Normal Full Blood Count Research Articles

Progressive Telomere Shortening in Aplastic Anemia

Improved survival in aplastic anemia (AA) has shown a high incidence of late clonal marrow disorders. To investigate whether accelerated senescence of hematopoietic stem cells might underlie the pathophysiology of myelodysplasia (MDS) or paroxysmal nocturnal hemoglobinuria (PNH) occurring as a late complication of AA, we studied mean telomere length (TRF) in peripheral blood leukocytes from 79 patients with AA, Fanconi anemia, or PNH in comparison with normal controls. TRF lengths in the patient group were significantly shorter for age than normals (P < .0001). Telomere shortening was apparent in both granulocyte and mononuclear cell fractions, suggesting loss at the level of the hematopoietic stem cell. In patients with acquired AA with persistent cytopenias (n = 40), there was significant correlation between telomere loss and disease duration (r = −.685; P < .0001), equivalent to progressive telomere erosion at 216 bp/yr, in addition to the normal age-related loss. In patients who had achieved normal full blood counts (n = 20), the rate of telomere loss had apparently stabilised. There was no apparent association between telomere loss and secondary PNH (n = 13). However, of the 5 patients in the study with TRF less than 5.0 kb, 3 had acquired cytogenetic abnormalities, suggesting that telomere erosion may be relevant to the pathogenesis of MDS in aplastic anemia.

Progressive Telomere Shortening in Aplastic Anemia

AbstractImproved survival in aplastic anemia (AA) has shown a high incidence of late clonal marrow disorders. To investigate whether accelerated senescence of hematopoietic stem cells might underlie the pathophysiology of myelodysplasia (MDS) or paroxysmal nocturnal hemoglobinuria (PNH) occurring as a late complication of AA, we studied mean telomere length (TRF) in peripheral blood leukocytes from 79 patients with AA, Fanconi anemia, or PNH in comparison with normal controls. TRF lengths in the patient group were significantly shorter for age than normals (P < .0001). Telomere shortening was apparent in both granulocyte and mononuclear cell fractions, suggesting loss at the level of the hematopoietic stem cell. In patients with acquired AA with persistent cytopenias (n = 40), there was significant correlation between telomere loss and disease duration (r = −.685; P < .0001), equivalent to progressive telomere erosion at 216 bp/yr, in addition to the normal age-related loss. In patients who had achieved normal full blood counts (n = 20), the rate of telomere loss had apparently stabilised. There was no apparent association between telomere loss and secondary PNH (n = 13). However, of the 5 patients in the study with TRF less than 5.0 kb, 3 had acquired cytogenetic abnormalities, suggesting that telomere erosion may be relevant to the pathogenesis of MDS in aplastic anemia.

An unusual cause of peripheral neuropathy.

A 74-year-old man presented with a 2-month history of weight gain, lethargy and cold intolerance. He had had endoscopic retrograde cholangiopancreatography (ERCP) 3 years prior to admission. His free thyroxine...

Primary Antiphospholipid Syndrome Presenting as Budd-Chiari Syndrome

Primary Antiphospholipid Syndrome Presenting as Budd-Chiari Syndrome

Haemolytic uraemic syndrome complicated by disseminated extraneural cryptococcosis.

Case report (Dr R F Miller) A 33 year unemployed white man was admitted to hospital in January 1994 complaining of a 1 week history of diarrhoea, passing up to...

