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Thrombotic microangiopathy

Comprehensive testing to confirm diagnosis and facilitate treatment

Thrombotic microangiopathy (TMA) is a heterogenous group of rare disorders characterized by thrombocytopenia and microangiopathic hemolytic anemia and end organ damage that can occur due to ischemic injury of organs, such as renal injury or stroke. Because of the variety of TMA disorders and different treatment options for each, prompt and accurate diagnosis can significantly impact a patient’s outcome.

Thrombotic microangiopathy Test menu

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Optimizing treatment for challenging conditions

Plasma exchange — the treatment of choice for iTTP patients — has been shown to reduce morbidity from around 90% to less than 20%. TTP may be confirmed with ADAMTS13 activity and inhibition studies.

Patients diagnosed with STEC-HUS benefit from early supportive interventions. Intravenous volume expansion can potentially decrease renal damage. Antibiotics, which can cause the release of toxins, are to be avoided.

Management of TMA associated with other secondary causes involves identifying and treating the underlying cause. Medication-induced TMA is initially managed by withdrawing the causative medication. The diagnosis of aHUS, which is caused by a dysregulation of the complement alternative pathway, is one of exclusion. Complement serologic and genetic testing are useful to support a clinical diagnosis of aHUS, and management of the condition includes complement inhibition with medications such as eculizumab and ravulizumab.

Thrombotic microangiopathy

Thrombotic microangiopathies include the following diagnoses:

Congenital thrombotic thrombocytopenic purpura (TTP) and immune thrombotic thrombocytopenic purpura (iTTP).
Shiga toxin-producing E. coli hemolytic uremic syndrome (STEC-HUS).
TMA occurring in the setting of another underlying medical condition, including malignancy, hypertension, pregnancy, and rheumatologic disorders such as systemic lupus, erythematosus, and antiphospholipid antibody syndrome.
Transplant-associated TMA.
Medication-induced TMA.
Atypical hemolytic uremic syndrome (aHUS).

Key testing

ADAMP | ADAMTS13 Activity with Reflex Inhibitor Profile, Plasma
- Assists with the diagnosis of congenital or acquired thrombocytopenic purpura.
STFRP | Shiga Toxin, Molecular Detection, PCR, Feces
- Useful for the confirmation of STEC-HUS.
AHUSD | Atypical Hemolytic Uremic Syndrome Complement Panel, Serum and Plasma
- Detects deficiencies in the alternative pathway that can cause atypical-hemolytic uremic syndrome, dense deposit disease, and C3 glomerulonephritis.
ECULI | Eculizumab, Serum
- Monitors patients who need to be above a certain eculizumab concentration in order to improve the odds of a clinical response for therapy optimization.

Highlights

Complement Testing in the Diagnosis and Management of Thrombotic Microangiopathy

PACE / State of FLThis month’s “Virtual Lecture” discusses the clinical diagnosis and management, summarizes the testing modalities that guide diagnosis and management, and recognizes the utility of genetic testing as it relates to complement testing in diagnosing and managing thrombotic microangiopathy.

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Thrombotic Microangiopathies (TMA) [Test in Focus]

Meera Sridharan, M.D., Ph.D., explains Mayo Clinic Labs’ testing approach for atypical hemolytic uremic syndrome (aHUS). The serological complement panel examines nine analytes to gain a thorough understanding of the complement cascade to confirm diagnosis and direct care.

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