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Anaemia (Aplastic anaemia (Treatment (Immunosupresive therapy (…
Anaemia
Aplastic anaemia
- failure of all 3 cell lines produced in the bone marrow, resulting in anemia, leukopenia, and thrombocytopenia (pancytopenia). The marrow is empty (hypocellularity (aplasia)) with the absence of precursor cells.
Causes
- Primary: inherited (rarely) (Fanconi”s aneamia ) or IDIOPATHIC ACQUIRED (67% of cases)
- Secondary:
Chemicals, e.g. benzene
Drugs: chemotherapeutic, Antibiotics
Ionizing radiation
Infections: Viral, e.g. hepatitis, EBV, HIV, erythrovirus
Paroxysmal nocturnal haemoglobinuria
Miscellaneous, e.g. pregnancy
Clinical features
- Symptoms of anemia—fatigue, dyspnea
- Signs and symptoms of thrombocytopenia (e.g. bleeding, petechiae, bruising)
- Increased incidence of infections (due to neutropenia)
- transform into acute leukemia
Diagnosis:
Normocytic, normochromic anemia.
hypocelularity ( aplasia ) of the bone marrow
Treatment
Immunosupresive therapy ( antithymocyte globulin ATG + ciclosporin+ steroids )
Or Bone marrow transplatation
Supportive care: Transfusion ( RBC , Platelets concentrates )
bad prognosis
- associated with the presence of two of the following three features:
Neutrophil count of <0.5×109/L
Platelet count of <20×109/L
Reticulocyte count of <40×109/L.
Microcytic (< 80)
Iron Deficiency Anemia
symptoms
- General symptoms+
Symptoms of iron deficiency:
● soreness,
● Atrophy of the pappillae of the tongue
● pica
● koilonychia=Spoon-shaped nails
● brittle nails
● brittle hairs
● A syndrome of dysphagia and glossitis (Plummer–Vinson or Paterson–Brown–Kelly syndrome)
Treatment
- Find the cause.
- Oral iron replacement (ferrous sulfate, 200 mg three times daily).
Side effects include constipation, nausea, and dyspepsia.
- parenteral iron is required by occasional patients, e.g. intolerant to oral preparation, severe malabsorption, chronic disease
Iron dextran can be administered IV or IM
- causes of failure to respond to oral iron are:
Lack of compliance,
Continuing haemorrhage,
Incorrect diagnosis, e.g. thalassaemia trait.
Diagnosis
- Microcytic, hypochromic (MCH (mean corpuscular haemoglobin) <27 pg).
- low serum iron, high TIBC.
- Bone marrow biopsy—the gold standard
- Serum soluble transferrin receptors:
increases in iron deficiency
help to distinguish between iron deficiency and anaemia of chronic disease
- Serum ferritin: low (most reliable test available)
- there is inadequate iron for haemoglobin synthesis.
- Most common cause of anemia
- due to:
Chronic blood loss: GI bleeding, menstrual flow, trauma,
Increased requirements: infancy, pregnancy, lactation
Impaired absorption: achlorhydria, gastrectomia, celiac disease, Crohn disease diet
Thalassemias
β-Thalassemias
Clinical syndromes
- Thalassemia minor (trait) (heterozygous β-chain thalassemia).
The most common type of thalassemia
Anaemia is mild or absent
usually asymptomatic
RDW, serum ferritin and the iron stores are normal
Hemoglobin electrophoresis—Hb F and Hb A2 are elevated
Treatment: usually not necessary
- Thalassemia intermedia
symptomatic with moderate anaemia
do not require regular transfusions
Patients may have splenomegaly, bone deformities, leg ulcers, gallstones and infections.
- Thalassemia major (Cooley’s anaemia) (homozygous β-chain thalassemia)
occurs in Mediterranean populations
- features: bacterial infections, Severe anaemia, microcytic hypochromic, Extramedullary haemopoiesis that soon leads to hepatosplenomegaly and bone expansion, Growth retardation, Skull x-ray show “crew-cut” ‘hair on end’ appearance of bony trabeculation.
- Hemoglobin electrophoresis—Hb F and Hb A2 are elevated
- Treatment—frequent PRBC transfusions
- Defects are mainly point mutations rather than gene deletions
- In homozygous β-thalassaemia, either no normal β chains are produced (β0) or β-chain production is very reduced (β+). There is an excess of α chains.
- In heterozygous β-thalassaemia there is usually symptomless microcytosis with or without mild anaemia.
Management
- aims are to suppress ineffective erythropoiesis, prevent bony deformities
- Long-term folic acid
- Regular transfusions
- Iron overload (hemochromatosis) caused by repeated transfusions treated by desferrioxamine (a chelating agent that eliminates excess iron) or deferasirox (currently used)
- Bone marrow transplantation
- gene therapy
a-Thalassemias
- One-gene deletion: Silent carriers
Asymptomatic
Normal hemoglobin and hematocrit level
No treatment necessary
- Two-gene deletion (α-thalassaemia trait)
microcytosis with or without mild anaemia
HbH bodies seen on staining a blood film with brilliant cresyl blue.
Common in African-American patients
No treatment necessary
- often caused by gene deletions, although mutations of the α-globin genes may also occur.
- Deletion of one α-chain geneis on chromosome 16 the most common
- common in Asian populations
- Three-gene deletion: HbH disease
four β chains with low levels of HbA and Hb Barts. HbA2 is normal or reduced.
moderate anaemia (Hb 70–100 g/L) and splenomegaly (thalassaemia intermedia). The patients are not usually transfusion-dependent.
- Four-gene deletion
no α-chain synthesis and only Hb Barts is present
Infants are either stillborn at 28–40 weeks or die very shortly after birth. They are pale, oedematous and have enormous livers and spleens – a condition called hydrops fetalis.
