DVT etc

For those of you who are just beginning this wonderful process, here we can narrow down the symptoms and ask questions like "am I starting perimenopause?"

DVT etc

Postby biocce » Sun Mar 13, 2005 1:00 am

I don't know where to put this, so i'm putting it here and hoping that someone will move it if needed.

A very good friend of mine was recently diagnosed with Factor V Leiden (FVL). This only came to light after starting to use oral contraceptives, throwing a pulmonary embolism (or three) and nearly doing herself in playing a hockey game with while her blood clotted in bad places in her body.

I bring this up for those people interested in using HRT, without having used any other form of hormonal treatment in the past. Turns out it is not all that uncommon to have a clotting disorder, and if there is history of embolism in the family, a test for clotting disorders may be better than finding out the hard way, as my friend did.

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Postby drjudy » Sun Mar 13, 2005 10:16 am

Wow, what a close call for your friend. I've had one patient with a similar story, put on the birth control pill by her gyn. to handle perimenopause, and a subsequent clot from toe to thigh requiring emergency surgery. All due to undiagnosed Factor V Leiden, although a family history in retrospect did suggest a clotting problem. Here is some information I've written on:

Women who clot too much

Thrombophilia, the tendency of the blood to clot too easily, is the opposite of hemophilia, an unfortunate inherited condition where the blood scarcely clots at all. Neither one improves the outlook for a long and healthy life.

Unwanted blood clots (thrombosis), those that occur in the wrong place at the wrong time, are generally the result of an interaction between inherited and acquired tendencies to over-clot. Surgery, injury, prolonged immobilization, older age, pregnancy, birth control pills, and hormone replacement therapy (HRT) are all contributing risk factors to thrombosis. Thus, an older woman on HRT who falls, breaks her hip, and undergoes surgical repair, is at enormous risk for thrombosis in her injured leg. One of the most common causes of death after a broken hip is a pulmonary embolus, where such a clot breaks free from the veins in the legs and travels to the lungs, blocking blood flow there as well.
Until 1993, we could only identify an inherited thrombophilia in a minority of patients with venous thrombosis. We can now diagnose such genetic tendencies in 30% of those who've clotted but wished they hadn't. The most common causes are misguided genes for either clotting factor V (producing the abnormal and not so useful factor V Leiden) or prothrombin 20210. By taking hormones, whether oral contraceptives or HRT, women with factor V Leiden or goofed-up prothrombin 20210 (sounds like an address in Beverly Hills doesn't it?) are adding an acquired thrombophilia to an inherited one. What are the chances that this won't end up well?

20210 prothrombin mutation:

Researchers went sorting back through the HERS data to see if they could identify those who did poorly right out of the gate on HRT versus those who survived and thrived on the hormones. The women who had one abnormal copy of the mutant 20210 prothrombin gene were significantly more likely to have a nonfatal heart attack if they took HRT, which rose to a nearly 11-fold increased risk if they had high blood pressure as well. On the other hand, results of still another study showed that those women with a full load of normal prothrombin were twice as likely to have coronary artery disease if they didn't take HRT. These results suggest that identifying the 4% of the menopausal female population with variations in the 20210 gene highlights the remaining 96% of women whose hearts would prosper on HRT!

Factor V Leiden:

Women with factor V troubles would do well to avoid the pill. While women on the pill with normal factor V experience a 4-fold increase in risk of blood clots, those with the Leiden variety are at a whopping 35 times higher risk! This tendency to clot early, clot often, is even worse with the so-called "third generation" pills, including Desogen, Mircette, and Ortho-cept, because the progestogen used in these pills (desogestrel) causes a more profound thrombophilia. While prothrombin 20210 mutations also increase the risk of clotting on the pill, factor V Leiden does not seem to increase the risk of deep vein thrombosis in women on HRT but may be related to strokes.

