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Year 5 Haematology > 1. Systemic Disease > Flashcards

1. Systemic Disease Flashcards

1
Q

3 types of anaemia

A
  • iron deficiency
  • leukoerythoblasgtic
  • haemolytic = immune, non-immune-mediated
  • anaemia of inflammation (chronic disease)
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2
Q

Fe deficiency anaemia: causes, biochemical/lab findings

A

bleeding until proven otherwise (menorrhagia pre-menopausal women, GI blood loss in men and post-menopausal women)

Occult blood loss:

  • GI cancers = gastric, colorectal
  • UT cancers = RCC, bladder cancer

Lab findings:

  • low ferritin and TF saturation
  • raised TIBC
  • microcytic hypo chromic anaemia
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3
Q

Leucoerythroblastic anaemia: what is it, blood film, causes

A

red and white cell precursor anaemia

blood film

  • poikilocytosis (teardrop RBCs) and anisocytosis
  • nucleated RBCs
  • immature myeloid cells
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3
Q

Leucoerythroblastic anaemia: what is it, blood film, causes

A

red and white cell precursor anaemia

usually first manifestation of a BM malignancy

blood film

  • poikilocytosis (teardrop RBCs) and anisocytosis
  • nucleated RBCs
  • immature myeloid cells

Causes:

  • malignancy = haematopoietic (leukaemia, lymphoma, myeloma), non-haematopoietic (breast, bronchus, prostate)
  • severe infection = miliary TB, severe fungal infection
  • myelofibrosis = massive splenomegaly, dry tap on BM aspirate
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4
Q

Haemolytic anaemia: common lab features

A

shortened RBC survival

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5
Q

2 types of haemolytic anaemias

A

Inherited → defects of red cell

  • membrane = hereditary spherocytosis
  • cytoplasm/enzyme = G6PD deficiency
  • Hb = SCD (structural) or thalassaemia (quantitative)

Acquired → RBC healthy but due to defects in environment where RBC finds itself

  • immune mediated = warm/cold AIHA, PCH
  • non-immune mediated = PNH, MAHA, infection (malaria),
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6
Q

Warm vs Cold AIHA

A

BOTH DAT+ve, spherocytes, agglutination

Warm AIHA (80-90%) IgG, extravascular haemolysis – lymphoma, CLL, drug allergy, SLE, idiopathic

Cold AIHA (10-15%) IgM (or IgG), intravascular haemolysis – M. pneumoniae, EBV, CMV

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7
Q

DAT vs iDAT

A
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8
Q

DAT vs iDAT

A
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9
Q

Paroxysmal Cold Haemoglobinuria (PCH)

A

Hb in urine

viral infection = measles, syphilis, VZV

Donath-Landsteiner antibodies → stick to RBCs in cold → complement-mediated haemolysis on rewarming (self-limiting as IgG dissociate at higher tempo than IgM)

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10
Q

Non-immune mediated anaemia features

A

DAT -ve

Schistocytes, thrombocytopenia, DAT-ve, hereditary spherocytosis

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11
Q

Non-immune mediated anaemia: infection

A

MALARIA (commonest WW)

parasite enters RBC, causes it to die, shortening survival of RBC

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12
Q

PNH = paroxysmal nocturnal haemoglobinuria

A

Acquired loss of protective surface GPI markers on RBCs (platelets + neutrophils) → complement-mediated lysis → chronic intravascular haemolysis especially at night.

Morning haemoglobinuria, thrombosis (+Budd- Chiari syndrome – hepatic v thromb).

Diagnosis: immunophenotype shows altered GPI or Ham’s test +ve (in vitro acid-induced-lysis).

Treatment: iron/folate supplements, prophylactic vaccines/antibiotics. Expensive monoclonal antibodies (eculizumab) that prevents complement from binding RBCs

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13
Q

3 types of MAHA

A

Adenocarcinoma, HUS, TTP

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14
Q

Adenocarcinoma

A
  • 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)
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15
Q

HUS

A

E. coli toxin O157

triad: MAHA, thrombocytopenia, AKI

16
Q

TTP

A

Pentad = MAHA, thrombocytopenia, AKI, neurological impairment, fever

AI: ADAMTS13 mutation → deficiency in vWF cleaving protease

high vWF acts like cheese wire in blood vessels

tx = plasma exchange (NOT STEROIDS)

17
Q

Types of white blood cells in peripheral blood and bone marrow

A
18
Q

What do we ix when abnormal WBC

A

FBC = Hb, MCV, platelet count, WBC

Blood film = count, pancytopaenia?, which lineages abnormal?, morphology?

