Haematological Changes in Systemic Disease Flashcards by Georgia Leggett

What haematological manifestations arise from altered function of soluble proteins?

Haemostasis: FVIII deficiency = bleeding tendency

Thrombophilia: Protein C deficiency = thrombotic tendency

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What haematological disorders arise from abnormalities of cell number/ function?

WBC: Leukaemia, reactive leukocytosis, myeloma
RBC: Sickle cell, Thalassaemia

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What are the other broad etiological groups of haematological disorders?

Immune: AI disorders

Transfusion associated

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What conditions are caused by haematological deficiencies?

Factor VIII, IX, Protein C, Erythrocytes, Lymphocytes, Platelets

Factor VIII: Haemophilia A
Factor IX: Haemophilia B
Protein C: Pro-thrombotic
Erythrocytes: anaemia
Lymphocytes: Lymphopenia (HIV)
Platelets: ITP

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What conditions are caused by haematological excesses?

Erythrocytes
Granulocytes
Lymphocytes
Platelets

Erythrocytes: Polycythaemia

Granulocytes: Leukaemia (CML), reactive eosinophilia

Lymphocytes: Leukaemia (CLL)

Platelets: Essential thrombocythemia

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What are primary haematological disorders?

Inherited (germline gene mutated) or acquired (somatic gene mutated) DNA mutation(s)

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What are most haematological malignancies due to?

Acquired (somatic) gene mutations

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Give a primary and secondary condition causing raised erythrocytes

Primary: Polycythaemia Vera

Secondary: High altitude

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Name 2 inherited mutations of FIX and erythrocytes that cause primary haematological disorders

FIX
Deficiency: Haemophilia B (bleeding)
Excess: FIX Padua (thrombosis)

Erythrocytes
Deficiency: Hb S
Excess: Polycythaemia

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Name 2 ACQUIRED haematological mutations of erythrocytes that cause primary disorders

JAK2 V617F: Polycythaemia vera

PIG A: PNH Paroxysmal nocturnal haemoglobinuria

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Why are there no acquired DNA mutations in soluble factors to cause primary haematological disorder?

Soluble factors are secreted by endothelial cells or hepatocytes

Not by rapidly dividing cells which have greater risk of mutation

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Give a primary and secondary disorder causing reduced erythrocytes

Primary: Thalassaemia

Secondary: AI haemolytic anaemia

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What are secondary haematological disorders?

Changes in haematological parameters in response to a non-haematological disease/ condition

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What are the FVIII examples of secondary haematological disorders?

Excess: inflammatory response/ pregnancy
Deficiency: anti-FVIII auto-antibodies (acquired haemophilia A)

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What systemic condition can cause increased FVIII? What is the consequence of this?

Chronic inflammation

Increases thrombosis risk

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What systemic changes can cause increased or decreased erythrocytes?

Increased: Altitude/ hypoxia or EPO secreting tumour

Decreased: BM infiltration or deficiency disease (Vit B12 or Fe)
Shortened survival (Haemolytic anaemia)

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What systemic changes can cause increased or decreased platelets?

Increased: Bleeding, Inflammation, splenectomy

Decreased: BM infiltration or deficiency disease (Vit B12)
Shortened survival (ITP, TTP)

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What systemic changes can cause increased or decreased leucocytes?

Increased: Infection, Inflammation, corticosteroids

Decreased: BM infiltration or deficiency disease (Vit B12)

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What systemic disease would you associate with folate deficiency, macrocytic anaemia and Howell Jolly bodies?

Coeliac

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Give 2 examples of anomalous blood results that may be the first presentation of malignancy

Microcytic anaemia: GI cancer

Hypercalcaemia: Myeloma

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What is the cause of iron deficiency unless proven otherwise?

Bleeding

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What are the labratory findings in iron deficiency?

Microcytic hypochromic anaemia

Low ferritin

Low transferrin saturation

High TIBC

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What are 2 classes of reasons for occult blood loss?

GI:
Peptic ulcer or Gastric cancer
IBD or Colonic cancer

Urinary tract:
Renal cell carcinoma
Bladder cancer

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What is Leuco-erythroblastic anaemia and what are the signs in a blood film?

Variable degree of anaemia (mild-severe)

Teardrop RBCs (+aniso + poikilocytosis)
Nucleated RBCs
Immature myeloid cells

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Why is leuco-erythroblastic anaemia an important finding? What can cause this?

It implies abnormal BM infiltration Malignancy Myelofibrosis Severe infection (rarely)

What are the malignant causes of a leuco-erythroblastic anaemia?

Haematopoietic: Leukaemia, Lymphoma, Myeloma Metastatic: Breast, Bronchus, Prostate

What features would indicate myelofibrosis being causative of a leuco-erythroblastic anaemia?

Massive splenomegaly Dry tap on BM aspirate

Which infections could cause a leuco-erythroblastic anaemia?

Miliary TB Severe fungal infection

What are common laboratory features of all haemolytic anaemias?

Anaemia (though may be compensated) Reticulocytosis (high MCV) HIGH Unconjugated BR (pre-hepatic, excess BR) HIGH LDH (intracellular enzyme released) LOW Haptoglobins

What are the two groups of haemolytic anaemia?

