What is Splenic Sequestration Crisis?
Splenic sequestration is a serious problem that can occur in people, especially young children, with sickle cell anemia. It happens when there’s a sudden drop in hemoglobin (a protein that carries oxygen in the blood) by 2 g/dL, paired with an abnormally large spleen, known as splenomegaly.
The spleen, an organ that filters blood, is at a high risk of complications in people with sickle cell anemia. The spleen is divided into three parts: white pulp, red pulp, and a transitional zone. Each part has a role to play in the immune system.
Only a small percentage (around 10%) of the blood entering the spleen goes outside the blood vessels and into the parenchyma of the red pulp. Here, the red blood cells come into contact with cells like macrophages that remove abnormal cells or harmful organisms. In order for these cells to return to the bloodstream, they need to pass through small openings in the lining of the venous sinuses.
The white pulp of the spleen is mostly made up of T-cell periarteriolar sheaths and follicles, and contains B cells. These B cells are important in producing IgM antibodies, which help the immune system to fight against specific bacteria like Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenza type B.
In children with sickle cell anemia, the spleen gradually reduces in size and function over the first five years of life because of repeated episodes of self-destruction and scarring. However, children with less severe forms of sickle cell disease, such as hemoglobin SC disease or sickle cell-beta thalassemia, may still have some spleen function into adulthood. Research has shown that a treatment with a medication called hydroxyurea can help to maintain, and even improve, the function of the spleen.
What Causes Splenic Sequestration Crisis?
The molecule that carries oxygen through your blood is called adult type hemoglobin, which is found inside red blood cells (RBCs). It is made of two parts called alpha and beta-globin chains. Changes to the beta-globin can cause it to clump together when they’re not carrying oxygen. This makes the RBCs stiff and they take on a ‘sickled’ shape, like a crescent moon.
Sickle cell disease refers to disorders where both alpha and beta-globin chains are abnormal, and at least one has this sickling mutation. Sickle cell anemia specifically refers to people who have two copies of the sickle cell mutation.
Before we’re born, we make a type of hemoglobin (called fetal hemoglobin) that has a stronger attraction to oxygen and doesn’t have a beta-globin chain. During the first few months after birth, we start to make adult-type hemoglobin. If you have the sickle cell mutation, the negative effects of the changed beta-globin chain will start at this point.
People with sickle cell disease often experience what’s called a ‘vaso-occlusive event.’ This is where small blood vessels get blocked, causing problems like sudden intense pain, stroke, or a serious condition affecting the lungs called acute chest syndrome.
Inside the spleen (an organ in our body that helps the immune system), blood flows slowly through certain areas, exposing it to the immune system. In people with sickle cell disease, this can lead to the beta-globin chains clumping and the RBCs becoming sickled, which makes them unable to flow easily through the spleen. This can lead to areas of congestion and hardening in the spleen, and over time, can cause parts of the spleen to die off. However, in some cases, the blockage can spread, causing the spleen to rapidly fill with blood cells that can’t flow out. This can cause a sequestration crisis, where a large amount of the body’s blood gets trapped in the spleen.
Risk Factors and Frequency for Splenic Sequestration Crisis
Splenic sequestration crises, serious complications of sickle cell anemia, often show up first in children between 6 months to 5 years old. After this age, the spleen usually self-destructs, but the risk continues for people with specific types of this blood disorder, such as HbSC disease and sickle cell beta-thalassemia. Up to a fifth of sickle cell disease patients have experienced splenic sequestration as their first symptom.
The average age for children having these crises is 1.4 years and most happen before they turn 2 years old. Because the type of sickle cell disease can vary among children from one area to another, it’s hard to determine the exact number of patients. However, it is estimated to be between 7 to 30 percent. The chance of having more than one crisis is quite high, between 50 to 78 percent, and it’s even higher for children who encounter this event before turning 1.
- Splenic sequestration crises mostly occur between the ages of six months to five years.
- People with HbSC disease and sickle cell beta-thalassemia remain at risk even as adults.
- Up to 20% of sickle cell disease patients have experienced splenic sequestration as their first symptom.
