From the Guidelines
Diagnosis of Thrombotic Thrombocytopenic Purpura (TTP) should include a comprehensive diagnostic work-up with a focus on laboratory confirmation, particularly the presence of schistocytes on blood smear morphology and ADAMTS13 activity levels below 10% to rule out TTP, as recommended in the American Society of Clinical Oncology clinical practice guideline 1. The diagnostic criteria for TTP involve a combination of clinical and laboratory findings. Key components include:
- History and physical examination to identify new history of high-risk drugs, hypertension, or cardiac causes
- CBC with indices to assess thrombocytopenia
- Blood smear morphology to identify schistocytes, which is critical for diagnosis
- Serum creatinine to evaluate renal function
- ADAMTS13 activity to rule out TTP, with levels below 10% strongly supporting acquired TTP 1
- Additional tests such as homocysteine/methylmalonic acid, complement testing, reticulocyte count, and mean corpuscular volume to evaluate for other potential causes of thrombocytopenia and anemia The presence of the clinical pentad, including thrombocytopenia, microangiopathic hemolytic anemia, neurological abnormalities, renal dysfunction, and fever, can also support the diagnosis of TTP. However, not all features may be present, and laboratory confirmation is essential for accurate diagnosis. Initial laboratory evaluation should include a complete blood count, peripheral blood smear, comprehensive metabolic panel, coagulation studies, lactate dehydrogenase (LDH) levels, and haptoglobin levels. Additional testing, such as direct Coombs test, reticulocyte count, and tests to rule out other thrombotic microangiopathies, may also be necessary to confirm the diagnosis and guide treatment. Early diagnosis is critical, as untreated TTP has a high mortality rate, and prompt plasma exchange therapy can significantly reduce this risk 1.
From the Research
Diagnostic Criteria for Thrombotic Thrombocytopenic Purpura (TTP)
The diagnostic criteria for TTP include:
- Thrombocytopenia
- Microangiopathic hemolytic anemia
- Fever
- Neurological abnormalities
- Renal dysfunction
These criteria are often referred to as the "pentad" of TTP symptoms 2, 3, 4, 5, 6. However, it is noted that not all patients present with all five symptoms, and the presence of thrombocytopenia and microangiopathic hemolytic anemia is mandatory for the diagnosis of TTP 2, 4, 6.
Atypical Presentations of TTP
Atypical presentations of TTP can make diagnosis difficult, and it is essential to consider TTP as a differential diagnosis in patients with microangiopathic hemolytic anemia and thrombocytopenia, even if they do not present with the classic pentad of symptoms 3, 5. The use of ADAMTS13 assay can help confirm the diagnosis of TTP 5, 6.
Importance of Early Diagnosis and Treatment
Early diagnosis and treatment of TTP are crucial, as the disease can be fatal if left untreated 2, 4, 6. Plasma exchange therapy is the essential treatment for TTP, and initiation of therapy should not be delayed while waiting for laboratory confirmation 2, 4, 6.