Factor
XI Deficiency in Ashkenazi Jews:
Should
you get Tested?
It
is well known that Jews of Ashkenazi descent are prone to a variety of genetic
disorders. In fact, as many as one in four Ashkenazi Jews is a carrier for
at least one genetic disease. As an Ashkenazi Jewish physician and
researcher with an interest in genealogy, I want to call everyone’s attention
to Factor XI Deficiency: Why? Because I made it into my 80s unaware that I
had it, even though it had caused me serious medical problems more than
once. Because it is an inherited
condition you may not know you have it. And
especially, because it is a condition that a great many physicians are not
aware of.
A
few years ago I tripped and fell, landing on my left side. I broke a bone in my wrist and one in my
ankle, so the fall necessitated a trip to the Emergency Room. A really enormous hematoma (swollen bruise
filled with blood) had developed in my thigh and hip where I had hit the ground. When a routine blood test revealed that my hemoglobin
level was surprisingly low, it became obvious that there was a lot more
bleeding into the bruise than there should have been. I was admitted to the hospital for further
tests. The hematologist who saw me drew many tubes of blood and asked about any
family history of bleeding. I mentioned
that I had a first cousin whose intractable nosebleeds were not able to be corrected
by surgery. He had told me he had some
type of abnormal blood factor, but didn’t know what type. Most importantly, she asked me about my
ethnic background.
That’s
when I learned about a bleeding disorder known as Factor XI Deficiency (also
called Hemophilia C[1]) which
is quite common among Ashkenazi Jews. Often symptomless, one of the mutated
genes causing the disorder has been passed down through the generations, it is
believed, from the Jews who migrated to Poland and the Baltics after the
Destruction of the Temple in 70 CE, or possibly even from some time prior to
the reign of King David. A second mutated
gene is of more recent origin.
Factor
XI Deficiency is characterized by low levels of a blood protein called Factor
XI, a clotting factor present in blood plasma. (Clotting factors are
specific proteins that are necessary for proper clotting, the process by which
blood solidifies at the site of a wound to stop bleeding.) The mutations in the F11 gene that
give rise to Factor XI Deficiency are inherited in a recessive pattern: both
parents must carry mutated genes to pass Factor XI Deficiency on to their
children. If both parents are carriers of the mutated gene, even if the
parents are asymptomatic, each child has a 25% chance of developing the
disease. Males and females are affected equally. Among Ashkenazi Jews, the two gene mutations mentioned
above are quite common; a third mutation has been found among Iraqi Jews who stayed in the Middle East in
relative isolation for 2500 years, but is not as commonly found as the
mutations that affect Ashkenazim.[2] Factor XI Deficiency is also found in
Israel in smaller numbers among Sephardic Jews and Israeli Arabs. It is believed that 8% of Israeli Ashkenazi
Jews have Factor XI Deficiency, and that percentage is probably as high in the
United States. Between 8-13.4% of
Ashkenazi Jews here and in Israel are estimated to be carriers of the mutated
genes, even though they do not have Factor XI Deficiency. In contrast, its incidence in non-Jews in the
United States is very low, estimated at 1 in a million individuals.
Not
everyone with lowered levels of Factor XI has symptoms. But those who do may experience prolonged blood
flow from wounds, tooth extractions, tonsillectomies and other surgical
procedures, particularly from surgery involving the urinary or genital
tracts. Nose bleeds and easy bruising are not infrequent. More than
half the women so affected have heavy or prolonged menstrual periods or excessive
bleeding after childbirth, miscarriages, or abortions. Serious bleeding may
occur after circumcision; but thankfully, that is rare. Blood-thinning
medications like Pradaxa, Xarelto, and others, may cause internal bleeding. And the
thing is—you may have a Factor XI Deficiency, not know it, and go for decades until
symptoms seem to show up “out of the blue.”
That
certainly happened to me when I fell, but as I look back, it explains the four
units of blood I needed during back surgery during my thirties, the hemorrhage
that started many hours after prostate surgery, and massive bruising when I was
put on Pradaxa. Each “bleed” involved a
different doctor; and because I don’t remember ever having heard about Factor
XI Deficiency, there was no one to put the picture together. Had my condition
been known, Pradaxa would never have been prescribed for me, and the bleeds prior
to my fall might have been avoided. In
other words, those who know they have
Factor XI Deficiency may need specific therapy for surgery, accidents, and
dental extractions. Health care providers should be made aware of a history of
bleeding when a surgical procedure is planned. For severe cases,
appropriate management should involve a hematologist, an internist or family
physician, and the surgeon.
Should
you be tested for Factor XI Deficiency?
Bleeding
in individuals with this disorder is very variable, ranging from a complete
absence of symptoms to severe bleeding that requires multiple transfusions
after injury or surgery. The bleeding may be immediate or delayed. And
for some unexplained reason, there is a poor correlation between severity of bleeding
and laboratory measures of Factor XI coagulant activity. In other words, on
the basis of lab tests, some persons who would be expected to have major
bleeding problems may not, and some people who would be expected to have mild
symptoms may have serious bleeding. Not only that, the severity—or even
the presence—of excessive bleeding may vary widely over a particular
individual’s lifetime. If one knew for
sure that testing positive meant you were at risk for serious bleeding, then
you’d want to be tested. But this is not the case. Diagnosis requires the synthesis of a
bleeding history, family history, and specialized laboratory tests. You should consider being tested before
elective surgery if both your
parents are Ashkenazi Jews and if you or any family members have had bleeding
problems.
Robert A.
Davidoff, M.D.
Professor Emeritus
Departments
of Neurology, Pharmacology, and Physiology
University
of Miami School of Medicine
Miami,
Florida, USA
Author’s
Disclaimer:
The above was not written as a peer-reviewed medical article would have
been. I am not a hematologist. Nor am
I in any way an expert in Factor XI Deficiency.
I’ve written this to make my co-religionists aware of a genetic disease
that affects our community.
