Haematological changes in systemic disease Flashcards
What can be the first presentation of cancer?
Anaemia
What are the 4 main types of anemia associated with cancer/systemic disease?
- Iron deficiency anemia - Anaemia of chronic disease - Leucoerythroblastic anaemia - Haemolytic anaemias
What two types of cancer can also cause secondary polycythemia?
Renal cell cancer and liver cancer
What is the most common cause of Fe deficiency anaemia?
Occult blood loss e.g. GI cancers, urinary tract cancers
What are the laboratory findings for Fe deficiency anaemia?
- Reduced ferritin - Transferrin saturation - Low Hb - Low MCV
What is leuco-erythroblastic anemia?
Red cell and white cell precursor anaemia. Causes a variable degree of anaemia
What the morphological features of leuco-erythroblastic anaemia on a blood film?
- Tear drop red blood cells (aniso and poikilocytosis)
- Nucleated RBCs
- Immature myeloid cells
What does this blood film show?
Leuco-erythroblastic anaemia
- tear drop poikilocytes
- Nucleated red blood cells
- myelocytes
What are the 3 main causes of bone marrow infiltration that causes a leucoerythroblastic film?
- Cancer - haemopoietic e.g leukemia/lymphoma/myeloma. Or non-haempoitetic e.g. breast/bronchus/prostate
- severe infection e.g. miliary TB, severe fungal infection
- myleofibrosis - massive splenomegaly, dry tap on BM aspirate
What are the most common distinguishing features of haemolysis? (any aetiology)
- anaemia - though may be compensated
- reticulocytosis
- raised bilirubin (unconjugated)
- raised LDH - intracellular enzyme
- Reduced haptoglobins
What are the two pathogenic groups of haemolytic anaemias?
- Inherited - defects of the red cell
- Acquired - defects of the environment in which the red cell finds itself. Can be immune or non-immune
What test can distinguish between immune and non-immune types of acquired haemolytic anaemias?
Direct Antiglobulin (DAT or Coombs test)
- What are findings on haematological studies are associated with auto-immune haemolysis?
- What can be the underlying cause of auto-immune haemoloysis?
- Anaemia, reticulocytosis, raised unconjugated bilirubin, raised LDH, Positive DAT
- Idiopathic or underlying lymphoma/CLL/SLE
What are the two main causes of acquired haemolytic anaemia/non-immune/DAT negative?
- Infection - malaria
- Micro-angiopathic Haemolytic anaemia (MAHA)
- What are the main findings in blood studies for MAHA?
- What conditions are MAHA associated with?
- Red cell fragments, low platelets, DIC/bleeding
- Underlying adenocarcinoma and Haemolytic Uremic syndrome (E.coli infection)
What does this blood film show?
MAHA - Micro-angio-pathic haemolytic anaemia
- red cell fragments
- thrombocytopenia
Micro angiopathy can happen because of malignancy e.g. adenocarcinomas.
Describe the underlying mechanism
- Adenocarcinoma, low grade DIC
- Platelet consumption occurs
- Leading to fibrin deposition and degradation
- Red cell fragmentation occurs - microangiopat
- Bleeding occurs
What are the two main causes of true polycythemia in cancer?
True polycythemia is raised red cell mass
- Secondary raised EPO appropriate/inappropriate e.g. hepatocellular cancer, bronchial cancer, renal cancer
- Polycythemia vera (PV) e.g. Clonal myleoproliferative disorder acquired mutations in JAK2
What types of white blood cells are there?
- Normal mature phagocytes - neutrophils, eosinophils and basophils
- monocytes
- immunocytes - T and B lymphocytes, NK cells
Immature - blasts present in a small percentage. Many immature cells are not normal
What does this blood film show?
Chronic lymphocytic leukemia
- WBC increased mature cells
What does this blood film show?
Acute myeloid leukemia
- WBC increased immature cells
What can cause neutrophilia?
- Corticosteroids
- Underlying neoplasia
- Tissue inflammation e.g. colitis, pancreatitis
- myeloproliferative/leukaemic disorders
- infection
Most localised and systemic infections cause a neutrophilia. Which infections characteristically do not cause a neutrophilia?
- Brucella
- Typhoid
- many viral infections
What are the differences between
- Reactive neutrophilia
- Malignant neutrophilia?
