Case Review: Idiopathic Thrombocytopenic Purpura
Ronny Cohena, e, Christine A. Garciab, Derrick Menac, Mariely Castellanosc, Li-The Wud
aWoodhull Medical Center, Brooklyn, NY; NYU School of Medicine, NY, USA
bSt. George’s University School of Medicine, Grenada, West Indies
cWoodhull Medical Center, Brooklyn, NY, USA
dNorth Shore University Hospital, Forest Hills, NY, USA
eCorresponding author:Ronny Cohen, Woodhull Medical Center, NYU School of Medicine, 760 Broadway, Brooklyn, NY 11206, USA. Email: email@example.com
Manuscript accepted for publication January 13, 2012
Short title: Idiopathic Thrombocytopenic Purpura
Idiopathic Thrombocytopenic Purpura (ITP) is defined as a hematologic disorder, characterized by isolated thrombocytopenia without a clinically apparent cause. The major causes of accelerated platelet consumption include immune thrombocytopenia, decreased bone marrow production and increased splenic sequestration. The clinical presentation may be acute with severe bleeding, or insidious with slow development with mild or no symptoms. The initial laboratory tests useful at the first visit to predict future diagnosis were erythrocyte count, leukocyte count, anti-glycoprotein (GP) IIb/IIIa antibodies, reticulated platelets, plasma thrombopoietin level. Treatment should be restricted to those patients with moderate or severe thrombocytopenia who are bleeding or at risk of bleeding. It should be limited in duration unless demonstrated that symptomatic thrombocytopenia persists. Patients with mild, asymptomatic thrombocytopenia, discovered incidentally on a routine blood count, should not be treated. We present a case report on ITP and summarize the key points in the diagnosis and management of ITP.
Keywords: Idiopathic thrombocytopenic purpura; ITP; Platelets; Petechiae; Hematology
Idiopathic Thrombocytopenic Purpura (ITP) is defined as a hematologic disorder, characterized by isolated thrombocytopenia without a clinically apparent cause. It is postulated that platelet antibodies opsonizes the platelet membrane resulting in reduced platelet survival by the reticuloentothelial system . The major causes of accelerated platelet consumption include immune thrombocytopenia, decreased bone marrow production and increases splenic sequestration [1, 2]. The clinical presentation may be acute with severe bleeding, or insidious with slow development with mild or no symptoms .
The incidence of ITP is 1.6/ 10,000 per year in the United States. Some reports show it is more common in females but others shown no difference in gender distribution [3, 4]. Around 70% to 80% of children experience the acute form of the disease and recover within few weeks or months after diagnosis, whereas most adults have the persistent form and require therapy [5, 6].
The bleeding in ITP is mucocutaneous, manifesting as petechiae, purpura, easy bruising, epistaxis, gingival bleeding, and menorrhagia . ITP remains as a diagnosis of exclusion [1, 7, 8]. In those patients with immune thrombocytopenia, typical clinical findings are missing after a detailed clinical history and physical exam.
Diagnosis of ITP
The American Society of Hematology recommends a panel of tests for initial diagnosis of ITP which includes Complete Blood Count (CBC) and peripheral blood film. No other tests are considered necessary [1, 6]. A similar guideline is followed by British Committee for Standards in Haematology General Haematology Task Force [1, 9]. One study showed that these initial guidelines were not rigorous enough to make an accurate diagnosis of ITP [1, 10, 11]. The initial six laboratory tests useful at the first visit to predict future diagnosis were erythrocyte count, leukocyte count, anti-glycoprotein (GP) IIb/IIIa antibodies, reticulated platelets, plasma thrombopoietin level .
The platelet antibody is a hallmark of the autoimmune nature of ITP. This antibody has a preference to recognize the platelet surface GP IIb/IIIa, but due to the majority of the plasma antibody bound to platelet surfaces rather than in circulation [1, 12], the sensitivity of the test is reduced. The plasma level of the antibodies was not useful in the diagnosis of ITP [1, 13, 14]. This platelet antibody also can affect the proliferation and maturation of megakaryocytes.
Reticulated platelets are young platelet released into circulation containing elevated nucleic acid component, reflecting platelet turnover [1, 15, 16, 17]. Thrombopoietin is one of the main substances controlling the megakaryo-thrombopoiesis, but its levels are not consistently correlated with the absolute number of bone marrow megakaryocytes and platelets [1, 18].
Bone marrow aspiration and biopsy are only performed as a routine if the patient is over 60 years age without a robust response to treatment (50,000 × 109/L) . The testing for HIV and/or hepatitis C infection is indicated in at risk populations [19, 20].
