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. 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 systemic lupus, erythematosus, and antiphospholipid antibody syndrome
• Transplant-associated TMA
• Medication-induced TMA
• Atypical hemolytic uremic syndrome (aHUS)

Because of the variety of TMA disorders and different treatment options for each, prompt and accurate diagnosis can significantly impact a patient’s outcome.

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.

Key testing

ADM13 | ADAMTS13 Activity and Inhibitor Profile, Plasma

Useful for:

• Assisting with the diagnosis of congenital or acquired thrombocytopenic purpura

STFRP | Shiga Toxin, Molecular Detection, PCR, Feces

Useful for: 

• Confirmation of STEC-HUS

ECUMP | Eculizumab Monitoring Panel, Serum

Useful for:

• Therapeutic drug monitoring of eculizumab

AHUSD | Atypical Hemolytic Uremic Syndrome Complement Panel, Serum and Plasma

Panel uses several testing methods, including nephelometry, automated liposome lysis assay, and enzyme-linked immunosorbent assay (ELISA) to evaluate complement components for identification of the underlying cause of TMA.

Useful for:

• Detecting deficiencies in the alternative pathway that can cause atypical-hemolytic uremic syndrome, dense deposit disease, and C3 glomerulonephritis
• A second-tier test that aids in the differential diagnosis of thrombotic microangiopathies

AHUSP | Complement-Mediated Atypical Hemolytic-Uremic Syndrome (aHUS)/Thrombotic Microangiopathy (TMA) Gene Panel, Varies

Panel uses next-generation sequencing to evaluate 13 genes — ADAMTS13, C3, CD46 (MCP), CFB, CFD, CFH, CFHR1, CFHR3, CFHR5, CFI, DGKE, PLG, THBD — for complement function, complement component construction, and activation products.

Useful for:

• Establishing diagnosis, and in some cases, allowing for appropriate management and surveillance for disease features based on the gene involvement
• Providing a comprehensive genetic evaluation for patients with a personal or family history suggestive of complement-mediated HUS/atypical HUS (aHUS) or thrombotic microangiopathies (TMA)
• Identifying variants in genes encoding complement alternate pathway components and specific coagulation pathway genes known to be associated with increased risk for aHUS/TMA, allowing for predictive testing of at-risk family members

ECULI | Eculizumab, Serum

This test uses liquid chromatography-tandem mass spectrometry (LC-MS/MS) to assess patient response to eculizumab therapy and monitor levels of medication concentrations to optimize therapeutic response.

Useful for:

• Assessing the need for dose escalation
• Evaluating the potential for dose de-escalation or discontinuation of therapy in remission states
• Monitoring patients who need to be above a certain eculizumab concentration in order to improve the odds of a clinical response for therapy optimization