When is ITP not ITP?

Idiopathic thrombocytopenic purpura (ITP) is a disorder characterised by the destruction of antibody-sensitised platelets by macrophages, most notably in the spleen. It is primarily a diagnosis of exclusion as it is made after conditions associated with secondary thrombocytopenia have been excluded. There are 2 forms of ITP, acute and chronic. Acute ITP usually occurs in children between the age of 2 and 6 years. It is often preceded by vaccination or by a viral infection. Chronic ITP usually occurs in children more than 10 years of age, as well as in adults. ITP is caused by autoantibodies interacting with platelet membrane glycoproteins and resulting in accelerated destruction of platelets. As these autoantibodies diminish in strength and finally disappear, the platelet count returns to normal. This process takes up to 6 months in children with acute ITP and takes even longer in children with chronic ITP. Acute ITP is characterised by platelet counts less than 20 x

109/L and often less than 10 x 109/L. The clinical presentation is bruising with a petechial rash in an otherwise healthy child. Acute ITP affects males and females equally. Chronic ITP is characterised by a somewhat higher platelet count, less than 150 x 109/L and occurs predominantly in females by a 2:1 ratio. A full blood count, including platelet count, should be performed on all children suspected of having ITP. Features inconsistent with ITP should prompt further investigations. A bone marrow biopsy reveals normal or increased numbers of megakaryocytes in both acute and chronic ITP. Acute ITP is a self-limiting disorder requiring minimal or no therapy in the majority of cases. Corticosteroids or Intragam (IgG) may be given at the discretion of the clinician. Chronic ITP is also treated with corticosteroids or Intragam and may, in some cases, ultimately require splenectomy. An 8-year-old boy presented at the Paediatric Casualty Department with multiple bruises and mucocutaneous bleeding. He is said to have had a history…

Clostridium perfringens induced haemolytic anaemia

A 56-year-old female presents with a perforated bowel secondary to metastatic ovarian cancer. She has acute abdominal pain and is passing dark-red urine. A FBC is performed with the following results: Hb 75 g/L, WBC 14.3 x 109/L and Platelet count 163 x 109/L The blood film shows the presence of a marked number of micro spherocytes. The following Clinical Chemistry tests are performed: LDH 1936 IU/L NR 90-200  Urea  11.1  mmol/L  NR 2.9-7.1  Creatinine  206  umol/L  NR 60-110  Bilirubin total  507  umol/L  NR 0-25  ALP  48  U/L  NR 38-126  GGT  10   U/L  NR 0-30  AST  2550   U/L  NR <45  ALT  590   U/L  NR <45 A diagnosis of haemolytic anaemia secondary to Clostridium perfringens infection is made. Clostridium perfringens Clostridium perfringens is an anaerobic Gram-positive bacillus associated with 3 distinct disease states, namely, gas gangrene or clostridial myonecrosis, enteritis necroticans and clostridium food poisoning. Clostridium perfringens is a saprophytic organism inhabiting the bowel and genital tract. It has

no pathophysiological significance in the absence of clinical infection. Clostridium perfringens produces at least 12 antigenic protein toxins, the most common of which is the alpha toxin. These toxins react with lipoprotein complexes on cell surfaces, liberating potent haemolytic substances known as lysolecithins resulting in cell lysis. This process leads to a haemolytic anaemia, which may be so severe, the end result is death. During this process of cell lysis, large amounts of CO2 and hydrogen are produced. This leads to intense abdominal swelling hence the term gas gangrene. A foul-smelling odour is given off from the necrotic tissue. When a patient presents with bowel perforation, clostridia are released into the surrounding tissues, giving rise to tissue necrosis. This process is a rapid one proceeding up to 10cm per hour. The patient develops severe haemolytic anaemia. Haemoglobinemia and haemoglobinuria occur. The serum becomes a brilliant red colour resulting in dissociation between the haemoglobin and the haematocrit level. A leucocytosis with a left…

