Scully M, Hunt BJ, Benjamin S, et al; British Committee for Standards in Haematology. Guidelines on the diagnosis and management of thrombotic thrombocytopenic purpura and other thrombotic microangiopathies. Br J Haematol. 2012 Aug;158(3):323-35. doi: 10.1111/j.1365-2141.2012.09167.x. Epub 2012 May 25. PubMed PMID: 22624596.
Neunert C, Lim W, Crowther M, Cohen A, Solberg L Jr, Crowther MA; American Society of Hematology. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood. 2011 Apr 21;117(16):4190-207. doi: 10.1182/blood-2010-08-302984. Epub 2011 Feb 16. Review. PubMed PMID: 21325604.
Definition and EtiologyTop
Immune thrombocytopenia (ITP), formerly termed idiopathic thrombocytopenic purpura, is an acquired immune disease characterized by isolated thrombocytopenia (here defined as platelet counts <100,000 microL) with no known causes. Etiology is unknown.
Clinical Features and Natural HistoryTop
ITP is classified on the basis of its duration as newly diagnosed ITP, persistent ITP (3-12 months), or chronic ITP (≥12 months). In adults the disease is usually chronic and asymptomatic, and it is associated with remissions and relapses. In ~10% of adult patients ITP resolves spontaneously. Typical manifestations include epistaxis, gingival bleeding, and heavy and prolonged menstrual bleeding; in some patients the only features are cutaneous petechiae and bruising. Petechiae are usually located on the mucous membranes and the skin of distal portions of extremities. Tissue injury causes excessive bleeding, but gastrointestinal and central nervous system hemorrhages are rare.
1. Complete blood count (CBC): Isolated thrombocytopenia, increased mean platelet volume (MPV), increased numbers of young platelets.
2. Bone marrow aspiration or biopsy might be considered in patients aged >60 years to exclude myelodysplastic syndrome, as well as in patients with treatment resistance who are planned for splenectomy or patients with relapse after splenectomy. Bone marrow examination is not generally useful in patients with suspected ITP.
3. Other studies: Tests for HIV, hepatitis C virus, Helicobacter pylori, parvovirus B19, Epstein-Barr virus, and cytomegalovirus infections; antinuclear antibodies (to exclude systemic lupus erythematosus); pregnancy test. Immunologic testing (detection of antiplatelet antibodies) is of no value in the diagnosis of ITP.
Isolated thrombocytopenia with an otherwise normal CBC in a patient in whom other causes have been excluded.
Other causes of thrombocytopenia: see Disorders of Platelets.
Treatment is not necessary in patients who are not bleeding. “Prophylactic treatment” might be considered in patients with extreme thrombocytopenia (eg, <20,000-30,000/microL) or prior to a procedure.
1. Glucocorticoids: Cycles of dexamethasone 40 mg/d for 4 days every 14 or 28 days (1-4 cycles) or alternatively oral prednisone 1 to 1.5 (usually 1) mg/kg/d for 2 to 4 weeks, until platelet counts increase to >50,000/microL, then taper the dose. In most patients glucocorticoids must be discontinued because of adverse effects. Use long-term prednisone therapy in patients in whom low-dose prednisone (≤10 mg/d) maintains a platelet count that provides effective hemostasis and attempts to discontinue the treatment cause bleeding. In patients treated with glucocorticoids for >3 months, prevention of osteoporosis is necessary (see Osteoporosis). In patients not responding to prednisone, the drug should be discontinued within 4 weeks.
2. Patients with H pylori infection should be considered for H pylori eradication therapy, as this may lead to an improvement in the platelet counts (see Peptic Ulcer Disease).
3. Intravenous immunoglobulin (IVIG) might be considered as a first-line therapy in patients with life-threatening hemorrhage, those with inability to take glucocorticosteroids, those requiring immediate surgery, or in pregnant patients with imminent delivery.
1. Splenectomy: Indications for splenectomy are considered on a case-by-case basis in patients with ITP and primary resistance to glucocorticoids or those who need long-term glucocorticoid therapy to maintain adequate platelet counts. Before splenectomy a trial of second-line pharmacotherapy may be used (see below). In the majority of cases splenectomy is performed after ≥6 months of diagnosing the disease, as spontaneous remissions have been observed even after 6 months of diagnosis. In the case of symptomatic severe thrombocytopenia (<10,000/microL) in a patient treated with appropriate doses of glucocorticoids for >2 weeks, earlier splenectomy (before 6 months) may be justified. The most common complications of splenectomy include infections and venous thrombosis. Splenectomy leads to remission in up to 65% of patients. In the remaining patients continued glucocorticoid therapy at the lowest possible dose is necessary, and if this is ineffective, other second-line agents are used. To optimize the preoperative platelet count (usual goal >50,000/microL), IVIG or anti-D immunoglobulin may be administered; use of a thrombopoietin-receptor agonist may also be considered in the perioperative period. At least 2 weeks before splenectomy (and if this is not feasible, as soon as possible after splenectomy) the patient should receive vaccines against Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae; the vaccinations should be repeated every 5 years.
2. Second-line agents:
1) IVIG: 1 g/kg/d for 1 to 2 days. In some patients glucocorticoids may enhance the response to IVIG; their combined use may reduce infusion-associated reactions and prevent aseptic meningitis.
2) Rituximab is widely used as a second-line agent in patients with ITP. Although associated with a good initial response in many patients, long-term results of rituximab use have been disappointing, with recrudescent thrombocytopenia in the majority of patients.
3) Anti-D immunoglobulin.
4) Thrombopoietin-receptor agonists: Romiplostim, eltrombopag.
5) Other drugs used in the case of resistance to glucocorticoids or contraindications to glucocorticoids and splenectomy: Immunosuppressive agents (cyclophosphamide, azathioprine, cyclosporine [INN ciclosporin], vincristine, vinblastine, mycophenolate mofetil, rituximab), danazol, and dapsone.
In patients being prepared for surgery or after a massive hemorrhage, use intravenous methylprednisolone 1 g/d for 3 days or IVIG 1 g/kg/d for 2 days; in patients with severe hemorrhagic complications, both agents may be used in combination. In the case of life-threatening complications, administer platelet concentrate, optimally in combination with IVIG treatment.
Oral glucocorticoids are generally used as first-line agents in patients requiring therapy. IVIG might be considered in selected patients. Vaginal delivery is recommended (platelet counts should be ≥30,000/microL), and cesarean section should only be performed for obstetric indications. Epidural analgesia is usually not administered to patients with platelet counts <80,000/microL.