Prothrombotic Risk Factors In Children Research Articles

Inherited prothrombotic risk factors in children with hereditary angioedema

Aim: Hereditary angioedema is characterized with recurrent mucocutaneous angioedema, abdominal pain, edema of larynx and extremities. Dermal vascular thrombosis and systemic coagulation may occur in patients with hereditary angioedema due to inhibition of activated factor XII, thrombin and plasmin. Aim of this study was to screen patients with HAE for prothrombotic genetic risk factors before treatment.Material and Methods: Ten patients with hereditary angioedema who were followed up at our clinic were included in our study. The type and frequency of attack, use of prophylaxis and family history of hereditary angioedema were questioned and prothrombotic risk factors were studied.Results: Among the 10 included patients, five of them were male (50%) and five were female (50%). Four patients had abdominal edema (40%), four patients had edema of hands, feet and face (40%). One patient (10%) had heterozygous factor V G1691A mutation, another one had also heterozygous protrombin G20210A mutation. The heterozygous methylene tetrahydrofolate reductase (MTHFR) mutation were identified in seven patients (70%) and homozygous MTHFR mutation were found two patients (20%).Conclusion: In patients with hereditary angioedema, evaluation of protrombotic risk factors was crucial to estimate attack frequency-severity and treatment related thrombosis risk.Keywords: Hereditary angioedema; prothrombotic risk factors; C1 inhibitor; thrombosis.

Cerebral Sinus Venous Thrombosis and Prothrombotic Risk Factors in Children: A Single-Center Experience From Turkey

Cerebral sinus venous thrombosis (CSVT) is a rare cerebrovascular disease that may be life-threatening, especially in children. The purpose of this study was to assess the clinical presentation, radiologic imaging, underlying conditions, treatment, and outcomes of children with CSVT. In total, 23 consecutive children aged between 1 month to 18 years with CSVT, who were followed-up in Erciyes University Children's Hospital, were retrospectively enrolled in the study from January 2000 to December 2016. The median age of the 23 children (13 female patients, 10 male patients) at initial diagnosis was 60 months (1 to 204 mo). The most common clinical manifestation was headache/irritability (n=9). The most common site of the CSVT was the transverse sinus (n=16). The most common prothrombotic risk factor was protein C deficiency (n=4). Underlying risk factors were detected in 15 patients. Genetic risk factors such as protein C deficiency, infections, trauma, malignancies, autoimmune hemolytic anemia, neurometabolic disorders, asphyxia, and cardiac malformations were common risk factors. Six children died. Multiple sinus involvement and parenchymal hemorrhages were seen in 4 and in 3 of the 6 children who died, respectively. Protein C deficiency seemed to be relatively high in the presented children. Multiple sinus involvement and additional parenchymal hemorrhages represent poor prognostic features.

Inherited prothrombotic risk factors in children with extrahepatic portal vein obstruction(EHPVO). A case–control study

Inherited prothrombotic risk factors in children with extrahepatic portal vein obstruction(EHPVO). A case–control study

THU-415 - Inherited prothrombotic risk factors in children with extrahepatic portal vein obstruction: a case-control study

THU-415 - Inherited prothrombotic risk factors in children with extrahepatic portal vein obstruction: a case-control study

Multiple presence of prothrombotic risk factors in Croatian children with arterial ischemic stroke and transient ischemic attack

AimTo determine the frequency of inherited and acquired prothrombotic risk factors in children with arterial ischemic stroke (AIS) and transient ischemic attacks (TIA) in Croatia.MethodsWe investigated 14 prothrombotic risk factors using blood samples from 124 children with AIS or TIA and 42 healthy children. Prothrombotic risk factors were classified into five groups: natural coagulation inhibitors (antithrombin, protein C, protein S), blood coagulation factors (FV Leiden and FII 20210), homocysteine, lipid and lipoprotein profile (lipoprotein (a), triglycerides, total, high- and low-density lipoprotein), and antiphospholipid antibodies (lupus anticoagulant, anticardiolipin, and antiphosphatidylserine antibodies).ResultsThe most common prothrombotic risk factor was elevated lipoprotein (a), which was identified in about 31% of patients and in 24% of controls. Natural coagulation inhibitors were decreased in about 19% of patients, but not in controls. Pathological values of homocysteine, blood coagulation factor polymorphisms, and antiphospholipid antibodies were found in similar frequencies in all groups. Fourteen children with AIS and TIA (11.3%) and no children from the control group had three or more investigated risk factors.ConclusionThe presence of multiple prothrombotic risk factors in children with cerebrovascular disorder suggests that a combination of risk factors rather than individual risk factors could contribute to cerebrovascular disorders in children.