- Reactive neutrophilia - reaction and increase in neutrophils in response to infection/inflammation. Presence bands and toxic granulation
- Malignant neutrophilia - neutrophilia, basophilia, plus immature cells myleocytes, and splenomegaly. This suggests a myleoproliferative (CML)
*neutroPENIA plus myeloblasts - AML - Acute Myeloid Leukemia
What does this show?
Reactive neutrophilia
- Nuclear polymorphs
- neutrophilia
- toxic granulation
What does this blood film show?
Chronic Myeloid Leukemia
- Neutrophilia
- Basophilia
- Immature cells such as myleocytes
- splenomegaly
What can cause a reactive eosinophilia?
- Parasitic infection
- Allergic diseases e.g. asthma, rheumatoid
- Underlying neoplasms esp. Hodgkin’s, T-cell NHL
- Drugs - reaction erythema multiforme
What are the underlying cause of Chronic Eosinophilic leukemia?
Eosinophils form part of the ‘clone’.
FIP1L1-PDGFRa fusion gene
What conditions/chronic infections/ haematological disorders can moncytosis be seen?
- TB, Brucella, typhoid
- Viral, CMV, Varicella zoster
- Sarcoidosis
- Chronic myelomonocytic leukemia (MDS)
What in the following categories causes an elevated neutropil count?
- Infection
- Inflammation
- Neoplasia
- Myeloproliferative
- Bacterial infections
- Auto-immune and Tissue necrosis
- All types
- CML
What in the following categories causes an elevated eosinophil count?
- Infection
- Inflammation
- Neoplasia
- Myeloproliferative
- Parasitic infections
- Allergic e.g. asthma, atopy, drug reactions
- Hodgkin’s and NHL
- N/A
What in the following categories causes an elevated Basophil count?
- Infection
- Inflammation
- Neoplasia
- Myeloproliferative
- Pox viruses
- N/A
- N/A
- CML
What in the following categories causes an elevated monocyte count?
- Infection
- Inflammation
- Neoplasia
- Myeloproliferative
- Chronic e.g. TB, Brucella
- N/A
- N/A
- CMML
What is the difference between a secondary and primary lymphocytosis?
SECONDARY lymphocytosis - is reactive, and is a polyclonal response to an infection or chronic inflammation
PRIMARY lymphocytosis - is a monoclonal lymphoid proliferation, as seen in CLL, NHL
What are the causes of a reactive lymphocytosis?
- EBV, CMV, Toxoplasma
- Infectious hepatitis, rubella, herpes infections
- Autoimmune disorders
- Sarcoidosis
What conditions has the following lymphocytes?
- Normal blood film
- Infective mononucleosis
- CLL and NHL
- Acute lymphoblastic leukemia
- Normal blood - mature lymphocytes
- IM - Recactive/atypical lymphocytes
- CLL and NHL - small lymphocytes and smear cells
- ALL - Lymphoblasts
- What does this blood film show?
- What could this be a sign of?
- Lymphocytosis
- Could be EBV infection or early CLL
What does this blood film show?
CLL - Chronic lymphocytic leukemia
What does this blood film show?
Acute lymphoblastic leukemia
presence of lymphoblasts
What does flow cytometry show?
Known as immunophenotyping - flow cytometry looks at the antigens expressed on the cells.
Blue - CD4
Green - CD34
Purple - CD7
Is EBV monoclonal or polyclonal?
Polyclonal, and B cells so amount of kappa and lambda light chains are normal, and in usual proportions
What are the 2 different light chains that B cells can have?
Kappa and Lambda
Is CLL monoclonal or polyclonal?
CLL is monoclonal. One mother B cell with the mutation will proliferate meaning only one of the light chains, either kappa or lambda will be produced. This means that one light chain is measured to be a lot higher than the other. This is usually a sign of a worse prognosis.
What is the diagnosis?
39 year old woman
Had breast cancer over 4 years ago
Presents with jaundice and hepatomegaly
Hb = 87
Bilirubin = 50, conjugated (elevated)
DAT negative
Blood film - nucleated red blood cells
Bone marrow metastases from breast cancer
What is the diagnosis?
45 year old male
3 week history of sore throat
Recent episode of shingles
EBV IgG serology positive
FBC: Raised lymphocytes, normal neutrophils
Blood film: Reactive lymphocytes, no abnormal cells
Monoclonal
Mature B cells, monoclonal
CLL
