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Thrombotic thrombocytopenic purpura as the first manifestation of human immunodeficiency virus infection
BRIEF CLINICAL
netics of pentamidine involve avid tissue binding in the kidneys and liver, and even after cessation of therapy, the drug persists in the urine for six to eight weeks [3]. These qualities of pentamidine may have accounted for the recrudescence of hyperkalemia in our patient after the drug was discontinued. Daily monitoring of BUN, creatinine, and glucose is currently among the laboratory tests recommended before, during, and after pentamidine therapy [1,2]. We would like to specifically recommend that serum potassium be added to this list of tests. Clinicians should be aware that isolated life-threatening hyperkalemia, out of proportion to possible coexistent mild renal insufficiency, can occur during and after pentamidine treatment. STEVENPELTZ,M.D. SHEREENHASHMI,M.D.
Patient 1. A Sl-year-old black man wasadmitted to Kings County Hospital with watery diarrhea for three weeks, 30-pound weight loss over the same period of time, and dehydration. The patient denied any history of intravenous drug abuseor homosexuality. Results of physical examination were unremarkable. His hemoglobin level was 11.5 g/dL, his white blood cell count was 17,900/mm3 with a normal differential count, and his platelet count was 137 X 10/mm3. He had elevated blood urea nitrogen (26 mmol/L) and creatinine (576 rmol/L) levels. His prothrombin time (PT) and partial thromboplastin time (PTT) were normal. On the fifth hospital day, the patient became lethargic and disoriented. A second complete blood count showeda hemoglobin level of 7.6 g/dL, a white blood cell count of 12,100/mm3 with a normal differential, and a platelet count of 67 X Trenton Affiliated Hospitals 103/mm3. His reticulocyte count Residency Program was 2.7% and his coagulation proHelene Fuld Medical Center file, including PT, PTT, fibrinoand gen, and fibrin split products, was St. Francis Medical Center within normal limits. His blood Trenton, New Jersey urea nitrogen was 22.3 mmol/L and 1. Physicians’ Desk Reference, 43rd ed. Oradell, New his creatinine was 718 pmol/L. His Jersey: Medical Economics Company, 1989; 1206lactate dehydrogenase level was 1207. significantly elevated (854 IU/L). 2. Western KA, Perera DR, Schultz MG: Pentamidine Total and direct bilirubin, alkaline isethionate in the treatment of Pneumocystis carinii pneumonia. Ann Intern Med 1970; 73: 695-702. phosphatase, and liver function 3. Sands M. Kron MA, Brown RB: Pentamidine: a retest results were all normal. Urinalview. Rev Infect Ois 1985: 7: 625634. ysis showed 2+ protein, zero to two Submitted July 26. 1989. and accepted August 7, erythrocytes, and two to four leu1989 kocytes per high-power field, and there were no casts. Review of the THROMBOTIC THROMBOCYTOperipheral blood smear showed PENIC PURPURA AS THE FIRST pronounced erythrocyte fragmenMANIFESTATION OF HUMAN tation with many schistocytes, IMMUNODEFICIENCY VIRUS polychromatophilia, and nucleated INFECTION red blood cells. Bone marrow aspirate demonstrated mild erythroid Thrombotic thrombocytopenic hyperplasia and megaloblastic purpura (TTP) is a rare disease changes. The number of megacharacterized by microangiopathic karyocytes was normal. A computhemolytic anemia, thrombocytopeed tomographic scan of the head nia, fever, neurologic abnormalirevealed cerebral atrophy. A lumties, and renal failure [I]. Recently, bar puncture was performed and it has been suggested that TI’P analysis of the cerebrospinal fluid may be associated with the various showed no evidence of infection. stagesof the acquired immunodefiThe clinical diagnosis of ‘M’P was ciency syndrome (AIDS) [2,3]. We made and the patient was treated reviewed the cases of all the pa- with aspirin, dipyridamole, stetients with TTP admitted to the roids, and exchange transfusions. Kings County and Brooklyn VeterOn the eighth hospital day, the paans Administration Hospitals in tient became anuric and hemodialthe last three years. Two of five pa- ysis was initiated. On the 11th hostients had evidence of human im- pital day, the patient developed an munodeficiency virus (HIV) infec- abscesson a line site and septicetion, and in both casesTTP may mia. The abscesswas drained and have been the presenting manifes- he was given appropriate antibiottation. ics. On the 14th hospital day, a secDecember
