Diagnosis And Clinical Characteristics Of Inherited Activated Protein C Resistance

Abstract

The diagnostic strategies and clinical characteristics of thrombophilia associated with heterozygous or homozygous factor V Leiden mutation have been determined according to the literature and to a personal study in 51 families. Factor V mutation was present in the 51 propositi and in 84 out of 125 family members (81 heterozygous, 3 homozygous). Venous thrombosis was observed in all the propositi, in 17 of the 84 family members with the mutation and in 6 of the 41 with a normal APC resistance test and no mutation. An associated protein C or protein S deficiency was present in 5 families (10 %). The most frequent clinical manifestations were superficial or deep vein thrombosis and/or pulmonary embolism, but also thrombosis at an unusual site (cerebral, mesenteric or central retinal vein). A causal relationship is frequently difficult to demonstrate. A precipitating factor was observed in 84 % of cases and a recurrent thrombotic episode occured in 50 % of propositi. The risk of thrombosis associated with pregnancy was high in the post-partum period, especially in homozygous women. In the 28 homozygous subjects, markers of coagulation activation were frequently elevated in untreated patients. Finally, the efficacy of anticoagulant treatment is suggested but the long period often observed between treatment interruption and a recurrence does not militate in favour of long term treatment.

Aetiology of Venous Thrombosis

“…Several studies quickly followed that discovery and proved a positive association between FVL and VTE, showing that heterozygous carriers of the mutation are at higher risk of developing VTE by 10-fold while homozygous carriers have a much higher risk ratio reaching 140-fold (Dahlbäck et al, 1993;Zöller et al, 1994;Bertina et al, 1994;Hoagland et al, 1996;Dahlbäck, 1997;Faioni et al, 1997;Alderborn et al, 1997;Bontempo et al, 1997). Moreover, most homozygous cases were found to get at least one VTE event in their life time, and at an earlier time of their life (Samama et al, 1996;Florell & Rodgers, 1997). The identification of APC-R/FVL and its high risk value have exploded a massive rush in researches to study this new disease, its prevalence and its relationship with VTE in almost every part of the world.…”

“…Only 10% of TFPI is present as a free active form in the blood while the majority is in combination with lipoproteins. Deficiency in TFPI may lead to a hypercoagulable state and hence VTE (Novotny et al, 1989;Novotny, 1994;Samama et al, 1996;Cella et al, 1997;Ehsan & Plumbley, 2002). TFPI decreased activity was noticed to contribute in developing thrombosis in women using oral contraceptives, and in patients with paroxysmal nocturnal haemoglobinuria (Maroney & Mast;2008).…”

“…Acquired risk factors, including trauma, surgery, immobilization, pregnancy, use of oral contraceptives and LA have been reported to greatly increase the risk of developing VTE in individuals who have FVL. This may explain why in women who have FVL mutation there is an increased incidence of VTE during pregnancy especially in the last trimester and during delivery (Samama et al, 1996;Florell & Rodgers, 1997;Perry & Pasi, 1997;Rotmensch et al, 1997;Hallak et al, 1997). Further, women who are heterozygous for the FVL and take oral contraceptives are at 34-fold increased risk for developing VTE (Melichart et al, 1996;.…”

Factor V Leiden mutation in Arabs in Kuwait by real-time PCR: different values for different Arabs

“…[1][2][3][4][5][6] It is present in a high number of Caucasians, 1,4,6,7,[10][11][12][13][14][15][16][17][18][19][20] but it is very rare in other ethnic groups. 7,17,[20][21][22][23][24][25] Few studies on Arabs showed that the prevalence of FVL was 0-27% in different Arabic countries, [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] being as low as zero in countries like Saudi Arabia, 7,29,40 Oman 34 and Yemen, 27 whereas being relatively very high (27%) in Palestinians (Israeli Arabs).…”

“…FVL was reported to be highly present in populations of Caucasian origin living in Europe, United States and Australia, with a prevalence of 15-65% among VTE patients and 1-15% in the normal populations studied. 1,4,6,7,[10][11][12][13][14][15][16][17][18][19][20] On the other hand, FVL was almost absent in other populations such as Africans, South-East Asians, Chinese, Japanese, American Indians, Greenland Eskimos and Aboriginals of Australia. 7,17,[20][21][22][23][24][25] In Kuwait, VTE is quite common.…”