An 8 year old child with Pfeiffer syndrome presented at the Paediatric Casualty Department. She had a two week history of severe pallor and progressive lethargy. Pfeiffer syndrome is a genetic disorder characterised by craniosynostosis, visual impairment and ocular proptosis. It is thought to be associated with deficiencies associated with fibroblast growth factor receptors on chromosome 8 and 10. This young child was of short statue. She had dysmorphic features and was blind. She demonstrated reduced exercise tolerance, unable to keep up with her siblings. She had a history of complex neurosurgical and plastic surgery. She had difficulty in eating solids hence her dietary intake was pureed solids; meats, fish and dairy products. Her parents had become Jehovah Witnesses in 2006. A full blood count was performed with the following results: Hb 23 g/L, WBC 6.8 x 109/L and Platelet count 259 x 109/L. The RBC was 1.97 x1012/L, Hct 0.100, MCV 51.8 fL

and RDW-CV 23.1%. The Reticulocyte count was 1.5% and absolute count 29.4 x 109/L. The blood film revealed a marked microcytic, hypochromic anaemia with elliptocytes and pencil cells consistent with a severe iron deficiency anaemia. Iron studies were performed with the following results: Iron 1.2 µmol/L, Transferrin 3.8 g/L, Iron saturation 1.3% and Ferritin 1 µg/L. Parvovirus B19 was negative and the Hb EPG was normal. Bone marrow trephine showing sheets of plasma cells The Medical Dilemma was now clearly an acute life threatening event. The child had cardiac signs and was at risk of cardiac failure or arrest. She was in need of intensive care. There was also a need to acknowledge the religious beliefs of the family. At this point a hospital administrator was called. The parents reluctantly consented for a blood transfusion. Meanwhile the child's father contacted support from the Jehovah Witness community to attend the hospital. Consent to transfuse was withdrawn. The possibility of an iron transfusion and administration of erythropoietin was…

Late one evening, a full blood count was received on a full term neonate who had just been delivered by caesarean section. The clinical notes read 'pallor'. The results from the analyser were as follows: Hb 64 g/L, MCV 118.9 fL, reticulocyte count 13.4 % (254 x 109/L), WBC 16.2 x 109/L and platelets 278 x 109/L. A Hb result of 64 g/L is abnormally low for a newborn neonate; the normal range being 121 - 191 g/L in the above laboratory. A repeat specimen was requested. The Hb was now 60 g/L, confirming the initial result. Whilst the blood film was being stained a direct antiglobulin test (DAT) was performed with a negative result. Both the infant and mother were group O positive and an antibody screen performed on the mother was negative. The total bilirubin was 140 umol/L, NR (0-150 umol/L). The infant was transfused with two units of packed

cells. The blood film revealed a nucleated red cell count (NRBC) of 674 NRBCs / 100 WBCs. The normal range being 1-25 NRBCs / 100 WBCs. The blood film image (x 400) demonstrates the markedly increased number of red cell precursors while the blood film images (x 1000) demonstrate marked dyserythropoiesis. Note the nuclear budding and cytoplasmic bridging, classical features of dysplasia. A differential diagnosis on this infant would include a fetomaternal bleed or less probably Congenital Dyserythropoietic Anaemia (CDA). A Kleihauer test was performed on the mother to check for a fetomaternal bleed. The Kleihauer test was positive; the presence of 3.84 % fetal cells translated to a transplacental haemorrhage of 95.84 mls. Hence the initial diagnosis of a fetomaternal bleed was confirmed. Some degree of fetomaternal transfusion occurs in approximately 50% of all pregnancies. The most frequently observed causes of occult haemorrhage prior to birth include abdominal or multiple trauma, amniocentesis in the third trimester, post external cephalic version, placental tumours and spontaneous haemorrhages. Haemoglobin values…

