Normocytic anaemia Flashcards
What are the conditions associated with anaemia of chronic disease?
- Chronic infections, eg Tuberculosis
- Chronic inflammation, eg Rheumatoid Arthritis, Inflammatory Bowel Disease
- Malignancies
- Acute variant (eg. severe sepsis, myocardial infarct)
- Others eg. Cardiac failure
What are the investigations in patients with anaemia of chronic disease?
High ferritin: Ferritin is an acute phase reactant. In the presence of inflammation, iron deficiency can be confidently diagnosed if ferritin less than 60 ug/L (94% PPV)
Low transferrin: Transferrin is a negative acute phase reactant. In inflammation, its levels decrease and since iron is bound to transferrin, serum iron levels naturally decrease as well
Low serum iron
Low/normal iron saturation of transferrin
Reticulocyte count: Inappropriately low reticulocyte count
Supportive findings
- Clinical presence of source inflammation +/- fever
- High inflammatory markers: ESR, CRP, ferritin
Aplastic anaemia is defined as ________________ of the bone marrow; there are no ________________ in the peripheral blood or bone marrow. It is usually an acquired condition but may rarely be inherited. Most of the time normocytic but can be macrocytic.
pancytopenia with hypocellularity (aplasia);
leukaemic, cancerous or other abnormal cells
What are the primary causes of aplastic anaemia?
Idiopathic 70-80%
Inherited (rare):
- Fanconi’s anaemia
- Dyskeratosis congenita
What are the secondary causes of aplastic anaemia?
Chemicals: benzene, toluene, glue sniffing
Drugs: Cytotoxic drugs in chemotherapy, antibiotics (chloramphenicol, penicillamine, phenytoin, carbamazepine, carbimazole, azothioprine)
Insecticides
Ionizing radiation
Infections eg: hepatitis, EBV, HIV, CMV, TB
Paroxysmal Nocturnal Haemaglobinuria
Pregnancy
What are the primary causes of pancytopenia?
Aplastic Anemia
Megaloblastic anaemia
Bone marrow infiltration or replacement:
- Hodgkin’s and non-Hodgkin’s lymphoma
- Acute leukaemia
- Myeloma
- Secondary carcinoma: Myelofibrosis
Fanconi’s anaemia is a multisystem disease with chromosomal instability. Patients are extremely sensitive to radiation and hence ______________ should be avoided. If they have a stem cell transplant, do not use typical doses of radiotherapy. It can present with congenital abnormalities such as ____________
Genetics: Autosomal recessive, multiple genes involved which affects the DNA repair pathway. Chromosomal instability resulting in spontaneous chromosomal breakage and hypersensitivity to DNA cross-linking agents (mitomycin C, diepoxybutane).
Clinical course: May appear normal until 5-10 years. Progressive marrow failure develops over extended interval. 10% terminate in _______________
Treatment: supportive, androgens, BM transplantation
X-rays and CT scans
skeletal abnormalities (hypoplastic thumbs, short stature, radial ray, congenital hip, vertebral, rib), skin pigmentation (café au lait spots, hyper/hypo pigmentation), microphthalmia etc.
acute leukaemia.
Patients with dyskeratosis congenita present with _________, ________, __________, __________.
Pathophysiology: there is a mutation in 2 genes (_____, _______), resulting in defective telemorase function and progressive telomere shortening. The early loss of stem cells from the defective telomerase function leads to progressive development of disease features.
abnormal skin pigmentation (89%), nail dystrophy (88%), bone marrow failure (85.5%) and leukoplakia (78%).
DKC1, TERC
What are the clinical manifestations of marrow failure?
The clinical manifestations of marrow failure from any cause are anaemia, bleeding and infection.
Anaemia: Fatigue, breathlessness
Thrombocytopenia:
- Bleeding is often the predominant initial presentation of aplastic anaemia with bruising with minimal trauma or blood blisters in the mouth.
- Physical findings include ecchymoses, bleeding gums and epistaxis.
Neutropenia:
- Mouth infections are common.
- Lymphadenopathy and hepatosplenomegaly are rare in aplastic anaemia.
- Also ask about recurrent infections
What are the investigations required for aplastic anaemia?
- FBC: Pancytopenia
- Reticulocyte count: The virtual absence of reticulocytes
- Blood film examination
- Bone marrow trephine: Hypocellular or aplastic bone marrow with increased fat spaces
- HbF% in children: prognostic factor
- Genetic study for congenital causes: Peripheral blood chromosomal breakage analysis
- Vitamin B12 and folate
- LFTs, Viral studies (especially hepatitis A, B and C as there is strong association). Viruses found to be able to cause aplastic anemia = Viral Hep, HIV, CMV, EBV.
- ANA and antidsDNA – for SLE
- Chest X-ray
- Abdominal U/S and echocardiogram
- Peripheral blood mutation analysis for dyskeratosis congenita
What is the treatment for aplastic anaemia?
The treatment of aplastic anaemia depends on providing supportive care while awaiting bone marrow recovery and specific treatment (oxymetholone, growth factors) to accelerate marrow recovery.
The main danger is infection and stringent measures should be undertaken to avoid this. Any suspicion of infection in a severely neutropenic patient should lead to immediate institution of broad-spectrum parenteral antibiotics.
Supportive care including transfusions of red cells and platelets should be given as necessary. The cause of the aplastic anaemia must be eliminated if possible.
Bone marrow transplantation is the treatment of choice for patients under the age of 40 with an HLA-identical sibling donor, where it gives a 75–90% chance of long-term survival
Immunosuppressive therapy is recommended for:
- Patients with severe disease over the age of 40
- Younger patients with severe disease without an HLA-identical sibling donor
- Patients who do not have severe disease but who are transfusion-dependent.
What is the camitta criteria that defines severe aplastic anaemia?
Severe aplastic anaemia is defined by the Camitta criteria, with bone marrow <20% cellularity and fulfilling 2 of 3 of the peripheral blood features listed below:
- Reticulocytes < 1% (20 x 109/L)
- Neutrophils <0.5 x 109/L
- Platelets <20 x 109/L
