Homozygous Factor v Leiden Mutation in Sickle Cell Anaemia

Kordes, Uwe; Janka-Schaub, G. E.; Kulozik, Andreas E.; Schneppenheim, Reinhard

doi:10.1046/j.1365-2141.2002.3242_1.x

Cited by 3 publications

(2 citation statements)

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“…Hyperhomocysteinemia is considered to be a risk factor for several thrombotic events, including the cerebral and peripheral types, as well as coronary disease (Engbersen et al, 1995;Khan and Dickerman, 2006). However, there are several studies providing evidence that the mutations G1691A on Factor V and G20210A on the prothrombin gene are associated with an elevated risk of deep vein thrombosis and with the main causes of hereditary thrombophilia (Kordes et al, 2002;Khan and Dickerman, 2006;Ercan et al, 2008).…”

Section: Introductionmentioning

confidence: 97%

MTHFRPolymorphic Variant C677T Is Associated to Vascular Complications in Sickle-Cell Disease

Hatzlhofer

Bezerra

Santos

et al. 2012

Genetic Testing and Molecular Biomarkers

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Vaso-occlusion is a determinant for most signs and symptoms of sickle-cell anemia (SCA). The mechanisms involved in the pathogenesis of vascular complications in SCA remain unclear. It is known that genetic polymorphisms associated with thrombophilia may be potential modifiers of clinical features of SCA. The genetic polymorphisms C677T and A1298C relating to the enzyme methylenetetrahydrofolate reductase (MTHFR), a clotting Factor V Leiden mutation (1691G→A substitution of Factor V Leiden), and the mutant prothrombin 20210A allele were analyzed in this study. The aim was to find possible correlations with vascular complications and thrombophilia markers in a group of SCA patients in Pernambuco, Brazil. The study included 277 SCA patients, divided into two groups: one consisting of 177 nonconsanguineous SCA patients who presented vascular manifestations of stroke, avascular necrosis, leg ulcers, priapism, and acute chest syndrome (group 1); and the other consisting of 100 SCA patients without any reported vascular complication (group 2). Molecular tests were done using either polymerase chain reaction (PCR) restriction fragment length polymorphism or allele-specific PCR techniques. Comparisons between the groups were made using the χ(2) test. The 677 CT and TT genotypes showed a significant risk of vascular complications (p=0.015). No significant associations between the groups were found when samples were analyzed for the MTHFR A1298C allele (p=0.913), Factor V G1691 (p=0.555), or prothrombin G20210A mutation (p=1.000). The polymorphism MTHFR C677T seemed to be possibly predictive for the development of some vascular complications in SCA patients among this population.

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Section: Introductionmentioning

confidence: 97%

MTHFRPolymorphic Variant C677T Is Associated to Vascular Complications in Sickle-Cell Disease

Hatzlhofer

Bezerra

Santos

et al. 2012

Genetic Testing and Molecular Biomarkers

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“…However, among nine studied SCD patients with vascular complications of stroke or deep vein thrombosis they found only one patient to be a carrier for FVL. Also, Kordes et al46 reported no medical history of deep vein thrombosis in two SCA patients homozygous for FVL mutation from Iraq. Fawaz et al47 have compared the prevalence of FVL mutation and prothrombin gene variant in SCD patients and controls from Eastern Saudi Arabia.…”

Section: Genetic Of Thromboembolismmentioning

confidence: 99%

Sickle Cell Disease and Venous Thromboembolism

Rahimi¹,

Parsian²

2011

Mediterr J Hematol Infect Dis

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Hemoglobin S in homozygous state or in combination with one of the structural variants of Hb D-Punjab, Hb O-Arab, Hb C or β-thalassemia mutation results in sickle cell disease (SCD) that is characterized by chronic hemolytic anemia and tissue injury secondary to vasooclusion. A chronic hypercoagulable state in SCD has been established with the increased risk of thromboembolic complications in these patients. The goal of present review is to survey of the literature related to thromboembolic events and genetic risk factors involved in the manifestation of these events in SCD patients with focus on studies from Mediterranean countries. Also, this review covers the pathogenesis of hypercoagulability and alteration in the components of hemostasis system.

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Role of the Hemostatic System on Sickle Cell Disease Pathophysiology and Potential Therapeutics

Pakbaz

Wun

2014

Hematology/Oncology Clinics of North America

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SynopsisRecent studies suggest that sickle cell disease is a hypercoagulable state contributing to the vasoocclusive events in microcirculation resulting in acute and chronic sickle cell related organ damage. In this article, we will review the existing evidence for contribution of hemostatic system perturbation to sickle cell disease pathophysiology. We will also review the data showing increased risk of thromboembolic events, particularly newer information on the incidence of VTE. Finally, the potential role of platelet inhibitors and anticoagulants in SCD will be briefly reviewed.Keywords sickle cell; thromboembolism; hypercoagulable; anti-platelets; anticoagulants IntroductionSickle cell disease (SCD) is the result of homozygous or compound heterozygous inheritance of mutation in the β-globin gene. The resulting substitution of the hydrophilic amino acid glutamic acid at the sixth position by the hydrophobic amino acid valine, leads to the production of hemoglobin S (HbS). HbS polymerizes when deoxygenated and this polymerization is associated with cell dehydration and increased red cell density [1][2][3] . The dense, rigid and sickling red cells lead to vaso-occlusion and impaired blood flow 2,4 , and is thought to underlie acute (painful episodes, acute chest syndrome) and chronic (avascular necrosis, renal insufficiency) complications of the disease. Also, intracellular polymerization ultimately damages the red cell membrane and leads to chronic and episodic extra-vascular and intravascular hemolytic anemia, hemolysis linked nitric oxide (NO) dysregulation and endothelial dysfunction 5 resulting leg ulcer, pulmonary hypertension (PHTN), priapism and stroke 6 .Corresponding author: Ted Wun, MD. Authors contact information Address/Phone/Fax (for both authors): University of California, Davis Cancer Center, 4501 X St., Ste. 3016, Sacramento, CA 95817, Phone: (916) Fax: (916) 734-7946, zahra.pakbaz@ucdmc.ucdavis.edu, ted.wun@ucdmc.ucdavis.edu ZP has no conflict of interest.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptSeveral investigators have reported increased thromboembolic events and alteration in hemostatic system in SCD both under steady state and during acute events. This suggests that perturbation in hemostatic system may contribute to SCD pathophysiology. Changes that have been described include increased expression of tissue factor on blood monocytes 7-9 and endothelial cells 10,11 , abnormal exposure of phosphatidylserine on the red cell surface 12,13 and i...

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Homozygous Factor v Leiden Mutation in Sickle Cell Anaemia

Cited by 3 publications

References 8 publications

MTHFRPolymorphic Variant C677T Is Associated to Vascular Complications in Sickle-Cell Disease

MTHFRPolymorphic Variant C677T Is Associated to Vascular Complications in Sickle-Cell Disease

Sickle Cell Disease and Venous Thromboembolism

Role of the Hemostatic System on Sickle Cell Disease Pathophysiology and Potential Therapeutics

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