What is Hemolytic Anemia?
Anemia is a condition where a person has lower than normal levels of hemoglobin, the substance in our blood that carries oxygen. The World Health Organization (WHO) states that anemia in men is identified when hemoglobin levels are less than 13 g/dL and for women, it’s less than 12 g/dL. However, these values can differ based on various factors like age, race, the effects of chemotherapy, and even special situations like being an older adult, an athlete, a smoker, or living in high altitude areas. These varying conditions suggest that different hemoglobin levels can indicate anemia.
Identifying and treating the causes of any type of anemia early is of utmost importance. This is because hemoglobin, rich in iron, helps red blood cells carry oxygen from the lungs to other parts of the body. Red blood cells have a unique shape that helps optimise this oxygen transfer. Hence, if your body doesn’t get enough oxygen, you can experience symptoms like fatigue, weakness, dizziness, headaches, breathlessness, or irregular heartbeat.
Anemia can be categorized into three types based on the average size, or mean corpuscular volume (MCV), of your red blood cells. They are microcytic, normocytic, and macrocytic anemia. This classification helps doctors identify and treat the exact type of anemia.
Normocytic anemia, specifically hemolytic anemia, occurs when red blood cells are destroyed, leading to reduced hemoglobin levels. This condition, with an MCV of 80 to 100 fL, results from the breakdown of hemoglobin and efforts of bone marrow to produce more blood cells. Hemolytic anemias can be caused by either intrinsic or extrinsic factors.
What Causes Hemolytic Anemia?
Hemolytic anemia is a condition where your red blood cells are destroyed faster than your body can replace them. This disease can have many different causes, and can be categorized in a number of ways: it can be a sudden (acute) or long-term (chronic) condition, it can be caused by immune system issues or not, it can occur within the blood vessels or outside of them, it can be inherited (genetic) or occur later in life (acquired), and it can be due to issues with the red blood cells themselves or outside factors.
The ‘intracorpuscular’ label is used when the problem is within the red blood cells themselves. For instance, issues with the hemoglobin (the molecule in red blood cells that carries oxygen) can cause problems, such as in diseases like sickle cell disease or thalassemia. Sickle cell disease happens because of a wrong code in a gene, causing a buildup of a type of hemoglobin and eventually leading to the breakdown of red blood cells. Thalassemia, a common inherited cause of hemolytic anemia, is due to an defects that lowers the production of one part of the hemoglobin molecule.
There are also diseases called membranopathies, which involve changes to the structure of the red blood cell membrane. Examples include hereditary spherocytosis and hereditary elliptocytosis, which are generally inherited and can have different levels of severity. Conditions like these can affect anyone, but diagnosing them can be challenging due to their varied severity and inconsistent symptoms.
Enzymopathies are another type of hemolytic anemia that involves a decrease in ‘metabolic abilities’, basically the efficiency of a red blood cell. This category includes disorders like G6PD deficiency and pyruvate kinase deficiency, both of which can alter the shape of red blood cells and lead to their destruction. G6PD deficiency, for example, is usually passed down from mothers to sons and can be triggered by certain foods or medicines to cause a breakdown of red blood cells.
On the other hand, ‘extracorpuscular’ labels refer to outside factors that lead to red blood cell damage. These can be mechanical, like damage from artificial heart valves, immune-related, like reactions to blood transfusions, or due to infections such as from malaria. Even medications used to treat these infections can also cause harm to red blood cells due to their chemical properties.
Risk Factors and Frequency for Hemolytic Anemia
Two important databases, the NHANES-III (the third U.S. National Health and Nutrition Examination Survey) and the Scripps-Kaiser, help differentiate between the health of ‘normal’ individuals and those with abnormal health metrics.
From these databases, it has been found that the hemoglobin levels in men between the ages 20 to 59, and women from 20 to 49, don’t vary significantly. This information is useful in studying individuals who fall out of these normal ranges.
- African Americans typically show a lower normal limit for hemoglobin concentration, lower serum transferrin saturation, higher serum ferritin levels, lower bilirubin levels, and lower leukocyte counts.
- This is believed to be a result of a higher prevalence of alpha-thalassemia and G6PD deficiency amongst African Americans. G6PD deficiency impacts millions of people globally.
- Hyper (HE), although it can be found worldwide, is more commonly seen in malaria-endemic regions of West Africa. Multiple forms of anemia are prevalent in these regions because they are believed to offer some protection against malaria.
