Haemophilia and thrombophilia

2003 ◽  
Vol 23 (01) ◽  
pp. 36-40 ◽  
Author(s):  
C. Escuriola ◽  
K. Kurnik ◽  
R. Schobess ◽  
S. Horneff ◽  
A. Kosch ◽  
...  
Keyword(s):  
Risk Factors ◽  
Factor Viii ◽  
Protein C ◽  
Methylenetetrahydrofolate Reductase ◽  
Haemorrhagic Stroke ◽  
Type I ◽  
Haemophilia A ◽  
Factor V ◽  
Severe Haemophilia ◽  
Prothrombotic Risk Factors

SummaryFor the study presented here 135 pediatric PUP patients with haemophilia consecutively admitted to German pediatric haemophilia treatment centers were investigated. In addition to factor VIII activity, the factor V (FV) G1691A mutation, the factor II (FII) G20210A variant, methylenetetrahydrofolate reductase (MTHFR) T677T genotype, elevated lipoprotein a (Lp a), antithrombin, protein C, and protein S were investigated. 103 out of 122 HA patients (FVIII activity <1%) were suffering from severe HA. The prevalence of prothrombotic risk factors in children with severe haemophilia A (HA) did not differ from previously reported data: FV GA 5.8%, FII GA 3.9%, MTHFR TT 10%, elevated Lp a 7%, protein C type I deficiency 1.1%. The first symptomatic bleeding leading to diagnosis of severe haemophilia occurred with a median age of 1.6 years (range: 0.5-7.1 years) in children carrying prothrombotic risk factors compared to non-carriers (0.9 years (0.1-4.0; p = 0.01). Two patients presenting with neonatal stroke due to elevated Lp a and the FII GA variant showed haemorrhagic stroke transformation triggered by severe haemophilia. In addition, when haemophilia A was corrected by administration of factor VIII concentrates eight out of 25 children with central lines in place developed catheter-related thrombosis. Conclusion: The data of this multicentre cohort study demonstrate that the clinical phenotype of severe haemophilia A in childhood is clearly influenced by the coinheritance of prothrombotic risk factors.

Symptomatic Onset of Severe Hemophilia A in Childhood is Dependent on the Presence of Prothrombotic Risk Factors

2001 ◽  
Vol 85 (02) ◽  
pp. 218-200 ◽  
Author(s):  
S. Halimeh ◽  
K. Kurnik ◽  
R. Schobess ◽  
C. Wermes ◽  
R. Junker ◽  
...  
Keyword(s):  
Risk Factors ◽  
Protein C ◽  
Hemophilia A ◽  
Protein S ◽  
Type I ◽  
Factor V ◽  
Severe Hemophilia ◽  
Multicenter Cohort Study ◽  
Prothrombotic Risk Factors ◽  
Reported Data

SummaryIt has been recently suggested that the clinical phenotype of severe hemophilia A (HA) is influenced by co-inheritance with the factor V G1691A mutation. We therefore investigated 124 pediatric PUP patients with hemophilia (A: n = 111) consecutively admitted to German pediatric hemophilia treatment centers. In addition to factor VIII activity, the factor V (FV) G1691A mutation, the prothrombin (PT) G20210A variant, antithrombin, protein C, protein S and anti-thrombin were investigated. 92 out of 111 HA patients (F VIII activity < 1%) were suffering from severe HA. The prevalence of prothrombotic risk factors in children with severe HA was no different from previously reported data: FV G1691A 6.5%, PT G20201A 3.2%, and protein C type I deficiency 1.1%. No deficiency states of antithrombin or protein S were found in this cohort of hemophilic patients. The first symptomatic bleeding leading to diagnosis of severe hemophilia (< 1%) occurred with a median (range) age of 1.6 years (0.5-7.1) in children carrying defects within the protein C pathway or the PT gene mutation compared with non-carriers of prothrombotic risk factors (0.9 years (0.1-4.0; p = 0.01). The cumulative event-free bleeding survival was significantly prolonged in children carrying additionally prothrombotic defects (log-rank/Mantel-Cox: p = 0.0098). In conclusion, data of this multicenter cohort study clearly demonstrate that the first symptomatic bleeding onset in children with severe HA carrying prothrombotic risk factors is significantly later in life than in non-carriers.

