13 8
Clinical and laboratory observations
of this entity in children. Heparin is used much less frequently in this age group and is usually given in the setting of cardiopulmonary bypass, extracorporeal membrane oxygenation, or dialysis, which may not necessitate prolonged exposure to heparin. 5 Many children are also treated during infancy and may not have an immune system competent to mount an immune response. It is also possible that, because children do not have other risk factors for thrombosis, thrombosis may not occur as frequently and thrombocytopenia may be overlooked or attributed to other, nonspecific causes, such as suspected but unproved infection. We conclude that HIT may occur in the pediatric age group and recommend that platelet counts be monitored in children receiving heparin therapy. Clinicians should remain aware of this possibility in children who have thrombocytopenia while receiving heparin therapy. Diagnostic studies to rule out thrombosis and a 14C-serotonin-release test should be carried out in patients with any symptoms suggestive of thrombosis. Prospective studies of children receiving heparin therapy are warranted and will better define this drug-induced complication in the pediatric age group.
The Journal of Pediatrics July 1992
REFERENCES
1. Warkentin TE, Kelton JG. Heparin and platelets. Hematol Oncol Clin North Am 1990;4:243-64. 2. Warkentin TE, Kelton JG. Heparin-induced thrombocytopenia. Annu Rev Med 1989;40:31-44. 3. Miller ML. Heparin-induced thrombocytopenia. Cleve Clin J Med 1989;56:483-90. 4. Warkentin TE, Kelton JG. Heparin-indueed thrombocytopenia. In: Coller BS, ed. Progress in hemostasis and thrombosis. Philadelphia: WB Saunders, 1991:1-34. 5. Bell WR. Heparin-associated thrombocytopenia and thrombosis. J Lab Clin Med 1988;111:600-5. 6. Oriot D, Wolfe M, Wood C, et al. Severe thrombocytopenia induced by heparin in an infant with acute myocarditis. Arch Fr Pediatr 1990;47:357-9. 7. Howe SE, Lynch DM, Lynch JM. An enzyme-linked immunosorbent assay for the quantification of serum platelet-bindable IgG. Transfusion 1984;24:348-52. 8. Schiffer CA, Young V. Detection of platelet antibody using a micro-enzyme-linkedimmunosorbent assay (ELISA). Blood 1983;61:811-7. 9. Cola C, Ansel J. Heparin-induced thrombocytopenia and arterial thrombosis: alternative therapies. Am Heart J 1990; 118:368-74. 10. Kelton JG, Sheridan D, Santos A, et al. Heparin-induced thrombocytopenia:laboratory studies. Blood 1988;72:925-30.
Effects of ursodeoxycholic acid on liver function in patients with cystic fibrosis and chronic cholestasis C. G a l a b e r t , PhD, J. C. M o n t e t , PhD, D. L e n g r a n d , A. L e c u i r e , C. S o t t a , C. F i g a r e l l a , PhD, MD, a n d J. P. C h a z a l e t t e , MD From the Laboratoire de Biochimie et Centre d'Etudes et Recherches sur la Mucoviscidose, H6pital Ren6e Sabran (Hopitaux de Lyon) Glens, Hy~res, France, Groupe de Recherche sur les Glandes Exocrines (INSERM), Marseille, France, and Laboratoire de Biochimie, H6pital de la Croix Rousse (Hopitaux de Lyon), Lyon, France
Ursodeoxycholic acid, 10 to 20 m g / k g per day, was administered for I year to 22 patients with cystic fibrosis and chronic cholestasis, resulting in significantly improved liver enzyme values. However, evidence of cholestasis continued, as shown by the pattern of alkaline phosphatase isoenzymes. (J PEDIATR1992;121: 138-41) Exocrine secretions in patients with cystic fibrosis are generally dehydrated because of an epithelial transport defect. The abnormal biliary secretion is considered an important Supported by grants from the Association Fran~aise.de Lutte contre la Mucoviscidoseand the Caisse R6gionale d~:A~suranceMaladie du Sud-Est. Submitted for publication Aug. 7, 1991; accepted Feb. 3, 1992. Reprint requests: C. Galabert, PhD, Laboratoire de Biologic, Hopital Ren6e Sabran (Hopitaux de Lyon) Giens, 83406, Hy6res Cedex, France. 9/26/36785
factor in the hepatopathy in CF, 1causing inspissation in the biliary ductules, which leads to plug formation, cholestasis, subsequent .inflammation, duetular proliferation, and finally focal biliary cirrhosis and multilobular cirrhosis. 2 Additionally, bile acid malabsorption and fecal loss of taurine lead to the enrichment of bile with hydrophobic, potentially cytotoxic bile acids) Ursodeoxycholic acid, a hydrophilic bile acid 4 with potent choleretic properties, 5 has been shown to protect the hepatocyte against the cytotoxic effects of hydrophobic bile acids.6, 7 Recently UDCA was proposed for the treatment
Volume 121 Number 1
Clinical and laboratory observations
1 39
T a b l e . Liver function tests, retinol-binding protein, and fecal fat before and after 1 year of U D C A t r e a t m e n t in 22 patients with C F and chronic cholestasis Parameters
ALP total (U/L) ALP-1 (U/L) ALP-2 (U/L) ALP-3 (U/L) AST ( U / L ) ALT (U/L) GGT (U/L) 5'-Nu (U/L) Bilirubin (~mol/L) BA (#mol/L) Fasting Postprandial RBP (mg/L) Fecal fat~: (gm%)
Normal range
Pretreatment values
Posttreatment v a l u e
p*
Clinical and laboratory observations
of this entity in children. Heparin is used much less frequently in this age group and is usually given in the setting of cardiopulmonary bypass, extracorporeal membrane oxygenation, or dialysis, which may not necessitate prolonged exposure to heparin. 5 Many children are also treated during infancy and may not have an immune system competent to mount an immune response. It is also possible that, because children do not have other risk factors for thrombosis, thrombosis may not occur as frequently and thrombocytopenia may be overlooked or attributed to other, nonspecific causes, such as suspected but unproved infection. We conclude that HIT may occur in the pediatric age group and recommend that platelet counts be monitored in children receiving heparin therapy. Clinicians should remain aware of this possibility in children who have thrombocytopenia while receiving heparin therapy. Diagnostic studies to rule out thrombosis and a 14C-serotonin-release test should be carried out in patients with any symptoms suggestive of thrombosis. Prospective studies of children receiving heparin therapy are warranted and will better define this drug-induced complication in the pediatric age group.
