Immune Thrombocytopenic Purpura: Pearls and Pitfalls
- Aug 28th, 2016
- Patrick Ng
Authors: Patrick C Ng, MD (EM Chief Resident, SAUSHEC Emergency Medicine Department) and Brit Long, MD (@long_brit, EM Attending Physician, SAUSHEC Emergency Medicine Department) // Edited by: Jennifer Robertson, MD, MSEd and Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital)
A 7-year-old male, previously healthy and born at term, presents to the emergency department (ED) accompanied with his parents with a chief complaint of knee pain and subsequent difficultly walking. The child woke up with the knee pain, and it progressed throughout the day to the point where the child could not bear weight. Oral acetaminophen and ibuprofen provided minimal pain relief at home. To add to the history, the patient was seen recently in the ED for a fever, nonproductive cough, and runny nose approximately 14 days prior. He was diagnosed with a viral syndrome, and his symptoms resolved with supportive care. A review of systems (ROS) is negative for numbness, weakness, fever, nausea, vomiting, or pedal edema. Surgical history is significant for a circumcision shortly after birth. There are no significant medical problems in the family.
On examination in the ED, vital signs are all within normal limits. The child holds his left knee in approximately 120 degrees of flexion. He displays significant pain with extension and flexion of the knee. There is no obvious deformity, nor is there any significant swelling or joint line tenderness. He has no tenderness on the tibial tuberosity or with manipulation of the patella. The rest of the child’s exam is unremarkable.
His workup consists of x-rays of the left lower extremity, revealing a knee effusion and mild soft tissue swelling, and a normal basic metabolic panel (BMP). His complete blood count (CBC) reveals a platelet count of 6,000/ uL. A diagnosis of hemarthrosis is made and it is likely secondary to immune thrombocytopenic purpura (ITP). Thus, the child is admitted for further management.
Immune Thrombocytopenic Purpura (ITP)
Immune thrombocytopenic purpura was once known as idiopathic thrombocytopenic purpura until it was discovered that the pathophysiology of the thrombocytopenia involved the host immune system . In ITP, thrombocytopenia occurs secondary to antiplatelet antibodies that are produced in the spleen. These antibodies first bind to platelets, followed by phagocytosis of the platelet/antibody complex by the reticuloendothelial system [1,8,9]. ITP is the leading cause of thrombocytopenia in children . It is defined as a platelet count of <100,000/uL. Other common characteristics of ITP include petechiae and/or purpura, normal hemoglobin and white blood cell (WBC) count, and the absence of other signs of identifiable causes of thrombocytopenia. Acute ITP typically resolves within 6-12 months and often occurs shortly after an infection or a vaccination [2,3]. The disease is considered chronic if the thrombocytopenia lasts longer than 6-12 months without another identified etiology. ITP can occur in both children and adults. Approximately 80% of ITP seen in children is acute. Adults are typically affected with the chronic form . Regardless of the patient’s age and his or her form of ITP, the most feared complication of the disease is major bleeding. This includes, but is not limited to, life threatening gastrointestinal bleeding and intracranial hemorrhage. According to Farhangi et al, the overall risk of serious bleeding in children with ITP is 3%, while the risk of intracranial hemorrhage (ICH) is 0.5% . Most cases present with less significant bleeding, however. In a retrospective analysis of infants with ITP from 1987 to 2002, the majority were found to present with purpura and active mucosal bleeding . Other studies have found serious bleeding rates ranging from 2.9% to 17%. The definitions of serious bleeding were defined differently in each study, however ICH, bleeding with a drop in hemoglobin, bleeding that required hospitalization or blood transfusion, epistaxis requiring cautery or nasal packing, and/or gross hematuria were all included as definitions of severe bleeding [5, 6,7]. In a more in 2008, Neunert et al reported on 1106 ITP patients enrolled into the Intercontinental Childhood ITP Study group (ICIS). In this report, the authors conclude that severe bleeding is uncommon at diagnosis of ITP in children . Finally, there a few reports, in form of case studies, that focus on other complications of ITP such as spontaneous hemarthrosis, as in the case above. The rates of such presentations are not well characterized in the literature but are important for the emergency physician to recognize as a potential presentation .
Some studies describe ITP as a more serious disease in adults due to higher ICH rates (5%) as compared to children . Typically, adult cases have a more insidious onset, often without any preceding infection on history and physical .
The clinical presentation of ITP, particularly in children, is variable. There is no consensus on how to predict the chances of serious bleeding on initial presentation. Recognizing this is important as the emergency medicine provider must maintain a high degree of suspicion for a major bleed, particularly in patients with platelet counts <50,000/ uL and in those with wet purpura (mucosal sites with purpura).
What are the key ED laboratory studies?
The laboratory tests that are essential include CBC and peripheral smear, as the hemoglobin, WBC, and WBC morphology may suggest other diagnoses such as malignancy. Thrombocytopenia is essential to making the diagnosis of ITP.
So you have a patient with plt count 20,000/uL. Is this ITP?
History and physical, CBC, and peripheral smear can suggest a more sinister condition. Evaluate closely for a history of joint/bone pain or a family history of easy bruising. These are signs of malignancy or familial coagulopathy, respectively. Examination findings that are not consistent with ITP include soft tissue or bony abnormalities, a non-petechial rash, hepatosplenomegaly, and lymphadenopathy. Laboratory findings such as an abnormal hemoglobin, an abnormal WBC morphology, and abnormal WBC count suggest another etiology.
Is there a scoring system available?
