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J Fontcuberta

Publications and source records attributed to J Fontcuberta.

At least 37 records · Page 2Linked to original sources
PubMed2001

Low molecular weight heparin versus oral anticoagulants in the long-term treatment of deep venous thrombosis.

PURPOSE: The purpose of this study was to evaluate whether low molecular weight heparin (LMWH) could be equal or more effective than conventional oral anticoagulants (OAs) in the long-term treatment of deep venous thrombosis (DVT). METHODS: One hundred fifty-eight patients with symptomatic DVT of the lower limbs confirmed by means of duplex ultrasound scan were randomized to receive 3 to 6 months' treatment with nadroparine calcium or acenocoumarol. Quantitative and qualitative duplex scan scoring systems were used to study the evolution of thrombosis in both groups at 1, 3, 6, and 12 months. RESULTS: During the 12-month surveillance period, two (2.5%) of the 81 patients who received LMWH and seven (9%) of the 77 patients who received OAs had recurrence of venous thrombosis (not significant). In the LMWH group no cases of major bleeding were found, and four cases (5.2%) occurred in the OA group (not significant). The mortality rate was nine (11.1%) in the LMWH group and 7.8% in the OA group (not significant). The quantitative mean duplex scan score decreased in both groups during the follow-up and had statistical significance after long-term LMWH treatment on iliofemoral DVT (1, 3, 6, and 12 months), femoropopliteal DVT (1-3 months), and infrapopliteal DVT (first month). Duplex scan evaluation showed that the rate of venous recanalization significantly increased in the common femoral vein at 6 and at 12 months and during each point of follow-up in the superficial and popliteal veins in the LMWH group. Reflux was significantly less frequent in communicating veins after LMWH treatment (17.9% vs 32.2% in the OA group). The reflux rates in the superficial (22.4% in the LMWH group, 30.6% in OA group) and deep (13.4% vs 17.7%) venous system showed no significant differences between groups. CONCLUSIONS: The unmonitored subcutaneous administration of nadroparine in fixed daily doses was more effective than oral acenocoumarol with laboratory control adjustment in achieving recanalization of leg thrombi. With nadroparine, there was less late valvular communicating vein insufficiency, and it was at least as efficacious and safe as oral anticoagulants after long-term administration. These results suggest that LMWHs may therefore represent a real therapeutic advance in the long-term management of DVT.

Acenocoumarol↗
PubMed2001

Systematic study of occult pulmonary thromboembolism in patients with deep venous thrombosis.

PURPOSE: This study was carried out to evaluate the prevalence and extension of pulmonary thromboembolism (PTE) in symptom-free patients with symptomatic deep venous thrombosis (DVT) of lower limbs and to evaluate their possible implication in the adequate treatment of thromboembolic disease. MATERIALS AND METHODS: We prospectively studied, using noninvasive examination (pulmonary spiral computed tomography [CT] angiography), 159 consecutive patients with acute DVT confirmed by duplex scanning without symptoms of PTE. CT was repeated at 30 days to study evolution of these clinically occult PTE. RESULTS: We observed silent PTE in 65 patients (41%) in all levels of lower limb venous thrombosis. Prevalence of PTE showed significant association with male sex (P =.001) and previously diagnosed heart disease (P =.023). There was no significant association between the level of DVT and the presence of PTE nor the DVT side and thromboembolic pulmonary localization. Of the 65 patients with positive CT exploration results for PTE, 52 had characteristics of acute PTE, 10 had chronic PTE, and 3 patients had both. Chronic PTE was found more frequently in patients with previous episodes of DVT (P =.024). A total of 165 pulmonary artery-affected segments were found at several locations: 5 main, 35 lobar, 58 interlobar, and 67 segmental. Multiple segments were affected in 59% of patients. Repeat CT examinations were performed at 30 days in 53 of 65 patients with positive CT scanning results. In 48 cases (90.6%) PTE had completely disappeared. CONCLUSIONS: Silent PTE occurred frequently in association with clots of lower limbs. The CT scan had a good availability and cost-effectiveness to detect clinically underestimated PTE. The incorporation of this exploration in the systematic diagnostic strategy of most patients with DVT to establish the extension of thromboembolic disease at diagnosis may be useful in the evaluation of added pulmonary artery symptoms and treatment strategies.

