Haematology - Haematology of systemic disease Flashcards
which anaemias can cancer present with?
- iron def
- anaemia of chronic disease
- leucoerythroblastic anaemia
- haemolytic anaemia
how could cancer cause a secondary polycythaemia?
- renal cell cancers and liver cancers can secrete EPO
what is the most common cause of iron def anaemia?
occult blood loss
- GI cancers (gastric, colon)
- Urinary tract cancers (renal cell carcinoma, bladder cancer)
Laboratory findings of iron def anaemia
- low ferritin
- low transferrin saturation
- high TIBC
what is leucoerythroblastic anaemia?
red and white cell precursor anaemia
what are the morphological features on blood film of leucoerythroblastic anaemia?
- teardrop red blood cells (aniso and poikilocytosis)
- nucleated RBCs (normally have no nucleus)
- immature myeloid cells
what tends to cause leucoerythroblastic anaemia?
bone marrow infiltration
causes of bone marrow infiltration and so leucoerythroblastic anaemia
- CANCER (haemopoietic = leukaemia/ lymphoma/ myeloma, non haemopoietic = breast/bronchus/prostate)
- SEVERE INFECTION (miliary TB, severe fungal infection)
- MYELOFIBROSIS (massive splenomegaly, dry tap on BM aspirate)
what is haemolytic anaemia?
shortened red cell survival
what are the distinguishing features of haemolytic anaemia?
- anaemia
- reticulocytosis
- raised unconjugated bilirubin
- raised LDH (intracellular enzyme, released when cells break down)
- reduced haptoglobins
what are the 2 main groups of haemolytic anaemia?
- inherited (defects of red cell)
- acquired (defects of the environment)
what are the inherited haemolytic anaemias?
- membrane: hereditary spherocytosis
- cytoplasm/enzymes: G6PD def
- haemoglobin: sickle cell disease, thalassemia
what are the acquired haemolytic anaemias?
- immune mediated
- non-immune mediated
what is the test to distinguish immune mediated and non-immune mediated haemolytic anaemia?
DAT or Coombs’ test
what does DAT +ve mean?
acquired haemolytic anaemia is mediated through immune destruction of RBCs
how can AI haemolytic anaemia appear on blood film?
formation of spherocytes
what systemic disorders is AI haemolytic anaemia associated with?
- cancers of immune system (lymphoma)
- disease of immune system (SLE)
- infection (disturbs immune system)
What is non-immune haemolytic anaemia?
red cell breakdown not caused by immune system
DAT negative
causes of non-immune haemolytic anaemia?
infection e.g. malaria
can be caused by microangiopathic haemolytic anaemia (MAHA)
what are the key features of MAHA?
- RBC fragments
- thrombocytopenia
- DIC/bleeding
- usually caused by underlying carcinoma
what is mechanism of MAHA?
- underlying carcinoma release lots of procoagulant cytokines
- activate coagulation cascade
- erratic cytokine release = DIC
- activation of coagulation cascade in parts of microvasculature = fibrin strands
- RBCs pushed through fibrin strands by BP
- causes RBCs to fragment
what is true polycythaemia? causes?
raised red cell mass
- polycythemia vera (PV)
- secondary (raised EPO)
What is PV?
clonal myeloproliferative disorder
acquired mutation in JAK 2
what can cause a secondary polycythaemia?
raised EPO
- appropriate (high altitude, hypoxic lung injury, cyanotic heart disease)
- inappropriate (hepatocellular carcinoma, bronchial carcinoma, renal cancer)
what are the normal mature white blood cells?
Phagocytes - granulocytes (neutrophils, eosinophils, basophils) - monocytes Immunocytes - T lymphocytes - B lymphocytes - NK cells
what are the immature WBCs and where should you find these?
- blasts
- promyelocytes
- myelocytes
- normal in BM not normal in peripheral blood
difference between acute and chronic leukaemia?
- mature white cells raised in CHRONIC
- immature blast cells raised in ACUTE
what are the causes of neutrophilia?
- corticosteroids (due to demargination)
- underlying neoplasia
- tissue inflammation (e.g. colitis, pancreatitis)
- myeloproliferative/leukaemia disorders
- infection
which diseases DO NOT cause a neutrophilia?
- brucella
- typhoid
- many viral infections
how would a reactive neutrophilia appear on blood smear?
- band cells (stage in neutrophil maturation, sign that bone marrow is releasing more WBCs)
- toxic granulation
- signs of infection/ inflammation
how does malignant neutrophilia appear?
- neutrophilia + basophilia + immature myelocytes + splenomegaly = myeloproliferative disorder (CML)
- neutrophilia + myeloblasts = AML
when do you see a monocytosis?
RARE seen in some chronic infections/ primary haematological disorders - TB, brucella, typhoid - Viral: CMV, VZV - Sarcoidosis - chronic myelomonocytic leukaemia
what causes a reactive eosinophilia?
- parasitic infection
- allergic diseases (e.g. asthma, RA)
- underlying neoplasma (Hodgkin’s, T cell lymphoma, NHL)
- drug reaction (e.g, erythema mutliforme)
how do you interpret a lymphocytosis?
- secondary (reactive): more common, response to infection/ chronic inflammation
- primary (monoclonal lymphoid proliferation e.g. CLL, NHL)
causes of a reactive lymphocytosis?
- infection (EBV, CMV, Rubella, Herpes)
- AI disorders
- Sarcoidosis
how is immunophenotyping carried out?
- monoclonal antibodies targeted at different antigens
- antibodies fluorescently labelled
- passed through flow cytometer
- can determine stage of maturation by antigens present
how can immunophenotyping be used to find lymphoproliferative disorders?
- raised lymphocyte count with even mix of kappa and lambda = reactive lymphocytosis
- lymphoproliferative disorders = overwhelming majority of either kappa or lamdba