Splenic Marginal Zone Lymphoma

An 86 year old male presented to the Casualty Department with chest pain. On clinical examination he was noted to have a splenomegaly. No lymphadenopathy was detected. A FBC was performed with the following results: Hb 114 g/L, WBC 13.5 x 109/L and platelet count 258 x 109/L The blood film showed a mild lymphocytosis. 23% of the lymphocytes had the appearance of those seen in splenic marginal zone lymphoma in that they had round nuclei with cytoplasmic villi distributed towards one pole of the cell. Immunophenotyping and cytogenetics were performed on the bone marrow with the following results: Immunophenotype: SIg+, HLA-DR+, CD19+, CD20+, CD22+, CD23+(weak), CD10-, 11c+, CD25-, FMC7+, CD3-, CD5- and CD103+ Cytogenetics: del(7q) A diagnosis of splenic marginal zone lymphoma (SMZL) was made. Splenic marginal zone lymphoma SMZL is a rare B-cell lymphoma occurring in elderly patients. It comprises less than 1% of all the lymphoid neoplasms. SMZL is characterised by a large spleen while lymphadenopathy is rare.

The bone marrow (BM) and peripheral blood (PB) are often involved. The PB shows a moderate lymphocytosis with white cell counts of less than 25 x 109/L. The lymphocytes appear as villous lymphocytes. Morphologically these lymphocytes range from small to medium in size with round to irregular shaped nuclei, coarse chromatin pattern, an occasional nucleolus and abundant pale blue cytoplasm. The cytoplasm may exhibit fine projections or villi confined to one pole of the cell. Some of the lymphocytes may appear plasmacytoid. The differential diagnosis includes other small B-cell lymphomas/leukaemias including chronic lymphatic leukaemia, hairy cell leukaemia, mantle cell, follicular and lymphoplasmacytic lymphoma. Immunophenotyping shows strong expression of surface immunoglobulin (SIg) and positivity for B-cell antigens (CD19, CD20 and CD22). HLA-DR and FMC7 are also positive. CD5 is variable; CD10 and CD103 are negative although in 6% of cases CD103 may be positive. CD23 is negative to weak positive. CD11c and CD25 may be either positive or negative. The…

Acute Lymphoblastic Leukaemia occuring in a young child

An 11-year-old male presented to the Casualty Department with an anterior mediastinal mass. A full blood count was performed with the following results: Hb 98 g/L, WBC 37.5 x 109/L and platelet count 35 x 109/L. A differential white cell count showed an absolute lymphocytosis with 64% lymphoblasts. A diagnosis of acute lymphoblastic leukaemia (ALL) was made from the blood film. Bone marrow and trephine biopsies were performed. (See Figure 1) A morphological examination of the peripheral blood revealed two populations of lymphoblasts. There were small blasts with a high nuclear to cytoplasmic ratio, dense chromatin pattern and inconspicuous nucleoli and larger heterogeneous blasts with cleaved nuclei, fine chromatin and prominent nucleoli. The bone marrow biopsy resulted in a dry tap. This is often the case, especially in children. The marrow was densely packed with blast cells and fibrous tissue making aspiration impossible. The trephine revealed a bone marrow packed with blasts. Cytochemistry and immunophenotyping were performed on the bone marrow.

The blasts showed focal positivity with the acid phosphatase stain. Immunophenotyping showed the following results: HLA-DR-, CD3-, CD19-, CD117-, CD2+, CD4-, CD5+, CD7+, CD8+, CD34+, TdT+, CD1a+, Cyto3+ These findings were consistent with Precursor T-Cell acute lymphoblastic leukaemia. Cytogenetics showed 46 XY t(11;14)(p13;q11) Figure 1 Precursor T-Cell ALL Approximately eighty percent of childhood acute leukaemias are lymphoblastic of which eighty to eighty five percent have the B-progenitor phenotype. Children with Precursor B-Cell ALL are usually younger children under six years of age. Ten to fifteen percent of children with acute lymphoblastic leukaemia, usually older children and adolescents, present with Precursor T-Cell ALL. T-Cell ALL almost invariably presents with a high white cell count and bulky extramedullary disease. The children have a lymphadenopathy, hepatosplenomegaly and an anterior mediastinal thymic mass. T-Cell ALL may also present with central nervous system (CNS) involvement. Eighty to eighty five percent of children with B-Cell ALL go into remission and remain relapse-free survivors. T-Cell ALL…