Trimethoprim-induced aseptic meningitis and uveitis

We wish to report a case of trimethoprim-related uveitis and aseptic meningitis confirmed by rechallenge. An 18-year-old woman presented with a recent history of recurrent urinary tract infections. The first infection, 5 months previously, was treated with a 7-day course of trimethoprim. She made an uneventful recovery. 2 months later a recurrent urinary tract infection was diagnosed and trimethoprim was again prescribed. Within hours of the first dose of trimethoprim, she described the onset of headache, red and sore eyes, and neck ache. She was reviewed in the emergency department and her therapy was changed to co-amoxyclav. She completed a 7-day course. Her eye pain endured for 2 weeks. A subsequent urinary tract infection, 1 month later, was again treated with co-amoxyclav and she made an uncomplicated recovery. 2 months later she presented to the emergency department with headache, fever, painful red eyes, and photophobia. Earlier in the day she had attended her local medical officer, with a recurrence of urinary tract symptoms. A clinical diagnosis of cystitis was made and she was prescribed trimethoprim. She took her first dose about 4 h before her hospital presentation. On examination, she appeared unwell but was orientated and responsive. Her temperature was 37·5oC. Neck stiffness and a positive Kernig’s sign were both elicited and slit-lamp examination of both eyes revealed white cells in the anterior chamber and a proteinaceous “flare”, consistent with a bilateral anterior uveitis. Small non-tender anterior and posterior cervical lymph nodes were palpable. Her large joints were tender on passive movement. Investigations revealed an ESR of 22, a normal full blood count, white cell count, electrolytes, urea, creatinine, and liver function tests. Urine microscopy showed 11 to 100 10 white cells. Urine cultures yielded a mixed growth. A high vaginal swab showed no growth. For Chlamydia trachomatis, direct fluorescence on a cervical swab and C trachomatis urinary PCR were negative. Cerebrospinal fluid (CSF) microscopy showed 1 red cell, 3 polymorphonuclear cells, and 2 monocytes 10/L. The CSF was sterile. The CSF protein was elevated at 0·66 g/L. Blood cultures were negative. Immunological studies showed a negative antinuclear antibody, and a normal rheumatoid factor. There was no history of previously diagnosed sexually transmitted diseases in either the patient or her sexual partner. She denied any recreational illicit drug use and only occasionally drank alcohol. She was a non-smoker. Her only regular medication was the oral contraceptive pill. In the absence of other infectious or autoimmune diagnoses, an adverse drug reaction to trimethoprim is most likely. Trimethoprim-induced aseptic meningitis has been described in previous case reports. The potential to produce this adverse effect has been shown to occur independently of the combination with sulphonamide drugs. Uveitis, by contrast, has been attributed to the systemic use of sulphonamide derivatives. Of interest, most of these cases were reported in people treated with co-trimoxazole, and none was re-challenged with trimethoprim alone to determine if this drug was capable of inducing uveitis. To our knowledge this is the first case report of trimethopriminduced uveitis. It is possible that this diagnosis is missed due to the frequent use of this drug in combination with sulphamethoxazole for which this particular adverse drug reaction has been well described.

Prevalence and haemopoietic effects of low serum vitamin B12 levels in geriatric medical patients.

The clinical significance of low serum vitamin B12 levels in elderly people is controversial. We aimed to document the prevalence of a low serum vitamin B12 (< 175 pmol/l) in patients referred to a geriatric medical unit, and to determine whether haemopoiesis is commonly affected in elderly patients with low serum vitamin B12. We studied prospectively 472 consecutive referrals to a geriatric medical unit; fifty-six (13%) had a low serum vitamin B12 level, of whom nineteen (34%) of the fifty-six also had evidence of Fe deficiency (serum ferritin < 45 ng/ml). Low vitamin B12 was associated with a raised mean erythrocyte volume (MCV; mean 96.0 (SD 6.7) fl), compared with a control group (91.7 (SD 6.0) fl; P = 0.001). However, only thirteen (23%) of the fifty-six patients with a low vitamin B12 had an MCV > or = 100 fl. Mean haemoglobin (Hb) levels were not significantly reduced in those with a low vitamin B12. In a subsequent study the haematological response to intramuscular hydroxocobalamin was examined in thirty-four patients with a low serum vitamin B12. Treatment resulted in a significant fall in MCV and rise in Hb; these effects could be detected both in those patients with an initially normal full blood count (change in MCV -1.2 (SD 1.2); Hb +0.5 (SD 0.6); P < 0.01) and in those with macrocytosis and/or anaemia (-9.1 (SD 11.8); +0.8 (SD 1.2); P < 0.05). A low serum vitamin B12 is common in geriatric medical patients. This is usually associated with an upset in erythropoiesis, although the abnormalities are often subtle and may not be apparent on inspection of the full blood count. Elderly patients with serum vitamin B12 < 175 pmol/l should be assumed to have vitamin deficiency even if their full blood count is normal.

