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Biomedical subjects

Armando D'Angelo

Publications and source records attributed to Armando D'Angelo.

At least 19 recordsLinked to original sources
PubMed2006

Phosphorylcholine coating may limit thrombin formation during high-risk cardiac surgery: a randomized controlled trial.

BACKGROUND: During cardiopulmonary bypass, blood contact with the large nonendothelial surfaces of the extracorporeal circuit induces activation and consumption of platelets and plasma coagulation factors. Phosphorylcholine (Pc) coating of oxygenators has been designed to improve surface biocompatibility. We evaluated the effects of a Pc-coated oxygenator on blood coagulation in patients undergoing high-risk open heart surgery and receiving tranexamic acid. METHODS: Thirty-nine patients undergoing reoperative valvular or combined procedures were randomized to the use of an oxygenator treated with Pc coating (Pc group) or of a standard oxygenator (control group). Platelet count, soluble CD40 ligand, fibrinogen, antithrombin, D-Dimer, prothrombin fragment 1.2 (F1.2), and free plasma hemoglobin levels were measured at baseline, at aortic unclamping, and at arrival in the intensive care unit. RESULTS: Postoperative bleeding, need for blood products, and clinical outcomes were similar in the two groups. At unclamping, F1.2, a marker of in vivo thrombin formation, increased to a greater extent in control patients than in Pc patients (p = 0.02), and in the latter group of patients was positively correlated with aortic cross-clamp times (r = 0.70). Relative to baseline values, the percent decrease in platelet count, fibrinogen, and antithrombin levels was not significantly different in Pc patients and in control patients after adjustment for multiple comparisons, but the percent decrease in platelet counts was negatively correlated with F1.2 levels in the entire series of patients (r = -0.62, p < 0.0001). All the evaluated parameters were similar in the two groups of patients at arrival in the intensive care unit. CONCLUSIONS: For patients undergoing high-risk open heart surgery and receiving tranexamic acid, a phosphorylcholine-coated oxygenator may reduce intraoperative thrombin formation and the associated consumption of platelets, fibrinogen, and antithrombin.

Aged↗
PubMed2006

Moderate hyperhomocysteinemia and early-onset central retinal vein occlusion.

PURPOSE: To evaluate the prevalence of moderate fasting hyperhomocysteinemia (HHcy) and postmethionine load (PML) HHcy among patients with early-onset central retinal vein occlusion (CRVO). METHODS: The prevalence of fasting HHcy and that of PML HHcy were evaluated in a consecutive series of 58 patients with CRVO who were younger than 56 years of age (mean age, 40.3 years) and in 103 controls (mean age, 39.6 years). Plasma folate, vitamin B12, and pyridoxal-5'-phosphate (PLP) levels were measured in 42 patients and 67 controls. RESULTS: Mantel-Haenszel odds ratios for CRVO patients were 3.00 (95% confidence interval [CI], 0.83-10.8) for fasting HHcy, 3.50 (95% CI, 1.07-11.4) for PML HHcy, and 3.00 (1.18-7.6) for fasting HHcy and PML HHcy in subjects with normal fasting total homocysteine (tHcy) levels. Moderate HHcy was associated with reduced plasma levels of folate and PLP (P < or = 0.04). There was no significant dependence of fasting and PML tHcy levels on any traditional risk factor evaluated. CONCLUSIONS: Moderate HHcy is an independent risk factor for early-onset CRVO.

Adult↗
PubMed2006

Perioperative management of a heterozygous carrier of Glanzmann's thrombasthenia submitted to coronary artery bypass grafting with cardiopulmonary bypass.

Glanzmann's thrombasthenia is a congenital hemorrhagic disorder transmitted as an autosomal recessive trait and characterized by altered production and/or assembly of the platelet membrane glycoprotein IIb/IIIa receptor. We describe the perioperative management of a heterozygous carrier of Glanzmann's thrombasthenia submitted to cardiac surgery with cardiopulmonary bypass and the case was complicated by early excessive postoperative bleeding.

