Haematological Disease Flashcards
Immune Thrombocytopaenic Purpura physiology
immune-mediated reduction in the platelet count. Antibodies are directed against the glycoprotein IIb/IIIa or Ib-V-IX complex. It is an example of a type II hypersensitivity reaction.
ITP in children is typically more acute than in adults and may follow an infection or vaccination.
ITP features
non-blanching petechial rash in a healthy child following a respiratory tract infection is a common scenario for ITP.
- bruising
- petechial or purpuric rash (pinpoint, erythematous)
- haematoma and subconjuctival haemorrhages
- bleeding is less common and typically presents as epistaxis or gingival bleeding
Ix for ITP
-
full blood count
- should demonstrate an isolated thrombocytopenia
- blood film
-
bone marrow examinations is only required if there are atypical features e.g.
- lymph node enlargement/splenomegaly, high/low white cells
- failure to resolve/respond to treatment
Mx for ITP
acute, benign, self-limiting (6-8 wks), manage at home → avoid activities that may result in trauma
life- or organ-threatening bleeding = IVIG + oral/IV corticosteroid + plt transfusion + antifibrinolytics (aminocaproic + tranexamic acid)
major bleeding = IVIG (OR anti-D Ig) + corticosteroid
Chronic disease
- mycophenolate mofeil
- rituximab
- eltrombopag (TPO receptor agonist)
- 2nd line: splenectomy (if persistent)
ALL epidemiology and explanation
80% of childhood leukaemias
2-5 years peak incidence
boys > girls
- Blood cells in the body are made by the bone marrow – a spongy material inside the bone.*
- The bone marrow makes special cells called stem cells, which can become red cells, white cells and platelets.*
- Normally, these stem cells aren’t released into the blood until they are fully developed.*
- In ALL, large numbers of these white cells are released before they are ready (blast cells). As the number of blast cells increases, the number of red cells and platelets decreases, leading to symptoms.*
- Blast cells are also less effective at fighting bacteria and viruses which leaves you more vulnerable to infections.*
ALL features and RFs
Bone marrow failure:
- anaemia = lethargy, pallor
- neutropenia = frequent/severe infections
- thrombocytopenia = easy bruising, petechiae
Other features:
- bone pain (2o to BM infiltration)
- reticula-endothelial infiltration = hepatosplenomegaly
- fever 50% cases (infection/constitutional symptom)
- organ infiltration → CNS → headache, nausea, vomiting, nerve palsies, testicular enlargement
RF = previous chemo, smoking, overweight, genetic disorders, decreased immunity
ALL Ix’s
FBC → decreased Hb, thrombocytopenia, leukaemia blast cells, increased LDH
clotting → +/- DIC
LFTs + U+Es → check renal function before chemo
CXR → to identify mediastinal massess
BM aspiration + biopsy = ESSENTIAL TO CONFIRM DIAGNOSIS
- >20% blasts in BM/peripheral blood
- ID immunological and cryogenic characteristics to given prognostic information → identify translocations
Immunological phenotyping → further sub classify
Poor prognostic factors for ALL
- age < 2 years or > 10 years
- WBC > 20 * 109/l at diagnosis
- T or B cell surface markers
- non-Caucasian
- male sex
Mx of ALL: induction
Very aggressive condition, develops rapidly, needs treatment ASAP
NICE →refer any child with unexplained petechiae or hepatosplenomegaly for immediate specialist assessment
Urgent FBC if = pallor, unexplained fever, generalised lymphadenopathy, unexplained bruising, persistent bone pain, unexplained bleeding
Induction
Inpatient = hospital/specialist centre
Supportive care
- fluid = UO 100ml/hour
- Blood transfusion (bleeding, low platelet count) = eliminate more than 99% leukaemia cells, restore normal haemostasis, correct anaemia and previous performance status
- prophylactic abx, antifungals, antivirals
- prophylactic haematopoietic GFs (e.g. CSF filgrastim) in those at risk of febrile neutrophaenia
- allopurinol/rasburicase = prevent tumour lysis syndrome
- norethisterone = female patients to suppress periods during theroapy and periods of thrombocytopenia
ALL mx NO CNS disease vs CNS involvement
NO CNS disease
Induction chemotherapy
- vincristine, anthracyclines (doxorubicin, daunorubicin), prednisolone
- dexrazone (prevent cardio toxicity from doxorubicin)
- rituximab (if CD20+ ALL)
- TKI (imatinib) for Philadelphia Chr+ patients
CNS involvement
- cytotoxic drugs penetrate poorly into CNS
- standard induction therapy WITH intensified intrathecal therapy
- intrathecal methotrexate (+ cytarabine and hydrocortisone) aka triple
- consolidation = high dose cytarabine (HDAC) or high dose methotrexate (HDM) to ensure good BB penetration
Mx of ALL: consolidation and maintenance therapy, prognosis and support
outpatient (months)
- remission = leukaemia blasts eradicated and normal marrow function restored
- remission rates 95%
- continuing chemotherapy`of moderate-high intensity usually continued for relatively long time (up to 3 years)
relapse, refractory or residual disease
- high dose chemotherapy, w/wo total body irradiation followed by BM transplantation, is used as an alternative to conventional chemotherapy after a relapse
Febrile neutropenia/
