Cytopenia and Approach to Anaemia Flashcards
General pathogenesis of cytopenias and anaemia
Decreased production (BM) or Increased destruction (RE system, shortened RBC life-span)
Cytopenia: types
Isolated cytopenia (anaemia, leucopenia, thrombocytopenia) - neutropenia <2.5 = significant; <1 = risk of infection; <0.5 = recurrent infections; <0.2 = serious fatal infections
Pancytopenia: Bilineage or trilineage (more likely global cause affecting BM)
Anaemia: signs and symptoms, approach to management
Low RBC and Hb
==> decrease O2 carrying capacity and tissue hypoxia
Symptoms
- SOB, fatigue, weakness, decreased exercise tolerance, palpitation, angina, headache, visual disturbances
Signs
- pallor, hyperdynamic circulation (bounding pulse, tachycardia)
- cardiomegaly: CHF
Approach to anaemia: Aetiology + Need for transfusion
- Can classify based on causes
- -> failed RBC production vs loss/destruction of RBC
- Can classify based on red cell indices
Expected blood picture for failed RBC production vs destruction of RBC in anaemia
Production problem
- low or normal reticulocytes
Destruction e.g. HA
- reticulocytosis
- -> BM production reserve can increase by 6x ==> responding BM increases erythropoiesis to compensate for peripheral destruction ==> young RBC spills into PB
Classification of anaemia based on red cell indices
Microcytic (<80), hypochromic (central pallor >1/2) anaemia
- Fe deficiency
- Thalassemia
- Chronic disease (some cases)
- Lead poisoning (inhibits Hb synthesis)
Normochromic normocytic
- Chronic disease (inflammation e.g. TB, IE, SLE, RA, Crohn’s; malignancy)
- acute blood loss
- mixed deficiencies e.g. Fe and B12
- HA (sometimes reticulocytosis causes high MCV)
Macrocytic
- megaloblastic
- non-megaloblastic
Differentiating causes of microcytic hypochromic anaemia
Iron profile
Fe deficiency
- Ferritin very low, Fe low, TIBC high, % saturation low
- further Ix: GI workup for occult bleed
Thalassemia
- profile normal or some parameters increased
- further Ix: Hb pattern, family counselling
Chronic disease (defective release of Fe from macrophages)
- Ferritin high/N, Fe low, TIBC low, % saturation low
- Further Ix: underlying disease
Sideroblastic (rare; failed protoporphyrin synthesis)
- all increase, TIBC normal
- further Ix: BM and underlying cause
Bone marrow failure syndrome - causes
Pancytopenia: decrease in RBC, WBC, Plt and reticulocytopenia
Production problem
- primary: aplastic anaemia (fat), acute leukaemia (blast), myelofibrosis (fibroblast), MDS (immature cells), cytotoxic therapy
- secondary: BM infiltration by carcinoma, granuloma, lymphoma, myeloma etc
Mixed production and destruction problems (more often isolated cytopenia or bilineage)
- autoimmune diseases – e.g. SLE (attack mature red cells)
- paroxysmal nocturnal haemoglobinuria – increased complement sensitivity leading to lysis
Increased destruction (isolated cytopenia/bilineage) - hypersplenism -- splenic pooling = increased time for RE destruction
Aplastic Anaemia: characteristic features, pathogenesis, causes
HYPOPLASTIC BM
PANCYTOPENIA
Pathogenesis: substantial reduction in pluripotent stem cells due to defects or immune reaction –> inability to divide and populate BM
Primary causes
- congenital (Fanconi’s anaemia)
- acquired (idiopathic)
Secondary causes
- industrial (insecticides)
- post-viral infection
- iatrogenic (cytotoxics)
- hypersensitivity (chloramphenicol, gold)
Diagnosis of Aplastic Anaemia
- CBC
- pancytopenia (production problem) - Peripheral smear
- no abnormal cells - BM study (BIOPSY IS MANDATORY)
- hypocellularity
Fanconi’s Anaemia: inheritance, manifestations, prognosis, diagnosis, treatment
Inheritance: recessive
Manifestations
- growth retardation, congenital defects of skeleton (microcephaly, absent radi or thumbs)
- renal tract defect – horseshoe kidney
- skin hypo/hyperpigmentation
- mental retardation
10% develop AML
Diagnosis: increased random chromosomal breaks (chromosomal stress test to elicit DNA repair pathway defect)
Treatment: androgens (support haemopoiesis) +/- HSCT
Acquired aplastic anaemia: likely pathogenesis, causes, treatment
Likely autoimmune origin (T cells suppress stem cells)
Causes
- ionising radiation, chemicals (benzene, insecticides), cytotoxics, chloramphenicol, post viral infections e.g. HAV
Treatment
- ATG and cyclosporin (immunomodulation of T cell effects), HD methylprednisolone,
- aandrogens, HSCT
Myelofibrosis: causes, blood smear picture
Primary: malignancy
Secondary: response to marrow infiltration and irritation
–> BM failure
Blood smear:
- leucoerythroblastic blood picture with blasts, nucleated RBC and myelocytes suggesting BM irritation
- tear drop cells
Approach to pancytopenia
ALWAYS NEED BM TREPHINE BIOPSY AND ASPIRATION to evaluate production status and possibility of:
- aplastic anaemia (cellularity)
- acute leukaemia (immunophenotyping)
- infiltration (special stains e.g. cytokeratin for CA, ZN stain)
Isolated cytopenias due to decreased production - causes
Pure red cell aplasia (WBC normal)
- congenital (Diamond-Blackfan syndrome) or acquired (parvovirus B19, AI disease, thymoma/lymphoma)
Pure amegakaryocytic thrombocytopenia
- acquired (pre-MDS - not full blown leukaemia yet or AML)
Agranulocytosis
- HSR with selective damage of granulocytic precursors by drugs e.g. anti-thyroid, anticonvulsants, gold
Lymphopenia
- AIDS, congenital immunodeficiency syndrome, B/T cell deficiency
Monocytopenia
- hairy cell leukaemia
Neutropenia
- chemotherapy, drugs (gold, chloramphenicol), immune (SLE), infection (HIV, MTB), congenital
Isolated cytopenias due to increased destruction - causes
Immune destruction
- autoimmune or alloimmune
- RBC (common) –> HA
- WBC –> Neutropenia
- Plt (common in children) –> ITP
Mechanical destruction: heart valves (RBCs)
Infection: malaria, typhoid fever (WBCs)
Drug induced