Myelodysplastic / myeloproliferative diseases: Chronic myelomonocytic leukaemia

n 83-year-old female presented to the Casualty Department with lethargy and splenomegaly. A FBC was performed with the following results: Hb 89 g/L, WBC 140.8 x 109/L and Platelet count 23 x 109/L. A differential white cell count showed an absolute neutrophilia and monocytosis. There was a left shift in the myeloid line with some dysplastic changes in both the neutrophils and the monocytes. A diagnosis of chronic myelomonocytic leukaemia was made. Myelodysplastic / myeloproliferative diseases: Chronic myelomonocytic leukaemia Chronic myelomonocytic leukaemia (CMML) is a clonal disorder closely resembling chronic myeloid leukaemia (CML). It is characterised by a persistent monocytosis of >1 x 109/L in the peripheral blood; absence of the Philadelphia chromosome and BCR/ABL fusion gene; dysplasia involving one or more cell lineages and < 20% blasts in the bone marrow. CMML occurs predominantly in patients over 50 years old. The peripheral blood is characterised by a monocytosis, usually in the range of 2-5 x 109/L. The

percentage of monocytes is almost always >10% of the total white blood cell count. The monocytes are mature and often display abnormal nuclear morphology. Blasts and promonocytes account for approximately 20% of the white cells. The total white cell count may be normal or slightly decreased. A neutropenia or neutrophilia may be present. Neutrophil precursors usually comprise fewer than 10% of the total white cell count. Some cases of CMML are associated with an eosinophilia. The eosinophil count is >1.5 x 109/L. Elevated eosinophil counts may be associated with tissue damage secondary to degranulation of the eosinophils. Dysplasia is a feature of all three cell lineages occurring in both the peripheral blood and bone marrow. Dysgranulopoiesis: hypolobulated or abnormally lobulated nuclei with abnormal cytoplasmic granulation of the monocytes. Dyserythropoiesis: normocytic/macrocytic red cells. Dysmegakaryopoiesis: thrombocytopenia with atypical large platelets. CMML is divided into two categories according to the number of blasts in the peripheral blood and bone marrow. CMML-1: <5% blasts in the…

Anaemia secondary to a parvovirus infection

A 9-month-old child presented to the Casualty Department with pallor and a maculopapular rash on the face. A full blood count was performed and the following results noted: Hb 84 g/L, WBC 15.5 x 109/L, Platelet count 422 x 109/L and Reticulocyte count 0.6 %. The blood film showed a normochromic normocytic anaemia with a reticulocytopenia. A Hb EPG was performed with no abnormality detected A bone marrow examination revealed an erythroblastopenia together with giant proerythroblasts scattered throughout the marrow. Such findings may be associated with a parvovirus infection. Parvovirus serology was performed: Parvovirus B19 IgG and parvovirus B19 IgM were both positive. Parvovirus B19 infection The human parvovirus was discovered in 1975 in the sera of normal blood donors whilst screening for the hepatitis B virus. The term parvovirus is derived from the Latin ‘parvum’ meaning ‘small’. Parvoviruses are amongst the smallest DNA containing viruses infecting man. They are extremely stable, resisting heat inactivation at 56ºC

for more than 60 minutes. Parvovirus infection is a common infection in humans. Approximately 50% of children have detectable parvovirus B19 IgG in their blood by the age of fifteen and more than 90% of the elderly are also seropositive. The parvovirus has an unusual predilection for rapidly growing cells, particularly red cell precursors in the bone marrow. It uses the P antigen as a receptor to enter the red cell. The P antigen is also present on granulocytes and megakaryocytes. Once inside the cell the parvovirus inhibits growth by inducing cell cycle arrest and apoptosis. This process gives rises to a severe haemolytic anaemia when the red cells are infected. When the granulocytes and megakaryocytes are infected an aplastic crisis may occur. Parvovirus infection is also responsible for causing aplastic crises in children with a chronic haemolytic state such as hereditary spherocytosis. It can produce prolonged pancytopenia in an otherwise healthy child and frequently produces a prolonged pancytopenia in children with deficient…

