The Autoimmune Connection: Essential Information for Women on Diagnosis, Treatment, and Getting On With Your Life (47 page)

Low platelet counts that delay clotting can cause very heavy menstrual periods that last longer than a week. For some women who have had ITP for years with no other symptoms, heavy periods may simply seem “normal.” Iron replacement may be important.

Some women who experience heavy menstrual bleeding take oral contraceptives (OCs) to regulate their cycles and lessen bleeding. While this is generally safe for most women with ITP, a few will have the estrogen component of the oral contraceptives worsen their ITP. Therefore when possible we use OCs low in estrogen and high in progesterone, says Dr. Bussel.

But a note of caution. Some women with low platelets have antiphospholipid antibodies as described earlier in this chapter. For those women who test positive for these antibodies, birth control pills containing estrogens may be dangerous in that they increase the risk of blood clotting. So it is wise to have aPL checked before going on birth control pills if you have a history of ITP. It may seem paradoxical that low platelets that cause bleeding can be
associated with aPL that can cause blood clotting; however this is a situation that can happen.

Many cases of ITP are first diagnosed during pregnancy, and, in fact, the disease can be triggered by pregnancy. (There is a separate, nonautoimmune problem called gestational thrombocytopenia that often occurs during the third trimester, where platelet counts may drop slightly to around 80,000 but return to normal after delivery.)

It was previously thought that pregnant women with ITP might experience some worsening of their disease. But this may not always be the case, says Daniel W. Skupski, MD, professor of OB/GYN at the Weill Medical College of Cornell University.

Dr. Skupski and colleagues studied 96 pregnancies in 53 women over a 16-year period to look at the severity of ITP in pregnancy, recording how often women had bleeding episodes (especially around the time of delivery), and kept track of whether the disease worsened or improved over time. “Major bleeding complications were limited to one case of early placental separation and four cases of postpartum hemorrhage, which is no different from the rate of these types of problems in women without ITP,” says Dr. Skupski. “It appeared that, as a general rule, ITP improved in the early part of pregnancy, returned to baseline later in pregnancy, was not different in severity during pregnancy as opposed to when not pregnant, and did not appear to worsen in subsequent pregnancies.”

During pregnancy your platelet counts will be monitored, and if need be, you’ll be put on oral corticosteroids if they drop too low. IVIG is used only when clearly indicated. “Our experience with IVIG is that it doesn’t produce problems for the pregnancy or for the fetus,” says Dr. Skupski. When platelet counts were below 50,000 around the thirty-eighth week of pregnancy, treatment with IVIG produced an increased count such that labor could be induced and epidural anesthesia could safely be used. Premature births do not seem to be associated with ITP.

Marked neonatal thrombocytopenia
can occur in up to 15 percent of infants born to women with ITP, because of maternal antibodies crossing the
placenta. Having a previous baby born with thrombocytopenia increases the chance another child will be affected. Your platelet count does not have any bearing on your baby’s.
²⁵
That’s because autoantibodies against the platelets may be present in the mother but not necessarily result in low counts. However when crossing the placenta, which all IgG isotypes do, they can attack the fetal platelets.

In neonatal thrombocytopenia, a baby may be born with a low platelet count or platelets may begin to drop in the first week after delivery. Oral corticosteroids and intravenous immunoglobulin can help bring platelet counts up. However, the baby’s platelet count usually stabilizes and starts to rise within three to four weeks, as maternal antibodies gradually decrease (interestingly maternal antibodies may not fully clear until about six months).

While ITP itself doesn’t appear to worsen because of pregnancy, in some women platelet counts may settle at a lower level after giving birth and dip further with each subsequent pregnancy, says Dr. Skupski. This may be because the disease tends to worsen over time, rather than any effect of pregnancy. And it does not necessarily cause bleeding or other symptoms.

Estrogen therapy (ET) for menopausal symptoms may lower platelet counts in some women with ITP, says Dr. Bussel. Preliminary studies suggest that taking a higher dose of progestin for 10 days every month together with estrogen may counter those effects. Progestin also prevents overgrowth of cells in the uterus that can lead to cancer, and women who have not had a hysterectomy are generally advised to take combined hormone replacement therapy.

