Thrombotic risk factors and cardiovascular events after endovascular intervention for peripheral arterial disease.

OBJECTIVES: Few data are available on thrombophilic risk factors and clinical outcome in patients undergoing percutaneous transluminal angioplasty (PTA) for peripheral arterial disease (PAD). We investigated the role of homocysteine, fibrinogen, Factor VIII (FVIII), lupus anticoagulant (LAC) and FII G20210A, and FV R506Q (FV Leiden) mutations as prognostic factors in 230 patients who underwent PTA for PAD (Fontaine's stages: IIb through IV; aged 69 ± 1 years). DESIGN AND METHODS: A prospective study. Major adverse cardiovascular events (MACE) were the composite 'end' point. RESULTS: During the follow-up (24.3 ± 1.5 months), 96 (41.7%) patients reached the 'end' point. According to Cox regression analysis, diabetes and critical limb ischaemia were predictors of MACE, whereas each single thrombophilic alteration was not. Thrombophilic alterations were more frequent in patients that reached the 'end' point, and the patients with two alterations (hazard ratio (HR) 2.55 confidence interval (CI): 1.20-5.46, p = 0.015) and those with three or more alterations (HR 2.91 CI: 1.31-6.45, p = 0.009) had an increased risk for MACE versus those without alterations. Thrombophilic alterations were not associated with limb loss during the follow-up. CONCLUSION: The presence of multiple thrombophilic alterations in patients who underwent PTA for PAD is associated with increased risk of arterial thrombotic events.

Mitochondrial function and superoxide generation from submitochondrial particles of aged rat hearts.

A decrease in heart function with ageing might be related to an impairment of mitochondrial function, since these organelles produce the greatest fraction of ATP in the myocyte. Mitochondria extracted from Wistar rat hearts at 3, 14, 18 and 24 months of age were employed to evaluate the changes of the respiratory activity during lifetime. A slight decrease of the respiratory rate (QO2) was observed in the 14 month group with respect to the 3 month group when succinate was used as substrate, whereas the respiratory control index (RCI) in the presence of glutamate or succinate increased in the 24 month group. The latter result may be related to a condition of moderate hypertrophy that generally occurs in the ageing heart. Submitochondrial particles (SMP) were also prepared to study the superoxide radicals (O2-) production at the level of rotenone or antimycin-inhibited regions of the respiratory chain. A strong elevation in the O2- generation was observed in the antimycin-inhibited region at 14 months of age; on the contrary, the rate of O2- production remained unchanged in the 24 month group in comparison to the youngest group. These observations correlate well with the enhanced tissue level of oxidized glutathione that was observed at 14 and 18 months of age. The products of lipid peroxidation (TBARS) did not change in the rat heart at any of the ages measured, whereas the levels of fluorescent substances progressively increased beginning from 18 months of age, with a greater extent in the mitochondrial compartment. The present study suggests that age does not substantially affect mitochondrial respiration and energy output in the rat heart, while a greater production by cardiac mitochondria of superoxide anions in the adult rats (14 months) might accelerate the fluorescent pigment formation.

Activation of blood coagulation after abrupt or stepwise withdrawal of oral anticoagulants--a prospective study.

The occurrence of a "rebound hypercoagulable state" in patients after dicontinuation of oral anticoagulants is still a matter of debate and no definite recommendation can be made on the best procedure for anticoagulant withdrawal. The present study investigated the changes in the levels of markers of activated blood coagulation in 32 patients (pts) in whom warfarin treatment (for venous thromboembolic disease) was randomly withdrawn abruptly (n = 17, group A) or gradually (n = 15, group B: 2/3 of initial dose the 1st week, 1/3 the 2nd weeks and nothing from the 3rd week on). Blood was sampled at baseline, once a week for the first three weeks and after 2 months. At the 1st week group A had significantly higher F1+2 and TAT values (p < 0.001); at the 2nd week F1+2 levels remained higher (p < 0.05) though INR values were not different from those of group B. After baseline, higher than normal F1+2 levels were recorded in 32/66 (48%) controls in group A vs 15/60 (25%) in group B (p < 0.01); at the 2nd week, 10/17 (59%) patients in group A vs 1/15 (7%) in group B still had higher than normal F1+2 levels (p < 0.01). The values of areas under curve (AUC) and maximum concentrations of all variables were not statistically different in the two groups; however, very high levels were observed in a few cases of group A. Thrombotic events (one DVT recurrence and one thrombophlebitis in a varicose vein) occurred in 2 pts of group A, both with high F1+2 and TAT AUC values.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of diets containing different amounts of precursor and derivative fatty acids on serum TXB2.

Dietary precursor and derivative polyunsaturated fatty acids influence metabolic parameters, such as eicosanoid synthesis. We have studied the effect of dietary intakes of lipids containing different amounts of precursor and derivative fatty acids (olive oil, olive-blackcurrant-fish oil mixture, blackcurrant-fish oil mixture, MCT (medium chain triglycerides)-soyabean oil mixture) on serum thromboxane B2 (TXB2) in four groups of rats. Plasma fatty acid composition showed differences related to dietary intakes. TXB2 levels were similar in all conditions except in the group receiving the mixture of olive-blackcurrant-fish oils which showed lower values.

