(Actu Puediutr Jpn 1992; 34: 469
-
472)
Disseminated Intravascular Coagulation Syndrome in Anorexia Nervosa Kenji Katamura, M.D., Fuminori Ishimoto, M.D., Masue Yamasaki, M.D., Masaki Yoshimura, M.D. and Toshirou Kisa, M.D. Department of Pediatrics, Shimane Prefectural Central Hospital, Shimane, Japan
A 15 year old boy with anorexia nervosa developed disseminated intravascular coagulation syndrome (DIC). Because of severe cachexia he had been admitted to the Shimane Prefectural Central Hospital. During his hospitalization he developed generalized massive ecchymosis. Laboratory data revealed not only DIC but also multiple organ complications. The patient was treated intravenously with FOY@(gabexatemesilate, a protease inhibitor), heparin, a transfusion of fresh frozen plasma, antithrombin I11 concentrates and platelets. Intravenous hyperalimentation was also administered. The laboratory data, the general condition and the emotional state of the patient improved remarkably. We emphasize the importance of keeping in mind coagulopathy as a complication in anorexia nervosa.
Key Words Anorexia nervosa, Disseminated intravascular coagulation syndrome, Multiple organ complications
Case Report A 15 year old boy was admitted to the Pediatric Department of Shimane Prefectural Central Hospital because of profound weight loss. The patient had lost about 25% of his initial bodyweight over 4 months. Laboratory examinations revealed no abnormal data at this point. During the personal assessment, however, he revealed that he did not think his weight loss was severe, and that he had reduced his food intake for fear of becoming fat. Besides reducing his diet, he
Received December 3, 1991 Revised March 13, 1992 Accepted March 26, 1992 Correspondence address: Kenji Katamura, M.D., Department of Pediatrics, Shimane Prefectural Central Hospital, 1 16 Imaichi-cho, Izumo-city, Shimane 693, Japan.
had also habitually used a kind of herbal medicine as a laxative. At this point, weight loss was suggested to be psychogenic in nature and he was referred to the Department of Psychiatry. Psychotherapy was begun by a psychiatrist and anorexia nervosa was diagnosed. The patient was later discharged so he could prepare for the upcoming high school entrance examination, but the anorexia persisted. One week later, he was readmitted to the Department of Psychiatry because of general fatigue. At that time his weight was 35.2 kg, a 37% loss of his original weight (56 kg). He could barely walk. His serum total protein level was 6.7 g/dl (albumin 4.6 g and globulin 2.1 g/dl), total bilirubin 1.3 mg/dl, urea nitrogen 44.6 mgl dl, and creatinine 1.2 mg/dl. The serum glutamate oxaloacetate transaminase (GOT) was 45 U (normally, 8-40), glutamic-pyruvic transaminase (GPT) 48 U (normally 5-35), the
470 (86) Katamrira el a/.
LDH 1204 U and amylase 1549 U. The serum sodium was 132.6 mEq/l, potassium 4.5 mEq/l, chloride 96.2 mEq/l and bicarbonate 22.9 mEq/l. The diagnosis was disseminated intravascular coagulation syndrome (DIC) with multiple organ complications. The patient was treated intravenously with 1.5 mg/kg per hr FOY@ (gabexate mesilate, a proteinase inhibitor), 7 U/ kg per hr heparin and maintenance fluids. Five hours later the platelet count had been reduced to 27.00O/pl. He received a transfusion consisting of 5 units of platelets, 1,500 units of antithrombin I11 concentrates and two packs of fresh frozen plasma. The treatment and the change of the laboratory examinations are shown (Fig. 1, Table 1). On the second hospital day, the patient was fully conscious and there was no further increase in his subcutaneous hemorrhages. The platelet count had increased to 65,00O/pI. The prothrombin time had decreased to 21.6 sec with a control of 1 1.6 sec, and the activated partial thromboplastin time had decreased to 102.4 sec with a control of 38.4 sec. The fibrinogen level rose to 72 mg/dl. The total serum protein was 6.1 g/dl, total bilirubin 2.8 mg/dl, urea nitrogen 65.4 mg/dl and creatinine 1.4 mg/dl. The serum GOT was 180 U, GPT 195 U, LDH 943 U and
