Today, we offer such medical treatment to children with hemophilia that they can do the same things as their healthy peers

How many people in Poland suffer from hemophilia?

Hemophilia is an inborn hemorrhagic diathesis. There are a total of approximately 6 thousand patients with such bleeding conditions, as long as the severe forms are concerned. In this group, there are around 3 thousand hemophilia patients, adults and children combined. Hence, the disease is classified as a rare condition. 

What are the characteristics of the disease?

In hemophilia, there is a shortage of a blood clotting factor. Which specific factor it is depends on the type of the disease. In type A hemophilia, factor eight is missing, in type B - factor nine, in type C - factor eleven. Depending on the severity of the shortage, the form of the disease can be severe (<1% of the clotting factor reference value), moderate (1-5%), or mild (5-50%).

Why does the disease affect boys almost exclusively?

Hemophilia is a sex-linked genetic disorder. In most cases, transmission occurs through inheritance. A mother who is a carrier of a defective gene on the X chromosome can transmit the gene, and the risk of the child inheriting it is 50%. If the mutated gene is inherited by a boy, he is certain to develop the disease. If it is inherited by a girl, she will be a carrier but will not develop the disorder. For her to actually develop the disease, she would have to inherit the defective gene both on the X chromosome from the mother and on the X chromosome from the father. This is an extremely rare occurrence.
In about 30% of all cases of hemophilia, new mutations are involved. It means that a child with hemophilia can be born in a family in which nobody was suffering from the disease and the mother is not a carrier. 

How do you find out possible blood clotting disorders in a child?

The first symptoms can be observed already in the first year of life. They primarily include major hemorrhages following the first vaccinations or injections, i.e. bleeding to a buttock or thigh. Another concerning sign could be prolonged gum bleeding in the course of teething. Subsequent symptoms occur when the child starts crawling. These are large hemorrhages, significantly larger than those observed in same-age children, for example on elbows or buttocks after first falls, as well as large bruising after blood sample collection. Another characteristic symptom is a limp in one leg of a toddler.

Is hemophilia verified in a lab test?

Yes. If we can see that a child develops bruises easily or has a bleeding tendency, we check the basic coagulation system: APTT - Activated Partial Thromboplastin Clotting Time, or INR - Prothrombin Time. Based on these two tests, we can diagnose most inborn clotting disorders. Severe forms of clotting disorders are usually determined in children under 3 years of age. But sometimes the diagnosis may come later. I myself had a case of a patient whose hemophilia was diagnosed in the 5th year of life. And it was only because his mother decided to have his three milk teeth removed. Before that, the child had been treated for a different disease.

Historically, a lot of children with hemophilia used to die - what was the cause of that?

A hundred years ago, children with hemophilia would live to 9-10 years on average. This was due to heavy bleeding, to the central nervous system, to the abdomen and obviously to joints. These children would soon become infirm. They were usually unable to move by themselves at the age of 4 or 5 years. There was no knowledge of how to treat them. The only available treatment was pain alleviation, and the pain accompanying bleeding to a joint is very strong indeed. It was alleviated through hypnosis, opium, herbs. The patient was simply put to sleep. The famous Rasputin treated tsarevich Alexei Nikolaevich of the Romanov dynasty with hypnosis. Interestingly, some say there would be no Russian revolution if not for hemophilia. After all, the country needed a strong Tsar. 

 
Let us now return to our times. How is hemophilia treated today? 

By 2008, we applied treatment on demand in children. In practice, a patient with bleeding would come to a hospital to receive the clotting factor they needed. They would then return home to wait for the next hemorrhage, as we may say. Unfortunately, this kind of treatment failed to prevent serious complications. Bleeding to joints caused inflammation in synovial membrane. Bleeding was recurrent, so that joints became more severely damage, ultimately leading to hemophilic arthropathy. Today, these patients at an adult age use wheelchairs and experience enormous problems with walking.
Such complications can be prevented. Since 2008, within the scope of the pediatric program, preventative treatment is provided to all children with a severe form of hemophilia. 

What is this treatment?

