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S Fedi

Publications and source records attributed to S Fedi.

At least 19 recordsLinked to original sources
PubMed2001

High cysteine levels in renal transplant recipients: relationship with hyperhomocysteinemia and 5,10-MTHFR polymorphism.

BACKGROUND: Long-term survival of renal transplant recipients seems to be influenced by the occurrence of thromboembolic complications and cardiovascular disease. Preliminary data available in the literature found high levels of cysteine (Cy) as a risk factor for deep venous thrombosis independently of high homocysteine (tHcy) levels, but no data are available about Cy levels in renal transplant recipients. METHODS: To investigate Cy, tHcy, and plasminogen activator inhibitor-1 (PAI-1) levels and the prevalence of 5,10-methylenetetrahydrofolate reductase (MTHFR) in renal transplantation, we studied 70 stable renal transplant recipients and 66 age- and sex-matched normal subjects as controls. RESULTS: Cy, tHcy, and PAI-1 levels were significantly higher in renal transplant recipients with respect to controls (Cy: 254 micromol/L [117-466] vs. 198 micromol/L [99-331], P<0.001; tHcy: 17.0 micromol/L [4.0-68] vs. 8.1 micromol/L [2.0-24.0], P<0.00001; PAI-1: 16.8 IU/ml [5.1-45.5] vs. 7.9 IU/ml [4.0-18.0], P<0.00001). High Cy levels were detected in 35.8% of patients. Hyperhomocysteinemia, both in the fasting state and postmethionine loading test, was diagnosed in 90% of cases. The odds ratios for Cy and tHcy levels within the fourth quartile with respect to the other quartiles were markedly increased in renal transplant recipients even after adjustment for prevalent cardiovascular risk factors, glomerular filtration rate, tHcy and, Cy, respectively (Cy: 29.0 micromol/L [95% CI 7.0-111]; tHcy: 29.9 micromol/L [95% CI 7.5-118.1]). Fasting tHcy levels correlated well with PAI-1 (r=0.65; P<0.0001) but not with Cy levels (r=0.10; P=0.4). The prevalence of the MTHFR 677TT genotype in renal transplant recipients was not significantly higher in patients than in controls (mutant allele frequency: 0.48 in patients and 0.47 in controls) and was associated with significantly higher fasting and postmethionine tHcy levels both in controls and patients. After 2 months of vitamin supplementation, tHcy (Pre: 17.0 micromol/L [4.0-68]; Post: 7.5 micromol/L [2.3-21.9]; P<0.0001) and PAI-1 levels (Pre: 16.8 IU/ml [5.1-45.5]; Post: 10 IU/ml [2.0-25]; P<0.001) were significantly decreased, whereas Cy levels showed a small decrease that did not reach statistical significance (Pre: 254 micromol/L [117-466]; Post: 209 micromol/L [168-300]; P=0.3). Patients with the MTHFR 677TT genotype had the major percentage of decrease of tHcy levels with respect to the other genotypes. CONCLUSION: In conclusion, this study demonstrates the presence of elevated Cy plasma levels in renal transplant recipients. Vitamin supplementation reduces tHcy but not Cy levels, and the amount of decrease seems to be influenced by the MTHFR genotype.

5,10-Methylenetetrahydrofolate Reductase (FADH2)↗
PubMed2001

Activation of the immune system and coronary artery disease: the role of anti-endothelial cell antibodies.