Treatment of ITP
The treatment of ITP depends on disease presentation. If the patient is experiencing profound bleeding with very low platelet counts (10,000 to 20,000/UL), initial treatment with IV-Immunoglobulin (IV-Ig) or combined with IV methylprednisolone. It may be supplemented with either IV anti-D or with high dose dexamethasone until the platelet count exceeds 50,000/UL. Transfusion of platelet is warranted if life threatening hemorrhage occurs [1, 9].
In non-emergency situations, prednisone (1 - 2 mg/kg/day can be initial treatment), if intolerant to corticosteroids, intravenous IV Ig anti-D can be used [1, 21]. But if platelet remains < 20,000/UL or there is a need for a rapid response, prednisone may be supplemented with IV methylprednisolone and/or IV anti-D .
More than three quarters of adult patients will fail to achieve a lasting response . The standard of practice for corticosteroids non-responders and platelet counts below 30,000/UL after 4 - 6 weeks of therapy is splenectomy , but it may be delayed for up to three years, particularly patients with insidious onset ITP .
Patients who have chronic ITP, defined as persisting for more than 6 months, will ultimately need to be treated with other options. Monoclonal antibodies such as Rituximab may also be used. It is postulated that mechanisms of macrophage blockade by opsonized B cells may account for the early responses [1, 23]. Immunosupresants such as Danazol has been shown to improve platelet count in significant number of refractory ITP patients. It is believed to restore suppressor T-cell function and decrease antibodies production by decreasing the number of available Fc receptors [3, 24]. Cyclosporine, Mycophenolate Mofetil and chemotherapeutic agents such as azathioprine, vinca-alkaloid, cyclophosphamide and interferon have been used with similar success.
Other alternatives are plasma exchange, interferon, colchicine, dapsone, vitamin C, mycophenolate mofetil, protein A Immunoadsorption, thrombopoietin and thrombopoietin like agents. Further studies are warranted for these agents in order to evaluate efficacy, toxicity and adverse effects . Protein A immunoabsorption, thrombopoetin and thrombopoetin-like agents can raise platelet count temporarily. Eradication of H. pylori infection has been reported to improve platelet count in patient with active infection.
We present a case report on ITP. Although not an uncommon entity, there is still much to be learned and this case review will summarize some of the key points in the diagnosis and management of ITP.
A 76 year old Hispanic male presented to the emergency department for generalized pain and was found to have low platelet count. The patient was in his usual state of health until 3 weeks prior to presentation when he developed unspecific low back pain and multiple joint pain mainly on his right shoulder. After further questioning patient admitted to having 1 episode of hematuria and epistaxis which were self-limited. Patient denied hematuria, hemoptysis, gingival or gastrointestinal bleeding.
The patient has a past medical history of hypertension, diabetes mellitus type 2, chronic anemia and thrombocytopenia. His past surgical history include left inguinal hernia repair 4 years ago. No significant family history or bleeding disorders were reported. He denied alcohol, drugs or tobacco abuse. His medications were unknown.
Upon arrival to the emergency department, he was alert, awake and oriented, with a blood pressure of 127/72 mmHg, heart rate 100 bpm, temperature 98.4 oF, respiratory rate 18 breaths/min. No orthostatic changes were documented. Physical examination revealed a cooperative and well-appearing man, not in any apparent distress. The pupils were equally round and reactive to light and accommodation. The neck was supple, there were no carotid bruits. No signs of gum bleeding were noticed. The chest was clear to auscultation bilaterally. The heart rate was regular. Auscultation revealed a normal S1 and S2. There were no additional sounds. Abdominal examination revealed no hepatosplenomegaly, bowel sounds were present, no abdominal tenderness, guarding or rebound was found. The extremities revealed no clubbing or edema. Examination of the skin was remarkable for petechiae. Joints were non-tender and non-erythematous, range of movement was normal. The neurologic examination revealed 5/5 motor responses bilaterally in both upper and lower extremities. No sensory deficits were present. Deep tendon reflexes were 2+ in all four extremities. Guaiac was positive.
Laboratory findings were as follows: Hb 7.8 gr/dL (baseline between 8 gr/dL and 9 gr/dL), Hct 24.4%, WBC: 6.8 x 103 per uL, MCV: 84 fL, Platelets: 10,400 per UL, PTT: 28.2 sec, PT: 11.8 sec, INR: 1.02. WBC smear was normal. RBC smear showed hypochromic, macrocytic 1+, microcytic 1+, anisocytosis, basophilic stippling. Hemolysis work up was negative.Abdominal ultrasound showed unremarkable spleen and liver.