lactic dehydrogenase (LDH) 548 U (normally 150-400), the amylase 227 U (normally 90-280). Ten days later, some petechiae were noticed, and they increased rapidly. Thirteen days later he developed generalized massive ecchymosis and complained of severe fatigue. The patient was transferred to the Pediatric Department to be examined for any bleeding tendencies. He was cachectic and slightly drowsy but well oriented. Temperature was 36.6-C. pulse rate 60 beats/min and respiration 28/min. The blood pressure was 1 14/82 mmHg. The hemoglobin was 16.0 g/dl, hematocrit 44.8Y0, white cell count 9.40O/pl with 1% band forms. 50% polymorphonuclear neutrophils, 44% lymphocytes and 5% monocytes. The platelet count was 47,0OO/p1. The prothrombin time was 26.6 sec. with a control of 11.6 sec; the activated partial thromboplastin time was over 180 sec, with a control of 38.4 sec. The fibrinogen was 55 mg/ dl, antithrombin III was 65% (normally. 80120%) and D-dimer was 1,000-2,000 ng/ml (normally < 200 ng/rnlf. The level of fibrin split products was 10 pgirnl (normally, < 10 pg/ml). The total protein was 5.9 g/dl (albumin 4.0g and globulin 1.9 g/dl), total bilirubin 2.5 mg/dl. urea nitrogen 92.4 mg/dl and creatinine 1.8 mg/ dl. The serum GOT was 440U. GPT 270U. Treatment
Plateiet
Heparin1
FOY 5 units of platelet 160 ml of fresh frozen plasma 1500 units of anlilhrombin 111
Plasma
fibrinogen
a:
'0 tot
1
2
3
d
5
6
7
8
9
10
11
I2
13
-2
i
1
i
1
Time (days)
Fig. 1 : Treatment and change of laboratory examinations after hospitalization
Acta Paediatr Jprt
DIC in anorexia nervosa (87) 47 1 Table 1. Improvement of liver, pancreas and renal function Time course (hospital days)
Function
- 13
1
2
3
GOT (U) 45 GPT (U) 48 LDH (U) 548 Amylase (U) 221 Creatinine (mg/dl) 1.2 BUN (mg/dl) 44.6 BUN, blood urea nitrogen.
440
180 195 943 688 1.4 65.4
121 159 654 1.0 38.4
270
1204 1549
1.8 92.4
amylase 688 U. The intravenous administration of FOY@was continued and antithrombin I11 and two packs of fresh frozen plasma were transfused. The intravenous administration of heparin was ceased. On the third hospital day, the platelet count was 57,00O/pl. The prothrombin time was 16.1 sec and the activated partial thromboplastin time was 56.3 sec. The fibrinogen level was 103 mg/dl, antithrombin I11 was 118%, and D-dimer was 500-1,000 ng/ml. The level of fibrin split products was below 10 pglml. The serum GOT continued to decrease to 127U, the GPT to 159 U and the amylase to 654 U. The urea nitrogen was 38.4 mg/dl and the creatinine was 1.O mg/dl. Tube feeding was also commenced. On the fourth hospital day, the platelet count decreased to 41,0OO/p1, but the other coagulation data improved further. On the sixth hospital day, the platelet count still remained around 40,0OO/pl. The serum GOT was 96 U, the GPT 131 U and the amylase 292 U. The urea nitrogen was 11.6 mddl and the creatinine 0.7 mg/dl. The patient refused tube feeding and started eating on his own. On the eighth hospital day, intravenous hyperalimentation was also administered; On the ninth hospital day, the platelet count had increased to 67,0OO/p1. The prothrombin time was 13.6 sec with a control of 11.3 sec, and the activated partial thromboplastin time was 38.6 sec with a control of 38.4 sec. The fibrinogen level was 271 mg/dl, antithrombin I11 was 84% and D-dimer was 500-1,000ng/ml. The level of fibrin split products was below 10 pg/ml. At this point the administration of intravenous F O P was ceased. On the sixteenth hospital
Vol. 34 No. 4 August 1992
6 96 131
-
292
-
11.6
41
13 10 336 136 0.5 7.3
day, the patient’s weight was 35 kg. He recovered his usual appetite and began gaining weight. The subcutaneous ecchymosis became faint. On the thirty-third hospital day, intravenous hyperalimentation was stopped. The patient’s weight at this point was 39.0 kg. On the forty-first hospital day, the serum GOT was 13 U, GPT 10 U, LDH 336 U, amylase 136 U, urea nitrogen 7.3 mg/dl and creatinine 0.5 mg/dl. The patient was discharged 103 days after his initial admission. His weight was 44.3 kg and his emotional state had improved remarkably.