Adolescent↗
PubMed2001

Genetic regulation of plasma levels of vitamin K-dependent proteins involved in hematostatis: results from the GAIT Project. Genetic Analysis of Idiopathic Thrombophilia.

Vitamin K-dependent proteins play a critical role in hemostasis. We have analysed the genetic and environmental correlations between measures of several vitamin K-dependent proteins in 21 Spanish extended families, including 397 individuals. Plasma functional levels of factors II, VII, IX, X, protein C and functional protein S were assayed in an automated coagulometer. Antigenic levels of total and free protein S were measured using an ELISA method. A maximum likelihood-based covariance decomposition analysis was used to assess the heritability of each trait and the genetic and environmental correlations between all possible pairs. All of the plasma levels had a significant genetic component (heritability) ranging from 22% to 52% of the phenotypic variance. Among the 28 possible pairs of genetic correlations, 18 were significant at a level of p < 0.05 and six exhibited a p-value between 0.05 and 0.10. Positive environmental correlation was observed for 25 of the pairs (p < 0.05). We conclude that genetic effects account for a large proportion of the observed phenotypic variation in vitamin K-dependent proteins. Some of the genes appear to pleiotropically influence all of these traits, since most pairs of phenotypes exhibit significant genetic correlation. However, since these phenotypes show a high degree of environmental correlation, it is also likely that the same environmental factors influence them co-jointly.

Adolescent↗
PubMed2001

Risk of thrombosis associated with oral contraceptives of women from 97 families with inherited thrombophilia: high risk of thrombosis in carriers of the G20210A mutation of the prothrombin gene.

BACKGROUND AND OBJECTIVES: Oral contraceptives (OC) and inherited thrombophilia are well-known risk factors associated with venous thromboembolism (VTE). However, there are only few studies on the risk of VTE in women with inherited thrombophilia who use oral contraceptives. DESIGN AND METHODS: We performed a retrospective family cohort study of 325 women belonging to 97 families with inherited thrombophilia, including antithrombin, protein S and C deficiencies, the factor V Leiden mutation (FVL) and the G20210A mutation of the prothrombin gene (PT20210A) to determine the risk of VTE associated with OC intake. RESULTS: For carriers of the PT20210A mutation, the risk of VTE in OC users was 3-fold higher (95% CI 1.3-6.8) than that in non-carriers. Carriers of FVL mutation taking OC showed an OR of 1.4 (95% CI 0.6-3.3), indicating a tendency to increase the risk of VTE. INTERPRETATION AND CONCLUSIONS: Because of the high prevalence of the PT20210A (6.5%) and FVL (2%) mutations in the general Spanish population and the increased risk of VTE associated with OC intake, genetic screening for these mutations should be considered in potential OC users belonging to families with thrombophilia.

Adolescent↗
PubMed2001

Contribution of prothrombin 20210A allele and factor V Leiden mutation to thrombosis risk in thrombophilic families with other hemostatic deficiencies.

BACKGROUND AND OBJECTIVES: The aims of this study were to compare the lifetime probability of developing thrombosis in 722 relatives of 132 thrombophilic families of symptomatic probands with recognized thrombophilic defects and to determine the prevalence of the factor V Leiden (FVL) mutation and the 20210A allele of the prothrombin gene (PT20210A) in these families. DESIGN AND METHODS: The study included 722 members belonging to 132 unrelated families. The propositi were patients who had been referred to our Thrombosis Unit. The families were selected through a symptomatic proband. Once a patient with a deficiency or mutation was identified, family members were screened for the same defect. RESULTS: The prevalence of FVL and PT20210A in families with other thrombophilic defects was higher than expected. Compared with non-deficient individuals, the risk of venous thrombosis was increased in subjects with antithrombin (AT), protein S (PS) and protein C (PC) deficiencies, and in carriers of FVL and PT20210A mutations. The risk of thrombosis was significantly increased for individuals with combined genetic defects (PC-FVL, PS-FVL, PS-PT20210A and FVL-PT20210A). The ages at the time of 50% thrombosis-free survival were as follows: 34 years for AT deficiency, (19 years with FVL, 21 years with PT20210A), 62 years for PC deficiency (33 years with FVL, 44 years with PT20210A), 37 years for PS deficiency (24 years with FVL, 36 years with PT20210A), 50 years for the FVL mutation (52 years with PT20210A), and 65 years for the PT20210A mutation. As for clinical characteristics, no differences were observed except for the higher frequency of oral contraceptive-related thrombosis in women who were carriers of PT20210A or FVL. INTERPRETATION AND CONCLUSIONS: Based on these results, screening for FVL and PT20210A mutation is recommended in patients with other thrombophilic defects. To the best of our knowledge, this is the first family study, including the PT20210A mutation, that compares genetic risk factors for thrombosis and the lifelong probability of developing thrombosis.

