of COVID-19 and should not systematically modify our strategy on prophylactic anticoagulant treatment, which is already revised upwards in this pathological condition. Registration URL: https://www.cliniâcaltrâials.gov; Unique identifier: NCT04335162.
Subject(s)
Antiphospholipid Syndrome/epidemiology , Coronavirus Infections/epidemiology , Pneumonia, Viral/epidemiology , Protein S Deficiency/epidemiology , Thrombosis/epidemiology , Aged , Antibodies, Antiphospholipid/blood , Antiphospholipid Syndrome/blood , Antiphospholipid Syndrome/diagnosis , Biomarkers/blood , COVID-19 , Coronavirus Infections/blood , Coronavirus Infections/diagnosis , Female , France/epidemiology , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/diagnosis , Prevalence , Prognosis , Protein S/analysis , Protein S Deficiency/blood , Protein S Deficiency/diagnosis , Risk Factors , Severity of Illness Index , Thrombosis/blood , Thrombosis/diagnosisSubject(s)
Blood Proteins/genetics , Mutation, Missense , Humans , Prevalence , Protein S , Protein S Deficiency/blood , Protein S Deficiency/epidemiology , Protein S Deficiency/genetics , Sweden/epidemiology , Venous Thromboembolism/blood , Venous Thromboembolism/epidemiology , Venous Thromboembolism/geneticsSubject(s)
Blood Proteins/genetics , Molecular Epidemiology , Mutation , Adolescent , Adult , Aged , China/epidemiology , Female , Humans , Male , Middle Aged , Protein S/genetics , Protein S Deficiency/epidemiology , Protein S Deficiency/genetics , Young AdultABSTRACT
Congenital deficiency of protein S (PS), an anticoagulant factor, leads to venous thrombosis, with onset predominantly beginning in adolescence. In the present study, gene analysis of six unrelated Japanese families diagnosed with congenital PS deficiency identified five missense mutations in the PROS1 gene - c.757C>T (Ala139Val; A139V), c.1346 G>T (Cys449Phe; C449F), c.1352G>A (Arg451Gln; R451Q), c.1424G>T (Cys475Phe; C475F) and c.1574C>T (Ala525Val; A525V) - and one frameshift mutation, c.2135delA (Asp599ThrfsTer13; D599TfsTer13). C449F, R451Q, A525V and D599TfsTer13 are novel mutations. Results from ELISA to measure PS antigen levels in culture supernatant showed that the A139V variant was similar to wild-type, but other variants showed reductions when compared with wild-type. Results from pulse-chase analysis confirmed that the A139V variant exhibited secretion equivalent to wild-type, but for the other variants, there was no extracellular secretion, and it had nearly all been degraded inside the cell within six hours. Results from pulse-chase analysis using proteasome inhibitors also showed that intracellular degradation of mutant protein was inhibited. Activity of the A139V variant was decreased to 71% of wild-type, and the phospholipid binding capacity fell to as low as 45%. These results suggest that although the A139V variant has normal secretion, it has abnormal phospholipid binding capacity, and therefore causes type II PS deficiency, in which PS activity is decreased. It is also thought that with the other variants, misfolding due to amino acid mutations causes nearly all PS to be degraded intracellularly, therefore leading to type I PS deficiency.
Subject(s)
Blood Proteins/genetics , Frameshift Mutation , Mutation, Missense , Protein S Deficiency/genetics , Protein S/genetics , Adolescent , Adult , Asian People/genetics , Blood Proteins/metabolism , Female , Genotype , Humans , Japan/epidemiology , Male , Phospholipids/metabolism , Protein Binding , Protein S/metabolism , Protein S Deficiency/epidemiology , Protein S Deficiency/metabolismABSTRACT
Genetic risk factors predispose to thrombophilia and play the most important etiopathogenic role in venous thromboembolism (VTE) in people younger than 50 years old. At least one inherited risk factor could be found in about half of the cases with a first episode of idiopathic VTE.Roughly, genetic risk factors are classified into two main categories: loss of function mutations (such as deficiencies of antithrombin, protein C, protein S) and gain of function mutations, (such as prothrombin mutation G20210A, factor V Leiden). A revolutionary contribution to the genetic background of VTE was brought by the achievements of the genome-wide association studies which analyze the association of a huge number of polymorphisms in large sample size.Hereditary thrombophilia testing should be done only in selected cases. The detection of hereditary thrombophilia has impact on the management of the anticoagulation in children with purpura fulminans, pregnant women at risk of VTE and may be useful in the assessment of the risk for recurrent thrombosis in patients presenting an episode of VTE at a young age (<40 years) and in cases with positive family history regarding thrombosis.
