Pancytopenia due to vitamin B12 deficiency associated with Graves' disease

Pancytopenia has a broad differential diagnosis, which can be narrowed depending on the cellularity of the bone marrow. The authors describe a complex patient with a history of Graves' disease who presented with pancytopenia, initially suspected of being due to aplastic anemia. He was later diagnosed with Vitamin B12 deficiency as a result of pernicious anemia. The potentially striking hematologic effects of cobalamin deficiency and the autoimmune basis for concurrent Graves' disease and pernicious anemia are reviewed.     

Symptomatic Helicobacter pylori infection: prospective study of epidemiological, diagnostic and therapeutic aspects in children in Tunisia]

CASE REPORT: The patient was a boy born in June, 1990. The proband's father had a history of nonspherocytic hemolytic anemia. The patient was anemic at birth (Hb 11.9 g/dl) and had a hemolytic attack on postnatal day 2. His hemolysis became well compensated, and his second hemolytic episode occurred at three years of age. CLINICAL AND LABORATORY FINDINGS: The patient's mental development had so far been normal and he has no neurological symptoms. His only clinical manifestation has been compensated hemolytic anemia with a hemoglobin concentration of about 11.0 g/dl and a reticulocyte count of 3-6%. He was positive on the Heinz body formation test, and target cells were seen on his peripheral blood smear. The osmotic fragility test yielded slightly increased value. Decreased reduced glutathione (GSH) was observed (4.4 mg/dlRBC) (normal range: 63.9 +/- 9.6), and he also had decreased glutathione synthetase (GS) activity of 0.03 U/gHb (0.38 +/- 0.08 U/gHb). A diagnosis of GS deficiency was made. Decreased glutathione S-transferase (GST) activity was also found (0.57 U/gHb) (normal range: 6.65 +/- 1.20). DISCUSSION: GS deficiency has been reported in about 30 families all over the world. This patient was the first Japanese patient with red cell GS deficiency.     

Estimation of vaccine effectiveness using the screening method

We report the clinical, radiologic, and postmortem findings in two patients with paroxysmal nocturnal hemoglobinuria (PNH) who developed cerebral venous thromboses (CVTs). In contrast with those in most published cases, our patients did not have focal neurologic signs. Antemortem diagnosis of CVT had been made by MR cerebral venograms. We conclude that (1) PNH should be considered in any patient with stroke associated with iron deficiency anemia, hemolysis, hemoglobinuria, or hemosiderinuria; (2) PNH should be in the differential diagnosis of CVT; (3) the latter could present without focal neurologic signs; and (4) MR cerebral venography may be a reliable diagnostic alternative to cerebral angiography when CVT is suspected.     

A 44-month clinical-brain MRI follow-up in a patient with B12 deficiency

We report a 51-year-old woman with vitamin B12 deficiency who presented with slight megaloblastic anemia and severe neurologic deficits associated with multiple focal and confluent T2-weighted white matter hyperintensities on brain MRI. Forty-four months after initiation of hydroxocobalamin therapy, there was clinical improvement and striking reduction in the MRI abnormalities. B12 deficiency should be considered in the differential diagnosis of neurologic disorders associated with multiple areas of white matter hyperintensities on T2-weighted brain MRI.     

Conn''s syndrome. Primary hyperaldosteronism caused by adrenal gland adenoma

The authors report on 2 children with pernicious anemia, sisters, who presented with hypermelanosis as one of the clinical manifestations. The hypermelanosis disappeared with adequate treatment of vitamin B12 deficiency. Vitamin B12 deficiency should be considered in the differential diagnosis of a child presenting with hyperpigmentation and macrocytic red cell indices.     

