Longitudinal assessment of hemostatic adaptations in pregnant mares: Evidence of a physiological hypercoagulable state.

Overview

• This study investigated how pregnancy affects blood clotting mechanisms in mares, showing that as pregnancy progresses, mares develop a stronger tendency for their blood to clot, which is a normal adaptation to support pregnancy and delivery.

Introduction and Hypothesis

• Pregnancy involves complex changes in the body’s hemostatic system, which controls blood clotting and prevents excessive bleeding.
• These changes help support the development of the placenta and protect against hemorrhage during delivery.
• The researchers proposed that pregnant mares would gradually exhibit a procoagulant (higher clotting) state throughout their pregnancy.
• Such a state would be visible through measurable changes in markers of coagulation and fibrinolysis (breakdown of clots).

Study Design and Methods

• Subjects: 15 healthy Spanish Purebred mares that became pregnant and 15 non-pregnant mares of the same breed and age as controls.
• Data Collection: Monthly blood samples were taken from conception until term (delivery) in pregnant mares; controls were sampled to provide baseline values.
• Measured Parameters:
  • Platelet (PLT) count – platelets assist in clot formation.
  • Prothrombin time (PT) – measures how long it takes blood to clot via one pathway.
  • Activated partial thromboplastin time (aPTT) – measures clotting time via a different clotting cascade pathway.
  • Antithrombin III (ANT-III) activity – a natural anticoagulant that reduces clotting.
  • Fibrinogen (FIB) concentration – protein vital for clot formation.
  • D-dimer (D-D) levels – breakdown product of fibrin indicating clot turnover.

Results

• Early Gestation:
  • PT and aPTT times in pregnant mares were similar to non-pregnant controls, indicating no initial clotting changes.
  • ANT-III activity, fibrinogen, and D-dimer levels were also comparable at this early stage.
• Mid to Late Gestation:
  • PT decreased from about 11.5 seconds to 10.8 seconds, indicating faster clot formation (significant at P < 0.05).
  • aPTT decreased from around 44.8 seconds to 41.2 seconds, again showing faster clotting.
  • ANT-III activity dropped from 101% to 86%, suggesting reduced anticoagulant activity, promoting clotting.
  • Fibrinogen increased substantially from 202 mg/dL to 291 mg/dL, meaning more clotting protein was available.
  • D-dimer rose from 225 ng/mL at mid-gestation to 495 ng/mL near term, indicating increased clot formation and breakdown (higher fibrin turnover).
  • None of the mares showed clinical signs of thrombosis, meaning these changes were physiological, not pathological.
• Control Group:
  • Non-pregnant mares maintained stable hemostatic values throughout the study period.

Interpretation and Implications

• The progressive changes in clotting times, anticoagulant activity, fibrinogen, and D-dimer levels support a gestation-dependent shift toward a hypercoagulable state in pregnant mares.
• This hypercoagulable state likely helps the maternal body prepare for delivery by minimizing bleeding risks and supporting placental health.
• The increased fibrin turnover (as evidenced by elevated D-dimer) suggests active remodeling and balance between clot formation and breakdown.
• These adaptations are physiological and should not be mistaken for disease or pathological clotting disorders.
• The findings highlight the importance of using gestation-specific reference ranges when evaluating coagulation tests in pregnant mares to avoid misdiagnosis.

Conclusions

• Pregnant mares experience significant physiological changes in their hemostatic system as pregnancy advances, characterized by enhanced coagulation and fibrinolytic activity.
• Understanding these natural adaptations is critical for proper veterinary care and management of pregnant mares, ensuring appropriate interpretation of coagulation markers.