When should I suspect Immune Thrombocytopenic Purpura (ITP) in a patient, particularly in children and young adults, presenting with bleeding or bruising, and a history of easy bruising or bleeding gums?

When to Suspect Immune Thrombocytopenic Purpura (ITP)

Suspect ITP in any patient presenting with isolated thrombocytopenia (platelet count <100 × 10⁹/L) accompanied by petechiae, purpura, or mucosal bleeding, particularly when the complete blood count is otherwise normal and there are no systemic symptoms, organomegaly, or lymphadenopathy. 1, 2

Classic Presentation Requiring High Suspicion

In Children and Adolescents

• Acute onset of petechiae and bruising developing over 24-48 hours, often 2-4 weeks following a viral illness or recent vaccination (particularly MMR) 1
• Scattered petechiae on skin and several small bruises on extremities without other bleeding manifestations 1
• No fever, bone pain, joint pain, or constitutional symptoms — these features are NOT typical of ITP and should prompt investigation for alternative diagnoses 1
• Normal physical examination except for bleeding manifestations — specifically no lymphadenopathy, hepatosplenomegaly, or skeletal abnormalities 1

In Adults and Young Adults

• Gradual or acute onset of easy bruising, petechiae, epistaxis, gingival bleeding, or menorrhagia in otherwise healthy individuals 1, 3, 4
• Female predominance in adults, with incidence increasing with age 3
• May be completely asymptomatic with thrombocytopenia discovered incidentally on routine blood work 3, 4

Essential Laboratory Findings That Support ITP Diagnosis

Complete Blood Count Characteristics

• Isolated thrombocytopenia (platelet count <100 × 10⁹/L) with normal hemoglobin and white blood cell count 1, 5
• Hemoglobin may show microcytic anemia only if attributed to chronic blood loss from bleeding 1, 5
• White blood cell count and differential are normal, though atypical lymphocytes may occasionally occur in children 5

Peripheral Blood Smear Features

• Few large platelets with normal morphology — this is the hallmark finding 1, 2
• Normal red blood cell morphology without schistocytes or poikilocytosis (unless polychromatophilia from bleeding response) 5, 2
• Normal white blood cell morphology without immature or abnormal cells 5
• Absence of platelet clumping — must exclude pseudothrombocytopenia from EDTA-dependent platelet agglutination 1, 5, 6

Red Flags That Argue AGAINST Primary ITP

Clinical Red Flags Requiring Alternative Diagnosis Investigation

• Fever at presentation — suggests infection, malignancy, or systemic inflammatory disease 1
• Lymphadenopathy or splenomegaly — excludes primary ITP and mandates workup for lymphoproliferative disorders, autoimmune diseases, or infections 1, 5
• Hepatomegaly — suggests liver disease, storage disorders, or infiltrative processes 1, 5
• Bone or joint pain — raises concern for leukemia, bone marrow infiltration, or rheumatologic disease 1
• Non-petechial rash — suggests vasculitis, drug reaction, or systemic autoimmune disease 1, 5
• Skeletal or soft-tissue morphologic abnormalities — may indicate inherited syndromes or congenital disorders 1

Laboratory Red Flags Requiring Bone Marrow Examination

• Anemia not explained by blood loss — suggests bone marrow failure, hemolysis, or infiltrative process 1, 5
• Leukopenia or leukocytosis with abnormal white cell morphology — raises concern for leukemia or myelodysplastic syndrome 1, 5
• Schistocytes on peripheral smear — indicates thrombotic microangiopathy (TTP/HUS), not ITP 5, 6, 2
• Predominantly giant platelets approaching red blood cell size — suggests inherited thrombocytopenia, not ITP 1, 5
• Immature or abnormal cells on smear — mandates bone marrow evaluation for hematologic malignancy 1, 5

Family and Personal History Features That Increase Suspicion

History Supporting ITP Diagnosis

• No family history of thrombocytopenia or bleeding disorders 1
• Recent viral illness (1-4 weeks prior) in children 1, 3, 7
• No chronic medical conditions or systemic autoimmune diseases 1, 4
• No risk factors for HIV or hepatitis C (though testing still mandatory in adults) 1, 5

