What is the most common single malignancy in childhood?
What are the presenting complaints of ALL
Malaise Weightloss Fever Myalgia,arthralgia Lymphadenopathy Hepatosplenomegaly Anaemia,thrombocytopenia Leucopenia or leucocytosis
The aetiology of ALL is unclear but in the pathogenisis of ALL what two events are crucial?
Loss of control of proliferation
What are the most common side effects of cyclophosphamide?
Haemorrhagic cystitis Myelosuppression Alopecia Anorexia Nasal congestion
What is used to reduce the incidence of haemorrhagic cystitis when giving cyclophosphamide?
Cyclophosphamide end product is acrolein which is toxic to the bladder. Concurrent administration of "Mesna" inactivates acrolein in the urine.
What are the common side effects of dactinomycin?
Myelospression Nausea Vomiting Oral mucositis Oesophagitis Pharyngitis Diarrhoea Fever Malaise Myalgia Alopecia Acne Rash
What is the core drug used in ALL maintenance therapy?
What are the side effects of mercaptopurine?
Myelosuppression Hepatotoxicity N&V Mucusitis Rash Diarrhoea Hypoglycaemia
What are the three mechanisms which cause acute renal failure after a transfusion reaction?
Renal vasoconstriction caused by toxic substance released from haemolysed blood.
Circulatory shock from loss of circulating blood cells
Renal tubular blockage from haemoglobin precipitation in the renal tubules.
What is this cell and what does it indicate?
Note "owls eye" appearance
Pathognomonic of Hodgkins Lymphoma.
It is the malignant cell.
Outline the Ann Arbor staging system with Cotswald modification adapted for NHL.
- single lymph node region (stage I)
- single extralymphatic organ or site (stage IE)
- two or more involved lymph node regions on the same side of the diaphragm (stage II)
- localized involvement of an extralymphatic organ or site (stage IIE).
- lymph node involvement on both sides of the diaphragm (stage III),
- localized involvement of an extralymphatic organ or site (stage IIIE) or spleen (stage IIIS), or both (stage IIIES).
- diffuse or disseminated involvement of one or more extralymphatic organs (eg, liver, bone marrow, lung), with or without associated lymph node involvement.
The presence or absence of systemic symptoms should be noted with each stage designation. (A = asymptomatic; B = presence of fever (>38 degrees C), sweats, or weight loss >10 percent of body weight over six months.)
The acute lymphoblastic form of NHL is derived from the same T-and B-lineage lymphoid cells as ALL.
What is the difference in pre-B-cell and T-cell derivation?
In ALL, 80% are pre-B-cell derived and 20% T-cell derived.
The reverse is true of NHL.
In an otherwise well toddler with significant nutritional iron deficiency anaemia, what is the expected time interval between commencing iron therapy and a reticulocytosis becoming evident on a blood film?
A. 3 days.
B. 7 days.
C. 14 days.
D. 30 days.
E. 60 days.
A. 3 days.
What is cold agglutin disease?
Usually IgM antibodies (rarely IgG or IgA) directed against polysaccharides antigens on RBCs. Binding of antibodies activates the classical pathway of the complement cascade.
On exposure to cold, RBC destruction due to cold agglutins - haemolytic anaemia.
Regularly occurs with M. Pneumoniae and Infectious Mononucleosis. Can occur with lymphoma.
Detected by direct Coombs test.
Treatment - avoid cold, rutiximab (monoclonal anti CD 20 antibody), plasmapheresis (if severe or for surgery)
What are warm agglutins?
IgG antibodies that react with protein antigens on RBCs at body temperature.
Can be due to viral infxn, autoimmune disease, immune deficiency, immune system malignancies,
Diagnosis by anitigen or complement on RBC with direct Coombs test.
Treatment best with corticosteroids, splenectomy if poor response.
Prothrombin Time (PT) looks at what pathway and what factors?
Factors VII, V, X, II
aPTT looks at what pathway and what factors?
Factors VIII, IX, XI, XII
What is tran examic acid used for?
Anti-fibrinolytic - prevents breakdown of clot.
Used in pts with Haemophilia esp if dental surgery etc.
Works best in mouth, nose and bladder.
What is main drug used in treatment of bleeding disorders?
DDAVP - desmopressin
Describe Fanconi Anaemia
Autosomal recessive or X-linked
30% phenotypically normal
Hypopigmented spots and café-au-lait spots
Abnormality of thumbs
Microcephaly or hydrocephaly
Median age 7 yrs
May take years to develop haematological signs
diagnosis by lymphocyte stress test
- Short stature
- Hypopigmented spots and café-au-lait spots
- Abnormality of thumbs
- Microcephaly or hydrocephaly
- Developmental delay
What is Schwachman-Diamond syndrome?
