Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Noonan's syndrome is characterised by a dysmorphic facies, congenital heart disease, and short stature, and is inherited as an autosomal dominant trait. Because abnormal bleeding has also been reported, we investigated a group of patients for coagulation-factor deficits. Of the 72 individuals studied (37 male, 35 female, mean age 11.4 years), 47 (65%) had a history of abnormal bruising or bleeding. 29 patients (40%) had a prolonged activated partial thromboplastin time. Specific abnormalities in the intrinsic pathway of coagulation (partial factor XI:C, XII:C, and VIII:C deficiencies) were found in 36 patients (50%). Multiple abnormalities among these 36 patients included combined factor XI:C and XII:C deficiencies (4 patients) and factor XI:C and VIII:C deficiencies (4), and 1 patient had combined factor VIII:C, XI:C, and XII:C deficiency. There was poor correlation between a history of abnormal bleeding and coagulation-factor deficit. In five families, similar coagulation-factor deficiencies were present in first-degree relatives with the syndrome. The pattern of inherited bleeding abnormalities seen in Noonan's syndrome suggests autosomal regulation of the intrinsic coagulation pathway.
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PMID:Coagulation-factor deficiencies and abnormal bleeding in Noonan's syndrome. 134 91

Four groups of patients were studied. Group I: Congenital cyanotic heart disease (CCHD), consisting of 24 subjects aged 5 to 28 (1.4); 18 males and 4 females. Group II: Acyanotic congenital heart disease (ACHD), consisting of 34 patients aged 5 to 42 (20.1); 17 males and 17 females. Group III: Rheumatic heart disease (RHD), consisting of 30 patients aged 11-54 (42.4); 9 males and 21 females. Group IV: Atherosclerotic heart disease (AHD), consisting of 35 patients aged 36 to 65 (49.2); 33 males and 2 females. The haematocrit value (Hct) was the highest in the CCHD group. Total amount of heparin (mg/kg) used during cardiopulmonary bypass was 5.4 in CCHD, 4.66 in ACHD, 4.8 in RHD and 4.6 in AHD group. Mean protamine values was 4.02; 4; 4.03; and 4 respectively. Although the difference of Hct value was statistically different between CCHD and RHD group (p less than 0.001), heparin need was not (p less than 0.1). One-way analysis of variance (F test) showed no difference for heparin need between the four groups (F3.119 = 0.64). Prothrombin time (PT) and activated partial thromboplastin time (aPTT) showed a positive correlation (r = 0.36 and r = 0.25) with heparin need in CCHD group but no correlation was found in RHD group.
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PMID:Heparin need of the patients with cyanotic congenital heart disease during cardiopulmonary bypass. Comparison of cyanotic, acyanotic, rheumatic and atherosclerotic subjects. 274 17

We identified a consecutive series of 12 children with noncyanotic congenital cardiac lesions with loss of the largest plasma von Willebrand factor (vWF) multimers determined by SDS-agarose electrophoresis. Seven had previous histories of mucocutaneous hemorrhage; ten had a prolonged bleeding time. Analysis of the factor VIII molecular complex revealed that six patients had reduced vWF measured both immunologically (vW:Ag) and by ristocetin cofactor assay (vW:rist). All had normal or borderline normal factor VIII procoagulant (F VIII) concentrations. Three children had prolonged partial thromboplastin times due to concurrent factor XII deficiency; none had laboratory evidence of intravascular coagulation. Five of the children were restudied after surgical correction of their cardiac lesions. Four had normalization of vWF multimers; the fifth, whose vWF was abnormal postoperatively, had a residual pressure gradient across a previous pulmonary artery banding site. Multimeric abnormalities were not found in the parents of three patients. Thus some patients with noncyanotic congenital heart disease may have an acquired abnormality of vWF that is normalized with correction of the abnormal hemodynamic state.
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PMID:Loss of the largest von Willebrand factor multimers from the plasma of patients with congenital cardiac defects. 348 79

The incidence of abnormal results of coagulation tests and the risks for postoperative hemorrhage were assessed in 235 patients with congenital heart disease. Preoperatively, the prothrombin time, partial thromboplastin time, activated partial thromboplastin time, thrombin time, or platelet count was abnormal in 45 of the 235 patients (19%), a significantly higher incidence than that expected in a normal population (P less than 0.002). Prolonged values for the prothrombin time or the partial thromboplastin time or activated partial thromboplastin time were seen most frequently. Further evaluation in eight of the patients with prolonged prothrombin time or partial thromboplastin or activated partial thromboplastin time showed decreased levels of either factor VII or IX in six of them, suggesting that impaired vitamin K-dependent carboxylation is commonly present. Normal results of preoperative coagulation tests do not exclude the presence of a major bleeding diathesis (von Willebrand's disease was later diagnosed in a patient with such findings). The use of blood products during subsequent cardiac operations was not significantly different in patients with normal or abnormal test results. Two of the three patients who required reoperation and were found to have a nonsurgical cause of bleeding had abnormalities in two or more of the preoperative coagulation tests. This finding suggests that abnormal results of preoperative coagulation tests may be predictive of defective hemostasis in the postoperative period.
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PMID:Preoperative evaluation of hemostasis in patients with congenital heart disease. 357 26

