Immune Thrombocytopenia (ITP)


Immune thrombocytopenia (ITP), formerly known as idiopathic thrombocytopenia purpura, is a hematologic syndrome in which the immune system produces autoantibodies to antigens on the surface of platelet membranes. The autoantibodies target the antigens, covering the platelet surface. Macrophages then target the affected platelets, which eventually undergo phagocytosis. The premature death of affected platelets, combined with the inability of the bone marrow to replace the platelets rapidly, decreases the number of functional circulating platelets, causing several notable signs and symptoms.1

Signs and Symptoms

ITP affects the ability of blood to clot, resulting in manifestations that reflect an increased tendency to bleed. These include the following: 

Thrombocytopenia, the primary sign of ITP,  is characterized by circulating platelet levels lower than 100,000/µL. Normal platelet counts usually range from 150,000 to 450,000/µL. Typically, lower platelet counts increase the risk for bleeding.2 

Purpura or ecchymoses, also known as dry purpura, are large, purplish bruises or areas of discoloration visible on the skin. Bruising indicates that blood has leaked from blood vessels and has collected underneath the surface of the skin. Bruises commonly develop near joints as a consequence of frequent movement.2-4 Patients with ITP bruise easily, and episodes of bleeding are difficult to control.3 

Petechiae are tiny, pinpoint red or purple dots caused by small amounts of bleeding from broken capillaries under the skin. The dots may look like a rash; however, rashes blanch when pressure is applied, whereas petechiae do not.3 These microvascular hemorrhages often occur on dependent regions of the body, such as the hands and feet,4 but also may form on the eyelids, mouth, arms, legs, buttocks, and stomach.5 They may also develop in areas of the body subjected to prolonged pressure, such as the back of a patient who is bedridden.1

Mucosal bleeding, also known as wet purpura, is associated with systemic bleeding. Epistaxis (nosebleeds), gingival bleeding during dental procedures, blood blisters in the mouth, and gastrointestinal bleeding occur more frequently in people with ITP.3,4,6

Fatigue may result from a loss of blood during frequent episodes of bleeding or bleeding that is difficult to control.3 

Intracranial hemorrhage, although very rare, is a serious complication in patients with a diagnosis of ITP. Often the result of a head injury, it occurs in 0.5% to 1% of children and 1.5% of adults with ITP.1,2,7 Approximately half of pediatric cases are fatal.1 The likelihood of intracranial hemorrhage increases when the platelet count drops to below 10×109/L.1 Symptoms of intracranial hemorrhage include severe headache, blurry vision, loss of consciousness, difficulty staying awake, hypertension along with bradycardia, and retinal hemorrhage.1,3

Other manifestations of ITP include heavy menstrual bleeding, hematuria, hematemesis, and, depending on the location of gastrointestinal bleeding, very dark, tarry stools (melena) or bright red stools (hematochezia).2-4

Read more about ITP diagnosis

Asymptomatic Patients

In general, a decreased platelet count correlates with an increased risk for bleeding; however, many patients with ITP remain asymptomatic despite their low platelet counts.7,8 One study of 245 adults with a diagnosis of ITP reported that 28% of them were asymptomatic despite low platelet counts.9

Read more about ITP clinical trials

Age Affects the Clinical Manifestations of ITP

The clinical manifestations of ITP vary with age. Older patients experience more severe or rare manifestations of bleeding, including gastrointestinal bleeding and intracranial hemorrhage, which may be secondary to comorbidities such as hypertension or disorders that increase risk for falling and therefore risk for head trauma.10 Bleeding complications are more severe when the platelet levels drop below 10,000/µL.2,7,10

Read more about ITP comorbidities

Thrombotic Events

Although ITP is commonly associated with an increased risk for bleeding, paradoxically, patients with ITP are also at greater risk for thromboembolic events. Although the mechanism of action for the increase in thrombotic events is unknown, scientists have proposed that antiphospholipid antibodies may predispose patients with ITP to thrombosis; however, further studies are needed to confirm this hypothesis.4

One study confirmed that patients with primary ITP demonstrate an increased incidence of venous (adjusted hazard ratio [aHR], 1.58; 95% CI, 1.01-2.48), arterial (aHR, 1.37; 95% CI, 0.94-2.00), and combined (both arterial and venous; aHR, 1.41; 95% CI, 1.04-1.91) thromboembolic events in comparison with the general population.11

Read more about ITP complications

References

  1. Kessler CM. Immune thrombocytopenia (ITP): practice essentials. Medscape. Updated January 7, 2021.  Accessed October 6, 2022.
  2. Idiopathic thrombocytopenic purpura. Johns Hopkins Medicine. Accessed October 6, 2022.
  3. Immune thrombocytopenia. Cleveland Clinic. Accessed October 6, 2022.
  4. McCrae K. Immune thrombocytopenia: no longer ‘idiopathic.’ Cleve Clin J Med. 2011;78(6):358-373. doi:10.3949/ccjm.78gr.10005
  5. Petechiae. Cleveland Clinic. Accessed October 6, 2022.
  6. Immune thrombocytopenia. Seattle Children’s Hospital. Accessed October 6, 2022.
  7. Arnold DM. Bleeding complications in immune thrombocytopenia. Hematology. 2015;2015(1):237-242. doi:10.1182/asheducation-2015.1.237
  8. Immune thrombocytopenia (ITP). Mayo Clinic. Accessed October 6, 2022.
  9. Neylon AJ, Saunders PWG, Howard MR, Proctor SJ, Taylor PRA, Northern Region Haematology Group. Clinically significant newly presenting autoimmune thrombocytopenic purpura in adults: a prospective study of a population-based cohort of 245 patients. Br J Haematol. 2003;122(6):966-974. doi:10.1046/j.1365-2141.2003.04547.x
  10. Kayal L, Jayachandran S, Singh K. Idiopathic thrombocytopenic purpura. Contemp Clin Dent. 2014;5(3):410-414. doi:10.4103/0976-237X.137976
  11. Sarpatwari A, Bennett D, Logie JW, et al. Thromboembolic events among adult patients with primary immune thrombocytopenia in the United Kingdom General Practice Research Database. Haematologica. 2010;95(7):1167-1175. doi:10.3324/haematol.2009.018390

Reviewed by Harshi Dhingra, MD, on 10/13/2022.

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