The Journal of Pediatrics July 1992
REFERENCES
1. Warkentin TE, Kelton JG. Heparin and platelets. Hematol Oncol Clin North Am 1990;4:243-64. 2. Warkentin TE, Kelton JG. Heparin-induced thrombocytopenia. Annu Rev Med 1989;40:31-44. 3. Miller ML. Heparin-induced thrombocytopenia. Cleve Clin J Med 1989;56:483-90. 4. Warkentin TE, Kelton JG. Heparin-indueed thrombocytopenia. In: Coller BS, ed. Progress in hemostasis and thrombosis. Philadelphia: WB Saunders, 1991:1-34. 5. Bell WR. Heparin-associated thrombocytopenia and thrombosis. J Lab Clin Med 1988;111:600-5. 6. Oriot D, Wolfe M, Wood C, et al. Severe thrombocytopenia induced by heparin in an infant with acute myocarditis. Arch Fr Pediatr 1990;47:357-9. 7. Howe SE, Lynch DM, Lynch JM. An enzyme-linked immunosorbent assay for the quantification of serum platelet-bindable IgG. Transfusion 1984;24:348-52. 8. Schiffer CA, Young V. Detection of platelet antibody using a micro-enzyme-linkedimmunosorbent assay (ELISA). Blood 1983;61:811-7. 9. Cola C, Ansel J. Heparin-induced thrombocytopenia and arterial thrombosis: alternative therapies. Am Heart J 1990; 118:368-74. 10. Kelton JG, Sheridan D, Santos A, et al. Heparin-induced thrombocytopenia:laboratory studies. Blood 1988;72:925-30.
Effects of ursodeoxycholic acid on liver function in patients with cystic fibrosis and chronic cholestasis C. G a l a b e r t , PhD, J. C. M o n t e t , PhD, D. L e n g r a n d , A. L e c u i r e , C. S o t t a , C. F i g a r e l l a , PhD, MD, a n d J. P. C h a z a l e t t e , MD From the Laboratoire de Biochimie et Centre d'Etudes et Recherches sur la Mucoviscidose, H6pital Ren6e Sabran (Hopitaux de Lyon) Glens, Hy~res, France, Groupe de Recherche sur les Glandes Exocrines (INSERM), Marseille, France, and Laboratoire de Biochimie, H6pital de la Croix Rousse (Hopitaux de Lyon), Lyon, France
Ursodeoxycholic acid, 10 to 20 m g / k g per day, was administered for I year to 22 patients with cystic fibrosis and chronic cholestasis, resulting in significantly improved liver enzyme values. However, evidence of cholestasis continued, as shown by the pattern of alkaline phosphatase isoenzymes. (J PEDIATR1992;121: 138-41) Exocrine secretions in patients with cystic fibrosis are generally dehydrated because of an epithelial transport defect. The abnormal biliary secretion is considered an important Supported by grants from the Association Fran~aise.de Lutte contre la Mucoviscidoseand the Caisse R6gionale d~:A~suranceMaladie du Sud-Est. Submitted for publication Aug. 7, 1991; accepted Feb. 3, 1992. Reprint requests: C. Galabert, PhD, Laboratoire de Biologic, Hopital Ren6e Sabran (Hopitaux de Lyon) Giens, 83406, Hy6res Cedex, France. 9/26/36785
factor in the hepatopathy in CF, 1causing inspissation in the biliary ductules, which leads to plug formation, cholestasis, subsequent .inflammation, duetular proliferation, and finally focal biliary cirrhosis and multilobular cirrhosis. 2 Additionally, bile acid malabsorption and fecal loss of taurine lead to the enrichment of bile with hydrophobic, potentially cytotoxic bile acids) Ursodeoxycholic acid, a hydrophilic bile acid 4 with potent choleretic properties, 5 has been shown to protect the hepatocyte against the cytotoxic effects of hydrophobic bile acids.6, 7 Recently UDCA was proposed for the treatment
Volume 121 Number 1
Clinical and laboratory observations
1 39
T a b l e . Liver function tests, retinol-binding protein, and fecal fat before and after 1 year of U D C A t r e a t m e n t in 22 patients with C F and chronic cholestasis Parameters
ALP total (U/L) ALP-1 (U/L) ALP-2 (U/L) ALP-3 (U/L) AST ( U / L ) ALT (U/L) GGT (U/L) 5'-Nu (U/L) Bilirubin (~mol/L) BA (#mol/L) Fasting Postprandial RBP (mg/L) Fecal fat~: (gm%)
Normal range
Pretreatment values
Posttreatment v a l u e
p*