Inherited Pro-Thrombotic Risk Factors in Children of South Moravia Region, Czech Republic

Abstract 5136 Introduction:Pro-thrombotic risk factors are associated with increased risk of thrombosis. Some of them are inherited, but clinical manifestation of thrombosis in childhood is rare. It is most likely to appear in the adulthood. When leading to thrombosis during childhood, risk factors must be either very strong (e. g. homozygous deficiency of natural coagulation inhibitors), or must act together with other, usually acquired factors. Aims:- To analyse data of children referred for thrombophilia screening to Thrombosis Haemostasis centre, Dpt. of Paediatric Haematology University Hospital Brno, Czech Republic in years 2005–09.- To specify the characteristics of that cohort and identify the reasons for referral.-To determine prevalence of respective risk factors (RF) in children within study cohort.-To analyse possible correlation between related RF findings (ProC Global and FV Leiden, Protein C, Protein S; homocystein and MTHFR C677T polymorphism). Methods:We have collected data of all consecutive children aged from 0 to 18 years referred to our out-patient clinic for assessment of inherited thrombophilia in years 2005–2009 for any reason. Data recorded for each patient were as follows: age, gender, reason for assessment, thrombotic event and its type (if applicable) and vascular anomalies. Laboratory examinations done: FV Leiden mutation, Prothrombin gene mutation G20210A, MTHFR C677T polymorphism, protein C, protein S and Antithrombin levels, coagulation activity of F VIII, ProC Global test, homocystein and lipoprotein (a) level. Data were statistically analyzed to reach the aims of the study. Results:Data of 849 Caucasian children aged 0–18 years were available for analysis, 475 girls (55. 9 %) and 374 boys (44. 1 %). Median age was 11 years at the time of referral, boys 10 years, girls 13 years. Reasons for thrombophilia screening were as follows: family history of thrombosis/thrombophilia (70. 6 %), vascular anomaly (10. 8 %), thrombotic event (8 %) and others (10. 6 %). Thrombophilia screening was in more than 70 % of children performed before 15 years of age. Thrombotic event has been recorded in 79 patients (9. 3 %), both arterial (37. 6 %) and venous (63. 3 %). Adolescent patients had significantly more thrombotic events than younger children. Most of them were venous thromboses. Ischemic strokes and other arterial events were relatively more frequent in younger children. Frequency of “positive” laboratory findings in the studied cohort were as follows: MTHFR 60. 3 %, positive ProC Global test findings 58. 1 %, FV Leiden (heterozygous)37 %, hyperlipoproteinemia (a) 28. 5 %, protein S deficiency 11. 3 %, high FVIII activity 9. 4 %, Prothrombin gene mutation (heterozygous) 7. 7 %, Antithrombin deficiency 2. 7 %, elevation of homocystein 1. 6 % and protein C deficiency 1 %. Findings have confirmed high sensitivity of ProC Global test to the pathology in protein C pathway, particularly to FV Leiden mutation (sensitivity 98. 4 %). There was no statistically significant relation between homocystein level and MTHFR polymorphism status. Prevalence of RF in study cohort was found to be similar to the literature data. Deficiencies of natural coagulation inhibitors (AT, PC and PS) were rare, pro-thrombotic mutations were more frequent. Data suggest, that role of inherited pro-thrombotic risk factors in the development of thrombotic event in children is not the major one. It is very likely, that more potent risk factors, often acquired ones, are often important for development of thrombotic event during childhood. Conclusions:In our centre, we assessed proximately 170 children referred for thrombophilia screening per year. The incidence is thus 8 children per 10000. During 2005–09the main reason for referral was positive family history, but children were often referred in younger age, than recommended. The evidence available to date suggests that it is neither necessary nor useful to examine asymptomatic children before they reach puberty. Finding of inherited thrombophilia, and thus possibility to use measures preventing eventual thrombotic event, are more important in adolescence and adulthood rather than in younger age. In children with thrombotic event, however, it is recommended to screen for inherited risks. Diagnosis and treatment of thrombotic event in children requires a specialised care and relevant expertise of the Paediatric Thrombosis Haemostasis centre. Disclosures:No relevant conflicts of interest to declare.