- The median age of children with a sequestration crisis is 1.4 years, with three-quarters of episodes occurring before age two.
- Exact prevalence estimates are difficult to provide due to variations in sickle cell disease, but it’s reported to be between 7 to 30%.
- Chance of recurrence is between 50% – 78% and higher for those who experienced their first crisis before one year of age.
Signs and Symptoms of Splenic Sequestration Crisis
Splenic sequestration crises are a common complication in people with sickle cell disease. It involves a sudden episode characterized by paleness, weakness, and a fast heart rate. Young children with this condition usually have a larger than normal spleen, which can be felt 1 to 2 cm below the left rib cage. However, during a sequestration crisis, there’s a notable increase in the size of the spleen, beyond its usual enlargement. This can cause significant abdominal discomfort and bloating. It’s important to note that in many instances, these crises can be associated with unstable body circulation or hemodynamic instability at the time of presentation to the clinic.
Testing for Splenic Sequestration Crisis
When a person comes in with a suspected acute splenic sequestration crisis, which essentially means a sudden, painful enlargement of the spleen, the doctor uses multiple methods to confirm the diagnosis. The process usually starts with the doctor asking the patient about their symptoms and doing a thorough physical examination.
Blood tests are also a crucial part of this process. The doctor will likely order a complete blood count with differential, and a reticulocyte count. This helps them gauge the severity of the anemia, an illness that leaves you feeling weak and tired because you don’t have enough healthy, oxygen-carrying red blood cells. The reticulocyte count, which measures how fast immature red blood cells called reticulocytes are being made in the bone marrow and released in the blood, helps to rule out other causes of acute anemia, an instance when the body doesn’t have enough red blood cells. For example, an aplastic crisis is a severe condition where the body’s bone marrow doesn’t produce new blood cells.
Typically, they don’t have to do an imaging test like an ultrasound or a CT scan if the doctor can feel that the spleen is enlarged during the physical exam. However, an ultrasound could be considered if they’re unsure. Patient discomfort often limits this, though, because the spleen is a sensitive organ. If there’s still doubt about the diagnosis, the doctor may order a contrasted computed tomography (CT) scan of the abdomen as well where they use a special dye to make the spleen show up clearer.
Treatment Options for Splenic Sequestration Crisis
If you suddenly have acute spleen sequestration (where the spleen traps and destroys red blood cells faster than normal), doctors will try to restore your normal blood volume. This is usually done by giving you a blood transfusion which can boost your hemoglobin levels directly and prompt your spleen to release any trapped red blood cells.
It is crucial to monitor this process and control how much blood is being transfused. The aim is to boost your levels, but not so much that it causes complications. Normally, your spleen should start to shrink back to its regular size within 6 to 12 hours after the transfusion. During this time, you might need multiple transfusions and will also be given fluids intravenously (through a needle into a vein), unless your anemia is extremely severe.
Plans to avoid future instances of spleen sequestration can be tricky. Most kids experience autosplenectomy, which is a natural shrinkage of the spleen, by the time they’re 5. This eliminates the risk of sequestration. However, doctors sometimes choose to preemptively remove the spleen (a procedure known as a splenectomy) to prevent recurrent sequestration, but this can increase the risk of infections. As a compromise, a partial splenectomy has been suggested to preserve some immune function while reducing sequestration risks.
Another preventive measure is routine blood transfusions until the spleen autoinfarcts (effectively shuts down on its own). This approach can help reduce the amount of sickled cells (misshapen red blood cells) in your body, and raise baseline hemoglobin. However, there’s a danger of iron overload and alloimmunization (a reaction of the immune system), which can complicate future transfusions.
Lastly, some families might opt for expectant management, which means closely observing the patient’s condition without going for an immediate transfusion. This might be a suitable option for some, as indicated by a detailed case review.
What else can Splenic Sequestration Crisis be?
An acute aplastic crisis is a condition that can suddenly cause symptoms including pale skin, fatigue, and anemia. However, this is often linked with a lack of reticulocytes – a type of blood cell – and the absence of splenomegaly, or an enlarged spleen.