Aged↗
PubMed2006

Lipoprotein(a), fibrinogen and vascular mortality in an elderly northern Italian population.

BACKGROUND AND OBJECTIVES: High lipoprotein a [Lp(a)] and fibrinogen levels are suggested risk factors for coronary heart disease (CHD) and stroke morbidity and mortality. Experimental data strongly suggest that the mechanisms of atherothrombosis include an interaction between fibrinogen and Lp(a), but little clinical evidence of a synergism between these two parameters has been reported. DESIGN AND METHODS: Within the frame of a prospective population study conducted in the area of Cremona (Lombardy, Italy), 343 women and 216 men aged > or =65 years were evaluated for clinical and biochemical cardiovascular risk factors. Lp(a) levels > or =30 mg/dL were observed in 22.7% and 23.9% of men and women, respectively. Fibrinogen levels were higher in women (p<0.0001). After a median follow-up of 6.3 years 107 deaths were recorded, of which 33 were due to CHD or ischemic stroke. RESULTS: The combined incidence rate of CHD and stroke mortality increased from 10.8 (per 1000 person-years) for subjects with either Lp(a) > or =30 mg/dL or fibrinogen within the 5th quintile of the gender-specific distribution to 38.4 for subjects with both Lp(a) > or =30 mg/dL and fibrinogen within the 5th quintile. Age (p<0.0001), insulin (p<0.0002) and the combination of high Lp(a) and fibrinogen (hazard ratio=3.11, p=0.014), but not fibrinogen or Lp(a) levels in isolation, were independent predictors of CHD and stroke mortality. In a subgroup of 447 subjects in whom C-reactive protein (CRP) was measured, CRP levels were not predictive of combined CHD and stroke mortality. INTERPRETATIONS AND CONCLUSIONS: Based on these results obtained in a relatively small population of elderly subjects, the association of high Lp(a) and fibrinogen levels appears to carry an increased risk of pooled CHD and stroke mortality.

Aged↗
PubMed2005

Reduced in vivo oxidative stress following 5-methyltetrahydrofolate supplementation in patients with early-onset thrombosis and 677TT methylenetetrahydrofolate reductase genotype.

The protective role of folate in vascular disease has been related to antioxidant effects. In 45 patients with previous early-onset (at age <50 years) thrombotic episodes and the 677TT methylenetetrahydrofolate reductase genotype, we evaluated the effects of a 28 d-course (15 mg/d) of 5-methyltetrahydrofolate (MTHF) on homocysteine metabolism and on in vivo generation of 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha), a reliable marker of oxidative stress. At baseline, patients' fasting total homocysteine (tHcy) was 11.5 micromol/l (geometric mean) and urinary excretion of 8-iso-PGF2alpha was 304 pg/mg creatinine, with the highest metabolite levels in the lowest quartile of plasma folate distribution (P < 0.05). After 5-MTHF supplementation, plasma folate levels increased approximately 13-fold (P < 0.0001 versus baseline); tHcy levels (6.7 micromol/l, P < 0.0001) and urinary 8-iso-PGF2alpha (254 pg/mg creatinine, P < 0.001) were both significantly lowered, their reduction being proportional to baseline values (r = 0.98 and r = 0.77, respectively) and maximal in patients with the lowest pre-supplementation folate levels (P < 0.05). The effects on folate (P < 0.0001) and tHcy (P = 0.0004) persisted for at least up to 2 months after withdrawing 5-MTHF. In parallel with long-lasting tHcy-lowering effects, a short-course 5-MTHF supplementation reduces in vivo formation of 8-iso-PGF2alpha in this population, supporting the antioxidant protective effects of folate in vascular disease.

Adult↗
PubMed2005

Morphological and functional differences in haemostatic axis between kidney transplanted and end-stage renal disease patients.

