Haematological Changes in Systemic Disease Flashcards
What can cause haematological disorders?
Haemostasis & Thrombophilia: Altered function of soluble proteins e.g. FVIII deficiency, Protein C deficiency, Platelet function & interaction with endothelial surfaces
Haematological oncology: Primary abnormalities of white cell production
and differentiation, leukaemia lymphoma myeloma
Red cell disorders: Inherited (sickle cell, thalassaemia) acquired
Immune haematology: Autoimmune cytopenias
What can deficiencies cause?
Factor VIII: Haemophilia A
Factor IX: Haemophilia B
Protein C: Pro-thrombotic
Erythrocytes: anaemia
Lymphocytes: Lymphopenia (HIV)
Platelets: ITP
What can excesses cause?
Erythrocytes: Polycythaemia
Granulocytes: Leukaemia (CML), reactive eosinophilia
Lymphocytes: Leukaemia(CLL)
Platelets: Essential thrombocythemia
What are primary haematological disorders?
Primary disorders arise from DNA mutation(s)
What are some examples of primary haematological disorders?
Germline/inherited (gene mutated)
- FIX
- Erythrocytes e.g. beta Thalassaemia or Chuvash polycythaemia
Somatic/acquired (gene mutated)
- Erythrocytes e.g. JAK2 V617F: Polycythaemia vera
- Myeloid/granulocytes e.g. BCR-ABL1: Chroinic myeloid leukaemia
- Soluble factors
- No acquired (somatic) DNA mutations, not rapidly dividing cells (hepatocytes /endothelial cells)
What are secondary haematological disorders?
Secondary disorders are changes in haematological parameters secondary to a non-haematological disease
What are some examples of secondary haematological disorders?
Erythrocytes
- Exces: cyanotic heart disease
- Deficiency: anti-RBC antibodies: Immune haemolysis
Factor VIII
- Excess: inflammatory response
- Deficiency: anti-FVIII auto-antibodies (acquired haemophilia A)
What can cause increased FVIII?
Inflammation
What can cause increased or decreased erythrocytes?
Raised - Altitude/hypoxia or Epo secreting tumour
Reduced - BM infiltration or deficiency disease (Vit B12 or Fe) Shortened survival (Haemolytic anaemia)
What can cause increased or decreased platelets?
Raised - Bleeding, Inflammation, splenectomy
Reduced - BM infiltration or deficiency disease (Vit B12) Shortened survival (ITP, TTP)
What can cause increased or decreased leucocytes?
Raised - Infection, Inflammation, corticosteroids
Reduced - BM infiltration or deficiency disease (Vit B12)
What is the cause of iron deficiency unless proven otherwise?
Bleeding
What are some reasons for occult blood loss?
GI cancers: Gastric, Colonic/rectal
Urinary tract cancers: Renal cell carcinoma, Bladder cancer
What is Leuco-erythroblastic anaemia and what are the signs in a blood film?
Variable degree of anaemia
Teardrop RBCs (+aniso and poikilocytosis)
Nucleated RBCs
Immature myeloid cells
What are causes of leucoerythroblastic film?
Malignant
Haemopoietic: leukaemia/lymphoma/myeloma
Non Haemopoietic: metastatic-breast/bronchus/prostate
Myelofibrosis
Massive splenomegaly
Dry tap on BM aspirate
Severe infection
Miliary TB
Severe fungal infection
What are common laboratory features of all haemolytic anaemias?
Anaemia (though may be compensated)
Reticulocytosis
Unconjugated bilirubin raised (pre-hepatic)
LDH raised
Haptoglobins reduced
What are the two groups of haemolytic anaemia?
Primary (inherited)
Secondary (acquired)
What are the features of primary inherited haemolytic anaemia?
Defects of the red cell/Germline DNA mutation.
