Accuracy and Precision of Point-of-Care International Normalized Ratio in Patients With Liver Disease.

OBJECTIVE: To determine if the CoaguChek XS Pro Point-of-Care (POC) device can accurately and precisely measure the international normalized ratio (INR) compared with the gold standard laboratory INR in pediatric and adult patients with liver disease. METHODS: This prospective cohort study included 15 pediatric patients without liver disease, 13 pediatric patients with liver disease, and 17 adult patients with liver disease. The accuracy of the POC INR values was determined using the correlation and Bland-Altman limits of agreement. The accuracy of the coagulometer INR was assessed by calculating the proportion of POC INR measurements that were ≤15% of their corresponding laboratory INR. RESULTS: A comparison of INR measurements showed an excellent correlation in pediatric patients without liver disease ( r = 0.82), pediatric patients with liver disease ( r = 0.89), and adult patients with liver disease ( r = 0.96). Fourteen (93%) POC INR values were ≤15% in pediatric patients without liver disease from its paired laboratory INR. All 13 paired measurements were ≤15% in pediatric patients with liver disease. In adult patients with liver disease, 12 (71%) POC INR values were ≤15% of their paired laboratory INR. CONCLUSIONS: In patients with liver disease, the CoaguChek XS Pro provides an accurate measure of the INR compared to laboratory INR measurements.

NullCanada: A novel α1-antitrypsin allele with in cis variants Glu366Lys and Ile100Asn.

BACKGROUND: α1-Antitrypsin (A1AT) deficiency predisposes patients to pulmonary disease due to inadequate protection against human neutrophil elastase released during inflammatory responses. A1AT deficiency is caused by homozygosity or compound heterozygosity for A1AT variants; individuals with A1AT deficiency most commonly have at least one Z variant allele (c.1096G > A (Glu366Lys)). Null variants that result in complete absence of A1AT in the plasma are much rarer. With one recent exception, all reported A1AT variants are characterized by a single pathogenic variant. CASE: An 8 years old patient from Edmonton, Alberta, Canada, was investigated for A1AT deficiency. His A1AT phenotype was determined to be M (wild type)/Null by isoelectric focusing (IEF) but M/Z by targeted genotyping. Gene sequencing revealed two heterozygous variants: Z and Ile100Asn (c.299 T > A). The Ile100Asn substitution is predicted to disrupt the secondary structure of an α-helix in which it resides and the neighbouring tertiary structure, resulting in intracellular degradation of A1AT prior to hepatocyte secretion. METHODS: Family testing was conducted to verify potential inheritance of an A1AT allele carrying the two mutations in cis, as this arrangement of the mutations would explain "Z" detection by genotyping but not by IEF. Molecular modeling was used to assess the effect of the variants on A1AT structure and stability. DISCUSSION: Carrier status for a novel variant NullCanada with in cis mutations (c.[299 T > A;1096G > A], p.[(Ileu100Asn;Glu366Lys)]) was confirmed. A sibling was identified as having A1AT deficiency on the basis of compound heterozygosity for two alleles: NullCanada and the common Z allele. A separate pedigree from the Maritimes was subsequently recognized as carrying NullCanada. CONCLUSION: In cis mutations such as NullCanada may be more common than previously described due to failure to detect such mutations using historical testing methods. Combined approaches that include gene sequencing and segregation studies allow recognition of rare A1AT variants, including in cis mutations.

Coagulopathy in Children With Liver Disease.

It was thought that a high international normalized ratio predicted bleeding in patients with chronic liver disease (CLD) and patients were "autoanticoagulated." Contrary to this belief, while patients with CLD experienced bleeding, they also developed thromboses. In the last decade, the prevailing literature challenged the idea that an elevated international normalized ratio increased bleeding risk. The global assays of coagulation such as thromboelastography (TEG)/rotational thromboelastometry and thrombin generation assays provide additional insight into coagulation processes. It has become apparent that a parallel reduction of procoagulant and anticoagulant factors leave patients in a new "balanced" state, albeit a fragile one, where the balance can be easily disrupted. The inherent differences in coagulation between children and adults such as differences in levels of procoagulant and anticoagulant factors, underlying liver disease, and the paucity of studies in children make extrapolation of these findings to the pediatric population problematic. Ultimately, this is an area that requires further investigation to avoid inappropriate use of blood products and medication.

Are We Overdoing Pediatric Lower Gastrointestinal Endoscopy?

INTRODUCTION: Lower gastrointestinal endoscopy (LGIE)/colonoscopy is frequently performed for rectal bleeding, recurrent abdominal pain, and the diagnosis of inflammatory bowel disease (IBD). Although these are common indications, the causes of isolated rectal bleeding and recurrent abdominal pain in the otherwise well child have not been described. METHODS: A retrospective analysis of patients who had had an LGIE/colonoscopy from January 2001 to December 2010 was performed. The following data were collected: demographic data, indication, distance reached, macroscopic findings, microscopic findings, diagnosis, additional procedures, and complications. RESULTS: There were a total of 999 colonoscopies. The colonoscopy was normal in 390 of 999 (39%). The commonest indication for colonoscopy was a diagnosis of suspected IBD, 449 of 999 (45%). IBD was confirmed in 282 of 449 (63%), but colonoscopy was normal in 143 of 449 (32%) of suspected IBD. Colonoscopy was performed for rectal bleeding in 197 of 999 (20%) of whom 141 of 197 (72%) were normal. There were 46 (5%) colonoscopies performed for recurrent abdominal pain, which were all normal. Our completion rate to the cecum and beyond was 521 of 999 (52%). Our perforation rate during the 10 years was 0.2%. CONCLUSIONS: Colonoscopy is a safe procedure in pediatrics; however, 39% of colonoscopies in this series were normal. Many of these could have been avoided by eliminating colonoscopy in patients with recurrent abdominal pain in the absence of other clinical features, conservative management with laxatives for those with fresh blood per rectum typical of anal fissures, and fecal calprotectin screening before endoscopy in patients with suspected IBD.