Thromb Haemost 1993; 69(05): 418-421
DOI: 10.1055/s-0038-1651626
Original Article
Clinical Studies
Schattauer GmbH Stuttgart

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

Barbara Schmidt
The Departments of Pediatrics, Medicine and Pathology, McMaster University, Hamilton, Ontario, Canada
,
Patsy Vegh
The Departments of Pediatrics, Medicine and Pathology, McMaster University, Hamilton, Ontario, Canada
,
Marilyn Johnston
The Departments of Pediatrics, Medicine and Pathology, McMaster University, Hamilton, Ontario, Canada
,
Maureen Andrew
The Departments of Pediatrics, Medicine and Pathology, McMaster University, Hamilton, Ontario, Canada
,
Jeffrey Weitz
The Departments of Pediatrics, Medicine and Pathology, McMaster University, Hamilton, Ontario, Canada
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Received 27. April 1992

Accepted after revision 22. Januar 1993

Publikationsdatum:
25. Juli 2018 (online)

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.

 
  • References

  • 1 Bick RL. Disseminated intravascular coagulation and related syndromes: A clinical review. Semin Thromb Hemostas 1988; 14: 299-338
  • 2 Hathaway WE, Mull MM, Pechet GS. Disseminated intravascular coagulation in the newborn. Pediatrics 1969; 43: 233-240
  • 3 Feinstein DI. Diagnosis and management of disseminated intravascular coagulation: The role of heparin therapy. Blood 1982; 60: 284-287
  • 4 Weitz JI, Koehn JA, Canfield RE, Landman SL, Friedman R. Development of a radioimmunoassay for the fibrinogen-derived peptide Bβ1-42. Blood 1986; 67: 1014-1022
  • 5 Pelzer H, Schwarz A, Heimburger N. Determination of human thrombin-antithrombin III complex in plasma with an enzyme-linked immunosorbent assay. Thromb Haemostas 1988; 59: 101-106
  • 6 Clauss A. Gerinnungsphysiologische Schnellmethode zur Bestimmung des Fibrinogens. Acta Haematol 1957; 17: 237-246
  • 7 Greenberg CS, Devine DV, McCrae KM. Measurement of plasma fibrin D-dimer levels with the use of a monoclonal antibody coupled to latex beads. Am J Clin Pathol 1987; 87: 94-100
  • 8 Hirsh J, Deykin D, Poller L. “Therapeutic range” for oral anticoagulant therapy. Chest 1986; 89 (Suppl. 00) 11S-15S
  • 9 Andrew M, Paes B, Milner R, Johnston M, Mitchell L, Tollefsen DM, Powers P. Development of the human coagulation system in the fullterm infant. Blood 1987; 70: 165-172
  • 10 Andrew M, Paes B, Milner R, Johnston M, Mitchell L, Tollefsen DM, Castle V, Powers P. Development of the human coagulation system in the healthy premature infant. Blood 1988; 72: 1651-1657
  • 11 Hathaway W, Corrigan J. Report of scientific and standardization subcommittee on neonatal hemostasis. Normal coagulation data for fetuses and newborn infants. Thromb Haemostas 1991; 65: 323-325
  • 12 Hudson IRB, Gibson BES, Brownlie J, Holland BM, Turner TL, Webber RG. Increased concentrations of D-dimers in newborn infants. Arch Dis Child 1990; 65: 383-389
  • 13 Muntean W, Danda M, Rosegger H. Thrombin-antithrombin III complex and D-Dimer in neonates: Signs of thrombin generation during birth. In: Perinatal Thrombosis and Hemostasis. Suzuki S, Hathaway WE, Bonnar J, Sutor AH. (eds). Springer-Verlag; Tokyo: 1991
  • 14 Schmidt B, Vegh P, Weitz J, Johnston M, Caco C, Roberts R. Thrombin/antithrombin III complex formation in the neonatal respiratory distress syndrome. Am Rev Respir Dis 1992; 145: 767-770
  • 15 Buchanan GR. Coagulation disorders in the neonate. Pediatr Clin North Am 1986; 33: 203-220
  • 16 Boisclair MD, Ireland H, Lane DA. Assessment of hypercoagulable states by measurement of activation fragments and peptides. Blood Rev 1990; 4: 25-40
  • 17 Nossel HL, Wasser J, Kaplan KL, LaGamma KS, Yudelman I, Canfield RE. Sequence of fibrinogen proteolysis and platelet release after intrauterine infusion of hypertonic saline. J Clin Invest 1979; 64: 1371-1378
  • 18 Balakrishnan G, Brownlie J, Webber R, Gibson B. Enhanced thrombin generation in patients receiving intensive care. Arch Dis Child 1991; 66: 1413-1415
  • 19 Henriksson P, Ekelund H. Abnormal proteolysis in sick newborns. Acta Paediat Scand 1975; 64: 327-336
  • 20 Langley PG, Forbes A, Hughes RD, Williams R. Thrombin-antithrombin III complex in fulminant hepatic failure: evidence for disseminated intravascular coagulation and relationship to outcome. Eur J Clin Invest 1990; 20: 627-631
  • 21 Owen J. For the Fibrinogen Subcommittee of the Scientific and Standardization Committee of the International Society on Thrombosis and Hemostasis. The utility of plasma fibrinopeptide assays. Thromb Haemostas 1989; 62: 807-810