“However, because it can lower platelet counts, I generally do not advise women to take estrogen for osteoporosis prevention. There are other drugs that are more effective for this purpose,” he adds. “If a woman feels that she needs estrogen for menopausal symptoms, I would advise her to do so in conjunction with measuring platelet counts regularly, to make sure it is not having any adverse effects on her ITP.”

Nonhormonal menopausal remedies may be helpful for some women. However, red clover (sold under the brand name of
Promensil
) can promote bleeding and should not be used by women with bleeding disorders like thrombocytopenia.

If you’ve ever taken prednisone or other corticosteroids, you have an increased risk of osteoporosis, so you should have regular bone mineral density testing, especially after menopause. You also need to take supplemental calcium and vitamin D, and possibly drugs, to prevent or treat osteoporosis. (See
page 57
.)

As you get older, you’re more likely to be taking one or more medications for other health problems, such as high blood pressure or high cholesterol. There are prescription drugs (as well as over-the-counter drugs and supplements) that can lower platelet counts. For example, the cholesterol-lowering drug
atorvastatin (Lipitor)
binds to plasma proteins and may infrequently cause severe thrombocytopenia. Tylenol can also reduce platelet counts, as can the heartburn medicine
cimetidine (Tagamet).

Women with cardiovascular disease may need low-dose aspirin (81 mg a day), but it needs to be monitored carefully. “I advise women to take aspirin if their platelet counts are 50,000 to 60,000 and they are stable. They will get the same benefits from aspirin just as other people with cardiovascular disease do,” says Dr. Bussel. “If you don’t take prophylactic aspirin because you have ITP, and your platelet counts improve, you can run the risk of strokes and heart attacks. So it is something that must be used cautiously.”

Other drugs for heart-related conditions can affect platelet counts, including diuretics like
chlorothiazide
and
chlorthalidone
;
digoxin
(any digitalis preparation); calcium channel blockers like
diltiazem
(
Cardizem
), and antiarrhythmics such as
procainamide (Pronestyl-SR)
.

Many commonly used antibiotics like
ampicillin
,
cephalosporin
, and
sulfamethoxazole
can also affect platelet counts. So alert your hematologist to all medications you’re taking.

Some forms of vasculitis are thought to be separate from autoimmune diseases, while others are a consequence of systemic inflammatory disease that can inflame and damage blood vessels, such as scleroderma or lupus.

There are autoantibodies that act against components of blood vessel walls, including the cells lining the inside of the vessel (
endothelial cells
) and the thin cell membrane that separates the vessel lining from the smooth muscle (
basement membrane
). When autoantibodies attack the vessel wall, it causes immune complexes to form inside the wall and attract inflammatory cells. (Immune complexes are latticelike structures created when antibodies bind to antigens.) Immune complexes that form in the blood of lupus patients may also attach themselves to the endothelial cells, damaging the blood vessel lining. Some evidence suggests that this may also occur in rheumatoid arthritis and in Sjögren’s syndrome. Autoantibodies in diseases like lupus may also cause blood vessel damage.

The vasculitides that occur independently such as
giant cell arteritis
or
Takayasu’s arteritis
, are believed to be caused by damage from autoreactive T cells, which provokes an inflammatory reaction in the blood vessel wall. Overexpression of the inflammatory cytokine
tumor necrosis factor alpha (TNFα)
, involved in diseases like rheumatoid arthritis and Crohn’s disease, is also thought to contribute to vasculitis.

Much of the pathophysiology of vasculitic diseases has not been worked out. Different immune cell types are in each, and different layers of the vessel wall are affected.

Vasculitis can also be triggered by a past or present infection (including hepatitis) that leads to formation of immune complexes, by certain cancers, or by an allergic reaction to medication (such as sulfa drugs,
sulfonamides
). In most cases the trigger is not known.

Genes also play a role. Some forms of vasculitis cluster in families and may affect certain racial groups more often. Caucasians (especially those of Scandinavian descent) are more prone to temporal arteritis and polymyalgia rheumatica (PMR); Asian women are more susceptible to Takayasu’s arteritis.