THE IMPORTANCE OF COPPER IN THE TREATMENT OF ANEMIA

Transcription

1 Keio Journal of Medicine Vol. 3. No. 1, March, 1954 THE IMPORTANCE OF COPPER IN THE TREATMENT OF ANEMIA MITSUTO HASEGAWA* and SOGEN ITO Department of Internal Medicine, School of Medicine Keio University (Received on March 11th, 1954) INTRODUCTION The blood of lower animals contains hemocyanin, copper compound, and that of mammals, hemoglobin, iron compound, but it has been confirmed since the study of Hart et. al(1) that copper is also essential for hematopoiesis of mammals. However, there is a discrepancy among the opinions of investigators whether or not copper is necessary for the treatment of anemia. There is no text-book on hematology(2-6) which at least explains the importance of copper as a remedy for anemia at present. Even the well known hematologist as Cartwright(7) doubts its importance referring that copper deficiency anemia is scarcely found and "it would be expected to occur in children reared solely on an unpasteurized milk diet in an area of the world where the copper content of the soil is extremely low." We have experienced several cases which attracted our keen attention as to the necessity of copper through determining serum iron and serum copper of various diseases, and observing their proceedings. LABORATORY TESTS AND THEIR RESULTS Serum copper was determined according to the way of Gubler, Cartwright et. al(8) with diethyldithiocarbamate solution. Their normal value of copper is which is very close to the former. About 360 suspected anemic patients were examined at the Keio University Hospital during the period from autumn of 1951 to summer of Thirteen of them showed a decrease of serum copper, the values being lower than 80mcg per 100ml. These did not include the cases in which hypocupremia accompanied with hyperferremia due to the iron administered previously. These will be described later. These thirteen cases are classified into two categories. One is hypochromic microcytic with hypoferremia and the other is hyperchromic macrocytic with serum iron of normal or higher

2 26MITSUTO HASEGAWA and SOGEN ITO amounts. As to the chief complaints and symptoms of the latter, four of them had petechiae and eruption but the blood platelet count was normal and diagnosed as non-thrombocytopenic purpura. The other two cases had complaints of gastric disturbances. A) Hypochromic Microcytic Anemia with Hypocupremia and Copper Deficiency Anemia which Occurs during Iron Administration Ferrous gluconate was chiefly administered for these anemias in our clinic. This agent produces no gastric disturbance, and moreover, increases the level of serum iron more rapidly and markedly than the reduced iron administered orally. Seven patients of this group demonstrated a rise of serum iron and copper to normal levels simultaneously, with Gm. of ferrous gluconate a day for two weeks in the most effective cases. Two cases of them are shown in Table 1. However, it was observed in all other iron deficiency anemias that a decrease of serum copper occurred during iron therapy. In some cases of this group the hemoglobin level was not increased more over despite of iron therapy alone. The following two were closely studied, one of which was treated with reduced iron and the other with ferrous gluconate. Table 1 Treatment of Ferrous Gluconate CASE 1. Patient: Age 24, office girl. Chief Complaint: General malaise. History of the Present Disease: Her present complaint commenced in October 1952 and was associated with a pain in the right chest. She was diagnosed as exudative pleurisy of the right side and treated with Paraaminosalicylic acid and Streptomycin. She had no fever, coughing and expectoration. She developed anemia, increased sedimentation rate (mean rate 82.5) and

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4 28MITSUTO HASEGAWA and SOGEN ITO was discontinued temporarily at the end of the second week and the change of both serum iron and copper caused by the oral administration of ferrous gluconate was examined three days later. It was found that serum copper decreased remarkably on one hand and the rise of serum iron was very slight on the other hand. (Fig. 1, (1)) Then, the daily FIG.I CASE I. 24 year old FIG.II CASE II. 22 year old

