What is Hyperviscosity Syndrome?
Hyperviscosity syndrome, or HVS, is a serious health issue often linked to cancer that typically manifests three main symptoms: problems with the nervous system, changes in vision, and bleeding from the mouth and nose. This condition occurs when the blood becomes too thick. This thickness or viscosity can be due to abnormalities in the shape of red blood cells, or because of unusually high levels of different blood components such as proteins, red and white blood cells, or platelets.
Oftentimes, HVS is triggered by a condition called Waldenstrom macroglobulinemia, a type of cancer affecting the blood. Hence, HVS is often associated with an increased presence of proteins in the blood. To manage this condition, doctors often use supportive measures like giving intravenous fluids and treating the root cause, often a blood-related condition. In some cases, a procedure called plasmapheresis might be used, where the blood is filtered to remove excess proteins or cells that are making it too thick.
What Causes Hyperviscosity Syndrome?
Hyperviscosity, or the thickening of blood, can happen when there’s an unusual increase in the elements of the blood. These could be either cells like red or white blood cells, and platelets, or non-cellular components like proteins. Various health conditions can cause this thickening.
Some conditions like polycythemia vera, leukemia, and thrombocytosis increase the number of blood cells and lead to hyperviscosity. Sickle cell disease and spherocytosis are other conditions that can cause thickening of blood due to the abnormal shapes of red blood cells they create.
On the other hand, non-cellular elements of the blood can also increase either singly or multiply and lead to hyperviscosity. Diseases like myeloma, Waldenstrom macroglobulinemia, and cryoglobulinemia each increase a single type of protein and can cause this thickening.
Rheumatic conditions such as seropositive rheumatoid arthritis, systemic lupus erythematosus, and Sjogren’s syndrome, and also diseases like Castleman disease and HIV infections that increase multiple types of proteins can cause hyperviscosity as well.
Risk Factors and Frequency for Hyperviscosity Syndrome
Hypergammaglobulinemia is often the cause of a condition called Hyperviscosity Syndrome (HVS), particularly a type known as Waldenstrom macroglobulinemia. This condition develops in more than 30% of people with Waldenstrom macroglobulinemia at some point in their lives due to large, star-shaped molecules called IgM pentamers, which are very viscous or sticky. The second most common cause of HVS is something known as myelomas. Of all HVS cases tied to myelomas, about 25% are caused by a molecule called IgA, with less than 5% being caused by IgG myelomas.
- Hypergammaglobulinemia often leads to a condition known as Hyperviscosity Syndrome (HVS), specifically a type called Waldenstrom macroglobulinemia.
- Over 30% of people with Waldenstrom macroglobulinemia will develop HVS due to large, sticky molecules called IgM pentamers.
- Myelomas are the second most common cause of HVS.
- About 25% of HVS cases caused by myelomas are due to a molecule called IgA. Less than 5% are caused by another type of molecule called IgG myelomas.
Signs and Symptoms of Hyperviscosity Syndrome
Hyperviscosity syndrome (HVS) is not easy to diagnose and requires a thorough medical history check along with a detailed physical examination. It’s crucial to ask about any personal or family history of blood disorders. This condition often shows itself through a combination of symptoms affecting the skin, brain, and vision.
- Common signs are bleeding from the skin or moist surfaces in the body, like a bloody nose, bleeding gums, or gastrointestinal bleeding. This is due to a disruption in how blood platelets function.
- Neurological symptoms can also occur, and these range from headaches and neurological disorders to loss of consciousness, confusion, difficulty balancing, hearing problems, seizures, and stroke. These symptoms occur because blood flow to the brain decreases and abnormal proteins accumulate around nerve fibers.
- Vision issues may also occur, including blurred or double vision. This is due to changes in the tiny vessels in the eyes, like blood clotting or bleeding. Eye examination can reveal swelling of the optic nerve, retinal hemorrhages, or a classic “sausage link” or “boxcar” enlargement of retinal veins.
- Less common symptoms include heart and lung issues, such as heart failure, shortness of breath, heart valve problems, or heart attacks. Kidney damage may also occur, likely due to poor blood supply to the kidneys.
Since the diagnosis of HVS relies heavily on recognizing these symptoms, a comprehensive medical history and a detailed physical examination are crucial.
