Haem - Haematological Changes in systemic disease Flashcards
What is the difference in cause of blood cancers and soluble factor disorders
Blood cancers: acquired somatic mutations
Soluble factors: germline mutations (cells that produce the factors do not have as rapid a turnover rate e.g.hepatocytes, endothelial cells)
Give examples of primary inherited disorders of the blood
FIX deficiency: haemophilia B
FIX excess: FIX padua
Erythrocyte deficiency: HbS
Erythrocyte excess: polycythaemia
Give examples of primary acquired disorders of the blood
Erythrocyte excess: JAK2 → polcythaemia vera
Erythrocyte deficiency: PIG A → PNH paroxysmal nocturnal haemoglobinuria
Give examples of secondary disorders of the blood involving the following: FVIII, erythrocytes, platelets, leucocytes
FVIII excess: inflammatory response/pregnancy
FVIII deficiency: anti-VFIII auto-antibodies (acquired haemophilia A)
Erythrocyte excess: Raised altitude, EPO secreting tumour
Erythrocyte deficiency: vitamin B12/folate deficiency, haemolytic anaemia
Platelet excess: bleeding, splenectomy, inflammation
Platelets low: vitamin B12/folate deficiency, ITP, TTP
Leucocyte excess: infection, inflammation, steroid use
Leucocytes low: BM infiltration, vitamin B12/folate deficiency
What is often the first sign of systemic disease in the blood and give examples where this might be the case
Anaemia
Folate deficiency and Howell Jolly bodies → Coeliac
Fe deficiency → after delivery - PPH
Leucoerythroblastic anaemia → leukaemia
Haemolytic anaemia → immune haemolytic anaemia
What are the laboratory findings in iron deficiency anaemia
Microcytic hypochromic anaemia
Reduced ferritin, transferrin saturation
Raised TIBC
What are the causes of iron deficiency anaemia
Blood loss
GI: Peptic ulcer or gastric cancer, IBD,Colonic cancer
Urinary tract: Renal cell carcinoma, Bladder cancer
What are the morphological features of leuco-erythroblastic anaemia
Teardrop RBCs (+Aniso and poikilocytosis)
Nucleated RBCs (should not leave the bone marrow)
Immature myeloid cells/myelocytes (should not leave the bone marrow)
What does leuco-erythroblastic leukaemia imply
Implies bone marrow infiltration
Haemopoietic malignancy: leukaemia, lymphoma myeloma
Metastatic malignancy: breast, bronchus, prostate
Myelofibrosis
Severe infection: miliary TB, severe fungal infectin
What are the types of haemolytic anaemia
Acquired:
- Immune mediated
- Non-immune mediated
Inherited
- membrane disorders
- cytoplasm/enzyme disorders
- Hb disorders
What are the laboratory findings in haemolytic anaemia
Anaemia (though may be compensated)
Reticulocytosis (may cause modest elevation of MCV )
Bilirubinaemia (unconjugated/pre-hepatic cause)
LDH raised
Haptoglobins reduced
What is the most common group of acquired haemolytic anaemias
Immune haemolytic anaemia
What are the causes of immune haemolytic anaemia
Lymphoma, chronic lymphocytic leukaemia
Auto-immune: SLE
Infection e.g. mycoplasma
Idiopathic
What are the laboratory features of immune haemolytic anaemia
Spherocytes
Positive Coombs DAT (direct antiglobulin test)
Anaemia (though may be compensated)
Reticulocytosis (may cause modest elevation of MCV )
Bilirubinaemia (unconjugated/pre-hepatic cause)
LDH raised
Haptoglobins reduced
What are the causes of non-immune haemolytic anaemia
Micro-angiopathic haemolytic anaemia (MAHA):
Underlying adenocarcinoma
Haemolytic uraemic syndrome
Low grade DIC
What are the laboratory features of non-immune haemolytic anaemia
RBC fragments
Thrombocytopenia
Anaemia (though may be compensated)
Reticulocytosis (may cause modest elevation of MCV )
Bilirubinaemia (unconjugated/pre-hepatic cause)
LDH raised
Haptoglobins reduced