Swedish researchers have proven already in the 1970s that if a clotting factor is administered regularly to patients with severe hemophilia, bleeding will be prevented. Clotting factor has to be given three times a week to hemophilia A patients, or twice a week to hemophilia B patients. Such was the protocol followed for more than ten years. Afterwards, however, observations from multiple clinics indicated partial inefficiency of the procedure. It turned out that when clotting factor was given to children on Mondays, Wednesdays and Fridays, bleeding would occur on a Sunday. For this reason, an application was designed to indicate the present level of the clotting factor. The application has a battery icon. When the battery is green, it means that the factor level is high and the protection is full. Yellow icon indicates first shortage of the factor and the need to be particularly careful. Red means that the safety threshold has been exceeded and bleeding may occur easily. The app is fed with data, i.e. the clotting factor decrease curve in a particular patient. The only next step is to provide real-time input of when the patient received the factor. 
With this app, patients are fully aware of when they can go running, jumping and having fun, and when they should receive their clotting factor. 

When does the prevention treatment start?

We start after the first year of life of our little patient. We administer all concentrates intravenously. It is completely impractical for parents to bring their child to a hospital to get the factor every other day. That’s why we install a port, which is an implantable venous access device, in the patient. We instruct the parents how to use it, and the entire prevention treatment takes place at home.
With this kind of treatment, children and adolescents with hemophilia will not develop hemophilic arthropathy. Moreover, their lifestyles would not differ much from the lifestyles of other children their age. We currently follow the definition established by the Society of Hemophilia Patients 2020, according to which the goal of hemophilia treatment is that children affected by the disease can grow in the same way as their healthy peers. And so they do. Their expected lifespan is the same as the average in the general population.

 
Is the administration of the clotting agent the only form of hemophilia treatment?

No, this kind of treatment has to be comprehensive. When a pregnant woman is a hemophilia carrier (because she was tested for it) and we can see in the ultrasound that she is expecting a boy, there is 50% risk of the child being born with the disease. Such new mother should deliver her baby at a specialized location, such as our hospital. If the boy is born with the disease, specialists in various fields will immediately start the care in a collaborative procedure among several hospital departments. Care of specialists in various medical fields is needed at a later stage as well, not only hematologists but also rehabilitation professionals, pediatricians, dentists, orthopedists who know how to deal with this kind of patient.
We have 15 pediatric institutions in Poland. Our hospital is the coordinating unit. Specifically, when a pediatric patient with a severe form of hemophilia is diagnosed somewhere in Poland, they will first be received at the nearest pediatric care facility that treats the disease. If treatment is unsuccessful there, the patient comes to us. We can offer comprehensive treatment, including rehabilitation, dental care, orthopedic treatment, etc. We have all the necessary specialists. We are the second hospital in Poland and the only pediatric facility in Poland to be certified in the field of European Hemophilia Comprehensive Care. This is a proof that we deliver superior quality integrated care to hemophilia patients. 

What about the children with milder forms of hemophilia?

They do not receive preventative care. But they receive a special patient book with the details of their diagnosis and instructions on what to do in case of emergency. Since 2019, they also receive a special procedure sheet, which is updated yearly. This sheet shows details of the medications received by the child. In addition, parents of children with mild and moderate hemophilia receive the clotting factor. Just in case. In the event of a serious injury, if the child gets to hospital emergency, the parents take the factor with them, together with all the documentation. If neither the parents nor the local hospital have the factor, it will be brought within 20 minutes from the nearest Regional Blood Donation and Blood Treatment Center or from another hospital. 

What is the future of hemophilia treatment, are scientists working on new therapies?

The progress in treatment is enormous. Soon, new clotting factor concentrates developed with the recombination method will be available. Antigen treatment research is proceeding as well. Antigens are administered subcutaneously to replace the clotting factor. In my opinion, it is a matter of several years before they become common in treatment of hemophilia. But the real breakthrough can be expected of genetic therapy. FDA in the United States has already approved it. In this kind of therapy, an adenovirus is implanted in the liver and starts producing the clotting factor. This costs about 5 million US dollars, but according to the Americans this is still cheaper than lifelong treatment of hemophilia. 

Interviewed by Iwona Kołakowska
Photo by Michał Teperek
University Communication and Promotion Office