Authors: Rita Baron-Faust,Jill Buyon
Having low platelets can affect menstrual periods and can complicate pregnancy; some cases of ITP may even be caused by pregnancy.
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.
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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.
Vasculitis
means inflammation of blood vessels, and the different disorders that result (
vasculitides
) can affect every type of blood vessel from the major arteries to the tiny capillaries, from small venules to large veins.
Inflammation from vasculitis causes two types of damage. It can weaken a section of the blood vessel wall, causing it to stretch and bulge out like a tiny balloon (an
aneurysm
). In rare cases, the bulging vessel wall can become so
weak that it ruptures and bleeds. In other cases, the inflamed blood vessel wall becomes narrowed, restricting blood flow (
ischemia
). A blood vessel may even close off (
occlusion
), blocking blood flow altogether. Sometimes the body compensates for hampered blood supply by rerouting blood to other blood vessels (
collateral blood supply
), but sometimes there simply isn’t enough collateral flow and the affected tissue dies (
infarction
).
Vasculitis can affect one organ, such as the kidneys, or it can affect several organ systems at once (
systemic vasculitis
); symptoms can vary depending on the parts of the body affected. Vasculitis is often called the “great mimicker” because its symptoms can mimic those of other diseases.
Women are at particular risk for two types of systemic vasculitis:
Takayasu’s arteritis
, which affects the aorta and its branches, and
giant cell arteritis
(
GCA
, also called
temporal arteritis
), an inflammation of the arteries that primarily supply the head.
Other types of systemic vasculitis include
polyarteritis nodosa
,
eosinophilic granulomatosis with polyangiitis (EGPA)
, formerly termed
Churg-Strauss syndrome
, and
granulomatosis with polyangiitis (GPA)
, formerly called
Wegener’s granulomatosis
.
26
Different forms of vasculitis are now classified in terms of the size of the blood vessels that are affected. GCA and Takayasu’s are both considered
large vessel vasculitis
under this new nomenclature.
27
Vasculitides that affect
medium-sized
vessels are polyarteritis nodosa and Kawasaki disease.
Small vessel vasculitis
is associated with
antineutrophil cytoplasmic antibodies (ANCA)
. ANCA-associated vasculitis includes GPA and EGPA (a rare disease).
Takayasu’s is nine times more common in women and typically occurs before age 40; GCA affects two to three times more women than men, usually later in life.
GPA affects men and women equally at any age and can be life threatening. It most often affects the upper respiratory tract (the sinuses, nose, and trachea) but can also cause problems in the ears, eyes, skin, lungs, heart, kidneys, and the nervous system.
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.
The symptoms of vasculitis can be nonspecific; inflammation can often provoke body-wide symptoms such as fever, fatigue, aches, and a general feeling of just being ill. There may be appetite loss, weight loss, and an absence of energy.
Other symptoms depend on the area of the body or even the type of blood vessel that’s affected, says Hal J. Mitnick, MD, a clinical professor of medicine at the New York University School of Medicine with a special expertise in vasculitis. “Vasculitis affects the venous system more often than the arterial system, probably because veins are ‘leakier’ than arteries.” explains Dr. Mitnick. The damage caused by vasculitis in the smallest veins (venules) may allow leakage of both plasma and red blood cells. “The most common syndrome is leukocytoclastic vasculitis, predominantly an inflammation of the venules,” he adds.
When red blood cells leak from the venules, it usually produces a rash you can feel that has some bruising associated with it, called
palpable purpura.
When the rash appears as flesh-colored hives that don’t go away in less than 24 hours, it’s due to inflammation that doesn’t usually involve red cell leakage. This is called
urticarial vasculitis
.
Vasculitis in the blood vessels of the eyes can cause vision loss, or if the kidneys are affected it can lead to progressive kidney failure and/or high blood pressure. Some forms of vasculitis have specific symptoms:
Giant cell arteritis (GCA)
causes inflammation that damages large- and medium-sized arteries, often the temporal arteries along the sides of the head at the temples, just in front of the ears (hence the disorder’s other name, temporal arteritis). It usually occurs after age 50 (the average age of a GCA patient is 70).
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Eighty percent of people with GCA have severe, throbbing headaches, usually in the temples or forehead on one or both sides of the head. The scalp over the affected blood vessels may feel tender and sore (it may even hurt to brush or comb your hair). Many women with GCA have facial or jaw soreness (especially with chewing), says Dr. Mitnick. Depression is also common. If the ophthalmic artery is blocked, it can cause vision loss. If larger arteries leading to the arms or legs are affected, women may have fatigue or aching in the limbs or intermittent claudication, muscle aching during exercise.
Muscle aches or pain can also be due to coexisting
polymyalgia rheumatica (PMR)
. PMR occurs in about 30 percent of women with giant cell arteritis. It is often characterized by the rapid onset of muscle pain or aching in the large muscle groups, especially those around the shoulders and hips. Symptoms of PMR can be somewhat vague, and it’s not uncommon for it to be initially misdiagnosed as an infection, rheumatoid arthritis, or other illness that affects muscles (or even cancer).
Takayasu’s arteritis
, chronic inflammation of the aorta and its branches, has two phases: The systemic phase causes body-wide symptoms of inflammation as well as joint pains and nonspecific aches and pains. In the occlusive phase, women develop symptoms because of the closing off of the affected blood vessels, usually during repetitive activities (
claudication
). Most commonly, sharp pains occur in the arms while cutting meat, or in the calves of the legs while walking. A woman may also experience dizziness when abruptly standing up after sitting or lying down, headaches, and visual problems.
Takayasu’s is often called the “pulseless disease” because it can result in a pulse that’s barely felt. This occurs because blood vessels are narrowed to such an extent that the normal push of blood being pumped through the aorta from the heart cannot be felt in the wrist, neck, elbow, or lower extremities. When a stethoscope is placed over an affected blood vessel, a whooshing sound called a bruit (pronounced
broo-ee
) can be heard as blood pushes through narrowed blood vessels.
Although high blood pressure is common in Takayasu’s (from narrowing of arteries in the kidneys), restricted blood flow in the arms or ankles can make it difficult to get an accurate blood pressure reading. Unfortunately, the disease can be present for some time before symptoms appear, and some women are not diagnosed until they suffer a stroke or other complication of the occlusive phase.
Granulomatosis with polyangiitis
(
GPA
, formerly
Wegener’s granulomatosis
), results from inflammation in blood vessels in a variety of tissues and can produce the same body-wide inflammatory symptoms as other forms of vasculitis. This can cause inflammation of the nose or sinuses, with a persistent runny nose (
rhinorrhea
), nasal crusts and sores, nosebleeds, nasal discharge, and facial pain. When GPA affects the middle ear, it can cause middle ear inflammation (
otitis media
), pain, and hearing loss. Respiratory tract symptoms include a cough, bloody phlegm, and chest pain. You may also experience hoarseness, vocal changes, wheezing, or shortness of breath, caused by inflammation of the trachea. GPA can also affect the kidneys.