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Laboratory Testing for ADAMTS13 for Thrombotic Thrombocytopenia Purpura and Beyond
Emmanuel J Favaloro1,2,3, Leonardo Pasalic1,4, Giuseppe Lippi5
1Department of Haematology, Sydney Centres for Thrombosis and Haemostasis, Institute of Clinical Pathology and Medical Research (ICPMR), Westmead Hospital, Westmead, NSW, Australia.
Abstract:
ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13), also called von Willebrand factor (VWF) cleaving protease, acts as a moderator of VWF activity. ADAMTS13 cleaves VWF multimers, thereby reducing VWF activity in blood. When ADAMTS13 is absent (e.g., in patients with TTP [thrombotic thrombocytopenia purpura]), accumulation of VWF in plasma can occur, particularly as "ultra-large" VWF multimers, with this leading to adverse outcomes such as thrombosis. Relative ADAMTS13 deficiencies also occur in several other conditions, including secondary thrombotic microangiopathies (TMA), cancer, and with severe infections such as in COVID-19 (coronavirus disease 2019). These situations might therefore be accompanied with relative loss of ADAMTS13, thereby potentially also leading to pathological VWF accumulation, with this then generating a prothrombotic milieu, thus contributing to enhance the risk of thrombosis. Laboratory testing for ADAMTS13 can aid in the diagnosis of such disorders (i.e., TTP, TMA), and help guide their management, with testing now accomplished using various assays. As most presentations of TTP reflect an acquired condition due to anti-ADAMTS13 antibodies, there may also be a need to test for these, as this will also influence clinical management. We herein provide an overview of TTP, note other conditions in which low levels of ADAMTS13 may be present, and then detail laboratory testing for both ADAMTS13 and associated inhibitors.
Insights
ADAMTS13 enzyme deficiency can cause thrombotic thrombocytopenia purpura (TTP) and other thrombotic microangiopathies (TMA). Laboratory testing for ADAMTS13 and its antibodies is crucial for diagnosing and managing these conditions.
Area of Science:
- Hematology
- Biochemistry
- Pathology
Background:
- ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) cleaves von Willebrand factor (VWF) multimers, regulating VWF activity.
- Absence or deficiency of ADAMTS13 leads to accumulation of ultra-large VWF multimers, promoting thrombosis.
- Low ADAMTS13 levels are implicated in thrombotic thrombocytopenia purpura (TTP), secondary thrombotic microangiopathies (TMA), cancer, and severe infections like COVID-19.
Purpose of the Study:
- To provide an overview of TTP and other conditions associated with low ADAMTS13 levels.
- To detail laboratory testing methodologies for ADAMTS13 and its inhibitors.
- To highlight the diagnostic and management utility of ADAMTS13 testing.
Main Methods:
- Review of existing literature on ADAMTS13 function, deficiency, and associated disorders.
- Description of various laboratory assays used for ADAMTS13 activity and inhibitor testing.
- Discussion of the clinical relevance of testing for ADAMTS13 and anti-ADAMTS13 antibodies.
Main Results:
- ADAMTS13 deficiency is a hallmark of TTP and contributes to thrombotic events in other conditions.
- Laboratory tests for ADAMTS13 and its antibodies are essential for accurate diagnosis and treatment guidance.
- Testing aids in differentiating TTP from other thrombotic microangiopathies and guides management strategies.
Conclusions:
- ADAMTS13 testing plays a critical role in the diagnosis and management of TTP and related thrombotic disorders.
- Identifying anti-ADAMTS13 antibodies is important as it influences treatment decisions in acquired TTP.
- Understanding ADAMTS13's role and testing capabilities improves patient outcomes in thrombotic microangiopathies.
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