1989
The American
OBSERVATIONS
ond set of stool cultures grew Enthistolytica, and the patient began to receive oral metronidazole. On the 20th hospital day, the patient was noted to have oral candidiasis. On the 23rd hospital day, three separate blood culture8 were positive for Cryptococcus neoformans, and treatment with intravenous amphotericin was begun. On the 35th hospital day, the patient’s respiratory status deteriorated, requiring endotracheal intubation. The patient underwent alveolar lavage with an irrigation catheter, and the diagnosis of herpes pneumonitis was made. All this time, the patient was receiving treatment for the TTP but had no response.The steroids were gradually tapered and were discontinued on the 26th hospital day. The patient died on the 45th hospital day. Patient 2. A 52-year-old black man, a former intravenous drug abuser (IVDA) with a history of chronic pancreatitis, presented to the Brooklyn Veterans Administration Hospital with nausea,vomiting, and lethargy for the last three days before admission. The result of physical examination was unremarkable. His hemoglobin level was 6.8 g/dL, his white blood cell count was 9,50O/mms with a normal differential, and his platelet count was 11 X 103/mm3.His coagulation profile was normal. A review of his peripheral blood smear showed many schistocytes. The blood urea nitrogen was 11 mmoll L, the creatinine was 89 pmol/L, the lactate dehydrogenase was 3,270 IU/L, the total bilirubin was 53 pmol/L, and the direct bilirubin was 3.4 ccmol/L. A gingival biopsy was performed and the findings were consistent with TTP. The patient was treated with steroids, aspirin, dipyridamole, and plasma in,fusions, and had an excellent response to treatment. His blood counts were normalized, hi8 neurologic status returned to normal, and he was discharged. Twelve months later, he was hospitalized for an exacerbation of chronic pancreatitis. At that time, the patient’s serum was tested and was found to be positive for HIV antibody by both enzyme-linked immunoabsorbent and Western blot assays. There were no clinical manifestations of HIV disease.Two months later, he was readmitted becauseof recurrent TTP. At this time, his CD4/CD8 ratio was 0.3 and the absolute CD4 and CD8 counts were amoeba
Journal
of hledlclne
Volume
87
699
BRIEF CLINICAL
OBSERVATIONS
0.29 x 103/mm3 and 1.02 X 103/ mms, respectively. The patient was treated again with steroids and plasma infusions and had a good response. Comments. We describe here two patients with evidence of HIV infection and TI’P. The first patient had no known risk factors for HIV infection. During his hospitalization for TTP, he developed opportunistic infections consistent with AIDS. The second patient represents an IVDA, seropositive for antibody to HIV, presenting with TTP but no other clinical manifestations of HIV disease. We assume that this patient was seropositive at the time of his first presentation with TTP, as he was a former IVDA, and he denied any risky behavior during the time between diagnosis of TTP and the testing for HIV antibody. These two cases further support a possible association between TTP and HIV infection. Thus, in the current clinical era, it would seem appropriate to examine all patients presenting with TTP for evidence of HIV infection. LEONIDAS C. PLATANIAS, M.D. DINO PAIUSCO, M.D. STEVEN BERNSTEIN, M.D. MANDAKOLATHVR R. MURALI, M.D. State University of New York/ Health Science Center at Brook:; Brooklyn
Veterans
Administration Hospital Brooklyn, New York
1. Byrnes JJ. Moake JL: Thrombotic thrombocytopenit purpura and haemolytic uremia syndrome: evolving concepts of pathogenesis. Clin Haematol 1986: 15: 413-W. 2. Leaf AN. laubenstein U. Raphael B. et aC Thrombotic thrombocytopenic purpura associated wrth human immunodeficiency virus type 1 (HIV-l). Ann Intern Med 1988: 109: 194-197. 3. Nair JMG. Bellevue R. Bertoni M. Dosik H: Thrombotic thrombocytopenic purpura in.patients with the acquired immunodeficiency syndrome (AIOS)-related complex. Ann Intern Med 1988: 109: X9-212. Submitted
April 20. 1989.
