Value of Rotational Thromboelastometry and Impedance Aggregometry for Evaluating Coagulation Disorders in Patients With Cyanotic and Nongenetic Congenital Heart Disease.

Adults with cyanotic congenital heart diseases (CCHD) have a higher risk for bleeding, but also for thrombosis. Rotational thromboelastometry (RT), using tissue factor (EXTEM), a contact activator (INTEM) or cytochalasin (FIBTEM), assesses coagulation by determining the time to initiation of clotting (CT) and clot firmness (MCF) including platelet-fibrin-interaction. The aim of this study was to evaluate RT and whole blood impedance aggregometry (IA) in CCHD compared with a control group without chronic cyanosis (NCCHD). These were used to establish normal reference ranges. We prospectively included 124 patients (76 CCHD, 48 NCCHD). Mean oxygen saturation in CCHD was 81.5%, and 98% in NCCHD (p <0.001). Fifty-five CCHD and 1 NCCHD had pulmonary hypertension. Eisenmenger syndrome was present in 39 CCHD (51.3%). Hemoglobin, hematocrit, and reticulocyte levels were significantly higher in CCHD, and they also showed more thrombocytopenia. Platelet aggregation was under normal range in 89.5% of CCHD after triggering with ADP, in 85.5% after triggering with arachidonic acid (ASPI) and in 73.7% after TRAP-6. RT showed significantly longer clotting times and reduced clot firmness in both EXTEM and INTEM tests. FIBTEM-MCF was also significantly reduced. Moderate inverse correlation was found between platelet count and erythrocytes (r = -0.608, p <0.001). Significant correlations were found between platelet number and RT-parameters as well as with all IA parameters. In conclusion, according to RT and IA, CCHD present hypocoagulable disorders. No signs of hypercoagulability were found.

Neurodevelopmental evaluation of children with cyanotic congenital heart disease.

BACKGROUND: The aim of the study was to perform a neurodevelopmental evaluation of the children with cyanotic congenital heart disease and to determine the factors that affect the neurodevelopmental status. METHODS: The study was performed in the Pediatric Cardiology Department of Behcet Uz Children's Hospital between February and August 2013. Children between the age of six to forty-two months were included in the study and were evaluated in three groups (two patient groups and the control group). In group A, patients with isolated cyanotic congenital heart disease were enrolled. Group B consisted of the patients with cyanotic congenital heart disease with other concomitant diseases. Group C included the healthy control group. For the neurodevelopmental evaluation Bayley Scale of Infant Development- II (BSID-II) was used. Mental Developmental Index (MDI) and Psychmotor Developmental Index (PDI) scores were calculated. Factors possibly effective on neurodevelopment were evaluated. RESULTS: Thirty eight patients (32 in group A and 6 in group B) and 33 healthy subjects in group C were included in the study. Mean age of the patient group was 22.5±11.2 months. In group A mean MDI Score (82.5±14.7) was significantly lower than group C (92.3±6.9) (P=0.001). Similarly mean PDI Score in group A (82.0±18.2) was found significantly lower than group C (92.5±7.4) (P=0.003). When group A and B were compared, mean MDI and PDI scores were lower in group B, but the difference was not statistically significant. For group A, according to the psychomotor development index, 41.6% of the patients were found to be mildly to severely retarded. In terms of the mental development index, 34.4% of the patients had moderate or mild retardation. The sex, socioeconomic status, gestational age, birth weight, comorbidities, history of surgery and reoperation, length of stay in intensive care unit were not found influential on the MDI and PDI scores of the patients. CONCLUSIONS: Mental-motor retardation is frequently encountered in children with cyanotic congenital heart disease. These patients may benefit from motor, language, speech, developmental and educational therapies. For this reason, these children have to be under regular follow up for neurodevelopmental status.

Burr Hole Aspiration of Brain Abscess in Children with Cyanotic Heart Disease.