History Suggesting Alternative Diagnosis

• Family history of low platelets or easy bruising — suggests inherited thrombocytopenia 1
• Thrombocytopenia present since early life — indicates congenital or inherited disorder 1
• Chronic alcohol use — causes bone marrow suppression 5
• Multiple medications, particularly recent antibiotic use — raises concern for drug-induced thrombocytopenia 1, 5

Age-Specific Considerations for Suspicion Threshold

Children (Age <18 Years)

• High index of suspicion for acute ITP following viral illness with sudden onset petechiae/bruising 1
• 75-80% of children achieve spontaneous remission within 6 months 1, 3
• Risk of intracranial hemorrhage is extremely low (0.1-0.5%) even with severe thrombocytopenia 3

Adolescents

• Higher likelihood of developing chronic ITP compared to younger children 1
• Should be managed more cautiously as natural history resembles adult ITP 1

Adults (Age ≥18 Years)

• Spontaneous remission is much less common than in children 1, 4
• Age >60 years mandates bone marrow examination regardless of typical presentation to exclude myelodysplastic syndrome or malignancy 1, 5
• Female predominance with chronic course more typical 3, 4

Mandatory Testing to Exclude Secondary Causes Before Diagnosing Primary ITP

Required in ALL Adults

• HIV testing — mandatory regardless of risk factors, as HIV-associated ITP may precede other symptoms by years 1, 5, 6
• Hepatitis C virus testing — mandatory as HCV can cause clinically indistinguishable thrombocytopenia 1, 5, 6
• H. pylori testing — should be considered as eradication can resolve thrombocytopenia 5, 6

Required in Children/Adolescents with Risk Factors

• HIV testing if risk factors present (transfusion history, maternal HIV, high-risk behaviors in adolescents) 1, 5
• Hepatitis C testing if risk factors present 1

Additional Testing in Specific Clinical Scenarios

• Immunoglobulin levels (IgG, IgA, IgM) — may be considered to exclude common variable immune deficiency, as ITP can be presenting feature 1
• Antinuclear antibodies — NOT routinely recommended in children, but may be useful in adults with suggestive features of systemic lupus erythematosus 1
• Antiphospholipid antibodies — if thrombosis present or recurrent pregnancy loss 1, 5
• Direct antiglobulin test — if hemolytic anemia suspected (Evans syndrome) 1

When Bone Marrow Examination IS Required Despite Suspected ITP

Absolute Indications

• Age ≥60 years — to exclude myelodysplastic syndrome, leukemia, or other malignancies 1, 5
• Systemic symptoms present (fever, weight loss, night sweats, bone pain) 1, 5
• Abnormalities beyond isolated thrombocytopenia on CBC (anemia not from bleeding, leukopenia, leukocytosis) 1, 5
• Atypical peripheral smear findings (schistocytes, immature cells, predominantly giant platelets) 1, 5
• Organomegaly or lymphadenopathy on physical examination 1, 5

Relative Indications

• Failure to respond to first-line ITP therapies (IVIg, corticosteroids, anti-D) 5
• Before splenectomy in patients with persistent disease 1
• Persistent thrombocytopenia lasting >6-12 months without improvement 5

Common Diagnostic Pitfalls to Avoid

• Never diagnose ITP without personally reviewing the peripheral blood smear — automated counts miss pseudothrombocytopenia, giant platelets, and schistocytes 5
• Never skip HIV and HCV testing in adults — these infections are clinically indistinguishable from primary ITP and may precede other symptoms by years 1, 5
• Never assume ITP when platelet counts are normal or high-normal — ITP by definition requires thrombocytopenia <100 × 10⁹/L 6, 2
• Never ignore splenomegaly, hepatomegaly, or lymphadenopathy — these findings exclude primary ITP and mandate aggressive pursuit of alternative diagnoses 1, 5
• Never overlook drug history — review ALL medications including over-the-counter drugs and herbal supplements for potential drug-induced thrombocytopenia 1, 5
• Never delay bone marrow examination in patients ≥60 years — age alone mandates evaluation regardless of how "typical" the presentation appears 1, 5