Anaemia and polycythemia Flashcards
What is the lifespan of a RBC
110-120 days
List causes of rapid intravascular red blood cell destruction
1) mechanical haemorlysis associated with DIC
2) Massive burns
3) Toxins (snake bite)
4) Infections (malaria, or clostridium sepsis)
5) Severe glucose 6 phosphate dehydrogenase deficiency with exposure to oxidant stress
6) ABO incompatibility transfusion reaction
7) Cold agglutinin haemolysis
Discuss clinical signs of anaemia
Vitals
Skin
- pallor
- diaphoresis
- jaundice
- cyanosis
- purpura, ecchymoses, petachiae
- evidence of penetrating wound
CVS
-S3-4, murmus
Abdo
- hepatoslenomegaly
- rectal and pelvic exam
- masses
- stool haemoglobin testing
Give a differential for aneaemia caused by reduction in RBC production
Hypochromic microcytic anaemia
- Iron deficiency
- Thalassemia
- Sideroblastic anaemia or lead poisoning
- Chronic disease
Macrocytic
- Vit b12 deficiency
- Folate deficiency
- liver disease
- hypothyroidism
Normocytic
- primary bone marrow involvement (aplastic anaemia, myeloid metaplasia with meylofibrosis)
- Resulting from underlying disease (hypoendocrine state (thyroid, adrenal, pituitary) uremia, chronic disease, liver disease
Discuss iron defiency anaemia
Most common gorm in women of childbearing age.
Diagnosis is made by hypochromic microcytic anaemia + iron studies
Fasting iron <60
Total iron binding capcity > 400 - raised
Saturation <15%
Serum ferritin <10mg/ml - this can be raised as acute phase reactant
Treated with oral iron replacement
300mg (60mg of elemental iron) or 3mg/kg.day - generally well tolerated although it may cause nausea and vomting or constipation. Patient should be warned that stools can turn black
Discuss thalassemia
HB molecule is present as two paired globin chains each type of HB is made up of two different globins. Normal adult HB is made up of two alpha and two beta chains.
Although there are many variations in thalassemia only three are commonly considered
1) THalassemia major (homozygous B chain thalassaemia) occurs predominantly in Mediterranean populations.
Usually becomes apparent in the first 6 months of life with the decline in foetal Hb. It is characterised by severe haemolytic anaemia, hepatosplenomegaly, jaundice, failure to thirve and premature death. If patients survive they are transfusion depenedent and die due to iron deposition in tissues particularly in the myocardium or infection
2) Thalassemia minoe (hetrozygous B chain thalassaemia) - mild anaemia and other wise asymptomatic
Discuss investigation and management of thalassaemia
Microcytic hypochromic anaemia.
Therapy consist of blood transfusions where the goal of transfusion therapy incude correction of anaemia, supression of erythropoiesis and inhibition of GIT iron absorption.
Iron chelation therapy is often required
Bone marrow transplantation from human leukocyte antigen identical donors has resulted in disease free survivial in 60-90% of cases
Discuss sideroblastic anaemia
Involves a defect in porphyrin synthesis. The resultant impaired haemoglobin production causes excess iron to be deposited in the metochondria.
