<h2><span style="color:#932c87;">More treatment options are needed for patients with ITP<sup>1</sup>,</span></h2>
<p>Current treatment goals in ITP are to stop active bleeding and reduce the risk of further bleeding. Response rates for ITP treatments vary widely from 18% to 80% as measured by improved platelet counts. Some currently available treatments may also be associated with unfavorable side effect profiles and dosing regimens or offer a limited duration of response.</p>

US, patient with ITP

Tracey,

MD, Director of Clinical Hematology at Massachusetts General Hospital

David Kuter,

<table border="1" cellpadding="1" cellspacing="1" style="width:100%;">
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   <td style="background-color: rgb(147, 44, 135);">
    <h3><span style="color:#ffffff;">Ongoing research aims to better address the multiple dimensions of ITP by targeting the underlying pathology of the disease.<sup>3,4</sup></span></h3></td>
  </tr>
 </tbody>
</table>

<h2>The following investigational agents aim to address the underlying pathology of ITP<sup>3,4</sup>:</h2>

<p style="text-align: center;"><strong>Bruton’s tyrosine kinase (BTK) inhibitors,</strong><br>
  which inhibit macrophage phagocytosis leading to a decrease in platelet destruction, prevent the production of autoantibodies, and may inhibit inflammation</p>

<p style="text-align: center;"><strong>Neonatal Fc receptor (FcRn) blockers,</strong><br>
  which increase platelet antibody clearance, leading to a decrease in peripheral platelet destruction and immune response</p>

<p style="text-align: center;"><strong>Recombinant immunoglobulin multimers,</strong><br>
  which decrease platelet destruction and increase antiplatelet antibody clearance</p>

<p style="text-align: center;"><strong>Complement inhibitors,</strong><br>
  which decrease complement-dependent cytotoxicity</p>

<p style="text-align: center;"><strong>Plasma cell-depleting therapies,</strong><br>
  which decrease antiplatelet antibodies</p>

<p style="text-align: center;"><strong>B cell activating factor (BAFF) inhibitors,</strong><br>
  which reduce B cell survival and consequently decrease antiplatelet antibodies</p>

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   <td style="background-color: rgb(147, 44, 135);">
    <h3><span style="color:#ffffff;">The clinical significance of these mechanisms is currently under investigation.</span></h3></td>
  </tr>
 </tbody>
</table>

References

Future of ITP

IMMUNE-THROMBOCYTOPENIC-ITP

HEMATOLOGY

<h2><span style="color:#932c87;">ITP is characterized by low platelet counts and symptoms like bleeding and bruising<sup>1</sup></span></h2>
<p>ITP is an acquired autoimmune disorder characterized by low platelet counts that result from both increased platelet destruction and/or impaired platelet production.<sup>2-4</sup></p>

<p>The time since diagnosis helps classify ITP as newly diagnosed, persistent, or chronic.<sup>5</sup></p>

<p style="text-align: center;"><strong>Multiple symptoms of ITP are related to bleeding and can include<sup>6-10</sup>:</strong></p>

<p>Petechiae and purpura, usually on the extremities</p>

<p style="text-align: center;"><strong>In some studies, severe bleeding occurred in approximately 7% to 10% of adult patients and typically correlated with lower platelet counts.<sup>11,12*</sup></strong></p>
<p data-font="legal"><sup>*</sup>As seen in a cross-sectional study of 302 French patients, as well as in a systematic review of 147 clinical studies of adults and children with primary ITP.<sup>11,12</sup></p>

<p>While platelet counts below 100,000/μL can indicate ITP, the lack of a specific diagnostic test means other potential causes of thrombocytopenia must be ruled out.<sup>2</sup></p>
<p>It is also important to determine if ITP is primary or secondary to another condition. There are multiple causes of secondary ITP, including chronic lymphocytic leukemia (CLL),&nbsp;<em>Helicobacter pylori&nbsp;</em>infection, and COVID-19 infection.<sup>2,14</sup></p>
<p>ITP can occur in people of all ages. The incidence of ITP ranges from 2 to 4 cases per 100,000 person-years in adults and children.<sup>2,15</sup></p>
<p>The prevalence of ITP is estimated to be 58 per 100,000 adults and between 4.1 and 9.3 per 100,000 children (ages 1 to 18 years).<sup>16,17</sup></p>