The patient was admitted to the intensive care unit for close monitoring. Prednisone 80 mg orally daily and intravenous immunoglobulin 30 grams daily for five days were started. Platelets improved to 147,000 per UL and steroids were tapered down, subsequently platelets dropped again to 11,000 per UL. The patient was started again on intravenous immunoglobulin and steroid dose was increased with good response of platelet count.
The etiology of ITP may be genetic as well as acquired factors. The pathogenesis is presumed to be related to platelet destruction and/or inhibition of platelet production via the production of specific autoantibodies. The case we presented is only one of the estimated 22 million cases diagnosed each year in the US. Although not an uncommon entity, there is much to be learned in the diagnosis and management of ITP.
There is marked variability in the clinical presentation of ITP. Our case was insidious in onset, but it can also be very abrupt and acute. The bleeding manifestations of thrombocytopenia are described as mucocutaneous to distinguish them from coagulation disorders such as hemophilia. Petechia, purpura, and easy bruising are expected in ITP. Less common are epistaxis, gingival bleeding, and menorrhagia. Uncommon findings are GI bleeding, gross hematuria and intracranial hemorrhage . It is important to note that the clinical manifestations of thrombocytopenia vary with patient age. Older patients have more severe and rare bleeding manifestations, such as gastrointestinal bleeding and possibly intracranial hemorrhage secondary to co-morbidities such as hypertension.
Clinically important bleeding does not appear to occur in these patients unless the platelet count is less than 10,000/UL. However, the standard of practice among many physicians is to initiate treatment in adult patients with ITP when the platelet count is less than 30,000/UL. There is no "gold standard" test that can establish its diagnosis. The diagnosis of ITP is in part one of exclusion, requiring that other causes of thrombocytopenia be ruled out. A presumptive diagnosis of ITP is made when the history, physical examination, complete blood count, and examination of the peripheral blood smear do not suggest other etiologies for the patient's isolated thrombocytopenia. The only recommended further tests in such patients are HIV testing in patients with risk factors for HIV infection, and bone marrow aspiration in patients over 60 years of age to rule out myelodysplastic syndrome. In patients with presumed ITP, severe thrombocytopenia, and/or clinical bleeding, urgent hematologic consultation is appropriate and recommended. For asymptomatic patients with modest degrees of thrombocytopenia, consultation is less urgent, but should be pursued in order to establish a baseline, should treatment be required in the future. Contrary to common practice of many physicians, there is still no evidence that antiplatelet antibody studies are important for the diagnosis of ITP.
Major bleeding is rare in patients with platelet counts > 10,000/UL. The major goal for treatment of ITP is to provide a safe platelet count to prevent major bleeding and avoid unnecessary treatment of asymptomatic patients with mild to moderate thrombocytopenia. In addition, the efficacy of therapy is uncertain among asymptomatic patients with severe thrombocytopenia. Morbidity from side effects of platelet transfusion exceeds any problems caused by their ITP.
Spontaneous remissions are unusual in adults. In children 70 to 80 percent have complete remission of the disease within six months with no specific therapy. All adults with severe and symptomatic thrombocytopenia are usually treated with glucocorticoids. Adults presenting with mild and asymptomatic thrombocytopenia, with platelet counts greater than 30,000 to 50,000/UL, appear to have a stable and benign course without any treatment. Nevertheless, since spontaneous remissions are unusual in adults with ITP, treatment to increase the platelet count is always initiated in patients with thrombocytopenia severe enough to constitute a risk for bleeding.
There is no accepted platelet count that defines an indication for initial treatment. Patients with initial platelet counts above 30,000 to 50,000/UL, require careful follow-up but no specific initial therapy. Asymptomatic patients with even lower platelet counts may be carefully followed without specific treatment, since major bleeding does not occur unless the platelet count is < 10,000/UL. The decision to treat ITP is based on the platelet count, degree of bleeding, and patient's lifestyle. Corticosteroids, typically prednisone, are the backbone of the initial treatment. When the dose of corticosteroids is reduced or when the treatmentis stopped, remission is sustained in only 10 to 30% of cases.Regimens that include dexamethasone may lead to higher ratesof sustained remission. Other effective initial treatments includeintravenous immune globulin and Rh0(D) immune globulin for patientswho are Rh-positive. Sustained remission with these agents is uncommon.Splenectomy is the traditional second-line treatment for patientswho do not have a response to corticosteroids or who do nothave a sustained remission with low doses of corticosteroids. In such cases, splenectomy can be curative. Complete or partialremission occurs in more than two-thirds of patients who undergosplenectomy, but the relapse rate is 15 to 25%. The risks associatedwith splenectomy are small, but patients who have undergonethe surgery have a lifelong increased risk of bacterial sepsis.