On the basis of the role of immuno-mediated inflammation in atherosclerosis we investigated, (1) the prevalence of anti-endothelial cell antibodies (AECA) in ischaemic heart disease (IHD); (2) if beta2-glycoprotein I (beta2-GPI) was the target antigen of AECA; (3) the relationship between AECA, tissue factor (TF) and tissue factor pathway inhibitor (TFPI). In 93 consecutive IHD patients undergoing percutaneous transluminal coronary angioplasty (PTCA) and 105 controls AECA were detected by ELISA on human umbilical vein endothelial cells (HUVEC). AECA positive sera were evaluated for anti-beta2-GPI antibodies by ELISA. TF and TFPI plasma levels were assessed by ELISA. Twelve of 93 (12.9%) IHD patients and only one of 105 controls (0.95%) were AECA positive. The prevalence of AECA was higher in unstable angina (UA) than in effort angina (EA) (P=0.01). Three of 12 AECA positive sera resulted positive for anti-beta2-GPI and showed a marked decrease in EC-binding when tested on HUVEC cultured in serum-free medium. The binding was restored by the addition of beta2-GPI. TF and TFPI levels were similar in AECA positive and AECA negative patients. The rate of angiographically documented clinical recurrences was 66.7% in the AECA positive and 14.8% in the AECA negative group (P=0.0004) with a significant relationship between restenosis and AECA (P<0.0001), unchanged by the inclusion of cardiovascular risk factors in the regression model. Our results suggest a 'role' for AECA in the immune-mediated inflammation in UA beta2-GPI is not the only AECA target antigen. AECA are not responsible for high TF and TFPI levels. The high rate of clinical recurrences after PTCA, confirmed by angiography, in AECA positive patients is in line with such a role and suggests further large-scale 'ad hoc' studies.

Angioplasty, Balloon, Coronary↗
PubMed2001

Lipoprotein (a) and anticardiolipin antibodies are risk factors for clinically relevant restenosis after elective balloon percutaneous transluminal coronary angioplasty.

Recent reports have shown the importance of new risk factors for cardiovascular disease. We investigated the relationship between Lp(a), fibrinolytic parameters and anticardiolipin antibodies (aCL) and the occurrence of clinical recurrence owing to restenosis after elective balloon percutaneous transluminal coronary angioplasty (PTCA) without stenting. In 167 patients, undergoing PTCA, Lp(a) plasma levels, aCL, euglobulin lysis time (ELT), plasminogen activator inhibitor-1 (PAI-1) activity and tissue-type plasminogen activator (t-PA) plasma levels were evaluated before the procedure. During follow-up 29 patients underwent clinical recurrence due to restenosis. Lp(a) levels were significantly higher in patients with restenosis in comparison to those without (P<0.05); an earlier restenosis was observed in patients with Lp(a) values >450 mg/L. Kaplan-Meier survival estimate showed an earlier occurrence of restenosis in patients with base-line Lp(a)>300 mg/l associated with aCL positivity. High Lp(a) plasma levels play a role in the occurrence of clinical recurrence due to restenosis after elective balloon PTCA without stenting; the association with aCL accelerates the development of restenosis.

Adult↗
PubMed2000

Risk factors for cardiovascular disease in renal transplant recipients: new insights.

Long-term survival of renal transplant recipients appears to be influenced by the occurrence of thromboembolic complications and cardiovascular disease. In order to investigate the prevalence of new hemostasis-related risk factors for venous and arterial thrombosis, we investigated 63 renal transplant recipients and 66 age- and sex-matched control subjects. We assayed antiphospholipid antibodies [lupus anticoagulant (LA) and anticardiolipin antibodies (aCL)], lipoprotein (a) [Lp(a)], plasminogen activator inhibitor-1 (PAI-1), and total homocysteine (tHcy) levels. We found a significantly higher prevalence of positivity for LA (P < 0.001); no difference was detected in the prevalence of aCL between patients and controls. PAI-1 levels were significantly higher in renal transplant recipients than in controls [12.3 IU/ml (2-45.5) vs 7.9 IU/ml (4-18.0); P < 0.0001] with an odd ratio (OR) of 11.8 (4.9-28.5) in univariate analysis and of 5.8 (2.1-15.4) in multivariate analysis. Lp(a) levels were higher in patients then in controls [159 mg/l (1-992) vs 100.5 mg/l (10-412); P < 0.005] with an OR of 5.9 (1.9-18.4) in univariate analysis and of 3.5 (0.9-13.4) in multivariate analysis. Fasting levels of tHcy were significantly higher in renal transplant recipients [7.0 micromol/l (4.0-68) vs 8.1 micromol/l (2.0-24.0); P < 0.00001] with an OR of 40.4 (14.7-111) in univariate analysis and of 33.1 (11.1-115.5) in multivariate analysis. After methionine loading test, we documented levels of tHcy above the 90th percentile of controls in 60/63 patients (95%). Finally, we found a significant correlation between tHcy and PAI-1 plasma levels (r = 0.76; P < 0.000001). Our results show a high prevalence of hemostasis-related risk factors for arterial and venous thrombosis in renal transplant recipients, suggesting the need for the investigation of these patients for the presence of these risk factors in order to improve their long-term survival and to tailor therapy.