End-stage renal disease (ESRD) is characterized by several atherothrombotic abnormalities, and kidney transplant seems to improve most of them. However, because it is not clear which mechanism is responsible for such improvement, our purpose was to clarify that point.We conducted a cross sectional study involving 30 ESRD patients, 30 ESRD kidney-transplanted patients (Ktx) and 30 healthy controls (C) to evaluate platelet morphology and function, atherothrombotic profile, endothelial abnormalities and cytokine levels involved in the insulin resistance/endothelial dysfunction. (i) Platelet morphology: The ESRD group showed platelet size similar to the other two groups (ESRD=3518x10(3)+/-549x10(3) nm2, C=3075x10(3)+/-197x10(3) nm2, Ktx=2862x10(3)+/-205x10(3) nm2) with similar platelet granules and number. (ii) Platelet surface glycoprotein: The CD41 and P-Selectin were similar between groups. (iii) Platelet intracellular calcium: Resting intracellular calcium was statistically higher in ESRD compared to the C group (ESRD=182.1+/-34.5, Ktx=126.7+/-14.1, C=72.0+/-11.0 nM, P<0.01). (iv) Hypercoagulability markers and natural anticoagulants: The Ktx and ESRD groups showed higher levels of hypercoagulability markers compared to the C group. A reduction in antithrombin activity was evident in ESRD compared to the Ktx group (P=0.03). (v) Endothelial morphology: The ESRD group showed a thickened vessel basal membrane compared to the Ktx and C groups with more endothelial sufference. (vi) Insulin resistance and pro-inflammatory cytokine profile: The ESRD showed a higher homeostasis model assessment provided equations for estimating insulin resistance (HOMA-IR) compared to the Ktx and C groups (ESRD=2.6+/-0.3, Ktx=1.8+/-0.2, C=1.1+/-0.1, P=0.005) and increased soluble tumor neurosis factor alpha (sTNFalpha) (P<0.05) and soluble vascular cell adhesion molecule (sVCAM) levels (P<0.01). Positive correlations were evident among HOMA-IR and sTNFalpha (P<0.001) and sVCAM (P=0.01), respectively. In a small subgroup of ESRD who underwent Ktx (five pts), our findings were confirmed at 1 year of follow-up, suggesting an improvement of almost haemostatic abnormalities. Kidney transplant is associated with a better atherothrombotic profile in ESRD, platelet intracellular calcium and cytokines seem to be most influenced by the transplant, while most morphological abnormalities are retained.

Adult↗
PubMed2005

The association between hyperhomocysteinemia and ischemic stroke in patients with non-valvular atrial fibrillation.

BACKGROUND AND OBJECTIVES: Atrial fibrillation is complicated by a high rate of ischemic stroke. Previous studies have shown that an increased level of circulating total plasma homocysteine (tHcy) is an independent predictor of stroke, but it is unclear whether it is also predictive of stroke in patients with atrial fibrillation. The objective of this study was to evaluate whether increased tHcy is an independent predictor of cardio-embolic stroke in patients with non-valvular atrial fibrillation. DESIGN AND METHODS: We studied 163 consecutive patients (77 males and 86 females; mean age 72.3+/-8.8 years) with permanent (n=118) or paroxysmal (n=45) atrial fibrillation of non-valvular origin hospitalized for cardiac reasons. Ischemic stroke, documented by nuclear magnetic resonance or computerized tomography imaging, had occurred at an average of 2 years before hospitalization in 40 patients (16 males and 24 females, mean age 74.8+/-8.8 years). Fasting tHcy levels were determined by high performance liquid chromatography. RESULTS: Multivariate analysis adjusting for traditional cardiovascular risk factors, thromboembolic risk factors and predictors of tHcy (glomerular filtration rate, uric acid, gender) and fibrinogen levels (age, alcohol intake) showed that total homocysteine (OR: 1.056; for each 1 micromol/L increase, 95% C.I.: 1.00-1.12; p=0.042) and fibrinogen (OR: 1.008 for each 1 mg/dL increase; 95% C.I.: 1.00-1.014; p=0.016) were independently associated with ischemic stroke. With respect to patients in the first quartile of the tHcy distribution (4.6-7.5 micromol/L), patients in the fourth quartile of the tHcy distribution (18.7-67.1 micromol/L) had a 2.73-fold increased probability of ischemic stroke INTERPRETATION AND CONCLUSIONS: In patients with non-valvular atrial fibrillation hospitalized for cardiac reasons, increased fasting tHcy levels are independently associated with a history of ischemic stroke.

