Week 4: Haematology Flashcards
What is a full blood count?
A set of data that tells you information about the RBC, WBC, platelets and other blood components?
What are some important pieces of information to do with RBC?
Haemoglobin levels
Cell size (MCV: Mean Corpuscular Volume)
Number of cells
Haematocrit (% of blood that is cellular)
Why are bone marrow examinations performed?
To investigate blood count
What is Haematopoeisis?
The process of blood cell formation
__________ stem cells are the primitive precursor cells that differentiate under control of ___________ and ___________ to form blood cells
Pluripotent Stem cells
Growth Factors and Cytokines
What are the 3 components of coagulation (aka Virchow’s Triad)?
Clotting factors - circulating proteins
Platelets - derived from megakaryocytes
Endothelium - blood vessel lining
What is Haemostasis?
The process of stopping bleeding
Primary Haemostasis disorders are associated with _______________________.
Platelet malfunction
Secondary Haemostasis disorders are associated with _______________________.
Clotting factor malfunction
What are the primary Haemostasis disorders?
vWF Deficiency
Haemophillia
Platelet Dysfunction
What are the secondary Haemostasis disorders?
DIC Anticoagulation Vitamin K Deficiency Hepatic Failure Renal Failure
What is Haemophilia A?
An inherited X-linked deficiency in Factor VIII that causes spontaneous or after trauma bleeding and bleeding into the joints (Haemarthroses)
How do we diagnose Haemophilia A?
Family history (Females are carriers) Factor VIII levels
How do we treat Haemophilia A?
Prophylaxis
Factor VIII replacement
What is Thrombocytopenia?
Low thrombocyte levels
What is Thrombocytosis?
Elevated thrombocyte levels, it has an increased risk of clotting
What is platelet dysfunction?
A disorder where you can’t aggregate your platelets
What is Thrombosis?
The formation of a blood clot that obstructs blood flow in a vessel
What are some causes of thrombosis
Obesity Oral contraceptives/Pregnancy Prolonged immobility Surgery Malignancy Inheritance
If you have type A blood you have __ antigens and __ antibodies
A
B
If you have type B blood you have __ antigens and __ antibodies
B
A
If you have type AB blood you have __ antigens and __ antibodies
A+B
No A or B
If you have type O blood you have __ antigens and __ antibodies
No A or B
A + B
Haemoglobin is made in the ____________
Mitochondria
___________ regulates RBC production. __% is made in the ________. It’s release is stimulated by __________.
Erythropoetin
90% made in the kidney
Low blood O2
What are the requirements for Erythropoeisis?
Iron, cobalt
Vitamin B12, folate, thiamine
Amino acids
Other cytokines
RBC are removed in the ________. Iron is stored as _______ and Globin is ________________. Haem is broken down to ________ which is excreted by the ________.
Spleen
Ferritin
Degraded to AAs
Billibrubin, excreted by the liver
Define Anaemia:
Reduction in haemoglobin, Also reduced red cell count & haematocrit:
Males:
What causes anaemia?
Reduced bone marrow production
Increased loss of RBC
Premature destruction (haemolysis)
What are the symptoms of anaemia?
Shortness of breath Fatigue Tachycardia / chest pain Generalised weakness Pale: mouth mucosa (Hb
Anisocytosis is?
Variation in red cell size
Poikilocytosis is?
Variation in RB cell shape
Hypochromasia is?
RBC are Pale (reduced colour)
Polychromasia is?
RBC have Many colours
Microcytic is?
Small red cells
Macrocytic is?
Large red cells
Schistocyte is?
Fragmented red cell
Spherocytes is?
Spherical red cell
Acanthocyte is?
Spiculated RBC membrane
State the primary causes of anaemia related to reduced bone marrow production:
Bone marrow failure - erythropoeisis fails to occur
Red cell aplasia - erythropoeisis fails to occur properly
State the secondary causes of anaemia related to reduced bone marrow production:
Infection Drugs Infiltration Absence of “ingredients” BM hypoxia
How do we classify anaemia based on cell size?
Microcytic
Normocytic
Macrocytic
What are some causes of microcytic anaemia?
