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DOI: 10.1055/s-0038-1650391
Inherited Prethrombotic Disorders and Infectious Purpura
Publikationsverlauf
Received 27. Juli 1995
Accepted after resubmission 13. März 1996
Publikationsdatum:
11. Juli 2018 (online)
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Summary
Patients with severe meningococcal infection are characterized by extensive microvascular thrombosis, consumption coagulopathy and secondary hemorrhages. The contribution of the inherited prethrombotic disorders to the severity of the disease course is not established yet. Here, we report on the levels of protein C, protein S, antithrombin and the presence of the factor V Leiden mutation (R506Q) in 50 patients with meningococcal disease, as determined 6 to 58 months after hospital discharge. In addition, we recalled the parents of 16 deceased patients to screen for the mutation in factor V, an abnormality which results in resistance to activated protein C. Among the patients, the prevalence of the genetic risk factors for thrombosis was not higher than expected on the basis of their prevalence in the general population. Moreover, the prevalence of the factor V Leiden mutation was not increased among the parents of the deceased patients. The individual plasma levels of protein C, protein S, and antithrombin did not differ between the patients with or without severe purpura. The present data constitute circumstantial evidence that primary defects in the natural anticoagulant systems do not play a major role in the severity of the disease course. Screening of patients with infectious purpura for inherited thrombotic risk factors is therefore not indicated.
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References
- 1 Laursen B, Faber V, Brock A, Gormsen J, Sorensen S. Disseminated intravas-cular coagulation, antithrombin III and complement in meningococcal infections. Acta Med Scan 1981; 209: 221-227
- 2 Leclerc F, Hazelzet J, Jude B, Hofhuis W, Hue V, Martinot A, Van der Voort E. Protein C and S deficiency in severe infectious purpura of children: a collaborative study of 40 cases. Intensive Care Med 1992; 18: 202-205
- 3 Powars D, Larsen R, Johnson J, Hulbert T, Sun T, Patch MJ, Francis R, Chan L. Epidemic meningococcemia and purpura fulminans with induced protein C deficiency. Clin Infect Dis 1993; 17: 254-261
- 4 Fijnvandraat K, Derkx B, Peters M, Bijlmer R, Sturk A, Prins MH, van Deventer SJH, ten Cate JW. Coagulation activation and tissue necrosis in meningococcal septic shock: Severely reduced protein C levels predict a high mortality. Thromb Haemost 1995; 73: 15-20
- 5 Taylor FB, Chang A, Esmon CT, D’Angelo A, Vigano-D’Angelo S, Blick KE. Protein C prevents the coagulopathic and lethal effects of Escherichia coli infusion in the baboon. J Clin Invest 1987; 79: 918-925
- 6 Taylor FB, Chang A, Ferrell G, Mather T, Catlett R, Blick K, Esmon CT. C4b-Binding protein excerbates the host response to Escherichia coli. Blood 1991; 78: 357-363
- 7 Redens TB, Emerson TE. Antithrombin III treatment limits disseminated intra-vascular coagulation in endotoxemia. Circ Shock 1989; 28: 49-58
- 8 Bertina RM, Koeleman RPC, Koster T, Rosendaal FR, Dirven RJ, de Ronde H, van der Velden PA, Reitsma PH. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994; 369: 64-67
- 9 Svensson PJ, Dahlbäck B. Resistance to activated protein C as a basis for venous thrombosis. N Engl J Med 1994; 330: 517-522
- 10 Perkins WP, Downie I, Keefe M, Chisholm M. Cutaneous necrosis in pregnancy secondary to activated protein C in hereditary angioedema. J Roy Soc Med 1995; 88: 229-30
- 11 Westendorp RGJ, Langermans JAM, de Bel CE, Meinders AE, Vanden-broucke JP, van Furth R, van Dissel JT. Release of tumor necrosis factor: An innate host characteristic that may contribute to the outcome of meningococcal disease. J Infect Dis 1995; 171: 1057-1060
- 12 Tait RC, Walker ID, Reitsma PH, Islam SIAM, McCall F, Poort SR, Conkie JA, Bertina RM. Prevalence of Protein C deficiency in the healthy population. Thromb Haemost 1995; 73: 87-93
- 13 Deutz-Terlouw PP, Ballering L, van Wijngaarden A, Bertina RM. Two ELISA’s for measurement of protein S, and their use in the laboratory diagnosis of protein S deficiency. Clin Chim Acta 1990; 186: 321-134
- 14 Tait RC, Walker ID, Islam SIAM, McCall F, Conlie JA, Wight M, Mitchell R, Davidson JF. Protein C activity in healthy volunteers - Influence of age, sex, smoking and oral contraceptives. Thromb Haemost 1993; 70: 281-285
- 15 de Ronde H, Bertina RM. Laboratory diagnosis of APC-resistance: a critical evaluation of the test and the development of diagnostic criteria. Thromb Haemost 1994; 72: 880-886
- 16 Ferguson JH, Chapman OD. Fulminating meningococcal infections and the so-called Waterhouse-Friderichsen syndrome. Am J Path 1947; 24: 763-795
- 17 Hardman JM. Fatal meningococcal infections: The changing pathologic picture in the ‘60s. Military Medicine 1968; 12: 951-964
- 18 Bohm N. Adrenal, cutaneous and myocardial lesions in fulminating endo-toxinemia. Path Res Pract 1982; 174: 92-105
- 19 Moore KL, Andreoli SP, Esmon N, Esmon CT, Bang NU. Endotoxin enhances tissue factor and suppresses thrombomodulin expression of human vascular endothelium in vitro. J Clin Invest 1987; 79: 124-130
- 20 Koster T, Rosendaal FR, Briët E, van der Meer FJM, Colly LP, Trienekens PH, Poort SR, Reitsma PH, Vandenbroucke JP. Protein C deficiency in a controlled series of unselected outpatients: an infrequent but clear risk factor for venous thrombosis. The Leiden Thrombophilia study. Blood 1995; 85: 2756-2761
- 21 Tait RC, Walker ID, Perry DJ, Islam SIAM, Daly ME, McCall F, Conkie JA, Carrell RW. Prevalence of antithrombin deficiency in the healthy population. Br J Haematol 1994; 87: 106-112
- 22 Rivard GE, David M, Farrell C, Schwarz HP. Treatment of purpura fulminans in meningococcemia with protein C concentrate. J Pediatr 1995; 426: 646-652
- 23 Brandtzaeg P, Kierulf P, Gaustad P, Skulberg A, Bruun JN, Halvorsen S, Sorensen E. Plasma endotoxin as a predictor of multiple organ failure and death in systemic meningococcal disease. J Inf Dis 1989; 159: 195-204
- 24 Girardin E, Roux-lombard P, Grau GE, Suter P, Gallati H. the J5 study group, Dayer J-M. Imbalance between tumour necrosis factor-alpha and soluble TNF receptor concentrations in severe meningococcaemia. Immunology 1992; 76: 20-23