Discussion To our knowledge, two cases of anorexia nervosa complicated by DIC or by coagulopathy have been reported [I, 21. However, this patient, unlike the others, had not only DIC but also multiple organ complications, at least in the liver, kidney and pancreas. He was treated by transfusion of fresh frozen plasma, platelets and antithrombin 111 and intravenous FOY@,which is a serine proteinase inhibitor that was originally developed as a drug for pancreatitis [3]. After its development, FOY@was found to have a potent anticoagulative effect [4], and is now used widely in Japan as a treatment for DIC. In treating DIC in anorexia nervosa, one must not only treat the syndrome but also try to improve the cachexia as soon as possible. To treat the cachexia is essential, for if the patient does not gain weight, the possibility of developing DIC continues to be a threat. Since this weight gain is essential to the well-being of the patient, intravenous hyperalimentation is needed even after
472 (88) Kacamitru et al. the patient begins eating. Treating the cachexia is also effective in improving the patient’s emotional state. With respect to the pathophysiology of DIC in anorexia nervosa, one also needs to consider the multiple organ hypofunction and the hypercoagulative conditions that may occur as a result of venous stasis, which causes hypoperfusion and leads to hypoxia and malnutrition of multiple organs. Such a condition could readily result in multiple organ complications followed by DIC. Venous stasis may also precipitate thrombosis by causing vascular endothelial damage through local hypoxia [ 5 ] and by retarding the clearance of activated clotting factors from an area of vascular injury [6]. A high incidence of thrombosis has also been reported in patients with stroke and paraplegia and in patients immobilized before surgery [ 7-91. The present case had been bedridden almost all day due to cachexia, and consequently developed generalized ecchymosis. We also had much trouble drawing venous blood from this patient because of a slow blood flow. DIC. therefore, might be triggered by multiple organ dysfunction based on the hypercoagulative condition of the patient. In summary, we have presented a case study of a 15 year old boy with anorexia nervosa complicated by DIC and multiple organ disorders. The patient was treated intravenously with FOY@and heparin and received a transfusion of antithrombin 111 concentrates. fresh
frozen plasma and platelets. Intravenous hyperalimentation was also used to improve the cachexia as soon as possible. The laboratory data, general condition and emotional state improved remarkably. One must keep in mind coagulopathy as a complication in anorexia nervosa. References 1. Brotman AW, Stern TA. Case report of cardiovascular abnormalities in anorexia nervosa. Am J Psychiatry 1983; 140: 1227-1228. -.7 Stutor AH. Schdtte B. Aschoff W et al. Intravascular coagulation in anorexia nervosa. Dtsch Med Wochenschr 1977: 102: 1469-1472. 3. Tamura Y, Hirano M, Okamura K et al. Synthetic inhibitors of trypsin, plasmin, kallikrein, thrombin, C,y and C , esterase. Biochim Biophys Acta 1977; 4 8 4 417-422. 4. Ohno H, Kambayasi J. Chang SW et al. FOY: [Ethyl-p-(6-guanidinohexanoyl)benzoate] methanesulfonateasa serineproteinase inhibitor. 11. In iivo effect on coagulofibrinolytic system in comparison with heparin or aprotinin. Thromb Res 198 1; 24: 445-452. 5. Hamer JD, Malone PC, Silver IA. The PO, in venous valve pockets: Its possible bearing on thrornbogenesis. Br J Surg 1981; 68: 166-170. 6. Shattil SJ. Diagnosis and treatment of recurrent venous thromboembolism. Med Clin N Am 1984; 68: 577-600. 7. Warlow C. Ogston D, Douglas AS. Venous thrombosis following strokes. Lancet 1972; I : 13051306. 8. Cope C, Reyes TM, Skwersky NJ. Phlebographic analysis of the incidence of thrombosis in hemiplegia. Radiology 1973: 109: 58 1-584. 9. Heatley RV, Hughes LE, Morgan A et al. Preoperative or postoperative deep vein thrombosis? Lancet 1976: 1: 437-439.