Subject(s)
Antithrombin III Deficiency/genetics , Protein C Deficiency/genetics , Protein S Deficiency/genetics , Thrombophilia/genetics , Venous Thromboembolism/genetics , Antithrombin III Deficiency/complications , Antithrombin III Deficiency/diagnosis , Antithrombin III Deficiency/epidemiology , Europe/epidemiology , Factor V/genetics , Gene Expression , Genetic Predisposition to Disease , Humans , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Mutation , Prevalence , Protein C Deficiency/complications , Protein C Deficiency/diagnosis , Protein C Deficiency/epidemiology , Protein S Deficiency/complications , Protein S Deficiency/diagnosis , Protein S Deficiency/epidemiology , Prothrombin/genetics , Risk Factors , Thrombophilia/complications , Thrombophilia/diagnosis , Thrombophilia/epidemiology , Venous Thromboembolism/diagnosis , Venous Thromboembolism/epidemiology , Venous Thromboembolism/etiologyABSTRACT
The prevalence of protein S (PS) deficiency in Asian patients with venous thromboembolism is around 8-30%, higher than that in Caucasian populations. The present study reports the genotypes (including one novel mutation) and phenotypes of children with PS deficiency at a tertiary care institute. A total of six patients were included, three with arterial ischemic stroke, two with cerebral venous sinus thrombosis, and one with deep vein thrombosis. PS mutations were identified in four patients: p.R355C, p.G336D, p.E67A, and p.N188KfsX9. p.N188KfsX9 is a novel mutation with less than 20% PS activity noted in heterozygotes.
Subject(s)
Protein S Deficiency/epidemiology , Protein S Deficiency/genetics , Sinus Thrombosis, Intracranial/genetics , Stroke/genetics , Thromboembolism/epidemiology , Thromboembolism/genetics , Venous Thrombosis/genetics , Adolescent , Child , Child, Preschool , Female , Genotype , Humans , Male , Phenotype , Polymerase Chain Reaction , Protein S Deficiency/pathology , Retrospective Studies , Thailand/epidemiologyABSTRACT
This prospective study aimed to evaluate pregnancy outcome and complications in women with recurrent pregnancy loss (RPL) and protein S (PS) deficiency, who received low dose aspirin (LDA) or LDA plus heparin (LDA/H) therapies. Clinical characteristics, pregnancy outcome and complications of 38 women with two or more RPL and <60% of plasma free PS antigen were compared among three groups: antiphospholipid antibody (aPL)-negative women who received LDA (group A), aPL-negative women who received LDA/H (group B) and aPL-positive women who received LDA/H (group C). Gestational weeks (GW) at delivery in group C (median 32 GW) were earlier than 40 GW in group A and 38.5 GW in group B (p < 0.05). The birth weight in group C (median 1794 g) was less than 2855 g in group B (p < 0.05). The incidences of fetal growth restriction (37.5%), pregnancy-induced hypertension (37.5%), and preterm delivery (62.5%) in group C were higher than those (4.5%, 0%, and 4.5%, respectively) in group B (p<0.05). Women with RPL, PS deficiency, and positive aPL had high risks for adverse pregnancy outcome and complications, even when they received LDA/H therapy. Among women with RPL, PS, and negative aPL, there was no difference in these risks between LDA alone and LDA/H therapies.
