Resistance to activated protein C in unselected patients with arterial and venous thrombosis

Abstract

Four hundred and ninety-three consecutive patients referred for arterial or venous thrombosis were screened for congenital and acquired abnormalities of blood coagulation predisposing to thrombosis, and were compared to 341 age-and sex-matched controls. The aim of the study was to determine the prevalence and clinical characteristics of resistance to activated protein C (APC), a defect shown to have different prevalences in different ethnic groups and to be associated with an increased risk of thrombosis. Seventy-three (15%) patients had both APC resistance and the 1691 G to A factor V gene mutation, compared to 6/341 (2%) controls. Seven patients had antithrombin deficiency (1.4%), 11 had protein C deficiency (2.2%), and 4 had protein S deficiency (0.8%). The relative risk of thrombosis in APC-resistant patients was 9.4. Resistance to APC was associated mainly with venous thrombosis, the most frequent being deep-vein thrombosis of the lower limbs. Fifty-eight percent of APC-resistant patients had an associated risk factor at the first thrombotic event: pregnancy and oral contraceptive intake were associated with the first thrombotic episode in 35% and 30% of women, respectively. APC resistance is the most frequent defect of blood coagulation in the general population and in the unselected thrombotic population studied by us. Am. J. Hematol. 55:59-64, 1997.

Oral contraceptive induced thrombi of the right heart of a heterozygous protein C-deficient woman—a case report

“…A decreased response to activated protein C is common during pregnancy and during use of oral contraceptives, but the clinical relevance of these findings have yet to be determined [14]. Conditions associated with acquired protein C deficiency are DIC, deep venous thrombosis, pulmonary embolus, severe liver disease, postoperative patients, infection, malignancy, L-asparaginase therapy, ARDS, HUS and TTP [9,16]. Also, protein C levels may be decreased in postoperative patients, but the role of this decrease in contributing to or causing postoperative deep venous thrombosis is unclear.…”

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.…”

“…1,2 This apparently simple point mutation was found to lead to a condition called activated protein C resistance, which causes, in carriers of the mutation, a serious clinical condition known as 'hypercoagulability' or 'thrombophilia' , which is very often manifested clinically as venous thromboembolic disorders (VTE). [3][4][5][6] VTE is a significant cause of morbidity and mortality in many countries, including Kuwait, with an annual incidence of 1 out of 1000. 3,4,7,8 Studies have shown that people with FVL had a higher risk of developing VTE (10-fold and 140-fold increased risk in heterozygous and homozygous carriers, respectively).…”

“…3,4,7,8 Studies have shown that people with FVL had a higher risk of developing VTE (10-fold and 140-fold increased risk in heterozygous and homozygous carriers, respectively). 1,2,5,6,[9][10][11][12] Several studies were conducted worldwide to determine the prevalence and risk of FVL in different countries and ethnic groups. 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.…”