What is Amegakaryocytic Thrombocytopenia?
Amegakaryocytic thrombocytopenia refers to a serious type of thrombocytopenia – a health condition where you have a low platelet count, affecting your blood’s clotting ability. This condition is unique because it is characterized by a low or non-existing number of megakaryocytes, which are large cells in your bone marrow that create platelets. Additionally, there are no other observable abnormalities in your bone marrow.
There are two kinds of amegakaryocytic thrombocytopenia: congenital (you are born with it) and acquired (develops later in life). When you have congenital amegakaryocytic thrombocytopenia, you are born with severely low platelets and potential bleeding issues. This condition can also lead to your bone marrow failing to function correctly as you grow up. On the other hand, acquired amegakaryocytic thrombocytopenia generally appears later in life, possibly due to your immune system attacking your own body in error.
Doctors typically only conclude that you have acquired amegakaryocytic thrombocytopenia after ruling out other possible conditions. This diagnosis is often confirmed following uncontrolled bleeding after unsuccessful treatments for immune thrombocytopenia, another platelet-related disorder.
To diagnose these conditions, your doctor may need to sample your bone marrow or carry out genetic testing. In the case of congenital amegakaryocytic thrombocytopenia, doctors look for specific mutations in a gene known as c-MPL. If you have acquired amegakaryocytic thrombocytopenia, your doctor would observe a lack or low number of megakaryocytes in your bone marrow.
For congenital amegakaryocytic thrombocytopenia, the only permanent remedy is a transplant from another person’s healthy bone marrow or blood stem cells. For acquired amegakaryocytic thrombocytopenia, treating the underlying health condition along with immune-suppressing medications is the preferred course of action.
What Causes Amegakaryocytic Thrombocytopenia?
Congenital Amegakaryocytic Thrombocytopenia
Congenital amegakaryocytic thrombocytopenia is an inherited condition that can lead to low platelet count and is typically caused by errors in the gene c-MPL, which is responsible for controlling specific platelet functions. There are about 41 known variations of these mistakes in the c-MPL gene that could cause this condition. There are two main types of this condition.
Type 1 occurs when there’s a complete loss of a specific function of the platelet due to mistakes in the c-MPL gene. As a result, people born with this condition have a severe shortage of platelets. This makes them highly prone to bleeding inside the skull and their bone marrow tends to fail early in life, usually by about 33 months old.
On the other hand, Type 2 happens due to mistakes in the gene that change the platelet and thereby its response. These children are born with a mild shortage of platelets, but their count usually normalizes in their first year of life. But they still face bone marrow failure, though at a slower rate compared to those with Type 1, generally occurring between ages 3 and 6.
Sometimes, additional genetic variations can affect Type 2. Mistakes in specific genes can stop the liver from producing a vital factor for platelets and cause bone marrow failure. These genetic variations come with distinctive signs like a bone joint disorder known as radioulnar synostosis.
Acquired Amegakaryocytic Thrombocytopenia
The exact way that acquired amegakaryocytic thrombocytopenia happens is unknown. However, researchers have suggested three possible ways:
One way could be due to something from the outside interfering with how platelets mature. Examples of such interferences include viruses, certain treatments or therapies, exposure to harmful substances, alcoholism, and deficiency of vitamin B12.
Alternatively, disturbances from within the body’s immune system could also be to blame. These can include antibodies that block the functions of platelets. This condition has also been observed in people with various immune and hormonal disorders. The way these patients respond to certain medications further suggests that the problem could be linked to the immune system.
Lastly, this condition could also be an early sign of an issue with the body’s stem cells. This means it could be a precursor to certain diseases, including particular types of blood cancers and disorders. There are also associations between this condition and other abnormal genetic patterns. This further suggests that the origin of acquired amegakaryocytic thrombocytopenia lies in early cells involved in platelet formation.
Risk Factors and Frequency for Amegakaryocytic Thrombocytopenia
Congenital amegakaryocytic thrombocytopenia is a very rare condition; less than 100 cases have been reported. It seems to be slightly more common in females, and having closely related parents might be a contributing factor. Frequently, people might confuse it with other conditions, like neonatal alloimmune thrombocytopenia or primary aplastic anemia, especially when it progresses to pancytopenia, a condition where there is a reduction of red and white cells and platelets in the blood.