Current guidelines for heparin therapy in pediatric patients have been extrapolated from trials in adult patients without rigorous evaluation of efficacy and safety. We prospectively monitored consecutive pediatric patients receiving systemic doses of heparin over 10 mo at one institution using a predetermined nomogram to monitor maintenance therapy. Sixty-five consecutive children; 38 males and 27 females, received systemic doses of heparin. Thirty children had deep venous thrombosis and/or pulmonary embolism; 11 had arterial thrombi, most frequently after diagnostic angiography; and the remaining 24 received heparin prophylactically, for congenital heart disease. Twenty-nine (45%) of the 65 patients were less than 1 y of age and 22 (34%) were 10 y or older. Congenital heart disease was the predominant diagnosis under 1 y and deep venous thrombosis in older children. After a bolus dose of 50 U/kg, 39% of children (n = 30) achieved a minimal level activated partial thromboplastin time (APTT). Sixty-eight percent of children achieved a minimal level APTT by 24 h and 81% by 48 h. For all 65 children, APTT values were within the therapeutic range 43% of the time. APTT values outside the therapeutic range were twice as likely to be low as high. The average amount of heparin required to maintain therapeutic APTT values for children was 22 U/kg/h: 28 U/kg/h for infants < 1 y and 20 U/kg/h for the rest. Bleeding was rare (2%) and mild. Documented recurrent thrombotic disease was more common (7%) with associated morbidity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Heparin therapy in pediatric patients: a prospective cohort study. 813 3

Severe coagulation defects often develop in neonates undergoing cardiac surgery, both as a result of the surgical intervention, and as pre-existing defects in the hemostatic mechanisms. The following case report describes a newborn patient with complex congenital heart disease and respiratory failure whose pre-operative coagulopathy was aggressively managed prior to surgical correction. A 5-day-old, 2.5 kg child presented with interrupted aortic arch, ventricular septal defect, atrial septal defect, and patent ductus arteriosus. On admission, he was in respiratory arrest suffering from profound acidemia. In addition, the child was hypothermic (30.1 degrees C), septic (Streptococcus viridans), and coagulopathic (disseminated intravascular coagulation-DIC). The patient was immediately intubated and initial coagulation assessment revealed the following: prothrombin time (PT) 48.9 s (international normalized ratio (INR) 15.7), activated partial thromboplastin time (aPTT) >106 s, platelet count 30,000 mm(3), fibrinogen 15 mg dL(-1) and antithrombin III (AT-III) 10%. Before cardiac surgery could be performed, the patient's DIC was corrected with the administration of cryoprecipitate (15 ml), fresh frozen plasma (300 ml), and platelets (195 ml). In spite of the large transfusion of fresh frozen plasma, the AT-III activity, measured as a percentage, remained depressed at 33. Initial thromboelastographic (TEG) determination revealed an index of +2.02, and following 100 IU administration of an AT-III concentrate, declined to -2.32. Sequential TEG profiles were performed over several days, with the results used to guide both transfusion and medical therapy. The congenital heart defect correction was subsequently performed with satisfactory initial results, but the patient developed a fungal infection and expired on the 16th post-operative day. The present case describes techniques of coagulation management for a newborn with both a severe hemostatic defect and congenital heart disease.
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PMID:Pre-operative coagulopathy management of a neonate with complex congenital heart disease: a case study. 1078 72

This study was undertaken to screen children with congenital heart disease for coagulation abnormalities and to compare the groups of cyanotic and acyanotic children with congenital heart disease with respect to abnormalities of the coagulation system. Following investigations were done in all the patients: complete blood count, erythrocyte sedimentation rate, peripheral smear examination, bleeding time, prothrombin time, activated partial thromboplastin time, assay of fibrinogen, D-dimer, factors VII and VIII and antithrombin III. Red cell indices were determined in 12 control, 12 acyanotic and 20 cyanotic children. Twenty-five patients each, with echocardiographically proven cyanotic and acyanotic congenital heart disease under 12 years of age constituted the study group; as many children of the same age group were included as the control group. The results showed isolated abnormalities of laboratory tests with equal frequency (28%) in acyanotic and cyanotic groups but coexisting abnormalities of more than one test were seen in significantly larger number of cyanotic children (5/25 and 16/25, respectively). A significant association was noted between thrombocytopenia and a high haematocrit in cyanotic patients. It is concluded that laboratory abnormalities of tests of haemostasis are more common in cyanotic congenital heart disease patients. The patterns of laboratory abnormalities suggest a chronic compensated disseminated intravascular coagulation at a subclinical level, reduced synthesis of clotting factors and/or deranged platelet aggregation in different subgroups of patients.
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PMID:Haemostatic changes in children with cyanotic and acyanotic congenital heart disease. 1125 79