- As a general note, hemolytic anemias affect a wide variety of people, regardless of age, race, and sex. This is because there are many types of this disorder that can be either inherited or developed later in life.
Signs and Symptoms of Hemolytic Anemia
Anemia is a condition that can cause different signs and symptoms. Some people might not have any symptoms at all, while others might feel out of breath, weak, or tired. They might also experience a fast heart rate, known as tachycardia. In certain types of anemia where blood cells are destroyed, additional symptoms like yellowing of the skin (jaundice) or blood in the urine (hematuria) might occur. If the condition has been present for a long time, patients might develop other symptoms like swollen lymph nodes, an enlarged liver or spleen, and a condition called cholestasis, where bile cannot flow properly from the liver.
Specific symptoms combined with anemia can provide clues to the cause. For example, diarrhea and a particular type of anemia known as hemolytic anemia can suggest a condition called hemolytic uremic syndrome. Likewise, blood in the urine along with lab tests supportive of hemolytic anemia could indicate a condition known as paroxysmal nocturnal hemoglobinuria (PNH).
It is essential for doctors to get a full medical history and perform a physical examination, as these can help link the symptoms to a diagnosis.
Testing for Hemolytic Anemia
If a doctor suspects that a patient has hemolytic anemia, a kind of anemia where red blood cells break down earlier than they should, they’ll typically rely on various laboratory tests for a confirmation. These tests can include measuring the count of new or immature red blood cells (reticulocyte count), checking the levels of an enzyme called lactate dehydrogenase (LDH), assessing the amount of unconjugated bilirubin in the body, and evaluating the levels of a protein called Haptoglobin.
When red blood cells break down, they release LDH, causing levels of this enzyme to rise. Haptoglobin is a protein that attaches itself to hemoglobin, the oxygen-carrying part of red blood cells. When a lot of red blood cells are breaking down, haptoglobin gets used up, leading to its decrease in the body. Moreover, the breakdown of red blood cells also leads to an increase in unconjugated bilirubin, a waste product that the body struggles to get rid of quickly enough.
To figure out if the immune system is causing the red blood cells to break down, additional tests called warm and cold agglutinin tests and a direct antiglobulin test (DAT) might be done.
In some conditions like sickle cell disease, where red blood cells are not normal and break down easily, the levels of hemoglobin, an important part of red blood cells, can also provide valuable insight. Strong evidence has shown that a low hemoglobin level could imply a high rate of red blood cell breakdown. Clinical measures like LDH levels, reticulocyte count, and indirect bilirubin can validate the same.
Treatment Options for Hemolytic Anemia
In layman’s terms, for severe cases of an illness known as hemolytic anemia, immediate treatments may be necessary. These can include blood transfusions, a process called plasmapheresis, or using medications to increase urine production.
When a patient is experiencing severe anemia, particularly with active bleeding, blood transfusions are usually the go-to treatment. However, once it’s known that hemolysis, or the destruction of red blood cells, is the cause of anemia, other specific treatments can be explored. This, of course, will often depend on what exactly caused the anemia in the first place.
In some cases, when the cause remains uncertain, a test called the ‘Coombs test’ can be performed. This helps differentiate whether the hemolysis is being caused by an immune reaction or another cause.
For patients with Sickle Cell Disease (SCD), there are several possible treatment options that have proven to work. These can include blood transfusions, medication like hydroxyurea, agents that stimulate red blood cell production, and bone marrow transplants.
If the disease G6PD deficiency is suspected, a blood smear test should be done promptly. This is faster than other complex tests and remains vital even when other tests might give false negative results. Once the diagnosis is confirmed, these patients must be guided to avoid certain medications and foods that can worsen the situation.
People with a certain complication of PNH live in fear of a clot forming in their blood vessels, a situation known as a thromboembolic event. Some doctors prescribe medication to prevent blood clot formation, but more research is needed to set the best treatment regimes and figure out who can benefit most from these medications.
Lastly, other treatment options such as spleen removal (splenectomy), steroids, monoclonal antibodies or immunosuppressants have been used for specific conditions like autoimmune hemolytic anemias, HS, and SCD.
What else can Hemolytic Anemia be?
To diagnose hemolytic anemia, doctors typically look for a high number of immature red blood cells (known as reticulocytes) in a blood test. This happens because the body’s bone marrow is working overtime to make more red blood cells. However, this could also be seen in conditions like blood loss anemia, so it’s important to consider other factors too. Physicians also thoroughly examine the patient’s medical history and look at other lab results, including tests for LDH, haptoglobin, and indirect bilirubin.