Subject(s)
Abortion, Habitual , Antibodies, Antiphospholipid/blood , Aspirin/pharmacology , Birth Weight , Fetal Growth Retardation , Fibrinolytic Agents/pharmacology , Heparin/pharmacology , Hypertension, Pregnancy-Induced , Pregnancy Complications, Hematologic , Premature Birth , Protein S Deficiency , Abortion, Habitual/epidemiology , Adult , Aspirin/administration & dosage , Comorbidity , Drug Therapy, Combination , Female , Fetal Growth Retardation/blood , Fetal Growth Retardation/drug therapy , Fetal Growth Retardation/epidemiology , Fibrinolytic Agents/administration & dosage , Heparin/administration & dosage , Humans , Hypertension, Pregnancy-Induced/blood , Hypertension, Pregnancy-Induced/drug therapy , Hypertension, Pregnancy-Induced/epidemiology , Pregnancy , Pregnancy Complications, Hematologic/blood , Pregnancy Complications, Hematologic/drug therapy , Pregnancy Complications, Hematologic/epidemiology , Premature Birth/blood , Premature Birth/drug therapy , Premature Birth/epidemiology , Protein S Deficiency/blood , Protein S Deficiency/drug therapy , Protein S Deficiency/epidemiologyABSTRACT
BACKGROUND: The early diagnosis of inherited thrombophilia in children is challenging because of the rarity and hemostatic maturation. METHODS: We explored protein C (PC), protein S (PS), and antithrombin (AT) deficiencies in 306 thromboembolic patients aged ≤20 y using the screening of plasma activity and genetic analysis. RESULTS: Reduced activities were determined in 122 patients (40%). Low PC patients were most frequently found in the lowest age group (0-2 y, 45%), while low PS or low AT patients were found in the highest age group (16-20 y; PS: 30% and AT: 20%). Genetic study was completed in 62 patients having no other causes of thromboembolism. Mutations were determined in 18 patients (8 PC, 8 PS, and 2 AT genes). Six of eight patients with PC gene mutation were found in age 0-2 y (75%), while six of eight patients with PS gene mutation were in 7-20 y. Two AT gene-mutated patients were older than 4 y. Four PC-deficient and two PS-deficient patients carried compound heterozygous mutations. All but one PC gene-mutated patient suffered from intracranial thromboembolism, while PS/AT gene-mutated patients mostly developed extracranial venous thromboembolism. CONCLUSION: Stroke in low PC infants and deep vein thrombosis in low PS/AT school age children could be targeted for genetic screening of pediatric thrombophilias.
Subject(s)
Activated Protein C Resistance/epidemiology , Antithrombin III Deficiency/epidemiology , Protein C Deficiency/epidemiology , Protein S Deficiency/epidemiology , Thromboembolism/etiology , Thrombophilia/genetics , Activated Protein C Resistance/blood , Activated Protein C Resistance/diagnosis , Activated Protein C Resistance/genetics , Adolescent , Age of Onset , Antithrombin III/analysis , Antithrombin III/genetics , Antithrombin III Deficiency/blood , Antithrombin III Deficiency/diagnosis , Antithrombin III Deficiency/genetics , Cerebrovascular Disorders/epidemiology , Cerebrovascular Disorders/etiology , Child , Child, Preschool , DNA Mutational Analysis , Factor V/genetics , Female , Genotype , Humans , Infant , Japan/epidemiology , Male , Promoter Regions, Genetic/genetics , Protein C/analysis , Protein C/genetics , Protein C Deficiency/blood , Protein C Deficiency/diagnosis , Protein C Deficiency/genetics , Protein S/analysis , Protein S/genetics , Protein S Deficiency/blood , Protein S Deficiency/diagnosis , Protein S Deficiency/genetics , Prothrombin/genetics , Thromboembolism/epidemiology , Thrombophilia/blood , Thrombophilia/diagnosis , Thrombophilia/epidemiologyABSTRACT
We evaluated the effect of reduced activities of protein C (PC) and protein S (PS) on the progression of peripheral arterial disease (PAD). We measured PC and PS activities in 106 patients with PAD and 44 patients with abdominal aortic aneurysm (AAA) in the same period. The incidences of PC deficiency in PAD and AAA were 4.7% and 4.5%, respectively, and those of PS were 14.1% and 11.4%, respectively; these incidences were much higher than those in the normal population. The PC and PS activities were significantly lower in patients having critical limb ischemia (CLI) than in patients with intermittent claudication. In particular, lower PC activity and female gender were determinant factors of CLI in multivariate logistic regression analysis. We suggest that PC deficiency is an independent predictor for the progression of CLI.
