Advertisement

European Journal of Pediatrics

, Volume 155, Issue 1, pp 20–25 | Cite as

Purpura fulminans in severe congenital protein C deficiency: Monitoring of treatment with protein C concentrate

  • F. -M. Müller
  • W. Ehrenthal
  • G. Hafner
  • D. Schranz
Hematology/Oncology

Abstract

This report describes the successful use of protein C concentrate to treat severe purpura fulminans in a homozygous protein C-deficient infant for 8 months until oral anticoagulation was initiated. While fresh frozen plasma was previously used in such cases to replace protein C in the acute phase, the availability of a monoclonal antibody purified protein C concentrate now allows specific replacement of protein C, avoiding problems of fluid overload. An occlusive-hydrocolloid bandage proved to be effective in local treatment of skin lesions. D-dimer, fibrin monomer, thrombin-antithrombin complex and prothrombin fragment 1+2 were useful markers in monitoring and optimizing protein C replacement therapy.

Key Words

Purpura fulminans Severe congenital protein C deficiency Protein C concentrate Coagulation marker 

Abbreviations

aPTT

activated partial thromboplastin time

DIC

disseminated intravascular coagulation

F1+2

prothrombin fragment 1+2

FM

fibrin monomer

t-PA

tissue plasminogen activator

TAT

thrombin-antithrombin complex

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Andrew M, Vegh P, Johnston M, Bowker J, Ofosu F, Mitchell L (1992) Maturation of the hemostatic system during childhood. Blood 80: 1998–2005PubMedGoogle Scholar
  2. 2.
    Auberger K (1992) Evaluation of a new protein-C concentrate and comparison of protein-C assays in a child with congenital protein-C deficiency. Ann Hematol 64: 1–6Google Scholar
  3. 3.
    Broekmans AW, Veltkamp JJ, Bertina RM (1983) Congenital protein C deficiency and venous thromboembolism. N Engl J Med 309 (6): 340–344PubMedGoogle Scholar
  4. 4.
    Casella JF, Lewis JH, Bontempo FA, et al (1988) Successful treatment of homozygous protein C deficiency by hepatic transplantation. Lancet I: 435–438Google Scholar
  5. 5.
    Clouse LH, Comp PC (1986) The regulation of hemostasis: the protein C system. N Engl J Med 314 (20): 1298–1304PubMedGoogle Scholar
  6. 6.
    Comp PC, Elrod JP, Karzenski S (1990) Warfarin-induced skin necrosis. Semin Thromb Hemost 16 (4): 293–298PubMedGoogle Scholar
  7. 7.
    Comp PC, Esmon CT (1981) Generation of fibrinolytic activity by infusion of activated protein C into dogs. J Clin Invest 68: 1221–1228PubMedGoogle Scholar
  8. 8.
    Conard J, Bauer K, Gruber A, Griffin JH, Schwarz HP, Horellou MH, Samama MM, Rosenberg RD (1993) Normalization of markers of coagulation activation with a purified protein C concentrate in adults with homozygous protein C deficiency. Blood 82: 1159–1164PubMedGoogle Scholar
  9. 9.
    Dempfle CE, Dollman M, Lill H, Puzzovio D, Dessauer A (1993) Binding of a new monoclonal antibody against N-terminal heptapeptide of fibrin polymerization site “A”: effects of fibrinogen and fibrinogen derivatives, and pretreatment of samples with NaSCN. Blood Coagul Fibrinolysis 4: 79–86PubMedGoogle Scholar
  10. 10.
    De Stefano V, Mastrangelo S, Schwarz HP, Pola P, Flore R, Bizzi B, Leone G (1993) Replacement therapy with a purified protein C concentrate during initiation of oral anticoagulation in severe protein C congenital deficiency. Thromb Haemost 70: 247–249PubMedGoogle Scholar
  11. 11.