The spectrum of ITP presentations can range from asymptomatic to life threatening bleeds. An objective measurement of bleeding in patients with ITP can be accomplished using the ITP Bleeding Scale (IBLS) and/or ITP-specific bleeding assessment tool (ITP-BAT) [11,12]. The ITP-BAT scoring system is more prevalent in the literature. In essence, the scoring system takes into account the bleeding manifestations by organ system: Skin(S), visible Mucosae (M) and Organs (O) with Gradation of severity (SMOG). The emergency provider (EP) may not be specifically calculating this score upon initial evaluation, as it is primarily used to evaluate the patient’s response to treatment. However, the EP should be aware of this score, paying particular attention to the specific organ systems to evaluate for major bleeding when considering the diagnosis of ITP.
The initial treatment is targeted at blunting the activity of the reticuloendothelial system and is primarily based on expert opinion. Treatment and admission is indicated in patients that have a major bleeding episode and/or platelet counts < 10,000/ uL . Corticosteroids are the initial treatment for non-life threatening bleeds. Examples of corticosteroid regimens include prednisolone/prednisone at 1-2mg/kg per day or dexamethasone at 40mg/day for 4 days . For ITP patients with major bleeds, treatment includes IVIG at 1g/kg, IV methylprednisolone 1g/d x 3 days, and platelet transfusions [9,10,13].
Patients may present with wet or dry purpura and management of both is similar. However, it is important to make this clinical distinction. Wet purpura indicates active bleeding which puts patients at increased risk for anemia. These patients may need to be monitored more closely, with serial laboratory studies and more frequent physical examinations to assess for the extent of bleeding. These patients may also require more aggressive transfusions cases of severe bleeding.
Newer therapeutic approaches with medications such as rituximab, cyclophosphamide, vinca alkaloids, and mycophenolate mofetil have been explored in cases of refractory ITP . Splenectomy serves as an effective second line therapy in cases refractory to initial treatments . These approaches are more often needed in adults.
- ITP can present with severe, life threatening bleeding including, but not limited to, intracranial hemorrhage.
- Physical examination should focus on signs of bleeding intracranially, intra-abdominally, in the skin, and from the mucosa.
- Initial workup includes CBC, WBC morphology, and peripheral smear.
- Initial management of steroids and admission should be considered depending on the clinical presentation.
- There are atypical presentations of ITP such as hemarthrosis that the EP should consider.
- Emergency physicians should maintain a broad differential, as subtle abnormalities in the workup other than low platelets can suggest alternative diagnoses such as malignancy.
- Lusher JM, Zuelzer WW. Idiopathic thrombocytopenic purpura in childhood. J Pediatr 1966;68:971-9.
- Fargangi H, Ghasemi A, Banihashem A, Badiei Z, Jarahi L, Esami G, Langaee T. Clinical Features and Treatment Outcomes of Primary Immune Thrombocytopenic Purpura in Hospitalized Children Under 2-Years Old. Iran J Ped Hematol Oncol. 2016; 6(1): 24-31.
- Kuhne T. Idiopathic thrombocytopenic purpura of childhood: a problem-oriented review of the management. Transfus Apher Sci 2003 Jun;28(2):243-8.
- Sandoval C, Visintainer P, Ozkaynak MF, Tugal O, Jayabose S. Clinical features and treatment outcomes of 79 infants with immune thrombocytopenic purpura. Pediatr Blood Cancer 2004 Jan;42(1):109-12.
- Watts RG. Idiopathic thrombocytopenia purpura: a 10-year natural history study at the Children’s hospital of Alabama. Clin Pediatr (Phila). 2004 Oct;43(8):691-702.
- 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.
- Neunert CE, Buchanan GR, Imbach P, Bolton-Maggs PH, Bennett CM, Neufeld EJ. Severe hemorrhage in children with newly diagnosed immune thrombocytopenic purpura. Blood 2008 Nov 15;112(10):4003-8.
- Moller DE, Goldstein K. Hemarthrosis and idiopathic thrombocytopenic purpura. J Rheumatol 1987 Apr;14(2):382-3.
- George JN, Woolf SH, Raskob GE, Wasser JS, Aledort LM, Ballem PJ, et al. Idiopathic Thrombocytopenic Purpura: A Practice Guideline Developed by Explicit Methods for The American Society of Hematology. Blood 1996;88:3-40.
- Stasi R. Pathophysiology and therapeutic options in primary immune thrombocytopenia. Blood Transfus 2011 Jul; 9(3): 262-273.
- Page LK, Psaila B, Provan D, Hamilton JM, Jenkins JM, Elish AS, et al. The immune thrombocytopenic purpura (ITP) bleeding score: assessment of bleeding in patients with ITP. British Journal of Haematology 138, 245-248.
- Rodeghiero F, Michel M, Gernsheimer T, Stasi R. Standardization of bleeding assessment in immune thrombocytopenia: report from the International Working Group. Blood 2013;121(14).
- Stasi R, Provan D. Management of immune thrombocytopenic purpura in adults. Mayo Clin Proc 2004 Apr;79(4):504-22.
- Supe A, Parikh M, Prabhu R, Kantharia C, Farah J. Post-splenectomy response in adult patients with immune thrombocytopenic purpura. Asian J Transfus Sci 2009 Jan; 3(1):6-9.
- Kojouri K, Vesely SK, Terrell DR, George JN. Splenectomy for adult patients with idiopathic thrombocytopenic purpura: a systematic review to assess long-term platelet count responses, prediction of response and surgical complications. Blood 2004;10:2623-34.