An array of third-line therapies is available for patients who decline splenectomy and for those in whom surgery is not indicatedor must be delayed. Rituximab, the monoclonal antibody againstCD20+ B cells, has an overall response rate of 25 to 50%, andmany durable responses have been observed with this agent, with relatively few side effects. Other agents that have inducedresponses when used as third-line treatment include Rh0(D) immuneglobulin, intravenous immune globulin, azathioprine, cyclophosphamide,danazol, alkaloids, dapsone, combination chemotherapy,cyclosporine, and mycophenolate mofetil. The decision to chooseone of these agents is usually based on the physician's preferenceand experience with each agent. With the exception of Rh0(D) immune globulin, which is active only in patients with a spleen,these agents can be useful in patients in whom splenectomy failsand who therefore require medical therapy. The major difficultieswith many of these third-line therapies are modest responserates and, frequently, a slow onset of action-an effectmay not be evident for several months. In addition, bone marrowsuppression and an increased risk of infection complicate treatmentwith many of the immunosuppressive agents. In patients with active bleeding, platelet transfusion can be used. Thrombopoetin like agents can be useful to raise platelet count temporarily [25, 26]. For patient with active H. pylori infection, eradication of this infection should be done .
The initial treatment of ITP includes: (1) Treatment should be restricted to those patients with moderate or severe thrombocytopenia who are bleeding or at risk of bleeding; (2) Treatment should be limited in duration unless it is demonstrated that symptomatic thrombocytopenia persists; and (3) Patients with mild, asymptomatic thrombocytopenia, discovered incidentally on a routine blood count, should not be treated.
Butros LJ, Bussel JB. Intracranial hemorrhage in immune thrombocytopenic purpura: a retrospective analysis. J Pediatr Hematol Oncol. 2003 Aug. 25(8):660-4. [Medline].
Fogarty PF, Segal JB. The epidemiology of immune thrombocytopenic purpura. Curr Opin Hematol. 2007 Sep. 14(5):515-9. [Medline].
Nilsson T, Norberg B. Thrombocytopenia and pseudothrombocytopenia: a clinical and laboratory problem. Scand J Haematol. 1986 Oct. 37(4):341-6. [Medline].
Jubelirer SJ, Harpold R. The role of the bone marrow examination in the diagnosis of immune thrombocytopenic purpura: case series and literature review. Clin Appl Thromb Hemost. 2002 Jan. 8(1):73-6. [Medline].
Calpin C, Dick P, Poon A, Feldman W. Is bone marrow aspiration needed in acute childhood idiopathic thrombocytopenic purpura to rule out leukemia?. Arch Pediatr Adolesc Med. 1998 Apr. 152(4):345-7. [Medline]. [Full Text].
Sandler SG, Tutuncuoglu SO. Immune thrombocytopenic purpura - current management practices. Expert Opin Pharmacother. 2004 Dec. 5(12):2515-27. [Medline].
Tarantino MD, Buchanan GR. The pros and cons of drug therapy for immune thrombocytopenic purpura in children. Hematol Oncol Clin North Am. 2004 Dec. 18(6):1301-14, viii. [Medline].
[Guideline] Neunert C, Lim W, Crowther M, Cohen A, Solberg L Jr, Crowther MA. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood. 2011 Apr 21. 117(16):4190-207. [Medline]. [Full Text].
Mazzucconi MG, Fazi P, Bernasconi S, et al. Therapy with high-dose dexamethasone (HD-DXM) in previously untreated patients affected by idiopathic thrombocytopenic purpura: a GIMEMA experience. Blood. 2007 Feb 15. 109(4):1401-7. [Medline]. [Full Text].
Borst F, Keuning JJ, van Hulsteijn H, Sinnige H, Vreugdenhil G. High-dose dexamethasone as a first- and second-line treatment of idiopathic thrombocytopenic purpura in adults. Ann Hematol. 2004 Dec. 83(12):764-8. [Medline].
Cheng Y, Wong RS, Soo YO, et al. Initial treatment of immune thrombocytopenic purpura with high-dose dexamethasone. N Engl J Med. 2003 Aug 28. 349(9):831-6. [Medline]. [Full Text].
Imbach P, Barandun S, d'Apuzzo V, et al. High-dose intravenous gammaglobulin for idiopathic thrombocytopenic purpura in childhood. Lancet. 1981 Jun 6. 1(8232):1228-31. [Medline].
Anderson D, Ali K, Blanchette V, et al. Guidelines on the use of intravenous immune globulin for hematologic conditions. Transfus Med Rev. 2007 Apr. 21(2 suppl 1):S9-56. [Medline].
Sandler SG. Treating immune thrombocytopenic purpura and preventing Rh alloimmunization using intravenous rho (D) immune globulin. Transfus Med Rev. 2001 Jan. 15(1):67-76. [Medline].