and accepted in revised form August 7. 1989
POLYCYTHEMIA SECONDARY TO HEPATIC HEMANGIOMA WITH ABNORMAL SECRETION OF ERYTHROPOIETIN Raised serum concentrations of erythropoietin and presence of erythropoietin activity in extracts of tumoral tissue have been report-
700
December
1989
The American
Journal
ed in a few patients with erythrocytosis associatedwith hepatic tumor [l]. Most frequently, patients have hepatocellular carcinoma. We herein report on a patient with polycythemia related to hepatic hemangioma with elevated serum and tumor tissue erythropoietin concentrations. To our knowledge, this is the fist report in the literature. Case Report. A 37-year-old man was admitted for asymptomatic polycythemia. On examination, blood pressure was 140/90 mm Hg. The left lobe of the liver was enlarged and the spleen and the kidneys were not palpable. The urine was normal. Hematocrit was 55% and hemoglobin was 17 g/dL; white blood cell count was 5,700/mm3, with a normal differential count; platelet count was 275,000/mm3. Prothrombin time, liver enzymes, alpha-fetoprotein and carcinoembryonic antigen were in the normal range. An automated blood chemistry scan was normal. Abdominal computed tomography disclosed a homogeneous hypervascular solid mass,10 cm in diameter, in the left hepatic lobe. The spleen and the kidneys were normal. Serum erythropoietin was 353 mU/mL (normal, 14 mU/mL) (A. Boffa, M.D., Institut National de Transfusion Sanguine, Paris). Selective subhepatic vein catheterization revealed a raised serum erythropoietin level (492 mU/mL). A left hepatic lobectomy was performed 20 months after admission. The right lobe appeared free of disease and no other involvement was evident within the abdomen. Microscopic examination revealed a typical hemangioma. Erythropoietin activity in tumoral extract was 672 mU/g of fresh tissue.Two months later, the hematocrit returned to 36%and the hemoglobin level to 11.2 g/dL. Comments. Erythrocytosis caused by an inappropriate stimulus to e hropoiesis is rarely observed [2r” . About half of the tumors causing olycythemia are renal tumors [2Pbut only 2% to 3% of kidney cell carcinomas are accompanied by this disorder, since benign renal lesions such as cysts and hydronephrosis can also be responsible for erythrocytosis. Among other tumors associated with polycy-
of Medlclne
Volume
87
themia, the most frequent onesare hepatoma. Erythrocytosis occurs in 3%to 12%of patients with hepatocellular carcinoma [3]. Pathogenesisof this paraneoplastic phenomenon is poorly understood [4]. As liver is the site of erythropoietin clearance, hepatic dysfunction could result in increased serum erythropoietin concentrations. Only a small proportion of hepatoma sampleshave seldomshowed an erythropoietic activity. In one case, the tumor extract served as a substrate for the renal erythropoietic factor, perhaps leading to generation of an increased amount of erythropoietin [5]. Other types of hepatic mass can be observed in erythrocytosis: angiosarcoma [4], hamartoma [6], hepatic metastasis of a small renal tumor that secreted erythropoietin. Association of hemangioma with erythrocytosis has not been documented before this time in the literature [7,8]. In our case, we have demonstrated an increased serum erythropoietin concentration related to a hemangioma, producing a biologically active erythropoietin leading to erythrocytosis. As well as other usually involved tumors, hepatic hemangioma should be considered as a possible cause of polycy-themia.
