Platelet Disorders: 6 Common Types of Inherited Platelet Disorders

Platelets are a type of blood cells. They are responsible for making our blood clot. Having a platelet disorder, therefore, means that injured blood vessels will not clot quickly, bleed more than usual, and also heal more slowly. Platelets play a critical role in the healing of all types of injuries that result in bleeding. The body needs platelets to form blood clots and stop the bleeding.¹

In some people, platelets fail to function in the way they should. This is known as a platelet disorder or a platelet function disorder. Such types of disorders are usually inherited, but they can also be acquired. Acquired platelet function disorders are generally caused by some health conditions, certain medications, and sometimes even some foods.²

On the other hand, inherited platelet disorders include the following:³

• Glanzmann’s Thrombasthenia
• Bernard Soulier disease
• Harmansky Pudlak Syndrome
• Jacobsen syndrome
• Lowe syndrome
• Platelet release and storage pool defects
• Thrombocytopenia with absent radius (TAR) syndrome
• Thrombotic thrombocytopenic purpura (TTP)

Read on to find out everything you need to know about the different types of platelet disorders.

Simply put, platelets are a type of blood cells. Our blood is made up of different kinds of cells, including red blood cells, white blood cells, and platelets. All these cells are present in a liquid known as plasma.

Platelets, also known as thrombocytes, work together with proteins known as clotting factors to help the body stop bleeding at an injury site. When a blood vessel gets damaged, platelets are the first to show up on the location of the injury. They work by covering the injured spot in layers or by clumping together at the site to block the blood flow at the earliest. They are also responsible for kick-starting a complicated chemical reaction that forms a mesh made from a substance known as fibrin.⁴ This chemical reaction also has to always follow the same strict pattern – with each clotting protein being turned on in a particular order. Clotting proteins are known as coagulation factors. Once all the factors have been turned on, the blood will form a clot, which stops the bleeding from the injury site.⁵

The later stages of blood clotting involve strengthening of the clot as the body gets ready to heal from the injury.

Platelets are manufactured in the bone marrow from stem cells. Large bone marrow cells known as megakaryocytes are formed, then they mature, and finally die, which is when they release the platelet cells. Over half of all new platelets circulate in the bloodstream, while the rest is kept in storage in the spleen. Platelets have a very short life, and within just over a week’s time, the body destroys them and produces new ones.^6,7

In people with a platelet disorder, the plug at the site of bleeding does not form properly. The bleeding tends to go on for longer than it normally should. Platelet disorders can also impact the later stages of clotting, which can prove to be especially dangerous after a severe injury or surgery.

There are several groups of disorders that affect the platelets in the body. These include:

• Thrombocytopenia: There condition occurs when there are too few platelets in circulation within the body.⁸
• Thrombocythaemia: A condition where there are too many platelets in circulation in the body.⁹
• Dysfunction Disorders: These disorders develop when there is the exact number of platelets in circulation, but these platelets are not working properly.

All these disorders cause disruption in the clotting process, leading to abnormal clot formation and increased bleeding. Usually, symptoms of a platelet disorder are similar, involving bleeding from the nose, mouth, or the digestive system, bruising easily from minor trauma, and excessive bleeding after surgery or injury. These symptoms typically become apparent soon after birth once the umbilical cord is cut or later on during childhood while teething or when the child starts to become more mobile and falls or gets injured.

A genetic mutation usually causes the majority of all platelet disorders. The exact manner in which the mutation that causes any type of platelet disorder is passed on from the parent to child depends on which specific platelet disorder you have. Unless there are other affected people in a family, there is no way of really knowing whether a person is a carrier or not, as carriers remain healthy and free from clotting problems. In some cases, the genetic mutation may occur sporadically, simply out of the blue, with no previous family members having a history of any type of clotting disorders.¹⁰

When it comes to acquired platelet function disorders, there are three leading causes – medications, diseases, and foods. Sometimes, supplements may also be a cause of acquired platelet function disorders.¹¹

Platelet function is impacted in different ways. There could be certain changes that occur in the way the body sends signals to the platelets. Platelets may become less sticky, or platelet disease can also be affecting the other stages of the clotting process.

