Haematological Changes in systemic disease Flashcards by Raunak Chandiramani

What are the principles of haematological disorders?

How well did you know this?

Not at all

Perfectly

What are the deficiencies you can get in haematological disorders? What are the excesses in haematological disorders?

How well did you know this?

Not at all

Perfectly

What are primary blood disorders?

Primary - disorder in the DNA

Secondary - another factor affecting blood

How well did you know this?

Not at all

Perfectly

What are secondary blood disorders?

Primary - disorder in the DNA

Secondary - another (non-haematological) factor affecting blood

How well did you know this?

Not at all

Perfectly

What are the haematological changes seen in systemic disease?

How well did you know this?

Not at all

Perfectly

How would anaemia be a sign of malignancy?

Anaemia may be 1st presentation of malignancy/systemic:

Fe deficiency
Leucoerythroblastic anaemia
Haemolytic anaemias

How well did you know this?

Not at all

Perfectly

How do we assess Fe deficiency anaemia?

Occult blood loss
- GI cancers – gastric, colorectal
- Urinary tract cancers (less commonly) – Renal cell carcinoma (physician’s tumour), Bladder cancer
Lab findings
- Mycrocytic hypochromic anaemia
- Reduced ferritin, transferrin
- Raised TIBC
Fe deficiency is bleeding until proven otherwise
- Menorrhagia in pre-menopausal women
- GI blood loss in men and post-menopausal women

How well did you know this?

Not at all

Perfectly

What is leuco-erythroblastic anaemia? Describe its morphology in a blood film.

Red and white cell precursor anaemia of variable degree
Morphology on peripheral blood film
- Teardrop RBCs – aniso and poikilocytosis
- Nucleated RBCs
- Immature myeloid cells

How well did you know this?

Not at all

Perfectly

What does this show?

Nucleated (normal in BM) RBCs (left purple cell)

Immature myeloid cells (right purple cell)

Leucoerythroblasctic - teardrop poikilocytes

How well did you know this?

Not at all

Perfectly

What are the causes of a leucoerythoblastic film?

BONE MARROW INFILTRATION

Malignant

Severe infection (very rare)

Myelofibrosis

How well did you know this?

Not at all

Perfectly

Describe the features of haemolytic anaemia?

Haemolytic anaemia –> shortened RBC survival

Common lab features of all haemolytic anaemias
Anaemia – may be compensated
Reticulocytosis
Unconjugated bilirubin raised – pre-hepatic
LDH (lactate dehydrogenase) raised –> released from broken down RBCs
Haptoglobins reduced

How well did you know this?

Not at all

Perfectly

What are the 2 groups of haemolytic anaemias?

Inherited –> defects of the red cell
- Membrane – hereditary spherocytosis
- Cytoplasm/enzyme – G6PD deficiency
- Haemoglobin – SCD (structural) or thalassemia (quantitative)
Acquired –> RBC is healthy but is due to defects in the environment where the RBC finds itself (focus of Y5)
- (1) Immune-mediated (direct antiglobulin test (DAT) (AKA Coombs Test) +ve)
- (2) Non-immune mediated (DAT -ve)

How well did you know this?

Not at all

Perfectly

What does this show?

Spherocytes –> DAT +ve (feature of acquired autoimmune haemolytic anaemia=

How well did you know this?

Not at all

Perfectly

Name causes of immune mediated anaemia (DAT+)

How well did you know this?

Not at all

Perfectly

What are examples of DAT negative causes of acquired haemolytic anaemia?

How well did you know this?

Not at all

Perfectly

What does this show?

MAHA
- RBC fragments
- Thrombocytopenia

How well did you know this?

Not at all

Perfectly

Why do you get fragments in MAHA?

Underlying pathogenesis –> DIC so inappropriate clotting in microvasculature
Fibrin strands set up across the vessels
As RBCs pass them they become fragmented

Adenocarcinoma

Underlying adenocarcinoma releases granules into circulation
These are pro-coagulant and activate the coagulation cascade
Platelet activation, fibrin deposition, degradation
Red cell fragmentation due to low-grade DIC
Bleeding (low platelet and coagulation factor deficiency)

Lecuoerythroblastic anaemia

No MAHA - reticulocytes low (infiltration of the bone marrow - cant make reticulocytes)

What white cells would you expect to see in the peripheral blood film and the bone marrow?

What are the types of white blood cells seen in the peripheral blood and bone marrow

How would you investigate an abnormal WBC?

In the FBC
- Hb and MCV WBC and automated differential
- Platelet count
Blood film – need to know:
- How high or low is the count
- Is this part of a pancytopenia (RBC/platelets are abnormal too)?
- Which lineages are abnormal –> 1 lineage raised + others suppressed, or all suppressed?
- Normal or abnormal morphology? Mature should be in PB; immature should never be in PB

What are the causes of neutrophilia? How would you evaluate it

Causes of a neutrophilia:
- Corticosteroids
- Underlying neoplasia
- Tissue inflammation –> colitis or pancreatitis
- Myeloproliferative or leukemic disorders
- PYOGENIC INFECTION (most likely)Infections that don’t produce a neutrophilia:
  - Brucella
  - Typhoid
  - Viral infections
Evaluating neutrophils:
- Reactive/infection:
  - Neutrophilia, toxic granulation, no immature cells
  - Only neutrophils, heavy granulation, vacuoles in the neutrophils
- Malignant –> massively raised:
  - Neutrophilia/basophilia + immature cells (myelocytes) + splenomegaly = CML
  - Neutropenia + myeloblasts = AML

What is this?