Subject(s)
Intermittent Claudication/epidemiology , Ischemia/epidemiology , Peripheral Arterial Disease/epidemiology , Protein C Deficiency/epidemiology , Aged , Aged, 80 and over , Aortic Aneurysm, Abdominal/blood , Aortic Aneurysm, Abdominal/diagnosis , Aortic Aneurysm, Abdominal/epidemiology , Critical Illness , Cross-Sectional Studies , Disease Progression , Female , Hospitals, Teaching , Humans , Incidence , Intermittent Claudication/blood , Intermittent Claudication/diagnosis , Ischemia/blood , Ischemia/diagnosis , Japan/epidemiology , Logistic Models , Male , Multivariate Analysis , Peripheral Arterial Disease/blood , Peripheral Arterial Disease/diagnosis , Protein C/analysis , Protein C Deficiency/blood , Protein C Deficiency/diagnosis , Protein S/analysis , Protein S Deficiency/blood , Protein S Deficiency/diagnosis , Protein S Deficiency/epidemiology , Risk Factors , Sex FactorsABSTRACT
Hereditary protein S deficiency is an autosomal dominant disorder leading to recurrent venous thrombosis and, less commonly, to arterial thrombosis. Cases of skin necrosis have been documented in patients with protein C or S deficiency while being treated with warfarin. We describe herein a patient with protein S deficiency who developed significant skin necrosis without being exposed to warfarin. She had a protracted clinical course resulting in gangrene and transmetatarsal amputation. Recognition of this rare complication and an earlyhematology referral may prevent dismal outcomes in patients with protein S deficiency.
Subject(s)
Protein C/analysis , Protein S Deficiency/complications , Skin Diseases, Vesiculobullous/etiology , Skin/pathology , Female , Humans , Ischemic Attack, Transient/complications , Ischemic Attack, Transient/epidemiology , Middle Aged , Necrosis , Protein S Deficiency/epidemiology , Skin Diseases, Vesiculobullous/epidemiology , Smoking/epidemiologyABSTRACT
BACKGROUND: The prevalence of thrombophilic abnormalities in patients with cerebral vein thrombosis has been reported to be similar to that in patients with deep vein thrombosis of the lower limb. The role of gender-specific risk factors (pregnancy, oral contraceptives) is well established, whereas that of other acquired risk conditions is debated. MATERIALS AND METHODS: We screened 56 patients with cerebral vein thrombosis and 184 age- and sex-matched apparently healthy controls for prothrombin (factor II, FII) G20210A and factor V Leiden polymorphisms; protein S, protein C, and antithrombin deficiency; anticardiolipin antibodies; hyperhomocysteinaemia and other putative risk factors. RESULTS: The G20210A polymorphism was found in 29.1% of patients and in 5.7% of controls (odds ratio [OR] 7.1; P<0.0001; adjusted OR 12.67, P<0.0001). Frequencies of factor V Leiden and hyperhomocysteinaemia were not significantly different in patients and controls, nor were the other thrombophilic tests and some established cardiovascular risk factors, such as smoking, obesity or overweight and arterial hypertension. Conversely, 53.7% of the women who developed cerebral vein thrombosis did so while assuming oral contraceptives (OR 6.12; P<0.0001), with a further increase of risk in FII G20210A carriers (OR 48.533). Some associated diseases (onco-haematological disorders and infections) also had a significant role. Over a median 7-year follow-up, irrespective of the duration of antithrombotic treatment, 9/56 (16%) patients had further episodes of venous/arterial thrombosis. No significant risk factor for recurrent thrombosis was identified. DISCUSSION: In spite of the limitations of the sample size, our data confirm the role of FII G20210A mutation in this setting and its interactions with acquired risk factors such as oral contraceptives, also highlighting the risk of recurrent thrombosis in cerebral vein thrombosis patients.