Sandler SG, Novak SC, Roland B. The cost of treating immune thrombocytopenic purpura using intravenous Rh immune globulin versus intravenous immune globulin. Am J Hematol. 2000 Mar. 63(3):156-8. [Medline]. [Full Text].
Gaines AR. Acute onset hemoglobinemia and/or hemoglobinuria and sequelae following Rh(o)(D) immune globulin intravenous administration in immune thrombocytopenic purpura patients. Blood. 2000 Apr 15. 95(8):2523-9. [Medline]. [Full Text].
Chun NS, Savani B, Seder RH, Taplin ME. Acute renal failure after intravenous anti-D immune globulin in an adult with immune thrombocytopenic purpura. Am J Hematol. 2003 Dec. 74(4):276-9. [Medline]. [Full Text].
[Guideline] Rajasekhar A, Gernsheimer T, Stasi R, James AH. 2013 Clinical Practice Guide on Thrombocytopenia in Pregnancy. American Society of Hematology. Available at http://www.hematology.org/Clinicians/Guidelines-Quality/Quick-Reference.aspx. Accessed: December 1, 2016.
Gottlieb P, Axelsson O, Bakos O, Rastad J. Splenectomy during pregnancy: an option in the treatment of autoimmune thrombocytopenic purpura. Br J Obstet Gynaecol. 1999 Apr. 106(4):373-5. [Medline].
Stasi R, Evangelista ML, Stipa E, et al. Idiopathic thrombocytopenic purpura: current concepts in pathophysiology and management. Thromb Haemost. 2008 Jan. 99(1):4-13. [Medline]. [Full Text].
Audia S, Mahévas M, Samson M, Godeau B, Bonnotte B. Pathogenesis of immune thrombocytopenia. Autoimmun Rev. 2017 Jun. 16 (6):620-632. [Medline].
Chan H, Moore JC, Finch CN, Warkentin TE, Kelton JG. The IgG subclasses of platelet-associated autoantibodies directed against platelet glycoproteins IIb/IIIa in patients with idiopathic thrombocytopenic purpura. Br J Haematol. 2003 Sep. 122(5):818-24. [Medline].
Crow AR, Lazarus AH. Role of Fcgamma receptors in the pathogenesis and treatment of idiopathic thrombocytopenic purpura. J Pediatr Hematol Oncol. 2003 Dec. 25 suppl 1:S14-8. [Medline].
Sandler SG. The spleen and splenectomy in immune (idiopathic) thrombocytopenic purpura. Semin Hematol. 2000 Jan. 37(1 suppl 1):10-2. [Medline].
Segal JB, Powe NR. Prevalence of immune thrombocytopenia: analyses of administrative data. J Thromb Haemost. 2006 Nov. 4(11):2377-83. [Medline]. [Full Text].
Moulis G, Palmaro A, Montastruc JL, Godeau B, Lapeyre-Mestre M, Sailler L. Epidemiology of incident immune thrombocytopenia: a nationwide population-based study in France. Blood. 2014 Nov 20. 124(22):3308-15. [Medline].
Danese MD, Lindquist K, Gleeson M, Deuson R, Mikhael J. Cost and mortality associated with hospitalizations in patients with immune thrombocytopenic purpura. Am J Hematol. 2009 Jul 16. [Medline].
Medeiros D, Buchanan GR. Major hemorrhage in children with idiopathic thrombocytopenic purpura: immediate response to therapy and long-term outcome. J Pediatr. 1998 Sep. 133(3):334-9. [Medline].
Arnold DM. Bleeding complications in immune thrombocytopenia. Hematology Am Soc Hematol Educ Program. 2015 Dec 5. 2015 (1):237-42. [Medline].
KUhne T, Imbach P, Bolton-Maggs PH, et al, for the Intercontinental Childhood ITP Study Group. Newly diagnosed idiopathic thrombocytopenic purpura in childhood: an observational study. Lancet. 2001 Dec 22-29. 358(9299):2122-5. [Medline].
Michel M, Rauzy OB, Thoraval FR, et al. Characteristics and outcome of immune thrombocytopenia in elderly: results from a single center case-controlled study. Am J Hematol. 2011 Dec. 86(12):980-4. [Medline].
Heitink-Pollé KM, Nijsten J, Boonacker CW, de Haas M, Bruin MC. Clinical and laboratory predictors of chronic immune thrombocytopenia in children: a systematic review and meta-analysis. Blood. 2014 Nov 20. 124(22):3295-307. [Medline].