CML

What causes eosinophilia?

Reactive
- Parasitic infection
- Allergic diseases –> asthma, rheumatoid, polyarteritis, pulmonary eosinophilia
- Underlying neoplasms –>Hodgkin’s, T-cell NHL
- Drugs –> reaction erythema multiforme
- Chronic eosinophilic leukaemia
  - Eosinophils part of clone
  - FIP1L1-PDGFRa fusion gene

What causes monocytosis?

* Monocytosis (rare, seen in some chronic infections and primary haematological disorders): * TB, brucella, typhoid * Viral, CMV, varicella zoster * Sarcoidosis * Chronic myelomonocytic leukaemia (CMML, myelodysplastic syndrome)

What are the causes of high and low lymphocyte

* Lymphocytosis [HIGH WCC] * EBV, CMV, Toxoplasma * Infectious hepatitis, rubella, herpes infections * Autoimmune disorder * Sarcoidosis * Lymphopenia [LOW WCC] * HIV * Auto immune disorders * Inherited immune deficiency syndromes * Drugs (chemotherapy)

How can you evaluate lymphocyte morphology?

* Evaluating Lymphocytosis morphology * Mature lymphocytes (PB) * Reactive/atypical lymphocytes (IM) * Small lymphocytes and smear cells (CLL/NHL) * Immature lymphoid cells in PB * Lymphoblasts (ALL) * Clonality in a B-cell lymphocytosis [light chain restriction] * Polyclonal = kappa and lambda (reactive) * Monoclonal (kappa ONLY or lambda ONLY (malignant)

What does this show?

ALL

What are haemato-oncological diagnoses based on?

* Morphology * Architecture of tumour * Cytology * Cytochemistry * Immunophenotype * Flow cytometry - T or B cells? * Immunohistochemistry * Cytogenetics - chromosomal abnormality * Conventional karyotyping * Fluorescent in-situ hybridisation * Interphase FISH * Metaphase FISH * Molecular genetics * Mutation detection * Direct sequencing * Pyrosequencing * PCR analysis * Gene expression profiling * Whole genome sequencing

Classify the malignany cells in leukaemia and aim to link to their normal cell counterpart

* Primitive lymphoid blast cells expressing B cell marker \> B cell Acute lymphoid leukaemia * Mature lymphoid cells expressing T cell antigens and involving skin\> cutaneous T cell lymphoma * Mature erythrocytes with JAK2 mutation\> polycythaemia vera

What is normal myeloid differentiation?

Describe the formation of myeloproliferative neoplasms (chronic)

Overproduction of cells that are functional

Describe the formation of acute myeloid leukaemia

No healthy mature cells

What mutations affect: * Cell proliferation * Impair block cellular differentiation * Prolong cell survival

* Acquired somatic mutations cause leukaemia and lymphoma: * Cellular proliferation (type 1) --\> mutations in Tyrosine Kinase genes --\> excess proliferation * BCR-ABL = CML * JAK2 = MPD * Impair/block cellular differentiation (type 2) --\> mutations in transcription factors block differentiation. If present with proliferation mutation, can lead to leukaemia * PML RARA in APL * Prolong cell survival --\> mutations in apoptosis genes in leukaemia: * BCL2 = follicular lymphoma

What is the morphology and immunophenotype of B cell acute lymphoblastic lymphoma

* TdT +ve (indicates immature cells; used in VDJ rearrangement) * CD19 +ve (indicates B-cell lineage) * Surface Ig -ve (abnormal - occurs late in maturaton)

What is the morphology and immunophenotype of multiple myeloma

* TdT -ve (normal) * Surface Ig +ve (normal) * CD138 +ve (abnormal)

What is the histopathologists classification used for?

Precise classification is then used to… * Predict the likely course (i.e. polycythaemia vera is an indolent disorder) * Choose the appropriate treatment (i.e. ABL tyrosine kinase inhibitor for CML)

What are the clinical problem associated with leukaemia and lymphoma?

* Lympho-haemopoietic failure (a dispersed organ) * Bone marrow: anaemia, infection (neutrophils) bleeding (platelets) * Immune system: recurrent infection * Excess of malignant cells * Erythrocytes (polycythaemia): impair blood flow to lead to stroke or TIA * Enlarged lymph nodes (lymphoma) compress structures, bowel, vena cava, ureters, bronchus * Impair organ function * CNS lymphoma * Skin lymphoma * Other problems

* B cell acute lymphoblastic leukaemia * **Mature B cell lymphoproliferative disorder** (e.g. CLL) * No abnormal cells in the blood (all mature cells) * Infectious mononucleosis (e.g. EBV) * IgG serology is historical (past infection), IgM is current * Would expect 50/50 proliferation of Kappa/Lambda * T cell acute leukemic lymphoma

Autoimmune haemolytic anaemia