Membrane: e.g. Hereditary Spherocytosis
Cytoplasm/enzymes: e.g. G6PD deficiency
Haemoglobin: Sickle cell disease (structural); Thalassaemia (quantitative)
What are the features of secondary acquired haemolytic anaemia?
Defects of the environment (systemic disease) in which the red cell finds itself:
Non Immune (DAT –ve)
Immune mediated (Direct Antiglobulin Test (DAT) (aka Coombs test) +ve)
What are the features of DAT +ve haemolytic anaemia and what is it associated with?
Spherocytes
Associated with systemic diseases involving Immune system
- Malignancy: e.g. Lymphoma or CLL
- Autoimmune: e.g. SLE
- Infection: e.g. mycoplasma
- Idiopathic
What is associated with DAT -ve haemolytic anaemia?
Infection: Malaria
Micro-angiopathic Haemolytic anaemia (MAHA)
- Underlying adenocarcinoma
- Haemolytic uraemic syndrome
What is microangiopathy associated with and what happens?
Adenocarcinomas, low grade DIC
- Platelet activation
- Fibrin deposition and degradation
- Red cell fragmentation (microangiopathy)
- Bleeding (low platelets and coag factor deficiency)
USUALLY associated with malignancy
What are some causes of neutrophilia?
Corticosteroids
Underlying neoplasia
Tissue inflammation (e.g.colitis, pancreatitis)
Myeloproliferative/leukaemic disorders
PYOGENIC INFECTION
What would you expect to see in a blood film for an infection?
Neutrophilia + toxic granulation no immature cells
What would you expect to see in a blood film for CML?
Neutrophilia plus basophilia & immature cells myelocytes
What would you expect to see in a blood film for AML?
Neutropenia plus myeloblasts suggests acute leukaemia (AML)
What are some causes of eosinophilia?
Reactive eosinophilia
- Parasitic infestation
Allergic diseases e.g. asthma, rheumatoid, polyarteritis,pulmonary eosinophilia.
Underlying Neoplasms, esp. Hodgkin’s, T-cell NHL (reactive eosinophilia)
Drugs (reaction erythema multiforme)
Chronic eosinophilic leukaemia
Eosinophils part of the “clone”
FIP1L1-PDGFRa Fusion gene
What is monocytosis?
Rare but seen in certain chronic infections and primary haematological disorders.
- TB, brucella, typhoid
- Viral; CMV, varicella zoster
- Sarcoidosis
- Chronic myelomonocytic leukaemia (MDS)
What are some causes of increased lymphocytes?
EBV, CMV, Toxoplasma
Infectious hepatitis, rubella, herpes infections
Autoimmune disorders
Sarcoidosis
What are some causes of decreased lymphocytes?
Infection HIV
Auto immune disorders
Inherited immune deficiency syndromes
Drugs (chemotherapy)
What are differentials for unusual blood films with lymphocytosis?
Mature lymphocytes (PB)
- Reactive/atypical lymphocytes (IM)
- Small lymphocytes and smear cells (CLL/NHL)
Immature Lymphoid cells in PB
- Lymphoblasts (Acute Lymphoblastic Leukaemia)
How do you determine if B-cell lymphocytosis is malignant or reactive?
If it is polyclonal (Kappa and Lambda chain diversity) then it is reactive, if it is monoclonal, then it is malignant.
What are the three types of acquired somatic mutations?
Cellular proliferation (type 1)
Impair/block cellular differentiation (type 2)
Prolong cell survival (anti-apoptosis)
What are examples of cellular proliferation?
Mutations in Tyrosine Kinase genes cause excess proliferation (no effect on
differentiation)
- BCR-ABL1 CML
- JAK2 MPD
What are examples of impaired/blocked cellular differentiation?
Mutations in nuclear transcription factors may block differentiation. If present along with a proliferation mutation can cause acute leukaemia
PML-RARA in acute promyelocytic leukaemia
What are examples of prolonged cell survival?
Mutations in apoptosis genes may occur in lymphomas
- BCL2 and Follicular lymphoma
