Selective extrinsic coagulation pathway amplification with preserved intrinsic function in normal singleton pregnancy: a cross-sectional study with trimester-specific gestational reference intervals from a Nigerian Obstetric Cohort

Abstract

Background: Normal pregnancy induces a procoagulant haemostatic transformation through differential upregulation of coagulation factors and suppression of fibrinolysis. The extrinsic coagulation pathway, driven by tissue factor (TF) and factor VII, is theorised to be preferentially amplified during gestation, while the intrinsic (contact-activation) pathway remains functionally stable. However, direct empirical evidence from sub-Saharan African obstetric populations is absent, and population-specific gestational coagulation reference intervals are unavailable for Nigerian clinical practice.

Objectives: This study aimed to test the hypothesis that the extrinsic coagulation pathway is selectively amplified, while the intrinsic pathway remains stable, during normal singleton pregnancy in a Nigerian obstetric cohort; and to generate trimester-stratified gestational reference intervals for prothrombin time (PT), international normalised ratio (INR), and activated partial thromboplastin time (APTT).

Methods: A cross-sectional case-control study was conducted at three public tertiary hospitals in Ibadan, Oyo State, Nigeria. A total of 266 participants were enrolled: 216 healthy singleton pregnant women (56 in the first trimester [T1], 82 in T2, 78 in T3) and 50 non-pregnant controls. PT and APTT were measured by the manual water-bath tilting-tube method; INR was derived from the PT ratio. One-way analysis of variance with post hoc Tukey’s honestly significant difference test was applied; results are reported in accordance with the STROBE checklist for observational studies.

Results: PT was significantly shorter in all trimester groups versus controls (F_3,262 = 4.065, P = 0.008; η² = 0.044): T1: 14.37 ± 1.22 s; T2: 14.64 ± 1.31 s; T3: 14.20 ± 1.31 s; controls: 14.93 ± 0.96 s. INR was similarly lower in pregnant groups (F_3,262 = 4.894, P = 0.003; η² = 0.053). In contrast, APTT did not differ significantly across groups (F_3,262 = 0.558, P = 0.643; η² = 0.006). Trimester-specific gestational reference intervals for PT (11.6–16.8 s at T3) were substantially below the non-pregnant lower limit of 13.0 s.

Conclusions: Normal pregnancy in a Nigerian population is characterised by selective amplification of the extrinsic coagulation pathway with complete preservation of intrinsic pathway function, consistent with TF-mediated procoagulant activation as the dominant gestational haemostatic mechanism. Locally derived gestational reference intervals differ substantially from non-pregnant values; their adoption would reduce misclassification of physiological coagulation changes in antenatal haemostasis monitoring.