Inherited thrombophilia: Part 1 (original) (raw)
Related papers
Inherited Thrombophilia in Arterial Disease: A Selective Review
Seminars in Hematology, 2007
Thrombophilia may be defined as an acquired or congenital abnormality of hemostasis predisposing to thrombosis. Because arterial thrombosis is usually linked with classical risk factors such as smoking, hypertension, dyslipidemia, or diabetes, a thrombophilia workup is usually not considered in case of arterial thrombosis. The most accepted inherited hemostatic abnormalities associated with venous thromboembolism are factor V Leiden (FVL) and factor II (FII) G20210A mutations, as well as deficiencies in antithrombin (AT), protein C (PC), and protein S (PS). This review focuses on the link between these abnormalities and arterial thrombosis. Overall, the association between these genetic disorders and the three main arterial complications (myocardial infarction [MI], ischemic stroke [IS], and peripheral arterial disease [PAD]) is modest. Routine screening for these disorders is therefore not warranted in most cases of arterial complications. However, when such an arterial event occurs in a young person, inherited abnormalities of hemostasis seem to play a role, particularly when associated with smoking or oral contraceptive use. These abnormalities also seem to play a role in the risk of premature occlusion after revascularization procedures. Therefore thrombophilia tests may be informative in a very restricted population with arterial events. Anticoagulants rather than antiplatelet therapy may be preferable for these patients, although this remains to be proven.
Incidence and clinical characteristics of hereditary disorders associated with venous thrombosis
American Journal of Hematology, 1991
At present, different congenital defects in several proteins—antithrombin III (AT III), protein C (PC), protein S (PS), and plasminogen (PLG)—are known to be causes of hereditary predisposition to thrombosis (thrombophilia).The incidence of these hereditary disorders in our 204 patients (106 males and 98 females) with venous thromboembolism were 4% (three cases deficient in PC, three in PS, two in PLG, and one patient in AT III). Their families were studied. In all cases the disorders were inherited as an autosomal dominant trait.The first thrombotic episodes occurred at a age of below 40 years. There was no relationship between protein levels and the occurrence of thrombosis, although a significant relationship was observed between a positive history of thromboembolic disease and a diagnosis of protein deficiencies.We evaluated the differences between primary thrombosis and secondary thrombosis. The most common thrombotic sites were the deep veins. There were no differences between males and females. Evaluation of PC, PS, AT III, and PLG in patients with thromboembolic disease should be considered.
An overview of genetic risk factors in thrombophilia
Srpski arhiv za celokupno lekarstvo, 2010
Thrombophilia is a multifactorial disorder, involving both genetic and acquired risk factors that affect the balance between procoagulant and anticoagulant factors and lead to increased tendency to thrombosis. The concept that thrombophilia could be associated with genetic defects was first proposed in 1965 after the discovery of familiar antihrombin III deficiency. Further family studies showed that deficiency of protein C or protein S also increased thrombotic risk. In the coming years the advent in DNA technology, especially the invention of PCR reaction, played an important role in the identification of the exact nature of these deficiencies and opened new possibilities in the genetic research of thrombophilia. The breakthrough came with the discovery of activated protein C resistance and Factor V Leiden mutation. Shortly afterwards a mutation in the 3? untranslated region of Factor II gene (FII G20210A) associated with increased concentration of factor II in plasma, was describ...
The investigation and management of inherited thrombophilia
Clinical & Laboratory Haematology, 1999
Inherited thrombophilia can be defined as a genetically determined tendency to venous thromboembolism. Genetic risk factors for venous thrombosis include antithrombin deficiency, protein C deficiency, protein S deficiency, activated protein C resistance due to the factor V gene Leiden mutation, inherited hyperhomocysteinaemia, elevated factor VIII levels and the prothrombin gene G20210 A variant. A genetic risk factor is now identifiable in up to 50% of unselected patients with venous thrombosis. Individuals with inherited thrombophilia may develop venous thrombosis at a young age, or they may present with thrombosis at an unusual site or in the apparent absence of any precipitating event. A family history of thrombosis is suggestive of inherited thrombophilia. Laboratory investigations for inherited thrombophilia should include testing for activated protein C resistance and the factor V gene Leiden mutation, and screening for deficiencies of antithrombin, protein C or protein S. Screening for the prothrombin gene G20210 A variant, and measurement of plasma factor VIII and homocysteine levels should be considered in individual cases. In recent years the multifactorial nature of thrombophilia, both circumstantially and on a genetic level, has become increasingly apparent. Individuals with more than one inherited thrombophilia risk factor are particularly prone to thrombosis and their identification is a priority.