Aged↗
PubMed2004

Intrasurgical plasmin enzyme in diabetic macular edema.

PURPOSE: To evaluate in a prospective study the efficacy of intrasurgical autologous plasmin enzyme (APE) in producing posterior vitreous detachment. DESIGN: Consecutive, interventional case series. METHODS: A group of 12 eyes of 11 patients with diabetic macular edema secondary to posterior vitreous cortex contraction was considered. A quantity of 0.1- to 0.2-ml containing 0.8 to 1.2 IU of APE prepared by our Coagulation Service was injected into the vitreous body 25 minutes before surgery. The efficacy of the APE was subjectively evaluated. A control group of 10 eyes with the same clinical characteristics underwent the same surgery without APE injection. Complete eye examinations, including optical coherence tomography, were performed on all patients before surgery and during the 1-year follow-up period. RESULTS: During surgery in the APE-treated group, the posterior vitreous cortex was judged adherent in three cases, partially detached in six cases, and totally detached in three cases. In two cases a complete collapse of the vitreous body was observed. During surgery in the non-APE-treated group, the posterior vitreous cortex was judged still adherent in nine of 10 eyes and partially detached in 1 eye. Comparing the postoperative results between the APE-treated group and the non-APE-treated group, we found no significant differences in final postoperative retinal thickness (P = .2552), whereas we found a significant difference in final visual acuity (P = .0121). CONCLUSIONS: Autologous plasmin enzyme was useful in inducing a pharmacologic posterior vitreous detachment and in facilitating surgery. It did not seem to interfere with the final retinal thickness, and it ameliorates the final visual acuity.

Aged↗
PubMed2004

Effects of tranexamic acid on postoperative bleeding and related hematochemical variables in coronary surgery: Comparison between on-pump and off-pump techniques.

OBJECTIVES: Bleeding and inflammation are major complications of extracorporeal circulation. Off-pump coronary artery bypass grafting may reduce the rate of complications, but it can only be applied in selected cases. Pilot studies have shown a potential benefit from the use of antifibrinolytic drugs, but efficacy in randomized double-blind studies evaluating off- and on-pump coronary artery bypass grafting has not been proved. METHODS: We enrolled 102 patients scheduled for on-pump (n = 51) or off-pump (n = 51) coronary artery bypass grafting. Patients were separately double-blind randomly assigned to treatment with tranexamic acid (1 g as 20-minute bolus before skin incision, followed by continuous infusion of 400 mg/h, with 500 mg added to priming in patients undergoing on-pump coronary artery bypass grafting) or placebo (saline solution of equivalent volume). Bleeding in the first 24 postoperative hours was the primary outcome. Requirement for allogeneic transfusions, thrombotic complications, outcomes, and monitoring of coagulation, fibrinolysis, and inflammation were also recorded. RESULTS: Tranexamic acid reduced total postoperative bleeding by 43% in patients undergoing on-pump coronary artery bypass grafting and by 27% in those undergoing off-pump coronary artery bypass grafting (P <.0001), with 80% reduction in bleeding exceeding 600 mL (P <.001), 58% reduction in the requirement for all allogeneic transfusions (P =.07), and no apparent effect on thrombotic complications or outcome. This was associated with a reduction in plasma D-dimer levels (P <.0001), to a greater degree in patients undergoing on-pump coronary artery bypass grafting (P <.0001), and interleukin 6 levels (P <.0001), to a greater degree in patients undergoing off-pump coronary artery bypass grafting (P <.001). CONCLUSIONS: By affecting fibrinolysis, tranexamic acid significantly reduces bleeding both in off- and on-pump coronary artery bypass grafting and may modulate inflammation in these surgical settings.