Autoantibodies↗
PubMed2000

Videolaparoscopic cholecystectomy induces a hemostasis activation of lower grade than does open surgery.

BACKGROUND: Tissue injury after trauma and surgery may induce alterations in blood coagulation and fibrinolysis, and the hypercoagulable state observed after surgery can be associated with the risk of postoperative thromboembolic complications. Recently, videolaparoscopic (VLPS) cholecystectomy has been introduced, and its advantages over the open procedure seem related to the reduced surgical trauma. The aim of this study was to investigate hemostatic system alterations in patients who undergo open and VLPS cholecystectomy. METHODS: Fibrinogen, prothrombin fragment F1+2, D-dimer, and plasminogen activator inhibitor type-1 (PAI-1) activity was determined in 10 patients who underwent open (group A) and 10 patients who underwent VLPS cholecystectomy (group B), respectively. Blood samples were obtained the day of surgery in the morning (B1), after anesthesia (A1), 1 hour after the start of surgery (S1), then 30 min (E.05) and 24 h (E.24) after the surgery. RESULTS: No significant differences were observed in baseline values between groups A and B for the parameters investigated. At 24 h after surgery, fibrinogen increased significantly (p < 0.05) in group A and also was significantly higher than in group B (p < 0.05). In group A, a marked increase in F1+2 levels (p < 0.01) was observed in all the samples, with the maximum values on the first day after surgery (3.7 nmol/l; 1.2-6.0 nmol/l), whereas in group B, a slight but significant increase in F1+2 levels (2.1 nmol/l; 1.1-3.9 nmol/l; p < 0.01) was observed only 30 min after the end of surgery. In both groups A and B, D-dimer markedly increased after surgery, without statistical significant differences between the two groups at any time. The PAI-1 activity plasma levels remained in the normal range during and after surgery in both groups. CONCLUSIONS: These results indicate that VLPS surgery induces an activation of the clotting system that, although of low degree and short duration, can lead to a transient prothrombotic state.

Adult↗
PubMed2000

Angiotensin converting enzyme DD genotype affects the changes of plasma plasminogen activator inhibitor-1 activity after primary percutaneous transluminal coronary angioplasty in acute myocardial infarction patients.

Angiotensin converting enzyme (ACE) DD genotype, and plasminogen activator inhibitor (PAI-1) 4G/4G genotype have been reported to affect PAI-1 activity in control subjects and atherosclerotic patients, but no data are available on the influence of angiotensin II type 1 receptor (AT1R) A1166C polymorphism on the inhibitor levels. The degree of fibrinolytic activation after percutaneous transluminal coronary angioplasty (PTCA) has been found to affect the risk of restenosis. The aim of this study was to investigate the possible influence of ACE I/D, AT1R A1166C, and PAI-1 4G/5G polymorphisms on the changes of PAI-1 activity after primary successful percutaneous transluminal angioplasty. In 29 consecutive acute myocardial infarction patients, undergoing primary successful angioplasty, genotyping of ACE I/D, AT1R A1166C, and PAI-1 4G/5G polymorphisms was performed by polymerase chain reaction and restriction fragment length polymorphism analysis, and PAI-1 plasma activity (chromogenic method) was assessed before and after angioplasty. Following angioplasty, PAI-1 activity increased in 10 of 29 patients and decreased or remained unchanged in 19 of 29. ACE DD genotype was significantly (P = 0.04) associated with an increase of PAI-1 activity post angioplasty (OR DD/ID+II = 6.5, CI 95% 4.83-8.22). Whereas no effect of PAI-1 4G/5G and AT1R A1166C polymorphisms on PAI-1 response to angioplasty was demonstrated, these data suggest that renin-angiotensin system genes are involved in the regulation of the fibrinolytic response to balloon injury, possibly affecting angiotensin converting enzyme activity. This interaction between the renin-angiotensin system and hemostasis may be a mechanism by which ACE DD genotype affects the risk of restenosis after percutaneous transluminal angioplasty.

