Immune Thrombocytopenia (ITP)


Immune thrombocytopenia (ITP) is an acquired disease in which isolated thrombocytopenia (a peripheral platelet count of less than 100,000/µL) develops in the absence of any initiating or underlying etiology. ITP is characterized by antibody-mediated platelet destruction and suppression of megakaryocyte and platelet production due to immune deregulation. Approximately 80% of cases are primary (idiopathic) and 20% are secondary to various associated diseases.1

ITP is more common in pregnant women and women of childbearing age. Children with the disease have a good prognosis, and in most cases the disease goes into remission. The course is more chronic in adults, although spontaneous remission is also possible and typically occurs a few months after the initial diagnosis. The mortality rate is higher in patients who are older and who do not respond to initial treatment.2 ITP is a diagnosis of exclusion based on the patient’s medical history, physical examination findings, laboratory testing, and peripheral blood smear.1 

Laboratory Testing for ITP

For a diagnosis of ITP, some basic tests are required, and some supplementary tests are of potential utility. A basic evaluation should start with the patient’s personal and family medical history that includes the patient’s medication history. This examination and patient’s symptoms can guide the diagnostic approach of laboratory testing order.3

Basic Laboratory Testing for ITP

After examination, laboratory blood work should then be conducted and may include: complete blood cell count, peripheral blood film, quantitative immunoglobulin testing, blood group (Rh) determination, Helicobacter pylori, hepatitis C virus, and HIV testing.1 

Additional Laboratory Testing for ITP

Additional tests that may be of value include: antiphospholipid antibodies (immunoglobulin G [IgG] and IgM anti-2 glycoprotein I antibodies, IgG and IgM anticardiolipin antibodies), circulating lupus anticoagulant, thyroid-stimulating hormone, antithyroid antibodies, antinuclear antibodies, anti-DNA antibodies, pregnancy test in women of childbearing years, and polymerase chain reaction for parvovirus and cytomegalovirus. It is also important to rule out haematological emergencies, such as disseminated intravascular coagulation (DIC). Tests for DIC include prothrombin time, kaolin time, fibrinogen level, and platelet count.1 

Hemogram Testing for ITP

A blood smear is the initial step used to confirm a low platelet count. If platelet aggregation is observed on the blood smear, a different anticoagulant (ethylenediaminetetraacetic acid [EDTA] rather than citrate) should be used to eliminate the possibility of false thrombocytopenia (pseudothrombocytopenia), which is seen frequently in clinical practice.1 A low platelet count (thrombocytopenia) is the predominant finding in ITP, which typically is an incidental finding on a hemogram.3 Laboratory testing usually shows abnormally low platelets levels (<40 x 109/L) for longer than 3 months. The peripheral blood film also may show large or giant platelets and tiny platelet fragments.4

Read more about ITP diagnosis

Bone Marrow Examination for ITP 

Bone marrow examination is often not necessary for ITP diagnosis. However, if the diagnosis is unclear, the patient is older than 60 years, blood tests reveal abnormalities besides thrombocytopenia, or splenectomy is being considered, bone marrow aspiration is required.2 

Examination of the bone marrow aspirate and biopsy samples that reveals an increased number of megakaryocytes would confirm a diagnosis of ITP.4 The bone marrow in ITP is normocellular for age with a normal morphological appearance of erythroid and myeloid precursors. Megakaryocytes can appear large and immature because of the increased destruction of peripheral platelets, even though their morphology is usually normal.5 

Megakaryocyte morphology must be carefully examined in elderly patients to rule out an early form of myelodysplastic syndrome. Histological sections from bone marrow biopsy specimens or marrow clots also show normal cellularity. Signs of hypoplasia or increased marrow fibrosis are absent.5 

Read more about ITP signs and symptoms

Platelet-Bound Antibodies Testing for ITP 

Another group of tests for ITP directly measure platelet-bound IgG. Radioisotopes, flow cytometry, or other techniques are used to identify direct binding of a labeled antibody probe (either polyclonal or monoclonal).6 A direct Coombs test detects antiplatelet antibodies bound to platelets. An indirect Coombs test uses a pool of normal donor platelets to detect free antiplatelet antibodies in the serum, typically anti-glycoprotein IIb/IIIa antibodies. 

Other techniques that can be used to identify antiplatelet antibodies include enzyme-linked immunosorbent assay (ELISA), radiolabeled Coombs antiglobulin test, fluorescein-labeled Coombs antiglobulin test, lymphocyte activation by autologous platelets, and lymphocyte activation by platelet-antibody immune complexes.4 A negative antiplatelet antibody test result does not rule out a diagnosis of ITP. These tests are not required to diagnose ITP, so their routine use is not recommended.5

Read more about ITP prognosis

References

  1. Găman M-A, Găman AM. Pathophysiology, diagnosis and treatment of immune thrombocytopenia. International Journal of Medical Students. 2017;5(1):32-36. https://doi.org/10.5195/ijms.2017.171
  2. Zainal A, Salama A, Alweis R. Immune thrombocytopenic purpura. J Community Hosp Intern Med Perspect. 2019;9(1):59-61. doi: 10.1080/20009666.2019.1565884
  3. Ozcelik F, Keskin U, Kılıçaslan E, Kale E. (2020) Laboratory tests used in the diagnosis of immune thrombocytopenia and general treatment approaches. J Hematal Oncol Res. 2020;3(4):22-36. doi:10.14302/issn.2372-6601.jhor-20-3372 
  4. Justiz Vaillant AA, Gupta N. ITP-immune thrombocytopenic purpura. StatPearls [Internet]. Updated July 8, 2022. Accessed October 16, 2022.
  5. Kessler CM. Immune thrombocytopenia (ITP) workup. Medscape. Updated January 7, 2021. Accessed October 12, 2022. 
  6. Kelton JG, Vrbensky JR, Arnold DM. How do we diagnose immune thrombocytopenia in 2018? Hematology Am Soc Hematol Educ Program. 2018;30;2018(1):561-567. doi:10.1182/asheducation-2018.1.561

Reviewed by Kyle Habet, MD, on 10/27/2022.