It’s also worth noting that hemolysis (the destruction of red blood cells) can be observed in several uncommon conditions, from a disorder called paroxysmal nocturnal hemoglobinuria to situations like blood transfusions or using mechanical devices to support the circulation of blood. Therefore, a wide range of possibilities must be considered.
To help distinguish between these conditions, doctors often rely on case reports. These reports can help distinguish between conditions that cause hemolysis within the blood vessels (like PNH) and those that are associated with mechanical heart valves. For example, kidney damage is less likely to occur in patients with mechanical heart valves, unless they already have an underlying kidney disease.
What to expect with Hemolytic Anemia
Anemia, or a lower-than-normal amount of red blood cells, can raise the risk of death in various chronic diseases such as kidney disease, heart failure, and cancer. Landmark clinical trials like TRICC, TRISS, and TRACS have aimed to find out the lowest level of anemia that can be tolerated without increasing the risk of death.
For hemolytic anemias, where the body destroys red blood cells faster than it can produce them, the outcome can vary. It depends on the cause of the anemia and how early it’s diagnosed and treated.
Research indicates that patients with Sickle Cell Disease (SCD) – a type of hemolytic anemia, tend to fare worse. Particularly, if their hemoglobin (the protein in red blood cells that carries oxygen) levels fall below 8 g/dL, they are more likely to face serious complications, such as strokes, and a higher risk of death.
People diagnosed with autoimmune hemolytic anemia – where the body’s immune system mistakenly destroys its own red blood cells, are at increased risk of multiple episodes of the disease. Moreover, if these patients have severe anemia at the beginning of the disease, they often respond less to various types of treatment.
Glucose-6-phosphate dehydrogenase (G6PD) deficiency – is a type of hemolytic anemia where the main treatment is to avoid agents causing oxidative stress. Though this condition rarely leads to death, these patients are more susceptible to serious infections and resulting complications.
Possible Complications When Diagnosed with Hemolytic Anemia
Hemolytic anemia is a health condition where your red blood cells (RBCs) get destroyed faster than your body can replace them, and this can affect various organs in your body. When these red blood cells are destroyed, the subsequent reactions that occur can lead to other complications.
In illnesses like sickle cell disease (SCD), the ongoing destruction of red blood cells decreases the amount of oxygen available for your tissues, leading to oxygen deprivation, or hypoxia. When your tissues don’t get enough oxygen, you can experience fatigue and muscle pain. It’s also been observed that the worse the anemia, the worse the health outcomes for those with SCD.
One risk associated with this condition is the danger of your blood vessels getting blocked, causing ischemia and increasing the risk of blood clots. Thromboembolism, or the obstruction of a blood vessel by a clot, is even the most common cause of death in people suffering from paroxysmal nocturnal hemoglobinuria (PNH), a rare and life-threatening disease. About 15% to 44% of PNH patients will experience at least one incident of thromboembolism during their illness.
Excess hemoglobin and iron resulting from the destruction of red blood cells can also cause complications in the kidneys, reducing their functionality. Deposits of iron and a protein called hemosiderin have been observed in the kidneys during PNH, leading to decreases in kidney function.
Other diseases, like Wilson disease, can cause liver disease and neurological issues if they are not diagnosed and treated early. One of the key symptoms in young patients with Wilson disease is hemolysis.
Many individuals with hereditary spherocytosis (HS) are not diagnosed until they reach adulthood and begin to show symptoms. These often include recurrent gallstones, and in the most severe cases, these individuals may require regular blood transfusions.
Potential Impact:
- Fatigue and muscle pain
- Risk of blood vessels getting blocked
- Decreases in kidney functionality
- Impact on liver and potential neurological issues
- Recurrent gallstones
- Requirement for regular blood transfusions in severe cases
Preventing Hemolytic Anemia
Hemolytic anemia is a complex condition with many different types. To manage this disease, patients often need a group of healthcare professionals and experts dedicated to their specific type of hemolytic anemia. While some patients can manage their condition with medication or by avoiding certain triggers, for others, the situation can become quite severe.
It is critical for patients to be well-informed about the disease and its symptoms. This includes understanding when their condition might be worsening, or recognizing the early signs of infections. Knowledge of these can help them avoid further health problems linked to their disease.