The objective of this study was to investigate the correlation between factor XIII (FXIII) activity and disseminated intravascular coagulation (DIC) parameters and also to evaluate the clinical usefulness of DIC diagnosis. Citrated plasma from eighty patients with potential DIC was analyzed for FXIII activity. The primary patient conditions (48 male and 32 female, mean age, 51 years) were malignancy (n = 29), infection (n = 25), inflammation (n = 6), heart disease (n= 3), thrombosis (n = 2), injury (n = 2), and other miscellaneous conditions (n = 13). FXIII testing was performed using the CoaLinkTM FXIII Incorporation Assay Kit (PeopleBio Inc.). Among 80 patients who were suspected to have DIC based on clinical analysis, 46 (57.5%) fulfilled the overt DIC criteria (DIC score > = 5) according to the International Society of Thrombosis and Haemostasis. FXIII levels in the plasma were significantly decreased in overt DIC compared to non-overt DIC patients (mean 75.1% and 199.7% respectively, p < 0.0001). Interestingly, we found a significant inverse correlation between DIC scores and FXIII activity. In addition, FXIII activity significantly correlated with other hemostatic markers that included platelet count, prothrombin time, activated partial thromboplastin time, fibrinogen, and D-dimer. FXIII levels were significantly lower in patients with liver or renal dysfunction. In conclusion, FXIII cross-linking activity measurements may have differential diagnostic value as well as predictive value in patients who are suspected to have DIC.
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PMID:Plasma factor XIII activity in patients with disseminated intravascular coagulation. 1664 48

Although a significant minority of patients with cyanotic congenital heart disease (CCHD) are thrombocytopenic, the pathogenesis and prevalence have not been established. This study was designed to address these 2 issues. We included 105 patients with CCHD (60 men and 45 women; aged 21 to 54 years). Systemic arterial oxygen saturations were 69% to 78%. Hematocrits were 62% to 74% with normal iron indexes. In 26 of 105 patients (25%), platelet counts were <100x10(9)/L. The diagnosis was Eisenmenger syndrome in all 26 patients with thrombocytopenia. Platelet production was determined by flow cytometric reticulated platelet counts. Megakaryocyte mass was determined indirectly by thrombopoietin levels. Disseminated intravascular coagulation was based on prothrombin time, activated partial thromboplastin time, and D-dimers. Platelet activation was determined by levels of platelet factor 4 and beta thromboglobulin. Reference ranges were derived from 20 normal acyanotic controls. A reduction in absolute reticulated platelet counts implied decreased platelet production (p<0.001). Normal thrombopoietin levels implied normal megakaryocyte mass. Normal prothrombin time, activated partial thromboplastin time, and D-dimers excluded disseminated intravascular coagulation. Normal platelet factor 4 and beta thromboglobulin indicated absent or minimal platelet activation. Twenty-five percent of the patients with CCHD were thrombocytopenic because platelet production was decreased despite normal megakaryocyte mass. We hypothesized that right-to-left shunts deliver whole megakaryocytes into the system arterial circulation, bypassing the lungs where megakaryocytic cytoplasm is fragmented into platelets, thus reducing platelet production. In conclusion, platelet counts in CCHD appear to represent a continuum beginning with low normal counts and ending with thrombocytopenia.
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PMID:Pathogenesis of thrombocytopenia in cyanotic congenital heart disease. 1682 3

The aim of this study was to investigate the possible suitability of the calibrated automated thrombography to determine the coagulation status of pediatric patients with congenital heart disease. Thrombin generation was measured in 60 patients with congenital heart disease using the calibrated automated thrombography and compared to data using standard coagulation parameters such as prothrombin, antithrombin, tissue factor pathway inhibitor, prothrombin fragment 1.2 (F 1.2), and activated partial thromboplastin time. A significant positive correlation was observed between prothrombin and the endogenous thrombin potential (P < 0.01; r = 0.295) as well as between prothrombin and peak height (P < 0.01; r = 0.581). A significant negative correlation was seen between tissue factor pathway inhibitor and endogenous thrombin potential (P < 0.01; r = -0.480) and between tissue factor pathway inhibitor and peak height (P < 0.01; r = -0.234). No statistically significant correlation was found between antithrombin and parameters of continuous thrombin generation. Significant correlation was seen neither between activated partial thromboplastin time and F1.2 nor between activated partial thromboplastin time and prothrombin. The data presented here indicate that calibrated automated thrombography measurements determine thrombin generation more accurately and therefore reflect better the coagulation status of pediatric patients with congenital heart disease then standard global coagulation assays such as activated partial thromboplastin time.
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PMID:Pediatric patients with congenital heart disease: thrombin generation measured by calibrated automated thrombography. 1860 87


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