Differences in perioperative coagulation between Japanese and other ethnic groups undergoing laparoscopic cholecystectomy.

BACKGROUND: Japanese patients experience fewer episodes of postoperative thrombosis than those in certain other countries. To investigate this phenomenon, we measured perioperative coagulation activation markers and conducted thromboelastography (TEG) in 27 Japanese patients undergoing laparoscopic cholecystectomy. METHODS: D-dimer, thrombin-antithrombin complex (TAT), and prothrombin fragment 1+2 (F1+2) were measured as coagulation activation markers. TEG was performed to measure reaction time (R), clot formation time (K), maximum amplitude (MA), and maximum elastance (ME). These measurements were performed before and after the operation and the day after the operation. RESULTS: Coagulation activation markers increased significantly postoperatively. With respect to TEG, MA and ME increased postoperatively. R and K did not change. CONCLUSION: Whereas clotting factor activation sthenia is common in Europe and North America, thrombocyte function sthenia occurs in Japanese patients. This difference may account for the differing incidences of phlebothrombosis in Japanese and white populations.

Risk of pulmonary embolism and/or deep venous thrombosis in Asian-Americans.

Several reports from Asian countries suggest a low prevalence of pulmonary embolism (PE) and deep venous thrombosis (DVT) in Asians, and sparse US data show that a slightly higher prevalence of PE/DVT in "nonwhites" than in whites is evident in all geographic regions except the Pacific region (California, Oregon, and Washington) where "nonwhites" include a larger proportion of Asians and Hispanics than in other US locations. We prospectively studied PE/DVT hospitalizations in 128,934 persons in relation to traits determined at health examinations in 1978 to 1985. Through 1994, 337 persons were subsequently hospitalized for PE and/or DVT (for PE first, n = 206). Cox proportional-hazards models with 9 covariates were used. In multivariate models, the following RRs (95% confidence intervals) were found for PE/DVT combined: black/white = 1.1 (0.4 to 1.4); Hispanic/white = 0.7 (0.3 to 1.5); and Asian/white = 0.2 (0.1 to 0. 5; p = 0.002). The lower risk of Asians was present in each sex and for persons first hospitalized for either PE or DVT. Covariates with significant positive relations to risk were age, male sex, body mass index, and a composite coronary disease risk/symptom variable; covariates not significantly related were education, marital status, smoking, and alcohol. These data suggest that Asians have very low risk of PE/DVT, which may account for US geographic variations in white/non-white risk differences. Possible explanations include the absence of hazardous mutations or unspecified PE/DVT protective traits in Asians.

Incidence of idiopathic deep venous thrombosis and secondary thromboembolism among ethnic groups in California.

BACKGROUND: Few studies have compared the incidence of deep venous thrombosis among ethnic groups. OBJECTIVE: To determine the incidence of deep venous thrombosis among ethnic groups. DESIGN: Analysis of the linked California Patient Discharge Data Set from 1991 to 1994. SETTING: California. PATIENTS: 17991 patients with idiopathic deep venous thrombosis (thrombosis without cancer or hospitalization within preceding 6 months) and 5573 patients with secondary thromboembolism (thromboembolism occurring within 3 months of seven different events). MEASUREMENTS: Ethnicity was determined by using race as documented in the data set. For idiopathic deep venous thrombosis, standardized age- and sex-adjusted incidences were calculated. For secondary thromboembolism, proportional hazards modeling was done. RESULTS: The annual incidence of idiopathic deep venous thrombosis per 1000000 persons older than 18 years of age was 230 for white persons, 293 for African Americans (rate ratio, 1.27 [95% CI, 1.07 to 1.51]), 139 for Hispanic persons (rate ratio, 0.60 [CI, 0.54 to 0.67]), and 60 for Asians and Pacific Islanders (rate ratio, 0.26 [CI, 0.22 to 0.30]). Compared with white persons, Asians and Pacific Islanders who developed secondary thromboembolism had a significantly lower relative risk (range, 0.22 to 0.61) for all seven conditions analyzed. CONCLUSIONS: Compared with white persons, Asians and Pacific Islanders have a very low incidence of idiopathic deep venous thrombosis and a very low relative risk for secondary venous thromboembolism.

High prevalence of antithrombin III, protein C and protein S deficiency, but no factor V Leiden mutation in venous thrombophilic Chinese patients in Taiwan.