Cimiez
B. TAILLAN F. SANDERSON J.G. FUZIBET H. VINTI A. PESCE P. DUJARDIN Hospital, BP 179 Nice, France
1. Davidson CS: Hepatocellular carcinoma and erythrocytosis. Semin Hematol 1976; 13: 115-119. 2. Balcerzak SP. Eromberg PA: Secondary polycythemia. Semin Hematol 1975; 12: 353-382. 3. Jacobson RJ. Lowenthal MN. Kew MC: Ervthrocvtosis in hepatocellular carcinoma. S Afr Med’J 19%; 53: 658-660. 4. Case records of the Massachusetts General Hospital. Case 20-1979. N Engl J Med 1979: 300: 11481154. 5. Gordon AS, Zaniani ED. Zaluskv R: A oossible mechanism for the erythrocytosis associated with hepatocellular carcinoma in man. Blood 1970: 35: 151-157. 6. Josephs BN, Robbins G, Levine A: Polycythemia secondary to hemartoma of the liver. JAMA 1962; 1979: 867-870. 7. Desaint B. Conrad M. Florent C, Najman A, Levy VG: La polyglobulie au tours des maladies du foie. Ann Gastroenterol Hepatol 1986; 22: 399-404. 8. Naughton BA: Evidence for an erythropoietin stimulating factor in patients with renal and hepatic disease. Acta Haematol 1983; 69: 171-179. Submitted
July 18. 1989.
and accepted
August 7, 1989
netics of pentamidine involve avid tissue binding in the kidneys and liver, and even after cessation of therapy, the drug persists in the urine for six to eight weeks [3]. These qualities of pentamidine may have accounted for the recrudescence of hyperkalemia in our patient after the drug was discontinued. Daily monitoring of BUN, creatinine, and glucose is currently among the laboratory tests recommended before, during, and after pentamidine therapy [1,2]. We would like to specifically recommend that serum potassium be added to this list of tests. Clinicians should be aware that isolated life-threatening hyperkalemia, out of proportion to possible coexistent mild renal insufficiency, can occur during and after pentamidine treatment. STEVENPELTZ,M.D. SHEREENHASHMI,M.D.
Patient 1. A Sl-year-old black man wasadmitted to Kings County Hospital with watery diarrhea for three weeks, 30-pound weight loss over the same period of time, and dehydration. The patient denied any history of intravenous drug abuseor homosexuality. Results of physical examination were unremarkable. His hemoglobin level was 11.5 g/dL, his white blood cell count was 17,900/mm3 with a normal differential count, and his platelet count was 137 X 10/mm3. He had elevated blood urea nitrogen (26 mmol/L) and creatinine (576 rmol/L) levels. His prothrombin time (PT) and partial thromboplastin time (PTT) were normal. On the fifth hospital day, the patient became lethargic and disoriented. A second complete blood count showeda hemoglobin level of 7.6 g/dL, a white blood cell count of 12,100/mm3 with a normal differential, and a platelet count of 67 X Trenton Affiliated Hospitals 103/mm3. His reticulocyte count Residency Program was 2.7% and his coagulation proHelene Fuld Medical Center file, including PT, PTT, fibrinoand gen, and fibrin split products, was St. Francis Medical Center within normal limits. His blood Trenton, New Jersey urea nitrogen was 22.3 mmol/L and 1. Physicians’ Desk Reference, 43rd ed. Oradell, New his creatinine was 718 pmol/L. His Jersey: Medical Economics Company, 1989; 1206lactate dehydrogenase level was 1207. significantly elevated (854 IU/L). 2. Western KA, Perera DR, Schultz MG: Pentamidine Total and direct bilirubin, alkaline isethionate in the treatment of Pneumocystis carinii pneumonia. Ann Intern Med 1970; 73: 695-702. phosphatase, and liver function 3. Sands M. Kron MA, Brown RB: Pentamidine: a retest results were all normal. Urinalview. Rev Infect Ois 1985: 7: 625634. ysis showed 2+ protein, zero to two Submitted July 26. 