A seven weeks old infant was admitted to hospital with a history of 'failure to thrive'. A full blood count was performed with the following results: Hb 123 g/L, WBC 10.2 x 109/L Platelets 586 x 109/L Examination of the blood film revealed a marked number of acanthocytes. A provisional diagnosis of abetalipoproteinaemia was made. The following chemistry tests were performed: Cholesterol 1.4 mmol/L NR (3.0-5.5) Triglyceride <0.1 mmol/L NR (<2.0) Apolipoprotein A1 0.78 g/L NR (1.10-2.00) Apolipoprotein B 0.07 g/L NR (0.60-1.25) Vitamin A 0.4 umol/L NR (0.5-1.8) Vitamin E <1 umol/L NR (5-14) Faecal fat 38 mmol/day NR (0-3.4) The above results confirmed a diagnosis of abetalipoproteinaemia. Abetalipoproteinaemia is a rare autosomal recessive disorder characterised by the presence of acanthocytic red cells in the peripheral blood. The primary defect is due to a mutation and lack of activity in the microsomal triglyceride transfer protein needed to bind lipids to the ?-apolipoprotein in plasma. Intestinal absorption of lipids is

defective. The plasma levels of cholesterol and triglyceride are extremely low and ?-apolipoprotein undetectable. There is an increase in sphingomyelin in the outer half of the red cell membrane bilayer increasing the surface layer of the cell. This ?-apolipoprotein defect leads to the production of acanthocytic red cells, about 50-90% of the red cells being acanthocytes. The sphingomyelin accumulates with cell ageing thus the nucleated precursor red cells and reticulocytes are not affected while the older red cells are affected. As a result of fat malabsorption and the absence of low density lipoproteins, which transport vitamin E, the red cells of patients with abetalipoproteinaemia are markedly deficient in vitamin E. The level of vitamin A is also reduced. Abetalipoproteinaemia usually presents in early childhood with diarrhoea and failure to thrive and is characterised clinically by fat malabsorption, spinocerebellar degeneration, pigmented retinopathy and acanthocytosis. The initial neurologic manifestations are loss of deep-tendon reflexes, ataxia and development of a spastic gait. They…

A 29 year old female presented to the Casualty Department feeling generally unwell. At 28 weeks gestation she was hypertensive with proteinuria. She had with her an Advanced Health Care Directive stating that no transfusions of whole blood, red cells, white cells, platelets or plasma be administered to her. She was admitted with a presumptive diagnosis of pre-eclampsia. A full blood count and coagulation studies were performed with the following results: Hb 103 g/L WBC 10.5 x 109/L Platelets 24 x 109/L PT 15.8 sec INR 1.2 APPT 27.4 sec Fibrinogen 1.4 g/L D- DIMER LIA >20.00 ug/ml She was severely thrombocytopenic with disseminated intravascular coagulation (DIC). The blood film and differential count showed the presence of 15% blast cells and 55% abnormal promyelocytes. A diagnosis of acute promyelocytic leukaemia (APL) was made. A bone marrow aspiration was performed. The differential count on the bone marrow showed the presence of 86% abnormal promyelocytes. Cytogenetics showed a t(15;17).

FISH confirmed a PML/RARA fusion. Immunophenotyping was as follows: CD45+, HLA-DR-, CD11b-, CD13+, CD15-, CD33+, CD34-, CD64+, CD117+, CD2+, CD22+ and MPO+ The above patient was transferred to a ward under joint obstetric and haematology care. A number of issues were before this medical team. They were presented with a patient with APL, DIC and severe thrombocytopenia. She was 28 weeks pregnant with pre-eclampsia and from deeply-held conviction, refused blood product support. Therefore performing a caesarean section was not safe. She was given steroids for fetal lung maturity as well as all trans retinoic acid (ATRA), the drug of choice for the treatment of APL. Over the next few days the white cell count steadily rose as did the urea, creatinine and liver function tests. Her hypertension was difficult to control. Labour was induced with failure to progress. On the ninth day after admission, a stillborn fetus was delivered vaginally. There was minimal blood loss. It is thought that the stillborn infant was…

In February 1999 a 29 year old female attended the Haematology Clinic at the Prince of Wales Hospital. She had a history of anaemia, neutropenia and thrombocytopenia. She was passing dark urine. A full blood count, reticulocyte count and coagulation studies were performed. The results were as follows: Hb 66 g/L Retic count 16.20% (absolute count 356.40 x 109/L) MCV 113.6 fL WBC 3.1 x 109/L Platelets 55 x 109/L PT 41.5 sec INR 4.2 APTT 45.7 sec Fibrinogen 5.6 g/L D-DIMER LIA <0.19 mg/L A urinary haemosiderin was performed which was strongly positive. A clinical chemistry profile was also performed: The LDH was raised at 3436 U/L. The test results, together with the clinical symptoms of the patient indicated that she had a severe haemolytic anaemia suggestive of Paroxysmal Nocturnal Haemoglobinuria (PNH). A Ham's test was performed. This is an acidified serum test which detects a population of red cells with sensitivity to complement-mediated lysis. The