Case report: An unusual presentation of gout

A 48-year-old male pipefitter presented with 6 months history of pain and swelling in the upper part of his right leg. Clinical examination revealed a non tender swelling on the anteromedial aspect of the upper tibia measuring about 5 cm in diameter. The lesion was clinically cystic with a hard margin. A plain radiograph (Fig. la,b) showed a large soft tissue mass related to the anteromedial border of the upper tibia, associated with adjacent periosteal reaction. At the knee joint there was joint space narrowing and juxtaarticular erosions. The haematological investigations showed normal full blood count, the ESR was 104. CRP 23 mg/1, negative Rheumatoid factor. Serum urate was 0.32 mmol/1 (Normal 0.1-0.42). A computerized tomography (CT~ scan (Fig. 2) confirmed the presence of a soft tissue attenuation mass which extended posteromedial to the upper tibia. It also showed the periosteal reaction. The bony cortex was intact. There was no soft tissue calcification and no evidence of medullary involvement. Technetium methylene diphosphonate (Tc MDP) scan performed at another hospital was reported as showing increased isotope uptake in the area of interest. There was no comment rega~'ding uptake around the knee joint. Based on the above information a soft tissue malignancy was felt to be the most likely diagnosis and the patient was referred to our hospital for further evaluation. An MRI scan of the lesion was undertaken. T1 weighted sagittal scans (Fig. 3a) showed a mass of low signal intensity, anterior to the tibia. This mass was seen to envelope the medial aspect o f the tibia extending superiorly in continuity with the knee joint. This mass was of intermediate to high signal on the T2 weighted sagittal scan (Fig. 3b). An axial proton density scan (Fig. 4) o f the knee joint showed extensive intermediate signal intensity within the joint associated with multiple joint erosions involving the tibia, femur and patella. Abnormal tissue could be seen interposed between the posterior aspect o f the tibia and all muscle groups applied to the back of the knee and tibia, i.e. both heads of Gastrocnemius and the blood vessels. The abnormal tissue remained closely applied to the bone expanding inferiorly and anteriorly accounting for the soft tissue mass seen on the plain films and the CT scan. The differential diagnosis from the radiological findings was of a synovial based tumour, pigmented villonodular synovitis (PVNS), rheumatoid arthritis, haemophilia, gout or a subperiosteal mass such

Hereditary ovalocytosis with compensated haemolysis

The clinical and laboratory phenotype of compensated haemolysis in a patient with hereditary ovalocytosis is reported. Clinical presentation was intermittent jaundice and abdominal pain due to pigment gall stones. Haematological analysis revealed an absolute reticulocytosis with an otherwise normal full blood count and biochemical evidence of haemolysis. Variable results were observed with blood grouping reagents. The patient's red cells were stomatocytic ovalocytic, rigid, resistant to malarial parasite invasion, defective in anion transport, and had the characteristic two linked mutations in the red cell band 3 gene.

85. Symptomatic Selenium Deficiency in a child on home parenteral nutrition (HPN)

A 2½ year old girl on long term HPN for microvillous atrophy presented with distal limb myalgia with normal power, reflexes & tone, & progressive inability to bear weight. Normal full blood count, electrolytes, creatine kinase and transaminases. Serum concentrations of Vitamins A, E & B12 folate zinc and copper were normal. Plasma selenium was very low at < 0.05 μmol/l (reference range (RR) 0.8-2.0 μmol/1); RBC glutathione peroxidase was undetectable at < 1μ/g Hb) and plasma glutathione peroxidase was 6μ/l (RR 90-35μ/l). RBC enzymes showed normal vitamins B1, B2, B6 status. Electromyogram was mildly abnormal. Muscle biopsy demonstrated atrophy of type II fibres & muscle selenium was 0.23μg/g dry weight (adult RR: 0.6-0.97 μg/g). Full cardiological evaluation was normal. Sodium selenite 15 μg/day was added to IV nutrition. Within 3 days muscle pain had improved; she began to crawl again & by 6 weeks she was walking normally. At 3 months, plasma selenium was 0.53 μmol/1. RBC glutathione peroxidase was 15 μ/g Hb. Sodium selenite supplements were reduced. Although biochemical evidence of selenium depletion is common in adults & children on HPN, associated clinical symptoms have rarely been reported. This is the youngest reported. Relationship between biochemical depletion & clinical symptoms is poorly understood, the dramatic response to selenium suggests that deficiency was the cause.