We studied the prevalence of antithrombin III (AT III), protein C (PC) and protein S (PS) deficiencies and factor V Leiden mutation in thrombophilia in Taiwan. Eighty-five consecutive and unrelated patients with otherwise unexplained venous thrombophilia were studied. Both antigen and activity of inhibitors were determined using commercial kits (Stago), activated PC sensitivity ratio (APC SR) by Coatest (Chromogenix), and factor V mutation by polymerase chain reaction with sequence specific primer. Of 85 patients, 41 were male, 44 female, and mean age 49.4 years (17-82 years). None had factor V mutation, or APC SR of less than 2; 50 (58.8%) showed a deficiency of inhibitor proteins; 34 (68.0%) were hereditary, 16 (32.0%) non-hereditary; 3 had an AT III deficiency, 16 a PC deficiency, 28 a PS deficiency, and 3 a combined deficiency. Thirty-five were non-deficient without a known cause. The average age at the first thrombotic episode was 48.5 years (13-81 years). Thrombosis occurred spontaneously in 39 (78.0%) of 50 deficient patients. In conclusion, a relatively higher prevalence of AT III, PC and PS deficiency (59%), but no factor V Leiden mutation, was found in venous thrombophilic Chinese patients in Taiwan compared to that in western countries. Screening for inhibitor protein deficiency in Chinese thrombophilic patients is highly recommended.

Ethnic distribution of factor V Leiden in 4047 men and women. Implications for venous thromboembolism screening.

OBJECTIVE: To estimate ethnic-specific prevalence rates of factor V Leiden, an inherited defect of hemostasis associated with risk of venous thrombosis. DESIGN: Survey of 4047 American men and women participating in the Physicians' Health Study (PHS) or in the Women's Health Study (WHS). All study participants were free of myocardial infarction, stroke, or venous thrombosis. MAIN OUTCOME MEASURE: Prevalence of G1691A Leiden mutation in the gene coding for coagulation factor V was determined in the PHS group using polymerase chain reaction techniques and, in the WHS group, a second-generation activated protein C (APC)-resistance screening test with genetic confirmation of all borderline and low-value results. RESULTS: In 2468 Caucasian Americans, carrier frequency of factor V Leiden was 5.27% (95% confidence interval [CI], 4.42%-6.22%). Carrier frequency was 2.21% in 407 Hispanic Americans, 1.23% in 650 African Americans, 0.45% in 442 Asian Americans, and 1.25% in 80 Native Americans. Thus, prevalence of factor V Leiden was less among minority subjects (P=.001). Carrier frequencies were similar in Caucasian men and women (5.53% vs 4.85% respectively, P=.5). CONCLUSION: These data indicate that prevalence of factor V Leiden is greater among Caucasians than minority Americans. These data have implications for clinicians considering whether to screen for factor V Leiden in high-risk groups such as those with prior venous thromboses or coexistent defects of anticoagulation and women at risk for postpartum thrombosis or seeking oral contraceptives.

Prevalence of factor V Leiden mutation in various populations.

Resistance to activated protein C (APC) is the most common inherited risk factor for venous thrombosis. Most cases of APC resistance are caused by the point mutation nt 1691 G-A in factor V gene, referred to as factor V Leiden mutation. As initially shown in a Dutch population, this mutation has a carrier rate of 2.9%, the most frequent genetic disposition for thrombophilia and deep venous thrombosis. By large-scale epidemiological studies we have determined the prevalence of factor V Leiden mutation in populations from Poland (200), Argentina (215), Venezuela (126), Costa Rica (196), and India (150). The prevalences have been estimated for Poland (Warsaw) 5.0%, Argentina (Buenos Aires) 5.1%, Venezuela (Valencia) 1.6%, Costa Rica (San José) 2.0%, and India (Punjab) 1.3%. Based on worldwide distribution, it can be hypothesized that the factor V Leiden mutation has originated and accumulated in central European Caucasians and spread over the world by migration.

Thrombophilia in ethnic Arabs in Kuwait.

One hundred and thirty unrelated patients with recurrent deep venous thrombosis were studied over a period of 4 years (1986-1990) in order to determine the possible etiology. Protein C levels were estimated in plasma both by chromogenic substrate assay and by immunoassay. Protein S levels in plasma was determined by immunoassay using antisera to human protein S. Antithrombin III (AT-III) was assayed using monospecific rabbit antiserum to human AT-III. Fifteen patients were found to have hereditary protein C deficiency (11.52%). Family studies revealed autosomal recessive inheritance in one patient and a dominant pattern in the remaining 14 patients. Protein S deficiency was found in eight cases (6.1%), AT-III deficiency was established in five cases (3.8%) and a fibrinolytic defect in 33 cases (25.4%). Thrombosis of visceral and cerebral vessels and a positive family history were more frequently found among patients who had hereditary deficiency of one or the other antithrombotic factor. Thrombophlebitis of superficial veins was found to be very common in patients with protein C and protein S deficiency and virtually absent in AT-III deficiency. The high frequency of protein C and protein S deficiency in this ethnic group is attributed to the high frequency of consanguinity.