    Dreyfus M, Magny JF, Bridey F et al (1991) Treatment of homozygous protein C deficiency and neonatal purpura fulminans with a purified protein C concentrate. N Engl J Med 325: 1565–1568PubMedGoogle Scholar
  12. 12.
    Egbring R, Seitz R (1989) Angeborene Hämostasestörungen mit Thromboseneigung. Internist 30: 577–586PubMedGoogle Scholar
  13. 13.
    Esmon CT (1989) The roles of protein and thrombomodulin in the regulation of blood coagulation. J Biol Chem 264: 4743–4746PubMedGoogle Scholar
  14. 14.
    Fiore CE, Tamburino C, Foti R, Grimaldi D (1990) Reduced axial bone mineral content in patients taking an oral anticoagulant. South Med J 83: 538–542PubMedGoogle Scholar
  15. 15.
    Garcia-Plaza I, Jimencz-Astorga C, Borrego D, et al (1985) Coumarin prophylaxis for fulminant purpura syndrome due to homozygous protein C deficiency. Lancet I: 634–635Google Scholar
  16. 16.
    Gerson WT, Dickerman JD, Bovill EG, Golden E (1993) Severe acquired protein C deficiency in purpura fulminans associated with disseminated intravascular coagulation: Treatment with Protein C Concentrate. Pediatrics 91: 418–422PubMedGoogle Scholar
  17. 17.
    Hartmann KR, Manco-Johnson M, Rawlings JS, et al (1989) Homozygous protein C deficiency: early treatment with warfarin. Am J Pediatr Hematol Oncol 11 (4): 395–401PubMedGoogle Scholar
  18. 18.
    Horowitz IN, Galuis AG, Gomperts ED (1992) Arterial thrombosis and protein S deficiency. J Pediatr 121 (6): 934–937PubMedGoogle Scholar
  19. 19.
    Hubbard AR (1988) Standardization of protein C in plasma: establishment of an international standard. Thromb Haemost 59: 464–467PubMedGoogle Scholar
  20. 20.
    Jones DW, Mackie IJ, Winter M, et al (1991) Detection of protein C deficiency during oral anticoagulant therapy—use of the protein C: factor VII ratio. Blood Coagul Fibrinolysis 2 (3): 407–411PubMedGoogle Scholar
  21. 21.
    Leclerc F, Hazelzet J, Jude B, et al (1992) Protein C and S deficiency in severe infectious purpura of children: a collaborative study of 40 cases. Intensive Care Med 18: 202–205PubMedGoogle Scholar
  22. 22.
    Mahasandana C, Suvatte V, Marlar RA, et al (1990) Neonatal purpura fulminans associated with homozygous protein S deficiency. Lancet 335: 61–62Google Scholar
  23. 23.
    Manco-Johnson MJ, Nuss R (1992) Protein C concentrate prevents peripartum thrombosis. Am J Hematol 40: 69–70PubMedGoogle Scholar
  24. 24.
    Manco-Johnson MJ, Marlar RA, Jacobson LJ, et al (1988) Severe protein C deficiency in newborn infants. J Pediatr 113: 359–363PubMedGoogle Scholar
  25. 25.
    Marlar RA, Mastovich S (1990) Hereditary protein C deficiency: a review of the genetics, clinical presentation, diagnosis and treatment. Blood Coagul Fibrinolysis 1 (3): 319–330PubMedGoogle Scholar
  26. 26.
    Marlar RA, Neumann A (1990) Neonatal purpura fulminans due to homozygous protein C or protein S deficiencies. Semin Thromb Hemost 16 (4): 299–304PubMedGoogle Scholar
  27. 27.
    Marlar RA, Montgomery RR, Broekmans AW (1989) Report on the diagnosis and treatment of homozygous protein C deficiency. Thromb Haemost 61 (3): 529–531PubMedGoogle Scholar
  28. 28.
    Marlar RA, Montgomery RR, Brockmans AW (1989) Diagnosis and treatment of homozygous protein C deficiency. J Pediatr 114: 528–534PubMedGoogle Scholar
  29. 29.
    Miletich JP (1990) Laboratory diagnosis of protein C deficiency. Semin Thromb Hemost 16 (2): 169–176PubMedGoogle Scholar
  30. 30.
    Mimuro J, Sakata Y, Wakabayashi K, et al (1987) Level of protein C determined by combined assays during disseminated intravascular coagulation and oral anticoagulation. Blood 69 (6): 1704–1711PubMedGoogle Scholar