5 COPPER IN THE TREATMENT OF ANEMIA29 administration of 10 mg. of copper sulfate was commenced which drew back the serum copper to normal iron tolerance test following the treatment level and the rise of serum iron was noticed in the for two weeks (Fig. 1, (2)). Three weeks later, copper sulfate was discontinued. Copper sulfate undoubtedly increased not only red blood cells but also hemoglobin. CASE 2. Patient: Age 22, female, no occupation. Chief Complaint: Palpitation. History of the Present Disease: Since February 1951 she had been complaining of palpitation and severe general malaise. Treatment consisted of blood transfusions, Mastigen (Liver extract), and Ovahormone (female sex hormone) with no relief. During the treatment, edema on the face and the legs developed. Emaceation was severe and accompanied by headache and dizziness which led to insomnia. Amenorrhea existed since January She was hospitalized in March Family History, Past History: Not significant. Physical Examination on Admission: Nutrition was slightly reduced. The skin and mucous membrane were markedly pale. Laboratory Tests: As shown in Table 2 blood was hypochromic and microcytic. The sedimentation rate was 40 mm. in an hour and 78 mm. in two hours. Urine and stool were negative. Wassermann test was negative. The total acid of gastric juice was -4 in the empty stomach and free hydrochloric acid was 18; secreted amount was 10 cc. Excretion time was 80 minutes, The liver - function tests were normal. Chest X-ray and electrocardiograph were negative. Basal metabolism rate was -11 per cent. Course of the Disease during the Hospitalization: Prior to the iron administration, it was found that serum iron showed rapid increase and serum copper was at the peak of the normal value through the iron tolerance test with ferrous gluconate (Fig. 2, Fig. 3, A (1)). Marked increase of erythrocytes and hemoglobin was found through the subsequent administration of 2 Gm. of ferrous gluconate a day, but iron administration for two weeks brought forth so remarkable decrease of serum copper that we had to carry out the iron tolerance test again, which demonstrated no rise of serum iron and showed that it was approaching to the limit of iron absorption. So we started to give 10 mg. copper sulfate daily. This increased the serum copper, hemoglobin and erythrocytes. It seems that the presence of normal serum copper level is essential for absorption of iron which was administered orally.

6 30MITSUTO HASEGAWA and SOGEN ITO We have experienced a number of such cases as above with slight deviations. In these cases, it is noted that the decrease in serum copper is proportionate to recovery from anemia brought about through iron treatment. This is possibly due to consumption of copper for blood cell formation as well as to requirement as a catalyst for the combination of porphyrin and iron in hemoglobin synthesis. B) Hyperchromic Macrocytic Anemia As described so far, four cases of this group had non-thrombopenic purpura, which demonstrated no anemic symptoms with comparatively high value of serum iron. The significance of the serum copper decrease has not been understood, but as one of the reason, we might say that the protein to be combined with copper had been saturated with iron when the serum iron level was so high. CASE 3. Patient: Age 27, a house wife. Chief Complaint: Swelling all over the body and diarrhea. History of the Present Diease: Around the delivery of a baby in November 1951, she began to complain of general edema and diarrhea, accompanied by anorexia, nausea and vomitting which lasted more than a month till the time she was treated. Treatment relieved the diarrhea but not the general weakness, abdominal distention and the progress of edema on legs. So she was admitted in March, She had marked anemia and complained of anorexia and insomnia. Urine was negative for alubmin. No menstrual flow after delivery. Family History; Past History: Not significant. Physical Examination on Admission : Patient had a normal physique but nourishment was definitely disturbed. Temperature 35.8 Ž., pulse 84, blood pressure 104/0. Her face was pale and swollen and conjunctive appeared markedly anemic. Slight heart murmurs were audible at the apex. Abdomen was considerably distended and fluctuation was noted. Otherwise negative. Laboratory Tests: Blood was hyperchromic macrocytic, as shown in Table 2. The sedimentation rate was 60 mm. in one hour and 86 mm. in two hours. Total serum protein was 3.71 Gm./dl., albumin 1.95 Gm./dl., globulin 1.76 Gm./dl., which were classified into ƒ 0.53, ƒà 0.46, ƒá A/G ratio was As to the gastric juice, total acid was 24 in empty stomach, free hydrochloric acid was 80, and its secreted amount was 25 cc. and the excretion time was 40 minutes. Specific gravity of the urine was and urobilin and urobilinogen were slightly positive. The Course during the Hospitalization: The iron tolerance test showed a slight increase in serum iron (Fig. 3 B1). Polytamin (Mixture of aminoacid)

7 COPPER IN THE TREATMENT OF ANEMIA31 FIG. III Oral Iron Tolerance Test FIG. IV

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