Thrombosis and Haemostasis, 2011
The utility of laboratory investigation of relatives of individuals with inherited thrombophilia is uncertain. To assess the risk of venous thromboembolism (VTE) among the carriers, we investigated a family cohort of 1,720 relatives of probands with thrombophilia who were evaluated because of VTE (n=1,088), premature arterial thrombosis (n=113), obstetric complication (n=257), or universal screening before pregnancy or hormonal contraception or therapy (n=262); 968 relatives were carriers of thrombophilia. A first deep venous thrombosis (DVT) occurred in 44 carriers and 10 non-carriers during 37,688 and 29,548 observationyears from birth, respectively. The risk of DVT among the carriers compared with non-carriers was estimated as a hazard ratio (HR). If the proband had VTE and factor V Leiden (FVL) and/or prothrombin (PT)20210A, the HR for DVT was 2.77 (95%CI 1.21-4.82) in the carriers overall, and 5.54 (95%CI 3.20-187.00) in those homozygous or double heterozygous for FVL and PT20210A. If the proband had VTE and a deficiency of antithrombin (AT), protein C or S, the HR for DVT was 5.14 (95%CI 0.88-10.03) in the carriers overall, and 12.86 (95%CI 2.46-59.90) in those with AT deficiency. No increase in risk was found among the carriers who were relatives of the probands who were evaluated for reasons other than VTE. In conclusion, familial investigation for inherited thrombophilia seems justified for probands with previous VTE, but appears of doubtful utility for the relatives of probands without VTE. This should be taken with caution regarding families with deficiency of natural anticoagulants, given the low number of cases analysed.
Frequency of hereditary thrombophilia: an AKUH experience
JPMA. The Journal of the Pakistan Medical Association, 2004
To determine the frequency of various causes of hereditary thrombophilia at a referral laboratory and the age and gender distribution. This is a descriptive study incorporating a retrospective analysis of requests for thrombophilia screening sent to Clinical laboratory, Aga Khan University Hospital from November 1995 to May 2002. Patients were screened for hereditary causes of thrombophilia including Protein C, Protein S, antithrombin III, Factor V Leiden and homocysteine. Frequency of each disorder; and age and sex distribution was determined. All the patients suspected clinically for thrombophilia were screened. Of the 2825 patients, 70 were diagnosed to have inheritance as a cause of thrombophilia with a frequency of 2.3% for protein C deficiency, 1.4% for protein S deficiency, 1.5% for antithrombin III deficiency, 14.2% for factor V leiden mutation and 2.0% for homocystenemia. All the causes of hereditary thrombophilia can be diagnosed by relatively simple laboratory methods, ho...
Prevalence of thrombophilia in asymptomatic individuals with a family history of thrombosis
Hippokratia, 2013
The present study investigates the prevalence of thrombophilia in individuals with first or/and second degree family history of thromboembolism. The study group consisted of 68 individuals with a first or second degree family history of venous or arterial thromboembolism, but without a personal history of thrombosis. The activity of ATIII, PC, PS, FVIII, FΧΙΙ and total homocysteine was measured on the ACL Advance coagulation analyzer. In addition, hemi-quantitative determination of CRP was performed to exclude an acute phase reaction. The existence of V-Leiden mutation was investigated by the modified pre-dilution method (1:5) with V-DEF. Prothrombin G20210A mutation was detected by the use of an in house PCR protocol. Family history was termed as follows: positive (thrombosis was reported in one parent and his/her family members) (group Α) or strongly positive (thrombosis was reported in both parents and their family members (group Β). Data analysis revealed decreased activity of A...
Pathogenesis & Laboratory approach to Thrombophilia
Eastern Journal of Medicine, 2009
Abstract. Thrombophilia is a term used for any hypercoagulable state, either inherited or acquired. The former is considered after excluding acquired predisposing causes like trauma, immobility, Dirseminated inta vascular cuagulation, pregnancy and anitphospholipid syndrome etc. It frequently results from interplay of genetic and acquired factors. An individual’s risk for DVT would be determined by the combination of his or her baseline propensity for thrombosis and the magnitude of the acute insult. Inherited hypercoagulable states may be secondary to deficiency of natural clotting inhibitors or elevated procoagulants or increased fibrinolytic factors . Amongst these, activated protein C resistance, is the commonest underlying cause .Testing for thrombophilia is best performed in stages. Highest-yield assays (screening tests) should be performed first and, if positive, should be followed by appropriate confirmatory tests. Cornerstone of initial treatment is heparin, either unfract...