Haematology Flashcards
Haematopoeisis
Process through which all types of mature blood cells are produced
What do Erythroid / megakaryocytic lineage cells give rise to?
Red cells and platelets
What do granulocyte/ macrophage lineage give rise to?
Granulocytes and monocytes
What do lymphoid lineage give rise to?
T cells, B cells and NK cells
Primitive haematopoeisis
Started in yolk sac
Give rise to red blood cells
When is primitive haematopoeissi replaced by definitive haematopoiesis at?
5-6 weeks gestation
What is definitive haematopoiesis?
Produces all blood cell types
Where are definitive heamtopoietic stem cells created?
Develop in the aorta-gonad mesonephros region of the dorsal aorta
When do HSC’s migrate to AGM to fetal liver and spleen?
6-7 weeks gestation
Liver is then the primary site of haematopoiesis
What is main site of heamtopoiesis at 3rd trimester and at birth?
Bone marrow
Originally occurs in all areas of bone marrow - restricted to axial skeleton and proximal ends of long bones later
What does metal Hb consist of? When does it start getting produced in gestation?
2 alpha chains, 2 gamma chains
Produced from 3-4 weeks of fatal life
What does the binding and releasing of oxygen cause?
Causes small configuration of globin chains in Hb molecule
Oxygen is unloaded, Hb molecule opens up allowing 2,3-diphosphoglcyerate (2-3 DPG) to enter reducing oxygen affinity and ensuring Hb molecule does not take up oxygen from tissues
What is average life span of RBC?
120 days in older children and adults
90 days in neonates
Iron absorption
Iron in diet is absorbed by enterocytes in duodenum either in Fe2+ form or as haem
Ferroportin, iron transporter protein, transports iron across basolatereal membrane of enterocyte into the blood stream
Iron binds to transferrin and transported to tissues
Transferrin
Transferrin can bind to 2 molecules of iron and deliver this to cells that express transferrin receptors
Ferritin
Storage of iron
Shows total body iron levels (in absence of inflammation)
Why are Hb values higher in utero? What are the values?
Higher oxygen affinity of HbF and fall during first few months of life
Neonate - <130
1-12 months <100
1- 12 years <110
Causes of Reduced MCV - microcytosis
Iron deficiency
Thalassaemia major or thalassaemia trait
Anaemia of chronic disease
Causes of increased MCV - macrocytosis
Folate deficiency
Vit B12 deficiency
Diamond-Blackfan anemia
Liver Disease
Hypothroidism
Diamon-Blackfan Aneamia
Genetic disorder
Presents with anaemia at birth or during infancy
50% physical abnormalaties - craniofacial abnormalities, thumb and growth restrictions
Autosomal dominant
Mutations in ribosomal protein genes - RPS19
Bone marrow biopsy
Treatment - steroids and regular blood transfusions
Transient erythroblastopenia
Parvovirus-induced red cell aplasia
TEC - presents 2 year olds
Transient red cell aplasia triggered by unknown infective agent
Recovery occurs spontaneously within 4-8 weeks
Normocytic with neutropenia
Blood tests for Haemolytic Anaemia
Reduced Hb
Raised reticulocytes - immature red blood cells
Raised unconjugated bilirubin
Raised LDH
Intravascular haemolysis
Occur in circulation
Depletion of haptoglobin
Increase LDH
Large numbers of fragmented RBCs (schisocytes)
Extravascular haemolysis
Takes place in spleen or liver - can occur in lung
Spleen or liver macrophage Fc receptors bind immunoglobulin attached to RBC
Inherited haemolytic disorders
Red cell membrane defects - hereditary spherocytosis, hereditary ellipocytosis
Red cell enzyme defects - G6PD deficiency and pyruvate kinase deficiency
Haemoglobinopathies - sickle cell disorders, thalassaemias
Acquired Haemolytic disorders
Autoimmune - idiopathic, SLE, JIA
Microangiopathic - HUS, TTP, haemangiomas
Infection - Malaria, septicaemia
Other - burns, lead poisoning
What conditions cause Positive DAT’s
Haemolytic disease of newborn
Autoimmune haemolytic anaemia
Drug-induced anaemia
Haemolytic transfusion reactions
Red cell enzyme defects
Glucose-6-phosphate dehydrogenase deficiency
Pyruvate kinase deficiency
What does G6PD do?
