W5 - Haematology in systemic disease Flashcards
What are the differences between primary and secondary haematological disorders?
Primary = disease within blood/BM
Secondary = non-haematological disease elsewhere, having affect on BM/blood
What is the cause of primary haematological disorders?
mostly all due to DNA mutations which could be:
a) germline/inherited
b) somatic/acquired
What do these germline mutations cause?
- Factor IX deficiency
- Factor IX excess
- B globin chain deficiency
- VHL gene mutation
- Factor IX deficiency => haemophilia B
- Factor IX excess => F IX pauda
- B globin chain deficiency => B thalassaemia
- VHL gene mutation => excess RBC => Chuvash Polycythaemia
What primary haematology disorders do JAK and BCR-ABL1 somatic mutations lead to?
- JAK mutations => excess RBCs => polycythaemia vera
- BCR-ABL1 => excess myeloid/granulocytes => CML
Which secondary haematological disorders does each of the below cause?
1) cyanotic heart disease
2) anti-RBC abs
3) Anti-FVIII auto-abs
- Cyanotic heart disease => hypoxia => excess RBCs
- Anti-RBC abs => immune-mediated haemolysis => reduced RBCs
- Anti-FVIII auto-abs (acquired haemophilia A) => deficiency in FVIII
What are typical laboratory findings of FBC suggestive of iron deficiency?
- microcytic RBCs
- reduced ferritin
- reduced transferrin saturation
- raised TIBC
- blood film: microcytic, hypochromic cells
Iron deficiency equates __________ until proven otherwise.
BLEEDING
2 cancerous causes of occult blood loss
- GI cancers (Gastric, colonic/rectal)
- Urinary tract cancers (RCC, bladder cancer)
Leuco-erythroblastic anaemia - 5 morphological features in blood film?
- Teardrop RBCs
- Anisocytosis (diff sizes)
- Poikilocytosis (diff shapes)
- Nucleated RBCs
- Immature myeloid cells
Causes of Leuco-erythroblastic film?
BM infiltration:
- malignant
- Haematopoietic: leukaemia/lymphoma/myeloma
- Non-haematopoietic: metastatic breast/bronchus/prostate - Myelofibrosis:
- Massive splenomegaly
- Dry tap on BM aspirate - Severe infection (rare):
- miliary TB
- Severe fungal infection
Common laboratory findings (5) of all haemolytic anaemias?
- anaemia
- reticulocytosis
- unconjugated bilirubin raised
- LDH raised
- haptoglobins reduced
Haemolytic anaemias can be _____ or _____
Inherited (primary)
Acquired (secondary)
Name 3 groups of inherited haemolytic anaemias
- Membrane - i.e., hereditary spherocytosis
- Cytoplasm/enzymes - i.e., G6PD deficiency
- Haemoglobin - i.e., Sickle cell disease, thalassaemia
Name acquired (2) haemolytic anaemias
- Non-immune (DAT -ve)
- Immune mediated (DAT aka Coombs test +ve)
What laboratory findings confirm immune-mediated haemolytic anaemia?
- Spherocytes
- RBC fragments
- DAT/Coombs test POSITIVE
What conditions (6ish) are associated with immune-mediated haemolytic anaemia?
Systemic diseases:
- malignancy: lymphoma, CLL
- autoimmune: SLE
- infection: mycoplasma
- idiopathic
What conditions (2) is non-immune mediated haemolytic anaemia associated with?
- Infection:
- malaria - Micro-angiopathic haemolytic anaemia (MAHA):
- Underlying adenocarcinoma
- HUS (haemolytic uraemic syndrome)
What are the blood film features of MAHA?
- RBC fragments (haemolysis)
- Thrombocytopaenia
Describe pathophysiology behind micro-angiopathy due to malignancy
Causes low grade DIC
- Platelet activation
- Fibrin deposition + degradation
- RBC fragmentation (microangiopathy)
- Bleeding (due to low platelets + coagulation factor deficiency)
Female 39, lymphoma stage 4 involving LNs, BM, liver.