Mutant MTHFR genes:

I bet you're thinking right now that you know a person or two with problems in their MTHFR genes. Well I don't mean those MTHFRs, but rather the mutant methylenetetrahydrofolate reductase (MTHFR) C677T gene type that causes high levels of homocysteine in the blood and is an inherited risk factor for cardiovascular disease. The MTHFR enzyme is involved in turning homocysteine into methionine, which is a good thing. Some people are better at this than others, a talent dependent on normal MTHFR genes and a generous supply of folate, and vitamins B6 and B12. Persons who are deficient in either MTHFR or B vitamins end up with too much homocysteine which increases the risk of cholesterol build-up in arteries, blood clots, spinal cord defects in their children, and maybe breast, cervical, and ovarian cancers as well.

This MTHFR mutation is common, found in up to 15% of Caucasians of European descent. African Americans have a very low incidence of this whacked-out enzyme. Checking for mutant MTHFR may be helpful for patients with early-onset heart disease or blood clots. The easiest approach to reining in the homocysteine levels, however, is for everyone, particularly pregnant women and those with a family history of early heart disease, to take a good multivitamin pill with at least 400 micrograms of folate.

I certainly agree with biocce that a careful family history about abnormal blood-clotting or heart disease, especially in a parent or sibling at a relatively young age, is important information when considering a prescription for hormone therapy. Here is some information on the relative safety in this respect of transdermal instead of oral hormone therapy:

Blood clotting effects

In the current uproar over the safety of hormone replacement therapy, experts have theorized that transdermal estrogen therapy--delivering the hormone through a skin patch--may be associated with fewer health hazards. A French study published in The Lancet in 2003 contains reassuring supportive data.

Paris investigators compared women with episodes of blood clots in the veins of the legs (venous thromboembolism or VTE) with clot-free controls. Women using oral estrogen therapy were more than three times as likely to develop VTE than were transdermal ERT users or those on no hormones at all. These results are consistent with studies that indicate that oral hormone therapy activates clotting by elevating blood levels of various proteins whereas transdermal therapy does not.

Lead author Dr. Pierre Scarabin notes "These data suggest that transdermal ERT might be safer than oral ERT with respect to thrombotic risk." Another study supports his theory.

Dr. Erik Adolf von Willebrand was apparently the "clot king" of Finland, because his name is all over the world of blood coagulation. Those suffering from von Willebrand's disease, which affects humans, dobermans, and shelties, are deficient in von Willebrand factor (vWF), a bloody predicament wherein victims bleed too much and clot too little.

Elevated levels of vWF are not so hot either; such derangements indicate a predisposition to clot too much and are a marker for atherothrombosis (clots perched upon cholesterol deposits in gummed-up blood vessels).
Knowing that oral estrogen is now linked with an increased risk of heart disease and stroke, investigators from Columbia University College of Physicians and Surgeons went looking for abnormal levels of vWF in postmenopausal women on either conjugated equine estrogens (Premarin) or transdermal estradiol (patches such as Vivelle or Climara).

Thirty-eight women in their late 50's took one or the other or nothing at all for a month. Blood samples were collected at baseline, and again at the end of the study, and were analyzed for lipid levels and vWF.

As expected, Premarin decreased total and LDL-cholesterol (a good thing) while increasing HDL-cholesterol (still good) and triglycerides (ooh, that's bad). Estradiol patches had no effect on any of these levels. But (eyebrows now rising in NYC research lab), oral Premarin users had a significant increase in vWF by study's end, while those who were patched in to hormones had no change at all. This may be one mechanism whereby oral hormones increase the risks of clotting and cardiovascular disease.

Finally, in a substudy of the data from the Women's Health Initiative, investigators compared the risk of developing blood clots in women across age and weight ranges. They found that the risk of clotting with HRT increased with weight and age, and that women with normal body mass indices (or BMI--a number that expresses your height and weight as a single value; increasing BMI levels over 25 indicate unhealthy levels of body fat) in their 50s were extremely unlikely to develop blood clots while on the traditional hormone therapy used in this study.

I appreciate biocce's bringing this matter to our attention,
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