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2004 Part XII: Hemostasis and Thrombosis Chapter 117: Thrombocytopenia 2005

Still under investigation is which glucocorticoid and dosing reg- No validated clinical or laboratory tests exist that can predict
imen is best for raising the platelet count. Prednisolone, dexametha- whether splenectomy will be effective in elevating platelet counts in ITP
sone and methylprednisolone are all used. Generally, oral prednisone patients. Although it has been suggested that ITP patients with predom-
1 to 2 mg/kg per day (or methylprednisolone at equivalent doses) is inant splenic sequestration (as determined by radioisotope techniques)
preferred as first-line therapy. 147,148 Patients usually respond to predni- have better response rates than patients with predominantly nonsplenic
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sone therapy within 3 weeks. In approximately two-thirds of patients, sequestration, these data have not been validated in other studies and
9
platelet counts increase to greater than 50 × 10 /L within 1 week, but the required radioisotope techniques are not widely available.
decrease again when the prednisone dose is decreased. 152,177 Although Over the past decade minimally invasive laparoscopic splenec-
no consensus exists regarding the duration of initial therapy, treatment tomy has gained preference over open splenectomy. Modern laparo-
should continue until platelet counts reach a safe range. In patients who scopic approaches reduce mortality rates (<1 percent), even in patients
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respond, the recommendation is to continue glucocorticoid therapy 1 with severe thrombocytopenia. The mortality rate increases in older
mg/kg per day for a total of 3 weeks before initiating a slow tapering of patients, in patients with severe thrombocytopenia, and in the presence
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doses. Sustained remission rates with glucocorticoid therapy are vari- of coexisting illnesses. 177,195 Postsplenectomy sepsis is a major cause of
able, reported rates ranging from 5 to 50 percent. 108,155,177 If the patient morbidity and mortality in ITP. Extended steroid or other immunosup-
does not respond to 3 weeks of prednisone therapy, other therapeutic pressive therapy preceding splenectomy may increase the risk of periop-
options should be considered. erative infection. To minimize the risk of sepsis, patients should be
In addition to the standard 1 to 2 mg/kg per day dose of predni- immunized at least 2 weeks before splenectomy with polyvalent pneu-
sone, lower 179,180 and higher doses 181–184 of prednisone, dexamethasone, mococcal vaccine, Haemophilus influenzae type B vaccine, and qua-
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and methylprednisolone have been investigated, with good results. The drivalent meningococcal polysaccharide vaccine. Interestingly, newer
major aim of the high-dose glucocorticoid regimes is to reduce duration studies of ITP patients undergoing splenectomy show enteric organ-
of therapy, and therefore reduce the side effects of the glucocorticoids. isms to be responsible for most of the cases of postsplenectomy sepsis,
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Studies with dexamethasone 40 mg/day for 4 consecutive days for one probably because of the widespread vaccination of ITP patients. Sple-
course, or with the same dose for four courses given every 2 weeks have nectomized patients should be informed to be alert for the symptoms
been reported to produce responses in 50 percent and 89.2 percent of and signs of infection and be prepared for an emergency situation. Any
newly diagnosed ITP patients, respectively. 185,186 High-dose methylpred- fever should be carefully evaluated, and the patient treated with broad-
nisolone therapy has also been shown to be effective, with an 80 percent spectrum antibiotics.
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response rate. Despite the favorable results of these studies, high-dose Splenectomy also increases the risk of thrombosis in ITP patients.
glucocorticoid regimens as first-line therapy still have not been vali- In a large cohort of 9976 ITP patients, in whom 1762 underwent sple-
dated with randomized controlled trials. ASH 2011 guidelines recom- nectomy; the cumulative incidences of abdominal venous thromboem-
mend longer courses of standard doses of glucocorticoids (prednisone 1 bolism and deep vein thrombosis/pulmonary embolism were increased
to 2 mg/kg per day) as a first-line treatment of ITP. 148 in splenectomized patients compared to nonsplenectomized patients
(1.6 percent vs. 1 percent for abdominal venous thrombosis, 4.3 per-
Splenectomy Splenectomy was demonstrated to be an effective treat- cent vs. 1.7 percent for deep vein thrombosis–pulmonary embolism,
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ment for patients with ITP a century ago and after the glucocorticoid respectively). Several mechanisms may contribute to this enhanced
era, it has been used for decades as a standard second-line therapy. The risk for thrombosis, including postsplenectomy thrombocytosis and a
spleen is the major site both for synthesis of antiplatelet antibodies and failure to clear platelets, other cells and microparticles that express the
for destruction of antibody-coated platelets. Splenectomy will decrease procoagulant lipid phosphatidylserine. Perioperative measures such as
antibody production and platelet destruction, and will be effective in antiembolic stockings and anticoagulant prophylaxis should be consid-
patients in whom antibody-mediated platelet destruction rather than ered in those cases.
platelet production is the major cause of thrombocytopenia. Although Both the time required to reach a normal platelet count and the
splenectomy has been reported to be less preferred in recent ITP cohorts magnitude of platelet recovery are accepted as useful predictors of the
because of the emergence of new therapies such as TPO receptor ago- long-term efficacy of splenectomy. In most cases, platelet counts recover
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nists and rituximab, splenectomy still produces the highest cure within 10 days. Patients who attain a normal platelet count within 3
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rates for ITP patients compared to all other therapies. Approximately days of splenectomy generally have a good long-term response. In
85 percent of patients with persistent or chronic ITP respond well to patients refractory to splenectomy, the presence of accessory splenic
splenectomy, and 60 to 66 percent of the patients remain in remission tissue should be suspected, particularly if the blood film shows no evi-
after 5 years. 189–191 These high cure rates makes splenectomy an impor- dence of splenectomy (i.e., pitting and Howell-Jolly bodies are absent
tant therapeutic option in the treatment of chronic ITP. The duration in the erythrocytes; Chap. 55). Such patients should be screened with
of the disease prior to splenectomy does not affect the outcome of the sensitive radionuclide or magnetic resonance scans to identify residual
procedure, as it can be effective even years after ITP is diagnosed. 192,193 or accessory splenic tissue.
Splenectomy can be performed during pregnancy (preferably during
the second trimester), and does not affect the response rates to other Intravenous Immunoglobulin IVIG was first shown to be effective in
treatments except anti-D therapy in chronic ITP patients. Also, the cost childhood ITP in 1981, then later in adult patients. IVIG rapidly
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of splenectomy is lower than that of newer treatments such as rituximab increases the platelet count in more than 75 percent of patients with
and TPO-receptor agonists. 191 chronic ITP and normalizes the platelet count in approximately 50 per-
On the other hand, splenectomy is an invasive procedure, causes cent of the patients. 177,178 The effect of IVIG is similar whether or not
the permanent loss of an organ, and increases the risk of serious bacte- the patient has undergone splenectomy and is transient, generally last-
rial infection, bleeding and thrombosis. Because ITP can remit sponta- ing only 3 to 4 weeks. Postulated mechanisms for the action of IVIG
neously, splenectomy should be postponed at least 6 to 12 months after include blockade of macrophage Fc receptors, which slows clearance
diagnosis if possible. 147,148 Splenectomy is not recommended in patients of antibody-coated platelets, antiidiotype neutralization of antiplatelet
with CVID, with chronic infections such as chronic hepatitis and HIV, autoantibodies, cytokine modulation, immunomodulation (increased
or with known thrombophilia. suppressor T-cell function and decreased autoantibody production),

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