Recent onset jaundice, hepatomegaly, 1 week history of SOB
- bloods:
Hb 87 g/L
MCV 102 fl
reticulocyte 190x10^ 9/L (20-92)
bilirubin 50 micromol/L
blood film: anaemia, spherocytes
The likely explanation for this anaemia is:
- iron deficiency
- anaemia of chronic disease
- leuco-erythroblastic anaemia
- MAHA
- autoimmune-haemolytic anaemia
- autoimmune-haemolytic anaemia
spherocytes => haemolysis => not congenital, therefore inherited autoimmune
Female 39 treated breast cancer 4 years previously
Recent onset jaundice, hepatomegaly
- bloods:
Hb 87 g/L
reticulocytes 15x10^9/L (20-92)
bilirubin 50 micromol/L conjugated
DAT -
The likely explanation for this anaemia is:
- iron deficiency
- anaemia of chronic disease
- leuco-erythroblastic anaemia
- MAHA
- autoimmune-haemolytic anaemia
The reticulocyte is DOWN – so this is infiltration of the BM and its not making enough RBC = leuco-erythroblastic anaemia
What are the two main categories of eosinophilia?
- Reactive eosinophilia
- Chronic eosinophilic leukaemia
What are the causes (4) of reactive eosinophilia?
- parasitic infections
- allergic diseases, i.e. asthma, RA, polyarteritis, pulmonary eosinophilia
- underlying neoplasm, i.e. Hodgkin’s, T cell NHL
- Drugs, i.e. reaction erythema multiforme
Name underlying causes (4) of monocytosis
- Bacterial: TB, brucella typhoid
- Viral: CMV, varicella zoster
- Sarcoidosis
- Chronic myelomonocytic leukaemia (MDS)
In lymphocytosis, what do mature lymphocytes in the peripheral blood film indicate the cause is?
- Reactive/atypical lymphocytosis
- if small lymphocytes + smear cells => CHRONIC LYMPHOID LEUKAEMIA (CLL) or Non-Hogkin’s lymphoma (NHL)
In lymphocytosis, what do immature lymphocytes in the peripheral blood film indicate the cause is?
Lymphoblasts => Acute lymphoblastic leukaemia (ALL)
In B Cell lymphocytosis, determine the importance of clonality (light chain test)
Polyclonal: kappa to lambda 60:40 ratio = REACTIVE lymphocytosis
Monoclonal: kappa or lambda ONLY (99:1 ratio) = lymphoid malignancy
Describe what the cells look like in chronic myeloproliferative neoplasm
Increased proliferation with normal differentiation = lots of mature myeloid cells
Describe the blood cell pathology in acute myeloid leukaemia (AML)
Increased proliferation with blocked differentiation = lots of immature precursor cells
Describe the 3 possible cell development issues arising from acquired somatic mutations that cause leukaemias/lymphomas
- Excess proliferation
- Impaired/blocked differentiation
- Prolonged cell survival (anti-apoptosis)
Cancer of B cell precursor is ________
Cancer of mantle zone B cell is ________
Cancer of plasma cell is __________
- B cell Acute lymphoblastic lymphoma
- Mantle cell lymphoma
- Multiple myeloma
Philadelphia chromosome is associated with ______
CML
Describe the immunophenotype of B cell ALL vs MM
B cell ALL:
- TdT +
- CD19 +
- surface Ig –
MM:
- TdT –
- CD138 +
- surface Ig +
What are the associated symptoms of lympho-haemopoietic failure –>
- BM failure?
- Immune system failure?
BM => anaemia, infections (neutrophils), bleeding (platelets)
Immune system => recurrent infections
What is one major complication of polycythemia?
Increased RBCs => increased viscosity => impaired blood flow => stroke or TIA
What is one major complication of lymphomas?
Massively enlarged LNs => compress structures, bowels, vena cava, ureters, bronchus
Describe some haematological tests for
A) morphology
B) immunophenotype
C) cytogenetics
D) molecular genetics
A) morphology => blood film, cytology, cytochemistry
B) immunophenotype => flow cytometry, immunohistochemistry
C) cytogenetics => conventional karyotyping, fluorescent in-situ hybridisation (interphase FISH, metaphase FISH)
D) molecular genetics => PCR, mutation detection (direct sequencing), gene expression profiling, whole genome sequencing
