APLASTIC ANEMIA

DR PATRICIA ESEIGBE MBBS, MPH (Liverpool), FWACP

LECTURER/CONSULTANT

DEPARTMENT OF FAMILY MEDICINE

BINGHAM UNIVERSITY/ BINGHAM UNIVERSITY TEACHING HOSPITAL, JOS.

JUNE, 2023.

​

OUTLINE

• INTRODUCTION
• PATHOGENESIS
• ETIOLOGY
• CLINICAL FEATURES
• DIAGNOSIS
• TREATMENT
• CONCLUSION
• BIBLIOGRAPHY

INTRODUCTION

• Aplastic anemia is a normocytic-normochromic anemia
• It is due to a loss of blood cell precursors leading to hypoplasia of the bone marrow, red blood cells (RBCs), white blood cells (WBCs), and platelets.
• Aplastic anemia is pancytopenia, panhypoplasia of the bone marrow
• Pure RBC aplasia is restricted to the erythroid cell line
• It is classified into primary (congenital or idiopathic acquired) or secondary

PATHOGENESIS

• Substantial reduction in number of hemopoietic pluripotent stem cells seem to be the underlying defect in all cases
• In addition, a fault in the remaining stem cells or an immune reaction against them
• Results in the inability to divide and differentiate sufficiently to populate the bone marrow
• Another suggested factor is a primary fault in the marrow microenvironment (but there is success in stem cell transplantation).

ETIOLOGY

• PRIMARY
• Congenital; Fanconi and Non-Fanconi types
• Idiopathic acquired
• SECONDARY
• Ionizing radiation
• Chemicals
• Drugs
• Viruses

Etiology -2

PRIMARY: CONGENITAL

Fanconi type

• An autosomal recessive pattern of inheritance
• Presents between ages 5 and 10 years
• Often associated with growth retardation and congenital skeletal defects such as microcephaly, absent radii or thumbs, congenital renal defects (pelvic or horseshoe kidney), hypo/hyper pigmentation of the skin, mental retardation

Dyskeratosis congenita

Diamond-Blackfan anemia: Pure red cell aplasia

Severe congenital neutropenia

​

Etiology -3

Idiopathic acquired

• Most common type
• Autoimmune T-cell mediated damage

SECONDARY

Secondary Aplastic anemia

• Commonly due to a direct damage to the hemopoietic marrow

Examples include Ionizing radiation such as accidental exposure to radiotherapy, radioactive isotopes, nuclear power stations

​

​

Etiology -4

Secondary causes cont’d

• Chemicals – Benzene, Organophosphates, DDT, other pesticides, Recreational drugs
• Drugs – Busulfan, Melphalan, Nitrosurea, Cyclophosphamide, Anthracyclines.

Rarely by Chloramphenicol, Gold salts, Sulphonamides, Anti-inflammatory, Anticonvulsant/anti-depressant

• Viruses – Viral Hepatitis, Epstein-Barr, HIV, Parvovirus B19, Cytomegalovirus

​

CLINICAL FEATURES

• Onset can be at any age
• Peak incidence is around 30 years
• Slight male predominance
• Can be acute or insidious
• Symptoms and signs are from anemia, neutropenia, or thrombocytopenia
• Pallor, other symptoms of anemia
• Petechiae, ecchymosis, bleeding from the gums, bleeding into the conjunctiva, or other tissues, epistaxis, menorrhagia, bruising
• Infections – various organisms
• The lymph nodes, liver, and spleen are not commonly enlarged.

DIAGNOSIS

• Complete blood count (CBC)
• Bone marrow examination

Findings include;

• Normochromic, normocytic or macrocytic anemia. Decreased Reticulocytes
• Leucopenia, especially in granulocytes
• Thrombocytopenia
• No abnormal cells in the peripheral blood
• Bone marrow shows hypoplasia, loss of hemopoietic tissue, with replacement by fat (75% of the marrow). Main cells present are lymphocytes and plasma cells, while megakaryocytes are reduced or absent

​

TREATMENT

General

• Remove the cause if known
• Supportive care initially including
• Blood transfusion, platelet concentrates
• Anti-fibrinolytic agent like tranexamic acid
• Prevent and treat infections with Antibiotics and antifungal agents
• Other supportive care
• A Hematologist must be involved in the management.

​

Treatment -2

Specific

• Depends on the severity of illness, age of the patient, and potential sibling stem cell donor
• Severity of illness is assessed by the reticulocyte, neutrophil and platelet counts, and the degree of marrow hypoplasia
• Relapse may occur
• Rarely, the disease may transform into myelodysplasia, or acute leukemia.

Treatment -3

Specific treatment cont’d

• Antilymphocyte or antithymocyte globulin (ALG or ATG); it benefits 50 – 60% of acquired cases, given with corticosteroids to reduce side effects
• Ciclosporin; effective too, and can be combined with ALG
• Alemtuzumab (Anti-CD52); commonly used when ATG has failed
• Androgens; beneficial in some Fanconi anemia patients but has marked side effects
• Haemopoietic growth factor

​

​

Treatment -4

Stem cell transplantation

• Allogeneic, identical twin or HLA-compatible sibling
• Offers the chance of permanent cure
• Is favored in younger patients (< 30 years old)
• Cure rates of up to 80% are obtainable
• Other forms of transplant are used in older patients

Surgery

• Thymectomy is considered in patients with thymoma-associated pure RBC aplasia.

CONCLUSION

• Aplastic anemia presents as subnormal hemoglobin, neutrophils, and platelets
• It is associated with a hypoplastic bone marrow
• It can be congenital or acquired
• Diagnosis is via CBC and bone marrow examination
• Supportive treatment is essential
• Specific treatment modalities are available
• Always seek the expertise of a Hematologist in suspected cases.

BIBLIOGRAPHY

• Porter RS and Kaplan JL. The MERCK Manual of Diagnosis and Therapy, 19^th ed. 2011 Merck & Co. Inc. USA

​

• Hoffbrand, A.V. & Moses, P.A.H. (2011) Essential Haematology. Wiley-Blackwell. Chapter 22

​

​

​

​

Thanks for listening!

God Bless You!

​