Acta Puediutr Jpn
-
472)
Disseminated Intravascular Coagulation Syndrome in Anorexia Nervosa Kenji Katamura, M.D., Fuminori Ishimoto, M.D., Masue Yamasaki, M.D., Masaki Yoshimura, M.D. and Toshirou Kisa, M.D. Department of Pediatrics, Shimane Prefectural Central Hospital, Shimane, Japan
A 15 year old boy with anorexia nervosa developed disseminated intravascular coagulation syndrome (DIC). Because of severe cachexia he had been admitted to the Shimane Prefectural Central Hospital. During his hospitalization he developed generalized massive ecchymosis. Laboratory data revealed not only DIC but also multiple organ complications. The patient was treated intravenously with FOY@(gabexatemesilate, a protease inhibitor), heparin, a transfusion of fresh frozen plasma, antithrombin I11 concentrates and platelets. Intravenous hyperalimentation was also administered. The laboratory data, the general condition and the emotional state of the patient improved remarkably. We emphasize the importance of keeping in mind coagulopathy as a complication in anorexia nervosa.
Key Words Anorexia nervosa, Disseminated intravascular coagulation syndrome, Multiple organ complications
Case Report A 15 year old boy was admitted to the Pediatric Department of Shimane Prefectural Central Hospital because of profound weight loss. The patient had lost about 25% of his initial bodyweight over 4 months. Laboratory examinations revealed no abnormal data at this point. During the personal assessment, however, he revealed that he did not think his weight loss was severe, and that he had reduced his food intake for fear of becoming fat. Besides reducing his diet, he
Received December 3, 1991 Revised March 13, 1992 Accepted March 26, 1992 Correspondence address: Kenji Katamura, M.D., Department of Pediatrics, Shimane Prefectural Central Hospital, 1 16 Imaichi-cho, Izumo-city, Shimane 693, Japan.
had also habitually used a kind of herbal medicine as a laxative. At this point, weight loss was suggested to be psychogenic in nature and he was referred to the Department of Psychiatry. Psychotherapy was begun by a psychiatrist and anorexia nervosa was diagnosed. The patient was later discharged so he could prepare for the upcoming high school entrance examination, but the anorexia persisted. One week later, he was readmitted to the Department of Psychiatry because of general fatigue. At that time his weight was 35.2 kg, a 37% loss of his original weight (56 kg). He could barely walk. His serum total protein level was 6.7 g/dl (albumin 4.6 g and globulin 2.1 g/dl), total bilirubin 1.3 mg/dl, urea nitrogen 44.6 mgl dl, and creatinine 1.2 mg/dl. The serum glutamate oxaloacetate transaminase (GOT) was 45 U (normally, 8-40), glutamic-pyruvic transaminase (GPT) 48 U (normally 5-35), the
470 (86) Katamrira el a/.
LDH 1204 U and amylase 1549 U. The serum sodium was 132.6 mEq/l, potassium 4.5 mEq/l, chloride 96.2 mEq/l and bicarbonate 22.9 mEq/l. The diagnosis was disseminated intravascular coagulation syndrome (DIC) with multiple organ complications. The patient was treated intravenously with 1.5 mg/kg per hr FOY@ (gabexate mesilate, a proteinase inhibitor), 7 U/ kg per hr heparin and maintenance fluids. Five hours later the platelet count had been reduced to 27.00O/pl. He received a transfusion consisting of 5 units of platelets, 1,500 units of antithrombin I11 concentrates and two packs of fresh frozen plasma. The treatment and the change of the laboratory examinations are shown (Fig. 1, Table 1). On the second hospital day, the patient was fully conscious and there was no further increase in his subcutaneous hemorrhages. The platelet count had increased to 65,00O/pI. The prothrombin time had decreased to 21.6 sec with a control of 1 1.6 sec, and the activated partial thromboplastin time had decreased to 102.4 sec with a control of 38.4 sec. The fibrinogen level rose to 72 mg/dl. The total serum protein was 6.1 g/dl, total bilirubin 2.8 mg/dl, urea nitrogen 65.4 mg/dl and creatinine 1.4 mg/dl. The serum GOT was 180 U, GPT 195 U, LDH 943 U and
