Immune Thrombocytopenia (ITP)

Impacted by a low platelet count, Immune Thrombocytopenia (ITP), also recognized as immune thrombocytopenic purpura, represents an autoimmune haematological disorder characterized by isolated thrombocytopenia without identifiable aetiology. Diagnosing ITP entails a thorough evaluation, designed to eliminate alternative, potentially severe, causes of thrombocytopenia.

The appropriate course of treatment is contingent upon the patients specific attributes and the prevailing clinical circumstances, allowing for a spectrum of options, ranging from close monitoring to medical or surgical interventions.

Within the European context, the incidence of adult ITP is estimated to be between 1.6 and 3.9 cases per 100,000 individuals annually.¹ The incidence rises with advancing age and exhibits a notable female predominance, with a female-to-male ratio of 3:1 among younger patients. A nationwide population study conducted in the United Kingdom reported a crude incidence rate of 3.9 cases per 100,000 person-years, with a more pronounced incidence observed in females.² Conversely, childhood ITP manifests an annual incidence ranging from 1.9 to 6.4 cases per 100,000, demonstrating an equal distribution between the sexes and a propensity for spontaneous remission.¹

Definition

An acquired autoimmune disorder, characterized by a reduced platelet count, typically less than 100,000 platelets per microliter (uL),³ is attributable to both platelet destruction and impaired platelet production. This condition occurs in the presence of normal bone marrow and the absence of other underlying causes of thrombocytopenia.

The pathophysiological mechanisms underlying thrombocytopenia in ITP are intricate and subject to ongoing research. Current evidence indicates a multifaceted process, including heightened platelet destruction within the spleen, primarily driven by antiplatelet antibodies, with a prominent focus on GPIIb-IIIa. Additionally, there is an inhibition of platelet production due to the suppression of normal megakaryocyte development by autoantibodies. Furthermore, T cell-mediated destruction of both platelets and megakaryocytes within the bone marrow contributes to this complex pathogenesis.^4,5

1. Primary ITP: Characterized by platelet destruction occurring independently of any other underlying medical condition.
2. Secondary ITP: Platelet destruction associated with a concurrent medical condition, known as secondary ITP (associated condition). These associated conditions may include:
   • Infectious diseases such as HIV, Hepatitis C, Helicobacter pylori, and immunodeficiencies
   • Autoimmune disorders, for instance, systemic lupus erythematosus, antiphospholipid syndrome, and autoimmune thyroid disease
   • Lymphoproliferative disorders
   • ITP triggered by specific medications
   • Cases related to vaccine exposure

A. Risk factors:

• • Females within the reproductive age bracket.⁶
  • Age: higher prevalence under the age of 10 and those aged 65 years and older.⁶

B. History:

• • The most prevalent complaints typically include minor bleeding during teeth brushing, recurrent nosebleeds, skin manifestations such as petechiae, purpura, or ecchymosis, and a pervasive sense of fatigue.
  • Acute headache, vision changes, and drowsiness or somnolence may suggest intracranial bleeding.
  • A history of recent viral illnesses, particularly in paediatric patients.
  • The presence of systemic symptoms should initiate a comprehensive evaluation for alternative pathologies. Indeed, the absence of these symptoms is more suggestive for ITP. These include unexplained weight loss, fever, and clinical indicators of autoimmune disorders like arthralgias, skin rashes, alopecia, and venous thrombosis.
  • Certain medications known to induce thrombocytopenia should be excluded such as heparin, alcohol, quinine/quinidine, and sulpha drugs.

C. Examination:

• • The physical examination is frequently unremarkable.
  • Look for bruising, petechiae, or other signs of bleeding, which may be attributable to thrombocytopenia.
  • Altered vital signs which may suggest occult internal bleeding (hypotension, unexplained tachycardia, or tachypnoea)
  • Signs of intracranial bleeding such as severe headache, altered conscious level or focal neurological deficits.
  • Lymphadenopathy and hepatosplenomegaly should be absent. The presence of these findings warrants further investigation into alternative aetiologies such as lymphoproliferative, autoimmune, or infectious disorders.

