ADAMTS13 Activity (A Disintegrin And Metalloprotease with a Thrombospondin Type 1 Motif, Member 13)

Physiology

Background

  • ADAMTS13 (A Disintegrin And Metalloprotease with a Thrombospondin Type 1 Motif, Member 13) is a Von Willebrand Factor-Cleaving Plasma Protease
    • Cleavage by ADAMTS13 is a Normal Function Which Prevents Ultralarge Von Willebrand Factor Multimers from Accumulating, Especially in Areas of High Shear Stress (Such as Small Arterioles and Capillaries)
    • Shear Stress Results in a Conformational Change in Von Willebrand Factor Multimers, Exposing the ADAMTS13 Cleavage Site
    • Physiologic Sites of ADAMTS13 Synthesis
      • Hepatic Stellate Cells: primary site of synthesis
      • Endothelial Cells: lesser site of synthesis
      • Megakaryocytes: lesser site of synthesis

Etiology of Decreased ADAMTS13 Activity

  • Hereditary Thrombotic Thrombocytopenic Purpura (Hereditary TTP) (Upshaw–Schulman Syndrome) (see Thrombotic Thrombocytopenic Purpura-Hereditary, [[Thrombotic Thrombocytopenic Purpura-Hereditary]])
  • Acquired Thrombotic Thrombocytopenic Purpura (Hereditary TTP) (see Thrombotic Thrombocytopenic Purpura-Acquired, [[Thrombotic Thrombocytopenic Purpura-Acquired]])
    • Relationship of Disease to ADAMTS13 Activity
      • Severe Reduction in ADAMTS13 Activity is Required for Clinical Manifestations of TTP
      • However, Reduction in ADAMTS13 Activity Alone is Not Sufficient to Cause Disease: other factors such as acute inflammation or a prothrombotic stimulus may be required to trigger the onset of disease
        • In addition, plasmin may substitute for ADAMTS13 in cleaving ultralarge Von Willebrand factor multimers
  • Cardiac Surgery: produces lesser degree of decrease in ADAMTS13 (which, by itself, is extremely unlikely to cause disease)
  • Last Two Trimesters of Pregnancy (see Pregnancy, [[Pregnancy]]): produces lesser degree of decrease in ADAMTS13 (which, by itself, is extremely unlikely to cause disease)
    • Lowest Levels Occur at 36-40 Weeks of Gestation and During Early Puerperium
  • Liver Disease (see End-Stage Liver Disease, [[End-Stage Liver Disease]]): produces lesser degree of decrease in ADAMTS13 (which, by itself, s extremely unlikely to cause disease)
  • Pancreatitis (see Acute Pancreatitis, [[Acute Pancreatitis]]): produces lesser degree of decrease in ADAMTS13 (which, by itself, is extremely unlikely to cause disease)
  • Sepsis (see Sepsis, [[Sepsis]]): produces lesser degree of decrease in ADAMTS13 (which, by itself, is extremely unlikely to cause disease)

Technique

  • High levels of free hemoglobin in the circulation (eg, in severe hemolytic anemia) or hemolysis in the blood sample after collection may interfere with laboratory measurement of ADAMTS13 activity, giving a false impression of severe deficiency

  • Low ADAMTS13 Activity (10-50%): may be seen in hospitalized patients with sepsis/malignancies

    • In addition, activity levels of 10-20% may be seen in TTP patients who have received blood products (since blood products contain fucntional ADAMTS13)
  • Normal ADAMTS13 Activity (>50%): considered normal

References

  • xxx