Aged↗
PubMed2000

High prevalence of mild hyperhomocysteinemia in patients with abdominal aortic aneurysm.

PURPOSE: In vitro studies have recently demonstrated that homocysteine interacts with the aortic wall by inducing both elastolysis and endothelial perturbation. The aim of this study was to evaluate homocysteine plasma levels and their relationships with aortic diameter and endothelial damage in patients with abdominal aortic aneurysm. SUBJECTS AND METHODS: Fifty-eight consecutive male patients (mean age, 69.5 +/- 6.6 years; age range, 49-78 years) who underwent abdominal aortic aneurysm surgery were enrolled in the study. Twenty-two of 58 patients had no clinical or instrumental evidence of atherosclerosis. Sixty control subjects were age matched and sex matched with the patients. In all of the subjects, we evaluated total homocysteine and thrombomodulin plasma levels and the distribution of the C677T methylenetetrahydrofolate reductase gene mutation. RESULTS: Hyperhomocysteinemia was found in 26 (48%) of the 58 patients with abdominal aortic aneurysm, and homocysteine plasma levels were significantly higher in patients than in control subjects (15.7 +/- 6.5 micromol/L vs 9.6 +/- 3.9 micromol/L; P <. 0001). In addition, the subgroup of patients with abdominal aortic aneurysm who did not show evidence of atherosclerosis showed homocysteine plasma levels significantly higher than those in the controls (14.8 +/- 6.1 micromol/L vs 9.6 +/- 3.9 micromol/L; P <. 001). A larger aneurysmal size was detected in hyperhomocysteinemic patients than in those with normal homocysteine plasma levels (5.09 +/- 0.84 cm vs 5.79 +/- 1.5 cm; P <.05). The genotype distribution of the C677T methylenetetrahydrofolate reductase mutation was as follows: TT 21%, TC 55%, and CC 24% in the patients; TT 10%, TC 58%, and CC 32% in the controls. Moreover, in patients a significant correlation (P <.005) between homocysteine plasma level and 677TT methylenetetrahydrofolate reductase genotype was found. Thrombomodulin plasma levels were significantly higher (P <.00005) in patients (median, 30 ng/mL; range, 10-164 ng/mL) than in controls (median, 19 ng/mL; range, 13-44 ng/mL), and thrombomodulin levels were significantly higher (P <.005) in hyperhomocysteinemic patients (median, 39.5 ng/mL; range, 15-164 ng/mL) than in normohomocysteinemic patients (median, 27.5 ng/mL; range, 10-85 ng/mL). In addition, in patients with abdominal aortic aneurysm, a direct significant correlation (P <.005) was found between homocysteine and thrombomodulin. CONCLUSIONS: These data indicate an association between the presence of AAA in patients selected for surgical treatment of AAA and elevated homocysteine plasma levels and suggest that homocysteine may induce endothelial perturbation and stimulation in these patients.

Aged↗
PubMed2000

Angiotensin-converting enzyme DD genotype, angiotensin type 1 receptor CC genotype, and hyperhomocysteinemia increase first-trimester fetal-loss susceptibility.