- Inherited disorders characterized by low production of the α- or β-globin chain of haemoglobin
- If iron deficiency anemia is suspected, but the anemia does not respond to iron therapy, obtain a hemoglobin electrophoresis to rule out α- and β-thalassemia.
Sideroblastic
anaemia
- Hereditary (X-linked) or acquired—acquired causes include myelodysplasia, myeloproliferative disorders, myeloid leukaemia, drugs (e.g. isoniazid), alcohol misuse and lead toxicity.
- presence of ring sideroblasts is the diagnostic feature
- Treatment: remove offending agents. Consider pyridoxine.
- Clinical findings: increased serum iron and ferritin, normal TIBC, TIBC saturation is normal/elevated, which distinguishes it from iron deficiency; ringed sideroblasts in bone marrow.
-
Reticulocyte index
Normal (< 2%)
MCV
(80–99) Normocytic
• Aplastic anemia, BM fibrosis
• Tumor, Renal failure, Endocrine
• Anemia of chronic disease
• Haemolytic anaemias
(<80) Microcytic *
-
Fe normal,
TIBC normal or low
-
-
-
(>100) Macrocytic
- megaloblastic & non-megaloblastic
Elevated (> 2%)
- Haemolytic.
- Haemorrhagic.
Macrocytic anaemia
Megaloblastic anaemia
Vitamin B12 deficiency
pernicious anaemia
- The most common cause of vitamin B12 deficiency in adults.
- PA: Autoimmune disorders with atrophic gastritis and consequent failure of intrinsic factor production and vitamin B12 malabsorption
- common in the elderly, more common in females.
- symptoms: Symptoms of anaemia + GI symptoms (Loss of taste , sore tongue, nausea, vomiting, constipations)+ Neurological symptoms (polyneuropathy, paraesthesiae, Dementia, psychiatric problems)
- Investigations: RDW –normal, Reticulocytes ↓, leukopenia, LDH : increased due to haemolysis, Serum bilirubin may be raised as a result of ineffective erythropoiesis.
Serum methylmalonic acid (MMA) and homocysteine (HC): raised in B12 deficiency.
Serum vitamin B12 is usually well below 160 ng/L.
Serum folate level is normal or high, and the red cell
folate is normal or reduced
- There is an association with other autoimmune diseases, like thyroid disease, Addison’s disease and vitiligo.
- higher incidence of gastric carcinoma with PA.
- Treatment:
Initiating therapy : vitamin B12 (Hydroxocobalamin) 1000 ug/daily-10-14 days.
Maintance therapy : 100-200 ug / month
higher incidence of gastric carcinoma-gastroscopy is necessary every 2 years
Folic acid deficiency
causes
- Poor intake ( Old age, Starvation, Alcohol)
- Cancer, GI Disease.
- Antifolate drugs (Anticonvulsants, Methotrexate)
- Physiological (Pregnancy), Pathological (Haematological), Malabsorption
-
- asymptomatic or similar as pernicious anaemia ( wihout neurological symptoms ).
- The serum homocysteine level is increased in both folate deficiency and vitamin B12 deficiency. However, serum methyl- malonic acid levels are only increased with vitamin B12 deficiency.
- characterised by the presence of erythroblasts with nuclear maturation because of defective DNA synthesis (megaloblasts) in the bone marrow.
- Megaloblastic changes occur in: Vitamin B12 deficiency, Folic acid deficiency, Myelodysplasia due to dyserythropoiesis.
non- megaloblastic
causes are:
Alcohol excess
Liver disease
Reticulocytosis
Hypothyroidism
haematological disorders (e.g. aplastic anaemia,
sideroblastic anaemia, pure red cell aplasia)
Drugs (e.g. hydroxycarbamide, azathioprine)
transfusion
blood
- not recommended unless:
Hb concentration is <7 g/dL, OR patient requires increased oxygen-carrying capacity (e.g coronary artery disease)
- 1 unit of packed RBCs increases Hb level by 1 point, and Hct by 3 points
- PRBCs (contain no platelets or clotting factors).
- Platelet transfusions—1 unit raises platelet count by 10,000.
- Whole blood only for massive blood loss (blood should be warmed to prevent a decrease in core body temperature).
- FFP:
all of the clotting factors, no RBCs/WBCs/platelets.
for high PT/PTT, coagulopathy, and deficiency of clotting factors, liver failure.
- Cryoprecipitate: factor VIII and fibrinogen, For hemophilia A, decreased fibrinogen (DIC) and vWD.
Posthaemorrhagic anaemia
- Normocytic, normochromic ,
- Low haemoglobin concentration -3-4 hours after bleeding
- Reticulocytosis –maximum 7-10 days after haemorrhage
- Erythroblast in peripheral blood film
- Leukocytosis 10-30 G/l
- thrombocythemia ( to 1000 G/l)
- Secondary iron deficiency
- having a lower-than-normal number of red blood cells or quantity of haemoglobin
- Causes: Haemorragic, Poor erythropoiesis, hemolysis
- Symptoms (all nonspecific): may be asymptomatic, Fatigue, Headache, Dizziness, Dyspnea, Palpitations.
- Signs: Pallor (noted in the conjunctiva), tachycardia, Hypotension, Systolic murmur
- Investigations: Peripheral blood (low Hb), Bone marrow (cellularity and abnormal infiltrates, Type of erythropoiesis (normoblastic or megaloblastic))
- When red cell mass decreases, compensatory mechanisms maintain oxygen delivery to the tissues. include:
Increased cardiac output ( HR & SV)
Rightward shift of the oxyhemoglobin curve
Expansion of plasma volume