Biomedical subjects

Steven R Tosone

Publications and source records attributed to Steven R Tosone.

5 recordsLinked to original sources

PubMed2006

Clinical measures of heparin's effect and thrombin inhibitor levels in pediatric patients with congenital heart disease.

In this investigation, we examined the relationship among three thrombin inhibitors, antithrombin III (ATIII), heparin cofactor II (HCII), and alpha-2-macroglobulin (alpha2M), and several clinical tests of heparin's effect in pediatric patients with congenital heart disease undergoing cardiopulmonary bypass. One hundred eighteen children were stratified into six age groups: <1 mo, 1-3 mo, 3-6 mo, 6-12 mo, 12-24 mo, and >10 yr. Baseline ATIII, HCII, and alpha2M values were measured. Baseline celite- and kaolin-activated clotting times (ACT) were also measured and repeated 3 min after a standard heparin dose of 400 U/kg. Differences in ACT values before and after heparin administration and a heparin dose-response relationship were calculated for each patient. Kaolin-activated ACT tests showed less variation after heparin administration than celite-activated tests. In contrast to what has been demonstrated in adults, ATIII showed no positive correlation with the clinical tests of heparin's effect nor did the other thrombin inhibitors. Additionally, patients <1 mo old had unexpectedly low levels of alpha2M accompanying their expected low levels of ATIII and HCII. Our findings raise concerns about the ability of heparin to adequately anticoagulate these neonates during cardiopulmonary bypass and, consequently, challenge the accuracy of ACT prolongation to truly reflect the extent of their anticoagulation.

Antithrombins↗

PubMed2005

An evaluation of the effects of a standard heparin dose on thrombin inhibition during cardiopulmonary bypass in neonates.

We compared the adequacy of heparinization in neonates and older children undergoing cardiopulmonary bypass (CPB) by measuring heparin activity, thrombin formation, and thrombin activity. Ten neonates and 10 older children were administered 400 U/kg of heparin before CPB. Heparin anti-Xa activity, prothrombin fragment 1.2 (F1.2), and fibrinopeptide A (FPA) were measured at baseline, after 30 min on CPB, immediately post-CPB, and 3 and 24 h post-CPB. Heparin anti-Xa activity was significantly decreased during and immediately post-CPB in the neonatal group. F1.2 and FPA levels in neonates were significantly higher at baseline, decreased with the commencement of CPB, and increased to levels higher than those in older children after CPB. Our data show that with standard heparin doses, neonates exhibit less heparin anti-Xa activity during CPB. Higher baseline levels of F1.2 and FPA present in neonates indicate preoperative activation of their coagulation systems as compared with older children. Although F1.2 and FPA levels initially decrease with the commencement of CPB, probably representing hemodilution, the subsequent increase in these markers indicates significantly more thrombin formation and activity during and after CPB. These results raise the concern that 400 U/kg of heparin may not adequately suppress thrombin formation and activity in neonates undergoing CPB.

Adolescent↗

PubMed2004

The short term effects of cardiopulmonary bypass on neurologic function in children and young adults.

OBJECTIVE: Cognitive deficits are common in adults following surgery utilizing cardiopulmonary bypass (CPB). A previous retrospective study suggested that surgical closure of an ASD in children was associated with neurologic injury, while transcather therapy was not. In a prospective study, we sought to determine whether neurologic deficits occur following repair of non-complex congenital heart lesions in school-age children and young adults. METHODS: Inclusion criteria were: age between 5 and 20 years, cardiac surgery utilizing CPB without deep hypothermic circulatory arrest, and no prior cardiac surgery. Patients underwent psychometric testing 1-3 days prior to surgery and re-evaluation 7-18 days after surgery. In order to determine the test/re-test effect an age-matched cohort of children undergoing transcather closure of ASD under general anesthesia was also evaluated. The primary outcome measures were verbal and picture memory. Additional psychometric tests included: computerized performance test (CPT) and Digit Span (DS). Forty-one patients were enrolled, 29 undergoing surgery with CPB and 12 controls. Surgical procedures included ASD closure (n=13), VSD closure (n=10), resection of sub-aortic stenosis (n=3), mitral valvuloplasty (n=3). Mild hypothermia was used in all cases. The mean duration of CPB was 54+/-22 min. RESULTS: There was no significant difference in any of the psychometric test scores between subjects undergoing surgery with CPB or controls. CONCLUSIONS: There are no marked adverse neurologic effects of CPB in school-age children and young adults undergoing non-complex open-heart surgery. These data are important in counseling patients and families and should be considered in the debate as to the relative merits of transcather versus open-heart repair of various heart lesions.

Adolescent↗

PubMed2004

Fibrinogen in children undergoing cardiac surgery: is it effective?

There is speculation based on laboratory tests and biochemical data regarding the functional integrity of the fibrinogen in young children. Recent investigations in adults have demonstrated that their fibrinogen level correlates with the thromboelastogram maximum amplitude (MA) after modification with a glycoprotein IIb/IIIa receptor blocker that uncouples platelet-fibrinogen interactions. We postulate that if the fibrinogen of young children is functionally intact then their fibrinogen levels should also correlate with modified thromboelastogram MA values as they do in adults. We compared modified and unmodified thromboelastogram variables of 250 children <2 yr old undergoing cardiac surgery with their fibrinogen levels and platelet counts. Five age groups were distinguished to determine if and when correlations become significant (<1 mo, 1-3 mo, 3-6 mo, 6-12 mo, and 12-24 mo). Fibrinogen levels correlated with modified thromboelastogram MAs only in the 12-24 mo group. In this 12-24 mo age group other correlations between fibrinogen levels and thromboelastogram variables influenced by fibrinogen also became significant, as did correlations noted in adults between platelet counts and thromboelastogram variables. We conclude that the fibrinogen of children <12 mo old with congenital heart disease is qualitatively dysfunctional.

Abciximab↗

PubMed2003

Tissue factor-activated thromboelastograms in children undergoing cardiac surgery: baseline values and comparisons.

UNLABELLED: Activation of clotting with tissue factor (TF) allows rapid evaluation of thromboelastograms but alters the values of thromboelastogram variables. We have performed TF-activated thromboelastograms in 250 children <2 yr old undergoing cardiac surgery to establish baseline values. Five groups were distinguished to evaluate the effects of quantitative deficiencies in coagulation factor levels during infancy: <30 days, 1-3 mo, 3-6 mo, 6-12 mo, and 12-24 mo. Activation of clotting (R and K values) was similar among groups. Infants 1-3 mo of age demonstrated increased clot strength compared with the other groups, a finding similar to previous evaluation of native thromboelastograms. The alpha and maximum amplitude values were numerically almost identical in each age group, a unique finding in activated thromboelastograms. Fibrinolysis was similar among groups. We believe that knowledge of baseline TF-activated thromboelastogram variables in young children will be useful in interpreting these thromboelastograms in clinical scenarios, in using these thromboelastograms as part of coagulopathy treatment algorithms, and during the application of more specific thromboelastogram modifiers. Additionally, the similarity of alpha and maximum amplitude values in each age group will allow even faster interpretation of thromboelastogram data. IMPLICATIONS: Baseline values for tissue factor-activated thromboelastograms in young children undergoing cardiac surgery have been established and will permit accurate use and interpretation of this thromboelastogram modification in evaluating and managing coagulopathies.

Algorithms↗