Inherited prothrombotic risk factors in children with first ischemic stroke

Stroke in children is a heterogeneous disorder. Over 100 risk factors for stroke have been reported and genetic predisposition to stroke has been established. The most frequently reported risk factors are congenital heart malformations, hemolytic anemias, collagen vascular diseases, some rare inborn metabolic disorders, trauma, infection and thrombophilia. The aim of this article is to provide an overview of investigated inherited prothrombotic risk factors in children with first ischemic stroke. Various prothrombotic risk factors have been investigated in pediatric stroke including elevated homocysteine and lipoprotein (a), antithrombin, protein C and protein S deficiency, Factor V Leiden, Factor II G20210A and plasminogen activator inhibitor-1 4G/5G polymorphism. Despite similar criteria for inclusion of different studies in meta-analyses investigating first ischemic stroke in children, the obtained results were not consistent for all prothrombotic risk factors. The discrepancies found could be explained by methodological issues like different sample sizes, patient populations included and lack of controls. In order to provide the necessary power for randomized control trials, multi-center, multi-national approaches like International Pediatric Stroke Study have been initiated with the aim to describe risk factors for childhood stroke and explore their relationship with presentation, age, geography, and infarct characteristics. Although it is evident from numerous studies that the frequency of inherited prothrombotic factors is increased in pediatric stroke, single thrombophilia does not fully explain stroke in a child as it represents only a mild risk factor. Further studies are needed, as improved understanding of underlying mechanisms will improve primary and secondary prevention of childhood stroke.

Genetic Prothrombotic Risk Factors in Children With Extrahepatic Portal Vein Obstruction

Genetic Prothrombotic Risk Factors in Children With Extrahepatic Portal Vein Obstruction

Ischemic Stroke in a 7-Month-Old Infant With Antiphospholipid Antibody and Homozygous C677T Methylenetetrahydrofolate Reductase (MTHFR) Polymorphism

Prothrombotic risk factors in children with ischemic stroke have been increasingly recognized with recent developments in technology. Extensive evaluation including a detailed family history is required to identify various inherited or acquired prothrombotic conditions. We report a 7-month-old male who presented with right hemiparesis. Acute cerebral infarction in the area supplied by the left lenticulostriate artery was confirmed through magnetic resonance imaging. De novo synthesis of antiphospholipid antibodies and homozygous methylenetetrahydrofolate reductase (MTHFR) polymorphism were identified as presumed prothrombotic risk factors. His twin sister and mother were also positive for antiphospholipid antibodies. Multiple risk factors for ischemic stroke should be considered, particularly in the perinatal and infancy period. This case also underlines the rare familial occurrence of antiphospholipid antibodies and its relationship to ischemic stroke in infancy.

Inherited Prothrombotic Risk Factors in Migraine, Stroke, or Transient Ischemic Attack

The prevalence and association of inherited prothrombotic risk factors in children with established diagnoses of stroke, transient ischemic attack, or migraine were studied at Zagreb University School of Medicine, Croatia.