Adolescent↗
PubMed2000

Genetic susceptibility to thrombosis and its relationship to physiological risk factors: the GAIT study. Genetic Analysis of Idiopathic Thrombophilia.

Although there are a number of well-characterized genetic defects that lead to increased risk of thrombosis, little information is available on the relative importance of genetic factors in thrombosis risk in the general population. We performed a family-based study of the genetics of thrombosis in the Spanish population to assess the heritability of thrombosis and to identify the joint actions of genes on thrombosis risk and related quantitative hemostasis phenotypes. We examined 398 individuals in 21 extended pedigrees. Twelve pedigrees were ascertained through a proband with idiopathic thrombosis, and the remaining pedigrees were randomly ascertained. The heritability of thrombosis liability and the genetic correlations between thrombosis and each of the quantitative risk factors were estimated by means of a novel variance component method that used a multivariate threshold model. More than 60% of the variation in susceptibility to common thrombosis is attributable to genetic factors. Several quantitative risk factors exhibited significant genetic correlations with thrombosis, indicating that some of the genes that influence quantitative variation in these physiological correlates also influence the risk of thrombosis. Traits that exhibited significant genetic correlations with thrombosis included levels of several coagulation factors (factors VII, VIII, IX, XI, XII, and von Willebrand), tissue plasminogen activator, homocysteine, and the activated protein C ratio. This is the first study that quantifies the genetic component of susceptibility to common thrombosis. The high heritability of thrombosis risk and the significant genetic correlations between thrombosis and related risk factors suggest that the exploitation of correlated quantitative phenotypes will aid the search for susceptibility genes.

Adolescent↗
PubMed2000

Linkage analysis demonstrates that the prothrombin G20210A mutation jointly influences plasma prothrombin levels and risk of thrombosis.

Association studies suggest that the G20210A mutation (G to A substitution at nucleotide position 20210) in the prothrombin gene (PT) is associated with increased plasma prothrombin activity and with increased risk for venous thromboembolism. To test directly for linkage between this PT variant and plasma prothrombin activity we performed a family-based study. The G20210A genotypes and plasma prothrombin activity levels were determined in 435 individuals belonging to 22 extended Spanish families. The sample was composed of 388 homozygous (G/G) normal individuals and 43 heterozygote (G/A) and 4 homozygote (A/A) carriers for the G20210A mutation. The results of variance-component linkage analysis yielded a highly significant lod score of 3.6 (P = 2.4 x 10(-5)) between this mutation and a quantitative trait locus (QTL) that influences prothrombin activity. Importantly, a conditional linkage analysis that simultaneously accounted for association with the G20210A variant completely eliminated the linkage signal, which indicates that this mutation affects the function of the prothrombin gene. Additionally, a bivariate linkage analysis of plasma prothrombin activity and thrombosis significantly improved the linkage signal for prothrombin activity (lod score = 4.7; P = 1.5 x 10(-6)) and provided strong evidence that this QTL has a pleiotropic effect on the risk of thrombosis (lod score = 2.43; P =.0004). These results represent the first direct genetic evidence that a QTL in the PT gene influences prothrombin activity levels and susceptibility to thrombosis and strongly support the conclusion that G20210A is a functional polymorphism. (Blood. 2000;95:2780-2785)

Adult↗
PubMed2000

Genetic determinants of hemostasis phenotypes in Spanish families.

