From the Guidelines
The laboratory workup for Thrombotic Microangiopathy (TMA) should include a comprehensive diagnostic evaluation, as outlined in the American Society of Clinical Oncology clinical practice guideline, which recommends a thorough history and physical examination, CBC with indices, blood smear morphology, serum creatinine, ADAMTS13, homocysteine/methylmalonic acid, complement testing, and evaluation of reticulocyte count and mean corpuscular volume 1. The initial step in the workup involves a thorough history and physical examination, with special consideration for new history of high-risk drugs, hypertension, or cardiac causes.
- Key laboratory tests include:
- CBC with indices to assess for anemia, thrombocytopenia, and other cytopenias
- Blood smear morphology to identify schistocytes, which are critical for the diagnosis of TMA
- Serum creatinine to evaluate renal function
- ADAMTS13 to rule out thrombotic thrombocytopenic purpura (TTP)
- Homocysteine/methylmalonic acid to assess for nutritional causes of macrocytosis
- Complement testing, including C3, C4, and CH50, to evaluate for complement-mediated TMA
- Additional testing should be guided by the clinical presentation and may include evaluation for infectious causes, such as Epstein-Barr virus (EBV), CMV, and human herpesvirus 6, as well as screening for diarrheal causes, such as Shiga toxin-producing E. coli 1. The goal of this comprehensive workup is to identify the underlying cause of TMA, whether it's ADAMTS13 deficiency in TTP, complement dysregulation in atypical hemolytic uremic syndrome (aHUS), or other mechanisms, and to guide appropriate therapy to improve outcomes in these potentially life-threatening conditions.
- It is essential to note that different TMA subtypes require specific treatments, and a timely and accurate diagnosis is crucial to initiate appropriate therapy, such as urgent plasma exchange for TTP or eculizumab for complement-mediated TMA.
From the Research
Laboratory Workup for Thrombotic Microangiopathy (TMA)
The laboratory workup for TMA involves several tests to confirm the diagnosis and identify the underlying etiology. The key tests include:
- A basic hematological evaluation, including a peripheral blood smear to identify schistocytes and thrombocytopenia 2
- Measurement of the blood level of ADAMTS13, a protease that splits von Willebrand factor, to differentiate TTP from other types of TMA 2
- Quantitative determination of ADAMTS13 activity and the ADAMTS13 inhibitor to confirm the diagnosis of TTP 2
- Tests to identify the presence of microangiopathic hemolytic anemia, such as lactate dehydrogenase (LDH) and indirect bilirubin 3, 4
- Tests to evaluate organ injury, such as serum creatinine and urine analysis 3, 4
Diagnostic Approach
The diagnostic approach for TMA involves a step-by-step process, including:
- Initial presentation and diagnostic workup to identify the presence of TMA 3
- Appropriate initial tests and referrals to specialists in hematology and nephrology 3
- Empiric treatments when appropriate, while awaiting laboratory results 3
- Confirmation of the etiological diagnosis and initiation of definitive treatment 3, 2
Importance of Early Diagnosis and Treatment
Early diagnosis and treatment of TMA are crucial to improve patient outcomes. Delayed diagnosis and treatment can lead to significant morbidity and mortality 3, 2, 4. A structured approach to identifying the presence of TMA and seeking the etiological diagnosis, including standardized lab panels, can help improve patient outcomes 3.