Do Coagulation Screening Tests Detect Increased Generation of Thrombin and Plasmin in Sick Newborn Infants?

Summary

Background: Disseminated intravascular coagulation (DIC) is usually diagnosed in sick infants who have prolonged clotting times, depletion of platelets and coagulation factors, and elevated levels of fibrin derivatives. However, the diagnostic accuracy of abnormal coagulation profiles in neonates at risk of DIC has been uncertain. Since DIC is characterized by activation of both the coagulation and fibrinolytic systems, the objective of this study was to determine whether coagulation screening tests correctly identify infants with biochemical evidence of increased thrombin and plasmin generation.

Methods: Non-surgical patients in a tertiary care nursery who were sick enough to require an indwelling arterial catheter for monitoring purposes, were enrolled in a prospective cohort study. Blood samples for thrombin/antithrombin III (TAT) complexes and the plasmin-derived fibrinopeptide Bβ1-42 were drawn 36 to 72 h after birth from a free-flowing arterial line. Platelet counts, D-Dimer levels, plasma fibrinogen concentrations and prothrombin times, expressed as International Normalized Ratios or INR, were measured at the same time.

Results: One hundred patients were studied. Fifty-seven infants had elevated levels of TAT (≥4 μg/l) and Bβ1-42 (≥4 nmol/l). The sensitivities of platelets <150 × 10⁹/l, D-Dimer >500 ng/ml, fibrinogen <1.5 g/l, and INR >1.5 were 39%, 30%, 12%, and 11%, respectively. Corresponding specificities were 88%, 91%, 98%, and 95%.

Conclusions: Abnormal coagulation screens in sick newborn infants strongly support a diagnosis of DIC. However, normal screens do not exclude activation of the coagulation and fibrinolytic systems.

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