Immune Thrombocytopenia (ITP):

An acquired autoimmune disorder characterized by a low platelet count of <100,000/uL resulting from platelet destruction and impaired platelet production (Neunert 2019)

Background

  • Incidence of ITP is estimated to be 2-5 per 100,000 persons in the general population (Neunert 2019)
  • Few randomized control trials exist to guide management, so recommendations primarily derived from expert consensus
  • Previously known as Idiopathic Thrombocytopenic Purpura and as Immune Thrombocytopenic Purpura, but renamed as etiology now known and purpura not always present
  • ITP is a diagnosis of exclusion. It is important to rule out other serious pathologies before assuming ITP is the cause of thrombocytopenia such as Thrombotic Thrombocytopenic Purpura (TTP) or Disseminated Intravascular Coagulation (DIC).

Pathophysiology

  • The patient’s immune system becomes sensitized to platelets, leading to the creation of antiplatelet antibodies.
  • Antiplatelet antibodies bind to platelets, triggering phagocytosis and destruction by the patient’s own immune system
  • As platelets are removed from circulation rather than forming platelet clumps, this does not lead to microvascular hemolysis or to end organ dysfunction as seen in other conditions such as TTP and DIC.
  • ITP may result from a primary autoimmune disorder or develop secondary to some other exposure, usually to a medication or virus.
    • Common viral triggers: HIV, HCV, CMV, EBV, herpes viruses and VZV (Kitamura 1994)
    • Common medication triggers:
      • Hundreds of drugs reported to trigger ITP
      • Highest rates of ITP reported with exposure to sulfamethoxazole/trimethoprim or quinidine/quinine (Kaufman 1993)
      • Other commonly used medications such as NSAIDs, penicillins, heparin, antiepileptics, and antiarrhythmics also implicated (Aster 2009)
    • First time presentation of ITP usually occurs in childhood. It is rarer in adults (Neunert 2019).

ED Evaluation

History

  • ITP is usually asymptomatic. Concurrent symptoms such as fever, headache, abdominal pain, chest pain should prompt directed workup towards those symptoms
  • Known history of ITP simplifies management
  • Any significant bleeding may indicate need for admission

Physical Exam

  • Petechiae and mild mucosal bleeding (such as gums when brushing teeth) common
  • Purpura may be present
  • Assess for any signs of bleeding:
    • Hypotension/tachycardia raises concern for GI bleeding
    • Abnormal neuro exam may suggest intracranial hemorrhage
    • Joint swelling may suggest hemarthrosis

Laboratory Testing

  • If patient has known ITP, only needed test is CBC to assess platelet count.
  • When diagnosis is unclear, a broader workup is needed to rule out other more dangerous pathologies. Signs of hemolysis or end organ dysfunction suggest more dangerous pathology.
  • Compete Blood Count
    • Thrombocytopenia expected
    • Low Hb may suggest either significant bleeding or RBC hemolysis
  • Basic metabolic panel
    • Normal in ITP. High BUN/creatinine indicative of end organ dysfunction
  • Hepatic panel
    • Normal in ITP. High bilirubin suggest hemolysis
  • PT/INR + aPTT
    • Normal in ITP
  • Haptoglobin + LDH
    • Normal in ITP. Low haptoglobin, high LDH suggests hemolysis
  • Fibrinogen
    • Normal in ITP. Low in DIC
  • D-dimer
    • Normal in ITP. High in DIC
  • Blood smear
    • Presence of schistocytes raises concern for other pathologies

Management

Observation Only:

Patients may be observed without treatment if the patient has:

  • Pre-existing diagnosis of ITP
  • No significant bleeding
  • Platelet count >30,000/uL
  • Access to reliable follow-up with hematologist within 1-3 days

Treatment:

Patients should begin treatment if:

  • Platelet count <30,000/uL AND no bleeding or only minor mucosal bleeding
  • Platelet count <50,000/uL with significant bleeding

First Line:

  • Corticosteroids
    • Prednisone (0.5 – 2.0mg/kg/day) or Dexamethasone (40 mg/day)
  • Intravenous Immunoglobulin (IVIG) may be used as alternate first line therapy if steroids are contraindicated
    • Usual dose 1g/kg

Second Line (after admission):

  • Thrombopoietin receptor agonist (eltrombopag or romiplostim)
  • Rituximab
  • Splenectomy

Indications for Hospital Admission:

  • Unclear diagnosis
  • Inability to arrange secure follow-up with hematologist within 1-3 days
  • Any significant bleeding
  • Platelet count <10,000/uL

Platelet Transfusion:

  • Transfusion is not routinely recommended
    • Administered platelets will be targeted by antiplatelet antibodies and destroyed, so are unlikely to be of much benefit
    • In contrast to TTP, platelet transfusions in ITP are not dangerous or harmful
  • Transfuse platelets when platelet count <10,000u/L
    • At platelet counts of <10,000/uL, the risk of spontaneous bleeding increases significantly

Take Home Points:

  • ITP is an autoimmune disorder leading to destruction of platelets
  • History, physical exam, and laboratory testing focus on ruling out more dangerous conditions such as TTP or DIC.
  • Asymptomatic patients with platelet counts >30,000/uL may be managed with observation only
  • Steroids are first line treatment for patients with significant thrombocytopenia or active bleeding
  • Platelet transfusions should not be administered until platelet count <10,000/uL

 

Read More:

ITP: https://www.hematology.org/ITPguidelines/

References

Aster RH, Curtis BR, Mcfarland JG, Bougie DW. Drug-induced immune thrombocytopenia: pathogenesis, diagnosis, and management. J Thromb Haemost. 2009;7(6):911-8. PMID: 19344362

Chosamata BI. The management of immune thrombocytopenic purpura. Malawi Med J. 2015;27(3):109-12. PMID: 26715957

Dimaggio D, Anderson A, Bussel JB. Cytomegalovirus can make immune thrombocytopenic purpura refractory. Br J Haematol. 2009;146(1):104-12. PMID: 19438507

Espinoza C, Kuhn C. Viral infection of megakaryocytes in varicella with purpura. Am J Clin Pathol. 1974;61(2):203–208. PMID: 4855807

Fogarty PF, Tarantino MD, Brainsky A, Signorovitch J, Grotzinger KM. Selective validation of the WHO Bleeding Scale in patients with chronic immune thrombocytopenia. Curr Med Res Opin. 2012;28(1):79-87. PMID 22117897

Kaufman DW, Kelly JP, Johannes CB, Sandler A, Harmon D, Stolley PD, Shapiro S. Acute thrombocytopenic purpura in relation to the use of drugs. Blood. 1993;82 :2714–8. PMID: 8219224

Kitamura K, Ohta H, Ihara T, Kamiya H, Ochiai H, Yamanishi K, et al. Idiopathic thrombocytopenic purpura after human herpesvirus 6 infection. Lancet. 1994;344(8925):830. PMID: 7916114

Magdi M, Rahil A. Severe Immune Thrombocytopenia Complicated by Intracerebral Haemorrhage Associated with Coronavirus Infection: A Case Report and Literature Review. Eur J Case Rep Intern Med. 2019;6(7):001155. PMID: 31410357

Neunert C, Terrell DR, Arnold DM, et al. American Society of Hematology 2019 guidelines for immune thrombocytopenia. Blood Adv. 2019;3(23):3829-3866. PMID: 31794604