Iron deficiency
Thalassaemia
Haemoglobinopathies
Anaemia of chronic disease
What are some causes of normocytic anaemia?
Blood loss Haemolytic - RBC membrane - Enzyme defects - Extrinsic Stem cell defects
What are some causes of macrocytic anaemia?
Megaloblastic Excess alcohol Liver disease Reticulocytosis Drug therapy Marrow failure
What does a low reticulocyte count suggest?
Failure of Erythropoeisis
What does a high reticulocyte count suggest?
Appropriate Bone marrow erythroid response
What are the causes of Iron Deficiency Anaemia?
Poor iron intake
Poor iron absorption
Chronic blood loss (Gut, uterine bleeding (menorrhagia) )
Increased iron utilisation (Neonates; puberty; pregnancy)
What is the Pathology of Iron Deficiency Anaemia?
Hypochromic and microcytic RBC with low MCV
How do we treat iron deficiency?
Iron Supplementation or Intravenous/Muscular if severe continuing until levels normalise
What are Haemoglobinopathies?
Genetic disorders of Hb synthesis that causes reduced or abnormal globin chains
i.e. Thalassaemia, Structural Haemaglobinopathies
What is Thalassaemia?
Reduced production of α or β globin chains
What are Structural Haemaglobinopathies?
Abnormal globin chain structure
i.e. HbS (Sickle Cell Anaemia)
What is β-Thalassaemia?
Mutations in the β-globin gene which causes reduced β-globin chain production .’. reduced haemoglobin
What are the 2 types of β-Thalassaemia?
Homozygous (thalassaemia major)
Heterozygous (thalassaemia minor)
What is thalassaemia major?
Homozygous form of β-Thalassaemia:
– Inherited defective gene from both parents
– Present at 3-6 months with severe anaemia
– Transfusion dependent; bone marrow transplant
What is thalassaemia minor?
Heterozygous form of β-Thalassaemia:
– Asymptomatic
There are __ genes involved in making the α-globin chains.
4 genes
What are the possible outcomes for α-Thalassaemia?
– α / αα and – α / – α = Τhalassaemia minor
– – / αα = Τhalassaemia minor
– – / – α = Haemoglobin H disease
– – / – – = Hb Barts hydrops fetalis
Structural Haemaglobinopathies are ussually caused by _______________ that cause a __________________. They are most common in the __ chain.
Point Mutations
Structural Abnormality
β
List the 3 most common types of Structural Haemaglobinopathies:
HbS: Occurs in Negro race;
βS gene
- Homozygous: HbS forms crystals: sickle shaped
RBC resulting in sickling crises (painful)
HbE: Thailand;
βE gene; target cells; common
HbC: West Africa;
βC gene; target cells
Megaloblastic Anaemia is a type of _________ anaemia that is caused by _______________________________.
Macrocytic
Deficiency of Vitamin B12 or folate
List some possible causes of Megaloblastic Anaemia other that B12/Folate deficiency:
– Liver disease
– Excess alcohol consumption
– Hypothyroidism
– Drug effects (e.g. chemotherapy drugs)
What is the pathology of Megaloblastic Anaemia?
• high MCV
• Hypersegmented neutrophils
• Hypercellular bone marrow
• Reduced serum vitamin B12 or RBC folate
• Intrinsic factor or Parietal cell antibodies (auto-
antibodies)
What is Normocytic Anaemia and what causes it?
Anaemia where the MCV is normal 80fL
Hereditary Haemolytic Anaemia can be caused by:
Red cell membrane defect
Biochemical (enzyme) defect
Acquired Haemolytic Anaemia can be caused by:
Immune haemolytic anaemia (antibodies) Drugs “Hole in the heart” fracturing red cells Multi-organ failure: kidney, liver Infections: malaria, Clostridial sepsis
RBC in Haemolytic anaemia are _________ they are ______ and have ____________.
Spherocytes
Small and have lost their central palour
Leukocytes can be classed as __________ or ________ and have an absolute count of ________.