lactic dehydrogenase (LDH) 548 U (normally 150-400), the amylase 227 U (normally 90-280). Ten days later, some petechiae were noticed, and they increased rapidly. Thirteen days later he developed generalized massive ecchymosis and complained of severe fatigue. The patient was transferred to the Pediatric Department to be examined for any bleeding tendencies. He was cachectic and slightly drowsy but well oriented. Temperature was 36.6-C. pulse rate 60 beats/min and respiration 28/min. The blood pressure was 1 14/82 mmHg. The hemoglobin was 16.0 g/dl, hematocrit 44.8Y0, white cell count 9.40O/pl with 1% band forms. 50% polymorphonuclear neutrophils, 44% lymphocytes and 5% monocytes. The platelet count was 47,0OO/p1. The prothrombin time was 26.6 sec. with a control of 11.6 sec; the activated partial thromboplastin time was over 180 sec, with a control of 38.4 sec. The fibrinogen was 55 mg/ dl, antithrombin III was 65% (normally. 80120%) and D-dimer was 1,000-2,000 ng/ml (normally < 200 ng/rnlf. The level of fibrin split products was 10 pgirnl (normally, < 10 pg/ml). The total protein was 5.9 g/dl (albumin 4.0g and globulin 1.9 g/dl), total bilirubin 2.5 mg/dl. urea nitrogen 92.4 mg/dl and creatinine 1.8 mg/ dl. The serum GOT was 440U. GPT 270U. Treatment
Plateiet
Heparin1
FOY 5 units of platelet 160 ml of fresh frozen plasma 1500 units of anlilhrombin 111
Plasma
fibrinogen
a:
'0 tot
1
2
3
d
5
6
7
8
9
10
11
I2
13
-2
i
1
i
1
Time (days)
Fig. 1 : Treatment and change of laboratory examinations after hospitalization
Acta Paediatr Jprt
DIC in anorexia nervosa (87) 47 1 Table 1. Improvement of liver, pancreas and renal function Time course (hospital days)
Function
- 13
1
2
3
GOT (U) 45 GPT (U) 48 LDH (U) 548 Amylase (U) 221 Creatinine (mg/dl) 1.2 BUN (mg/dl) 44.6 BUN, blood urea nitrogen.
440
180 195 943 688 1.4 65.4
121 159 654 1.0 38.4
270
1204 1549
1.8 92.4
amylase 688 U. The intravenous administration of FOY@was continued and antithrombin I11 and two packs of fresh frozen plasma were transfused. The intravenous administration of heparin was ceased. On the third hospital day, the platelet count was 57,00O/pl. The prothrombin time was 16.1 sec and the activated partial thromboplastin time was 56.3 sec. The fibrinogen level was 103 mg/dl, antithrombin I11 was 118%, and D-dimer was 500-1,000 ng/ml. The level of fibrin split products was below 10 pglml. The serum GOT continued to decrease to 127U, the GPT to 159 U and the amylase to 654 U. The urea nitrogen was 38.4 mg/dl and the creatinine was 1.O mg/dl. Tube feeding was also commenced. On the fourth hospital day, the platelet count decreased to 41,0OO/p1, but the other coagulation data improved further. On the sixth hospital day, the platelet count still remained around 40,0OO/pl. The serum GOT was 96 U, the GPT 131 U and the amylase 292 U. The urea nitrogen was 11.6 mddl and the creatinine 0.7 mg/dl. The patient refused tube feeding and started eating on his own. On the eighth hospital day, intravenous hyperalimentation was also administered; On the ninth hospital day, the platelet count had increased to 67,0OO/p1. The prothrombin time was 13.6 sec with a control of 11.3 sec, and the activated partial thromboplastin time was 38.6 sec with a control of 38.4 sec. The fibrinogen level was 271 mg/dl, antithrombin I11 was 84% and D-dimer was 500-1,000ng/ml. The level of fibrin split products was below 10 pg/ml. At this point the administration of intravenous F O P was ceased. On the sixteenth hospital
Vol. 34 No. 4 August 1992
6 96 131
-
292
-
11.6
41
13 10 336 136 0.5 7.3
day, the patient’s weight was 35 kg. He recovered his usual appetite and began gaining weight. The subcutaneous ecchymosis became faint. On the thirty-third hospital day, intravenous hyperalimentation was stopped. The patient’s weight at this point was 39.0 kg. On the forty-first hospital day, the serum GOT was 13 U, GPT 10 U, LDH 336 U, amylase 136 U, urea nitrogen 7.3 mg/dl and creatinine 0.5 mg/dl. The patient was discharged 103 days after his initial admission. His weight was 44.3 kg and his emotional state had improved remarkably.
