What is recurrent Acute Thrombocytopenic Purpura Disorder (ATPD) in a patient with a history of low platelet count and autoimmune disorders?

What is Recurrent ATPD?

The term "ATPD" (Acute Thrombocytopenic Purpura Disorder) is not standard medical terminology; the correct term is ITP (Immune Thrombocytopenic Purpura), and "recurrent" refers to patients who relapse after achieving initial response to treatment.

Definition and Pathophysiology

Recurrent ITP describes patients who initially respond to treatment (typically corticosteroids or splenectomy) but subsequently experience a return of thrombocytopenia weeks, months, or years later. 1, 2

• ITP is an autoimmune disorder where the immune system produces antibodies and cytotoxic T cells against platelet surface proteins, causing both increased platelet destruction and impaired platelet production 3, 4
• The condition involves immunologically mediated destruction of platelets in the absence of other identifiable causes of thrombocytopenia 5
• Approximately 20% of ITP patients who initially respond to splenectomy will relapse weeks, months, or years later 2

Classification by Duration

ITP is classified into three temporal categories 6:

• Newly diagnosed: Initial presentation
• Persistent: Duration of 3-12 months 1, 6
• Chronic: Duration ≥12 months 1, 6

Clinical Presentation of Recurrent Disease

When patients relapse, they typically present with 1:

• Bleeding symptoms: Bruising, petechiae, mucosal bleeding (epistaxis, gingival bleeding) 6, 7
• Severe manifestations: Gastrointestinal hemorrhage, hematuria, menorrhagia 6, 7
• Life-threatening complications: Intracranial hemorrhage (rare but serious, occurring in 1.4% of adults) 6
• Platelet counts: Typically <30 × 10⁹/L, often <10 × 10⁹/L in symptomatic patients 1

Evaluation of Recurrent Disease

In patients who relapse after initial splenectomy response, assessment for accessory splenic tissue should be considered, as accessory spleens are found in up to 12% of splenectomized ITP patients. 2

Critical Distinction:

• Relapsers (initial response then recurrence): Should be evaluated for accessory spleen 2
• Non-responders (never responded initially): Searching for accessory spleens is futile as response is extremely rare 2

Exclude Secondary Causes 3:

Essential screening includes:

• HIV testing (HIV triggers ITP via cross-reactive antibodies and impaired platelet production) 3
• Hepatitis C testing (HCV causes thrombocytopenia through multiple pathways including antibody cross-reaction) 3
• Immunoglobulin measurement to exclude common variable immune deficiency 3
• Medication review (quinidine, heparin, sulfonamides, sulfonylureas) 1

Red Flags Suggesting Secondary ITP 3:

• Splenomegaly, hepatomegaly, or lymphadenopathy 3
• Constitutional symptoms (fever, weight loss, bone pain) 3
• Abnormal hemoglobin, white blood cell count, or white cell morphology 3
• Non-petechial rash 3

Management of Recurrent Disease

For patients unresponsive to or relapsing after initial corticosteroid therapy, splenectomy remains the only treatment providing sustained remission off all treatments at 1 year and beyond in a high proportion of patients. 1

Treatment Algorithm for Recurrent ITP:

First-line re-treatment 1:

• Corticosteroids (prednisone is indicated for idiopathic thrombocytopenic purpura in adults) 8
• IVIg (1 g/kg as one-time dose, may be repeated) 1
• Anti-D immunoglobulin (for Rh(D)-positive patients) 1

Second-line options for refractory/recurrent disease 1:

• Rituximab: Pooled response rate of 62.5% in 313 patients, but long-term sustained remission rates disappointing (18-35% at >1 year) 1
• Thrombopoietin receptor agonists (eltrombopag): Sustained platelet response achieved in 60% of patients treated for 26 weeks versus 10% with placebo 9
• Splenectomy (if not previously performed): Most effective single treatment with highest sustained remission rates 1, 4

Treatment Thresholds 1:

• Platelet count <20,000: Treatment inappropriate to withhold regardless of symptoms 1
• Platelet count <50,000 with significant mucous membrane bleeding: Treatment mandatory 1
• Platelet count >10,000: Spontaneous serious bleeding rare (<5% of patients) 1

Prognosis and Mortality

Adults with ITP have a 1.3- to 2.2-fold higher mortality than the general population due to cardiovascular disease, infection, and bleeding. 3, 6

• Adult ITP is more likely to become chronic with lower spontaneous remission rates compared to children 6
• Children have high spontaneous remission rates (74% in children <1 year, 67% in ages 1-6 years, 62% in ages 10-20 years) 6
• Splenectomy achieves complete response in 88% of patients with appropriate selection 7