Evaluation of the Prothrombotic Risk Factors in Children with Leukemia

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5355-5355
Author(s):  
Aysegul Unuvar ◽  
Arzu Akcay ◽  
Ebru T Saribeyoglu ◽  
Deniz Tugcu ◽  
Zeynep Karakas ◽  
...  
Keyword(s):  
Risk Factors ◽  
Venous Thrombosis ◽  
Protein C ◽  
Screening Program ◽  
Prothrombin G20210a ◽  
Factor V ◽  
Vascular Events ◽  
Jugular Vein Thrombosis ◽  
G20210a Mutation ◽  
Prothrombotic Risk Factors

Abstract 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.

Risk Factors and Long-term Follow-up of Patients with the Immune Type of Heparin-Induced Thrombocytopenia

2002 ◽  
Vol 8 (4) ◽  
pp. 347-352 ◽  
Author(s):  
Edelgard Lindhoff-Last ◽  
Britta Wenning ◽  
Martina Stein ◽  
Frank Gerdsen ◽  
Rupert Bauersachs ◽  
...  
Keyword(s):  
Risk Factors ◽  
Factor Viii ◽  
Protein C ◽  
Protein S ◽  
Factor Xii ◽  
Factor V ◽  
Heparin Induced Thrombocytopenia ◽  
Long Term Follow Up

Dispositional risk factors for developing the immune-type of heparin-induced thrombocytopenia (HIT) are yet unclear. This article presents a long-term follow-up of patients with HIT to define possible risk factors that may increase the risk of HIT. The clinical course of acute HIT was analyzed retrospectively in 52 patients with HIT. Thirteen patients died;8 due to HIT. A follow-up investigation was performed in 28 of the remaining 39 patients 29 ± 12 months after the onset of HIT, including genotyping for the factor V G1691A- and the prothrombin G20210A-mutation, measurement of antithrombin, protein C, protein S, factor VIII, and factor XII activity as well as the concentration of antiphospholipid antibodies. The results were compared to an age- and sex-matched control group. New thromboembolic events and re-exposure to heparin were also documented. No difference between patients and controls was observed concerning the factor V Leiden mutation, the prothrombin mutation, factor XII, antithrombin, protein S, or protein C deficiency and antiphospholipid antibodies. Increased factor VIII activity was found in 16 of 21 HIT patients compared to 4 of 21 controls (p=0.0005). New thromboembolic events developed in 5 patients within 9 months after HIT. One patient had been re-exposed to heparin 9 months after acute HIT without any complications. Increased factor VIII activity was frequently observed in patients in whom HIT developed. Thromboembolic complications within the first months after onset of HIT occurred often.

Lipoprotein (a) and Genetic Polymorphisms of Clotting Factor V, Prothrombin, and Methylenetetrahydrofolate Reductase Are Risk Factors of Spontaneous Ischemic Stroke in Childhood

Blood ◽  
1999 ◽  
Vol 94 (11) ◽  
pp. 3678-3682 ◽  
Author(s):  
Ulrike Nowak-Göttl ◽  
Ronald Sträter ◽  
Achim Heinecke ◽  
Ralf Junker ◽  
Hans-Georg Koch ◽  
...  
Keyword(s):  
Risk Factors ◽  
Ischemic Stroke ◽  
Protein C ◽  
Methylenetetrahydrofolate Reductase ◽  
Rare Event ◽  
Clotting Factor ◽  
Prothrombin G20210a ◽  
Factor V ◽  
Protein C Deficiency ◽  
Lipoprotein A

Ischemic stroke is a rare event in childhood. In approximately one third of cases no obvious underlying cause or disorder can be detected. We investigated the importance of genetic risk factors of venous thromboembolism in childhood or stroke in adulthood as risk factors for spontaneous ischemic stroke in children. One hundred forty-eight Caucasian infants and children (aged 0.5 to 16 years) with stroke and 296 age-matched controls from the same geographic areas as the patients were analyzed for increased lipoprotein (a) [Lp(a)] levels >30 mg/dL; for the presence of the factor V (FV) G1691A mutation, the prothrombin (PT) G20210A variant, and the TT677 genotype of methylenetetrahydrofolate reductase (MTHFR); and deficiencies of protein C, protein S, and antithrombin. The following frequencies (patients v controls), odds ratios (ORs), and confidence intervals (CIs) of single risk factors were found: Lp(a) >30 mg/dL (26.4% v 4.7%; OR/CI, 7.2/3.8 to 13.8; P < .0001), FV G1691A (20.2% v 4%; OR/CI, 6/2.97 to 12.1; P < .0001), protein C deficiency (6% v 0.67%; OR/CI, 9.5/2 to 44.6; P = .001), PT G20210A (6% v 1.3%; OR/CI, 4.7/1.4 to 15.6; P = .01), and the MTHFR TT677 genotype (23.6% v 10.4%; OR/CI, 2.4/1.53 to 4.5; P < .0001). A combination of the heterozygous FV G1691A mutation with increased Lp(a) (n = 11) or the MTHFR TT677 genotype (n = 5) was found in 10.8% of cases, but only 0.3% of controls (OR/CI, 35.75/4.7 to 272;P < .0001). Increased Lp (a) levels, the FV G1691A mutation, protein C deficiency, the prothrombin G20210A variant, and the MTHFR TT677 are important risk factors for spontaneous ischemic stroke in childhood.

