Heredity & Clotting Factors

All that most laymen know about hemophilia is that it is an odd and dangerous disease of the blood that strikes men only, although it is transmitted by women. Medical researchers have learned a great deal more than that, but when the nation's expert hematologists gathered in Washington, they realized that much more was still to be learned. They are baffled by at least eight bleeding disorders that are caused by the lack of any one of ten different clotting factors in the blood.

Genetic Lottery. Classical hemophilia, known since ancient times, is caused by a severe shortage of clotting Factor VIII. This disease, which afflicted a dozen descendants of Queen Victoria, results from a defect in a recessive gene carried on the x (female) chromosome. If a hemophilic man marries a normal woman, all their sons are normal but all their daughters are carriers. If a carrier woman marries a normal man (see diagram), each son has a fifty-fifty chance of being a victim and each daughter has a fifty-fifty chance of being a carrier. No one can predict whether a child will be affected, because a sort of genetic lottery decides which of the mother's chromosomes the child inherits. (How Victoria got the defective gene is a mystery. Medical sleuthing has failed to show that she inherited it, so she may have developed it herself--perhaps even from a direct hit on her ovaries by cosmic rays./-)

Classical hemophilia has now been renamed hemophilia A, because in 1952 a boy in England was found to be suffering from what had seemed to be the same disease, but his trouble was actually caused by lack of clotting Factor IX. This affliction is now called hemophilia B. It is transmitted the same way as hemophilia A, but the two diseases can be distinguished by the fact that blood from a hemophilia A victim, which contains Factor IX, will clot blood from a hemophilia B victim. A hemophilia B's blood, with its Factor VIII, will make an A's blood clot. Of an estimated 100,000 victims of clotting disorders in the U.S., 50,000 have hemophilia A and 15,000 have B.

Another bleeding disorder that is similar in its effects on patients, but totally different in inheritance and incidence is von Willebrand's disease. This is the most common of a group of clotting disorders that are transmitted by genes on some other chromosome than the x--which chromosome, remains a mystery. But it is a nonsex chromosome, so boys and girls are equally likely to inherit the defective gene.

No Direct Measure. "The trouble is," said the University of North Carolina's Dr. Kenneth M. Brinkhous, director of the U.S.'s leading hemophilia research program, "we can only measure the clotting factors indirectly by their effects--usually in the test tube."

But progress is advancing from the lab to the bedside. Factor VIII is now being extracted from human plasma and concentrated about 30 times. It is given by intravenous drip to victims of hemophilia A and von Willebrand's disease when they have crises of massive bleeding. Except in such emergencies, the usual treatment for all the clotting disorders remains a transfusion of fresh whole blood or plasma--not to replace blood that the patient has lost, but to supply the missing clotting factor and thus keep him from losing more.

Contrary to common belief, it is not outward bleeding from a wound that cripples and eventually kills most hemophiliacs; it is internal bleeding, especially into the joints, that does the damage. "This," said Manhattan's Dr. Henry H. Jordan, "is more crippling than either polio or arthritis. But it's incredible what rehabilitation can do. Many patients can discard a brace, for example, after five or even ten years." Today, some hemophiliacs work as longshoremen and loggers.

/- She passed the gene to one son, two daughters: Leopold, who died at 31, was grandfather of Lord Trematon, who died at 21; Alice, who married Prince Louis of Hesse, had one hemophilic son who died at three, and two carrier daughters; Beatrice, who married Prince Henry of Battenberg, had two affected sons and a carrier daughter. Alice's elder carrier daughter Irene married Prince Henry of Prussia; one hemophilic son, Waldemar, lived to 56, but another died at four; Alice's younger carrier daughter Alexandra married Czar Nicholas II, was murdered with him and their hemophilic son, the Czarevitch Alexis. Beatrice's daughter Victoria Eugenie married Alfonso XIII of Spain, had two affected sons, Alfonso and Gonzalo, who bled to death after accidents.

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