Cholangiocarcinoma With Sepsis Associated With Percutaneous Transhepatic Biliary Drainage (PTBD)

Percutaneous transhepatic biliary drainage (PTBD) can be an alternative palliative treatment in resectable cholangiocarcinoma. One of the most common complications of PTBD is infection, with a prevalence of 3.6 – 67.4% in patients undergoing PTBD procedure, with mortality rate of 0.05-7%. We report a case of a 46-year old male with a history of fever 14 days after undergoing PTBD procedure. Physical examination revealed tachycardia, tachypnea, febris, jaundice, and decreased urine output. Laboratory results revealed hypochromic-microcytic anemia, leukocytosis, decreased renal function, elevated liver enzymes, obstructive icterus, hypoalbuminemia, and hyperkalemia. Blood and gall culture revealed a growth of Eschericia coli. The patient was given fluid resuscitation and antibiotic suitable to microbial sensitivity test, and treatment of acute kidney injury and hyperkalemia, including hemodialysis. The patient’s general condition improved after ten days of care, and was discharged on the twentieth day. Cholangitis is one of the most infectious complications following PTBD procedure. The prevalence of sepsis in biliary drainage procedures was reported 2.5-2.7%, with enteral bacteria gram-negative bacilli being the most common pathogen found in blood and bile. The administration of prophylactic antibiotics was not proven to decrease prevalence of infection. Bacterial translocation via portal vein due to loss of mucosal integrity in the intestines may contribute to bacteremia following PTBD procedure.

Red cell distribution width’s role in differentiating iron deficiency anemia from other hypochromic microcytic anemias

Background and objective: The red cell distribution width is suggested to be a more sensitive indicator for microcytic hypochromic anemia. Therefore, this study aimed to determine the role of red cell distribution width in the diagnosis of iron deficiency anemia from other causes of hypochromic microcytic anemia. Methods: This cross-sectional study involved the children patients who attended Rapareen Teaching Hospital in Erbil city in 2019 and were diagnosed with hypochromic microcytic anemia. Results: The red cell distribution width was determined in a group of 70 children with iron deficiency anemia and 30 cases with a non-iron deficiency (other hypochromic microcytic anemias). Patients with a higher socio-demographic status were more likely to have iron deficiency anemia than those with low socio-demographic status; 82.61% vs. 76.60%, respectively. The patients with symptoms were more likely to be diagnosed with iron deficiency anemia (P = 0.024). The mean red cell distribution width value was 14.38%, 15.73%, and18.02% among mild, moderate, and severely anemic children (P <0.001). Increasing red blood cells (r=-0.271), hemoglobin (r=-0.454), serum iron (r=-0.601), and serum ferritin (r=-0.560) lead to decrease red cell distribution width. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of red cell distribution width in diagnosing iron deficiency anemia in children patients were 77.14%, 63.33%, 83.08%, 54.29%, and 73.0%, respectively. Conclusions: This study showed that red cell distribution width has good sensitivity and specificity in diagnosing iron deficiency anemia. Keywords: RDW; IDA; RBC indices; Microcytic anemia; Serum iron.

Erythrocyte Indices and Long-term Blood Pressure Variability in Military Males

Backgrounds: Severe microcytic anemia has been associated with BP changes. Aims and Objectives: Whether the erythrocyte indices are associated with long-term BPV is unknown. This study aimed to investigate the association of hemoglobin levels and erythrocyte size with long-term blood pressure variability (BPV) in young males. Methods: This study included 1,112 healthy military males, averaging 32 years of age, in Taiwan. All participants took a measurement of systolic and diastolic BP (SBP and DBP) every two-year from 2012 to 2018 (2012-14, 2014-15, 2015-16, 2016-18). Lev-els of hemoglobin and mean corpuscular volume (MCV) of erythrocytes were obtained at the first visit. Long-term BPV was assessed by the standard deviation (SD) and aver-age real variability (ARV). Multivariate linear regression analysis with adjustment for the baseline BP levels and other covariates was used to elucidate the association. Results: Hemoglobin levels were borderline positively correlated with SD DBP (β and standard errors = 0.016 (0.009), P =0.06). In those with hemoglobin levels of 10.0-13.9 g/dL, hemoglobin was negatively correlated with SDSBP (β= -0.039 (0.018), P =0.03). In contrast, MCV levels were borderline positively correlated with SDSBP (β =0.085 (0.052), P =0.09). In those with MCV levels <80 fL, MCV was positively correlated with SDSBP and ARVSBP (β= 0.445 (0.210) and 0.286 (0.149), p = 0.03 and 0.05, re-spectively). Conclusion: There were inconsistent patterns for the associations of erythrocyte indices with long-term BPV. We found a U-shaped relationship of hemoglobin levels with sys-tolic BPV, whereas there was a positive linear relationship of hemoglobin and MCV levels with diastolic BPV, respectively.