Possible workup in the ED

In cases where the patient has a confirmed history of ITP, an FBC to evaluate the platelet count is typically sufficient for assessment. When the diagnosis is unclear or when there are additional concerning symptoms, a more extensive diagnostic workup is warranted to exclude more severe underlying conditions.

Possible workup in ED:

• FBC:
  • Thrombocytopenia expected (platelet count <100 10/L)
  • A decreased haemoglobin level (Hb) could indicate either substantial blood loss or red blood cell (RBC) haemolysis

• Renal function:
  • Normal in ITP
  • Elevated BUN and creatinine levels are indicative of potential end-organ dysfunction, which merits further evaluation

• Liver function test:
  • Normal in ITP
  • An increase in bilirubin levels may be a marker of haemolysis

• Coagulation profile:
  • Normal in ITP

• Blood smear:
  • Schistocytes may be indicative of conditions such as haemolytic anaemias, microangiopathic disorders, or mechanical damage to red blood cells. Further assessment is often necessary to determine the specific cause when schistocytes are observed.

• Fibrinogen:
  • Normal in ITP
  • Low in DIC

• D-dimer:
  • Normal in ITP
  • High in DIC

 

Other investigations

Other investigations to be considered:

1.HIV, HCV

• Testing should be conducted in high-risk patient populations, such as intravenous drug users. Negative results could provide supportive evidence for the diagnosis of ITP.

2. Thyroid Function Test

• Hyper- or hypothyroidism can lead to thrombocytopenia (albeit relatively uncommon causes). While not always part of the initial workup, it is important to conduct testing for thyroid function before elective splenectomy. This is to exclude all potential reversible causes of thrombocytopenia before subjecting the patient to the inherent risks associated with the procedure.

3. Quantitative immunoglobulins

• Testing may uncover common variable immunodeficiency or selective IgA deficiency.

4. Bone marrow biopsy/aspiration

• May be considered in individuals exhibiting abnormalities on a blood film. In the context of ITP, diagnostic findings typically reveal heightened megakaryocyte levels, with no indications of malignancy, flow cytometry, or cytogenetic abnormalities.

5. Pregnancy testing

• All women of childbearing age should undergo pregnancy testing. This is because certain treatments, such as rituximab, fostamatinib, and thrombopoietin receptor agonists, should be avoided during pregnancy.

A. In cases where the patient has pre-existing ITP, is not presenting with significant bleeding, and exhibits a platelet count exceeding 30,000/Ul. Do the following:

• No acute intervention in ED.
• Discuss the case with the haematology registrar/consultant on call for further advice and outpatient follow-up within 48 hours.

B. If Platelet counts <30,000/uL AND no bleeding or only minor mucosal bleeding or Platelet count <50,000/uL with significant bleeding:

• First-line treatment:

1. Corticosteroids
   • prednisolone: 1-2 mg/kg/day orally or methylprednisolone: 30 mg/kg/day orally or dexamethasone: 40 mg/day orally.
2. Intravenous Immunoglobulin (IVIG):
   • May serve as an alternative first-line therapy in situations where the use of steroids is contraindicated.
3. Anti-D immunoglobulin:
   • Patients who are Rh-positive and have not undergone splenectomy may derive benefits from anti-D immunoglobulin, as it has demonstrated the ability to raise platelet counts in over 70% of cases.⁷

• In all cases where there is life-threatening or organ-threatening bleeding (adults & children): This necessitates an urgent and comprehensive therapeutic approach encompassing platelet transfusion, corticosteroid administration, and intravenous immunoglobulin (IVIG) treatment. Haematology services should be involved early to assist with the management of these cases.

