Blood II Flashcards
describe anaemia of chronic diseases
- one of the most common anaemias
- associated w/ RED RBC prolif, impaired Fe UTILISATION
- associated w/ CHRONIC MICROBIAL INF (eg osteomyelitis), CHRONIC IMMUNE DISORDERS (eg rheumatoid arthiritis), NEOPLASM (Hodgkin’s lymphoma, lung carcinoma)
what is the pathogenesis of anaemia of chronic diseases
CYTOKINE DRIVEN INHIBITION OF RBC PRODUCTION
what are the lab features of anaemia of chronic diseases
- LOW serum iron
- LOW iron binding capacity
- INC storage iron in marrow macrophages
- RBC: normochromic/normocytic
microcytic and hypochromic (as in iron deficiency anaemia)
what are the clinical features of anaemia of chronic diseases
- anaemia not severe
- the most dominant symptoms are those of underlying diseases
what is the treatment for anaemia of chronic diseases
- treat UNDERLYING CONDITION
- patients may benefit from from EPO
what is aplastic anaemia
Defined as pancytopenia (anaemia, neutropenia, thrombocytopenia) with hypocellularity of bone marrow
how common is aplastic anaemia
Uncommon but serious condition
what is the cuase of aplastic anaemia
- May be inherited; more commonly acquired
- Probably results from failure or suppression of pluripotent stem cells
- Very occasionally, defect of the erythroid series only - “pure red cell aplasia”
MAJOR CAUSES:
1) Idiopathic
- Primary stem cell defect
- Immune mediated
2) Chemical agents
- Dose related (alkylating agents, benzene)
- Idiosyncratic (chloramphenicol)
3) Physical agents
- Whole body irradiation
4) Viral infections
- Hepatitis (unknown virus)
- Cytomegalovirus infection
5) Miscellaneous
- Infrequently, many other drugs and chemicals
what are the clinical features /symptoms and physical findings of aplastic anaemia
Symptoms - results of the deficiency of:
- Red blood cells (anaemia)
- White blood cells (susceptibility to infection)
- Platelets (bleeding)
Physical findings:
- Bruising, bleeding gums and epistaxis
- Mouth infection common
what investigations can be done for aplastic anaemia
1) Blood count
- Pancytopenia
- Low or absent reticulocytes
2) Bone marrow examination
- A hypocellular marrow withincreased fat spaces
how can we have a differential diagnosis of aplastic anaemia compared to other causes of pancytopenia
Bone marrow biopsy :bone marrow cellularity
what is the treatment for aplastic anaemia
- Withdrawal of offending agent
- Supportive care (infection control)
- Specific treatment (bone marrow transplantation; immunosuppressive therapy)
describe haemoglobin abnormalities
- Mostly caused by single point mutation
- Abnormal globin chain structure
- Imbalanced globin chain production
describe sickle cell
- disease of abnormal ß globin chains
- Common in people of African origin
- cause: : homozygous inheritanceof a gene coding for a haemoglobin variant (HbS) single base mutation (A –> T) causes (Glutamine –> Valine)
what is the pathogenesis of sickle cell
- HbS crystalline at low O2 tension
- causes Shortened RBC survival and Impaired passage through microcirculation
what are the clinical features of sickle cell
characterized by tissue infarction and chronic haemolysi:
- Vaso-occlusive crises (acute pain in hands/feet; severe pain in other bones)
- Anaemia (chronic haemolysis or acute fall in Hb)
- precipitated by other factors (infection, dehydration, cold, acidosis, hypoxia)
Heterozygous state (sickle cell trait): no symptoms
what investigationc can be done for sickle cell
management
Investigations:
- Blood count: Hb range 6-8 g/dl, reticulocytes 10-20%−Blood film: sickled RBC
MANAGEMENT:
−Asymptomatic: no treatment
−Avoid precipitating factors
−Acute painful attacks: supportive therapy
−Severe haemolysis: folic acid
−Infection: prophylaxis (antibiotics, vaccine)−Anaemia as indicated (transfusion, hydroxycarbamide)
what are thalassaemias
cause: : abnormalities of globin chain (a or b)synthesi
what is the pathogenesis of thalassaemias
imbalanced’globinchain production –> globin chains in RBC –> ineffective erythropoiesis& haemolysis
what are the types of thalassaemias
- b-thalassaemia major (b chain production↓):
Severe anaemia from infancy, Splenomegaly,Marrow expansion - b-thalassaemia minor:
Clinically mild - a-thalassaemia (a chain production↓):
Range from severe anaemia to clinically insignificant disease
what are the laboratory tests for thalassaemias
Blood count and film:
- Hypochromic/microcytic anaemia
- Reticulocytes ↑
−Nucleated red cell
Diagnosis by haemoglobin electrophoresis
- INC in Hb F and DEC in Hb A
what is an example of red cell enzyme deficiency
Glucose-6-phosphate dehydrogenase (G6PD) deficiency
(G6PD) deficiency causes what
haemolytic anaemia
what is (G6PD) deficiency
- G6PD deficiency is the chief RBC enzyme defect
- Affecting 100million people, mainly male
- A common heterogeneous X-linked trait, predominantly in Africa, Mediterranean and Middle East
describe G6PD
- G6PD is a vital enzyme in hexose monophosphate shunt, which maintains glutathione in the reduced state (GSH)
- GSH protect against oxidant injury in RBC
- G6PD deficiency reduces the ability of RBC to protect against oxidative injuries
- This leads to haemolysis
what is the genetics behind G6PD deficiency
- Over 400 G6PD variants; mostly single AA substitutions
- The most common types have normal activity:
- Type B+, almost all Caucasians and 70% black Africans
- Type A+, about 20% of black Africans
- Two common variants with reduced activity :
- African (A-) type, mild deficiency and more marked in older cells. Haemolysis is self-limiting
- Mediterranean type, both young and old red cells have very low enzyme activity; serious clinical consequenc
what are the clinical manifesations of G6PD deficiency
- Most are asymptomatic, but may get oxidative crisis when precipitate
- Neonatal jaundice
- Chronic haemolytic anaemia
- Acute haemolysis, precipitated by
- Ingestion of broad beans
- Administration of oxidising drugs (quinine, sulphonamides)
- Infection and acute illness
what investigations can be done for G6PD
- Blood count normal between attacks
- During an attack:
- Blood film – bite cells, blister cells
- Haemolysis (serum bilirubin↑)
- Measurement of G6PD level
what is the treatment for G6PD deficiency
- Avoid precipitating factors
- Transfusion if necessary
- Treat the underlying infection