It is not yet clear as to why or how platelet function gets affected, but some factors that are known to affect the functioning of platelets include:

Medications like:

• Antihistamines
• Aspirin
• Pain relievers like naproxen and ibuprofen
• Asthma medications
• Antibiotics
• Viagra (sildenafil)
• Chemotherapy drugs
• Antipsychotic and antidepressant medications
• Calcium channel blockers
• Cholesterol-lowering drugs known as statins
• Cocaine

Diseases like:

• Heart disease
• Autoimmune diseases
• Chronic Myeloproliferative disorders
• Myelodysplastic Syndrome
• Acquired von Willebrand disease
• Leukemia
• Liver failure
• Kidney failure
• Paraproteinemia
• Thrombotic Thrombocytopenic Purpura-Hemolytic Uremic Syndrome (TTP-HUS)
• Disseminated Intravascular Coagulation (DIC)

Foods and Dietary Supplements like:

• Vitamin E
• Omega-3 fatty acids like fish oil
• Ginkgo biloba
• Nitrites in foods like bacon and lunch meat
• Garlic
• Ginger
• Cloves
• Dong Quai
• Ginseng
• Willow bark
• Turmeric

The exact symptoms of platelet disorders depend on the cause and severity of the platelet disorder that you have. People with inherited platelet disorders are likely to have a lifelong history of having excessive bleeding or easy bruising after even minor injuries or minor surgeries like dental extractions. Boys may experience heavy bleeding after circumcision. In women, the first sign of platelet disorder is usually when they get their menstrual periods, and there is heavy bleeding.¹²

Other symptoms of platelet disorders may include the appearance of tiny red dots known as petechiae on the skin, along with bruising after minor injuries. Bruising may include ecchymoses, which are large purple bruises that show up after even minor injuries.^13,14

If you have acquired platelet function disorder, the symptoms will vary from person to person. They can either be mild or severe. Common symptoms include:

• Bleeding under the skin
• Unexplained bruising throughout the body
• Bleeding from the mouth, nose, or gums
• Heavy or prolonged menstrual bleeding
• Blood in the feces or vomit
• Small red bumps on the skin or petechiae
• Internal bleeding

As mentioned above, there are several different types of inherited platelet disorders, and the most common ones are described here.

Bernard Soulier is a type of macrothrombocytopenia, meaning there are several very large platelets present in the blood, along with a low platelet count, and prolonged bleeding time. This is a rare inherited disorder of blood clotting, and it causes people to bleed excessively and also bruise easily. The symptoms of this condition become apparent at birth itself and continue throughout life. Nosebleeds, excessive bleeding from injuries, and/or unusually heavy bleeding during the menstrual period in women are the common symptoms of Bernard Soulier disease. People with this condition also bruise easily, and the bruises tend to linger on.¹⁵

Bernard Soulier disease is so rare that it is known to affect only 1 in every 1 million people. It is caused by a mutation that affects a number of different genes.¹⁶

Glanzmann’s Thrombasthenia is a rare inherited platelet disorder that is characterized by the impaired functioning of platelets. Symptoms of Glanzmann’s thrombasthenia include abnormal bleeding, which can be severe in some cases. If this disease is left untreated or improperly treated, the hemorrhaging associated with Glanzmann’s thrombasthenia can become life-threatening.¹⁷

In people with Glanzmann’s thrombasthenia, the platelets are present in the body, but they are dysfunctional. They do not function properly because they are missing a protein on the outside that helps them stick together.¹⁸

Glanzmann’s thrombasthenia also affects around 1 in every 1 million people, though it is known to be more common in specific ethnic groups. The disease is caused by a mutation in the ITGA2B and ITGB3 genes.¹⁹

Symptoms of Glanzmann’s thrombasthenia can cause bruising and petechiae, nose bleeds, bleeding gums, and heavy menstrual bleeding in women. Sometimes there may be bleeding in the urinary tract or the gastrointestinal tract. In children, the most common symptom is heavy and frequent nosebleeds, which may even lead to anemia.

Jacobsen syndrome is also known as Paris-Trousseau syndrome. This rare genetic condition affects around 1 in every 100,000 people. It is a condition similar to Glanzmann’s thrombasthenia in that the platelets are present in the body, but they do not function properly. The platelets in a person with Jacobsen syndrome are oversized and unable to kick-start the clotting process.²⁰

Jacobsen syndrome is caused by a deletion in chromosome 11. The size of this deletion in chromosome 11 varies from person to person, and the severity of your symptoms also increases as the amount of the deletion increases. In most cases, the deletion can happen suddenly, without any family history of platelet disorders.²¹

Children with Jacobsen syndrome experience mild bleeding problems, but the condition is associated with other symptoms like attention deficit hyperactivity disorder (ADHD), learning disabilities, heart-related issues, and abnormalities with the face and skull (craniofacial).²²

Hermansky Pudlak syndrome is another condition where the platelets are present in the body but do not function properly. There are nine different types of Hermansky Pudlak syndrome, some of which are often associated with a type of albinism that affects the skin and eyes. Another type of Hermansky Pudlak syndrome also impacts the lungs, causing the lung tissue to thicken, leading to breathing difficulties.^23,24