Disseminated carcinomatosis of the bone marrow occurring 11 years after subtotal gastrectomy for gastric cancer]

A 44-year-old man was admitted to our hospital because of purpura, increased serum alkaline phosphatase, and thrombocytopenia. He had undergone subtotal gastrectomy for gastric cancer 11 years earlier. A biopsy specimen of the bone marrow revealed metastatic mucin-forming, moderately differentiated adenocarcinoma. Because the primary tumor was not detected in any other organ, the gastric cancer the patient was treated for 11 years earlier was suspected as the primary tumor. Microangiopathic hemolytic anemia and disseminated intravascular coagulation developed during the clinical course, and the patient deteriorated despite treatment with anticoagulants. Finally, he died of pulmonary carcinomatous lymphangitis. Autopsy revealed a small number of adenocarcinomatous cells in the lymphoduct of the remaining stomach in spite of its mucosa being intact. We concluded that the bone marrow was infiltrated by cancer cells which originated in the stomach 11 years before. It is unclear why adenocarcinoma cells remained dormant for as long as 11 years in the gastric lymphoduct and bone marrow.     

Acute methemoglobinemia and hemolytic anemia with phenazopyridine: possible relation to acute renal failure

An 18-year-old woman with no prior history of renal or hematologic dysfunction developed severe, acute methemoglobinemia after an overdose of phenazopyridine hydrochloride (Pyridium). The methemoglobinemia was reversed acutely with methylene blue, and during the course of ten days, the patient developed a hemolytic anemia with "bite cells" and acute renal failure. The patient recovered fully with conservative management. Several putative pathophysiologic explanations for the development of methemoglobinemia, hemolytic anemia, and renal failure following oxidative stress are considered and include a direct toxic effect on the renal tubules or methemoglobin-caused damage. Renal failure as a complication of phenazopyridine-related methemoglobinemia and hemolytic anemia should be borne in mind in cases of overdosage with this common drug.     

Idiopathic hypoparathyroidism--a rare disease?

Five patients with nonfamilial idiopathic hypoparathyroidism were observed in a peripheral hospital. There was no association with other autoimmune disorders such as hypothyroidism, adrenal insufficiency or pernicious anemia. Only in one patient with tetany was the diagnosis clinically obvious; all the others presented with unusual clinical symptoms. These manifestations of chronic hypocalcemia are presented, as well as the diagnostic workup and therapeutic management. We suggest that idiopathic hypoparathyroidism is not a very rare disease, but one which is often missed because of the unusual clinical picture.     

Thrombotic microangiopathy associated with Streptococcus pneumoniae bacteremia: case report and review

Thrombotic microangiopathy, a disease within the clinical spectrum of thrombotic thrombocytopenic purpura and hemolytic-uremic syndrome, was recognized in a previously healthy 50-year-old woman who presented with pneumococcal bacteremia complicated by thrombocytopenia, microangiopathic hemolytic anemia, renal failure, and disorientation. After treatment with plasma exchange and antibiotics, the patient's clinical condition improved. Discontinuation of plasma exchange resulted in a relapse of thrombocytopenia and microangiopathic hemolytic anemia that responded to reinitiation of this intervention. The production of the enzyme neuraminidase by Streptococcus pneumoniae is thought to contribute to the pathogenesis of the thrombotic process. Although pneumococcal infection has been associated with hemolytic-uremic syndrome in children, review of the literature on adults revealed only one such case (in a patient who had undergone splenectomy in the remote past). This report therefore documents an unusual complication of pneumococcal bacteremia in an immunocompetent adult.     

Admission-discharge policies for hysteroscopic surgery: a randomised comparison of day case with in-patient admission

Pernicious anemia is an autoimmune disease characterized by a gastric mucosal defect which results in an insufficiency of intrinsic factor to facilitate the absorption of the physiologic amount of cobalamin. Increased risk of cancers of the stomach has been reported for patients with pernicious anemia. We report here a case of a 65 year old woman who had been diagnosed as having pernicious anemia 16 months previously, was receiving monthly vitamin B12 injections, and developed early gastric cancer type IIa by routine follow-up gastroscopic examination. This patient underwent endoscopic mucosal resection for an early gastric cancer lesion with a free resection margin.     

