Immune Thrombocytopenia (ITP)


Immune thrombocytopenia (ITP) is associated with several types of comorbidities, including hematologic malignancies, vascular thromboembolic events, infections, dermatological conditions, constitutional conditions, organ problems, autoimmune conditions, and comorbidities related to ITP-induced bleeding events.1,2 Patients with chronic ITP who are older than 60 often have multiple age-related comorbidities along with ITP.3,4 

Hematologic Malignancies

Hematologic malignancies such as leukemia (adjusted incidence rate ratio [aIRR], 19.83; 95% CI, 5.84-67.34) and lymphoma (aIRR, 5.91; 95% CI, 2.61-13.37) are 3 times more likely to develop in patients with chronic ITP than in people who do not have ITP.1,3 However, some hematologic malignancies (eg, myelodysplastic syndrome and lymphoma), solid tumors, chemotherapy, and allogeneic stem cell transplant may contribute to secondary ITP. Approximately 2% to 5% of patients with chronic lymphocytic leukemia acquire secondary ITP.3

Thromboembolic Events

It seems paradoxical that rates of thromboembolic events are higher in patients with ITP, a condition characterized by bleeding due to low platelet counts and a decreased ability of the blood to form clots, than in the general population. However, many treatments for ITP, including splenectomy and thrombopoietin-receptor agonists (TPO-RAs), are associated with increased rates of thromboembolic events.5

Patients with ITP who undergo splenectomy are at higher risk for abdominal venous thromboembolism (AbVTE), venous thromboembolism (VTE), and sepsis.6 

In some cases, patient age and other personal risk factors, in addition to splenectomy, also correlate with a risk for both venous and arterial thrombosis 3 to 4 times greater than that of the general population.5 Indirect evidence also points to increased risk with TPO-RA usage, including a probability of venous and arterial thrombosis that is 3 to 4 times greater in patients treated with TPO-RAs than in those who are not exposed to TPO-RAs. Even if patients with ITP are not treated with TPO-RAs, their risk for venous thrombosis is 2 times greater than that of the general population.5

Read more about ITP treatment

Infection

Bacterial and viral infections, especially in children, can trigger the onset of ITP by activating the immune system to produce anti-platelet autoantibodies. In children, ITP often follows an infection with influenza or mumps.7 In adults, secondary ITP may be triggered by infection with human immunodeficiency virus, hepatitis B or C virus, Epstein-Barr virus, cytomegalovirus, or Helicobacter pylori.3,7 In addition, the risk for infection in patients with persistent ITP who undergo splenectomy is increased after removal of the spleen, which is involved in immune system function.3 

Read more about ITP surgical management

Dermatological Conditions

ITP is associated with purpura, the purple-red skin lesions caused by bleeding. Purpura is frequently the initial presenting symptom of ITP, although not in all cases.8 Other dermatological conditions associated with ITP include leg ulcers, rashes, exfoliation, eczema, stasis dermatitis, decubitus ulcers, pressure sores, folliculitis, tinea, and infected sebaceous cysts.2 

Read more about ITP signs and symptoms

Constitutional Conditions

Constitutional comorbidities associated with ITP include chills, rigors, malaise, and lethargy. It has been suggested that the pathogenetic pathways of these conditions are similar to those of ITP or predispose patients to ITP.2

Organ Inflammation and Failure

Researchers have found direct correlations between both chronic renal failure1,2 and ITP and pancreatitis9 and ITP. Patients with concurrent autoimmune pancreatitis have increased IgG4 levels that can target platelet glycoprotein (GP) IIb/IIIa in ITP patients and induce the formation of platelet-derived microparticles leading to ischemic changes in terminal organs including the pancreas, leading to pancreatitis.9 

Read more about ITP complications

Autoimmune Conditions

People with other autoimmune conditions, such as rheumatoid arthritis, lupus, and antiphospholipid syndrome, are at increased risk for the development of comorbid ITP.7 Sjögren syndrome and autoimmune thyroiditis also may trigger the onset of ITP.3 