BACKGROUND: Recent studies have described genetic mutations that affect the risk of thrombosis as a result of abnormal levels of such hemostatic parameters as protein C, protein S, and the activated protein C resistance ratio. Although these mutations suggest that genes play a part in determining variability in some hemostasis-related phenotypes, the relative importance of genetic influences on these traits has not been evaluated. METHODS AND RESULTS: The relative contributions of genetic and environmental influences to a panel of hemostasis-related phenotypes were assessed in a sample of 397 individuals in 21 extended pedigrees. The effects of measured covariates (sex, age, smoking, and exogenous sex hormones), genes, and environmental variables shared by members of a household were quantified for 27 hemostasis-related measures. All of these phenotypes showed significant genetic contributions, with the majority of heritabilities ranging between 22% and 55% of the residual phenotypic variance after correction for covariate effects. Activated protein C resistance ratio, activated partial thromboplastin time, and Factor XII showed the strongest heritabilities, with 71.3%, 83.0%, and 67.3%, respectively, of the residual phenotypic variation attributable to genetic effects. CONCLUSIONS: These results clearly demonstrate the importance of genetic factors in determining variation in hemostasis-related phenotypes that are components of the coagulation and fibrinolysis pathways and that have been implicated in risk for thrombosis. The presence of such strong genetic effects suggests that it will be possible to localize previously unknown genes that influence quantitative variation in these hemostasis-related phenotypes that may contribute to risk for thrombosis.

Adolescent↗
PubMed2000

Optimization of a simple and rapid single-strand conformation analysis for detection of mutations in the PROS1 gene: identification of seven novel mutations and three novel, apparently neutral, variants.

Anticoagulant protein S (PS) deficiency is a known risk factor for thrombophilia. The structure and high allelic heterogeneity of the PS gene (PROS1), together with the presence of a 97% homologous pseudogene, complicates PROS1 analysis. We have optimized a simple, fast, and non-isotopic Single-Strand Conformation Analysis (SSCA or SSCP) method for PROS1 mutation detection. This is accomplished through the analysis of the single-stranded and heteroduplex DNA fragments corresponding to 15 PCR segments that include part of the 5'-upstream region and the 15 PROS1 exons with their intron boundaries. To standardize the method, 13 known PROS1 mutations or allele variants in 10 different fragments were analyzed under different electrophoretic conditions. The results indicated that, using a combination of two different electrophoretic settings, all the allele variants could be detected as a single-strand band shift and/or by the presence of a heteroduplex. This method was used to analyze the PROS1 gene in 31 propositi with different types of PS deficiency and thrombosis. Ten different cosegregating mutations, seven of which are novel (143C->G, L-27H, G96X, M599T, P626L, 1418delA, and 1877delT), were identified in the five families suffering from type I or quantitative PS deficiency and in four of the nine families with coexistence of type I and type III phenotypes. No clearly co-segregating PROS1 mutations were identified in any of the 17 type III propositi analyzed, although eight of them were heterozygotes for the uncommon P460 allele of the S/P460 variant. Furthermore, five apparently neutral allelic variants, three of which are novel (-296C->T, 182G->C and T57S), were identified in a normal control, two type I/III and two type III PS-deficient pedigrees.

Alleles↗
PubMed2000

D-Dimer is an early diagnostic marker of coronary ischemia in patients with chest pain.

BACKGROUND: Chest pain is a frequent symptom in the emergency department and often presents a diagnostic challenge. Because coronary thrombosis is a hallmark of acute ischemic syndromes, the substrates of the coagulation and fibrinolysis cascades may be markers of coronary ischemia. The objective of this study was to determine the diagnostic value of several hemostatic markers in patients presenting to the emergency department (ED) with chest pain syndromes. METHODS: Two hundred fifty-seven consecutive patients with acute chest pain were studied in this prospective study conducted in an urban ED. D-Dimer levels were measured at admission to the ED in all patients. We also measured thrombin-antithrombin complexes, prothrombin fragment 1+2, activated factor VII, and fibrinogen. We used regression analysis to estimate the likelihood of myocardial infarction and the diagnostic value of D-dimer. RESULTS: D-Dimer and fibrinogen levels were significantly higher in patients with acute ischemic events (myocardial infarction and unstable angina) than in nonischemic patients (P <.01 and P =.02, respectively). The other hemostatic markers were not significantly elevated in patients with ischemic events. D-Dimer level >500 microg/L had an independent diagnostic value for myocardial infarction and increased the diagnostic sensitivity of the electrocardiogram and history from 73% to 92%. CONCLUSION: D-Dimer, an expression of ongoing thrombus formation and lysis, is a marker of substantial incremental value for the early diagnosis of acute coronary syndromes presenting with chest pain. It adds independent information to the traditional assessment for myocardial infarction. D-Dimer can be incorporated into clinical decision models in the ED.