Kuter DJ, Bussel JB, Lyons RM, et al. Efficacy of romiplostim in patients with chronic immune thrombocytopenic purpura: a double-blind randomised controlled trial. Lancet. 2008 Feb 2. 371(9610):395-403. [Medline].
Zheng T, Chunlei L, Zhen W, Ping L, Haitao Z, Weixin H, et al. Clinical-Pathological Features and Prognosis of Thrombotic Thrombocytopenic Purpura in Patients With Lupus Nephritis. Am J Med Sci. 2009 Sep 9. [Medline].
Rajantie J, Zeller B, Treutiger I, Rosthöj S. Vaccination associated thrombocytopenic purpura in children. Vaccine. 2007 Feb 26. 25(10):1838-40. [Medline].
Mantadakis E, Farmaki E, Buchanan GR. Thrombocytopenic purpura after measles-mumps-rubella vaccination: a systematic review of the literature and guidance for management. J Pediatr. 2010 Apr. 156 (4):623-8. [Medline].
Visentin GP, Liu CY. Drug-induced thrombocytopenia. Hematol Oncol Clin North Am. 2007 Aug. 21(4):685-96, vi. [Medline]. [Full Text].
Reese JA, Li X, Hauben M, Aster RH, Bougie DW, Curtis BR. Identifying drugs that cause acute thrombocytopenia: an analysis using 3 distinct methods. Blood. 2010 Sep 23. 116(12):2127-33. [Medline].
Sundell IB, Koka PS. Thrombocytopenia in HIV infection: impairment of platelet formation and loss correlates with increased c-Mpl and ligand thrombopoietin expression. Curr HIV Res. 2006 Jan. 4(1):107-16. [Medline].
Raife TJ, Olson JD, Lentz SR. Platelet antibody testing in idiopathic thrombocytopenic purpura. Blood. 1997 Feb 1. 89(3):1112-4. [Medline]. [Full Text].
Emilia G, Luppi M, Zucchini P, et al. Helicobacter pylori infection and chronic immune thrombocytopenic purpura: long-term results of bacterium eradication and association with bacterium virulence profiles. Blood. 2007 Dec 1. 110(12):3833-41. [Medline]. [Full Text].
Franchini M, Cruciani M, Mengoli C, Pizzolo G, Veneri D. Effect of Helicobacter pylori eradication on platelet count in idiopathic thrombocytopenic purpura: a systematic review and meta-analysis. J Antimicrob Chemother. 2007 Aug. 60(2):237-46. [Medline]. [Full Text].
Inaba T, Mizuno M, Take S, et al. Eradication of Helicobacter pylori increases platelet count in patients with idiopathic thrombocytopenic purpura in Japan. Eur J Clin Invest. 2005 Mar. 35(3):214-9. [Medline].
Sato R, Murakami K, Watanabe K, et al. Effect of Helicobacter pylori eradication on platelet recovery in patients with chronic idiopathic thrombocytopenic purpura. Arch Intern Med. 2004 Sep 27. 164(17):1904-7. [Medline]. [Full Text].
Hwang JJ, Lee DH, Yoon H, Shin CM, Park YS, Kim N. The Effects of Helicobacter pylori Eradication Therapy for Chronic Idiopathic Thrombocytopenic Purpura. Gut Liver. 2015 Sep 9. [Medline].
Ahn ER, Tiede MP, Jy W, et al. Platelet activation in Helicobacter pylori-associated idiopathic thrombocytopenic purpura: eradication reduces platelet activation but seldom improves platelet counts. Acta Haematol. 2006. 116(1):19-24. [Medline].
Michel M, Cooper N, Jean C, Frissora C, Bussel JB. Does Helicobacter pylori initiate or perpetuate immune thrombocytopenic purpura?. Blood. 2004 Feb 1. 103(3):890-6. [Medline]. [Full Text].
Lai SW, Lin HF, Lin CL, Liao KF. Immune thrombocytopenic purpura might be an early hematologic manifestation of undiagnosed human immunodeficiency virus infection. Intern Emerg Med. 2017 Mar. 12 (2):157-162. [Medline].
Schultz CL, Mitra N, Schapira MM, Lambert MP. Influence of the American Society of Hematology guidelines on the management of newly diagnosed childhood immune thrombocytopenia. JAMA Pediatr. 2014 Oct. 168(10):e142214. [Medline].
Gudbrandsdottir S, Birgens HS, Frederiksen H, Jensen BA, Jensen MK, Kjeldsen L, et al. Rituximab and dexamethasone vs dexamethasone monotherapy in newly diagnosed patients with primary immune thrombocytopenia. Blood. 2013 Mar 14. 121(11):1976-81. [Medline].
Cines DB, Blanchette VS. Immune thrombocytopenic purpura. N Engl J Med. 2002 Mar 28. 346(13):995-1008. [Medline].
