Clinical Aspects and Laboratory Problems in Hereditary Thrombophilia

Abstract

Hereditary thrombophilia is a multifactorial disease which is mono- or plurigenic and its clinical expression is associated with a heterogeneous expression. Factor V (FV) Leiden and FII gene mutations are more frequent than antithrombin, and protein C and S deficiencies. All thrombophilias are not the same. Heterozygous carriers of FV Leiden or FII gene mutation have a weaker risk of venous thrombosis. The mean age at the first episode is older in the former and higher rate of recurrences is observed in the latter. The cosegregation of mutations significantly increases the risk of thrombosis. Both mutations have a geographic and ethnic distribution in relation with a gene founder effect. Clinical expression consists of deep or superficial venous thrombosis with or without pulmonary embolism, thromboses at unusual sites (e.g. cerebral, portal, mesenteric) or with an increased incidence of fetal loss and abortion. A precipitating cause is present in more than 50% of patients. The risk pf arterial thromboses seems to be restricted to some protein S and FII gene mutations. Laboratory diagnosis strategy should be oriented by careful selection of patients and preanalytical variables should be considered. It is highly probable that other unindentified gene mutations are, at least partly, other causes of the heterogeneous expression of hereditary thrombophilia.

Prevalence of hereditary thrombophilia in patients with thrombosis in different venous systems

“…The prevalence of factor V Leiden, prothrombin G20210A, protein C, protein S, and antithrombin deficiency of each of the different thrombosis groups is summarized in Table II. In the 120 healthy individuals, all values were within the expected range and comparable to those found by previous reports [1,2]. In patients with a history of deep venous thrombosis in the lower extremities, the frequency of the thrombophilias was much higher and comparable to that reported in the literature: FV Leiden, prothrombin G20210A, protein C, protein S, and antithrombin Table III shows the frequency and type of circumstantial risk factors dependent upon the presence or absence of hereditary thrombophilia.…”

“…In this group of patients, the prevalence of hereditary thrombophilia has been well studied, as reflected by consistent and reproducible prevalence rates and risk estimations (reviewed in Refs. [1] and [2]). In particular, in patients with a first episode of a deep venous thrombosis in the lower extremity, activated protein C (APC) resistance, protein C deficiency, protein S deficiency, and antithrombin deficiency have consistently been found at frequencies of about 20%, 3%, 2%, and 1% in several controlled studies, respectively [1,2].…”

“…[1] and [2]). In particular, in patients with a first episode of a deep venous thrombosis in the lower extremity, activated protein C (APC) resistance, protein C deficiency, protein S deficiency, and antithrombin deficiency have consistently been found at frequencies of about 20%, 3%, 2%, and 1% in several controlled studies, respectively [1,2]. However, in patients with thrombosis in venous systems other than those in the lower extre-mities, the frequency of hereditary clotting defects is not well known.…”

Deep Venous Thrombosis and Thrombophilia: Indications for Testing and Clinical Implications

“…Superficial venous thrombosis on nonvaricose veins should also be considered as a manifestation of thrombophilia. 9,16 This has been particularly shown for PC and PS deficiencies as well as for factor V Leiden mutation.…”

Pregnancy‐associated venous thromboembolism (VTE) in combined heterozygous factor V Leiden (FVL) and prothrombin (FII) 20210 A mutation and in heterozygous FII single gene mutation alone

“…Citrated blood was centrifuged twice at 4000 g for 15 min and tested immediately or frozen in aliquots at −30°C. All measurements on frozen plasma samples were performed within 2 weeks of blood collection, and they were all performed in our laboratory using previously described methods (Samama et al , 1999).…”