Severe pyruvate kinase deficiency anemia. A case report

BACKGROUND: Pyruvate kinase deficiency is a rare cause of hemolytic anemia and, in its most severe form, requires splenectomy in childhood. During pregnancy, severe cases have been traditionally managed with prophylactic blood transfusions to keep the hemoglobin concentration above arbitrary thresholds of 7-8 g/dL. CASE: A case of severe pyruvate kinase deficiency anemia was managed conservatively without blood transfusions even though the hemoglobin concentration reached a nadir of 6.8 g/dL. The perinatal outcome was good. CONCLUSION: In cases of severe pyruvate kinase deficiency anemia, pregnancy per se might not be an indication for prophylactic blood transfusions.     

Influence of ranitidine on the morphine-3-glucuronide to morphine-6-glucuronide ratio after oral administration of morphine in humans

Hypophosphatemia in malnourished children during nutritional recovery (refeeding hypophosphatemia) is recognized as a cause of morbidity and mortality in adolescents with anorexia nervosa but has been only rarely reported to occur in younger children with other diagnoses. Over a 6-year period, we encountered three cases of refeeding hypophosphatemia in malnourished children admitted to a pediatric rehabilitation hospital. Two children had neurologic dysphagia and one had been starved by an abusive parent. The one patient who was symptomatic had obtundation, hemolytic anemia, rhabdomyolysis, and hepatocellular injury that began during refeeding and resolved with treatment. The signs and symptoms, pathophysiology, and treatment of refeeding hypophosphatemia are reviewed.     

Hemolysis and schizocytosis, malabsorption and the "folate trap": unusual semiological peculiarities associated with vitamin B12 deficiency

INTRODUCTION: Hemolysis and red cell fragmentation accompanying vitamin B12 deficiency may misdirect the diagnosis. Signs of malabsorption and abnormalities related to folic acid metabolism characterized by discrepancies between folic acid normal serum levels and erythrocytic folic acid levels may also exist. EXEGESIS: We report the occurrence of hemolysis and red cell fragmentation mimicking microangiopathic hemolytic anemia, malabsorption and folic acid deficiency in the course of vitamin B12 deficiency. Appropriate replacement therapy corrected all abnormalities. CONCLUSION: An association between hemolysis, malabsorption and folic acid deficiency should lead physicians to search for signs of vitamin B12 deficiency.     

A case of herpetiform pemphigus associated with autoimmune hemolytic anemia: detection of autoantibodies against multiple epidermal antigens

We report a case who was clinically and histopathologically diagnosed as herpetiform pemphigus (HP) and associated with autoimmune hemolytic anemia (AIHA). However, immunofluorescence studies demonstrated concurrent anti-cell-surface and anti-basement-membrane-zone antibodies in the patient's serum. Immunochemical studies showed that the patient's serum reacted with both the pemphigus foliaceus antigen and the two bullous pemphigoid antigens. Subsequently, the patient developed AIHA. Both anemia and skin lesions were successfully treated with oral prednisolone. We believe that this is the first case with HP in association with AIHA. The presence of autoantibodies against multiple antigens suggests an abnormal immunologic tolerance in the antibody production system in this patient.     

Tissue iron storage patterns in fetal hydrops associated with congestive heart failure

