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.
Discuss intrinsic membrane abnormalities
Altered shape is the main feature of autosomal dominant hereditary spherocytosis or elliptoctosis - the spleen sequesters these abnormal cells - clinical sequalae range from compensated asymptomatic anaemia to severe life threatening acquired aplastic crisis
Splenectomy is the treatment of choice
Discuss autoimmune haemolytic anaemia
Classified on the optimal temperature at which the atnibody reacts with the RBV membrane
Warm reacting antibodies (>37) are characterized by a higher incidence in younger patients, predominance in women, variable complement fixation and positve direct antiglobulin test result for IgG
COld reacting antibodies are seen predominantly in men and older patients wand with IgM complement fixation. THey may also be found in patients with infectious mononucelosis, mycoplasma and lymphoma may have raynauds
Discuss IX of haemolytics anaemia
The typical cell seen on smear in intravascular haemorlysis is the schizocyte and in extravscular is the spherocyte.
Extravascular may be seen in congenitial spherocytosis but more commonly indicates splenic activity against an antibody coated RBC memrbane.
Specific diagnosis may be made on smear such as with sickled cells or with Heinz bodies in G6PD
Haptoglobin levels will decrease due to binding with free HB
Plasma free HB and urinary HB can also be measured
LDH is released when RBC is broken down peripherally or in the marror
Hyperbilirubinaemia conjugagted and unconjugated
Direct and indirect Coombs
Discuss sickle cell disease
Genetically determines - replacement of glutamic acid by valine at the 6th position from the N-temrinal end of the beta chain.
This leads to formation of Hbs which tends to sickle in low oxygen tension areas
The result is a sickled cell that is less deformable and increased in viscosity and sludginf tendency of blood, and the sequestration of RBCs in the spleen and liver.
Clinical complex of thromboocclusive events, chronic haemolysis and organ injury is derived from this pathological process.
Discuss clinical features of sickle cell disease
Characterized by two major clinical features
1) haemolysis
2) acute vaso-occlusive events
Preceding infection, cold exposure and stress such as trauma are all potent precipitating factors.
The painful crisis is believed to have its origin in tissue ischemia caused by increased viscosity sludging and microvascular obstruction as a result of irreversibly sickled cells Sliding and vascular blockage cause stasis deoxygenation and local acidosis which promotes sickling continuing
Common presenting complaints include
1) acute spinal pain
2) abdominal pain (mesenteric occlusions)
3) chest pain (pulmonary vascular occlusion)
4) neuro infovlemtn (TIa, stroke, seizures)
5) respiratory embarressment and hypoxia
Discuss CNS features of sickle cell and indications for exchange transfusion
Neuro:
-TIA
-CVA
-Cerebral infarction
-spinal cord infarction
-vestibular hearing problems adn loss
neurolgoical complications occur in 25% of paitents with sickle cell anaemia by the time they are 45 years old
In the setting of stroke exchnage transfusions is recommended with the goals of HBs of less than 30% and a total Hb of limited to 100
-Lysis of patients with stroke secondary to sickle cell are the same as for any other CVA
EXCHANGE TRANSFUSION
- Neuro (tia, stroke or seiure)
- lung involvement (Pao2 <65 mmhg with fio2 .6%)
- sequestration syndromes
- priapism
Discuss acute chest syndrome
Is the most common pulmonary disease associated with sickle cell disease and one of the most common causes of deaht.
Patients with acute chest syndrome have fever, cough, chest pain, dyspnoea and new infiltrates on the chest radiograph. The injury postulated to be related to pulmoanry micorvascular sludging, infarction of the pulmonary parenchyma and bone marrow fat embolization from infarcted bone.
Macrovascular PE and infection also play a pathogenic role.
Cause is not fully clear but 54% of the cases are associated withi infection including mycoplasma and chlamydia
ABs choice is similar to pneumonia
List sickle cell complications by organ
Skin
-stasis ulcer
CNS
-CVA
Eye
-retinal haemorrhage,retinoapthy
Cardiac
-CCF
Pulmonary -intrapulmonary shunting embolism infarct infection
Vascular
-occlusive phenomenon at any site
Liver - hepatic infarct hepatitis resulting from transfusion, -hepatic sequestration -intrahepatic cholestasis
Spleen
-acute sequestration
Genital
- decreased fertility
- impotence
- priapism
Skeltal
-bone infarct
asceptic necrosis
Discuss sickle cell complcications in children
May have an acute splenic sequestration syndrome. This syndrome invovles acute splenic enlargement from increased intrasplenic sickling and obsruction
Child may be shocked
Discuss IX in sickle cell disease
Smear
Retic count – retic count is usually 3-4 times the upper limits of normal. 3% or lower than the patients usual value may suggest an aplastic crisis.
Retic count higher than 12% indicates rapid haemolysis
Discuss management of sickle cell disease
Antisickling agent hydroxyurea reduces the frequency of painful crises in adults with a history of three or more crises annually. Hydroxyurea can take weeks to take affect.
Other agents including clotriazole, magnesium and butyric acid
Bone marrow transplantation puffers the only known cure for sickle cell disease and is associated with survicial rates greater than 90%
Current therapies inclduing rest, adequate nutrition hydration, oxygenation, analgeisa transfusion and therapy for infection are directed toward symptomatic relieve and attempt to stop the cycle of deoxygneating sickling and intravascular sludging.
ANalgesia as needed for occlusive crisis
Describe clinical features of polycythemia
Range from mild headaches to fullblown syndrome of hypervolaemia (vertigo, dizziness, blurred vision and headache), hyperviscosity (venous thrombosis) and platelet dysfucntion( epistaxis, spont bruising and GI bleeding)
List causes of apparent polycythemia
Appropriately increased EPO caused by tissue hypoxia
- Congenital heart defect with right to left shunt
- pulmomary disease (copd)
- carboxyhaemoglobinaemia
- ALtitude
List causes of secondary polycythemia
Inappropriate autonomous EP
-REnal origin -carcinoma, hydronephrosis
-other lesions -uterine fibroids, hepatoma,
-congential overproduction
-pure or essential erythrocytosis
AIDS
Discuss primary polycythemia
Polycythemia vera is a myeloproliferative disorder found predominantley in middle aged or older patients
The most seriosu problems are thrombotic episodes (CVA, MI, DVT)
May be satisfcatorly treated by phlebotomy
Discuss diangostic criteria for polycythemia vera
Cat A
1) increased RBC mass
- -MEN >185
- -WOmen >165
2) normal arterial o2 saturation >92@
3) splenomegaly
Cat B
1) Thrombocytosis platelets >400
2) Leukocytosis WBC >12 wihtout fever or infection
3) Leukocyte alkaline phosphatase score >100
4) Vitamin B12 >900
For diagnosis all of cat a Present or the first 2 of cat a along with any 2 of cat b