Complications of pregnancy have been found to be related with thrombophilic polymorphisms that explain about 30% of obstetric complications. We evaluated the angiotensin converting enzyme (ACE) and the angiotensin type 1 receptor (AT1R) gene polymorphisms in the renin-angiotensin system (RAS) as possible risk factors for fetal loss. Fifty-nine women with a history of three or more first-trimester fetal losses and 70 healthy women with a history of normal pregnancies were enrolled in this study. Thrombophilic factors, ACE insertion/deletion (I/D) and AT1R A1166C polymorphisms, prothrombin G20210A and factor V Leiden mutations were analyzed. At univariate and multivariate analysis, a significant association between ACE DD and AT1R CC genotype and fetal loss was observed. The effect of the ACE DD genotype on the risk of fetal loss was higher in AT1R C allele carriers. The prevalence of hyperhomocysteinemia (Hcy) (defined as baseline plasma levels higher than the 95% percentile; cut-off, 10.5 micromol/l per l) was significantly higher in women with fetal loss, and an association between Hcy and fetal loss was detected. All patients showed normal antithrombin, protein C, protein S, and plasminogen activator inhibitor-1 (PAI-1) values. The presence of one risk factor not associated with others was found in 33 out of 59 patients (56%); ACE DD genotype was the most prevalent risk factor. Our results identify new possible predictive markers for fetal loss in RAS polymorphisms and Hcy. Large-scale studies are warranted to attribute clinical relevance to these polymorphisms as risk factors for complicated pregnancies.

Adult↗
PubMed2000

Effect of tourniquet use on activation of coagulation in total knee replacement.

Total knee replacement often is performed with tourniquet application. The advantages of a dry field, including fixation, are well known, but it still is debatable if tourniquet application increases deep vein thrombosis. Measurement of coagulation markers is a well accepted method of studying thrombogenesis activation intraoperatively and postoperatively. Twenty patients undergoing total knee replacement with subarachnoid anesthesia were assigned randomly to two groups: either with tourniquet application (Group I) or without tourniquet application (Group II). There were no differences between patients in the two groups in terms of age, gender, diagnosis (all had osteoarthritis), operative time, and total (intraoperative and postoperative) blood loss. Markers for thrombin generation and fibrinolysis were measured. Blood samples were drawn at four times: baseline before the operation; after bone cuts; after cement fixation (Group II) or 2 minutes after tourniquet deflation (Group I); and 1 hour after surgery. Markers of thrombin generation and fibrinolysis showed a significant increase from baseline in all the patients. In Group II these markers started to increase during surgery, whereas in Group I the increase occurred at the end of the procedure when the tourniquet was deflated. The total amount of thrombin generation was significantly higher in Group II (without tourniquet), whereas fibrinolysis was significantly greater in Group I. Total knee replacement is accompanied by a hypercoagulative state with or without the use of a tourniquet, but it seems to be higher when the tourniquet is not used. In addition, tourniquet application may increase fibrinolysis.

Aged↗
PubMed2000

Tissue factor and homocysteine levels in ischemic heart disease are associated with angiographically documented clinical recurrences after coronary angioplasty.

BACKGROUND: In ischemic heart disease (IHD) patients high plasma levels of Tissue Factor (TF), the trigger of coagulation cascade, are present. Homocysteine (Hcy) is a risk factor for coronary artery disease, and several different pathophysiological mechanisms by which Hcy may play a role in thrombus formation have been postulated in "in vitro" studies. We investigated the "in vivo" role of Hcy in affecting plasma levels of TF, its inhibitor Tissue Factor Pathway Inhibitor (TFPI) and hypercoagulability. METHODS AND RESULTS: We investigated 119 IHD patients who underwent PTCA and compared them with 103 healthy subjects. TF, TFPI, Thrombin-Antithrombin complexes (TAT) and Hcy levels were significantly higher in the patients than in the controls. A positive correlation was found between Hcy and TF (r = 0.54; p < 0.0001), Hcy and TFPI (r = 0.26; p <0.05) as well as Hcy and TAT (r = 0.33; p <0.0001) levels. An inverse correlation existed between folate intake and Hcy levels (r = -0.28; p = 0.001). Hcy levels within the first quartile and in the highest quartile were associated with a lower (p < 0.001) and higher (p <0.0001) rate of clinical recurrences, respectively. Patients with TF values in the first quartile had a lower rate of angiographically documented clinical recurrences as compared to those in the fourth quartile (p <0.01); those in the highest quartile of TF showed a higher rate of recurrences (p = 0.001). Multivariate analysis confirmed these results (first quartile of Hcy: OR 0.02, C1 0.002-0.27; fourth quartile of Hcy: OR 36.5, C1 3.6-365/first quartile of TF: OR 0.006, C1 0.001-0.44; fourth quartile of TF: OR 16.4, C1 3.0 - 90.0), also after adjustment for risk factors and Hcy and TF respectively. CONCLUSIONS: In this study we show that TF, TFPI and TAT levels are correlated with Hcy plasma levels in IHD patients, providing evidence of an "in vivo" pathophysiological mechanism of hyperhomocysteinemia. The observed association between angiographically documented clinical recurrences and TF and Hcy values awaits confirmation in studies designated to evaluate this issue on a larger number of patients.