Describe the pathogenesis of Micro-angiopathic haemolytic anaemia (MAHA)
- Inappropriate/unfocussed activation of coagulation
- Platelets are activated and they adhere to the vessel wall
- Platelets deposit fibrin, which degrades
- Red cells become fragmented as they pass through (microangiopathy)
- Leads to bleeding with low platelets and coagulation factor consumption
What cells are found in the bone marrow
- Blasts (myeloid and lymphoid) (<5% of BM cells)
- Promyelocytes
- Myelocytes
What are the causes of neutrophilia
Pyogenic infection: steroids, underlying neoplasia, tissue inflammation (colitis, pancreatitis, myocarditis, MI)
Reactive neutrophilia i.e. to infection
Malignancy
What is the difference in appearance of the blood/neutrophils in reactive neutrophilia and malignant neutrophilia
Reactive: heavy toxic granulation, vacuoles seen, no immature cells
Malignant:
- CML: neutrophilia + basophilia + myelocytes
- AML: neutrophilia + myeloblasts
What are the causes of eosinophilia (reactive and chronic)
Reactive eosinophilia
- Parasitic infestation
- Allergic diseases e.g. asthma, rheumatoid, polyarteritis, pulmonary eosinophilia.
- Neoplasms, esp. Hodgkin’s, T-cell NHL (reactive eosinophilia)
- Drugs (reaction erythema multiforme)
Chronic eosinophilic leukaemia (Malignant)
- Eosinophils part of the “clone”
- FIP1L1-PDGFRa Fusion gene
What are the causes of monocytosis
Chronic infections and primary haematological disorders:
TB, brucella, typhoid
Viral; CMV, varicella zoster
sarcoidosis
chronic myelomonocytic leukaemia (MDS)
What are the causes of lymphocytosis
EBV, CMV, Toxoplasma (Infectious mononucleosis IM)
infectious hepatitis, rubella, herpes infections
autoimmune disorders
Sarcoidosis
What are the causes of lymphopenia
Untreated infection HIV
Auto immune disorders
Inherited immune deficiency syndromes
Drugs (chemotherapy)
What does the morphology of lymphocytes tell you in lymphocytosis
Mature lymphocytes (PB)
- reactive/atypical lymphocytes (IM)
- small lymphocytes and smear cells (CLL/NHL)
Immature Lymphoid cells in PB
- Lymphoblasts; Acute Lymphoblastic Leukaemia (ALL)
Describe immunophenotyping of B cell lymphocytosis
Mature B cells express Immunoglobulin (usually IgM or IgG). The light chains will be either kappa or lambda expressing
- Polyclonal = kappa and lambda (reactive)
- Monoclonal = kappa ONLY or lambda ONLY (malignant)
What can mutations in tyrosine kinase cause and give an example
Excess proliferation (but no effect on differentiation)
BCR ABL → CML
JAK2 → MPD
What can mutations in nuclear transcription factors cause and give an example
Blocks differentiation
May cause acute leukaemia in conjunction with a proliferation mutation
PML RARA → acute promyelocytic leukaemia
What may mutations in apoptosis genes cause and give an example
Lymphoma
BCL2 → follicular lymphoma
What should be assessed when diagnosing blood cancers
- Morphology (cytology, cytochemistry)
- Immunophenotype (flow cytometry, immunohistology)
- Cytogenetics
- Molecular genetics (PCR, pyro-sequencing)
What are the common blood cancer presentations or problems
Lympho-haemopoietic failure
- Bone marrow (myeloid): anaemia, bacterial infection (neutrophils) bleeding (platelets)
- Immune system (lymphoid): recurrent viral or fungal infection
Excess of malignant cells
- Erythrocytes or leucocytes: impair blood flow >stroke or TIA
- Massively enlarged lymph nodes (lymphoma)> compress hollow tubes: bowel, vena cava, ureters, bronchus.
Infiltrate and impair other organ function
- CNS lymphoma
- Skin lymphoma
- Kidney failure (light chain deposition from myeloma)
Miscellaneous problems e.g. hypercalcaemia, hypermetabolism
