Pancytopenia

Pancytopenia is a reduction of all cells in the peripheral blood (RBCs, WBCs, platelets) → anaemia, leukopenia, thrombocytopenia.

It may happen as a result of decreased production due to bone marrow failure. It may be the result of immune-mediated destruction or non-immune-mediate sequestration in the periphery or spleen.

Causes of pancytopenia

🚢

There are numerous causes of pancytopenia. One way to remember some of the causes is the mnemonic ABCD MR SHIPS:

• Aplastic anaemia
• Bone marrow infiltration - such as leukemia and lymphomas, myeloma, and metastatic cancers.
• Chemotherapy
• DIC
• Megaloblastic anaemia
• Radiation
• Sepsis
• Hypersplenism
• Infection
• Paroxysmal nocturnal haemoglobinuria
• SLE

🔢 Classification

Decreased bone marrow production

1. Chemotherapy - this is the most common cause of transient pancytopenia. Especially when coupled with radiotherapy. It usually resolves in 1-2 weeks after cessation of treatment but some regimens are associated with longer periods.
2. Megaloblastic anaemia - most megaloblastic anaemias cause macrocytic anaemia without leukopenia or thrombocytopenia, but severe megaloblastic anaemia may lead to thrombocytopenia. It is usually due to vitamin B12 or folic acid deficiency.
3. Bone marrow infiltration - as mentioned previously this is haematological infiltration (with leukaemia, lymphoma, myelofibrosis) or non-haematological with breast, kidney, lung, prostate, thyroid cancer etc.). In children it may even be due to neuro lastima, rhabdomyosarcoma, Ewing’s sarcoma, retinoblastoma.
4. Gaucher’s disease - this is a congenital lysosomal storage disorder which infiltrates the bone marrow leading to reticulin fibrosis of the bone marrow. These patients have bone marrow infiltration coupled with massive splenomegaly and functional hypersplenism.
5. Infection - such as HIV.
6. Anorexia nervosa
7. Transfusion-associated graft-versus-host disease

Clonal disorders

1. Myelodysplastic syndrome - an acquired clonal disorder that is characterised by dysplastic haematopoiesis and may progress to acute myeloid leukaemia (AML).
2. Paroxysmal nocturnal haemoglobinuria - we will discuss this further in haemolytic anaemias.

Bone marrow failure

1. Fanconi’s anaemia - autosomal recessive disorder characterised by short stature, hyperpigmentation, skeletal anomalies, increased incidence of solid tumours and leukaemia.
2. Idiopathic aplastic anaemia - we will discuss this further below.

Increased destruction

1. Liver disease - hepatitis (autoimmune or viral), ALD, portal hypertension.
2. Hypersplenism
3. Haemophagocytic syndromes
4. Drug-induced immune pancytopenia - most frequently with quinine, sulfonamides, rifampicin.
5. Autoimmune lymphoproliferative syndrome

💯 Criteria

To determine if one has pancytopenia they should have:

• Anaemia - low Hb.
• Leukopenia - low WCC or low neutrophil count.
• Thrombocytopenia - low platelet count.

APLASTIC ANAEMIA

Aplastic anaemia (AA) is a form of pancytopenia with hypocellular marrow. This differs from pancytopenias with hypercellular marrow (bone marrow infiltration). It also has no abnormal cells. Its peak incidence is 30 years old.

Pathophysiology

Aplastic anaemias can be classified as either acquired or congenital. Acquired AA is mostly idiopathic.

😷 Presentation

• Recurrent infections
• Fatigue
• Pallor
• Bleeding or bruising

🔍 Investigations

1. 🥇 FBC - diagnosis of AA requires only two cytopenias.
1. Hb <100
2. Platelets <50
3. Neutrophil count <1.5
4. If there is macrocytosis it may suggest Fanconi anaemia or dyskeratosis congenita.
2. 🏆 Bone marrow biopsy - hypocellular marrow is the gold-standard diagnostic for AA. There should also be no abnormal cells present.

🧰 Management

Managing aplastic anaemia:

Non-severe disease

Solely required monitoring with regular FBCs. If there is some aetiological factor, it should be withdrawn or treated.

Severe disease

If >50 - immunosuppression is first-line. Agents such as ciclosporin, methylprednisolone, and antithymocyte immunoglobulin may be used.

If <50 - stem cell transplantation is first-line.

FANCONI ANAEMIA

A congenital form of aplastic anaemia. It is usually autosomal recessive but X-linked mutations have been identified.

Some features of Fanconi anaemia include:

1. Short stature
2. Pigmentation abnormalities
3. Renal and genital abnormalities

4. Solid tumours
5. Hearing loss
6. Pancytopenia

DYSKERATOSIS CONGENITA

It has a classic triad of:

1. Abnormal nails
2. Reticulated skin rash
3. Leukoplakia