Subject(s)
Cerebral Veins , Venous Thrombosis/epidemiology , Activated Protein C Resistance/epidemiology , Activated Protein C Resistance/genetics , Adult , Antibodies, Anticardiolipin/blood , Antithrombin III Deficiency/epidemiology , Antithrombin III Deficiency/genetics , Autoimmune Diseases/blood , Autoimmune Diseases/epidemiology , Cardiovascular Diseases/epidemiology , Case-Control Studies , Comorbidity , Contraceptives, Oral, Hormonal/adverse effects , Factor V/genetics , Female , Humans , Hyperhomocysteinemia/epidemiology , Male , Middle Aged , Neoplasms/blood , Neoplasms/epidemiology , Obesity/epidemiology , Promoter Regions, Genetic/genetics , Protein C Deficiency/epidemiology , Protein S Deficiency/epidemiology , Prothrombin/genetics , Recurrence , Risk Factors , Smoking/epidemiology , Thrombophilia/blood , Thrombophilia/epidemiology , Thrombophilia/genetics , Venous Thrombosis/blood , Venous Thrombosis/etiology , Young AdultABSTRACT
Thrombophilia is a well-established risk factor for a venous thromboembolic event (VTE), and it has been proposed that hereditary thrombophilia may substantially contribute to the development of VTE in young patients. We aimed to analyse the prevalence of thrombophilia with special regard to the age of VTE manifestation. The study cohort consisted of 1490 patients (58% females) with a median age 43 years at the time of their first VTE. At least one thrombophilic disorder was identified in 50·1% of patients. The probability of detecting a hereditary thrombophilia declined significantly with advancing age (from 49·3% in patients aged 20 years and younger to 21·9% in patients over the age of 70 years; P < 0·001). This may be primarily attributed to the decreasing frequencies of the F5 R506Q (factor V Leiden) mutation and deficiencies of protein C or protein S with older age at the time of the initial VTE event. Moreover, thrombophilia was more prevalent in unprovoked compared with risk-associated VTE (57·7% vs. 47·7%; P = 0·001). The decline in the prevalence of hereditary thrombophilia with older ages supports the use of a selected thrombophilia screening strategy dependent on age and the presence or absence of additional VTE risk factors.
Subject(s)
Thrombophilia/epidemiology , Venous Thromboembolism/epidemiology , Activated Protein C Resistance/epidemiology , Activated Protein C Resistance/genetics , Adolescent , Adult , Age of Onset , Aged , Aged, 80 and over , Antiphospholipid Syndrome/epidemiology , Child , Contraceptives, Oral/adverse effects , Cross-Sectional Studies , Factor V/genetics , Female , Humans , Male , Mass Screening , Middle Aged , Prevalence , Promoter Regions, Genetic/genetics , Protein C Deficiency/epidemiology , Protein C Deficiency/genetics , Protein S Deficiency/epidemiology , Protein S Deficiency/genetics , Prothrombin/genetics , Registries , Thrombophilia/genetics , Venous Thromboembolism/etiology , Young AdultABSTRACT
BACKGROUND AND AIM: The prevalence of inherited antithrombin (AT), protein C (PC), and protein S (PS) deficiencies in portal vein system thrombosis (PVST) and Budd-Chiari syndrome (BCS) are substantially varied in different studies. No quantitative syntheses of these studies have been performed. A systematic review and meta-analysis were conducted to examine the prevalence of inherited AT, PC, and PS deficiencies in these patients and to compare the prevalence with healthy subjects. METHODS: PubMed, EMBASE, and Cochrane Library databases were employed to identify all studies in which inherited AT, PC, and PS deficiencies in PVST and/or BCS were evaluated by family study or gene analysis. Prevalence and odds ratios of these inherited deficiencies were pooled; heterogeneity among studies was evaluated. RESULTS: Nine studies were included in our meta-analysis. The pooled prevalence of inherited AT, PC, and PS deficiencies were 3.9%, 5.6%, and 2.6% in PVST, and 2.3%, 3.8%, and 3.0% in BCS, respectively. Heterogeneity among studies was not significant except for the analysis of inherited PC deficiency in BCS. Three studies compared the prevalence of these inherited deficiencies between PVST patients and healthy subjects. The pooled odds ratios of inherited AT, PC, and PS deficiencies for PVST patients were 8.89 (95% confidence interval [CI] 2.34-33.72, P = 0.0011), 17.63 (95% CI 1.97-158.21, P = 0.0032), and 8.00 (95% CI 1.61-39.86, P = 0.011), respectively. Only one study demonstrated that no inherited deficiency was found in both BCS patients and healthy subjects. CONCLUSIONS: Inherited AT, PC, and PS deficiencies are rare in PVST and BCS. These inherited deficiencies increase the risk of PVST.