19
Q

Causes of neutrophilia

infections that don’t produce a neutrophilia

A

Pyogenic infection (most likely)

  • corticosteroids
  • underlying neoplasia
  • tissue inflammation → colitis or pancreatitis
  • myeloproliferative or leukaemic disorders

Infections that don’t cause neutrophilia:

  • brucella, typhoid, viral infections
20
Q

Reactive/infection vs malignant (e.g. CML and ALL) neutrophilia

A

Reactive/infection:

  • neutrophilia, toxic granulation, no immature cells
  • only neutrophils, heavy granulation, vacuoles in neutrophils

Malignant → MASSIVELY RAISED

  • neutrophilia/basophilia + immature cells (myelocytes) + splenomegaly = CML
  • neutropenia + myeloblasts = AML
21
Q

Reactive vs chronic eosinophilic leukaemia

A

Reactive

  • parasitic infection
  • allergic diseases → asthma, rheumatoid, polyarteritis, pulmonary eosinophilia
  • underlying neoplasms → Hodgkin’s, T-cell NHL
  • Drugs → reaction erythema multiform

Chronic eosinophilic leukaemia

  • eosinophils part of clone
  • FIP1L1-PDGFRa fusion gene
22
Q

Monocytosis: chronic infections and primary haematological disorders

A
  • TB, brucella, typhoid
  • vira, CMV, varcella zoster
  • sarcoidosis
  • CMML, myelodysplastic syndrome
23
Q

Summary of increased phagocyte count

A
24
Q

Summary of increased phagocyte count

A
25
Q

Lymphocytosis and lymphpaenia causes

A

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)
26
Q

Evaluating lymphocytosis morphology

A

Mature lymphocytes (PB)

  • Reactive/atypical lymphocytes (IM)
  • Small lymphocytes and smear cells (CLL/NHL)

Immature lymphoid cells (PB)

  • Lymphoblasts (ALL)
27
Q
A

Mature lymphocytes (PB)

  • Reactive/atypical lymphocytes (IM)
  • Small lymphocytes and smear cells (CLL/NHL)

Immature lymphoid cells (PB)

  • Lymphoblasts (ALL)
28
Q

Clonality in B-cell lymphocytosis (light chain restriction)

A
  • Polyclonal = kappa and lambda (reactive)
  • Monoclonal (kappa ONLY or lambda ONLY (malignant)
29
Q

leukaemia vs lymphoma

A

The simplest way to think about it is that lymphomas are solid tumors made up of blood cells. This kind of cancer usually causes enlarged lymph nodes or solid masses. Leukemia, on the other hand, is seen in the bloodstream – it’s a liquid kind of cancer and it flows and is pumped around with the blood

30
Q

Myeloid differentiation

A
31
Q

Myeloid differentiation

A
32
Q

What are the 3 acquired somatic mutations that cause leukaemia and lymphoma?

A

Cellular proliferation (type 1)

  • mutations in TK genes → excess proliferation
  • BCR-ABL = CML
  • JAK2 = MPD

Impair/block cellular differentiation (type 2)

  • mutations in TF block differentiation
  • PMBL RARA in APL (a type of AML)

Prolong cell survival

  • mutations in apoptosis genes in leukaemia
  • BCL2 = follicular lymphoma
33
Q

What parts of tissue biopsy do we look at to establish a diagnosis (4)

A

Gives LINEAGE and NORMAL COUNTERPART CELL

Morphology

  • Malignant cells; large or small, mature or immature?
  • Lymph node diffuse invasion or forming follicles?

Immunophenotype (flow cytometry or Immunohistology)

  • Myeloid or lymphoid? T or B lineage?
  • Stage of maturation precursor or mature?

Cytogenetics (translocations or FISH studies)

  • Confirm morphology e.g. Philadelphia Chromosome > CML
  • Prognostic information e.g. 17p del in CLL
  • t(8;14) activates c-myc oncogene in Burkitt Lymphoma

Molecular genetics (PCR, pyro sequencing)

  • JAK2 mutation in suspected polycythaemia vera
  • BCR ABL cDNA detection and quantification
34
Q

examples of morphology and immunophenotype in diagnosis

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)
A

B-cell acute lymphoblastic lymphoma [TOP]

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

Multiple myeloma [BOTTOM]

  • TdT -ve (normal)
  • Surface Ig +ve (normal)
  • CD138 +ve (abnormal)
35
Q

Clinical problems with systemic disease

A

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

36
Q

Summary

A
37
Q

Which is it? IDA, ACD, BM mets from breast Ca, MAHA, AIHA

A
38
Q

What is the likely diagnosis?

B cell ALL

Mature B cell lymphoproliferative disorder (e.g. CLL)

Infectious mononucleosis (e.g. EBV)

T cell acute leukaemia lymphoma

A

B cell ALL

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

T cell acute leukaemia lymphoma

Year 5 Haematology (7 decks)

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