Mild to moderate anaemia is seen with increased serum iron and ferritin levels
Smear may demonstrate iron containing incusion bodies in RBCS
Idiopathic is most common and is considered a preleukemic state
Secondary causes include -chloramphenicol -isoniazid -cycloserine -infection -carcinoma -leukamia _RA -lead toxicity
jSome patients with sideroblastic anaemia are deficient in pyridoxine and respond to treatment with 100mg of pyridoxine three time a day
Discuss macrocytic and megaloblastic anaemias
THe haem manifestation of a total body alteration in DNA synthesis, megaloblastic anaemia is caused by vit b12 and folic acid defiecny
Clinical features asscociated with megaoblastic anaemia
- lemon yellow skin from combination of pallor and low grade icterus
- Petchiae, mucusal bleeding from thrombocytopenia
- infection from leukopenia
- fatigue, dyepnoea on exertion postural hypotension from anaemia
- sore mouth or toungue from megaloblastosis of mucosal surfaces
- paraethesia and ataxia related to myelin abnormality in vit b12 defieincy
List causes of folate defiency
1) Inadeqyate dietary intake
- poor diet or overcooked or processed food diet
- alcoholism
2) inadqaute uptake
- malabsorption
3) inadequate use
- metabolic block caused by drugs such as methotrexate or trimethoprim
- enzymatic deficiency congenital or acquired
4) increased requirement
- pregnancy
- increased RBC turnover- ineffective eryhtropoeiss, haemolytic aneamia, chornic blood loss
- malignant disease
List causes of Vit b2 defiency
1) inadequate dietary intake
2) inadequate absorption
- Absent or inadequate intrinsic factor as seen in patients with pernicious gastrectomy and anaemia- in anaemia autoimmune antibodies acic against gastric parietal cells and intrinsic factor
- abnormal ileum
3) inadeaute use
4) increased requirement
5) increased excretion or destruction
Discuss aplastic anaemia
Rare but may have severe manifesations. It is suspected in anaemic patients with normal incdices a low reticulotyce count and a history of exposure ot certain drugs or chemicals
- Chloramphenical
- anticonvulsants
- insecticides
- solvents
- sulfonamides - bactrim, thiazides, acetazolamide, celecoxin
Autoimmune disease, viral hepatitis, radiation and pregnancy have all also been associated with aplastic anaemia
The aplastic state may extend to all cell lines and results from destruction by immune stimulated lymphocytes or failure of the marrow stem cell. On occasional only one line failes as in RBC aplasia.
Discuss clinical features of haemolytic anaemia
Intravascular haemolysis is usually associated with an acute process and has a dramatic appearance
-large number of RBCS may be lysed wihtin the circulation. THe pathological process primarily involves the handling of released HB and a compensatory response to decreased o2 carrying capability.
Free HB is initially bound to haptoglobin. This complex is carried to the liver converted to bilirubin conjugated and excreted.
The clinical picture of extravascular haemolysis is usually mild to moderate anaemia, intermittent jaundice and enlargement fo the spleen.
Discuss DDX of haemolytic anaemia and give DDX for MAHA
Intrinsic to the cell membrane
1) enzyme defect
- pyruvate kinase deficiency
- G6pD defiency
2) Membrane abnormalitiy
- spherocytosis
- eliptostamatocytosis
- paraxysmal nocturnal haemoglobinuria
- spur cell aneami
3) HB anormalities
- Haemoglobinopathies
- thalassemias
- unstable HB
Extrinsic to the cell memrbnea
1) immunologic
- alloantibodies
- autoantibodies
2) mechanical
- Microangiopathic haemolytic anaemia
- CVS such as proshtetic heart valve
3) enevironemtnal
- drgus
- toxins
- infection
- thermal
MAHA DDX
- DIC
- HELLP
- HUS
- Malignancy
- Malingnant htn
- snake envonming
- TTP
- Vasculitis
Discuss intrinsic enzyme defects
85-90% of the membrane sustaining energy production of the erythrocyte is through the anaerobic glycotic pathway. At least 8 known enzyme deficiencies are assocaited with this pathway with pyruvate kinase defiency being the most common. It manifest as haemolyitc jaundice and is usually diagnosed in infancy
the remaining 10-15% of RBC glycolysis occurs by way of the hexose monophosphate shunt - this bypass mechanisms occurs in the early stage of the glycolytic pathway and generates NADPH-which is important in maintaining reduced glutathione which is essential in the protection of HB from oxidant injury. A defiency in the first enzyme in this pathway G6PD occurs in 11% of Afrigcan amercan man
The clinical manifestation is usually an acute haemolytic episode that may be both intravascular and extravascular. It occurs 24-48 hours after the ingestion of an oxidant drug or after an acute infection.
