Primary Immune Thrombocytopenia (ITP)

Vocabulary practice flashcards covering definition, diagnostic criteria, classification phases, response criteria, pathophysiology, clinical grading, diagnostic workup, and treatment algorithms for Primary Immune Thrombocytopenia (ITP).

Primary Immune Thrombocytopenia (Primary ITP)

An acquired autoimmune disease characterized by isolated thrombocytopenia ($< 100 \times 10^9/\text{L}$ or $< 100\times 10^3/\text{L}$) with accelerated destruction and inadequate production of platelets, without other conditions to explain it; it is a diagnosis of exclusion that increases bleeding risk.

Secondary ITP

All forms of thrombocytopenia caused by an immune mechanism, excluding primary ITP.

Severe ITP

A presentation characterized by significant hemorrhage that mandates the initiation or modification of therapeutic treatment.

Newly Diagnosed ITP

The clinical phase of immune thrombocytopenia defined by a disease duration of $< 3\text{ months}$ from initial diagnosis.

Persistent ITP

The clinical phase of immune thrombocytopenia defined by a disease evolution between $3\text{ and }12\text{ months}$, during which spontaneous remissions may still occur.

Chronic ITP

The clinical phase of immune thrombocytopenia defined by a disease duration exceeding $> 12\text{ months}$.

Complete Remission (CR) in ITP

Achievement of a platelet count $> 100 \times 10^9/\text{L}$ accompanied by the complete absence of hemorrhage.

Response (R) in ITP

Achievement of a platelet count $\ge 30 \times 10^9/\text{L}$, representing an increase of more than two times baseline, and the absence of hemorrhage.

Non-Response (NR) in ITP

A platelet count $< 30 \times 10^9/\text{L}$, an increase of less than two times baseline, or the presence of hemorrhagic symptoms.

Loss of Response in ITP

A decline in platelets to $< 100 \times 10^9/\text{L}$ or hemorrhage if previously in CR; or platelets $< 30 \times 10^9/\text{L}$, less than double the baseline, or hemorrhage if previously achieving R.

Corticosteroid Dependence (Corticodependencia)

The ongoing need for repeated or maintained doses of glucocorticoids to sustain platelet levels $\ge 30 \times 10^9/\text{L}$ and/or prevent bleeding.

Refractory ITP

The failure to achieve a response or the loss of response following splenectomy, necessitating ongoing therapy to minimize bleeding risk.

Pathophysiological Cycle of Platelet Destruction

A four-step cycle: 1. Sensitization (platelet coated with anti-GP IIb/IIIa, Ib/IX antibodies), 2. Uptake (macrophage recognizes platelet via receptor $\text{Fc}\gamma$), 3. Phagocytosis (macrophage destroys platelet and presents GP antigens to CD4+ T cells via CD154/CD40), and 4. Amplification (activated T cells stimulate B cells via interleukin-2 to produce more anti-GP antibodies).

Cytotoxic CD8+ T Lymphocytes in ITP

Immune effector cells that mediate platelet cytotoxicity and directly target bone marrow megakaryocytes to inhibit platelet synthesis.

Epidemiology of Pediatric ITP

One of the most frequent causes of symptomatic thrombocytopenia in children, with an annual incidence of $1\text{ to }6.4\text{ per }100\,000\text{ children}$, a major peak at $2\text{--}5\text{ years}$, a minor peak in adolescence, and a slight male predominance in infants.

Differential Diagnosis: Non-Immune Thrombocytopenias

Disorders to rule out before diagnosing ITP, including congenital forms (Bernard-Soulier syndrome, type IIb von Willebrand disease, MYH9-related disease), bone marrow disorders (myelodysplastic syndromes, leukemias, aplastic anemia), thrombotic microangiopathies (TTP), chronic liver disease, and drug/toxin/alcohol ingestion.

Differential Diagnosis: Immune Secondary Thrombocytopenias

Immune conditions to exclude, such as post-transfusion purpura, alloimmune thrombocytopenia, drug-induced immune thrombocytopenia, recent vaccinations, viral infections (HIV, HCV), autoimmune disorders (lupus erythematosus, antiphospholipid syndrome), immunodeficiencies (CVID, ALPS), post-transplant, and lymphoproliferative disorders (CLL, NHL, HL).