• Second Line (after admission):
  • Thrombopoietin receptor agonist (eltrombopag or romiplostim)
  • Rituximab
  • Splenectomy

• Indications for Hospital Admission:
  • Unclear Diagnosis
  • Challenges in Arranging Timely Follow-Up
  • Significant Bleeding
  • Severely Low Platelet Count (<10,000/uL)

• Secondary prevention:
  • Patients with a platelet count below the range of 50-70 10/L are advised to exercise caution and try to minimize the risk of trauma. This includes avoiding activities such as contact sports and high-risk endeavours that could lead to injury or bleeding complications.
  • Patients should also be diligent in avoiding medications that could potentially impact platelet function, such as non-steroidal anti-inflammatory drugs (NSAIDs) or aspirin, as well as anticoagulants like warfarin, which can disrupt normal coagulation.

Key Learning Points

• Diagnosing ITP requires ruling out other causes of thrombocytopenia through a comprehensive assessment.
• The history, physical examination, and laboratory investigations are primarily directed towards excluding more serious conditions like Thrombotic Thrombocytopenic Purpura (TTP) or Disseminated Intravascular Coagulation (DIC).
• Asymptomatic patients with platelet counts exceeding 30,000/uL may undergo observation without immediate intervention.
• Steroids represent the initial treatment modality for individuals exhibiting substantial thrombocytopenia or experiencing active bleeding.

Pitfalls

• Failure to conduct a comprehensive evaluation may result in misdiagnosis of ITP, as other potentially severe causes of thrombocytopenia may be overlooked.
• Neglecting to evaluate for systemic symptoms indicative of alternative pathologies may lead to misdiagnosis or delayed treatment initiation.
• Delaying the involvement of haematology services in cases of severe thrombocytopenia or life-threatening bleeding may lead to inadequate management and poor patient outcomes.
• Neglecting to advise patients on secondary prevention measures, such as avoiding trauma or medications that affect platelet function, may increase the risk of bleeding complications.

1. Terrell DR, Beebe LA, et al. The incidence of immune thrombocytopenic purpura in children and adults: A critical review of published reports. Am J Hematol. 2010 Mar;85(3):174-80.
2. Schoonen WM, Kucera G, Coalson J, et al. Epidemiology of immune thrombocytopenic purpura in the General Practice Research Database. Br J Haematol. 2009 Apr;145(2):235-44. [Erratum in: Br J Haematol. 2009 Sep;147(1):157.]
3. Neunert C, Terrell DR, Arnold DM, et al. American Society of Hematology 2019 guidelines for immune thrombocytopenia. Blood Adv. 2019;3(23):3829-3866.
4. Nugent D, McMillan R, Nichol JL, et al. Pathogenesis of chronic immune thrombocytopenia: increased platelet destruction and/or decreased platelet production. Br J Haematol. 2009;146:585-596.
5. McKenzie CG, Guo L, Freedman J, et al. Cellular immune dysfunction in immune thrombocytopenia (ITP). Br J Haematol. 2013;163:10-23.
6. Segal JB, Powe NR. Prevalence of immune thrombocytopenia: analyses of administrative data. J Thromb Haemost. 2006;4:2377-2383.
7. Scaradavou A, Woo B, Woloski BM, et al. Intravenous anti-D treatment of immune thrombocytopenic purpura: experience in 272 patients. Blood. 1997 Apr 15;89(8):2689-700.
8. Carr JM, Kruskall MS, Kaye JA, et al. Efficacy of platelet transfusions in immune thrombocytopenia. Am J Med. 1986 Jun;80(6):1051-4.
9. Immune thrombocytopenia Investigations | BMJ Best Practice [Internet]. Last reviewed 2024.
10. Immune thrombocytopenia Treatment algorithm | BMJ Best Practice [Internet]. Last reviewed 2024.
11. Justiz Vaillant AA, Gupta N. ITP-Immune Thrombocytopenic Purpura. [Updated 2024 May 5]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-.
12. OHara S. EM@3AM: Idiopathic thrombocytopenic purpura [Internet]. emDOCs.net Emergency Medicine Education. 2018.
13. Idiopathic thrombocytopenic purpura [Internet]. Core EM.
14. Silverman MA. Immune thrombocytopenia (ITP) in Emergency Medicine Clinical presentation: History, physical examination [Internet]. Updated: 2023.