OBJECTIVE: To determine the efficacy of burr hole aspiration of brain abscess in children with cyanotic heart disease in terms of number of aspirations and residual abscess. STUDY DESIGN: Experimental study. PLACE AND DURATION OF STUDY: Department of Pediatric Neurosurgery at The Children's Hospital and The Institute of Child Health, Multan, from July 2010 to June 2014. METHODOLOGY: Pediatric patients of cyanotic heart disease with brain abscess were admitted. After taking history, clinical examination and necessary investigation, aspiration of abscess through a burr hole was performed. Data was collected through pre-designed proforma. Analysis of results was performed and comparison was made through statistical package for social sciences (SPSS-20). RESULTS: Total number of patients were 50 with 31 (62%) male and 19 (38%) female children. Patients' age ranged from 5-10 years with mean age of 7.44 ±1.11 years. Single abscess in supra tentorial was commonly found in 44 (88%) patients. Multiple abscesses were present in 4 (8%) patients. Cerebellum was involved in 2 (4%) patients. Abscess was completely aspirated in single attempt in 37 (74%) patients, two attempts in 9 (18%) patients, and three attempts in 4 (8%) patients. No bacterial growth on culture was reported in 32 (64%) patients. Culture was positive in 18 (36%) patients. Postoperative hematoma developed in 2 (4%) patients. No mortality was reported in early postoperative period. CONCLUSION: Aspiration of brain abscess in children with cyanotic heart disease through a burr hole is safe and successful.

Downregulation of microRNA­199a­5p protects cardiomyocytes in cyanotic congenital heart disease by attenuating endoplasmic reticulum stress.

Chronic hypoxia is a key pathological change in patients with cyanotic congenital heart defect (CCHD). It has been demonstrated that enhanced myocardial unfolded protein response (UPR) increases the capacity to buffer endoplasmic reticulum (ER) stress and to avoid subsequent apoptosis caused by the hypoxia that underlies CCHD. The present study was performed to determine the regulatory role of microRNAs (miRNAs) in this cytoprotective UPR process. The results revealed that miR­199a­5p was markedly downregulated in the cardiac tissue of patients with CCHD and in human myocardial cells cultured in hypoxic conditions. The two major UPR modulators, 78 kDa glucose­regulated protein (GRP78) and activating transcription factor 6 (ATF6), were potential target genes of miR­199a­5p in CCHD myocardial specimens. In addition, the miR­199a­5p mimic and inhibitor were evidently able to change GRP78 and ATF6 gene expression and ER stress­associated apoptosis in hypoxia­treated cardiomyocytes. The interaction between miR­199a­5p and the ATF6 and GRP78 3'­UTR binding sites in myocardial cells was also confirmed by luciferase assay. Thus, it is concluded that myocardial downregulation of miR­199a­5p favors the UPR against hypoxia­induced ER stress in CCHD, which contributes to myocardial protection.

The birth of a new era: the introduction of the systemic-to-pulmonary artery shunt for the treatment of cyanotic congenital heart disease.

Cardiac surgery was revolutionized on November 29, 1944, when Eileen Saxon underwent the first systemic-to-pulmonary artery shunt at Johns Hopkins University in Baltimore, Maryland, United States of America. The systemic-to-pulmonary artery shunt was initially developed in the laboratory and then applied to patients through the unique collaboration of Vivien Thomas, Alfred Blalock, and Helen B. Taussig. This innovation was the first operation to successfully treat cyanotic cardiac disease. The history of the first operation to successfully treat cyanotic heart disease is an extraordinary history of courage, innovation, and scientific breakthrough. Just as striking is perhaps the ability of the protagonists of this story to overcome seemingly insurmountable barriers of racial and gender discrimination and revolutionize medicine.

[Neonatal cyanosis due to fetal hemoglobin M-Osaka]. / Cyanose néonatale due à une hémoglobine fœtale M-Osaka.

The case of a newborn with isolated neonatal cyanosis on day 1 is reported. The basic investigations were sufficient to reach the diagnosis. A rare abnormal fetal hemoglobin was isolated. The prognosis of this disease is excellent and self-resolving.

Tiroides lingual una forma de patologia tiroidea amenazante de la vida / Lingual thyroid a life threatening form of thyroid pathology

Latiroides lingual es lavariante más común de tiroides ectópica benigna. Suele manifestarse en la infancia con hipotiroidismo o síntomas locales, como tos crónica y disfagia. Se diagnostica durante la niñez tras el comienzo de síntomas obstructivos, como la disfagia y disfonías progres ivas, obst rucción respiratoria intermitente, disnea, estridor laríngeo o sensación de cuerpo extraño. El diagnóstico por imagen ideal es la resonancia magnética. El objetivo de este artículo es presentar el caso de una lactante menor de 46 días, presentando estridor laríngeo, cianosis, disnea, secundaria a una disgenesia de tiroides debido a tiroides lingual, la cual la llevó a un hipotiroidismo secundario...(AU)

Seeking optimal relation between oxygen saturation and hemoglobin concentration in adults with cyanosis from congenital heart disease.