Aged↗
PubMed2004

Tissue factor and CCL2/monocyte chemoattractant protein-1 released by human islets affect islet engraftment in type 1 diabetic recipients.

Islet survival in the early posttransplantation period is likely to be influenced by inflammatory events in and around islets. Twenty-seven human islet preparations were transplanted by 24 infusions into 14 patients with brittle type 1 diabetes under the Edmonton protocol. Patients were monitored for their coagulation [cross-linked fibrin degradation products (XDPs)] and liver function test [aspartate and alanine aminotransferase (AST and ALT)] as markers of early posttransplant complications, and these were correlated with in vitro islet number, purification, volume, monocyte-chemoattractant protein-1 (CCL2/MCP-1) and tissue factor (TF) islet release. Consistent with activation of coagulation pathways and hepatic damage, serum XDP values increased early after 11 infusions and transaminase after 13 of 24 infusions. TF and CCL2/MCP-1 were detected in supernatants of 21 and 22 islet preparations, respectively. Serum XDP peak values were correlated with TF/equivalent islets (EI) (r(2)=0.26, P = 0.001) and CCL2/MCP-1/EI (r(2) = 0.42; P < 0.001); serum transaminase areas under the curve in the first week posttransplantation were correlated with CCL2/MCP-1/EI (r(2) = 0.55; P < 0.001 for ALT and r(2) = 0.51; P = 0.001 for AST) and TF/EI (r(2) = 0.31; P = 0.002 for ALT, and r(2) = 0.36; P = 0.002 for AST). These data suggest that reducing the islet proinflammatory state may be a means to reduce the early posttransplant complications and perhaps improve islet engraftment.

Chemokine CCL2↗
PubMed2004

Intraoperative moderate acute normovolemic hemodilution associated with a comprehensive blood-sparing protocol in off-pump coronary surgery.

UNLABELLED: We evaluated the blood-sparing effects of intraoperative moderate acute normovolemic hemodilution (ANH) combined with intraoperative tranexamic acid treatment and shed blood reinfusion in patients undergoing off-pump coronary artery bypass (OPCAB). One-hundred consecutive OPCAB patients (baseline hematocrit >34%) were prospectively randomized to tranexamic acid treatment (control group; 50 patients) or to tranexamic acid treatment plus normovolemic (1:1 replacement with colloids) withdrawal of 17% +/- 2% of the circulating blood volume (ANH group; 50 patients). All patients had shed blood reinfused with intraoperative bleeding in excess of 250 mL. The requirement for allogeneic transfusions, based on strict a priori defined criteria, was the primary end point of the study. Hematochemical evaluations, bleeding, major complications, and other outcomes were also recorded. Demographics, baseline hematochemical data, and operative characteristics were similar in the two groups. Patients in the ANH group had a median of 850 mL of blood withdrawn and showed a lower intraoperative minimum hematocrit (31% vs 37%; P < 0.0001). Two patients in the ANH group versus 10 patients in the control group (odds ratio, 0.17; 95% confidence interval, 0.03-0.89; P = 0.028) required transfusion of a significantly smaller number of packed red blood cell units (5 vs 24; P < 0.001). Postoperative hematochemical variables, bleeding, and outcomes were similar in the two groups of patients. Moderate ANH, combined with tranexamic acid administration and on-demand shed blood reinfusion, may reduce allogeneic transfusion requirements in OPCAB patients. IMPLICATIONS: We studied the blood-sparing effects of moderate acute normovolemic hemodilution (ANH) in 100 patients undergoing off-pump coronary surgery (OPCAB). Combined with tranexamic acid administration and shed blood reinfusion when the intraoperative bleeding exceeded 250 mL, ANH was effective in reducing the number of OPCAB patients who required allogeneic transfusions and the number of packed red blood cell units transfused.