Pyridoxine Response in Mouse Alas2 Knock-in Models of X-Linked Sideroblastic Anemia and X-Linked Protoporphyria

Introduction. Pyridoxal 5' Phosphate (PLP) is the cofactor form of vitamin B6 in ~60 human enzymes. The first enzyme of the heme biosynthesis pathway, delta-aminolevulinic acid synthase (ALAS), that catalyzes the condensation of glycine and succinyl-CoA to form 5-ALA the sole precursor of porphyrins and heme, is PLP dependent. The erythroid specific isoform of ALAS is ALAS2. Inherited ALAS2 mutations cause two rare diseases: X-linked Sideroblastic Anemia (XLSA), due to loss-of-function mutations located throughout the gene, and X-linked Protoporphyria (XLPP), due to gain-of-function mutations specifically located in the C-terminal domain. Male XLSA patients have a microcytic hypochromic anemia of variable severity characterized by abnormal erythroid mitochondrial iron deposits, in nucleated and enucleate cells (ring sideroblasts and siderocytes). XLPP patients develop acute photosensitivity, due to an abnormal erythroid accumulation of free protoporphyrin IX (PPIX), the substrate of ferrochelatase, the last enzyme in the pathway. In two-thirds of XLSA patients, the anemia is responsive to oral pyridoxine supplementation. Isoniazid, an antituberculosis agent, that can cause sideroblastic anemia by limiting PLP availability to ALAS2, may limit free PPIX accumulation in protoporphyric patients. While being well tolerated, isoniazid treatment of protoporphyric patients did not reduce erythroid free PPIX accumulation. Given these clinical findings, we sought to explore the effects of dietary supplementation and restriction of vitamin B6 in animal models of the diseases. Methodology. Using CRISPR-CAS9 editing technology, we generated C57BL/6N mouse models of p.R170H, p.R452H and p.R411H found in XLSA patients with B6-sensitive or -refractory disease, and p. Q548X, a XLPP allele. Fed our normal chow containing 8ppm of pyridoxine, XLSA mouse males develop phenotypes ranging from severe (p.R411H) to trivial (p.R170H) anemia; XLPP animals have the expected protoporphyric phenotype. At weaning, we fed XLSA, XLPP and control male littermates with diets with defined amounts of B6 (Envigo: 0ppm, 2ppm or 10ppm). We performed complete blood counts (CBC) and quantified erythroid free PPIX by flow cytometry after 2, 5 and 8 weeks on diet and evaluated steady state and stress erythropoiesis by flow cytometry at 8 weeks. Results. B6-depleted animals have a growth delay that is more severe in the XLSA animals. Similarly treated control and XLPP animals develop a mild microcytic anemia with siderocytes only after 8 weeks. XLPP depleted animals accumulate less free PPIX compared to normal diet, while a 2 ppm B6 diet did not affect free PPIX accumulation. On 0 ppm B6, all XLSA depleted animals developed a very severe anemia characterized by profound reticulocytopenia and massive splenomegaly. Blood smears revealed many fragmented red blood cells and siderocytes. Flow cytometry analyses reveal a blockage of erythropoiesis, at early stages of differentiation, in both the marrow and the spleen. Feeding with 2ppm B6, demonstrated variable responses in each of the three mutants, with the p.R411H being the most severe and the R170H being the least. Conclusion. All XLSA mutations are sensitive to B6 depletion. Thus, the tendency to develop B6 deficiency with age may account for later clinical presentations in patients with pyridoxine-sensitive mutations. The limited PPIX response and development of siderocytic anemia in B6 deficient XLPP animals may suggest why the B6 inhibitor isoniazid had limited clinical efficacy. Thus our novel XLSA and XLPP mice model the each disease accurately and have demonstrated their potential for evaluating experimental treatments. Disclosures Schmidt: Disc Medicine, Inc.: Research Funding. Fleming: Disc Medicine: Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees.

Aceruloplasminemia: MRI and Biochemical Profile Clue to Early Diagnosis in an Adolescent

Aceruloplasminemia (ACP) is a rare autosomal recessive genetic disorder with systemic and brain iron overload, secondary to ceruloplasmin gene mutation, usually presents in adults with neurological manifestations. An abnormal biochemical profile may be the only clue in an adolescent patient, that is, microcytic anemia, low transferrin saturation, hyperferritinemia, and should warrant a possible diagnosis of ACP, which can be established by low serum ceruloplasmin levels and appropriate genetic testing. We present a case of an adolescent patient in whom ACP was suspected when brain magnetic resonance imaging showed iron overload in basal ganglia, thalami, red nuclei, dentate nuclei, and choroid plexus and later on confirmed by biochemical profile. The final diagnosis was confirmed by the presences of a novel mutation on genetic analysis. To the best of our knowledge, our case is the second description of ACP with choroid plexus hemosiderosis.We proposed in this article that the combination of parenchymal and choroid plexus iron overload should prompt the suspicion of ACP.

A Case of Rheumatoid Arthritis Associated with Microcytic Anemia

Rheumatoid arthritis (RA) is one of the most common inflammatory arthritides. It is associated with multiple systemic features, including hematological manifestations such as anemia, neutropenia and thrombocytopenia. However, immune hemolytic anemia is extremely rare with only 3 reports indexed in medline, and one of them being due to methotrexate toxicity. Microcytic anemia is a condition in which the body's tissues and organs do not get enough oxygen. This lack of oxygen can happen because the body does not have enough red blood cells, or because the red blood cells do not contain enough hemoglobin, which is a protein that transports oxygen in the blood. Case Presentation: A 60 year old female a known case of rhematoid arthritis and hypothyrodisam in 2013 for last past 3 years. Who presented to us with history of recurrent anemia . In march 2021, she was admitted to hospital because of palpitations and shortness of breath due to severe anemia. Results of laboratory studies were hemoglobin, 6.9 gm/dl and haptoglobin, less than 29.8mg/dl. A diagnosis of anemia was made on the basis of the laboratory findings She was transfused with 1units packed red blood cells (pRBCs) over less than 6 hours. High-dose PSL (50 mg/day) was started, and the anemia improved. The hemoglobin level increased to 7.0 gm/dl within the 1st week. Conclusion: The differential diagnosis of various hematological disorders should include rheumatic autoimmune diseases among other causes of blood cell and hemostasis abnormalities. It is crucial that hematologists be aware of Treatment should be administered promptly, with rheumatological consultation.