Clinical Bleeding Severity Grades in Children

Classification according to Provan et al.: Grade I (Minor/minimal: $\le 100$ petechiae, $\le 5$ hematomas $\le 3\text{ cm}$), Grade II (Mild: $> 100$ petechiae, $> 5$ large hematomas $> 3\text{ cm}$), Grade III (Moderate: mucosal bleeding not requiring immediate medical care), Grade IV (Severe: mucosal or internal bleeding requiring immediate care), and Grade IV (Life-threatening: documented intracranial hemorrhage or potentially fatal hemorrhage).

Wet Purpura («Púrpura húmeda»)

Mucosal hemorrhage (e.g., brief epistaxis, intermittent gingival bleeding, menorrhagia) that qualifies as Grade III moderate bleeding when it does not require immediate emergency intervention.

Indications for Bone Marrow Aspiration in Children

Indicated strictly in pediatric patients with atypical clinical features, other cytopenias on CBC, lack of response to first-line therapy, or lack of spontaneous remission in untreated individuals.

Peripheral Blood Smear Deviations in Thrombocytopenia

Morphological clues suggesting alternate etiologies: giant platelets indicate MYH9-related disease; very small platelets indicate Wiskott-Aldrich syndrome; and schistocytes indicate microangiopathic hemolytic processes.

Direct Antiglobulin Test (Direct Coombs) in Typical ITP

A test that is characteristically negative in typical ITP; a positive result in a patient with ongoing hemolysis suggests autoimmune hemolytic anemia (Evans syndrome), provided IVIG or anti-D was not administered within the previous $2\text{ weeks}$.

Watchful Waiting (Conducta expectante)

Conservative management without pharmacological treatment indicated for patients with platelets $> 20 \times 10^9/\text{L}$ who are asymptomatic or exhibit only minimal cutaneous bleeding.

First-Line Glucocorticoid Therapy

Initial treatment of choice for ITP using oral prednisone ($1\text{ mg/kg/day}$ or $4\text{ mg/kg/day} \times 4\text{ days}$) or dexamethasone ($40\text{ mg/day} \times 4\text{ days}$, or $20\text{--}40\text{ mg/m}^2/\text{day} \times 4\text{ days}$); it produces a response within $3\text{--}5\text{ days}$ but carries a high frequency of rapid relapse.

Intravenous Immunoglobulin (IVIG / IgIV)

A first-line emergency therapy ($1\text{ g/kg/day} \times 2\text{ days}$ or $0.8\text{ g/kg/day} \times 1\text{ day}$) that blocks macrophage Fc receptors, achieving rapid responses in $24\text{--}48\text{ hours}$ in $90\text{--}95\%$ of patients, lasting $15\text{--}20\text{ days}$; reserved for severe bleeding.

Intravenous Anti-D Immunoglobulin (IgG anti-D)

A single-dose IV treatment ($50\text{--}75\,\mu\text{g/kg}$) reserved exclusively for Rh-positive patients that blocks macrophage Fc receptors, yielding an $80\%$ response rate within $4\text{--}5\text{ days}$ while predictably causing hemolysis with a hemoglobin decrease of $0.5\text{--}2\text{ g/dL}$.

Rituximab in Chronic ITP

A second-line anti-CD20 therapy ($375\text{ mg/m}^2/\text{week} \times 4\text{ weeks}$) acting on B-T cell interactions, providing an initial response rate of $40\text{--}50\%$ and a long-term sustained response rate of $25\%$ at $\ge 2\text{ years}$, with potential complications including serum sickness in up to $10\%$ of children.

Thrombopoietin Receptor Agonists (TPO-RAs)

Second-line agents (eltrombopag and romiplostim) that stimulate platelet production, achieving an initial response of $\approx 80\%$ without causing immunosuppression; their therapeutic effect persists only as long as administration continues and they generally do not induce cure.

Eltrombopag Dosing

An oral once-daily TPO-RA initiated at $25\text{ mg/day}$ for children aged $1\text{--}5\text{ years}$, $50\text{ mg/day}$ for children aged $6\text{--}17\text{ years}$, and $12.5\text{--}25\text{ mg/day}$ for patients of East Asian ancestry or those with moderate-to-severe hepatic impairment.

Splenectomy Complications and Prophylaxis

A surgical second-line therapy with a $60\text{--}70\%$ long-term response whose main risks are sepsis and portal vein thrombosis, requiring mandatory pre-operative vaccination against Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae.

Alternative Therapies for Refractory ITP

Immunosuppressive and cytotoxic agents used after splenectomy and second-line options are exhausted, including cyclophosphamide, azathioprine, mycophenolate mofetil, cyclosporine A, vincristine, vinblastine, and danazol.