Adult↗
PubMed2000

Evolution of leukotriene B4, peptide leukotrienes, and interleukin-8 plasma concentrations in patients at risk of acute respiratory distress syndrome and with acute respiratory distress syndrome: mortality prognostic study.

OBJECTIVE: To compare the evolution of plasma concentrations of leukotriene (LT) B4, LTC4, LTD4, and interleukin (IL)-8 in patients with acute respiratory distress syndrome (ARDS) and in patients at risk of ARDS and to assess the value of these mediators in predicting mortality rate from ARDS. DESIGN: A case-control study comparing ARDS patients and patients at risk of ARDS as well as survivors and nonsurvivors with ARDS. SETTING: Hospital intensive care unit, laboratory, and department of hematology. PATIENTS: Twenty-one patients with ARDS and 14 patients at risk of ARDS. INTERVENTION: Arterial blood samples were collected on days 0, 1, and 5 after admission to the intensive care unit. MEASUREMENTS AND MAIN RESULTS: LTs were extracted, separated by high-pressure liquid chromatography and quantified by enzyme immunoassay. IL-8 was analyzed by ELISA. Plasma concentrations of LTB4 and LTC4 plus LTD4 were significantly higher in ARDS patients than in patients at risk of ARDS during the first 24 hrs. Concentrations of IL-8 were also higher in ARDS patients than in patients at risk throughout the study, although the differences between the two groups were only significant on day 5. Only the plasma concentration of LTB4 on day 1 was a marker of ARDS (72.2% sensitivity, 84.6% specificity). A logistic regression analysis showed that LTB4 and IL-8, on day 1, were markers of mortality rate in patients with ARDS (70.0% sensitivity, 87.5% specificity). CONCLUSIONS: LTs are elevated during the early phases of ARDS, whereas IL-8 increases throughout the study. The evaluation of LTB4 and IL-8 may be useful prognostic indices in patients with early phase ARDS after admission to the intensive care unit.

Biomarkers↗
PubMed2000

Functional effects of the ABO locus polymorphism on plasma levels of von Willebrand factor, factor VIII, and activated partial thromboplastin time.

Lower levels of factor VIII and von Willebrand factor (vWF) have been reported in individuals with blood type O compared with individuals with other ABO blood types. However, this relationship has been demonstrated only by association studies and not by linkage studies. Also, it is not clear whether the ABO locus exerts a functional effect directly on these plasma factors or whether the ABO locus is in linkage disequilibrium with another locus that controls these factors. To distinguish between these 2 possibilities, we applied new statistical methods combining linkage and association tests in a pedigree-based sample. In contrast to most previous studies that used the ABO phenotypes, our study used the ABO genotypes, permitting us to distinguish AO from AA and BO from BB. Our results clearly showed significant linkage between the ABO locus and vWF antigen (P=0.00075). In addition, factor VIII coagulant activity and activated partial thromboplastin time showed suggestive linkage with the ABO locus (P=0.10 and P=0.13). All 3 plasma phenotypes showed significant differences between OO and non-OO genotypes. In addition, vWF antigen exhibited significant differences between O heterozygotes and non-OO homozygotes. This study is unique because it used a combined linkage and association test, which indicated that the ABO locus itself has a functional effect on these plasma phenotypes.

ABO Blood-Group System↗
PubMed2000

Platelet function during cardiopulmonary bypass not changed by two different doses of aprotinin.

BACKGROUND AND OBJECTIVE: Bleeding is one of the major complications of cardiopulmonary bypass (CBP) during cardiac surgery. A platelet function defect seems to be the main cause of the hemostatic problems associated with CBP. Controversial results have been reported concerning the possible protective mechanism of action of aprotinin on platelets. DESIGN AND METHODS: In this study we investigated the effect of two different dosages of aprotinin (high and pump-prime-only dose) on platelet reactivity in vitro and adhesion, activation and aggregation receptors on the platelet surface. RESULTS: The results obtained from 53 patients undergoing CBP showed a significantly deficient platelet aggregation in response to agonist in all groups without differences between aprotinin treated or not treated patients. No changes in platelet surface expression of glycoprotein (GP) IIb-IIIa, GPIb, GPIV and P-selectin, were observed during CBP between patients treated with aprotinin or not. INTERPRETATION AND CONCLUSIONS: These data suggest that inadequate platelet function induced by CBP is not a defect intrinsic to the platelet. We conclude that the hemostatic effect of aprotinin, regardless of the dose employed, is not mediated by protection of platelet function.

