Calling all doctors: Q re: female hemophiliacs

I’m re-reading a book about the daughters of Queen Victoria which has a short but appropriate discussion about hemophilia, considering the prevalence of it in her descending family. (It also has a short teaser about how maybe her royal father wasn’t really her father, since there was no hemophilia in either side of her family until she was born, but I digress, as did the book . . .) The discussion in turn includes a footnote to the effect that hemophilia rarely occurs in females and when it does the girl will always die at the onset of menses, because when she has her first period, she will bleed to death.

I’ve never heard of this, but then, I’ve never heard of a lot of things. So, doctor/medical types: Is that true? Maybe my understanding of menstruation is limited (even as a 35 year old woman), but I never understood the physical process to be one in which one is freely bleeding, as from a wound or an injury. So I’m curious as to how the natural removal of the uterine lining could be an occurrence grave enough to cause uncontrolled bleeding in a female hemophiliac. Is that still the case today, even with modern medicine? What could be done about it, short from a hysterectomy?

Sorry if some consider this question to be in the “TMI” category; it’s not intended to be. But I’m curious and, heck, that’s what General Questions is for, right?

My sister is a hemophiliac. I think she said Factor 8 Von Willebrand or Von Leidin type (sp?)- I’m not sure, but she’s certainly alive and around 50 years old.

Regarding menstruation, the uterine lining is built up and then shed, so I’m not sure that it is really considered active bleeding, but it’s a great question.

Surely someone smarter than me will show up soon to answer your questions better.

Menorrhagia (excessive menstrual bleeding) is in fact a well-known complication of inherited bleeding disorders, and hemophila A (factor VIII deficiency) is one of the most severe of the inherited bleeding disorders. Those few women unlucky enough to be affected by this sex-linked disorder could indeed bleed to death during a menstrual period; women who are merely carriers (having the defectivve gene on one of their two X chromosomes) can be demonstrated by laboratory testing to have prolonged clotting times and may have heavier-than-normal periods.

The endometrium is highly vascular, receiving blood from the uterus via many spiral arterioles. Part of menstrual shedding involves the spiral arterioles constricting, and a blood clot forming in the arteriole where the lining sloughs off. If the woman has a bleeding disorder that prevents those blood clots from forming… Well, you can imagine what happens next.

We now have recombinent factor VIII available, which can be used to control bleeding episodes in hemophiliacs. If a woman with hemophilia A began to hemorrhage during her menses, dosing her with factor VIII might be attempted if the hemorrhage wasn’t too rapid and massive; if it were, she’d need a hysterectomy.

Ca3799, from your description, your sister has either von Willebrandt’s disease or the factor V Leiden mutation. Von Willebrandt’s disease can cause prolonged bleeding, but it’s generally not as severe as the bleeding that results from hemophilia A. The factor V Leiden mutation, on the other hand, causes a hypercoagulable state that places the carrier at risk of developing dangerous blood clots. In either case, your sister isn’t a hemophiliac.

As to why it’s rare in females: The gene that, when defective, leads to hemophelia is carried on the X chromosome and is recessive. So a male, having only one of those, is runs a 50% chance of having the disorder if his mother is carrying the gene. A girl, of course, also has a 50% chance of getting her mother’s defective X, but she will also get her presumably healthy father’s X chromosome. However, if Dad has the gene, and Mom is a carrier, then there’s a 50% possibility of a daughter having it.

Of course, there’s always the possibility of a mutation arising. Some theorize that just such a mutation occurred in Queen Victoria herself or one of her immediate ancestors. It is probably coincidence that QV was also rumored to use marijuana regularly (it was legal at the time) to help control menstrual cramps.

It is doubtful that who her father was could have anything to do with it, unless her real father were a hemopheliac.

When the uterine lining is shed, there is definitely some actual bleeding. I would imagine that in the generations before clotting factors were available for treating this disorder, that it could definitely be fatal for a woman.

IANAD, this is based on general reading, etc.

Thanks for the responses. ARTEMIS, this:

. . . leads me to a second question. Why would a carrier female have clotting problems? I thought a carrier was basically a genetic “pass-through” who was symptomless, because they did not have the disease/disorder, they just carried the genetic potential for it forward. Are you saying that “carriers” for some disorders may have the disorder in some very minor form? I’m not challenging you, I’m just curious.

There are plenty of diseases that are present, though usually in a less severe form, in the heterozygous state (ie, one normal allele, and one mutant allele). The aforementioned Factor V Leiden is a perfect example.

The reason is that genes make proteins. Defective genes make defective proteins. Depending on what the protein does and how it functions, your body may be able to get by with only 50% normal proteins, or it may cause mild or serious problems.

With FVL, a heterozygote is at greater risk of having blood clots than is a person without the mutation, but a homozygote is at a much greater risk than a heterozygote.

Shit, Artemis. If you’re not a doctor, you should be.

Thanks for the info. I’m not very well informed about hemophilia.

My sister broke her arm which either didn’t or wasn’t set properly at first and had to be reset. When the cast came off, the bone was found to be badly set again requiring surgical correction. She was tested for the things you mentioned through the hemophilia center in Houston, I think because of something unusual about the callous (sp?), found to be deficient in factor 8, and was required to have factor 8 supplementation before during and after the surgical correction. Her doctor also sent her to hemophilia camp (where she said she was the oldes ‘camper’!) .

Does that story make sense to you? I’m asking because I got all this info from my sister who’s not a medical person so may have miscommunicated something and because she also wants me and my daughter to be tested. I’m currently uninsured so won’t do it for myself even thought I have a diagnosis of menorrhagia, but my daughters’ pedi doesn’t seem inclined to do any testing on my daughter.

Jodi, Smeghead nailed it. Women who are carriers of hemophilia A have only one normally working copy of the factor Vlll gene, and because of this they actually have lower than normal circulating factor Vlll levels in their blood. Not so much lower that they develop severe bleeding problems, like those unfortunate people with two defective copies of the gene, but low enough that it’s detectable in laboratory tests and may cause the woman some minor symptoms (very heavy periods, having cuts “ooze” a bit longer than most people.)

Guilty as charged - I’m a pathologist.

Thanks, DR. ARTEMIS! :slight_smile:

This is just an educated guess, but based on this information I suspect your sister may have von Willebrand’s disease. Factor Vlll binds in the blood to von Willebrand factor, which stabilizes it; a person with low levels of circulating von Willebrand factor may also have lower than normal levels of circulating factor Vlll because the free factor Vlll has a shorter half-life than factor Vlll bound to von Willebrand factor. Unlike hemophilia A, which is a sex-linked disorder, von Willebrand’s disease is an autosomal disorder and affects both women and men equally; there are several subtypes, too, some of which are very mild, others of which can cause more serious bleeding problems.

It would be a good idea to talk with your sister (or get her permission to talk directly to her doctor) and find out exactly what condition your sister has, and then pass that on to your own physician and to your daughter’s pediatrician. If neither of you are having serious bleeding problems, there’s no great rush to be tested - but the information COULD be potentially valuable in the future if problems should develop.