Bussel JB. Novel approaches to refractory immune thrombocytopenic purpura. Blood Rev. 2002 Mar. 16(1):31-6. [Medline].
McMillan R. Therapy for adults with refractory chronic immune thrombocytopenic purpura. Ann Intern Med. 1997 Feb 15. 126(4):307-14. [Medline].
Godeau B, Durand JM, Roudot-Thoraval F, et al. Dapsone for chronic autoimmune thrombocytopenic purpura: a report of 66 cases. Br J Haematol. 1997 May. 97(2):336-9. [Medline].
Facon T, Caulier MT, Wattel E, et al. A randomized trial comparing vinblastine in slow infusion and by bolus i.v. injection in idiopathic thrombocytopenic purpura: a report on 42 patients. Br J Haematol. 1994 Mar. 86(3):678-80. [Medline].
Emilia G, Morselli M, Luppi M, et al. Long-term salvage therapy with cyclosporin A in refractory idiopathic thrombocytopenic purpura. Blood. 2002 Feb 15. 99(4):1482-5. [Medline]. [Full Text].
Chalmers S, Tarantino MD. Romiplostim as a treatment for immune thrombocytopenia: a review. J Blood Med. 2015. 6:37-44. [Medline]. [Full Text].
FDA extends use of Promacta in young children with rare blood disorder. U.S. Food and Drug Administration. Available at http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm459430.htm. August 24, 2015; Accessed: September 23, 2015.
Kuter DJ, Rummel M, Boccia R, Macik BG, Pabinger I, Selleslag D, et al. Romiplostim or standard of care in patients with immune thrombocytopenia. N Engl J Med. 2010 Nov 11. 363(20):1889-99. [Medline].
Bussel JB, Hsieh L, Buchanan GR, Stine K, Kalpatthi R, Gnarra DJ, et al. Long-term use of the thrombopoietin-mimetic romiplostim in children with severe chronic immune thrombocytopenia (ITP). Pediatr Blood Cancer. 2014 Oct 24. [Medline].
Tarantino MD, Bussel JB, Blanchette VS, Despotovic J, Bennett C, Raj A, et al. Romiplostim in children with immune thrombocytopenia: a phase 3, randomised, double-blind, placebo-controlled study. Lancet. 2016 Jul 2. 388 (10039):45-54. [Medline].
Michel M, Wasser J, Godeau B, Aledort L, Cooper N, Tomiyama Y, et al. Efficacy and safety of the thrombopoietin receptor agonist romiplostim in patients aged ≥65 years with immune thrombocytopenia. Ann Hematol. 2015 Sep 4. [Medline].
Cheng G, Saleh MN, Marcher C, et al. Eltrombopag for management of chronic immune thrombocytopenia (RAISE): a 6-month, randomised, phase 3 study. Lancet. 2011 Jan 29. 377(9763):393-402. [Medline].
Lambert MP, Gernsheimer TB. Clinical updates in adult immune thrombocytopenia. Blood. 2017 May 25. 129 (21):2829-2835. [Medline].
Khan LR, Nixon SJ. Laparoscopic splenectomy is a better treatment for adult ITP than steroids--it should be used earlier in patient management. Conclusions of a ten-year follow-up study. Surgeon. 2007 Feb. 5(1):3-4, 6-8. [Medline].
Rescorla FJ, West KW, Engum SA, Grosfeld JL. Laparoscopic splenic procedures in children: experience in 231 children. Ann Surg. 2007 Oct. 246(4):683-7; discussion 687-8. [Medline].
Mikhael J, Northridge K, Lindquist K, Kessler C, Deuson R, Danese M. Short-term and long-term failure of laparoscopic splenectomy in adult immune thrombocytopenic purpura patients: A systematic review. Am J Hematol. 2009 Jul 16. [Medline].
Bell WR Jr. Role of splenectomy in immune (idiopathic) thrombocytopenic purpura. Blood Rev. 2002 Mar. 16(1):39-41. [Medline].
Rodeghiero F, Frezzato M, Schiavotto C, Castaman G, Dini E. Fulminant sepsis in adults splenectomized for idiopathic thrombocytopenic purpura. Haematologica. 1992 May-Jun. 77(3):253-6. [Medline].
Zarrabi MH, Rosner F. Serious infections in adults following splenectomy for trauma. Arch Intern Med. 1984 Jul. 144(7):1421-4. [Medline].
Beattie JF, Michelson ML, Holman PJ. Acute babesiosis caused by Babesia divergens in a resident of Kentucky. N Engl J Med. 2002 Aug 29. 347(9):697-8. [Medline].