Subject(s)
Portal System , Thrombophilia/complications , Venous Thrombosis/etiology , Antithrombin Proteins/deficiency , Asia/epidemiology , Budd-Chiari Syndrome/etiology , Europe/epidemiology , Humans , Odds Ratio , Prevalence , Protein C Deficiency/complications , Protein C Deficiency/epidemiology , Protein S Deficiency/complications , Protein S Deficiency/epidemiology , Thrombophilia/epidemiologyABSTRACT
OBJECTIVE: To explore the distribution and influence factors of protein C (PC), protein S (PS) and antithrombin (AT) activities and to determine the prevalence of their deficiencies in the Chinese Han healthy population. METHODS: Healthy volunteers including blood donors and individuals for routine check-up were recruited from 4 Chinese medical centers. The plasma levels of PC, PS and AT activities were measured. The plasma levels of activities were measured by chromogenic substrate assay (AT and PC) and clotting assay (PS). RESULTS: A total of 3493 healthy Chinese adults had been recruited in this study. Males had higher PS and PC activities than females, especially for PS (P < 0.01). PC activities increased with age in both sexes but decreased in men after 50 years old. There was no significant change with age were of PS in 50 years old, while there was a decline in males and a rise in females above 50 years old. AT tended to increase with age in women but decreased with age in men after 50 years old. Based on the age and gender, the general prevalence of PC, PS and AT deficiencies in the general Chinese Han population were 1.15%, 1.49% and 2.29%, respectively. CONCLUSION: PC, PS and AT activities have correlation with age and gender in Chinese Han population. Reference range should be laid down and deficiencies should be identified
Subject(s)
Antithrombins/metabolism , Protein C/metabolism , Protein S/metabolism , Adolescent , Adult , Aged , Aged, 80 and over , Antithrombin III/metabolism , Antithrombin III Deficiency/epidemiology , Asian People , Female , Humans , Male , Middle Aged , Plasma/metabolism , Prevalence , Protein C Deficiency/epidemiology , Protein S Deficiency/epidemiology , Young AdultABSTRACT
AIMS: To assess the prevalence of thrombophilia among Chinese women with venous thromboembolism (VTE) developed during pregnancy. METHODS: Based on information from a tertiary teaching unit, all recorded cases of deep vein thrombosis (DVT) and pulmonary embolism (PE) during pregnancy diagnosed between 1997 and 2005, were assessed for prevalence of thrombophilia. Fifty-five healthy women, who had at least one normal pregnancy but without any previous history of VTE, were recruited as controls. RESULTS: A total of 44 subjects completed thrombophilia screening, of whom 5 (11%) were confirmed to have thrombophilia [protein C (PC) deficiency (2), protein S (PS) deficiency (1), combined PC & PS deficiency (1) and antithrombin III deficiency (1)]. Homozygous 5,10-methylenetetrahydrofolate reductase (C677T) gene mutation was found in 6 (14%) subjects but not in the controls. There was no antiphospholipid syndrome, activated PC resistance, factor V Leiden or prothrombin gene mutations. CONCLUSION: In the Chinese population, PS and PC deficiencies are common thrombophilia for VTE during pregnancy and thrombophilia screening should be recommended in all pregnant women who suffer from VTE.
Subject(s)
Pregnancy Complications, Hematologic , Thrombophilia/epidemiology , Venous Thrombosis/epidemiology , Activated Protein C Resistance/epidemiology , Adult , Antithrombin III Deficiency/epidemiology , Asian People/ethnology , Case-Control Studies , Cohort Studies , DNA Primers/chemistry , Factor V/genetics , Female , Hong Kong/epidemiology , Humans , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Mutation , Pregnancy , Prevalence , Prospective Studies , Protein C Deficiency/epidemiology , Protein S Deficiency/epidemiology , Prothrombin/genetics , Pulmonary Embolism/epidemiologyABSTRACT
PURPOSE: To evaluate the prevalence of thrombophilic disorders in polycystic ovarian syndrome (PCOS) women with history of recurrent pregnancy loss (RPL). MATERIALS AND METHODS: This study was carried out in 184 women with history of RPL, of which 92 of them were diagnosed with PCOS and 92 patients were without known PCOS. The prevalence of thrombophilic disorders was compared between the two mentioned groups. RESULTS: According to the findings, 70.7% of PCOS women with history of RPL had thrombophilic disorders. The prevalence of protein C deficiency was significantly higher in PCOS group compared to the non-PCOS group (21.7% vs. 10.9%, p = 0.04). There was a trend toward higher prevalence of protein S deficiency in PCOS group compared to the control group, but the difference did not reach statistical significance (23.9% vs. 13%, p = 0.05). The prevalence of other thrombophilic disorders such as antithrombin III deficiency, homocysteine elevation, antiphospholipid antibody and Factor V Leiden was comparable between groups. CONCLUSION: The prevalence of thrombophilic disorders was more common in PCOS women than the normal group. The protein C deficiency is associated with PCOS in women with history of RPL. There was a trend toward higher prevalence of protein S deficiency in PCOS women, which needs further study.
