Inherited Platelet Disorders

Rare conditions difficult to diagnose, but manageable
Author: Rebecca A. Clay

When certified nursing assistant Julie Seminara injured herself while moving a nursing home patient back in 2001, her problems seemed serious but straightforward: She had three herniated discs in her neck and a torn shoulder. But she no idea she was about to embark on a seven-year search for a diagnosis.

Like her mother, Seminara had already been diagnosed with von Willebrand disease (VWD). But when she had trouble recovering from her shoulder surgery, she began to suspect something else was wrong, too. “I was 24, but healing like an 80-year-old woman,” says Seminara, now 34 and a physician assistant in Waco, Texas.

The doctors in the small town in Montana where she then lived couldn’t figure out what was wrong. Nor could a clinic in a large city. Later, Seminara borrowed textbooks from a hematology professor at her physician assistant school and tried to diagnose herself. Eventually, she sought help from a hematologist in Salt Lake City. Although initial tests came back normal, subsequent testing revealed she had a rare inherited platelet disorder, a condition in which platelets don’t work the way they should to stop bleeding. “I always say I won the wrong lottery twice,” says Seminara, laughing.

While Seminara’s VWD symptoms are mild, the platelet problem—believed to be a delta storage pool disorder—can be quite disruptive. In addition to impairing her body’s ability to heal, it can make problems like ovarian cysts or even hitting a hand against a table much more painful. Dropping a large textbook on her foot meant being in a cast for two months. Seminara has nosebleeds that gush for half an hour at a time and ooze for three to five days afterward. And she worries she won’t be able to have children because of the risk of postpartum bleeding. 

However, Seminara is convinced that having two rare disorders has made her a better healthcare provider. “If I can make a difference by being a provider and a patient at the same time and being on my soapbox about bleeding disorder awareness, maybe I can save someone from going through 31 years of trying to figure out what’s wrong with them.”

As Seminara’s experience shows, diagnosing rare inherited platelet disorders can be tricky. But once a problem is identified, individuals can get treatment when they need it and learn strategies for managing the disruptions these conditions can cause.

Understanding Platelet Function

When a blood vessel is damaged, platelets—cells that circulate in your blood—rush to the rescue. To stop the bleeding at the injury site, platelets attach themselves to the surface of the blood vessel, release chemical signals to attract other platelets and clump together to form what’s known as a platelet plug. Once the plug is ready, proteins called clotting factors arrive to strengthen its exterior.

A platelet disorder means that some part of this process is disrupted. As a result, a plug doesn’t form properly and the individual bleeds longer than normal.   

The problem can be with the receptors on the surface of platelets, which help them interact with or respond to other substances. In Bernard-Soulier syndrome, for example, the problem is an abnormality in the receptor for von Willebrand factor, resulting in platelets that can’t stick to the injured site the way they should. In Glanzmann thrombasthenia, the problem is an abnormality in the receptor for fibrinogen that keeps platelets from sticking to each other.

In storage pool disorders, which include release defects, delta storage pool deficiency and grey platelet syndrome, the problem lies on the inside of the platelet. In these disorders, it’s the absence or malfunctioning of granules—packets that store chemicals that signal other platelets and cells to head toward an injury—that causes the problem.

Although these are the primary platelet disorders, there are still more. “There are many platelet disorders that don’t have names, not because of their rarity but probably because of their intricacy,” says Leonard A. Valentino, MD, medical director of the Hemophilia and Thrombophilia Center at Rush University Medical Center in Chicago.

What all these disorders have in common are the symptoms they produce. For some people, symptoms are relatively mild, such as bruising, bleeding gums and frequent nosebleeds. But inherited platelet disorders can also be life-threatening. Women and girls can experience such heavy periods or severe postpartum problems that they’re hospitalized for bleeding or severe anemia. Platelet disorders can also cause excessive bleeding during dental procedures and surgery.

“The biggest thing we see in hemophilia treatment centers (HTCs) is 25- to 35-year-old women who’ve had horrendous periods,” says Valentino. Some resort to hysterectomies to stop the bleeding. “They can also have this psychological burden, because they can go for years with no one really understanding why they have such heavy periods.”

Diagnosing Platelet Disorders

While infections or use of medications like aspirin or Advil can trigger platelet dysfunction later in life, Bernard-Soulier, Glanzmann thrombasthenia and storage pool disorders are all inherited. 

That’s typically a surprise to couples, unless there has been a family history of bleeding disorders, says Valentino. “Many of these disorders are what we call autosomal recessive, meaning that both parents carry the trait but don’t manifest the disorder,” he says. That’s why these disorders—which affect both boys and girls—are more common in cultures with individuals with similar genetic backgrounds, he explains.