Screening for activated protein C resistance before oral contraceptive treatment: a pilot study.

The feasibility and cost-effectiveness of screening women for congenital thrombophilic alterations before oral contraceptive (OC) treatment was investigated. A total of 525 women (mean age 21.9 years, 73% aged < 25 years) were examined before their first OC course. At first screening, completely normal results were recorded in 485 (92.4%) women, the remaining showing single (n = 34) or multiple (n = 6) alterations. At second examination (possible in 37 of 40), activated protein C resistance (APCR) was confirmed in 21 cases (4.0%, 18 with factor V Leiden), protein C, or protein S reduction in 8 (1.5%) and 2 (0.4%) cases, respectively. No cases with antithrombin III deficiency were detected. The global estimated cost ($US) to detect one altered case was: $7795 for protein S, $2696 for antithrombin III (no case found), $1374 for protein C and $433 for APCR. The present study confirms that extensive thrombophilic screening before OC treatment is not currently advisable. APCR assessment, however, seems to have a favorable cost-effectiveness ratio: the alteration is frequent and has a synergistic effect with OC; sensibility and specificity of some methods are good; family history is unreliable to single out possible carriers; finally, carriers can be fully informed of their increased thrombotic risk if treated with OC and can receive thromboprophylaxis during life situations associated with high thrombotic risk (e.g., pregnancy and puerperium).

PIP: This article investigates the feasibility and cost effectiveness of screening women for congenital thrombophilic changes before oral contraceptive (OC) treatment. The study population included 525 women who were examined before their first OC course between September 1995 and May 1997 in Bologna, Italy. A completely normal result was seen in 92.4% women during the first screening, which was conducted before the first OC course. The second examination showed that activated protein C resistance (APCR) was confirmed in 21 cases (4.0%, 18 with factor V Leiden), and protein C and protein S reduction in 8 (1.5%) and 2 (0.4%) cases, respectively. Antithrombin III deficiency cases were not detected. The detection of one altered case is estimated to cost $7795 for protein S, $2696 for antithrombin III, $1374 for protein C, and $433 for APCR. The study confirmed that extensive thrombophilic screening before OC treatment was not advisable. However, APCR assessment was found to be cost-effective. The alteration was frequent and APCR had a synergistic effect with OC, and the sensibility and specificity of some methods for detection of APCR are good. Family history is not reliable for identifying possible carriers for the thrombophilic trait. Carriers can be fully informed of their high risk if treated with OC and can receive thromboprophylaxis in conditions where thrombotic risk is high.

D-dimer use for deep venous thrombosis exclusion in elderly patients: a comparative analysis of three different approaches to establish cut-off values for an assay with results expressed in D-dimer units.

INTRODUCTION: The use of adapted cut-off values in the elderly, combined with clinical probability (PTP), increases the proportion of patients in whom venous thromboembolism (VTE) can be safely excluded, compared with the conventional cut-off value of 500 µg/L fibrinogen equivalent units (FEU). We evaluated the clinical performance of three different approaches to establish cut-off values for a D-dimer assay whose results are expressed in D-dimer units (D-DU). METHODS: HemosIL D-dimer HS assay (Instrumentation Laboratory) was performed in 279 consecutive outpatients with suspected deep venous thrombosis (DVT) and nonhigh PTP. RESULTS: Considering patients >60 years, the number of negative D-dimer results increased using the modified (376 ng/mL if ≥60 years) and the age-adjusted cut-off (age years × 5 ng/mL if >50 years) compared to the conventional one (230 ng/mL for all patients; 54.6%, 58.2%, and 25.0%, respectively), with no false-negative results. The higher increase was observed in patients >80 years (43.9%, 56.1%, and 8.8%, respectively). CONCLUSION: For the HemosIL D-dimer HS, the use of specific cut-off values in older subjects with suspected DVT and nonhigh PTP increases the number of patients in whom DVT can be safely excluded.

Effects of a dried garlic preparation on fibrinolysis and platelet aggregation in healthy subjects.

The acute and chronic effects of a preparation of dried garlic powder (Sapec) in a total daily dose of 900 mg on fibrinolysis and platelet aggregation have been evaluated in a randomized, double-blind, placebo controlled cross-over study of 12 healthy subjects. Total euglobulin fibrinolytic activity and t-PA (tissue plasminogen activator) activity were significantly higher 4 and 6 h after garlic and placebo ingestion, and no differences were recorded between treatments. After 14 days of treatment, t-PA activity was significantly higher after garlic, with inter-treatment significance. No significant changes in PAI (Plasminogen Activator Inhibitor) activity and fibrinogen levels were recorded. Platelet aggregation induced by adenosine diphosphate and collagen, and especially beta-thromboglobulin (beta-TG) release after collagen stimulation were significantly inhibited 2 and 4 h after garlic ingestion; platelet aggregation values were also significantly lower after 7 and 14 days of garlic treatment. No significant changes were found in adenosine triphosphate release and serum TXB2 levels after acute garlic administration.