Protects cell from oxidative damage
Catalyses first step of pentose phosphate pathway
How is G6PD deficiency inherited?
X-linked disorder
What causes an acute haemolytic crisis in G6PD deficiency
Infection
Medications - co-trimoxazole, dapsone, nitrofurantoin, chloramphenicol, chloroquine, aspirin
Blood results in acute haemolytic crisis
Reduced Hb
Raised reticulocytes
Hyperbilibuinaemia
Increased LDH
Blood film in G6PD deficiency
fragmented red cells ‘bite’ cells and polychromasia
Heinz bodies (denatured hB)
Not in crises - blood film normal
Pyruvate kinase deficiency
Results in sufficient ATP production
Causes rigid cells and haemolysis
How is pyruvate kinase deficiency inherited?
Autosomal recessive
Pyruvate kinase deficiency blood film
Prickle red cells
Autoimmune haemolytic anaemia - what it is and types
Produce antibody against their own red cells
Types - warm and cold (depends if antibody binds most strongly at 37 degrees or 4 degrees)
Warm AIHA
usually IgG antibodies
Cold AIHA
usually IgM antibodies
Blood results in AIHA
unconjugates hyperbilirubinaemia
Raised LDH
Increased retidulocytes
Reduced heptoglobin levels
Postive DAT
Treatment in AIHA
Immunosuppressive treatment - steroids, azathioprine, cyclosporin
Lead poisoning - bloods and blood film
Microcytic anaemia
Blood film - basophilic strippling (basophilic granules seen in RBC)
Thalassaemias
Genetic defect that results in reduced rate of synthesis of alpha-globin or beta-globin chains
alpha thalassaemia
Gene deletion of a-globin
Normally inherit 4 (each copy of chromosome 16 has 2 copies)
Deletion of one or two = trait, asymptomatic
Loss of all 4 = a-thalassaemia major = death in utero or hydrops fetalis = death in few hours of birth
haemoglobin H disease
Deletion of 3 alpha globin genes = HbH disease
Microcytic hypo chromic
Splenomegaly
Excess of B-globin chain forms an abnormal Hb called HbH - consists of only B-globin chains
Detected - high-performance liquid chromatogaphy HPLC
Beta thalassaemia
mutations in B-globin gene (2 copies chromosome 11)
excess of a-globin as result - precipitate in erythrocytes = anaemia 2nd to ineffective erythropoiesis and haemolysis
Blood film - target cells, nucleated red blood cells and basophilic stippling
What age dose beta thalassaemia present?
3-6 months
Hb production switched from HbF to HbA
HbF = a-globin and gama globo
HbA = a-globin and beta-globing
6 month roughly 95% HbA
Treatment for B-thalassaemia major
Regular blood transfusions
Careful iron overload - iron chelation therapy started 10-15 RBC transfusions given or serum ferritin increases above 1000 - desferrioxamine
What causes Sickle Cell disease
Point mutation in b-globin gene= single amino acid change (valine for glutamine)
HbS is relatively insoluble and polymereizes when exposed to low oxygen tension
Creates sickle cells - dehydrated, rigid and less deformed = obstruct blood flow
Types of sickle cell disease
Sickle cell anaemia - homozygous for B-globin mutations HbSS
HbSC disease - single b-globin mutation in combination wit hHbC mutation HbSC
S B-thalassaemia - B-thalassaemia mutation in combination with B-globin
Types of sickle cell crisis
Veno-occlusive crisis (painful)
Sickle chest crisis
Splenic/ hepatic sequestration
Aplastic crisis - 2nd to parvovirus B19
Cerebral infarction
Management of sickle cell disease
- Avoid factors that may precipitate a crisis - cold, dehydration, over-strenuous exercise
- Twice daily penicillin proph. and vaccination
- Folic acid
What dose Bone marrow failure cause
Pancytopenia
Fanconi’s anaemia
Physical abnormalities - short stature, microcephaly, skin hyperpigmentation
Affected gene FANC genes BRCA 2
Triad of Shwachman-Diamond syndrome
-Bone marrow failure
-Pancreatic insufficiency
-Skeletal abnormalities
What is DIC
intravascular deposition of fibrinogen and consumption of coagulation factors and platelets
What triggers DIC
Infection
Malignancy
Blood transfusion
Liver failure
Widespread tissue damage
Coagulation screen - what does PT measure
II, V, VII, X
Extrinsic + common
What clotting factors does APTT test for
II, V, VIII, IX, X, XI, XII
Intrinsic and common
What clotting factors does thrombin time or fibrinogen test for
Fibrinogen
Steps of heamostatis
- Vasconstriction
- Temporary platelet plugging
- Coagulation cascade
- Fibrinolysis
- Regeneration
How do you test for 1st haemostatis (temporary platelet plugging(
Bleeding Tim e
PLT count
PLT aggregation
ANTI-PLATLETS
What test do you use ?for testing coagulation
PT
aPTT
TT
What is haemophilia A a factor defieicny of?
