Reference values — Tissue plasminogen activator inhibitor-1 (PAI-1) antigen (plasma)

PAI-1 is the major physiologic inhibitor of tissue plasminogen activator (tPA) and thus a key regulator of fibrinolysis. Levels rise progressively in normal pregnancy, contributing to the prothrombotic state.

Units Nonpregnant Adult First Trimester Second Trimester Third Trimester
ng/mL 4 – 43 16 – 33 36 – 55 67 – 92
PAI-1 antigen concentrations measured in plasma. Values may vary with assay, sample handling, and laboratory method; local reference ranges should be used if available.
Physiologic changes in pregnancy
  • Pregnancy is associated with a progressive increase in PAI-1, particularly in the second and third trimesters, reflecting increased synthesis by maternal vascular endothelium and the placenta.
  • Placental trophoblasts predominantly produce PAI-2, whereas PAI-1 is mainly endothelial and hepatic; both rise in pregnancy, leading to reduced fibrinolytic activity and a net prothrombotic state.
  • Rising estrogen levels and increased endothelial activation enhance PAI-1 production, while circulating tPA antigen also increases. The balance shifts toward inhibited plasmin generation despite elevated tPA.
  • The combined increase in PAI-1 and PAI-2 contributes to the physiological hypercoagulable state of pregnancy that helps limit bleeding at delivery but increases the risk of venous thromboembolism.
Causes of elevated PAI-1

Elevated PAI-1 reflects impaired fibrinolysis and is associated with prothrombotic and cardiometabolic conditions.

  • Normal pregnancy (particularly 3rd trimester — physiologic elevation)
  • Preeclampsia and other hypertensive disorders of pregnancy
  • Obesity, insulin resistance, metabolic syndrome, type 2 diabetes, gestational diabetes
  • Acute coronary syndromes, atherosclerotic cardiovascular disease
  • Inflammatory states and infections (systemic inflammatory response)
  • Nephrotic syndrome and some chronic kidney diseases
  • Chronic liver disease with increased endothelial/extrahepatic production
  • Smoking and certain medications that impair fibrinolysis
  • Genetic variants (e.g., PAI-1 4G/5G polymorphism) associated with higher PAI-1 levels
Causes of low PAI-1

Low PAI-1 is less common and may be associated with bleeding or enhanced fibrinolysis.

  • Rare congenital PAI-1 deficiency (may present with mucocutaneous or postsurgical bleeding)
  • Advanced liver failure with reduced synthesis of coagulation and fibrinolytic proteins
  • Disseminated intravascular coagulation with consumption of multiple hemostatic factors
  • Thrombolytic therapy (e.g., exogenous tPA) and some anticoagulant regimens
  • Severe malnutrition or cachectic states affecting protein synthesis
References
  1. Abbassi-Ghanavati M, Greer LG, Cunningham FG. Pregnancy and laboratory studies: a reference table for clinicians. Obstet Gynecol. 2009;114(6):1326–1331. PMID: 19935037.
  2. Lockitch G. Handbook of Diagnostic Biochemistry and Hematology in Normal Pregnancy. Boca Raton: CRC Press; 1993.
  3. James AH. Venous thromboembolism in pregnancy. Arterioscler Thromb Vasc Biol. 2009;29(3):326–331.
  4. Brenner B. Haemostatic changes in pregnancy. Thromb Res. 2004;114(5–6):409–414.
  5. Kario K, Matsuo T, et al. Marked increase of plasminogen activator inhibitor-1 and fibrinogen in pregnancy-induced hypertension. Thromb Haemost. 1990;63(3):366–370.