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

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Etiology of Decreased ADAMTS13 Activity

• Hereditary Thrombotic Thrombocytopenic Purpura (Hereditary TTP) (Upshaw–Schulman Syndrome) (see Thrombotic Thrombocytopenic Purpura-Hereditary)
• Acquired Thrombotic Thrombocytopenic Purpura (Hereditary TTP) (see 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
  • Epidemiology: produces lesser degree of decrease in ADAMTS13 (which, by itself, is extremely unlikely to cause disease)
• Last Two Trimesters of Pregnancy (see Pregnancy)
  • Epidemiology: 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 Cirrhosis)
  • Epidemiology: produces lesser degree of decrease in ADAMTS13 (which, by itself, is extremely unlikely to cause disease)
• Pancreatitis (see Acute Pancreatitis)
  • Epidemiology: produces lesser degree of decrease in ADAMTS13 (which, by itself, is extremely unlikely to cause disease)
• Sepsis (see Sepsis)
  • Epidemiology: produces lesser degree of decrease in ADAMTS13 (which, by itself, is extremely unlikely to cause disease)

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Technique

• Potential Interference with the Assay: 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

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References

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