Read more about ITP diagnosis

Platelet autoantibodies can bind to the receptors of the platelet membrane and interfere with the aggregation and adhesion of the platelets.3 The decreased number of functional, circulating platelets in ITP contributes to an increased risk for episodes of mucocutaneous bleeding. Bleeding-related comorbidities associated with ITP include ecchymoses, hemoptysis, hematuria, epistaxis, hematemesis, menorrhagia, and rectal and conjunctival hemorrhage.2 

Similar antibodies can also bind to the glycoprotein (GP) IIb/IIIa receptors and cause acquired Glanzmann’s thrombasthenia in patients with ITP.3

Platelet levels lower than 10,000/µL correlate with more serious and potentially life-threatening comorbidities, such as gastrointestinal or intracranial hemorrhage.10

Read more about ITP risk factors

In approximately two-thirds of patients with ITP who are older than 60 years, age-related comorbidities develop that include hypertension, diabetes, cardiovascular disease, pneumonia, cataracts, neuropsychiatric disease, and anemia.3 Specifically, the incidence of atrial fibrillation, cerebrovascular disease (stroke and transient ischemic attack), myocardial infarction, coronary artery disease, and venous thromboembolism increases with age in patients who have ITP.4 Most of these comorbidities correlate with increasing patient age rather than directly with ITP.3 

When researchers compared the comorbidities of 3131 patients with ITP vs those of 9392 people without ITP, they noted that the rates of diabetes (aIRR, 1.73; 95% CI, 1.36-2.20) and vascular events (aIRR, 1.70; 95% CI, 1.41-2.05) were higher among the patients with ITP.1 

Read more about ITP prognosis

References

  1. Enger C, Bennett D, Forssen U, Fogarty PF, McAfee AT. Comorbidities in patients with persistent or chronic immune thrombocytopenia. Int J Hematol. 2010;92(2):289-295. doi:10.1007/s12185-010-0636-3
  2. Feudjo-Tepie MA, Le Roux G, Beach KJ, Bennett D, Robinson NJ. Comorbidities of idiopathic thrombocytopenic purpura: a population-based study. Adv Hematol. 2009;2009:e963506. doi:10.1155/2009/963506
  3. Matzdorff A, Meyer O, Ostermann H, et al. Immune thrombocytopenia – current diagnostics and therapy: recommendations of a Joint Working Group of DGHO, ÖGHO, SGH, GPOH, and DGTI. Oncol Res Treat. 2018;41(Suppl 5):1-30. doi:10.1159/000492187
  4. Matzdorff A, Beer JH. Immune thrombocytopenia patients requiring anticoagulation—maneuvering between Scylla and Charybdis. Semin Hematol. 2013;50:S83-S88. doi:10.1053/j.seminhematol.2013.03.020
  5. Rodeghiero F. ITP and thrombosis: an intriguing association. Blood Adv. 2017;1(24):2280. doi:10.1182/bloodadvances.2017007989
  6. Boyle S, White RH, Brunson A, Wun T. Splenectomy and the incidence of venous thromboembolism and sepsis in patients with immune thrombocytopenia. Blood. 2013;121(23):4782-4790. doi:10.1182/blood-2012-12-467068
  7. Immune thrombocytopenia (ITP). Mayo Clinic. Accessed October 28, 2022.
  8. McCrae K. Immune thrombocytopenia: no longer ‘idiopathic.’  Cleve Clin J Med. 2011;78(6):358-373. doi:10.3949/ccjm.78gr.10005
  9. Wu SC, Lin SF, Fang CW, Tsai IJ, Yang WC. Immune thrombocytopenic purpura increased risk of subsequent pancreatitis: a nationwide population cohort study. Sci Rep. 2019;9(1):16923. doi:10.1038/s41598-019-53165-7
  10. Arnold DM. Bleeding complications in immune thrombocytopenia. Hematology. 2015;2015(1):237-242. doi:10.1182/asheducation-2015.1.237

Reviewed by Debjyoti Talukdar, MD, on 10/31/2022.