<h2><span style="color:#932c87;">The pathophysiology of ITP is complex and not fully understood<sup>2</sup></span></h2>

<p>In ITP, autoreactive B cells produce autoantibodies that target platelets for destruction by macrophages and impair megakaryocyte maturation, which then inhibits platelet production. Autoantibodies may also destroy platelets through other mechanisms. Cytotoxic T cells can also directly destroy or inhibit the production of platelets.<sup>2</sup></p>

<p><span style="color:#932c87;"><strong>Watch the mechanism of disease video to learn more about the underlying sources of ITP</strong></span></p>

<h2>Bruton’s tyrosine kinase (BTK) drives key processes in B cells and macrophages<sup>19,20</sup></h2>
<p>B cells are critical to autoantibody production and macrophages are critical to phagocytosis. Both of these processes are regulated by BTK.</p>

<ul>
 <li><strong>In B cells:</strong>&nbsp;The BTK pathway is crucial for proliferation, differentiation, and autoantibody production</li>
 <li><strong>In macrophages:</strong>&nbsp;Various signaling pathways dependent on BTK drive phagocytosis, degranulation, and the production of inflammatory cytokines</li>
</ul>

<h4><strong>BTK is also a critical driver of inflammation<sup>20</sup></strong></h4>
<p><strong>BTK plays a key role in the production or activation of these inflammatory markers:</strong></p>
<ul>
 <li>TNF-α</li>
 <li>IL-6</li>
 <li>NLRP3 inflammasome</li>
 <li>IFN-γ</li>
</ul>

<h2 style="text-align: center;"><span style="color:#932c87;">Next: ITP is about more than platelets</span></h2>
<p style="text-align: center;"><strong>Learn how ITP symptoms like fatigue and cognitive impairment impact patients’ quality of life.</strong></p>

What is ITP?

<p><strong>Platelets are one side of ITP, but when we look at it from another angle, we see the</strong></p>

<h3><span style="color:#932c87;">multiple dimensions of ITP</span></h3>
<p>Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by low platelet counts that can result in easy bruising and mucosal bleeding. Beyond platelet counts, ITP can significantly affect quality of life through symptoms such as fatigue and anxiety. Patients might also experience cognitive impairment, cerebral microbleeds, and thrombotic events.<sup>1-5</sup></p>

Understanding ITP

<h2><span style="color:#932c87;">Platelets are only one dimension of ITP<sup>1-3</sup></span></h2>
<p>ITP is a complex disease with potential ramifications beyond low platelet counts and the associated bleeding symptoms—including inflammation and its potential effects, and impacts on quality of life (QOL).</p>
<h4><strong>Ongoing research continues to support the presence of inflammation in patients with ITP<sup>3</sup></strong></h4>
<p><strong>Systemic inflammation in ITP is suggested by the presence of elevated inflammatory markers, including<sup>4-6</sup>:</strong></p>
<ul>
 <li>TNF-α</li>
 <li>IL-6</li>
 <li>NLRP3 inflammasome</li>
 <li>IFN-γ</li>
</ul>

<h2><span style="color:#932c87;">ITP affects the whole patient, not just their platelets<sup>1,7,8</sup></span></h2>
<p>In the Immune Thrombocytopenia World Impact Survey (I-WISh)* of 1507 patients with ITP and 472 HCPs:</p>

<p>ITP symptoms that impact QOL include fatigue, cognitive difficulties, and anxiety.</p>

<div>
 &nbsp;
</div>
<div>
 &nbsp;
</div>
<div>
 &nbsp;
</div>
<div>
 &nbsp;
</div>
<div>
 <h3>ITP has well-documented effects on patients’ QOL</h3>
</div>

black

<p data-font="legal"><sup>*</sup>I-WISh was an online, cross-sectional survey of patients with ITP and hematologists or hemato-oncologists who treat patients with ITP in 13 countries. The patient questionnaire collected information on demographics and diagnosis, symptoms of ITP, health-related quality of life (HRQOL) and emotion associated with ITP, impact of ITP on work, finances, and support, treatment received, and patient and physician relationship. The physician survey comprised 6 sections that collected information on demographics, diagnosis of ITP and patient caseload, symptoms of ITP, impact of ITP on aspects of patients’ physical, emotional, HRQOL, social health, treatment patterns, and patient and physician relationship. There were 2 questions about the emotional impact of ITP and the responses were based on a 7-point Likert scale (1 = never, 7 = a great deal). There was 1 additional question on the need for professional support.<sup>1</sup></p>
<h2><span style="color:#932c87;">Fatigue can be a major burden for patients with ITP<sup>9</sup></span></h2>