Crary SE, Buchanan GR. Vascular complications after splenectomy for hematologic disorders. Blood. 2009 Oct 1. 114(14):2861-8. [Medline].
Robinette CD, Fraumeni JF Jr. Splenectomy and subsequent mortality in veterans of the 1939-45 war. Lancet. 1977 Jul 16. 2(8029):127-9. [Medline].
Purcell PL, Crary SE, Adix LM, Alder AC, Buchanan GR. Postsplenectomy vascular complications: Feasibility of studying patients with splenectomy following trauma. Am J Hematol. 2009 May. 84(5):316-7. [Medline].
George JN, Woolf SH, Raskob GE, et al. Idiopathic thrombocytopenic purpura: a practice guideline developed by explicit methods for the American Society of Hematology. Blood. 1996 Jul 1. 88(1):3-40. [Medline]. [Full Text].
Facon T, Caulier MT, Fenaux P, et al. Accessory spleen in recurrent chronic immune thrombocytopenic purpura. Am J Hematol. 1992 Nov. 41(3):184-9. [Medline].
Woo JH, Park SH, Park YK, et al. Postsplenectomy recurrence of thrombocytopenia with an accessory spleen. Korean J Intern Med. 2004 Sep. 19(3):199-201. [Medline]. [Full Text].
Dolan JP, Sheppard BC, DeLoughery TG. Splenectomy for immune thrombocytopenic purpura: surgery for the 21st century. Am J Hematol. 2008 Feb. 83(2):93-6. [Medline].
Balagué C, Vela S, Targarona EM, et al. Predictive factors for successful laparoscopic splenectomy in immune thrombocytopenic purpura: study of clinical and laboratory data. Surg Endosc. 2006 Aug. 20(8):1208-13. [Medline].
Blanchette VS, Carcao M. Childhood acute immune thrombocytopenic purpura: 20 years later. Semin Thromb Hemost. 2003 Dec. 29(6):605-17. [Medline].
Roganovic J. Rituximab treatment in refractory idiopathic thrombocytopenic purpura in children. Eur J Pediatr. 2005 May. 164(5):334. [Medline].
Taube T, Schmid H, Reinhard H, von Stackelberg A, Overberg US. Effect of a single dose of rituximab in chronic immune thrombocytopenic purpura in childhood. Haematologica. 2005 Feb. 90(2):281-3. [Medline]. [Full Text].
Cooper N, Evangelista ML, Amadori S, Stasi R. Should rituximab be used before or after splenectomy in patients with immune thrombocytopenic purpura?. Curr Opin Hematol. 2007 Nov. 14(6):642-6. [Medline].
Zaja F, Volpetti S, Chiozzotto M, Puglisi S, Isola M, Buttignol S, et al. Long-term follow-up analysis after rituximab salvage therapy in adult patients with immune thrombocytopenia. Am J Hematol. 2012 May 21. [Medline].
George JN. Management of immune thrombocytopenia--something old, something new. N Engl J Med. 2010 Nov 11. 363(20):1959-61. [Medline].
McMillan R, Bussel JB, George JN, Lalla D, Nichol JL. Self-reported health-related quality of life in adults with chronic immune thrombocytopenic purpura. Am J Hematol. 2008 Feb. 83(2):150-4. [Medline].
Newland A. Thrombopoietin mimetic agents in the management of immune thrombocytopenic purpura. Semin Hematol. 2007 Oct. 44(4 suppl 5):S35-45. [Medline].
von dem Borne A, Folman C, van den Oudenrijn S, et al. The potential role of thrombopoietin in idiopathic thrombocytopenic purpura. Blood Rev. 2002 Mar. 16(1):57-9. [Medline].
Bussel JB, Kuter DJ, George JN, et al. AMG 531, a thrombopoiesis-stimulating protein, for chronic ITP. N Engl J Med. 2006 Oct 19. 355(16):1672-81. [Medline]. [Full Text].
Jamali F, Lemery S, Ayalew K, Robottom S, Robie-Suh K, Rieves D, et al. Romiplostim for the treatment of chronic immune (idiopathic) thrombocytopenic purpura. Oncology (Williston Park). 2009 Jul. 23(8):704-9. [Medline].
Bussel JB, Cheng G, Saleh MN, et al. Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura. N Engl J Med. 2007 Nov 29. 357(22):2237-47. [Medline].
Rice L. Treatment of immune thrombocytopenic purpura: focus on eltrombopag. Biologics. 2009. 3:151-7. [Medline]. [Full Text].
Cines DB, Bussel JB, McMillan RB, Zehnder JL. Congenital and acquired thrombocytopenia. Hematology Am Soc Hematol Educ Program. 2004. 390-406. [Medline]. [Full Text].