  31. 31.
    Nardi M, Karpatkin M (1986) Prothrombin and protein C in early childhood: Normal adult levels are not achieved unitl the fourth year of life. J Pediatr 109 (5): 843–845PubMedGoogle Scholar
  32. 32.
    O'Sullivan J, Chatuverdi R, Bennett MK, Hunter S (1992) Protein S deficiency: early presentation and pulmonary hypertension. Arch Dis Child 67: 960–961PubMedGoogle Scholar
  33. 33.
    Pabinger I, Kyrle PA, Speiser W (1990) Diagnosis of protein C deficiency in patients on oral anticoagulant treatment: comparison of three different functional protein C assays. Thromb Haemost 63 (3): 407–412PubMedGoogle Scholar
  34. 34.
    Pabinger-Fasching I, Lechner K, Niessner H, et al (1987) Protein C and coagulation factor levels during the initial phase of oral anticoagulant therapy (low dose regimen) in a patient with heterozygous protein C deficiency. Thromb Res 47: 705–708PubMedGoogle Scholar
  35. 35.
    Pelzer H, Schwarz A, Heimburger N (1988) Determination of human thrombin-antithrombin III complex in plasma with an enzyme-linked immunosorbent assay. Thromb Haemost 59: 101–106PubMedGoogle Scholar
  36. 36.
    Pelzer H, Schwarz A, Stüber W (1991) Determination of human prothrombin activation fragment 1+2 in plasma with an antibody against a synthetic peptide. Thromb Haemost 65: 153–159PubMedGoogle Scholar
  37. 37.
    Petrini P, Segnestam K, Ekelund H, Egberg N (1990) Homozygous protein C deficiency in two siblings. Pediatr Hematol Oncol 7 (2): 165–175PubMedGoogle Scholar
  38. 38.
    Reitsma PH, Poort SR, Allaart CF, et al (1991) The spectrum of genetic defects in a panel of 40 dutch families with symptomatic protein C deficiency type, I: heterogeneity and founder effects. Blood 78 (4): 890–894PubMedGoogle Scholar
  39. 39.
    Sanders CR, Majer RV, Green PJ (1989) Protein C deficiency: spontaneous healing of necrotic rash on warfarin (letter). Clin Lab Haematol 11 (1): 74–75PubMedGoogle Scholar
  40. 40.
    Schettini F, Mattia D de, Altomare M, et al (1985) Post-natal development of protein C in full-term newborns. Acta Paediatr Scand 74: 226–229PubMedGoogle Scholar
  41. 41.
    Schramm W, Spannagl M, Bauer KA, Rosenberg R, Birkner B, Linnau Y, Schwarz HP (1993) Treatment of coumarin-induced skin necrosis with a monoclonal antibody purified protein C concentrate. Arch Dermatol 129: 753–756PubMedGoogle Scholar
  42. 42.
    Seligsohn U, Berger A, Abend M, et al (1984) Homozygous protein C deficiency manifested by massive venous thrombosis in the newborn. N Engl J Med 310 (9): 559–562PubMedGoogle Scholar
  43. 43.
    Störtzer KE, Amiral J, Spannuth E (1988) Neue Methoden zur spezifischen Bestimmung von Fibrinspaltprodukten (D-Dimere). Lab Med 12: 51–59Google Scholar
  44. 44.
    Wehinger H, Geiger E, Freudenberg V, et al (1985) Schwerer hereditärer Protein-C-Mangel bei einem Neugeborenen mit Purpura fulminans—erfolgreiche Behandlung mit Phenprocoumon. Klin Pädiatr 197: 116–120Google Scholar
  45. 45.
    Witt I, Wehinger H (1990) Das Protein-C-System bei Kindern. Hämostaseologie 10: 125–129Google Scholar

Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • F. -M. Müller
    • 1
    • 3
  • W. Ehrenthal
    • 2
  • G. Hafner
    • 2
  • D. Schranz
    • 1
  1. 1.University Children's HospitalMainzGermany
  2. 2.Institute of Clinical ChemistryUniversity HospitalMainzGermany
  3. 3.University Children's HospitalAachenGermany

Personalised recommendations