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2002 Part XII: Hemostasis and Thrombosis Chapter 117: Thrombocytopenia 2003

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Although atypical lymphocytes and eosinophilia may occur in children than 10 × 10 /L, in those with platelet counts between 10 and 30 × 10 /L
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with ITP, leukocytosis and leukopenia with immature cells are not con- and significant mucosal bleeding, or in those with risk factors for bleed-
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sistent with the diagnosis. ing (see Table 117–5). The presence of extensive purpura or hemor-
Marrow examination, which is not always required to make a rhagic bullae in mucosal tissues (wet purpura) should be regarded as
diagnosis of ITP in adults, generally reveals a normal or increased a harbinger of life-threatening bleeding and treated as such. Because
number of megakaryocytes of normal morphology, although a ITP patients often have large platelets that may not be recognized by
decreased number of megakaryocytes does not rule out ITP. Erythro- automated cell counters, a blood film should be evaluated before start-
poiesis and myelopoiesis are normal. The international consensus ing therapy in ITP patients with very-low platelet counts who are not
report states that a marrow examination should usually be reserved bleeding. Identification of secondary ITP cases is very important, and
for patients older than age 60 years, for those with systemic symptoms management of these patients should include treatment of the underly-
or other signs, and for those for whom splenectomy is contemplated. ing pathology, if possible.
Biopsy for morphologic examination should be carried out, along with
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aspirate for flow cytometric and cytogenetic analysis. The ASH 2011 Emergency Treatment of Acute Bleeding Resulting from Severe
guidelines, however, conclude that a marrow examination is unneces- Thrombocytopenia Bleeding symptoms generally are not severe in
sary when the presentation is typical, even if the patients are older or adult patients with ITP, even with very-low platelet counts. However,
being considered for splenectomy. 148 life-threatening bleeding can occur, especially after trauma. Emergency
In ITP patients, initial workup should be targeted to exclude sec- treatment should be instituted in patients with intracranial or gastro-
ondary causes of thrombocytopenia (see Table 117–3). Testing for viral intestinal bleeding, massive hematuria or internal hematoma, or those
etiology (hepatitis C virus [HCV], HIV, and in endemic areas hepati- in need of emergency surgical intervention or about to go into labor.
tis B virus [HBV]) and Helicobacter pylori is also recommended. 147,148 Patients who experience significant bleeding should be hospitalized and
Quantitative immunoglobulin assessment should be considered monitored closely. Recommended treatment includes IVIG and parent-
for pediatric cases to rule out common variable immunodeficiency eral glucocorticoids in combination. IVIG is given as 1 g/kg per day for
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(CVID). Mild thrombocytopenia has been reported in patients with 2 days, and high-dose parenteral glucocorticoid therapy includes high-
hypo- or hyperthyroidism, which returns to normal after appropriate dose prednisone or methylprednisolone (1 g/day for 1 to 3 days). In
therapy. Thyroid-stimulating hormone (TSH) and antithyroid anti- most patients, IVIG increases the platelet count within 2 to 3 days. 147,148
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bodies may help to evaluate thyroid status in those patients. Other Although platelet transfusions may not increase the platelet counts
tests to consider include blood group analysis and a pregnancy test because the transfused platelets are destroyed rapidly, they nevertheless
for female patients of childbearing age, antiphospholipid antibodies, may contribute to the formation of platelet plugs at sites of bleeding
antinuclear antibody (ANA), viral polymerase chain reaction (PCR) and improve hemostasis. Platelet transfusion following IVIG infusion
for parvovirus, and cytomegalovirus (CMV). The results of these tests may increase the platelet count because IVIG may improve platelet sur-
can change the treatment strategy. On the other hand, the ASH 2011 vival. 147,148,170 Aminocaproic acid, which inhibits fibrinolysis, can be used
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guidelines do not recommend routine testing for antiphospholipid to reduce bleeding and is safe except in the presence of hematuria, in
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antibodies and ANAs in the initial workup of ITP, unless signs or which case it can cause thrombi of the glomeruli, renal pelves, and ure-
symptoms of an autoimmune disorder are present in the patient. Other ters. This agent does not affect platelet count or function. Aminocaproic
tests, such as TPO levels, reticulated platelets, PAIgG, platelet survival acid is usually administered intravenously (initial dose 0.1 g/kg over 30
studies, bleeding time, and serum complement levels are not recom- minutes, then given either by continuous infusion at 0.5 to 1.0 g/h or
mended for the diagnosis and management of ITP patients in either of as an equivalent intermittent dose every 2 to 4 hours). Aminocaproic
these guidelines. 147,148 acid also can be administered orally in a similar dose in emergency
situations because it is absorbed very rapidly from the gastrointestinal
Therapy and Course tract. 147,148 Vincristine can be used in combination with glucocorti-
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What little is known of the natural course of moderate or severe ITP coids and IVIG in older patients. Other hemostatic therapies, such as
derives from before the glucocorticoid era, and suggests that left recombinant factor VIIa and fibrinogen infusions, have been reported
untreated, ITP in adults typically is a chronic disease, in contrast to ITP to be effective in some ITP patients with life-threatening bleeding, but
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in children. In adults, the rate of spontaneous remission is reported as the risk-to-benefit ratio needs to be evaluated in controlled studies.
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9 percent, and can occur even after 3 years in patients who present Emergency splenectomy has been reported to be successful in refrac-
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with severe thrombocytopenia. Although ITP is a benign disease, side tory ITP with bleeding, but reports of its use in this situation are rare.
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effects of the therapies can cause serious morbidity and even mortal- Because of this, this therapy should only be considered in the most dire
ity. Treatment for patients with ITP should be based on bleeding signs circumstances. Although there are some case reports describing suc-
and symptoms and on the presence of factors that increase the bleeding cessful results with plasmapheresis, this treatment is not recommended
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risk (see Table 117–5). Possible side effects of the drugs and other treat- in current ITP guidelines.
ments used in ITP should always be considered. Glucocorticoid Therapy Glucocorticoids are accepted as the standard
therapy for initial treatment in adult patients with ITP. 147,148 Glucocorti-
Initial Management coids increase the platelet count in several ways, including by inhibiting
Observation Because a significant portion of ITP patients are diag- phagocytosis of antibody-coated platelets by macrophages, decreasing
nosed incidentally in routine evaluation, signs and symptoms of bleed- autoantibody production, and improving marrow platelet produc-
ing are important in determining whether any treatment is required. tion. 174,175 These agents also appear to reduce capillary leakage, thereby
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The primary therapeutic goal is not simply to increase the platelet count, decreasing blood loss. The major drawback of glucocorticoid therapy
but to reach a safe platelet count where the risk of bleeding is minimal. is that often the adverse effects of the treatment are worse than the dis-
Patients with no bleeding and consistent platelet counts in excess of ease itself. Important side effects, which can be severe, include facial
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30 × 10 /L do not require treatment and can be observed periodically. swelling (chipmunk or moon facies), weight gain, folliculitis, hyper-
These patients are at low risk for clinically important bleeding. Simple glycemia, hypertension, cataracts, osteoporosis, aseptic bone necrosis,
observation is not recommended for patients with platelet counts lower opportunistic infections, and behavioral disturbances. 177,178

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