On the other hand, acquired amegakaryocytic thrombocytopenia is likely more common than records suggest, as it’s often mistaken for immune thrombocytopenia. Women diagnosed with this condition are usually between the ages of 40 and 60. For men, it is common at very young or very old ages, specifically peaking at age 60.
Signs and Symptoms of Amegakaryocytic Thrombocytopenia
Thrombocytopenia is a medical condition characterized by low platelet count, generally less than 150,000 cells per microliter of blood. Congenital amegakaryocytic thrombocytopenia is a specific form of this condition that is present from birth or develops within the first month of life, often with a platelet count of less than 21,000 cells per microliter. In some cases, symptoms can even begin while the baby is still in the womb.
Common symptoms often include:
- Bruises or purple areas on the skin (purpura)
- Bleeding in the brain (intracranial bleeding)
- Repetitive bleeding in the rectum
- Bleeding in the lungs (pulmonary hemorrhage) soon after birth
There might also be a family history of thrombocytopenia. No distinct physical abnormalities linked to the congenital amegakaryocytic thrombocytopenia have been observed. However, some affected individuals might have neurological defects like crossed eyes (strabismus), missing cerebellum, malformations in the face, and brain abnormalities. The exact reason for these findings is still unclear but could either be due to the deficiency of a protein involved in platelet production (MPL) in the brain or long-term effects of intracranial bleeding.
Acquired amegakaryocytic thrombocytopenia, another form of the condition, is usually diagnosed when the standard treatment for immune thrombocytopenia, such as steroids or intravenous immunoglobulin therapy, fails and results in bleeding complications. The symptoms can include:
- Tiny red or purple spots on the skin (petechiae)
- Large areas of bruising (ecchymosis)
- Easy bruising
- Nosebleeds (epistaxis)
- Fatigue
People with this condition do not have an enlarged spleen (splenomegaly). In some rare cases, it can lead to serious complications like severe internal bleeding (hemoperitoneum).
Testing for Amegakaryocytic Thrombocytopenia
In the context of a child showing signs of thrombocytopenia, a condition characterized by lower than normal levels of platelets in the blood, a thorough evaluation is paramount. Such evaluation should take into account the child’s age, symptoms like fever, fatigue, unusual weight loss, and a decrease in appetite or energy — all of these could signal serious health conditions like cancer or autoimmune diseases. If your child has had a blood count test in the past, your doctor would find it useful to review those as well, as it would hint at whether the thrombocytopenia is a long-standing or recent condition.
It would be beneficial for the physician to know if your child has been recently sick or received any vaccines, as these could be the triggers for the platelet count drop. Symptoms like abdominal discomfort and bloody stools could indicate a bacteria-induced condition. The doctor would also review any medications your child might be taking because some, like cancer drugs, heparin, antibiotics, and anti-seizure medications, could lower platelet counts.
The physical examination is another crucial factor. The doctor will look for signs of bleeding, particularly in the skin and often in the lower parts of the body. They would also track how the bleeding patterns change over time. They’ll keep a keen eye on areas where medical devices have been used, like catheter insertions sites, drains, incisions, and venous access sites. Also, they would inspect the mouth and gums for any signs of bleeding. Other physical signs the doctor may look for could indicate the presence of various conditions. For instance, a short stature might signal a bone marrow issue, neurological issues may indicate certain syndromes, swollen lymph nodes could point to cancer or infection, and abdominal swelling could reveal issues like viral infections, cancer, or liver disease.
In addition to observing the platelet count, doctors would want to examine all blood cell types, platelet size and shape, and look for abnormalities in red and white cells in the lab test results. In some cases, a bone marrow biopsy might be required to diagnose conditions linked to very low platelet counts.
If your child has platelet counts less than 50,000 cells/μL, has normal-sized platelets, and is a newborn, a bone marrow sample could be tested for the c-MPL gene, a gene crucial for platelet production. If any abnormalities are found, this could confirm the diagnosis of congenital (inborn) amegakaryocytic thrombocytopenia, a rare condition where the bone marrow fails to produce enough platelets. If this condition is suspected, your doctor might also want to check for mutations in the THPO gene, as this can influence treatment options.