Diagnosing an inherited platelet disorder isn’t easy, even when symptoms prompt a visit to the doctor or hospital. For one thing, healthcare professionals outside an HTC may not suspect platelet disorders. “When you’re seeing people who aren’t trained to look for them, you may go for quite a long time without anyone understanding the severity of your problem,” says Jennifer Maahs, MSN, PNP, a hemophilia nurse practitioner at the Indiana Hemophilia & Thrombosis Center in Indianapolis. They might order a platelet count, but that won’t help with a diagnosis if a person has a normal number of platelets that aren’t functioning properly, she says.

Even when providers are looking for platelet dysfunction, they may not come up with a definitive answer. It takes a specialized laboratory to do platelet aggregation tests,and  there is no one laboratory test for all inherited platelet disorders, Maahs explains.

It can be especially hard to diagnose specific problems when they occur on the interior, rather than exterior, of the platelet. “We don’t have any means, other than in research labs, to go in and figure out the internal workings of the platelet,” Maahs says. “It’s like a little factory inside the platelet: We can look at the output to see if it’s working like we think it should, but if it’s not, we don’t know why.”      

Treating Platelet Disorders

Fortunately, the treatment for platelet disorders is generally the same no matter what the variety of inherited condition.

Most people don’t need treatment on a day-to-day basis, Valentino says. Bruising, one of the most common symptoms, doesn’t require any treatment at all unless the bruises are very painful or impair function. In those cases, the treatment is usually ice or painkillers. If symptoms are severe, antifibrinolytic drugs that prevent clots from breaking down, DDAVP and other medications can help. DDAVP is a synthetic version of a hormone that stimulates the release of von Willebrand factor and factor VIII.

Women and girls may be prescribed birth control pills or other hormonal suppressive medication to control excessive menstrual bleeding. They may also need iron replacement to treat anemia caused by prolonged blood loss over time. Individuals with inherited platelet disorders may also need additional medications, such as antifibrinolytics or factor products, after accidents and during dental work or surgical procedures.

Platelet transfusions are another option for controlling bleeding, but should be reserved for life-threatening situations, Valentino says. “In diseases like Glanzmann thrombasthenia, the administration of platelets can actually immunize patients against the platelets and render them ineffective,” he says. “If in the future they had life-threatening bleeding, the platelets in a transfusion would not be effective.”   

Learning how to minimize problems is also key, adds Maahs. “If a woman usually has heavy periods, for example, she might start medication on the first day instead of waiting to see if it’s going to get worse,” she says. Similarly, someone prone to nosebleeds could learn how to apply pressure, make sure there’s ice handy and carry a dark-colored towel to absorb the blood without alarming others. (Another option is a product like NasalCEASE®, over-the-counter bandages that also help clots to form.) “It’s really about planning ahead and being prepared,” says Maahs.    

HTCs can help patients or their parents learn those strategies and develop a treatment plan for managing any contingency, says Valentino. “Our patients have specified treatment plans for what to do for anything from bruising and nosebleeds to life-threatening bleeding,” he says.  

Something’s Not Right

Aspen Dosland’s family had no idea she had an inherited platelet disorder until the Dayton, Ohio, ninth grader turned 13 in 2010. But they did know something was wrong. “Aspen was just pale for a long time,” says her mother, Christine, dean of academic affairs for a two-year college in Cincinnati. Aspen was active in dance and volleyball, and her pediatrician assured the family there was no need to do blood tests.

But Aspen’s family was unconvinced. Finally, Aspen’s grandmother, who is a nurse, took her back to the pediatrician and demanded blood work. When the results came back, Aspen was sent to the hospital immediately. She was dangerously anemic from very heavy bleeding during her period. “She must have thought that was normal or was too embarrassed to come forward to tell me or one of her grandmothers,” Christine says.

After several months of testing, the family learned that Aspen had a storage pool disorder. She was given blood transfusions in the emergency room and now takes birth control pills to control her bleeding. Her sister, Savannah, 12, has since tested negative for the disorder.

In retrospect, there the family says Aspen showed other signs. “We always wondered why Aspen’s gums bled when she brushed her teeth,” Christine says. Plus, it seemed to take her a long time to heal from minor injuries. Christine wonders if she also has a platelet disorder. After all, her own menstrual bleeding became so bad she opted for a hysterectomy in her 40s.

Now 53, Christine and her husband, Christopher, have vowed to persist when they sense something’s not right and to have more open dialogue with their daughters. “We’re more in tune with what’s going on with Aspen and our other daughter,” Christine says. “What happened to Aspen had a good ending.”

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