Testing for Hyperviscosity Syndrome
If your doctor suspects you have a high level of thickness in your blood (a condition known as high serum viscosity), they can confirm this with a lab test. There’s some disagreement among experts about whether it’s best to measure the thickness of whole blood versus just the liquid part of your blood (serum), but most labs look at serum.
Thickness (viscosity) is measured in units called centipoise. For comparison, consider that water has a viscosity of 1 centipoise. Normal blood serum viscosity is 1.4 to 1.8 centipoise. Symptoms associated with increased blood thickness can start to appear when the viscosity reaches 3 centipoise, but they typically occur when it’s over 4 to 5 centipoise.
Additional tests might include a complete blood count (which measures the number of various types of blood cells), a full set of blood chemistry tests, a coagulation profile (to see how well your blood clots), and a urine test. If your blood protein is much higher than your albumin (a specific protein), that could suggest the presence of an abnormal protein (gammopathy). This can often be confirmed with a routine urine test. If your blood smear shows a stacked coin-like appearance of your red blood cells (known as rouleaux formation), this hints at a problem with serum, which could be due to increased serum viscosity. Sometimes, high serum viscosity can even cause lab equipment to malfunction, and if a lab sample can’t be analyzed, this might indicate an increase in viscosity.
Though not necessary to confirm a high serum viscosity diagnosis, measuring the amount of immunoglobulins (proteins that function as antibodies) in your blood can inform long-term treatment. This is most helpful if it’s measured before and after treatment.
Treatment Options for Hyperviscosity Syndrome
Hyperviscosity syndrome, or HVS, is a medical emergency related to cancer. Immediate treatment is necessary to prevent serious complications like blood clots, heart attack, and severe organ failure. Treatment should be tailored to the patient’s symptoms and their severity, not just the measured level of blood thickness. With swift intervention, most of the symptoms can usually be reversed. The treatment approach has two main goals: to manage immediate symptoms and to treat the underlying blood condition that caused HVS.
Treatment typically includes supportive care, plasma exchange (also known as plasmapheresis, a procedure to remove, treat, and return the liquid part of blood to the body), and cancer treatment drugs. Since patients with HVS are often dehydrated, which can worsen their condition, careful administration of fluids is crucial. Typically, 1 to 2 liters of saline solution is given when HVS is suspected.
Plasmapheresis, a more direct treatment, can swiftly reverse most HVS symptoms. It is generally safe and well tolerated by patients and can lower the thickness of your blood serum by 20% to 30%. This can be done daily until symptoms are resolved. It’s worth noting that patients could also have concurrent anemia or dilutional anemia (resulting from released fluids), which must be handled carefully. Transfusion of packed red blood cells can thicken blood, hence, doctors usually wait for plasmapheresis to reduce serum thickness before proceeding with transfusion.
In emergency situations where quick access to plasmapheresis is not possible, intravenous phlebotomy can be a temporary solution. In this procedure, about 1 to 2 units of the patient’s blood is removed and simultaneously replaced with saline solution. But this needs to be done cautiously as aggressive plasma exchange could result in the removal of necessary clotting factors, albumin, and platelets. Doctors only resort to phlebotomy when severe neurological symptoms like seizures or coma are present.
The definite treatment of HVS is to address its underlying cause with chemotherapy. Since plasmapheresis only treats the symptoms and not the root cause, chemotherapy is often started in conjunction with plasmapheresis. An oncologist, a doctor who specializes in cancer treatment, should guide this treatment. As soon as HVS is identified, a consultation with an oncologist is strongly recommended. If plasmapheresis or leukapheresis (a similar procedure that removes white blood cells) is necessary, patients might need to be transferred to a more specialized healthcare facility.
What else can Hyperviscosity Syndrome be?
The following list includes several health conditions that are potentially serious:
- Heart failure
- Hemorrhagic stroke (bleeding in the brain)
- Ischemic stroke (blocked blood vessel in the brain)
- Leukostasis (high white blood cell count)
- Multiple myeloma (type of bone marrow cancer)
- Polycythemia (high red blood cell count)
- Thrombocytosis (high platelet count)
- Waldenstrom macroglobulinemia (rare type of non-Hodgkin lymphoma)
