Page 882 - Clinical Immunology_ Principles and Practice ( PDFDrive )

854 Part Seven Organ-Specific Inflammatory Disease

Antiplatelet antibody testing to specific platelet glycoproteins TRAs. Initial dosing of eltrombopag should be reduced by 50%
is not routinely recommended; the test is neither sensitive nor in patients of Southeast Asian origin. Danazol is an attenuated
specific for ITP. Routine testing for anticardiolipin antibodies androgen administered orally and has been used, with some
is not recommended in the absence of symptoms of antiphos- success, as a steroid-sparing agent. Third-line therapy is reserved
pholipid syndrome. DAT should be obtained if hemolytic anemia for patients who are unresponsive to or ineligible for first- and
is suspected and in patients in whom anti-D antiglobulin treat- second-line therapies. These agents include cyclophosphamide,
ment is considered. Blood group Rh(D) typing should be obtained azathioprine, mycophenolate mofetil, cyclosporine, alemtuzumab,
if anti-D antiglobulin treatment is considered. and vinca alkaloids. One novel approach to ITP consists of
Where a microangiopathic process is evident, especially with blockade of the FcγIIIA receptors on macrophages in the spleen
concomitant renal failure, fever, or cognitive impairment, measure- that mediate uptake of antibody-bound platelets. Prior attempts
ment of ADAMTS13 (ADintegrin-like And Metalloprotease with at FcγIIIA receptor blockade to ameliorate ITP using mAbs to
ThromboSpondin type 13 motifs) is warranted to rule out TTP. FcγIIIA have improved platelet counts in half the patients refrac-
tory to other treatments but were abandoned because of nausea,
Therapy of ITP 53 vomiting, fever, and rarely anaphylaxis that were presumed to
be caused by immune stimulation from cross-linking of FcγIIIA
tHeraPeUtIC PrInCIPLeS receptors by bivalent IgG. Preclinical studies suggest monovalent
anti-FcγIIIA fused to albumin (to prolong the half-life) may
Immune Thrombocytopenic Purpura (ITP) block the FcγIIIA receptor without stimulating the immune
system, and this approach may be tested clinically, again. 54
• Primary goal—prevent bleeding
• Treatment not usually necessary if platelets >30 000/µL Therapy of ITP During Pregnancy and the
• Prednisone and/or intravenous immunoglobulin (IVIG) usual first
medications Neonatal Period
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• Anti-D may avert/delay splenectomy Patients with ITP with platelet counts higher than 20–30 × 10 /L
• Treat refractory ITP with immunosuppressives usually do not require treatment during the first and second
• Mycophenolate mofetil, cyclosporine, alemtuzumab, cyclophospha- trimesters of pregnancy; platelet counts should be monitored
mide, rituximab (not approved by the US Food and Drug Administra-
tion [FDA] for this use) more closely as delivery approaches. Obstetrical anesthesiologists
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• Splenectomy for persistent disease (immunize patient with pneu- recommend a minimum platelet count of 75 × 10 /L to allow
mococcal vaccine before surgery) administration of spinal or epidural anesthesia. A platelet count
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of at least 50 × 10 /L is generally considered adequate to allow
a Cesarean section. 52
In most circumstances, the goals of therapy are to keep the platelet First-line therapy consists of prednisone and IVIG. Prednisone
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count above 30 × 10 /L and to minimize toxicity. In the absence is initiated at a low dose (10–20 mg) and then adjusted to the
of hemostatic comorbidity, trauma, or surgery, intracranial minimum dose that produces a hemostatically effective platelet
hemorrhage is rare in patients with a platelet count above 20 × count. Corticosteroids may exacerbate hypertension, diabetes,
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10 /L. Treatment of ITP should be individualized, but first-line and osteoporosis during pregnancy and are associated with weight
therapy usually consists of corticosteroids supplemented with gain and psychosis. Corticosteroid use in the first trimester has
either IVIG or anti-Rh(D) in Rh(D)-positive, nonsplenectomized been associated with congenital anomalies, such as orofacial clefts,
patients. Intravascular hemolysis, disseminated intravascular and low-dose corticosteroids have no impact on the fetal platelet
coagulation, and renal failure have been reported with the use count. IVIG is an effective means of increasing the platelet count
of anti-Rh(D). Anti-Rh(D) should be avoided in patients with rapidly and is preferred over prednisone in this setting. The
underlying hemolysis or a positive result of the DAT that is not American Society of Hematology (ASH) guidelines consider
the result of prior therapy. Several uncontrolled studies suggest IVIG to be an appropriate first-line agent for severe thrombo-
that bolus oral therapy with oral dexamethasone for 1–4 cycles cytopenia or for thrombocytopenic bleeding in the third trimester.
increases response rates and prolongs remission duration. Anti-Rh(D) is safe and effective for the mother and fetus in
Second-line therapy should be initiated if there is absence of nonsplenectomized Rh(D)-positive patients. 33,52
a robust response at 1 month or once significant steroid related Second-level therapy before delivery may require utilizing
toxicity supervenes. Two-thirds of patients obtain a durable higher doses of corticosteroids combined with IVIG to achieve
long-term remission following splenectomy, and these patients an adequate platelet count. Splenectomy is an option for patients
should receive immunizations with the pneumococcal, Hae- who fail corticosteroids and IVIG. Remission of ITP is achieved
mophilus influenzae type b, and the quadrivalent meningococcal in 75% of patients. Splenectomy is optimally performed during
vaccines before splenectomy. A single course of rituximab the second trimester. The risk of inducing premature labor is
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(anti-CD20) (375 mg/m weekly for 4 weeks) is associated with high during the first trimester, and the enlarged uterus renders
40% complete remission at 1 year and 15–20% complete remission the procedure difficult if not impossible during the third trimester.
at 5 years. Patients who relapse after an initial response usually Vinca alkaloids, rituximab, danazol, thrombopoietin receptor
respond to a second course. Rituximab is contraindicated in agonists, and immunosuppressive drugs (other than azathioprine)
patients with active hepatitis B. Cases of multifocal leukoen- should be avoided during pregnancy. 33,52
cephalopathy have been reported in HIV-negative patients treated Management of parturition is based on the finding that there
with rituximab. The thrombopoietin receptor agonists (TRAs) is no correlation between platelet counts or ITP status of the
romiplostim and eltrombopag have shown significant sustained mothers and the development of neonatal thrombocytopenia.
activity in patients with ITP. Romiplostim is administered The most reliable predictor of neonatal thrombocytopenia is a
33
subcutaneously and eltrombopag orally. Increased bone marrow history of thrombocytopenia at delivery in a prior sibling. In
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reticulin fibrosis has been described in some patients receiving a large meta-analysis, fetal platelet counts below 50 × 10 /L were