Adult↗
PubMed1999

The influence of smoking on von Willebrand factor is already manifest in healthy adolescent females: the Floren-teen (Florence Teenager) Study.

The early onset of atherosclerosis and the involvement of physiological biochemical, and environmental factors in its pathogenesis is well documented. Few data are available on the role of risk factors related to hemostasis in the pathogenesis of atherosclerosis in the young and, in particular, little information is available on adolescent populations. In the Study of Preventive Medicine and Education Program (Floren-teen Study), von Willebrand factor, a risk factor for cardiovascular disorder, was studied, together with classical cardiovascular risk factors, in apparently healthy students from two high schools in Florence. Familial and personal history, physical examination, and cardiovascular risk factors were evaluated in 144 students (aged 17-19 years). Blood was withdrawn to assess von Willebrand factor (ELISA) and lipid parameters. Levels of von Willebrand factor were significantly higher (P<0.044) in smokers than in nonsmokers and were correlated with the number of cigarettes per day in the whole group (P=0.01) and in females (P=0.006). In females a positive correlation was observed between von Willebrand factor and high-density lipoprotein cholesterol (P=0.0365). There was no significant correlation between von Willebrand factor and blood pressure or between von Willebrand factor and physical activity. In conclusion, this study shows an association between levels of von Willebrand factor and smoking habits and is the first show that even a brief period of smoking affects levels of von Willebrand factor in healthy adolescent females independently of other risk factors. These results stress the relevance of extending prevention programs to reduce smoking in high school students.

Adolescent↗
PubMed1999

Electrophysiologic procedures and activation of the hemostatic system.

BACKGROUND: Thromboembolism occurs in 0.4% to 2% of the subjects undergoing radiofrequency ablation (RFA), but its mechanisms remain unclear. Our aim was to evaluate several parameters of the hemostatic system in relation to the electrophysiologic procedure. METHODS: Thirty consecutive patients were enrolled in the study. Fifteen underwent electrophysiologic study and 15 underwent radiofrequency ablation. Before the ablation procedure, all subjects were given an intravenous heparin bolus (2500 IU). Blood samples were drawn immediately before, at the end of, and 24 hours after the procedures. Spontaneous platelet aggregation in whole blood and in platelet-rich plasma, markers of clotting activation (prothrombin fragment 1+2 and the thrombin-antithrombin complex) and the fibrinolytic system (plasminogen activator inhibitor and D-dimer) levels were evaluated. RESULTS: At the end of the procedure, spontaneous platelet aggregation in whole blood, prothrombin fragment 1+2, thrombin-antithrombin complex, and D-dimer levels increased significantly in all patients. The hemostatic changes were more marked after RFA than after electrophysiology. Spontaneous aggregation in whole blood, prothrombin fragment 1+2, and thrombin-antithrombin complex levels at 24 hours after the procedure were similar to those observed before the procedure in both groups; D -dimer levels were still elevated with respect to preprocedure levels, with a trend toward higher levels in patients undergoing RFA rather than electrophysiology. A significantly more marked activation of coagulation (prothrombin fragment 1+2, P <.005) was found in patients in whom the mean duration of energy application was higher than 23.5 seconds. CONCLUSIONS: Our data suggest that antithrombotic prevention with a prolonged administration of heparin and/or the association of antiplatelet agents should be considered in patients undergoing RFA.

Adult↗
PubMed1999

Acquired activated protein C resistance in postmenopausal women is dependent on factor VIII:c levels.

