Poikilocytosis is a general term used to describe the presence of abnormally shaped red blood cells (RBCs) in the blood. Normal RBCs (also called erythrocytes) are disc-shaped, thicker at the edges than in the middle, with a diameter of 6.2 to 8.2 micrometres. Their maximum thickness ranges from 2 to 2.5 micrometres, with a thickness in the centre of 0.8 to 1 micrometre.

When 10% or more of red blood cells have an abnormal shape, the condition is called poikilocytosis. The shape of poikilocytes may vary, ranging from flat to crescent-shaped, elongated, teardrop, or they may exhibit thorn-like projections or any other abnormal characteristic.¹

Red blood cells are responsible for transporting oxygen from the lungs to tissues throughout the body. When red blood cells present abnormal sizes (anisocytosis) or shapes (poikilocytosis), it could indicate inefficiency in oxygen delivery potentially leading to anaemia.

This article explores poikilocytosis, a condition characterised by the presence of abnormally shaped erythrocytes. It discusses symptoms, causes, diagnosis methods, and treatment options.

Symptoms and causes

What are the symptoms of poikilocytosis?

Symptoms depend on the cause of poikilocytosis. The typical symptoms are the same as those observed in anaemia.

Anaemia symptoms include:

• Weakness or fatigue
• Dyspnoea (difficulty breathing)
• Arrhythmia (irregular heartbeat)
• A “whooshing” noise in the ear (pulsatile tinnitus)
• Pale skin
• Headache
• Dizziness
• Chest pain 

What are the causes of poikilocytosis?

The disease can either run in families or be acquired later in life. Inherited conditions can be caused by genetic variations or mutations in the DNA sequence involved in the structure and function of erythrocytes.

Specific cell types are more common in certain conditions.

Inherited causes of poikilocytosis include:

• Sickle cell anaemia: A disorder where some RBCs are shaped like sickles or crescent moons that become rigid and sticky slowing or blocking the blood flow
• Thalassemia: A genetic condition in which the body produces less haemoglobin than normal. It involves target cells or codocytes
• Hereditary spherocytosis: A form of haemolytic anaemia where RBCs are destroyed earlier than normal. It involves spherocytes, cells that have a round shape resembling a sphere
• Pyruvate kinase deficiency: A rare disease that results in red cell haemolysis. It involves echinocytes, also known as burr cells or crenated red cells
• Hereditary elliptocytosis: it involves elliptocytes (ovalocytes)
• McLeod syndrome: A rare genetic disorder where individuals display star-shaped red blood cells, also known as acanthocytes or spur cells¹

Acquired conditions that usually arise later in life.

Acquired causes of poikilocytosis include:

• Iron deficiency anaemia: A common form of anaemia caused by a lack of iron in the body. It involves elliptocytes (ovalocytes)
• Megaloblastic anaemia: A disease caused by a deficiency of either folate (vitamin B9) or vitamin B-12. It involves dacrocytes (teardrop cells) and elliptocytes
• Autoimmune haemolytic anaemia: A blood disorder in which the body mistakes red blood cells for foreign substances and attacks them. It involves schistocytes and spherocytes
• Myelofibrosis: A rare form of bone marrow cancer. It involves teardrop cells (dacrocytes)
• Lead poisoning
• Liver and kidney diseases involve echinocytes also known as burr cells
• Alcohol-related liver disease involves acanthocytes or spur cells
• Infections such as those caused by Plasmodium¹

Diagnosis and treatment

How is poikilocytosis diagnosed?

Poikilocytosis is diagnosed with a blood smear examination. The test can be done during a routine physical check-up or if the patient is manifesting any unexplained symptoms or signs of anaemia.

Some cell types are found in certain conditions.

In addition to the blood smear, additional tests are done to determine what is causing poikilocytosis.

Other frequently utilised diagnostic tests include: 

• Serum iron levels (iron studies)
• Vitamin B-12 tests
• Complete blood count (CBC): A CBC is often ordered along with a blood smear examination to provide information on blood cells including levels and size. Specific values on a CBC such as MCV, MCH, MCHC and RDW can provide additional information about red blood cells
• Healthcare providers may also order a liver function test¹

How is poikilocytosis treated?

The treatment strategy for poikilocytosis depends on identifying its root cause. When poikilocytosis is caused by a nutritional deficiency, such as low levels of iron, vitamin B12, or folate, the standard approach involves dietary supplementation to replenish these nutrients. Furthermore, managing the underlying conditions, such as celiac disease, which contribute to the deficiency, is essential in the treatment plan.

When poikilocytosis has a genetic origin, such as in thalassemia or sickle cell anaemia, treatment may require greater caution and extended duration depending on the patient’s genetic status (homozygous or heterozygous). Certain cases may require regular blood transfusions, while others might need a bone marrow transplant.

Individuals with poikilocytosis resulting from other factors, like liver disease (with target cells or acanthocytes) should receive tailored treatment. For some, a liver transplant may be necessary, while those with sepsis or severe infections may require antibiotics.¹ 

What are the complications associated with poikilocytosis?

Most causes of poikilocytosis can be managed or possibly reversed through appropriate treatment. When left untreated, certain causes may lead to severe debilitation or even life-threatening complications such as organ failure. When anaemia is left untreated in children, it can influence their growth and development.² Once the cause of poikilocytosis is established, healthcare providers can prescribe treatments to prevent complications.

What is the prognosis for poikilocytosis?

The prognosis for poikilocytosis depends on its underlying cause. Conditions like iron deficiency anaemia and megaloblastic anaemia have a generally good prognosis as they can be resolved by correcting the underlying nutritional deficiency. However, diseases such as sickle cell anaemia may have a less favourable prognosis due to possible issues such as infections and vaso-occlusive crises. Lifelong treatments may be necessary for effective management.¹ 

Epidemiology 

Sickle cell disease is an autosomal recessive disease meaning that the affected individuals must have two copies of the sickle haemoglobin gene to have the disease. Carriers are common in Africa, India, the Mediterranean, and the Middle East.

Thalassemia can be divided into alpha and beta. Alpha thalassemia is mostly found in sub-Saharan Africa, the Mediterranean, and typically in tropical regions. Beta thalassemia affects people in the Mediterranean. Hereditary spherocytosis is common in North American and European lineage while Pyruvate kinase deficiency is mostly found in northern Europe and Japan.¹

Summary

Poikilocytosis, characterised by irregularly shaped red blood cells, may indicate potential issues with oxygen delivery in the body. Typically, RBCs are disc-shaped, but in poikilocytosis they can vary in shape, being flat, crescent-shaped, elongated, or exhibiting abnormal projections. Symptoms may include weakness, difficulty breathing, or irregular heartbeat.

Causes may differ, from inherited disorders like sickle cell anaemia to acquired conditions such as iron deficiency anaemia, or autoimmune haemolytic anaemia. Diagnostic methods include blood tests and examination of blood smears under a microscope.

Treatment depends on the underlying cause and may include dietary supplements, medications, or even transfusions. In specific cases, untreated poikilocytosis can lead to severe complications like organ failure. Prognosis varies based on the underlying condition, with some cases being manageable with treatment, while others may need ongoing care and carry higher risks of complications.