Factor 8
What prolongs pt
Vit K defiency
warfarin
liver disease
factor VIII, III, x defiency
APS
heparin
DIC
What prolongs aPTT
heparin
Haemophillia
Liver disase
aPS
warfarin
DIC
What prolongs TT
Hypofibrinogen
Thombin inhibitor
Heparin
DIC
liver disease
warfarin
Where do DOACs act?
Antirhombin and X
MoA of heparin
Increased antithrombin
How does haemophilia present
Presents with joint and soft tissue bleeding
What are test results in haemophilia And B
Long aPTT, normal PT
Treatment for haemophilia
Recombinant sources of clotting factors
Complication of factor treatment
Development of inhibit antibodies that block efficacy of the factor
Most commonly ass. with factor 8
What else can be used as an alternative to factor concentrate in mild haemophilia A
Desmopressin
Stimulates release of factor VIII and von Willebrand factor
What is Von Willebrand factor
Large glcyoprotein present in endothelial cells and platelets
What are the two main functions of VWF
- Promote platelet adhesion to damaged endothelium
- To bind and stables factor VIII, protecting It from proteolytic degradation
Presentation fVWF disease
Mucosal bleeding
Menorrhagia
Easy brushing
How do you diagnose VWF disease
- prolonged APTT
- Factor VIII: C will be reduced
- VWF ristocetin cofactor assay
How do antifibrinolytics work? (Tranexamic acid)
Prevent plasminogen to plasmin
Plasmin breaks down strands in fibrongen
Which clotting factors are low at birth
Vitamin K dependent clotting factors
What is immune thrombocytopenia purpura
Diagnosis of exclusion
Treatment of ITP
Self-limiting
If fails to respond within 6 months (chronic iTP) - short course of steroids
With bone marrow sample prior to treatment
IV immunoglobulins can be used
How does rituximab work
Anti-CD20 monoclonal antibody
B cells involved in pathogenesis of ITP
Why is chicken pox an important cause of stroke in childhood
Reduction in anticoagulant Protein S - increases hisk of thrombosis
What does Protein C do?
Inhibits factors V and VIII
What does protein S do?
Enhances action sof protein C
What is the most common inherited thrombophillia
Factor V leiden Mutation
Prevents protein C bind to and inhibiting factor V
What are inherited risk factors of thrombosis
Defiencies of -
Antithrombin
Protein C
Protein S
Aquired risk factors of thrombosis?
Presence of central venous line
Malignancy
DIC
SLE
Trauma
Polycythaemia
ABO blood group system - group a
Antigens - A
Antibodies - Anti-B
Compatible groups - A, O
ABO blood group systems - group B
Antigens - B
Antibodies - Anti-A
Compatible groups - B, O
ABO blood groups - AB group
Anitgens - AB
Antibodies - none
Compatible group s- A, b, ab, O
ABO groups - O group s
Antigen - none
Antibodies s- Anti - A, anti -B
Compatible O
How to present RhD haemolytic disease of newborn?
Mum’s have blood group and antibody screen at booking
If were RhD negative - 28 weeks - another antibody screening to see if sensitisation
If lack anti-d antibodies in 2nd trimester - given anti-D prop 28- 34 weeks
If anti-D antibody detected - antibody levels need to be measured to predict risk of developing HDN
How to calculate volume of red cell transfusions
Volume to be transfused = weight x Hb increment x 4