Hypersplenism, on the other hand, is a more long-term health issue. It increases the spleen’s activities, leading to a larger spleen, anemia, a decrease in white blood cells or leukopenia, and a drop in platelets or thrombocytopenia. We don’t really know what triggers hypersplenism, but it can happen after a dangerous spleen condition known as an acute sequestration event.
In children with sickle cell disease experiencing severe abdominal pain, it’s important to consider other causes such as:
- Vaso-occlusive pain crisis (a common painful complication of sickle cell anemia)
- Pancreatitis (inflammation of the pancreas)
- Pyelonephritis (a type of kidney infection)
What to expect with Splenic Sequestration Crisis
Splenic sequestration, a condition where the spleen traps or “sequesters” blood cells, historically used to be the second leading cause of death in young children with sickle cell anemia. Sickle cell anemia is a health condition where there aren’t enough healthy red blood cells to carry adequate oxygen throughout your body.
However, over the past forty years, the number of deaths from this condition has decreased dramatically. Back in the 1980s, research showed that the death rates ranged from 12% to 44%. But recently the death rate from acute splenic sequestration has fallen to less than 1%. This shows a significant improvement in the medical treatments available for this condition.
Possible Complications When Diagnosed with Splenic Sequestration Crisis
In children, a severe anemia crisis or a quick collapse of the cardiovascular system might occur suddenly. Long-term issues often stem from attempts to prevent this crisis from happening again. The spleen is vital for producing antibodies, especially for fighting bacteria like Streptococcus pneumoniae. Children who’ve had their spleens removed have lower levels of a particular type of antibodies (IgM) circulating in their bodies, which increases their susceptibility to bacterial sepsis.
Even after streptococcal pneumonia and Hemophilus influenza type b vaccinations have reduced the number of such bacterial infections, children without spleens, particularly those younger than 5, have a higher risk of their bloodstream becoming infected with bacteria.
Long-term blood transfusion therapy increases the chances of your body producing antibodies against the new blood. This could make it difficult to find a suitable blood donor in the future. The excessive iron that can result from repeated blood transfusions can be managed with a type of therapy called chelation, but we’re still unsure about the long-term effects of this therapy.
- Sudden severe anemia in children
- Rapid collapse of the cardiovascular system
- Long-term health issues resulting from prevention attempts
- Increased risk of bacterial sepsis in children who’ve had their spleen removed
- Higher risk of bloodstream infection in spleenless children under 5, despite vaccinations
- Difficulty in finding suitable blood donor due to long-term blood transfusion therapy
- Excessive iron from repeat blood transfusions, manageable with chelation therapy
- Uncertain long-term effects of chelation therapy
Recovery from Splenic Sequestration Crisis
It is recommended that all children with sickle cell anemia start taking penicillin, an antibiotic, daily from the age of two months. Similarly, children who have had their spleen removed to avoid future health episodes linked to the accumulation of blood cells, have to continue taking this antibiotic. This is to reduce their risk of severe infections (sepsis) caused by certain bacteria. It’s important to note that children without a spleen need to receive a series of vaccines – the pneumococcal conjugate vaccine and the Hemophilus Influenzae type b series, as well as a yearly flu shot to boost their immune system.
Preventing Splenic Sequestration Crisis
Hydroxyurea, a medication that encourages the development of a type of hemoglobin that doesn’t cause sickling, or abnormal shapes, in red blood cells, has been notably effective in reducing the number of painful episodes in young children with sickle cell anemia. However, it hasn’t shown effectiveness in reducing the likelihood of the spleen trapping a large amount of blood cells, another complication of sickle cell anemia. How to prevent this issue is still a challenge.
Still, there has been progress in dealing with early complications of sickle cell disease, thanks to widespread newborn screening that tests for blood disorders. Because of this, parents and doctors can be better prepared for what might come next.
Parents should monitor their child’s spleen daily by gently pressing on the upper left side of the child’s belly. If the spleen feels like it’s gotten much bigger, parents should immediately get their child checked by their regular doctor or a blood disease specialist. Parents should also watch for signs such as sudden skin paleness, belly pain, and tiredness in their child. These signs could indicate a spleen crisis, where the spleen traps a large amount of blood, causing severe symptoms.