Activated protein C (APC) resistance is an established risk factor for venous thromboembolism. In 5% to 10% of patients with venous thromboembolism, the APC resistance phenotype is observed in the absence of factor V Leiden mutation. Moreover, some physiologic and pathologic conditions are associated with an "acquired" APC resistance, not caused by the Leiden mutation, such as inflammatory diseases, pregnancy, or oral contraceptive therapy. Several studies have demonstrated the effect of menopause on the hemostatic system, but no data are available about APC resistance. We found a high prevalence of APC resistance in postmenopausal women, not associated with factor V Leiden mutation. The mechanism that underlies this acquired APC resistance may be related to the higher levels of factor VIII, which showed a strong inverse correlation with APC resistance, whereas no correlation was found between the normalized APC ratio, factor V levels, and protein S values. Higher levels of factor VIII correlated with a marker of coagulation activation, such as prothrombin fragments 1 plus 2. Therefore, to identify women receiving hormone replacement therapy who have a greater risk for deep venous thrombosis, the APC resistance coagulation test should be used instead of the genetic study.

Activated Protein C Resistance↗
PubMed1999

Usefulness of screening for congenital or acquired hemostatic abnormalities in women with previous complicated pregnancies.

Activated protein C resistance (APCR) is a common cause of familial thrombophilia and venous thrombosis. The aim of the study was to investigate the prevalence of APCR associated with factor V Leiden mutation and its relevance in comparison to other risk factors for thromboembolic disorders in women with a history of previous complicated pregnancies (history of fetal loss in the second and third trimester n = 34, preeclampsia n = 46). The frequency of APCR was significantly higher in women with a history of fetal loss and preeclampsia (23.5 and 26.1%, respectively) compared with a control group (3.8%). The prevalence of antithrombin, protein C and protein S deficiencies and the presence of antiphospholipid antibodies were also investigated: the prevalence of at least one disorder was 41.2% in the group with previous fetal loss, 37.0% in the group with previous preeclampsia and 7.5% in the control group.

Activated Protein C Resistance↗
PubMed1999

High prevalence of anti-beta2 glycoprotein I antibodies in patients with ischemic heart disease.

Ischemic cardiac manifestations have been reported in a various percentage of patients with anti-phospholipid antibodies. As concerns the relationship between anti-beta2 glycoprotein I antibodies (anti-beta2-GPI) and ischemic heart disease (IHD), it was investigated in only one coronary primary prevention study. We investigated the prevalence of anti-beta2-GPI in a well characterized group of patients with different clinical manifestation of IHD. Sera from 37 patients (mean age 62.7 +/- 9.9) with IHD (20 with unstable angina-UA and 17 with effort angina-EA) and from 40 healthy subjects, matched for age and sex, were tested for the presence of IgG and IgM anti-beta2-GPI using an ELISA technique. Eleven/37 patients (29.7%) resulted positive for anti-beta2-GPI. A positivity for IgG anti-beta2-GPI was found in 10 patients, 1 patient was positive for IgM and 1 for both isotypes. The prevalence of anti-beta2-GPI in the control group resulted significantly lower (2.5%; p < 0.005) than in patients with IHD. Positivity for anti-beta2-GPI was found in 9/20 (45%) patients with UA and only in 2/17 patients (11.8%) with EA (p = 0.0365). IgG anti-beta2-GPI levels (median 7.7U/ml, range 2.6-24.1) were significantly higher in patients with UA compared to patients with EA (median 4.6 U/ml, range 2.3-11.5; p = 0.02) and controls (median 3.15 U/ml, range 2.3-9.0; p < 0.0001); also IgM levels resulted higher in patients with unstable angina. A positivity for anti-beta2-GPI was observed in 4/13 patients (30.8%) with a previous myocardial infarction (MI) and in 7/24 (29.2%) patients without a previous MI. Our findings suggest that anti-beta2-GPI could represent an expression of the T-cell activation detectable in patients with unstable angina. The lack of a significant difference in the prevalence of these antibodies in patients with or without a previous MI suggests that anti-beta2-GPI are not induced by tissue necrosis.