A case of thalassaemia in a three year old child

A 3-year-old child from Southeast Asia presents with pallor and fatigue at the paediatric casualty department. She is said to have a history of alpha thalassaemia, namely haemoglobin H disease (HbH). A full blood count is performed with the following results: Hb 78 g/L, MCV 75.3 fL, MCH 20.8 pg, Platelet count 358 x 109/L A blood film is examined with the following morphology: Anisocytosis, microcytes, hypochromasia, elliptocytes, polychromasia, target cells and coarse basophilic stippling. Morphologically the blood film is not suggestive of HbH disease. Coarse basophilic stippling is not a feature of HbH disease. Also the MCV and MCH are higher than that seen in HbH disease. Alpha thalassaemias are caused by a decrease in the production of alpha globin genes. This decrease in alpha genes is due to a deletion or mutation of one or more of the four alpha Aglobin genes located on chromosome 16. The alpha thalassaemias are divided

into four groups: One gene deletion – silent trait Two gene deletion – thalassaemia trait Three gene deletion – HbH disease Four gene deletion – hydrops foetalis The silent carriers have no clinical abnormalities. The haemoglobin level is within the normal range while the MCV is borderline normal. Those with alpha thalassaemia trait are clinically normal however the haemoglobin is low while the indicies are microcytic and hypochromic. The average MCV is 68 fL and the average MCH is 21 pg. Those with HbH disease are also clinically normal however their haemoglobin level is moderately low. The average MCV is 57 fL and the average MCH is 21 pg. Those with hydrops foetalis fail to produce alpha globin chains. They have four gamma chains or haemoglobin Barts. Also they are delivered stillborn, usually at 30 to 40 weeks. Haemoglobin H disease can be associated with a rare haemoglobin known as Haemoglobin Constant Spring (HbCS). HbCS is an alpha chain variant rather than a deletion. The alpha chain…

Suggestive but not diagnostic of dengue fever

A 62-year-old male returning from Fiji presents with fever, severe headache and myalgia. He is clinically very unwell and is admitted to intensive care. A full blood count is performed. The patient is severely pancytopenic:
Hb 110 g/L, WBC 0.43 x 109/L and Platelet count 14 x 109/L. Renal function and liver function tests are also performed:
 Urea 21.2 mmol/L and Creatinine 492 umol/L
 GGT 121 U/L, AST 249 U/L and ALT 95 U/L 
The patient also has acute renal failure and abnormal liver function tests. The blood film shows the presence of ‘Turk’ cells as well as a left shift with toxic changes. As the differential diagnosis for this patient is malaria, a malaria screen is performed. The result is negative. Pancytopenia and the presence of ‘Turk’ cells on the blood film are also suggestive of dengue fever. Serology for dengue fever is performed:
 IgG antibody is negative while IgM antibody is positive.
 A diagnosis of dengue haemorrhagic fever is

made. This patient died three days after admission to intensive care. Dengue fever and dengue haemorrhagic fevers are acute febrile diseases found in the tropics and Africa with a geographical spread similar to that of malaria. One major difference is that while malaria is not found in major cities, dengue occurs in developed tropical nations including Singapore, Taiwan, Fiji, Indonesia and Brazil. It is also found in northern Australia. Any one of four closely related virus serotypes of the genus Flavivirus, family Flaviviridae, causes dengue fever. Dengue fever is transmitted to humans by the Aedes Aegypti mosquito. The clinical features of dengue are a sudden onset of fever, severe headache, muscle and joint pain and a petechial rash on the lower limbs and chest. There may also be gastritis with abdominal pain, nausea, vomiting and diarrhoea. The fever lasts about six to seven days. The platelet count steadily drops during the period of fever. The platelet count returns to normal…

