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Do coagulation screening tests detect increased generation of thrombin and plasmin in sick newborn infants?
B Schmidt1, P Vegh, M Johnston
1Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.
Insights
Abnormal coagulation screening tests can help diagnose disseminated intravascular coagulation (DIC) in sick infants. However, normal results do not rule out coagulation and fibrinolytic system activation in neonates.
Area of Science:
- Neonatal Medicine
- Hematology
- Pediatric Critical Care
Background:
- Disseminated intravascular coagulation (DIC) diagnosis in neonates relies on abnormal coagulation profiles, but accuracy is uncertain.
- DIC involves simultaneous activation of coagulation and fibrinolytic systems.
- Biochemical markers of thrombin and plasmin generation are key to understanding DIC in infants.
Purpose of the Study:
- To evaluate the diagnostic accuracy of standard coagulation screening tests in identifying neonates with biochemical evidence of DIC.
- To assess if coagulation screening tests correctly identify infants with increased thrombin and plasmin generation.
Main Methods:
- Prospective cohort study of 100 non-surgical, critically ill infants in a tertiary care nursery.
- Blood samples collected via arterial catheter for analysis of thrombin/antithrombin III (TAT) complexes and fibrinopeptide B beta 1-42.
- Simultaneous measurement of platelet count, D-Dimer, fibrinogen, and International Normalized Ratio (INR).
Main Results:
- 57 out of 100 infants showed elevated TAT and B beta 1-42 levels, indicating DIC.
- Sensitivities for DIC markers: platelets < 150 x 10(9)/l (39%), D-Dimer > 500 ng/ml (30%), fibrinogen < 1.5 g/l (12%), INR > 1.5 (11%).
- Specificities were high: platelets (88%), D-Dimer (91%), fibrinogen (98%), INR (95%).
Conclusions:
- Abnormal coagulation screening tests in sick newborns are strong indicators of DIC.
- Normal coagulation screening results do not exclude the activation of coagulation and fibrinolytic systems in neonates.
- Further investigation may be needed for neonates with normal screens but high clinical suspicion for DIC.
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 B beta 1-42 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 (> or = 4 micrograms/l) and B beta 1-42 (> or = 4 nmol/l). The sensitivities of platelets < 150 x 10(9)/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.