Aged↗
PubMed1999

Tissue factor reduction and tissue factor pathway inhibitor release after heparin administration.

Elevated plasma levels of tissue factor (TF) and tissue factor pathway inhibitor (TFPI) and large amounts of monocyte procoagulant activity (PCA) have been documented in unstable angina (UA) patients. In in vitro experiments heparin is able to blunt monocyte TF production by inhibiting TF and cytokine gene expression by stimulated cells and after in vivo administration it reduces adverse ischemic outcomes in UA patients. TF and TFPI plasma levels and monocyte PCA have been investigated in 28 refractory UA patients before and during anticoagulant subcutaneous heparin administration (thrice daily weight- and PTT-adjusted for 3 days) followed by 5000 IU X 3 for 5 days. After 2-day treatment, immediately prior to the heparin injection, TF and TFPI plasma levels [(median and range): 239 pg/ml, 130-385 pg/ ml and 120 ng/ml, 80-287 ng/ml] were lower in comparison to baseline samples (254.5 pg/ml, 134.6-380 pg/ml and 135.5 ng/ml, 74-306 ng/ml). Four h after the heparin injection TF furtherly decreased (176.5 pg/ml, 87.5-321 pg/ml; -32.5%. p<0.001) and TFPI increased (240.5 ng/ml, 140-450 ng/ml; +67%, p<0.0001). After 7-day treatment, before the injection of heparin, TF and TFPI plasma levels (200 pg/ml, 128-325 pg/ml and 115 ng/ml, 70-252 ng/ml) significantly decreased (p<0.05) in comparison to the pre-treatment values. On the morning of the 8th day, 4 h after the injection of heparin TF plasma levels and monocytes PCA significantly decreased (156.5 pg/ml, 74-259 pg/ml and from 180 U/105 monocytes, 109-582 U/10(5) monocytes to 86.1 U/10(5) monocytes, 28-320 U/10(5) monocytes; - 38% and -55% respectively) and TFPI increased (235.6 ng/ml, 152-423 ng/ ml; +70%, p<0.001). In conclusion, heparin treatment is associated with a decrease of high TF plasma levels and monocyte procoagulant activity in UA patients. These actions of heparin may play a role in determining the antithrombotic and antiinflammatory properties of this drug.

Adult↗
PubMed1999

Procedure-dependence and tissue factor-independence of hypercoagulability during orthopaedic surgery.

The increased risk for deep vein thrombosis (DVT) after orthopaedic surgery has been well documented as well as hypercoagulable state during both total hip arthroplasty (THA) and total knee replacement (TKR). To investigate the influence of the surgical procedure [posterolateral (PL) or lateral (L) approach for THA, use of tourniquet (TQ) or not use of TQ for TKR] on the hypercoagulability and the role of extrinsic pathway activation and endothelial stimulation during orthopaedic surgery we have examined 40 patients (20 patients undergoing primary THA--10 with PL approach and 10 with L approach--and 20 patients undergoing TKR--10 with TQ application and 10 without TQ). Thrombin-antithrombin complexes (TAT), tissue factor (TF), tissue factor pathway inhibitor (TFPI), thrombomodulin (TM) and von Willebrand factor antigen (vWF:Ag) were analyzed before and during the orthopaedic surgery. During THA, TAT plasma levels increased more markedly in patients assigned to the L than PL approach (p <0.05); during TKR an elevation of TAT of higher degree (p <0.05) was observed when TQ was not applicated. Blood clotting activation was significantly (p <0.001) more relevant during THA than TKR. No changes in TF and vWF:Ag plasma levels were observed in all patients undergoing THA and TKR. TFPI plasma levels significantly (p <0.05) decreased 1 h after the end of the THA in group PL and group L, whereas they remained unaffected in the two groups of patients undergoing TKR. Similarly TM plasma levels significantly decreased during THA, but not during TKR. In conclusion, these results show that: 1) the site of surgical procedures and the type of approach affect the degree of hypercoagulability, 2) the blood clotting activation takes place in the early phases of orthopaedic surgery, without signs of extrinsic pathway and endothelial activation.

Aged↗