Ham's test was positive. A diagnosis of PNH was confirmed on the above patient. PNH is a rare, acquired, clonal disorder of the bone marrow characterised by a total or partial lack of proteins normally attached to the haemopoietic cell membrane by the glycosylphosphatidylinositol (GPI) anchor. This defect is due to a somatic mutation of the phosphatidylinositol glycan class A (PIG-A) gene on the X chromosome which encodes for a protein needed for the synthesis of GPI anchor. Without GPI anchor, an essential group of membrane proteins are either reduced or absent in all haemopoietic cell lines. These proteins include complement-regulating surface proteins namely decay-accelerating factor (DAF) or CD55, membrane inhibitor of reactive lysis protein (MIRL) or CD59 and the homologous restriction factor (HRF) or CD8 binding protein. All of these proteins interact with complement, particularly C3b and C4b, protecting cells against lysis. In their absence, haemopoietic cells are exposed to complement leading to uncontrolled amplification of the complement cascade and destruction of…

A 22 year old female, found to have severe anaemia by her General Practitioner, presented at the Haematology Clinic for further investigative studies. A full blood count and haemoglobin electrophoresis (EPG) were performed . The results were as follows: Hb 76 g/L 115-165 Hct 0.244 0.37-0.47 MCV 83.3 fL 80-100 MCH 25.9 pg 26.5-33.0 The blood film was mildly microcytic and hypochromic. There was an occasional nucleated red cell present while many of the red cells showed coarse basophilic stippling. The EPG results were as follows: Hb EPG Cellulose Acetate (pH 8.6) No abnormal band detected. Hb A2: 2.6 % 2.0-3.5 % Hb F: <1.0 % <1 % Hb H inclusions: not detected No abnormality detected. Iron studies were normal in this case. A bone marrow aspirate was performed. The marrow was hypercellular with increased erythropoiesis and mild dyserythropoiesis. No abnormal sideroblasts were seen. As coarse basophilic stippling in the red cells is a feature

of lead poisoning, a lead level was performed. The lead was found to be 5.0 umol/L with a normal range of 0-0.5 umol/L. The level of mercury was also examined and found to be <1 nmol/L with a normal range of ≤50 nmol/L. After questioning the patient in this case study it became evident that the patient had been taking a medication supplied to her by her Indian doctor. The medicine was in a powder form. A sample of this medication was sent for analysis which showed that the powder contained 12 % lead. Patients with lead poisoning clinically present with abdominal colic and constipation, peripheral neuropathy and anaemia. The anaemia is invariably a hypochromic microcytic anaemia as the ingestion of lead interferes with haem synthesis. It does so by inhibiting several enzymes directly involved with haem synthesis. Pyrimidine 5'-nucleotidase is one such enzyme. In its absence, pyrimidine nucleotides accumulate in the red cells, preventing iron from being incorporated into haem at a normal rate.…

A 56 year old male was transferred from a regional hospital to the intensive care ward at the Prince of Wales Hospital. He had extensive necrosis extending from the scrotum to his flank, axilla, and shoulder and spreading along his arm. He had necrotising fasciitis and was to have surgical debridement. He was too unwell for the Hyperbaric Chamber. A full blood count was received in the laboratory. The results were as follows: Hb 89 RR (130-180) g/L Hct 0.262 RR (0.40-0.54) MCV 87.9 RR (80-100) fL MCH 29.9 RR (26.5-33.0) pg WBC 39.9 RR (3.5-11.0) x

10 9/L Plats 80 RR (150-400) x 10 9/L The blood film showed an absolute neutrophilia with marked toxic granulation; moderate numbers of microspherocytes and thrombocytopenia. These features are classically found in Clostridium perfringens infection. This was a case of severe septicaemia and haemolysis secondary to necrotising fasciitis. See figure 1. The term necrotising fasciitis describes a condition of rapidly spreading infection, usually located in fascial planes of connective tissue resulting in tissue necrosis. Fascial planes are bands of connective tissue that surround muscles, nerves and blood vessels. The speed with which necrotising fasciitis spreads is directly proportional to the thickness of the subcutaneous layer. (more…)