In patients with cyanosis from congenital heart disease, erythropoiesis is governed by many factors that can alter the expected relation between the oxygen saturation (O(2sat)) and hemoglobin concentration. We sought to define the relation between the O(2sat) and hemoglobin in such patients and to predict an ideal hemoglobin concentration for a given O(2sat). Adults with congenital heart defects and cyanosis were studied prospectively using blood tests and exercise testing. Nonoptimal hemoglobin was defined as any evidence of inadequate erythropoiesis (i.e., iron, folate, or vitamin B(12) deficiency, increased erythropoietin, reticulocytosis, or a right-shifted oxygen-hemoglobin curve). For patients without these factors, a linear regression equation of hemoglobin versus O(2sat) was used to predict the optimal hemoglobin for all patients. Of the 65 patients studied, 21 met all the prestudy criteria for an optimal hemoglobin. For all patients, no correlation was found between O(2sat) and hemoglobin (r = -0.22). However, a strong linear correlation was found for those meeting the criteria for optimal hemoglobin (r = -0.865, p <0.001). The optimal hemoglobin regression equation was as follows: predicted hemoglobin = 57.5 - (0.444 × O(2sat)). A negative correlation was found between the hemoglobin difference (predicted minus measured) and exercise duration on cardiopulmonary exercise testing (r = -0.396, p = 0.005) and the 6-minute walk distance (r = -0.468, p <0.001). In conclusion, a strong relation between O(2sat) and hemoglobin concentration can be shown in stable cyanotic patients and used to predict an optimal hemoglobin. This relation might be useful in defining functional anemia in this group.

Intestinal microbiota and blue baby syndrome: probiotic therapy for term neonates with cyanotic congenital heart disease.

Necrotizing enterocolitis (NEC) is the most common intestinal emergency among premature infants. Risk factors in premature infants include immature intestinal immunity and an intestinal microbiota dominated by hospital-acquired bacteria. Some probiotics have been shown to decrease the incidence of NEC in premature infants. Among term infants, NEC is rare. However, among term infants with cyanotic congenital heart disease (CCHD), the incidence of NEC is similar to that of premature infants but with even greater mortality rates. Mechanisms by which NEC occurs in term infants with CCHD are unknown. Of central interest is the potential role of changes in the intestinal microbiota and whether these can be modified with probiotic bacteria; accordingly, we review the literature, propose hypotheses and present the rationale for future studies involving preliminary probiotic clinical trials.

Familial congenital cyanosis caused by Hb-M Yantai (alfa-76 GAC - TAC, Asp - Tyr)

Methemoglobin (Hb-M) is a rare hemoglobinopathy in China. We hereby report on a family living in Yantai, East China, with congenital cyanosis due to Hb-M mutation. The proband, a 65-year-old female, presented 63 percent oxygen saturation. Both Hb-M concentration and arterial oxygen saturation remained unchanged, even following intravenous treatment with methylene blue. There was also no change in blood-color (chocolate-brown) after adding 0.1 percent KCN. A fast-moving band (Hb-X) in hemolysates was found by cellulose acetate electrophoresis, the Hb-X/Hb-A ratio exceeding 10 percent. GT transition at 131nt of exon 2, although present in one of the alfa2-globin alleles, was not found in alfa1-globin alleles as a whole. This mutation leads to the aspartic acid to tyrosine substitution (Asp76Tyr). In this family, the novel mutation in the alfa2-globin gene resulted in a rare form of congenital cyanosis due to Hb-M. This hemoglobin was named Hb-M Yantai.

Reversed differential cyanosis in the newborn: a clinical finding in the supracardiac total anomalous pulmonary venous connection.