Presents in infancy with exocrine pancreatic dysfunction and bone marrow failure.
Rare autosomal recessive
Other clinical manifestations:
- skeletal abnormalities
- short stature
- increased risk for myelodysplasia/AML
Management is directed at specific manifestations.
Altered state of haemaglobin where ferrous (fe2+) ions of heme are oxidised to ferric (3+) form. Ferric hemes of methaemoglobin are unable to bind oxygen.
The oxygen affinity of remainder of hemes in tetramer is increased to oxygen delivery to tissues is decreased.
Can be genetic or due to toxins
- Cyanosis in presence of normal pO2 on gas
Deficiencies in what factors will not affect PT?
VIII, IX, XI, XII
Normal adult Hb HbA consists of
2 alpha + 2 beta chains
2 alpha and 2 delta chains
2 alpha and 2 gamma chains
2 alpha + 2 beta chains
2 alpha and 2 delta chains
2 alpha and 2 gamma chains
What do you expect to see in alpha and beta thalassemia?
Alpha thalassaemia trait
mild microcytic anaemia, diagnosis of exclusion unless specific genetic testing is obtained.
Beta thalassaemia major
severe anaemia, usually during the first year of life
absence or reduction in HbA relative to HbF on electrophoresis
Beta thalassaemia trait
increased levels of HbA2 or HbF on electrophoresis.
Iron deficiency can mask the diagnosis by lowering the levels of HbA2,
with iron replacement HbA2 levels will rise to the usual elevated levels.
- mild microcytic anaemia, diagnosis of exclusion unless specific genetic testing is obtained.
- severe anaemia, usually during the first year of life
- absence or reduction in HbA relative to HbF on electrophoresis
- increased levels of HbA2 or HbF on electrophoresis.
- Iron deficiency can mask the diagnosis by lowering the levels of HbA2,
- with iron replacement HbA2 levels will rise to the usual elevated levels.
What test do you do to confirm Hereditary spherocytosis?
Osmotic Fragility Test
Exposure to hypotonic saline causes RBCs to swell and the spherocytes lyse more readily than normal biconcave cells. This test is not specific for hereditary spherocytosis as may be abnormal in immune and other haemolytic anaemias and may be normal in up to 10- 20% of patients with hereditary spherocytosis
What is most likely to precipitate in renal tubules in tumour lysis syndrome?
What is ifosfamide known to cause?
Long term renal dysfunction
Fanconi syndrome (generalised dysfunction of prox tubule)
What is cryoprecipitate used for?
Cryoprecipitate contains concentrated factor VIII and fibrinogen. Its main use is for the replacement of fibrinogen in disseminated intravascular coagulation (DIC), massive transfusion or hepatic failure.
Anaemic pt with abdo pain and recent use of trimethoprim-sulfamethoxazole. Blood film below.
G6PD deficiency leads to two syndromes;
- episodic haemolytic anaemia, and
- chronic non-spherocytic haemolytic anaemia.
- Inducers include fava beans, infections and drugs such as Trimethoprim-sulfamethoxazole.
- Acute haemolysis is noted by marked drop in haemoglobin and haematocrit.
- Haemolysis evident on the blood film. Bite cells are visible, representing reticulocytosis.
- Diagnosis is by G6PD activity. Prevention of haemolysis involves avoidance of inducers. Supportive treatment is removal of inducing agent +/- blood transfusions.
What is Kasabach-Merit syndrome?
Kasabach-Merritt syndrome is a form of haemangioma that is rapidly enlarging, associated with a thrombocytopenia.
Microangiopathic haemolysis +/- haemorrhage due to severe anaemia can occur.
The marrow consists of immature megakaryocytes.
D-dimer elevation is non-specific, but occurs in DIC or acute deep vein thrombosis.
Haemangiomas most commonly present in the first two months of life.
What test is used to dx Fanconi Anaemia?
Chromosomal breakage analysis (a
high percentage of patients with Fanconi anaemia will have chromosomal breaks, gap or rearrangements in studies of peripheral blood lymphocytes).
Molecular Diagnosis can confirm the condition and also may be used to test relatives.
aPTT may be prolonged due to a factor deficiency or phospholipid antibody (i.e. lupus). How can you distinguish the difference with a prolonged aPTT?
50:50 correction test.
If the aPTT is still prolonged it is due to antibody, not factor deficiency.
50:50 correction test is when patients plasma is mixed in equal portions with normal plasma. This would correct for a factor deficiency.
Deficiencies in which factors will not be detected by the aPTT test?
VII and XIII
Normal PTT times require the presence of the following coagulation factors: I, II, V, VIII, IX, X, XI, & XII.