What are the diagnostic criteria and treatment options for a patient with suspected Immune Thrombocytopenic Purpura (ITP) presenting with isolated thrombocytopenia?

Diagnosis of Immune Thrombocytopenic Purpura (ITP)

ITP is diagnosed primarily through history, physical examination, complete blood count, and peripheral blood smear examination to exclude other causes of isolated thrombocytopenia—bone marrow examination is not routinely necessary in patients with typical features. 1, 2

Essential Diagnostic Criteria

The diagnosis requires a platelet count <100 × 10⁹/L with isolated thrombocytopenia and no other cytopenias (except microcytic anemia from chronic blood loss). 2, 3

Core Laboratory Findings

• Complete blood count must demonstrate isolated thrombocytopenia with normal hemoglobin (unless bleeding-related anemia), normal white blood cell count, and normal differential. 2, 4

• Peripheral blood smear must show: 2, 3

  • Decreased platelets with normal or slightly enlarged size
  • Normal red blood cell morphology (no schistocytes or poikilocytosis unless polychromatophilia from bleeding response)
  • Normal white blood cell morphology without immature or abnormal cells
  • Absence of giant platelets approaching red blood cell size

• Manual peripheral blood smear review by a qualified hematologist or pathologist is mandatory to exclude pseudothrombocytopenia from EDTA-dependent platelet clumping. 2

Physical Examination Requirements

• Physical examination should be entirely normal except for bleeding manifestations (petechiae, purpura, mucosal bleeding). 2, 3

• The presence of splenomegaly, hepatomegaly, or lymphadenopathy definitively excludes primary ITP and mandates investigation for secondary causes including lymphoproliferative disorders, autoimmune diseases, or infections. 2, 3

Mandatory Testing to Exclude Secondary Causes

All adults with suspected ITP must be tested for HIV and hepatitis C virus, regardless of risk factors, as these infections can be clinically indistinguishable from primary ITP and may precede other symptoms by years. 2, 3

• HIV antibody testing is required in all adults and in children/adolescents with risk factors. 1, 2

• Hepatitis C virus testing is required in all adults. 2, 3

• H. pylori testing should be considered, as eradication therapy can resolve thrombocytopenia in H. pylori-associated ITP. 2

When Bone Marrow Examination IS Required

Bone marrow examination is not necessary in typical ITP but becomes mandatory in specific situations: 1, 2

• Age ≥60 years to exclude myelodysplastic syndromes, leukemias, or other malignancies 2

• Persistent thrombocytopenia lasting >6-12 months 1

• Unresponsive to IVIg therapy 1

• Systemic symptoms present (fever, weight loss, bone pain) 2

• Abnormal blood count parameters beyond isolated thrombocytopenia (anemia, leukopenia, leukocytosis) 2

• Atypical peripheral smear findings (schistocytes, predominantly giant platelets, leukocyte inclusion bodies, immature cells) 2

• Before splenectomy in patients with persistent disease 1

Tests That Are NOT Indicated for Routine Diagnosis

The following tests are generally unnecessary and sometimes inappropriate when performed routinely: 1, 3

• Anti-platelet antibody testing (insufficient sensitivity/specificity, does not change management) 2
• ANA, direct antiglobulin test
• Lupus anticoagulant/antiphospholipid antibodies (unless clinical suspicion for antiphospholipid syndrome)
• Platelet-associated IgG
• Chemistry profile
• Coagulation studies (PT, aPTT) unless suspecting DIC
• Chest x-ray
• Abdominal CT/ultrasound (only if splenomegaly suspected on physical examination) 1, 4, 3

Critical Diagnostic Pitfalls to Avoid

• Never diagnose ITP without personally reviewing the peripheral blood smear, as automated counts can miss pseudothrombocytopenia, giant platelets, or schistocytes. 2

• Never skip HIV and HCV testing in adults, even without apparent risk factors—these infections may be clinically silent for years. 2

• Do not confuse gestational thrombocytopenia with ITP in pregnancy: gestational thrombocytopenia typically presents with platelet counts >70 × 10⁹/L in late gestation without prior thrombocytopenia history. 3

• Recognize that pseudothrombocytopenia from EDTA-dependent platelet clumping can falsely lower automated counts—always confirm with citrate tube or manual smear review. 2

• Missing drug-induced thrombocytopenia requires detailed medication history including over-the-counter medications, herbal supplements, and recent antibiotics (vancomycin, cefazolin, sulfonamides, quinine). 2

Disease Classification by Duration

Once diagnosed, ITP is classified temporally as: 3

• Newly diagnosed: from diagnosis to 3 months
• Persistent: 3 to 12 months
• Chronic: lasting more than 12 months

Special Population Considerations

Pregnant Women

For pregnant women with suspected ITP, additional testing includes: 4, 3

• Blood pressure measurement and liver function tests to exclude preeclampsia/HELLP syndrome
• HIV antibody testing if risk factors present

Pediatric Patients

• Bone marrow examination is unnecessary in children with typical ITP features (isolated thrombocytopenia, normal physical exam, no systemic symptoms). 2

• Consider inherited thrombocytopenias if family history present, giant platelets on smear, or atypical presentation. 2

Red Flags Requiring Additional Investigation

Any of the following findings suggest alternative diagnoses and require further workup: 2

• Non-petechial rash
• Lymphadenopathy or splenomegaly
• Abnormal hemoglobin, white blood cell count, or white cell morphology
• Schistocytes on peripheral smear (suggests thrombotic microangiopathy)
• Predominantly giant platelets (suggests inherited thrombocytopenia)
• Constitutional symptoms (fever, weight loss, bone pain)