When suspecting acquired amegakaryocytic thrombocytopenia, a version of the condition believed to occur later in life rather than at birth, a full blood count and peripheral smear are necessary. Tests to check liver functions such as hepatic enzymes, albumin levels, and coagulation testing are also crucial. Depending on the child’s symptoms, doctors may also recommend HIV and Hepatitis C testing, or check for other conditions such as lupus or antiphospholipid syndrome. In certain cases, other tests like chest cultures, prothrombin time, activated partial thromboplastin time, and fibrinogen tests could be recommended to check for conditions like sepsis or disseminated intravascular coagulation. For this condition, the presence of fewer than normal megakaryocytes, cells responsible for platelet production, in the bone marrow would confirm a diagnosis.
Treatment Options for Amegakaryocytic Thrombocytopenia
Congenital Amegakaryocytic Thrombocytopenia is a disorder that affects the blood. The only cure for this disease, especially if you have a certain mutation known as c-MPL, is through a treatment called allogeneic hematopoietic stem cell transplant. Physicians might suggest this treatment early in the illness, as waiting could lead to complications such as needing multiple transfusions, developing allergies to transfusions or getting infections. The ideal age for the treatment is around 38 months, but can range from 7 to 89 months.
The process of stem cell transplant involves using medicinally influential substances like busulfan, cyclophosphamide, and total body radiation. While these can lead to survival rates of around 80%, they may also result in side effects involving the lungs, mucus membranes, and liver, and can potentially cause infertility. For individuals receiving a transplant that isn’t a perfect match, there is a 19% chance of it failing in the first year. If the transplant is match, that risk goes down to 7%.
Non-myeloablative protocols are recent developments in this field, used to treat acquired aplastic anemia. These newer treatments allow patients to maintain their fertility, and generally have fewer adverse effects and better overall results.
Supportive treatments can include platelet transfusions, medications like tranexamic acid to slow down the breakdown of blood clots, avoidance of NSAIDs and aspirin. If the person develops pancytopenia (a condition where their body has too few red blood cells, white blood cells, and platelets), they may need to receive a transfusion of red blood cells and antibiotics.
Persons with a THPO variant of the disease do not benefit from a stem cell transplant, but medications like Romiplostim and Eltrombopag have found success.
Acquired Amegakaryocytic Thrombocytopenia is another form of the disease, and does not have a specific treatment plan. The goal here is to treat the underlying cause. Certain practices recommend various medications, therapies and procedures as possible treatments. Some physicians suggest starting with the least toxic and cost-effective of the treatments and watching to see how the patients respond. There’s also the need to keep in mind that not every medication works for everyone. Options for this disorder range from immune suppressants to therapies that bind antibodies to procedures like bone marrow transplants.
In some cases, initial improvement may be brief or non-existent. Treatment with a drug called cyclosporine can prove effective. If treatment is not successful or if the patient’s condition worsens, bone marrow transplantation could be considered. There have been reports of successful treatment with a combination of an antibody medication (tocilizumab) and cyclosporine. Other cases have seen positive responses to an agonist of the THPO receptor (like avatrombopag), despite resistance to similar treatments.
What else can Amegakaryocytic Thrombocytopenia be?
Congenital Amegakaryocytic Thrombocytopenia
When a newborn or infant has a low platelet count, also known as thrombocytopenia, the severity of the condition, the age when it began, and the mother’s health history all play a role in finding out the reason behind it. Some of the likely causes could be:
- Lack of oxygen during birth or problems with the placenta
- Infections since birth such as toxoplasmosis, rubella, cytomegalovirus, and herpes simplex viruses
- Sepsis, which is a severe infection that spreads through the body
- Congenital syphilis, an infection passed from mother to baby during pregnancy
- Chickenpox or parvovirus B19 infections
- Thrombocytopenia caused by medication due to antibodies that react to the drug
- Blood clotting disorders like disseminated intravascular coagulation or thrombosis
- Type 2B von Willebrand disease, a condition that affects blood clotting
- Various other conditions like Wiskott-Aldrich syndrome, Fanconi anemia, and conditions that result in high blood pressure during pregnancy
- Genetically linked conditions such as Trisomies 21, 18, 13, Turner syndrome
- Blood-related conditions such as neonatal leukemia, neuroblastoma, Kasabach-Merritt syndrome, etc.