Inherited Prothrombotic Risk Factors in Children With Stroke, Transient Ischemic Attack, or Migraine

The aim of this study was to investigate the prevalence and possible association of inherited prothrombotic risk factors in children with stroke, transient ischemic attack, or migraine. We performed genotypic analysis for factor V G1691A, factor II G20210A, methylenetetrahydrofolate reductase C677T, and 4 common platelet glycoprotein polymorphisms (human platelet alloantigen-1, -2, -3, and -5) in 150 children <18 years of age with established diagnoses of stroke, transient ischemic attack, or migraine. Children were classified into 5 groups, namely, childhood arterial ischemic stroke (N = 33), perinatal arterial ischemic stroke (N = 26), hemorrhagic stroke (N = 20), transient ischemic attack (N = 36), and migraine (N = 35). The control group consisted of 112 children < or =18 years of age from the same geographical region who had no history of neurologic or thromboembolic diseases. Heterozygosity for factor V G1691A was associated with approximately sevenfold increased risk for arterial ischemic stroke, perinatal arterial ischemic stroke, and transient ischemic attack. Increased risk for transient ischemic attack was found in carriers of the human platelet alloantigen-2b allele, human platelet alloantigen-5a/b genotype, and combined human platelet alloantigen-2b and human platelet alloantigen-5b genotype. The presence of the human platelet alloantigen-2b allele was associated with a 2.23-fold increased risk for migraine, whereas carriers of the human platelet alloantigen-3b allele had a lower risk for arterial ischemic stroke than did carriers of the human platelet alloantigen-3a allele. Factor V G1691A has an important role in susceptibility to arterial ischemic stroke, both in the perinatal/neonatal period and in childhood, as well as transient ischemic attacks. A minor impact of human platelet alloantigen polymorphisms suggests that platelet glycoprotein polymorphisms may increase the risk of transient ischemic attacks and migraine, but this should be confirmed in larger studies.

Evaluation of the Prothrombotic Risk Factors in Children with Leukemia

Pediatric patients with malignancy are at high risk of thromboembolic complications due to complex interactions of a variety of factors such as the malignancy, chemotherapy, central venous catheters (CVCs), infections, dehydration, and hereditary thrombophilia. In this study, deficiencies of protein C (PC), protein S (PS), and antithrombin (AT), activated protein C resistance (APCR), the factor V G1691A mutation, the prothrombin G20210A mutation, and increased factor VIII, IX, fasting homocysteine levels were assessed at the diagnosis of leukemia, retrospectively. The aim was to evaluate the role of the thrombophilic risk factors on vascular events during treatment period. Thirty children (11 F, 19 M) with leukemia (24 patients with ALL, 4 AML, one biphenotypic leukemia, one infant leukemia) were enrolled in this study. The median age of the patients was 56 months (range 7–215 months). All patients had CVCs, and thromboprophylaxis was not given to the any patients. We detected main prothrombotic risk factors at the diagnosis of leukemia as following: low PC (8/30), PS (11/30), AT activity (3/25), APCR (5/22), increased FVIII (5/22), FIX (2/22), and homocysteine levels (2/8), and FV Leiden mutation (1/24; heterozygous). The prothrombin G20210A mutation was not detected in any patient. The parents of these patients with abnormal test results were also evaluated to discriminate congenital or acquired deficiencies. In addition; PC, PS, AT levels were followed-up, and MTHFR genotype for the patients with high homocysteine levels was studied, also. In spite of, 24 of these 30 patients had at least one abnormal laboratory test result at the diagnosis of leukemia, venous thrombosis (7 with CVC-related venous thrombosis, one CVC-related jugular vein thrombosis and VOD, one vena saphena parva thrombosis) developed in 9 of 24 patients. In conclusion, leukemic children with at least one prothrombotic risk factor have high venous thrombosis risk. Further trials are needed to clarify the necessarity of screening program for thrombophilia and thromboprophylaxis in children with leukemia and CVCs, and, especially for the patients carrying hereditary prothrombotic risk factors.

“Classic” and “new” genetic prothrombotic risk factors in children with portal vein thrombosis

Aims. Portal vein thrombosis (PVT) is the most common single cause of portal hypertension in children. In almost half of the cases it is associated with a history of umbilical venous catheterization (UVC), whereas in the remaining cases it is idiopathic.