The newborn can experience two types of differential cyanosis (DC). The common type of DC occurs when oxygen saturation in the right hand is greater than in the foot. The second type of DC, reversed differential cyanosis (RDC), occurs when oxygen saturation is lower in the right hand than in the foot. This phenomenon is observed in transposition of the great arteries (TGA) with patent ductus arteriosis (PDA) and elevated pulmonary vascular resistance or in TGA with PDA and preductal aortic interruption or coarctation. This report describes a case of RDC not previously described involving an infant with supracardiac total anomalous pulmonary venous connection (TAPVC). In supracardiac TAPVC, RDC results from streaming of highly saturated superior vena cava (SVC) blood into the right ventricle, out the main pulmonary artery, through a PDA, and to the descending aorta, with streaming of more desaturated blood from the inferior vena cava (IVC) into the left atrium across the atrial septal defect (ASD)/foramen ovale. Therefore, as part of a neonatal examination to rule out congenital heart disease (CHD), simultaneous pre- and postductal oxygen saturations should be documented. The presence of RDC should initiate immediate full cardiac evaluation for CHD. Supracardiac TAPVC should be included in the differential diagnosis if RDC is observed.

Association of multiple vertebral hemangiomas and severe paraparesis in a patient with a PTEN hamartoma tumor syndrome. Case report.

The PTEN hamartoma tumor syndrome, manifestations of which include Cowden disease and Bannayan-Riley-Ruvalcaba syndrome, is caused by various mutations of the PTEN gene located at 10q23. Its major criteria are macrocephaly and a propensity to develop breast and thyroid cancers as well as endometrial carcinoma. Minor diagnostic criteria include hamartomatous intestinal polyps, lipomas, fibrocystic disease of the breasts, and fibromas. Mutations of PTEN can also be found in patients with Lhermitte-Duclos disease (dysplastic gangliocytoma of the cerebellum). The authors report the case of a 17-year-old girl who had a severe cyanotic cardiac malformation for which surgery was not advised and a heterozygous missense mutation (c.406T>C) in exon 5 of PTEN resulting in the substitution of cysteine for arginine (p.Cysl36Arg) in the protein, which was also found in her mother and sister. The patient presented in the pediatric emergency department with severe spastic paraparesis. A magnetic resonance imaging study of the spine showed vertebral hemangiomas at multiple levels, but stenosis and compression were maximal at level T5-6. An emergency T5-6 laminectomy was performed. The decompression was extremely hemorrhagic because the rapid onset of paraparesis necessitated prompt treatment, and there was no time to perform preoperative embolization. The patient's postoperative course was uneventful with gradual recovery. This represents the first report of an association of a PTEN mutation and multiple vertebral angiomas. The authors did not treat the remaining angiomas because surgical treatment was contraindicated without previous embolization, which in itself would present considerable risk in this patient with congenital cyanotic heart disease.

Congenital methemoglobinemia caused by Hb-MRatnagiri (beta-63CAT-->TAT, His-->Tyr) in an Indian family.

Hb-M is a very rare hemoglobinopathy in the Indian subcontinent. We report a family with Hb-M with lifelong cyanosis from the Ratnagiri district in western India. The propositus was a 11-year-old female child with a history of increasing cyanosis exacerbated by fever and weakness. Similar complaints were also noted in her mother and five maternal family members. There was no history of cardiac illness or exposure to drugs and chemicals. The methemoglobin level was 39.3% in the propositus and 21.1% in her mother with normal NADH-methemoglobin reductase activity. Abnormal absorption peaks by spectroscopic analysis, presence of hemoglobin instability, and a slow-moving band on starch gel electrophoresis supported the presence of Hb-M. Automated DNA sequence analysis of the beta globin gene showed a C-->T substitution at codon 63. This leads to a substitution of histidine (CAT) by tyrosine (TAT) at the beta 63 (E7) position, similar to Hb-M Saskatoon. We have named this variant as Hb-M(Ratnagiri).

[Non-respiratory cyanosis in the newborn]. / Niet-respiratoire cyanose bij de pasgeborene.

Four term babies, three boys and one girl, became cyanotic shortly after birth. In two cases the cause was maternal use of drugs: methemoglobinaemia due to use of a chromate and depression of the nervous system due to clomipramine. They recovered. A third child suffered cerebral infarction and was left with decreased left-arm function. The fourth child had a hypoplastic left heart and died. Central cyanosis in a newborn should be cause for concern. A thorough case history should be taken and extensive physical examination carried out. In case of doubt additional diagnostic tests should be performed.