This is the fourth part of our series about the condition based on our patient booklet “Fast Facts for Patients and Supporters: Pyruvate Kinase Deficiency”, which is freely available online. This article depicts how the anemia can be managed when treating pyruvate kinase deficiency.

At present, there are no approved drugs that directly treat PK deficiency, but it is possible to manage your symptoms. The type of supportive treatment you are given will depend on how the disease affects you.

Transfusions

It is not your level of hemoglobin, but how well you tolerate the hemolytic anemia caused by PK deficiency that will determine whether you need to have blood transfusions. In PK deficiency, the increase in 2,3-DPG in red blood cells means that more oxygen is released to the body. As a result, you may be able to tolerate moderate anemia with few symptoms.

Transfusions in Newborns and Young Children

The goal is to avoid transfusions if possible, but during the first years of life, red blood cell transfusions may be required to manage severe anemia. The transfusions may be needed to support normal growth and development and/or to avoid symptoms of anemia, including fatigue and poor feeding. For some young children, decreasing the frequency of transfusions to permit a lower hemoglobin level will allow the doctor to assess the child’s reticulocyte response and the true baseline hemoglobin level.

Transfusions in Older Children and Adults

There is no standard criteria or schedule when it comes to deciding whether to give an older child or adult a transfusion. The degree of anemia and the associated symptoms can vary between individuals.

You may never need a transfusion or may only have a transfusion in the setting of a hemolytic episode or aplastic crisis. Alternatively, you may require regular transfusion therapy and may consider opting for a splenectomy.

Splenectomy

If you receive frequent blood transfusions and/or have significant symptoms related to anemia, you may benefit from having surgery to remove your spleen.

Old or damaged red blood cells will continue to be removed in the liver, and so splenectomy is only partially effective in improving the hemolytic anemia.

Both open surgery and laparoscopic (minimally invasive or keyhole) surgery are performed under general anesthesia. The type of surgery may depend on the size of your spleen; your doctor will discuss this with you.

Most patients will spend at least a few nights in hospital after surgery.

Laparoscopic surgery usually results in less pain, a faster recovery and a shorter hospital stay. Several small openings are made in the abdomen, and the surgeon will use a slender tool called a laparoscope, with a light and camera on the end, to look into the abdominal area. Other medical instruments will be passed through the other openings to disconnect the spleen from the body’s blood supply before removing it. The surgical openings are closed using stitches or sutures.

Open surgery. A larger cut is made, often underneath the rib cage, to remove the spleen. The method used will depend on your overall health and the size of your spleen.

Partial splenectomy (only part of the spleen is removed) has not been reported to be beneficial in patients with PK deficiency.

Benefits and risks. Your hematologist can help you and your family weigh the potential benefits and risks to decide if splenectomy is the right option for you.

Risk of infection. The spleen is an important organ that helps your body to fight infections. Splenectomy raises the risk of infection from certain bacteria, such as pneumococcus, meningococcus and haemophilus. These infections can be very serious, even life-threatening, and the risk will remain for your lifetime.

Although the absolute risk of serious infection after splenectomy is very low, it is much higher in people who have had a splenectomy than in the healthy population. For this reason, surgery in children should be delayed when possible until they are at least 5 years old.

In determining the timing of splenectomy, the risk of a serious infection must be balanced against the risks of red blood cell transfusions and iron loading. After splenectomy, other infections for which you will be at higher risk include malaria (from mosquitos) and babesiosis (from ticks) in endemic areas.

How can I protect myself from getting an infection? After a splenectomy, you are likely to be given antibiotics to protect against the possibility of a serious infection. Some doctors recommend twice daily antibiotics for a period of time after splenectomy; others advise continuing antibiotics for life. You must seek urgent medical attention for all fevers, to be assessed and treated with broad-spectrum antibiotics (see box below).

It is very important that you have the recommended vaccines before splenectomy and then stay up to date with your immunizations (vaccines) after surgery. Ask your hematologist and/or general physician whether your vaccines are up to date.

IMPORTANT: After splenectomy, you are at risk of serious infection. See a doctor immediately if you develop a fever over 38.5°C (101.5°F). You must seek medical attention even if you have other infectious symptoms, such as a cough or congestion, or you have multiple family members with similar symptoms. A sample of your blood will be sent for laboratory tests (blood culture and complete blood counts) and you will be given intravenous or intramuscular broad-spectrum antibiotics.

Risk of blood clots. As a filtering organ, your spleen plays a role in protecting you from blood clots (thrombosis). Blood clots can form in the large veins of the arms or legs (deep vein thrombosis), the blood vessels around the liver (portal vein thrombosis) or other concerning locations. Clots in the arteries can also occasionally develop.

The risk of developing a blood clot after splenectomy for PK deficiency is approximately 10%. Some individuals take aspirin or other medications after splenectomy to decrease this risk. Consider speaking to your doctor about this.

Stem Cell Transplantation

A bone marrow (stem cell) transplant can cure PK deficiency. This has been carried out successfully in studies in animals with PK deficiency, but the procedure is associated with significant risks, including the development of new chronic medical issues and the risk of dying from complications related to the transplant.

In total, 16 individuals with PK deficiency have undergone stem cell transplantation in Europe and Asia, with a range of conditioning (preparation) regimens and management strategies. These patients had a high rate of graft-versus-host disease (i.e. the donor cells attacked the host’s own cells), a chronic complication that can cause issues related to the skin, gastrointestinal tract and other organs.

Most doctors think that the risk–benefit ratio is currently weighted in favor of splenectomy over stem cell transplantation. However, over time, the risks associated with transplantation may decrease and this may be an option for more patients.

Please check out the other posts of our series here:

• What Is Pyruvate Kinase Deficiency?
• What Causes Pyruvate Kinase Deficiency and How Is It Diagnosed?
• How Will Pyruvate Kinase Deficiency Affect Me or My Child?

Information based on Fast Facts for Patients and Supporters: Pyruvate Kinase Deficiency  (Karger, 2019).