Hermansky Pudlak syndrome affects around 1 in every 500,000 people, and it is believed to be caused by a mutation to several different genes.²⁵

The signs and symptoms of Hermansky Pudlak syndrome vary from person to person and depend on the exact type of the disease you have inherited. Nevertheless, the symptoms usually include reduced numbers of white blood cells and immunodeficiency that increase the risk of developing infections. Nearly all people with Hermansky Pudlak syndrome also have an eye condition known as nystagmus, where the eyes make up and down as well as side to side movements without being able to control these movements.²⁶

Another rare genetic condition that only affects males, Lowe syndrome, affects several parts of the body, including the kidneys, eyes, and brain. It is caused by a mutation on the OCRL gene present on the X chromosome.²⁷

The common symptoms of Lowe syndrome include cataracts and glaucoma in the eyes, Fanconi syndrome that affects the kidneys and reduced kidney function, weak muscle tone, nose bleeds, learning disabilities, as well as mild and easy bruising.²⁸

Thrombotic Thrombocytopenic Purpura (TTP) is a rare condition marked by abnormal clotting that affects the small blood vessels in the body, leading to a low number of platelets in circulation. TTP can either be a genetic or acquired condition.²⁹

If TTP is left untreated, the symptoms of the disease can be life-threatening ad may include neurological problems like anemia, fatigue, bruising, seizures, and weakness. Congenital TTP is treatment with plasma products that contain ADAMTS13, while plasma exchange is the standard treatment for acquired TTP, in combination with medications to reduce the immune response.³⁰

To diagnose platelet disorders, doctors will first take a detailed clinical history along with a family history. They will ask you about your symptoms and when they first appeared. They will also look at any other medications/supplements or treatment you are having for any other underlying health condition. A physical examination to check for signs of any bleeding or bruising will also be done.

Diagnostic tests will also be prescribed to find out if you have a platelet disorder. These tests may include:

• A complete blood count (CBC) that provides details of the number of blood cells in the body by type. It will let your doctor know if you have a healthy number of red blood cells, white blood cells, and platelets. This test also checks if the blood cells are present in the proper proportions.
• Partial Thromboplastin Time (PTT) test that looks at how much time it takes for your blood to clot.^31,32
• Prothrombin Time (PT) is another diagnostic test that checks your blood clotting time.³³
• Bleeding time studies test may be carried out to check how long it takes for your body to stop the bleeding after an injury.
• Platelet counts will be done to count your platelets.
• Platelet aggregation studies will be done to check how sticky your platelets are.³⁴
• A blood urea nitrogen (BUN)/creatinine test will be done to check kidney function.

Your doctor will also test you for any underlying conditions that may cause platelet function disorders. In case your doctor suspects an inherited disorder, they will try to determine the gene mutation as this can be helpful for planning your treatment, and it will also help diagnose any other family member as well.

Platelet disorders are quite rare, and there are several treatments available. The most common treatment is desmopressin (DDAVP) which works to increase the levels of platelets in the blood by releasing them from the spleen where they are being stored. Desmopressin is administered as an injection under the skin or into a vein. It can also be sniffed up the nose.³⁵

There is another medicine known as tranexamic acid that is administered to temporarily boost the proteins that help stabilize blood clots in the body. This is given orally by mouth, intravenously, or it can even be given topically where it is simply applied to the skin.³⁶

Platelet transfusions may be needed in very rare cases. In severe bleeding that requires treatment, you will be administered a coagulation factor known as Factor VIIa.³⁷

At the same time, it is important that people with any type of platelet disorder do not use Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) like ibuprofen. Taking this class of drugs can significantly increase the risk of bleeding as NSAIDs reduce the ability of platelets to stick together. If you are in pain, you should ask your doctor for other methods of pain relief instead.

Women may need to take additional precautions during their monthly periods. Your doctor may prescribe DDAVP or tranexamic acid before and during the periods. They may put you on the contraceptive pill or even recommend using an intrauterine device to manage the bleeding. In some cases, your doctor may prescribe an iron supplement if you develop anemia due to the heavy periods.

For very severe conditions, the only treatment in place currently is a stem cell or a bone marrow transplant. It is rarely used, and the success rate remains hotly debated.

The outlook for people with a platelet disorder depends on the exact type of disorder they have and the severity of their condition. Some of the life-threatening symptoms are manageable with treatment and careful monitoring, while other symptoms usually only cause problems in specific situations, like childbirth or surgery. Most people can continue to live their daily lives without experiencing severe symptoms. However, it is crucial that you be aware of your platelet disorder and take as much care as possible not to injure yourself.

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