To learn whether fetal congestive heart failure causes a characteristic tissue iron storage pattern, we selected 15 neonatal autopsy cases of hydrops fetalis in which both the clinical and gross autopsy findings suggested intrauterine congestive heart failure. The latter appeared to be due to functional causes in 10 (3 nonhemolytic anemia, 4 cardiac dysrhythmia, 3 dilated cardiomyopathy) and was associated with cardiac malformation in 5. We graded the amount of hepatocellular siderosis, reticuloendothelial siderosis, and renal tubular siderosis in Perls-stained microscopic sections of liver, spleen, and kidney and compared the iron storage pattern with that in 15 normally developed neonatal autopsy controls (4 preterm, 11 term) and a further 7 with hemolytic anemia (5 alpha-thalassemia, 2 parvovirus B19 infection). Liver cell siderosis was absent in the three cases with nonhemolytic anemia. It was increased in 11 of the remaining 12 cases, as in hemolytic anemia controls. Among the five cardiac malformation cases, three had proximal renal tubular siderosis (as in hemolytic anemia controls) attributed to turbulent blood flow through the heart. Among the five, hydrops appeared to be due to prenatal closure of the foramen ovale in one and to prenatal constriction of the ductus arteriosus in another. In one of the five, and despite complex malformation of the heart, hydrops appeared to be due to complete heart block. We concluded that, although clinical information and morphologic assessment of the heart were basic to identifying a cardiac cause of fetal hydrops, histologic assessment of the pattern of iron storage helped confirm the pathologic diagnosis. Analysis of the pathologic findings led to a scheme for categorizing cardiogenic fetal hydrops.     

EBV-induced expression and HLA-DR-restricted presentation by human B cells of alpha B-crystallin, a candidate autoantigen in multiple sclerosis

The first known human case of heme oxygenase-1 (HO-1) deficiency is presented in this report. The patient is a six-year-old boy with severe growth retardation. He has been suffering from persistent hemolytic anemia characterized by marked erythrocyte fragmentation and intravascular hemolysis, with paradoxical increase of serum haptoglobin and low bilirubin. An abnormal coagulation/fibrinolysis system, associated with elevated thrombomodulin and von Willebrand factor, indicated the presence of severe, persistent endothelial damage. Electron microscopy of renal glomeruli revealed detachment of endothelium, with subendothelial deposition of an unidentified material. Iron deposition was noted in renal and hepatic tissue. Immunohistochemistry of hepatic tissue and immunoblotting of a cadmium-stimulated Epstein-Barr virus-transformed lymphoblastoid cell line (LCL) revealed complete absence of HO-1 production. An LCL derived from the patient was extremely sensitive to hemin-induced cell injury. Sequence analysis of the patient's HO-1 gene revealed complete loss of exon-2 of the maternal allele and a two-nucleotide deletion within exon3 of the paternal allele. Growth retardation, anemia, iron deposition, and vulnerability to stressful injury are all characteristics observed in recently described HO-1 targeted mice. This study presents not only the first human case of HO-1 deficiency but may also provide clues to the key roles played by this important enzyme in vivo.     

Sickle cell--betao thalassemia variant with high hemoglobin F and mild clinical course

A 70 year old Black woman had chronic hemolytic anemia without recurrent painful crises. Hemoglobin pattern by electrophoresis was hemoglobin S (69 to 71 per cent), hemoglobin A2 (4.6 per cent) and hemoglobin F (24 to 27 per cent). No hemoglobin A was detected, and the hemoglobin F was distributed heterogeneously in the red cells. Reticulocyte alpha/nonalpha globin chain synthetic ratios were 1.44 to 1.62. Thus, the patient had a high hemoglobin F variant of S-beta zero (betao) thalassemia which has not been described previously. Her clinical course has been mild in comparison with S-betao thalassemia patients who do not have extremely elevated hemoglobin F levels.     

A simple rapid radiometric assay for pyrimidine-5'-nucleotidase

Pyrimidine-5'-nucleotidase deficiency appears to be an important cause of hemolytic anemia associated with basophilic stippling of the red cells. A new radiometric method for the assay of this enzyme has been developed. In this technique, 14C-CMP serves as substrate. The CMP which is not dephosphorylated to cytidine is bound to the barium sulfate precipitate which forms in the deproteinization process. The cytidine remains in solution and is counted. The method is simple and reproducible and can be carried out on large numbers of samples. Two patients with pyrimidine-5'-nucleotidase deficiency have been detected by means of this technique.     

Effect of riboflavin treatment on human red cell pyruvate kinase deficiency

The effect of riboflavin on six patients with hemolytic anemia due to hereditary pyruvate kinase deficiency was studied. Treatment over a period of four to six months produced no significant hematologic or enzymologic changes in the variants investigated.