Subject(s)
Abortion, Habitual/etiology , Polycystic Ovary Syndrome/complications , Thrombophilia/complications , Adult , Case-Control Studies , Female , Humans , Iran/epidemiology , Middle Aged , Polycystic Ovary Syndrome/blood , Polycystic Ovary Syndrome/physiopathology , Prevalence , Protein C Deficiency/complications , Protein C Deficiency/epidemiology , Protein S Deficiency/complications , Protein S Deficiency/epidemiology , Thrombophilia/epidemiologyABSTRACT
OBJECTIVES: To investigate the association of various risk factors including thrombophilia defects, in patients with varicose veins (VVs) and history of episodes of superficial vein thrombosis (SVT). MATERIALS AND METHODS: Two hundred and thirty patients with primary VVs were included in this prospective study. A total of 128 (43 men, age 56 ± 13) had an acute episode or a previous history of SVT, while 102 patients (27 men, age 48 ± 12) did not. Coagulation profile investigation included serum levels of protein C (PC), protein S (PS), anti-thrombin III (AT III), plasminogen (Plg), A(2) antiplasmin (A(2)Apl) and activated protein C resistance (APCR). This was performed at least 3 months after the SVT episode to ensure that the results were not altered. Age and body mass index (BMI) were also assessed. RESULTS: PC deficiency was detected in 3/128 (2.3%), PS deficiency in 19/128 (14.8%), AT III deficiency in 29/128 (22.7%), Plg deficiency in 9/128 (7%), A(2)Apl excess in 3/128 (2.3%) and APCR in 9/128 (7%) patients with SVT and 0/102 (0%), 3/102 (2.9%), 15/102 (14.7%), 6/102 (5.8%), 0/102 (0%) and 1/102 (0.9%) in the control group, respectively. BMI greater than 30 kg m(-2) was associated with SVT. In logistic regression analysis SVT was associated with PS deficiency (odds ratio (OR) 6.7, p = 0.004, 95% confidence interval (CI) 1.83-24.53), obesity (OR 3.5, p = 0.003, 95% CI 1.53-8.05) and age (OR 1.038, p = 0.001, 95% CI 1.01-1.06). CONCLUSIONS: Obesity, age and PS deficiency were found as factors associated with SVT episodes in patients with VVs.
Subject(s)
Thrombophilia/epidemiology , Varicose Veins/epidemiology , Venous Thrombosis/epidemiology , Age Distribution , Age Factors , Biomarkers/blood , Body Mass Index , Case-Control Studies , Comorbidity , Female , Humans , Male , Middle Aged , Obesity/blood , Obesity/epidemiology , Prevalence , Prospective Studies , Protein S Deficiency/blood , Protein S Deficiency/diagnosis , Protein S Deficiency/epidemiology , Risk Factors , Thrombophilia/blood , Thrombophilia/diagnosis , Varicose Ulcer/epidemiology , Varicose Veins/blood , Varicose Veins/diagnosis , Venous Thrombosis/blood , Venous Thrombosis/diagnosisABSTRACT
Inherited thrombophilia is defined as a genetically determined tendency to develop venous thromboembolism. In children, inherited thrombophilia contributes to the development of pediatric thromboembolic disease. As a consequence, pediatric hematologists are increasingly requested to test thrombophilia in pediatric patients with thrombosis or asymptomatic children from thrombophilic families. This article reviews the benefits and limitations of testing for thrombophilic disorders, for example, factor V Leiden, prothrombin mutation, and deficiencies of antithrombin, protein C, or protein S in childhood.