Postoperative deep-vein thrombosis in Asian patients is not a rarity: a prospective study of 88 patients with no prophylaxis.

Postoperative deep-vein thrombosis (DVT) is believed to be rare in Asians. We studied 88 consecutive patients in Malaysia who had operations for fracture of the proximal femur or for total hip or knee replacement. No patient had prophylaxis against DVT; bilateral ascending venography was performed between six and ten days after operation. A total of 55 patients (62.5%) showed venographic evidence of DVT. The prevalence was greatest after total knee replacement (76.5%), less after total hip replacement (64.3%) and smallest in the fracture group (50%). One patient developed symptomatic pulmonary embolism. In contrast to other reports from Asia, we found an incidence of postoperative DVT which is similar to that reported in Western populations. This suggests that the present practice of withholding routine prophylaxis against thromboembolism in Asian patients undergoing high-risk orthopaedic procedures should be reconsidered.

Factors determining the maintenance dose of warfarin in Chinese patients.

Chinese patients are reportedly more sensitive than Caucasians to the anticoagulant effect of warfarin. We examined warfarin dose requirements and their determinants in 151 Chinese out-patients on stable maintenance dose of warfarin with international normalized ratio of 2 to 2.5. Mean daily warfarin requirement was 3.3 +/- 1.4 mg, much lower than reported doses in Caucasian patients. The most important determinant was age (r = -0.43, p < 0.001), with progressively lower warfarin requirement with increasing age (p = 0.0001). There was a weaker association with body weight (r = 0.20, p = 0.01). Patients with chronic rheumatic heart disease tended to require a smaller dose than those with heart valve replacements (2.94 +/- 1.24 vs. 3.69 +/- 1.42 mg, p < 0.01). We confirm that Chinese patients require a smaller dose of warfarin for the same degree of anticoagulation. Age is the most important factor affecting dose requirement, although body weight and underlying disease also play a role.

Activated protein c resistance (APC) and inherited factor V (FV) mis-sense mutation in patients with venous and arterial thrombosis in a haematology clinic.

BACKGROUND: Inherited factor V (FV) mis-sense point mutation has recently been identified as a major cause of familial venous thrombosis. The incidence of this congenital haemostatic disorder in Australia is unknown. AIM: To examine the incidence of this congenital defect in patients with thrombosis attending a haematology clinic. METHODS: Individuals investigated or treated for venous and arterial thrombosis over a four month period, as well as those who were on anticoagulant for valvular replacement or arrhythmia were studied for the presence of FV mis-sense point mutation, FV Q506 (G to A at nucleotide position 1691) by a polymerase chain reaction based test, and activated protein C (APC) resistance using an APTT based coagulation assay. RESULTS: Forty-five patients with venous thromboembolism (VTE), 20 patients with coronary artery disease and 25 patients with valvular replacement or arrhythmia who were on anticoagulant were examined. The frequency of FV mis-sense point mutation in these three groups was 26.7%, 15% and 4% respectively. In this study, patients with FV Q506 were of a younger age and had a higher incidence of extensive thrombosis or recurrence as compared to those with the normal factor V gene. This mutation was found in a diverse group of people (four of the 12 patients were of non-European origin). Nearly 50% of these patients had other risk factors for VTE. The number of patients with a family history of VTE was similar for those with the FV mutation and the normal FV. CONCLUSION: This study confirms the high incidence of FV Q506 mutation in patients with VTE reported overseas. Several clinical features, i.e. young age of onset of VTE, high recurrence rate, diverse ethnic background and importance of associated risk factors are highlighted. The findings in this study also raise the possibility that this mutation may be a risk factor for arterial thrombosis. Large studies are required to substantiate these findings.

Three novel missense mutations in the antithrombin III (AT3) gene causing recurrent venous thrombosis.

The polymerase chain reaction and direct sequencing were used to determine the nature of the mutations in the antithrombin III (AT3) gene in seven unrelated patients with familial antithrombin III (ATIII) deficiency and recurrent venous thrombosis. Three novel mutations were found, two associated with a type I deficiency state (Pro80-->Thr and His120-->Tyr) manifesting reduced synthesis of ATIII. The other novel lesion (Met251-->Ile) was associated with a dysfunctional ATIII protein (type II ATIII deficiency) and is predicted to interfere either with a heparin-induced conformational change in the ATIII molecule or with docking to thrombin. A novel polymorphism (Tyr158-->Cys) was also found to occur in several individuals of Scandinavian origin.