Aplastic Crisis - Causes, Symptoms, and Management Protocols

Introduction

The aplastic crisis is characterized by failure in the production of red blood cells (erythrocytes) by the bone marrow. Generally, the aplastic crisis is a manageable clinical condition and exists only for a shorter duration. However, it becomes a medical emergency for patients with existing hemolytic disorders like sickle cell anemia. Severe aplastic crises are seen in children associated with parvovirus B19 infection.

Do Aplastic Crisis and Aplastic Anemia Mean the Same?

No, aplastic crisis and aplastic anemia are two separate medical conditions whose nomenclatures are often confused in clinical usage. This is because they both show similar clinical manifestations, such as decreased number of red blood cells and lowered hemoglobin levels.

• Aplasia refers to a defective formation, complete absence, and developmental cessation in the production of any particular tissue.

• Aplastic anemia is characterized by pancytopenia (total decrease in all the cellular components of blood), where there is a reduction not only in red blood cells but also in white blood cells and platelets due to hypocellular (reduced cells) bone marrow. Heredity causes, infection, immune disorders, exposure to chemicals, and radiation are some of the causes of aplastic anemia.

• Aplastic crisis refers to the failure of bone marrow to produce red blood cells, which commonly arises as a complication of hemolytic disorders or viral infections.

What Is Aplastic Crisis and What Are Its Causes?

The aplastic crisis is a transient shutdown of red blood cell production by the bone marrow. Although the aplastic crisis is a temporary condition, it turns into a potentially life-threatening complication due to various forms of chronic hemolytic conditions and also due to exposure to certain viruses. The predominant causes for an aplastic crisis are as follows:

• Sickle cell anemia.

• Thalassemia.

• Hereditary spherocytosis.

• Congenital dyserythropoietic anemias (CDAs).

• Parvovirus B19 infection.

• Other bacterial and viral infections (Streptococcus Pneumonia, salmonella, and Epstein-Barr virus).

• Erythrocyte enzyme deficiencies.

• Paroxysmal nocturnal hemoglobinuria.

• Autoimmune hemolysis.

• Inhaled oxygen therapy (excessive oxygen availability inhibits red blood cell production).

What Happens in an Aplastic Crisis?

Normally, erythropoiesis (synthesis and production of red blood cells) occurs in the bone marrow. Red blood cells develop from the erythroid (red blood cell lineage) precursors that differentiate from the pluripotent stem cells. Aplastic crisis occurs in two phases which include the aplastic phase characterized by the cessation of erythrocyte (red blood cell) production in the bone marrow for a short duration, followed by the recovery phase, where the bone marrow starts producing red blood cells. The sequential events in aplastic crisis are as follows:

• In the aplastic phase, the hematocrit levels and reticulocyte count decrease.

• Erythroblasts in the bone marrow disappear.

• Iron is not trapped in the abnormal red blood cells and remains unused, which accumulates in the serum.

• As the production of new red cells declines, old (non-functioning) red blood cells and micro spherocytosis (abnormal size and shape of RBCs) increase in peripheral blood circulation.

• The red blood cells lose their structural stability, and the osmotic fragility of their membrane increases.

• The presence of iron in the serum inhibits erythropoiesis in the bone marrow.

• The recovery phase is initiated by the destruction of abnormal red blood cells in the spleen.

• The appearance of reticulocytes in blood circulation indicates restoration of erythropoiesis in the bone marrow.

• Because of the reduced red blood cell lifespan in sickle cell disease, there is a rapid drop in hemoglobin levels, and also, the bone marrow stops producing red blood cells.

• In parvovirus B19 infection, the viruses destroy the precursors of red blood cells by bone marrow necrosis and halt their production, causing aplastic crisis and resulting in severe anemia.

What Are the Symptoms of Aplastic Crisis?

Red blood cells play a vital role in energy production, as they contain hemoglobin which carries oxygen to the tissues. During aplastic crises, oxygen transport is greatly disrupted, resulting in fatigue and generalized tiredness. There is an abrupt fall in Hb (hemoglobin) levels, decreased reticulocyte number, and an increase in enzymes like LDH (lactate dehydrogenase). Although the duration of these episodes lasts for only a few days, patients experience severe anemic symptoms because of continuous hemolysis, even in the absence of red blood cells.

Aplastic crisis usually lasts for eight to ten days. Aplastic crisis does not become a serious health condition in normal people since normal red blood cells last in blood circulation for 90 to 120 days. But in people with defective red blood cells (sickle cell anemia), red blood cells last only for 7 to 20 days. Severe anemia and associated symptoms develop in such cases.

• Fever with high temperature.

• Cough.

• Difficulty in breathing.

• Fatigue and weakness.

• Rapid heart rate (tachycardia).

• Flu-like symptoms.

• Low energy level and tiredness.

• Irritability.

• Pale skin (pale color of lips, nails, and fingertips).

• Febrile illness (in parvovirus infection).

• Bone pain.

• Malaise.

• Muscular cramps (vaso-occlusive pain).

• In pregnancy, parvovirus infection is transferred to the fetus resulting in hydrops fetalis (severe hemolysis in neonates) or stillbirth.

How Is Aplastic Crisis Diagnosed?

Aplastic crisis are detected by routine blood screening tests. However, the results would coincide with existing hemolytic disorders resulting in misdiagnosis. Hence additional parameters are to be assessed to confirm aplastic crisis. History of febrile illness to be suspected of parvovirus infection, particularly in pregnant mothers.

• Decreased number of red blood cells.

• Lower hemoglobin levels (less than 3 g/dL).

• Reduced hematocrit values (mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, and red cell distribution width).

• Noticeable fall in the reticulocyte (precursors of red blood cells) count in peripheral blood suggestive of aplastic crisis.

• Serum iron levels are increased due to hemolysis.

• Elevated enzyme levels due to the destruction of red blood cells and abnormal bone activity.

What Are the Management Protocols for Aplastic Crisis?

• Blood transfusion is the immediate treatment of choice in a severe aplastic crisis.

• Administration of red blood cell concentration, particularly in children.

• Supportive care to prevent secondary infections.

• Partial exchange transfusion is recommended for patients with cardiac insufficiency and congestive heart failure to prevent volume overload on cardiac functioning.

• In the case of parvovirus infection, anti-B19 immunoglobulin G (IgG) antibodies start circulating in the blood and remain detectable even after infection for several years. This provides immunity and protection from reinfection, particularly in children.

• Bone marrow transplantation is advised in case of failure to recover from the aplastic crisis.

Conclusion

Aplastic crisis occurs when the body is not able to produce sufficient red blood cells to meet its normal physiological breakdown. Generally, aplastic crisis is a self-limiting clinical condition where recovery occurs spontaneously within a week. It becomes a serious health concern in some people who already have hemolytic dysfunction. Procedures like blood transfusion and symptomatic therapeutic interventions would be lifesaving in patients with associated blood disorders.