Genetic prothrombotic risk factors in children with ischemic cerebrovascular disease

Genetic prothrombotic risk factors in children with ischemic cerebrovascular disease

Evaluation of Inherited Prothrombotic Risk Factors in Children with Acute Lymphoblastic Leukemia.

This retrospective study was designed to determine the prevalence of inherited prothrombotic risk factors (Factor V Leiden (FV) G1691A and prothrombin G20210A mutations, TT677 genotype of the methylenetetrahydrofolate reductase (MTHFR), protein C, protein S, antithrombin deficiencies) in a population of children with ALL treated according to the FRALLE 2000 study Protocol (High Risk and Standard Risk groups). The study was performed in 5 French Centers including Amiens, Angers, Paris Trousseau, Rouen and Saint-Etienne. From December 2000 to March 2006, 354 children aged 1 to 18 years old were consecutively admitted for ALL and were enrolled in the FRALLE 2000 Protocol. Among them, 281 patients were investigated for hereditary prothrombotic defects at the time of ALL diagnosis. Informed parental consent was required for gene analysis. Abnormal test results for protein S (functional activity and free protein S antigen concentration), protein C and antithrombin were controlled on a second blood sample after induction. In the population studied, the prevalence of one established prothrombotic risk factor was 19,2%: the FV G1691A mutation was diagnosed in 10 patients (3.6%), all heterozygous, 10 patients (3.6%) showed the heterozygous prothrombin G20210A mutation, the TT677 MTHFR genotype was found in 34 children (12.7%), 1 patient showed protein C deficiency (0.4%). No antithrombin deficiency was detected. The prevalence of inherited protein S deficiency could not be evaluated because of missing data in the family medical history. Combined prothrombotic defects were found in 2 patients (0.71%): heterozygous FV G1691A mutation combined with heterozygous prothrombin G20210A mutation in 1 patient and combined with TT677 MTHFR genotype in the second patient. Except for TT677 MTHFR genotype, the prevalence of hereditary prothrombotic risk factors in children with ALL in France were found within the prevalence reported for children treated for ALL (table 1) and comparable to the prevalence in healthy Europeans (Junker et al. 1999, Margaglione et al 2001, Mueller et al. 2005).Comparison of the prevalence of inherited prothrombotic risk factors in children with ALLCountryPopulationFV G1691A +/− ++PT G20210A +/− +/+MTHFR TT677ATPCNowakGöttl et al 1999 (n=301)GermanyALL children5.3% 0.3%2% 0%7.7%0.7%2.3%Mauz-Körholz et al. 2000 (n=108)GermanyALL children5.6% 0%2.8% 0%5.6%0%2.7%Mitchell et al. 2002 (n=60)CanadaALL children3.3% 0%2% 0%NENENEPresent study (n=281)FranceALL children3.6% 0% (n=277)3.6% 0%(n=279)2.7% (n=268)0%0.4%AT: antithrombin deficiency ; PC: protein C deficiency ; NE : non evaluated

Prothrombotic risk factors in children with hemiplegic cerebral palsy

The purpose of the present paper was to investigate the prevalence of prothrombotic risk factors associated with hemiplegic cerebral palsy (CP). Twenty-three hemiplegic CP patients were tested for inherited and acquired prothrombotic risk factors, except methylene tetrahydrofolate reductase (MTFR) polymorphism. A total of 56.5% of patients had at least one coagulation abnormality and 13% of them had two. Four patients (8.7%) had infection and congenital heart disease, who also had additional coagulopathy risk factors. Obstetric problems were detected in 56.5%. Coagulopathy risk factors were factor V Leiden mutation (21.7%), protein C deficiency (21.7%), elevated lipoprotein-a (13%), G20210A mutation of prothrombin (8.7%), and protein S deficiency (4.3%). Children with hemiplegic CP need to be evaluated for coagulopathic abnormalities.

19 Inherited prothrombotic risk factors in children with perinatal arterial stroke

19 Inherited prothrombotic risk factors in children with perinatal arterial stroke

Can family history predict risk of thrombosis?

