Page 880 - Clinical Immunology_ Principles and Practice ( PDFDrive )

852 Part Seven Organ-Specific Inflammatory Disease

very low count, or a previous pattern of frequent infection. The IMMUNE-MEDIATED THROMBOCYTPENIAS
indications for immunosuppressives, steroids, and splenectomy
are more complex. Immune Thrombocytopenia
tHeraPeUtIC PrInCIPLeS KeY COnCePtS
Immune Neutropenia Immune Thrombocytopenic Purpura
• Palliative treatment of neutropenia is reserved for patients with a • Antibody-mediated destruction or decreased production of platelets
neutrophil count below 500/mm or recurrent infection. • Both B and T cells important in etiology
3
• Recombinant granulocyte–colony-stimulating factor (G-CSF) is the most • Clearance of platelets mediated by Fcγ receptors
effective single agent for palliating neutropenia. • Diagnosis depends on:
• Immunosuppressive agents, steroids, and splenectomy are reserved • Clinical presentation of low platelets
for patients with persistent or refractory neutropenia or with other • Exclusion of other causes of thrombocytopenia
detrimental manifestations of systemic autoimmunity.
Colony-Stimulating Factors Immune thrombocytopenia (ITP) is an autoimmune syndrome
31
Controlled trials are lacking in this disease setting, but involving antibody and cell-mediated destruction of platelets.
granulocyte–colony-stimulating factor (G-CSF) or granulocyte ITP can occur in the absence of an identified predisposing factor
macrophage–colony-stimulating factor (GM-CSF) usually enhance (primary ITP) or in association to drug exposure or other
neutrophil counts in each of the clinical groups discussed. Because identified cause (secondary ITP). Recent recommendations from
of their safety, speed, and efficacy, they have replaced steroids an international working group recommend that a platelet count
9
and splenectomy as first-line symptomatic therapy. They should of <100 × 10 /L be required for diagnosis. 32
be used at the lowest effective dose, with particular caution in
patients with systemic autoimmune disease, as they are prone ITP During Pregnancy and the Neonatal Period
to leukocytoclastic vasculitis as a complication of therapy. 18 Gestational thrombocytopenia is the most common cause of
thrombocytopenia in pregnancy, affecting 5% of all pregnan-
Immunosuppressive Agents cies and accounting for 75% of cases of pregnancy-associated
Because disease is usually self-limiting and responsive to G-CSF, thrombocytopenia. Gestational thrombocytopenia develops in
immunosuppressive agents are seldom used in children with the late second or third trimester and is not associated with
primary immune neutropenia. Chronic low-dose methotrexate an increased incidence of pregnancy-related complications or
is considered first-line therapy for patients with Felty or LGL the delivery of thrombocytopenic offspring. Preeclampsia and
leukemia–associated neutropenia. Cyclophosphamide and HELLP (hemolysis, elevated liver enzymes, and low platelet count)
cyclosporine are considered second-line therapy for LGL leukemia, syndrome are also present in the third trimester and are associated
and purine analogues, splenectomy, and alemtuzumab are with thrombocytopenia. Thrombotic thrombocytopenic purpura
considered third-line therapy for LGL leukemia. (TTP) and hemolytic uremic syndrome need to be considered in
the differential diagnosis of thrombocytopenia of pregnancy. ITP
Other Therapy accounts for 5% of pregnancy-associated thrombocytopenia.
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Each of the following treatments can be effective in reversing Lack of hypertension, fever, hemolytic anemia, uremia, and liver
neutropenia, but their use has diminished considerably in recent function abnormalities serve to distinguish ITP from these other
years. IVIG can temporarily reverse neutropenia, particularly conditions.
in children, probably by blocking Fc receptors responsible for
triggering neutrophil destruction. However, G-CSF, which is more Neonatal Alloimmune Thrombocytopenia and
convenient to administer and at least as effective, has largely Posttransfusion Purpura
replaced use of IVIG. Neonatal alloimmune thrombocytopenia (NAT) caused by
Splenectomy and steroids can each reduce immune destruc- antihuman platelet antigen 1a (HPA-1a) antibodies occurs in
tion by suppressing the body’s capacity to clear IgG- and 1 : 1250 pregnancies in the Caucasian population. Severe hemor-
complement-coated cells. Over a longer time frame, these rhage occurs in 1 : 12 500–1 : 25 000 pregnancies. NAT is caused
treatments can also suppress antibody production, in the first by maternal antibodies against paternally derived antigens on
case by removing a major site of production and in the second fetal platelets, most commonly HPA-1a. These antibodies cross
by reducing antineutrophil antibody production and blocking the placenta and sensitize fetal HPA-1a–positive platelets, which
T-cell–mediated myelosuppression. They can reverse neutropenia are then removed in the spleen. Two percent of Caucasian women
in many patients, but their long-term impact on outcome remains carry the less frequent HPA-1b and can be immunized against
unclear. Given their risk and side effects, both modalities are HPA-1a during pregnancy (25%) or at the time of delivery
generally reserved for patients resistant to CSFs and low-dose (75%). The HPA-1a antigen is most efficiently presented by
immunosuppressives. HLA-DRB3*0101; 35% of the women at risk (with HPA-1b and
34
HLA- DRB3*01:01) are immunized. In most circumstances,
Prophylactic Antibiotics first-time cases of NAT are identified following the birth of a
Where recurrent infection is a problem, oral trimethoprim– markedly thrombocytopenic neonate; antenatal management
sulfamethoxazole (TMP-SMX) is commonly used for prophylaxis, is, thus, only possible in subsequent pregnancies. Screening all
particularly in children. This approach is very reasonable, given pregnancies for NAT is under evaluation in several countries.
its success in other immunocompromised groups, but it has not Treatment of NAT consists of maternal administration of high
been tested in a controlled trial. Immunization with pneumococcal doses of IVIG and corticosteroids. 35
vaccine is also recommended in situations where therapeutic Platelet transfusions can induce antibodies to either HPA or
splenectomy has been used or is being planned. antigens encoded by the major histocompatibility complex