Phagocytes or Leukocytes
4 - 11 x 10^9
Summarise Neutrophil Specs:
40-75% of WBC (count = 2.5-7.5 x10^9/L) Develop from primitive myeloblast in BM – Neutrophil migrates to tissue: Phagocytic function – Acquire specific granules – 2-5 nucleus segments – 6-10 hrs in blood
Summarise Eosinophil Specs:
1-5% of leucocytes (0.1-0.4 x10^9/L)
• 2-lobed nucleus; large orange granules
• Circulation time 3-8 hours
• Involved in allergy, parasitic infection
Summarise Basophil Specs:
Summarise Monocyte Specs:
- 2 - 8% of white cells (0.2-0.8 x10^9/L)
- Maturation from monoblast
- 20 -40 hrs in blood
- Mature to macrophage in tissue (mths-yrs)
- Grey cytoplasm; horseshoe-shaped nucleus
- Produce cytokines
With respect to leukocytes these mean?
- cytosis
- phillia
- cytopenia
Increased numbers
Increased numbers
Decreased numbers
List some reactive White Cell disorders
– Neutrophilia and neutropenia
– Lymphocytosis
– Monocytosis
– Eosinophilia
List some malignant White Cell disorders
– Leukaemias: acute and chronic
– Multiple myeloma
– Lymphoma
– Myeloproliferative neoplasms
Neutropillia is _______________________. It is usually caused by _________________________________________.
Increase in neutrophil count ( >8x10^9 )
Infection, Fever, Inflammation, Steroid therapy and neoplasms
Neutrophillia is often accompanied by left shift, which is __________________________________, and toxic granulation, which is _________________.
Presence of precursor neutrophils in the blood
Increase in granules
What are some causes of Neutropenia?
Congenital (rare
Drug-induced: Antibiotics; cytotoxics
Infections: Viral or bacterial
Bone marrow failure (pancytopenia)
Neutropenia is associated with an increased risk of __________ and ________________________, especially in the _______ and _______.
Severe and recurrent Bacterial Infection
Mouth
Throat
Lymphocytosis is commonly secondary to _________________. The morphology of the cells is ________.
Viral Infections
Altered
Monocytosis is _________ and is caused by ____________________, _________ and _______.
Uncommon
Chronic infections, Tuberculosis and Malaria
Eoisinophillia is common in ________ and ________ reactions and __________________.
Allergic and Drug Reactions
Parasite infection
Basophillia is very ________ as it is a manifestation of ________________________.
Rare
Chronic myeloid leukaemia
What is acute leukaemia?
Malignancy of the Precursors in the bone marrow, bone marrow gets replaced by leukaemic cells which causes a reduction in normal cells
Leukaemia blast cells ____________ but do not __________.
Proliferate
Mature
What are the 2 types of acute leukaemia?
Lymohoblastic ALL
Myeloblastic AML
Acute leukaemia affects ________. Lymphoblastic leukaemia predominately affects ___________.
All ages
Children
What are the symptoms of acute leukaemia?
Anaemia = Lethargy etc Leucopenia = Infections, fevers Thrombocytopenia = Bleeding, bruising
How do we treat acute leukaemia?
Aggressive Chemotherapy and Bone Marrow Transplant
B-Lineage ALL is the commonest in _________ (__% of cases). It is characterised by ______________. It has a poor prognosis for ________ and good prognosis for ________.
Children 85% of cases
Small “blast” cells
Adults
Children
What is Acute Myeloblastic Leukaemia and how do we treat it?
A clonal defect in the myeloblast
Treated with Chemotherapy and Transplantation
What is Chronic Leukaemia?
Malignant proliferation of mature lymphoid
or myeloid cells
What are the 2 types of Chronic Leukaemia?
Chronic lymphocytic leukaemia
Chronic myeloid leukaemia
Summarise Chronic lymphocytic leukaemia:
Disease of the elderly >60yo
Malignant proliferation of mature B lymphocytes
Progressive anaemia, thrombocytopenia & neutropenia
Treated with oral chemotherapy
Summarise Chronic myeloid leukaemia:
Disease of the middle ages 30-60yo
Characterised by:
• Leucocytosis: neutrophilia and precursors
• Blast cells (