Laura,

<p>In I-WISh, 1507 patients rated functional, psychological, and emotional aspects of their condition on a 7-point Likert scale, with a score of 5-7 indicating the greatest impact. In the survey<sup>1,9</sup>:</p>

<h3>reported fatigue at diagnosis (n=870/1507).<sup>9</sup>&nbsp;Of those,</h3>

<h3>rated that fatigue as severe (n=637/870)<sup>9</sup></h3>

<h3><span style="color:#932c87;">But HCPs may not perceive patients’ fatigue at the same levels<sup>9</sup></span></h3>
<h3>Of the HCPs surveyed in I-WISh:</h3>

<h3>reported hearing about fatigue at diagnosis (n=472) and rated<sup>9</sup></h3>

<h3>of that fatigue as severe (n=465)<sup>9</sup></h3>

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   <td style="background-color: rgb(147, 44, 135);">
    <h3><span style="color:#ffffff;">In the same survey, fatigue did not appear to be correlated with platelet counts.<sup>9</sup></span></h3></td>
  </tr>
 </tbody>
</table>

<h2><span style="color:#932c87;">Patients with ITP might also suffer from cerebral microbleeds (CMBs) and cognitive impairment<sup>10,11</sup></span></h2>
<h3>In a 2020 study in Blood,<sup>†</sup></h3>

<h2>&nbsp;</h2>
<h2>&nbsp;</h2>
<h2>&nbsp;</h2>
<h2>&nbsp;</h2>
<h2>of patients with ITP had CMBs (n=21/49)<sup>10</sup></h2>

<p data-font="legal"><sup>†</sup>A cross-sectional prospective study of 49 patients with ITP and nadir platelet counts &lt;30,000/μL and 18 age-matched healthy controls that used susceptibility-weighted magnetic resonance imaging (MRI) to detect CMBs as a marker of occult hemorrhage.<sup>10</sup></p>
<p>Based on these preliminary data, CMBs were associated with lower platelet count and longer disease duration. The strong association between CMBs and ITP duration could indicate that CMBs may accumulate over time.<sup>10</sup></p>
<h3>In a 2022 study in Blood,<sup>‡</sup></h3>

<h2>&nbsp;</h2>
<h2>&nbsp;</h2>
<h2>&nbsp;</h2>
<h2>&nbsp;</h2>
<h2>of patients with ITP experienced some level of cognitive impairment (N=69)<sup>11</sup></h2>

<p data-font="legal"><sup>‡&nbsp;</sup>A total of 69 patients completed the Cambridge Neuropsychological Test Automated Battery (CANTAB) to assess episodic memory, executive function, processing speed, working memory, and attention.<sup>11</sup></p>
<p>Many patients with ITP exhibit impairments in attentional function at least as severe as those observed in patients of similar age with mild traumatic brain injury, chronic fatigue syndrome, or moderate-severe depressive disorder.<sup>12</sup></p>
<p>&nbsp;</p>
<h2><span style="color:#932c87;">Patients are worried about their ITP<sup>1</sup></span></h2>

<p data-font="legal"><sup>§</sup>&nbsp;A limited number of population-based studies have reported that the rate of death among patients with ITP is comparable to the general population in patients younger than age 60. Mortality is higher than the general population in older patients and patients with comorbidities.<sup>13,14</sup></p>

<table border="1" cellpadding="1" cellspacing="1" style="width:100%;">
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   <td style="background-color: rgb(147, 44, 135);">
    <h3><span style="color:#ffffff;">Ask your patients with ITP about fatigue, cognitive impairment, and anxiety.</span></h3></td>
  </tr>
 </tbody>
</table>

<h2 style="text-align: center;"><span style="color:#932c87;">Next: Future of ITP</span></h2>
<p style="text-align: center;"><strong>There is an unmet need for ITP treatments that deliver rapid and durable improvements in platelet counts, bleeding symptoms, and patient QOL.<sup>15,16</sup></strong></p>

Living With ITP

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Immune Thrombocytopenic (ITP)

Latest Articles

Future of ITP

What is ITP?

Understanding ITP

Living With ITP