Adult↗
PubMed2000

Normalisation of tissue factor pathway inhibitor activity after glycaemic control optimisation in type 1 diabetic patients.

UNLABELLED: Increased plasma concentrations of various markers of endothelial damage have been observed in type I diabetic patients, particularly in those with microangiopathy. OBJECTIVE: To evaluate the effect of near-normalisation of glycaemic control on different markers of endothelial injury involved in haemostasis in poorly-controlled type 1 diabetic patients. MATERIAL AND METHODS: TFPI, thrombomodulin (TM), plasminogen activator inhibitor, tissue-type plasminogen activator and von Willebrand factor were measured in 14 poorly-controlled type 1 diabetic patients free of diabetes-related complications (8 men, 6 women; mean age 29.8 +/- 9.9 years) before (baseline) and after 3 months of intensive therapy and in 14 sex-, age- and BMI-matched control subjects. RESULTS: After a mean follow-up of 107 +/- 49 days (56-210), HbA1c decreased from 11.2 +/- 2.3 to 6.7 +/- 0.7% (p <0.0001). TFPI activity at baseline was higher than in the control group (126.9 +/- 34 vs 92.0 +/- 13%, p <0.005) and decreased after good glycaemic control was achieved (p <0.005), becoming similar to that in the control group (91.0 +/- 16.5%). The TFPI descent correlated with the variations observed in HbA1c (p <0.05; r = 0.54). TM levels at baseline were significantly higher than in the control group (42.3 +/- 9.1 vs 29.00 +/- 10.9; p <0.005) and did not change. The remaining parameters studied were similar between patients and controls and did not change after glycaemic optimisation. CONCLUSIONS: Optimisation of glycaemic control normalises the increased activity of TFPI but not the higher TM levels observed in poorly-controlled type I diabetic patients without chronic complications.

Adolescent↗
PubMed2000

The effect of two different doses of aprotinin on hemostasis in cardiopulmonary bypass surgery: similar transfusion requirements and blood loss.

BACKGROUND AND OBJECTIVES: Various dosages of aprotinin have proven to be effective in reducing blood loss and allogeneic transfusion requirements in cardiopulmonary bypass surgery, despite the controversy surrounding the precise hemostatic mechanisms of this drug. The aim of our prospective, randomized, double-blind study was to assess differences in blood loss and transfusion requirements and the effect of two dosages of aprotinin on hemostatic activation. DESIGN AND METHODS: Patients undergoing coronary artery bypass grafting received high-dose aprotinin (n=28), pump-prime-only (PPO) aprotinin (n=28), or placebo (n=28). RESULTS: The high-dose and the PPO groups had a significantly lower blood loss (985 mL [95%CI 845-1,102] and 1,255 mL, [95% CI 1,025-1,406], respectively) than the placebo group (1,416 mL, 95%CI 1,248-1,612]. Transfusion requirements were lower in the aprotinin-treated groups than in the patients receiving placebo (21 units and 15 units in the high and low-dose groups vs 59 units in placebo group). As far as concerns parameters of thrombin generation, the aprotinin groups showed a significant reduction of F1+2 prothrombin fragment but not of thrombin-antithrombin complexes. There were higher levels of natural anticoagulants, i.e. antithrombin, protein C and protein S, in the high-dose aprotinin group. As regards fibrinolysis parameters, D-dimer was lower in the aprotinin groups, and the levels of alpha2-antiplasmin and plasmin-alpha2-antiplasmin complexes were raised. In summary, both dosages of aprotinin were equally effective in reducing blood loss and transfusion requirements. There was a lower activation of coagulation and fibrinolysis in cardiopulmonary bypass patients treated with aprotinin: the levels of natural anticoagulants were less decreased in the high-dose group. No differences in thrombotic complications were observed between aprotinin groups. INTERPRETATION AND CONCLUSIONS: Our study shows that both dosages of aprotinin are safe and effective in reducing transfusion requirements. Considering the difference in cost of using a low-dose or high-dose schedule, the former should be recommended for patients undergoing cardiopulmonary bypass surgery.

Adult↗