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2006 Part XII: Hemostasis and Thrombosis Chapter 117: Thrombocytopenia 2007

immunosuppressive drugs, major adverse effects are marrow suppres- Other Therapies ITP patients with H. pylori infection should receive
sion and possible increased risk of secondary malignancy. 177,234 eradication therapy. Many other therapies, including interferon-α,
243
148
immunoadsorption with staphylococcal protein A, ascorbic acid,
245
244
Cyclophosphamide This alkylating drug can be used orally (50 to 200 colchicine, and plasmapheresis, have been studied for refractory
246
247
mg/day) or parenterally (1.0 to 1.5 g/m IV every 4 weeks) in patients ITP cases, but none has been clearly demonstrated to be effective.
2
with refractory ITP. 235,236 It increases platelet counts in 60 to 80 percent
of patients with ITP, and 20 to 40 percent of those patients will remain Accessory Therapies Adjunctive therapies include agents designed
in remission for 2 to 3 years after receiving 2 to 3 months of ther- to reduce bleeding without necessarily affecting the platelet count.
177
apy. Its beneficial action is linked to its immunosuppression. The major Aminocaproic acid or tranexamic acid, both of which inhibit fibrinoly-
complications of cyclophosphamide therapy are marrow suppression, sis, can be used for excessive mucosal bleeding. Local bleeding can be
hemorrhagic cystitis, infertility, alopecia, and secondary malignancy. controlled by compression and use of gelatin sponges, fibrin sealants,
or antifibrinolytic-embedded gauze. Avoiding the use of antiplatelet
Cyclosporine Cyclosporine is an immunosuppressive drug inhibiting drugs, contact sports, and activities that increase bleeding risk, and
T-cell function, and is primarily used to prevent rejection in patients educating patients about maintaining dental hygiene are very impor-
with organ transplantation. Although cyclosporine may induce a tant. Menorrhagia is a common problem in patients with chronic ITP;
durable remission in patients with ITP when used at relatively low gynecologic evaluation of uterine problems is crucial. Oral contra-
doses (2.5 to 3.0 mg/kg/day), experience with cyclosporine in ITP ceptives and hormonal intrauterine devices together with antifibrino-
237
patients is usually based on small case series. Cyclosporine has several lytic drugs may help to reduce excessive menstrual bleeding in these
side effects, some potentially serious, including fever, increased risk of patients.
opportunistic infections, gingival hyperplasia, diarrhea, peptic ulcer,
pancreatitis, renal dysfunction, elevated liver enzymes, hypertension,
peripheral neuropathy, convulsions, hirsutism, and increased risk of SECONDARY IMMUNE THROMBOCYTOPENIA
secondary malignancy.
Secondary ITP is defined as immune-mediated platelet destruction
Danazol This synthetic androgen, with reduced virilizing effects com- in the presence of other conditions, including infections, lymph-
pared to other androgens, has been used to treat patients with refractory oproliferative disorders, solid tumors, SLE, or the antiphospholipid
ITP. Given at doses of 400 to 800 mg/day for at least 6 months, reported syndrome (APS) (Fig. 117–4). ITP can sometimes be the presenting
response rates range from 10 to 80 percent. 177,234 Danazol is postulated to sign of the illness, or may develop during the course of the disease or
decrease Fc receptor numbers on phagocytic cells by antagonizing the with certain therapies. Thrombocytopenia in a patient with chronic
effects of estrogens. Danazol should not be given to pregnant women disease may develop for other reasons, and the diagnosis of immune-
153
or patients with liver disease. Common side effects of danazol therapy mediated platelet destruction may require more detailed tests. Generally,
are weight gain, fluid retention, seborrhea, hirsutism, secondary amen-
orrhea, vocal changes, acne, hepatic toxicity, headache, lethargy, cho-
lesterol spectrum abnormalities (i.e., reduced high-density lipoprotein SLE 5%
[HDL] cholesterol) and myalgia. Because liver dysfunction is common APS 2%
with these doses of danazol therapy, liver function should be evaluated CVID 1%
monthly. 153,177,234 CLL 2%

Dapsone Dapsone possesses antibacterial and antiinflammatory PRIMARY Evan’s 2%
effects; it is primarily used for leprosy, malaria, and some types of der- 80% ALPS, post-tx 1%
matitis. When used at a dose of 75 to 100 mg/day, dapsone may increase HIV 1%
platelet counts in patients with persistent, refractory, or chronic Hep C 2%
ITP. 147,238,239 The median time to response is long, up to 2 months. Partial H. pylori 1%
and CR rates are approximately 50 percent and 20 percent, respectively, Post vaccine 1%
but platelet counts return to baseline levels after discontinuation of the Misc. systemic
therapy. 238,239 The mechanism of dapsone action in ITP is not known. infection 2%
The most important side effects are nausea, headache, skin rashes, hep- Figure 117–4. Estimated fraction of the various forms of secondary
atitis, cholestasis, dose-dependent hemolysis, and methemoglobinemia. ITP based on clinical experience of the authors. The incidence of Heli-
Dapsone should not be given to patients with glucose-6-phosphate cobacter pylori (HP) ranges from approximately 1 percent in the United
dehydrogenase deficiency. States to 60 percent in Italy and Japan. The incidence of the HIV and
hepatitis C virus approximates 20 percent in some populations. Mis-
Vinca Alkaloids Both vincristine and vinblastine transiently increase cellaneous causes of immune thrombocytopenia, for example, post-
the platelet count in approximately 70 percent of ITP patients within transfusion purpura, myelodysplasia, drugs that lead to the production
5 to 21 days, but produce sustained remissions in only 10 percent of of autoantibodies, and other conditions, are not discussed further in
treated patients. 108,153,177,234 The recommended dose of vincristine is 1 to this chapter. Post marrow or solid-organ transplantation autoimmune
2 mg and of vinblastine is 0.1 mg/kg (maximum: 10 mg), both given lymphoproliferative syndrome (ALPS) occurred in approximately 1 per-
by bolus injection at 1-week intervals for a minimum of three courses. cent of the authors’ patients. In the absence of a systematic analysis of
It has been proposed that vinca alkaloids bind to platelet microtubules the incidence of secondary ITP, the data shown represent the authors’
assessment based on our experience and the findings reported in the
and thereby are transported to the spleen, where they subsequently literature. APS, antiphospholipid syndrome; CLL, chronic lymphocytic
inhibit the phagocytic functions of splenic macrophages. They may also leukemia, CVID, common variable immune deficiency; SLE, systemic
stimulate megakaryopoiesis. Peripheral neuropathy, neutropenia, jaw lupus erythematosus. (Reproduced with permission from Cines DB, Bussel
pain, alopecia, and constipation are complications of treatment with JB, Liebman HA, Luning Prak ET. The ITP syndrome: Pathogenic and clinical
vinca alkaloids. 234,240–242 diversity. Blood 113(26):6511–6521, 2009.)

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