Lipoprotein (a) and Genetic Polymorphisms of Clotting Factor V, Prothrombin, and Methylenetetrahydrofolate Reductase Are Risk Factors of Spontaneous Ischemic Stroke in Childhood

Blood ◽  
1999 ◽  
Vol 94 (11) ◽  
pp. 3678-3682 ◽  
Author(s):  
Ulrike Nowak-Göttl ◽  
Ronald Sträter ◽  
Achim Heinecke ◽  
Ralf Junker ◽  
Hans-Georg Koch ◽  
...  
Keyword(s):  
Risk Factors ◽  
Ischemic Stroke ◽  
Protein C ◽  
Methylenetetrahydrofolate Reductase ◽  
Rare Event ◽  
Clotting Factor ◽  
Prothrombin G20210a ◽  
Factor V ◽  
Protein C Deficiency ◽  
Lipoprotein A

Abstract Ischemic stroke is a rare event in childhood. In approximately one third of cases no obvious underlying cause or disorder can be detected. We investigated the importance of genetic risk factors of venous thromboembolism in childhood or stroke in adulthood as risk factors for spontaneous ischemic stroke in children. One hundred forty-eight Caucasian infants and children (aged 0.5 to 16 years) with stroke and 296 age-matched controls from the same geographic areas as the patients were analyzed for increased lipoprotein (a) [Lp(a)] levels &gt;30 mg/dL; for the presence of the factor V (FV) G1691A mutation, the prothrombin (PT) G20210A variant, and the TT677 genotype of methylenetetrahydrofolate reductase (MTHFR); and deficiencies of protein C, protein S, and antithrombin. The following frequencies (patients v controls), odds ratios (ORs), and confidence intervals (CIs) of single risk factors were found: Lp(a) &gt;30 mg/dL (26.4% v 4.7%; OR/CI, 7.2/3.8 to 13.8; P &lt; .0001), FV G1691A (20.2% v 4%; OR/CI, 6/2.97 to 12.1; P &lt; .0001), protein C deficiency (6% v 0.67%; OR/CI, 9.5/2 to 44.6; P = .001), PT G20210A (6% v 1.3%; OR/CI, 4.7/1.4 to 15.6; P = .01), and the MTHFR TT677 genotype (23.6% v 10.4%; OR/CI, 2.4/1.53 to 4.5; P &lt; .0001). A combination of the heterozygous FV G1691A mutation with increased Lp(a) (n = 11) or the MTHFR TT677 genotype (n = 5) was found in 10.8% of cases, but only 0.3% of controls (OR/CI, 35.75/4.7 to 272;P &lt; .0001). Increased Lp (a) levels, the FV G1691A mutation, protein C deficiency, the prothrombin G20210A variant, and the MTHFR TT677 are important risk factors for spontaneous ischemic stroke in childhood.

Prothrombotic Risk Factors in Children with Acute Lymphoblastic Leukemia Treated with Delayed E. coli Asparaginase (COALL-92 and 97 Protocols)

2000 ◽  
Vol 83 (06) ◽  
pp. 840-843 ◽  
Author(s):  
Christine Mauz-Körholz ◽  
Ralf Junker ◽  
Ulrich Göbel ◽  
Ulrike Nowak-Göttl
Keyword(s):  
Risk Factors ◽  
Methylenetetrahydrofolate Reductase ◽  
Lymphoblastic Leukemia ◽  
Protein S ◽  
Prothrombin G20210a ◽  
Factor V ◽  
E Coli ◽  
Prothrombotic Risk Factors ◽  
Reported Data