Transient Abnormal Myelopoiesis in a Newborn Infant

A newborn infant, one day old, presented with the following blood count: Hb 140 g/L, MCV 111.3 fL, WBC 112.5 x 109/L and platelet count 191 x 109/L The white cell differential included 87 percent blast cells. The blasts were large with rounded nuclei and moderate amounts of basophilic cytoplasm. Cytoplasmic blebs were present. Some of the blasts contained coarse azurophilic granules. The blast cells on this blood film appeared to be megakaryoblasts. The red cell precursors showed marked dysplastic changes. Flow cytometry was performed on the peripheral blood. A bone marrow aspiration was not attempted. The immunophenotype of the blast cells was as follows: HLD-DR-, CD7+, CD13-, CD33+, CD45-, CD41+ and CD61+ Cytogenetics were performed. In addition to the presence of trisomy 21 found in Down syndrome there was an additional chromosome 8 (trisomy 8). A provisional diagnosis of Transient Abnormal Myelopoiesis (TAM) was made on this infant. Newborn infants with Down syndrome

have an increased disposition for acute leukaemia. The leukaemia is predominantly acute megakaryoblastic leukaemia. Acute lymphoblastic leukaemia may occur but is less common. Acute leukaemia in the newborn is initially labelled as TAM. TAM is characterised by an uncontrolled proliferation of blast cells that regress spontaneously over weeks and months. However, in 25 to 30 percent of cases TAM will persist, in which case a diagnosis of congenital acute leukaemia will be made. Approximately 25 percent of cases with TAM will go on to develop acute megakaryoblastic leukaemia by the age of three years. Leukaemia associated with Down syndrome is often preceded by a myelodysplastic-like syndrome, as is the case in this patient. Most children with Down syndrome and acute myeloid leukaemia have an abnormal karyotype, most commonly trisomy 8 or less commonly trisomy 1 and 19 or tetrasomy 21. As the absolute blast cell count on this infant was extremely high, chemotherapy was commenced. Low-dose of cytarabine therapy was administered. The infant responded well initially…

A case of Burkitt cell leukaemia in a sixteen year old male

A 16-year-old male presented to the paediatric casualty department with a mass on the left-hand side of his face. He was otherwise feeling well. A full blood count was performed with the following results: Hb 107 g/L, WBC 10.2 x 109/L and platelet count 53 x 109/L. The blood film showed a leucoerythroblastic blood picture with 2% myelocytes, 54% blasts and 2 NRBC’s / 100 WBC’s. The red cells showed the presence of teardrop poikilocytes. A bone marrow biopsy was performed. It was hypercellular with 80% blast cells. The blasts were medium in size, containing round nuclei with a fine chromatin pattern and nucleoli. The cytoplasm was deeply basophilic and contained many lipid-containing vacuoles. Flow cytometry and cytogenetics were performed on the bone marrow sample with the following results: Immunophenotype: TdT-, HLA-DR-, SIg+, CD5-, CD10+, CD19+, CD20+, CD22+, CD23- and CD34- Cytogenetics: t(8;14)(q24;q32). A diagnosis of Burkitt cell leukaemia was made on this young male. Burkitt lymphoma/leukaemia is classified under

mature B-cell neoplasms by the World Health Organization (WHO). Burkitt lymphoma is a highly aggressive lymphoma, often occurring at extra-nodal sites. It is referred to as Burkitt cell leukaemia when the bone marrow is involved. There are three clinical variants of Burkitt cell lymphoma: Endemic Burkitt cell lymphoma: this variant occurs in equatorial Africa and Papua New Guinea. It is the most common malignancy of childhood occurring in children between the age of four and seven years. Sporadic Burkitt lymphoma: this variant occurs throughout the world. Occurring mainly in children and young adults, it is associated with the Epstein Barr virus (EBV). Immunodeficiency associated Burkitt lymphoma: this variant is primarily associated with the human immunodeficiency virus (HIV). Clinical presentation: The clinical presentation varies according to the particular variant. The majority of patients with the sporadic variant present with an abdominal mass while those with the immunodeficiency associated variant present with nodal and bone marrow involvement. All three variants may be…