Discussion To our knowledge, two cases of anorexia nervosa complicated by DIC or by coagulopathy have been reported [I, 21. However, this patient, unlike the others, had not only DIC but also multiple organ complications, at least in the liver, kidney and pancreas. He was treated by transfusion of fresh frozen plasma, platelets and antithrombin 111 and intravenous FOY@,which is a serine proteinase inhibitor that was originally developed as a drug for pancreatitis [3]. After its development, FOY@was found to have a potent anticoagulative effect [4], and is now used widely in Japan as a treatment for DIC. In treating DIC in anorexia nervosa, one must not only treat the syndrome but also try to improve the cachexia as soon as possible. To treat the cachexia is essential, for if the patient does not gain weight, the possibility of developing DIC continues to be a threat. Since this weight gain is essential to the well-being of the patient, intravenous hyperalimentation is needed even after
472 (88) Kacamitru et al. the patient begins eating. Treating the cachexia is also effective in improving the patient’s emotional state. With respect to the pathophysiology of DIC in anorexia nervosa, one also needs to consider the multiple organ hypofunction and the hypercoagulative conditions that may occur as a result of venous stasis, which causes hypoperfusion and leads to hypoxia and malnutrition of multiple organs. Such a condition could readily result in multiple organ complications followed by DIC. Venous stasis may also precipitate thrombosis by causing vascular endothelial damage through local hypoxia [ 5 ] and by retarding the clearance of activated clotting factors from an area of vascular injury [6]. A high incidence of thrombosis has also been reported in patients with stroke and paraplegia and in patients immobilized before surgery [ 7-91. The present case had been bedridden almost all day due to cachexia, and consequently developed generalized ecchymosis. We also had much trouble drawing venous blood from this patient because of a slow blood flow. DIC. therefore, might be triggered by multiple organ dysfunction based on the hypercoagulative condition of the patient. In summary, we have presented a case study of a 15 year old boy with anorexia nervosa complicated by DIC and multiple organ disorders. The patient was treated intravenously with FOY@and heparin and received a transfusion of antithrombin 111 concentrates. fresh
frozen plasma and platelets. Intravenous hyperalimentation was also used to improve the cachexia as soon as possible. The laboratory data, general condition and emotional state improved remarkably. One must keep in mind coagulopathy as a complication in anorexia nervosa. References 1. Brotman AW, Stern TA. Case report of cardiovascular abnormalities in anorexia nervosa. Am J Psychiatry 1983; 140: 1227-1228. -.7 Stutor AH. Schdtte B. Aschoff W et al. Intravascular coagulation in anorexia nervosa. Dtsch Med Wochenschr 1977: 102: 1469-1472. 3. Tamura Y, Hirano M, Okamura K et al. Synthetic inhibitors of trypsin, plasmin, kallikrein, thrombin, C,y and C , esterase. Biochim Biophys Acta 1977; 4 8 4 417-422. 4. Ohno H, Kambayasi J. Chang SW et al. FOY: [Ethyl-p-(6-guanidinohexanoyl)benzoate] methanesulfonateasa serineproteinase inhibitor. 11. In iivo effect on coagulofibrinolytic system in comparison with heparin or aprotinin. Thromb Res 198 1; 24: 445-452. 5. Hamer JD, Malone PC, Silver IA. The PO, in venous valve pockets: Its possible bearing on thrornbogenesis. Br J Surg 1981; 68: 166-170. 6. Shattil SJ. Diagnosis and treatment of recurrent venous thromboembolism. Med Clin N Am 1984; 68: 577-600. 7. Warlow C. Ogston D, Douglas AS. Venous thrombosis following strokes. Lancet 1972; I : 13051306. 8. Cope C, Reyes TM, Skwersky NJ. Phlebographic analysis of the incidence of thrombosis in hemiplegia. Radiology 1973: 109: 58 1-584. 9. Heatley RV, Hughes LE, Morgan A et al. Preoperative or postoperative deep vein thrombosis? Lancet 1976: 1: 437-439.
Acta Puediutr Jpn