Increased risk of thrombosis can lead to important medical complications including thrombotic stroke. Several genetic factors have been identified that predispose to increased risk of thrombosis. When genetic factors are suspected, it is often assumed that a positive family history will be useful in determining which patients deserve further workup. In this issue of The Journal, Johal et al evaluated family history as a screen for genetic prothrombotic risk factors in children with stroke. They found that family history was not associated with factor V Leiden or prothrombin G20210A mutations. A positive family history had a positive predictive value of only 23% and a negative predictive value of 89%. Clearly, family history has some weaknesses as a predictor in this setting. All children with stroke or other thrombotic episodes should have a workup for prothrombotic genetic abnormalities regardless of family history. Increased risk of thrombosis can lead to important medical complications including thrombotic stroke. Several genetic factors have been identified that predispose to increased risk of thrombosis. When genetic factors are suspected, it is often assumed that a positive family history will be useful in determining which patients deserve further workup. In this issue of The Journal, Johal et al evaluated family history as a screen for genetic prothrombotic risk factors in children with stroke. They found that family history was not associated with factor V Leiden or prothrombin G20210A mutations. A positive family history had a positive predictive value of only 23% and a negative predictive value of 89%. Clearly, family history has some weaknesses as a predictor in this setting. All children with stroke or other thrombotic episodes should have a workup for prothrombotic genetic abnormalities regardless of family history.

Family History is a Poor Screen for Prothrombotic Genes in Children with Stroke

To evaluate family history of early pathological thrombosis as a screen for genetic prothrombotic risk factors in children with stroke. A 5-year retrospective review of standardized pediatric stroke clinic evaluations of children with arterial ischemic stroke (AIS) or sinovenous thrombosis (SVT). A family history of early pathological thrombosis was defined as stroke, heart attack, or deep venous thrombosis before 50 years of age or multiple miscarriages in the parents or grandparents of the patient. We evaluated the association between family history and the presence of the Factor V Leiden mutation (FVL) and/or Prothrombin G20210A mutation (PTG) in these children. The study included 68 children. Thirteen (19.1%) had a positive family history of early pathological thrombosis, nine (13.2%) were heterozygous for FVL, and one (1.5%) was heterozygous for PTG. Family history was not associated with the presence of FVL (p = .36) or FVL combined with PTG (p = .40). For FVL, family history had a positive predictive value of 23.1% and a negative predictive value of 89.1%. A family history of early thrombosis is not associated with the presence of FVL or PTG in children with stroke. We recommend that all children with stroke receive a prothrombotic workup regardless of family history.

Risk factors for venous thrombosis in swedish children and adolescents

Conclusion: There are prothrombotic risk factors present in almost all children and adolescents with venous thrombosis. Summary: Venous thrombosis has an incidence of approximately 10/10,000 in adults and 0.07/10,000 children. (Haematologica 1999;84:59-70 and Journal Pediatr Hematol Oncol 1997;19:7-22). Little information, however, exists regarding prothrombotic risk factors in children with venous thromboembolism (VTE). The authors attempted to identify prothrombotic risk factors in adolescents and children following their first VTE event. There were 128 consecutive adolescents and children (newborn to 20 years) who were evaluated following referral to a regional coagulation center in southern Sweden. The prothrombotic risk factors evaluated included protein C, protein S, antithrombin; resistant to activated protein C; genotypes FV – G1691A, II-G20210A, MTHFR-C677T, MTHFR-A1298C, and coagulation factors VIII and XI. There was also a retrospective collection of clinical data. Identifiable genetic factors related to VTE were present in 53 of 83 (64%) subjects who had follow up blood sampling. Of these 17/83 (20%) had two or more inherited risk factors. There was a combination of acquired risk factors and genetic risk factors in 45/83 subjects (54%). At least 1 risk factor was present in 77/83 subjects (93%). There was a peak frequency of VTE in children less than 1 year of age with a second peak occurring during adolescents. Levels of coagulation factors VIII and XI were age appropriate and showed a normal Gaussian distribution. Comment: While venous thromboembolism is unusual in children and adolescents, the data here suggest that a VTE event in a child should be investigated with a detailed hypercoagulable panel. The yield is high enough to merit routine use in children with VTE.