Primary (inherited) Secondary (acquired)

What are the features of primary inherited haemolytic anaemia?

Inherited mutation of RBC **Membrane:** Hereditary Spherocytosis **Cytoplasm/ enzymes:** G6PD deficiency **Haemoglobin:** Sickle cell disease (structural); Thalassaemia (quantitative)

What are the features of secondary acquired haemolytic anaemia?

Defects of RBCs environment (systemic disease): Non Immune (DAT –ve) Immune mediated (DAT +ve) Direct Antiglobulin Test = DAT (aka Coombs test)

What are the features of DAT +ve haemolytic anaemia and what is it associated with?

Spherocytes A/W systemic diseases Malignancy: Lymphoma or CLL AI: SLE Infection: mycoplasma Idiopathic

What is associated with DAT -ve haemolytic anaemia?

Infection: Malaria Micro-angiopathic Haemolytic anaemia (MAHA): indicates underlying adenocarcinoma or Haemolytic uraemic syndrome

What is microangiopathy associated with and what happens?

Adenocarcinomas, low grade DIC 1. Platelet activation 2. Fibrin deposition + degradation 3. RBC fragmentation (microangiopathy, BP drives RBC through fibrin strands) 4. Bleeding (low platelets + coag factor deficiency) USUALLY a/w malignancy

What are 5 causes of neutrophilia?

PYOGENIC INFECTION Corticosteroids Underlying neoplasia Tissue inflammation (e.g.colitis, pancreatitis, MI) Myeloproliferative/ leukaemic disorders

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 + Myelocytes

What would you expect to see in a blood film for AML?

Neutropenia plus Myeloblasts

4 causes of reactive eosinophilia?

Parasitic infestation Allergic diseases: asthma, RA, polyarteritis, pulmonary eosinophilia. Underlying Neoplasms, esp. Hodgkin’s, T-cell NHL Drugs (reaction erythema multiforme)

What chronic infections and primary haematological disorders cause monocytosis?

RARE TB, brucella, typhoid CMV, VZV Sarcoidosis Chronic myelomonocytic leukaemia (MDS)

What are 4 causes of lymphocytosis?

EBV, CMV, Toxoplasma Infectious hepatitis, rubella, herpes infections AI disorders Sarcoidosis

What are 4 causes lymphopenia?

Infection: HIV AI disorders Inherited immune deficiency syndromes Drugs (chemotherapy)

What are the differentials for lymphocytosis with mature lymphocytes in the peripheral blood?

Reactive/ atypical lymphocytes: IM Small lymphocytes + smear cells: CLL/ NHL

How do you determine if B-cell lymphocytosis is malignant or reactive?

Reactive: Polyclonal (Kappa + Lambda chain diversity, 60:40) Malignant: Monoclonal (Kappa OR Lambda only, 99:1)

What are the three types of acquired somatic mutations?

Cellular proliferation (Type 1) Impair/ block cellular differentiation (Type 2) Prolong cell survival (Anti-apoptosis)

How do cellular proliferation mutations cause malignancy? Give 2 examples

Mutations in Tyrosine Kinase genes cause excess proliferation (no effect on differentiation) BCR-ABL: CML JAK2: MPD

How do mutations causing impaired/ blocked cellular differentiation lead to malignancy? Give an example

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

In which malignancies are there mutations that cause prolonged cell survival?

Mutations in apoptosis genes may occur in lymphomas BCL2 + Follicular lymphoma

Which white cells are found in the bone marrow?

Myeloblasts Lymphoblasts Promyelocytes Myelocytes

Which white cells are found in peripheral blood?

Phagocytes: Granulocytes + Monocytes Immunocytes: T + B lymphocytes, NK cells

List 3 types of granulocyte

Neutrophils Eosinophils Basophils

What malignancy causes secondary eosinophilia?

**Chronic eosinophilic leukaemia** Eosinophils part of the “clone” FIP1L1-PDGFRa Fusion gene

What is the differential for lymphocytosis with immature lymphoid cells in the peripheral blood (PB)?

Acute Lymphoblastic Leukaemia

What investigations are performed on a tissue biopsy to establish haematological malignancy diagnosis?

1. Morphology: architecture 2. Immunophenotype: flow cytometry or immunohistology 3. Cytogenetics: Translocations- fusion gene or de-regulated oncogene 4. Molecular genetics: PCR

What is determined in immunophenotyping?

Myeloid or Lymphoid T or B lineage Stage of maturation

How does lympho-haemopoietic failure manifest and present in patients?

BM (Myeloid): Anaemia, Bacterial infection (neutrophils), Bleeding (platelets) Immune system (Lymphoid): Recurrent viral or fungal infection

How does excess of malignant cells manifest and present in patients?

Erythrocytes/ Leukocytes: Impair blood flow- Stroke Massively enlarged LN-lymphoma: compress hollow tubes- bowel, vena cava, uterus, bronchus

Which organs may be infiltrated and impaired in haematological malignancy?

CNS lymphoma Skin lymphoma Kidney failure (light chain deposition from myeloma)

Give 2 miscellaneous problems caused by haematological malignancy

Hypercalcaemia Hypermetabolism

Haematological Changes in Systemic Disease Flashcards

(60 cards)