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Other Underproductive

Anaemias
What is Bone marrow failure ?
Primarily caused by stem cell injury
Inability of the BM to produce sufficient marrow
cells which include RBC, WBC and platelets

PANCYTOPENIA

Anaemia, leucopenia, thrombocytopenia


Epidemiology
Biphasic age distribution:
o Teens to 20s (inherited/constitutional)
o Elderly (acquired).
o Men = women are equally affected.
o Incidence: ~ 2 persons per million, higher in
East Asia ~4 persons per million
Causes
• Decreased Production
• Increased Destruction
Bone Marrow Failure

< 3 cell lines

Congenital Extrinsic Intrinsic

Genetic Abnormal humoral or


An abnormal or
cellular control of
mutations hostile marrow
hematopoiesis
microenvironment
Immunologic
suppression of
haematopoiesis
An acquired stem cell
injury
Clinical Features
• Anaemia - tiredness, weakness, pallor, breathlessness,
tachycardia.
• Neutropenia - recurrent or severe bacterial infections.
• Thrombocytopenia - easy bruising, petechiae, bleeding from the
nose and/or gums.
• Absence of hepatomegaly, splenomegaly or lymphadenopathy

Severe – 2 of the following:


• Neutrophils <0.5x109/l
• Platelets <20x109/l
• Reticulocytes<1%

Very Severe
• Neutrophils<0.2x109/l
• Infection present
Diagnostic criteria

• Pancytopenia, normal film


• Reticulopenia
• Hypocellular bone marrow – decreased
cellularity but normal cells
• Normal karyotype
Aplastic Anaemia
• Affects all cell lines
• Causes: Primary or Secondary
• Clinical Features: anaemia, neutropenia and
thrombocytopenia
• Examination : No organomegaly, facial and
skeletal abnormalities
Investigations
• FBC: - Normocytic, normochromic anaemia,
low reticulocyte, Leucopenia with normal
WBC, thrombocytopenia.
• Bone marrow aspiration and biopsy -
hypoplastic but normal cells
• Flow cytometry should be performed
according to established guidelines to screen
patients with suspected hematopoietic
malignancies
• Molecular genetic studies only performed
insuspected congenital types
Treatment
Supportive
• Transfusion support – packed cells and platelets
• Antibiotic therapy – prophylactic and empiric
• Haematopoietic growth factors – used along with
definitive therapies
Definitive
• Immunosuppressive therapy – Anti Lymphocyte Globulin/
Anti thymocyte globulin and Cyclosporin + eltrombopag

• Allogenic Stem cell transplant – matched sibling donor


Secondary Causes
• Paroxysmal Nocturnal Haemoglobinuria
• Toxins – benzene, organophosphates
• Drugs – chloramphenicol, cimetidine ​Nonsteroidal anti-inflammatory
drugs (NSAIDs) ​Sulphur drugs ,thiazide
diuretics, ​antimalarials, ​chemotherapy
• Infections – HIV, Hepatitis, EBV
• Autoimmune – RA, SLE
• Radiation
• Pregnancy - resolves with delivery or termination, possible
recurrence with subsequent pregnancy
Pure Red Cell Aplasia
Decreased RBC production, normal production
of other lines
Causes
• Idiopathic - Most common cause
• ​Thymoma
• ​Congenital form: Diamond-Blackfan syndrome
• Large granular lymphocyte leukemia/lymphoma
• ​Anti-erythropoietin antibodies
• Drugs including phenytoin, isoniazid, valproic acid,
chloramphenicol, azathioprine, and mycophenolate
12
• ​T-cell and B-cell lymphoproliferative disorders
• ABO-incompatible hematopoietic cell transplant
• ​Infection including parvovirus B10, mumps,
hepatitis, Epstein-Barr virus (EBV), and HIV
Clinical Features
• Symptoms of anemia: fatigue, dyspnea, pallor,
decreased exercise tolerance, angina
Diagnostic Workup
• Complete blood count (CBC) shows anemia that is often
severe, normocytic, and normochromic. White blood
cells and platelets are unaffected. Normal peripheral film
• Bone marrow aspiration and biopsy confirms diagnosis
• ​CT or MRI of the chest to rule out thymoma
• ​Viral studies as indicated
• ​Additional tests when an underlying hematologic
condition is suspected
Treatment
• Search for an underlying cause or offending drug and
treat accordingly
• Transfusion of packed red cells as needed
• Initial treatments – glucocorticoids, cyclosporine, and
cyclophosphamide are all reasonable. There have been
no randomized trials comparing these.
• Recurrent or refractory disease can be treated with
intravenous immunoglobulin (IVIG), plasmapheresis,
azathioprine, rituximab, alemtuzumab, or daclizumab.
• Hematopoietic stem cell transplantation may be
indicated in select cases.

.
Diagnostic approach to the patient with
pancytopenia
Diagnostic approach to Pancytopenia
• History – medications, previous chemotherapy or
radiation, toxic exposure, HIV risk factors, family history
• Physical examination – congenital anomalies,
organomegaly or lymphadenopathy
• Investigations – FBC, retics, smear, Vit B12 and folate,
LFTs, Connective tissue screen, BMA and biopsy,
Cytogenetics and flow cytometry (PNH)

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