- Autoimmune conditions where mother’s antibodies attack the baby’s blood cells
Acquired Amegakaryocytic Thrombocytopenia
In adults, there could be many reasons for low platelet count, commonly referred to as thrombocytopenia. Most often, it’s diagnosed as immune thrombocytopenia, which is typically found in patients who don’t respond to treatments like corticosteroids or IV immunoglobulin. However, other common causes could be:
- Liver disease
- Autoimmune reactions triggered by vaccines, foods, or other substances
- Conditions related to blood transfusion
- Blood clotting disorders like thrombosis or disseminated intravascular coagulation
- Conditions that occur after surgery
- Pregnancy-related thrombocytopenia
- Infections such as Epstein-Barr virus, chickenpox, leptospirosis, etc
- Side effects from medication or certain beverages
- Nutrient deficiencies like Vitamin B12, copper, and folic acid
- Conditions linked to blood such as paroxysmal nocturnal hemoglobinuria
- Autoimmune conditions like lupus, with or without antiphospholipid syndrome
- Conditions related to bone marrow failure
- Disorders that result in abnormal blood clotting, such as disseminated intravascular coagulation and others
What to expect with Amegakaryocytic Thrombocytopenia
Congenital amegakaryocytic thrombocytopenia is a condition that greatly impacts a person’s health, especially when it leads to a condition called pancytopenia, which is a significant reduction in red and white blood cells, and platelets in the body. Once someone reaches this stage, their outlook isn’t so good. Research has shown that about 30% of these patients may die due to problems caused by bleeding, while another 20% may lose their life due to complications related to a treatment called a hematopoietic stem cell transplant. This is where healthy blood stem cells are transplanted into the body to replace the cells that aren’t working properly.
Moreover, nearly half of all patients with this condition might develop a severe disease called aplastic anemia within their first year of life. This disorder happens when the body stops producing enough new blood cells. There are also reports signaling that these patients could possibly develop leukemia or myelodysplasia (a group of disorders caused by poorly formed blood cells or ones that don’t work properly) later in childhood.
Acquired amegakaryocytic thrombocytopenia, which is a condition that a person isn’t born with but develops, can alter a person’s health in different ways. Some people may achieve a long-term remission, which means their symptoms might disappear for a long time. However, others might experience ongoing periods of getting better and worse.
Worryingly, some might quickly get worse and develop serious conditions such as aplastic anemia, myelodysplastic syndrome, or leukemia even if they are undergoing treatment. If people develop aplastic anemia, their outlook could be poor.
Possible Complications When Diagnosed with Amegakaryocytic Thrombocytopenia
The complications that might arise from conditions like acquired amegakaryocytic thrombocytopenia and congenital amegakaryocytic thrombocytopenia encompass:
- Decline in different types of blood cells (Pancytopenia)
- Depletion of all blood cells (Aplastic anemia)
- Complications linked to bleeding
- Acute leukemia, a blood cancer
- Bleeding inside the brain (Intracranial hemorrhage)
- Increased chances of getting infections
- Complications related to blood transfusion
- Potential risk of death
- Myelodysplastic syndrome, a group of disorders caused by poorly formed blood cells
Preventing Amegakaryocytic Thrombocytopenia
Amegakaryocytic thrombocytopenia is a rare and serious condition that could lead to bone marrow failure. To prevent this, it’s crucial to diagnose and treat it early. Patients and their caregivers need to understand the associated risks, which include bleeding, developing aplastic anemia (a condition where the body stops producing enough new blood cells), myelodysplastic syndrome (a group of disorders caused by poorly formed blood cells), and acute myeloid leukemia (a type of cancer of the blood and bone marrow).
Diagnosing this condition can be invasive, as it involves a bone marrow biopsy – a procedure where a small sample of bone marrow is removed from your bone for lab testing.
In terms of treatment, especially for a type known as congenital amegakaryocytic thrombocytopenia, it may involve invasive procedures like hematopoietic stem cell transplant. This is a procedure where healthy stem cells are transplanted into your body to replace the faulty ones. Patients and their caregivers need to fully understand all the risks and benefits related to this treatment. They should strictly follow their treatment plans and immediately contact their doctor if they notice any signs of bleeding or infection. It’s also important to avoid certain activities like skiing, mountain climbing, and contact sports that increase the chance of bleeding or brain hemorrhage.
Treatment for another type, known as acquired amegakaryocytic thrombocytopenia, can be complicated. It may involve trial and error with several different immune-suppressing and immune-modifying drugs which may not always work. Patients may also need supportive platelet transfusions, which involve receiving platelets – the blood cells that help with clotting – from a donor. These transfusions, however, can come with their own risks.
Lastly, it’s essential for patients and caregivers to continue to educate themselves and stay aware of all that this condition entails. This will help them make informed decisions about their healthcare and how best to manage risks associated with this condition.
