A Cure for the Tsarevich
Could modern medicine have cured Tsarevich Alexei of hemophilia?
April 17 is World Hemophilia Day.
Hemophilia is a rare hereditary disorder (one in 50,000 people). Its main characteristic is decreased blood clotting, manifested by spontaneous and long-term mutations.
The title (from the Greek words haima, meaning blood, and philia, meaning tendency) was coined in 1828 by Friedrich Hopff, who described numerous cases of fatal clerical crimes in men. In 99% of cases, men are affected, but women are carriers of the "diseased" gene.
Why is the disease called "royal"?
Hemophilia is often called a "royal" disease, although it mostly affects ordinary people. This is all thanks to the British Queen Victoria (1819-1901), who was the first in her family to carry the "affected" gene (this occurs in 30% of cases). She and Prince Albert had nine children. As a result of dynastic marriages, the "affected" gene found its way into the ruling families of Germany, Spain, and Russia (Nicholas II was married to the Queen's favorite granddaughter, Alice of Hesse). Ten of Queen Victoria's descendants died of hemophilia.
In 1904, after four daughters, Nicholas II and Alexandra Feodorovna had a long-awaited son, the heir apparent—Tsarevich Alexei. The joy was short-lived, as the disease manifested itself almost immediately: bleeding began after birth, apparently from the umbilical cord. "By rough calculation, blood loss over two days amounts to 1/8 to 1/9 of the total blood volume," wrote Nicholas II.
The heir was treated by the best doctors and the most advanced methods of the time: not only healing mud from Lake Moinaki near Yevpatoria, delivered by destroyers (!), but also aspirin, which was first synthesized in 1853 and became available in tablet form in 1904. At the time, no one even suspected that aspirin had blood-thinning properties, and therefore was strictly contraindicated for hemophiliacs.
And then Grigory Rasputin appeared on the historical stage – a figure as powerful as he was controversial, whose role and significance historians still debate. It's not easy to explain, but it's a fact: Rasputin really did help the tsarevich cope with pain and bleeding. He forbade Alexei from taking any pills, including aspirin, and this undoubtedly helped. He treated him primarily with herbs (masks and tinctures contained rutin, vitamins K and C, which strengthen blood vessel walls) and, according to contemporaries, hypnosis.
How is it diagnosed and treated today?
Today, the screening test for hemophilia is the APTT (accelerated partial thromboplastin time). It measures the time it takes for blood to clot: if it takes 25-36 seconds, you're healthy. However, if it takes 37 seconds or more, and you're not taking blood thinners, hemophilia may be suspected. Further testing is needed.
We now know that hemophilia is caused by a deficiency of certain clotting factors—proteins synthesized in the liver. There are twelve known such proteins, and if one of the two—factor VIII or factor IX—is missing, we speak of hemophilia. When factor VIII is missing, it's called hemophilia A, which affects 85% of those diagnosed. When factor IX is missing, it's called hemophilia B—the same condition that Tsarevich Alexei had, which affects 15% of those diagnosed. Molecular genetic testing is available that can directly identify the mutation responsible for the disease. This testing is used to identify gene carriers. Prenatal diagnosis is now also available.
Now that science understands the mechanism of hemophilia, it also understands how to treat it: the deficiency of the missing proteins—factors VIII and IX—must be compensated. While previously treatment was with aspirin, oak bark, and blood transfusions, now the missing factor is administered intravenously. When calculating the dose, age, weight, and the initial level of this factor in the blood are taken into account, and then it is administered according to a specific schedule. This is called factor therapy. The missing protein begins to circulate in the bloodstream, enters into a cascade of reactions with other factors, and participates in the formation of the fibrin network that holds platelets together, thereby stopping bleeding.
A new treatment for hemophilia is currently being actively researched: gene therapy, which corrects the gene defect. A special messenger virus is produced in the laboratory, into which genetic material is immersed. The patient is then infected with this virus (which is harmless to humans). It reaches the liver via the bloodstream, penetrates it, and the liver begins to synthesize the missing factor.
"We are already at the clinical trial stage," says E. N. Parovichnikova, Director General of the National Medical Research Center of Hematology of the Russian Ministry of Health. "This virus does not integrate into DNA, but forms a plasmid. The missing factor begins to be produced, and it is not administered to patients." Of course, there are nuances; not everyone will have this for life. After all, the cell isn't integrated into the genome, doesn't reproduce, and can be washed out, requiring repeat gene therapy. But it exists!"
Scientists believe this method of hemophilia treatment is the future.