SummaryHereditary prothrombotic risk factors have been shown to increase the risk of venous thrombosis in children treated with the combination of E. coli asparaginase and steroids. In the present study the role of prothrombotic risk factors in children with ALL treated according to the COALL study protocol was investigated in 108 consecutively recruited childhood patients. The prevalence rates of prothrombotic risk factors [factor V G1691A mutation, the prothrombin G20210A variant, the TT677 methylenetetrahydrofolate reductase genotype, deficiencies of protein C, protein S, antithrombin, elevated lipoprotein (a)] in this cohort were within the range reported for healthy Caucasians, and comparable to previously reported data for other leukemic patients. Venous thromboembolism occurred in 3 of the 108 children (induction n = 1; reinduction n = 2: 2.8%), and none of these children carried a prothrombotic risk factor. The results of the present study, suggest that the role of hereditary and acquired disturbances of coagulation in the development of thromboses might depend on the treatment regimen.

Modulation of the activated protein C pathway in severe haemophilia A patients: The effects of thrombomodulin and a factor V-stabilizing fab

Haemophilia ◽  
2017 ◽  
Vol 23 (6) ◽  
pp. 941-947 ◽  
Author(s):  
D. F. Brophy ◽  
E. J. Martin ◽  
B. M. Mohammed ◽  
J. C. Barrett ◽  
J. G. Kuhn ◽  
...  
Keyword(s):  
Protein C ◽  
Activated Protein C ◽  
Haemophilia A ◽  
Factor V ◽  
Severe Haemophilia

ID: 7: VENOUS THROMBOEMBOLISM (VTE) AFTER ROUTINE KNEE ARTHROSCOPY IN 10 PATIENTS WITH PREVIOUSLY UNKNOWN FAMILIAL THROMBOPHILIA

2016 ◽  
Vol 64 (4) ◽  
pp. 918.1-918
Author(s):  
V Jetty ◽  
M Prince ◽  
P Wang ◽  
CJ Glueck
Keyword(s):  
Factor Viii ◽  
Knee Replacement ◽  
Protein C ◽  
Methylenetetrahydrofolate Reductase ◽  
Knee Arthroscopy ◽  
Factor V Leiden ◽  
Factor V ◽  
Protein C Deficiency ◽  
Venous Thromboembolic Events ◽  
Normal Controls

BackgroundTraditionally, elective knee arthroscopy has been thought to be an unlikely source of venous thromboembolic events (VTE) (0.6% to 18%) in contrast to total knee replacement (TKR) with incidence of ∼30%. Hence, there have been no guidelines for thromboprophylaxis in elective, routine knee arthroscopy.PurposeIn 10 patients with VTE after routine knee arthroscopy, our specific aim was to assess for familial and acquired thrombophilia, with contrast to 110 healthy normal controls and 17 patients after total hip and knee replacement (THKR).MethodsPatients were included if they had a VTE up to 6 months after either knee arthroscopy or THKR. In these patients, we measured Factor V Leiden, Prothrombin gene mutation (PTG), Plasminogen activating inhibitor gene (PAI-G) mutation, methylenetetrahydrofolate reductase (MTHFR) mutations, elevated Factors VIII and XI elevated homocysteine, Anticardiolipin IgG and IgM antibodies, Lupus anticoagulant, antigenic protein C, S (and free S), and antithrombin III deficiency. The same coagulation data was obtained for normal controls (n=110) and for 17 patients who had VTE after TKHR.ResultsAs summarized below, the major thrombophilias in the arthroscopy group were Factor V Leiden heterozygosity in 40%, high factor VIII in 50%, and high homocysteine in 30%. This pattern in the 10 patients with arthroscopy did not differ from that in 17 patients with THKR, who also differed from normal by having more frequent low proteins C and S.ConclusionAlthough VTE after knee arthroscopy is uncommon, we suggest that three common familial thrombophilias Factor V Leiden, high Factor VIII, and homocysteine routinely be measured before arthroscopy to facilitate post arthroscopy thromboprophylaxis.Abstract ID: 7 Table 1Incidence of VTE after knee arthroscopy and THKR versus normal controls. Factor V LeidenHigh Homocysteine (≥10.4 umol/L)High ACLA IgM (≥13MPL)High Factor VIII (≥150%)Protein C Deficiency (<73%)Low free protein S (≤66%)Arthroscopy (n=10)40%§30%†10%50%§25% (2/8)17% (1/6)THKR (n=17)18%†19% (3/16)18%†53%§27% (4/15)*30% (3/10)†Healthy, normal controls (n=110)2%5%2%7%6%2%*p<0.05; †p<0.025; §p<0.001.

Sign in / Sign up

Export Citation Format

Share Document