Aged↗
PubMed2004

Normalization of multiple hemostatic abnormalities in uremic type 1 diabetic patients after kidney-pancreas transplantation.

To evaluate the effects of kidney-pancreas transplantation on hemostatic abnormalities in uremic type 1 diabetic patients, we conducted a cross-sectional study involving 12 type 1 diabetic patients, 30 uremic type 1 diabetic patients, 27 uremic type 1 diabetic patients who had a kidney-pancreas transplant, 12 uremic type 1 diabetic patients who had a kidney-alone transplant, and 13 healthy control subjects. We evaluated platelet and clotting system. Platelets in the group of uremic type 1 diabetic patients were significantly larger than platelets in the other groups. Resting calcium levels were significantly higher in the uremic type 1 diabetic patients and uremic type 1 diabetic patients who had a kidney-alone transplant than in the type 1 diabetic patients who had a kidney-pancreas transplant and control subjects. CD41 expression was significantly reduced in platelets from the uremic type 1 diabetic patients compared with the other groups. Levels of hypercoagulability markers in the type 1 diabetic patients who had a kidney-pancreas transplant and, to a lesser extent, the uremic type 1 diabetic patients who had a kidney-alone transplant but not the uremic type 1 diabetic patients were similar to those of the control subjects. A reduction in natural anticoagulants was evident in the uremic type 1 diabetic patients, whereas near-normal values were observed in the type 1 diabetic patients who had a kidney-pancreas transplant and uremic type 1 diabetic patients who had a kidney-alone transplant. Hemostatic abnormalities were not observed in type 1 diabetic patients who had a kidney-pancreas transplant. This finding might explain the lower cardiovascular death rate observed in type 1 diabetic patients who had a kidney-pancreas transplant compared with uremic type 1 diabetic patients who had a kidney-alone transplant or uremic type 1 diabetic patients.

Adult↗
PubMed2003

Islet transplantation improves vascular diabetic complications in patients with diabetes who underwent kidney transplantation: a comparison between kidney-pancreas and kidney-alone transplantation.

BACKGROUND: The aim of this study was to evaluate the effects of islet transplantation on patient survival and diabetic vascular complications. METHODS: Thirty-seven type 1 uremic diabetic kidney transplant patients underwent islet transplantation (KI group). Uremic type 1 diabetic kidney-pancreas (KP group, n=162), kidney-alone (KD group, n=42) transplant patients, and uremic type 1 diabetic patients still on hemodialysis (HD+DM group, n=196) constituted the control groups for survival and endothelial morphology. RESULTS: Patient survival was similar in the KI and KP groups and higher than in the HD+DM group (P<0.05). Patients experiencing long-term islet function (KI-successful [KI-s], n=24) showed a better survival (100%, 100%, and 90%) than those in the KI group who lost islet function (KI-unsuccessful [KI-u], n=13) (84%, 75%, and 45%) at 1, 4 and 7 years, respectively (P=0.02). The cardiovascular death rate for the KI group (18%) was similar to the KD group (19%) but lower when the KI-s group is considered alone (5%), and showed a cardiovascular death rate similar to the KP group (8%). The KI-s group showed a good metabolic profile, with reduction of exogenous insulin requirement and persistent C-peptide secretion, as compared with the KI-u group. The endothelial morphology was evaluated with a skin biopsy obtained in all groups. The KI-s and the KP groups demonstrated decreased signs of endothelial injury compared with the KI-u and HD+DM groups. The KI group showed a better atherothrombotic profile than the HD+DM group, with higher levels of natural anticoagulant protein. CONCLUSIONS: Successful islet transplantation improves survival, atherothrombotic profile, and endothelial morphology in uremic type 1 diabetic kidney transplant patients.

Adult↗