1989. and accepted August 7, erythrocytes, and two to four leu1989 kocytes per high-power field, and there were no casts. Review of the THROMBOTIC THROMBOCYTOperipheral blood smear showed PENIC PURPURA AS THE FIRST pronounced erythrocyte fragmenMANIFESTATION OF HUMAN tation with many schistocytes, IMMUNODEFICIENCY VIRUS polychromatophilia, and nucleated INFECTION red blood cells. Bone marrow aspirate demonstrated mild erythroid Thrombotic thrombocytopenic hyperplasia and megaloblastic purpura (TTP) is a rare disease changes. The number of megacharacterized by microangiopathic karyocytes was normal. A computhemolytic anemia, thrombocytopeed tomographic scan of the head nia, fever, neurologic abnormalirevealed cerebral atrophy. A lumties, and renal failure [I]. Recently, bar puncture was performed and it has been suggested that TI’P analysis of the cerebrospinal fluid may be associated with the various showed no evidence of infection. stagesof the acquired immunodefiThe clinical diagnosis of ‘M’P was ciency syndrome (AIDS) [2,3]. We made and the patient was treated reviewed the cases of all the pa- with aspirin, dipyridamole, stetients with TTP admitted to the roids, and exchange transfusions. Kings County and Brooklyn VeterOn the eighth hospital day, the paans Administration Hospitals in tient became anuric and hemodialthe last three years. Two of five pa- ysis was initiated. On the 11th hostients had evidence of human im- pital day, the patient developed an munodeficiency virus (HIV) infec- abscesson a line site and septicetion, and in both casesTTP may mia. The abscesswas drained and have been the presenting manifes- he was given appropriate antibiottation. ics. On the 14th hospital day, a secDecember
1989
The American
OBSERVATIONS
ond set of stool cultures grew Enthistolytica, and the patient began to receive oral metronidazole. On the 20th hospital day, the patient was noted to have oral candidiasis. On the 23rd hospital day, three separate blood culture8 were positive for Cryptococcus neoformans, and treatment with intravenous amphotericin was begun. On the 35th hospital day, the patient’s respiratory status deteriorated, requiring endotracheal intubation. The patient underwent alveolar lavage with an irrigation catheter, and the diagnosis of herpes pneumonitis was made. All this time, the patient was receiving treatment for the TTP but had no response.The steroids were gradually tapered and were discontinued on the 26th hospital day. The patient died on the 45th hospital day. Patient 2. A 52-year-old black man, a former intravenous drug abuser (IVDA) with a history of chronic pancreatitis, presented to the Brooklyn Veterans Administration Hospital with nausea,vomiting, and lethargy for the last three days before admission. The result of physical examination was unremarkable. His hemoglobin level was 6.8 g/dL, his white blood cell count was 9,50O/mms with a normal differential, and his platelet count was 11 X 103/mm3.His coagulation profile was normal. A review of his peripheral blood smear showed many schistocytes. The blood urea nitrogen was 11 mmoll L, the creatinine was 89 pmol/L, the lactate dehydrogenase was 3,270 IU/L, the total bilirubin was 53 pmol/L, and the direct bilirubin was 3.4 ccmol/L. A gingival biopsy was performed and the findings were consistent with TTP. The patient was treated with steroids, aspirin, dipyridamole, and plasma in,fusions, and had an excellent response to treatment. His blood counts were normalized, hi8 neurologic status returned to normal, and he was discharged. Twelve months later, he was hospitalized for an exacerbation of chronic pancreatitis. At that time, the patient’s serum was tested and was found to be positive for HIV antibody by both enzyme-linked immunoabsorbent and Western blot assays. There were no clinical manifestations of HIV disease.Two months later, he was readmitted becauseof recurrent TTP. At this time, his CD4/CD8 ratio was 0.3 and the absolute CD4 and CD8 counts were amoeba
Journal
of hledlclne
Volume
87
699
BRIEF CLINICAL
OBSERVATIONS
0.29 x 103/mm3 and 1.02 X 103/ mms, respectively. The patient was treated again with steroids and plasma infusions and had a good response. Comments. We describe here two patients with evidence of HIV infection and TI’P. The first patient had no known risk factors for HIV infection. During his hospitalization for TTP, he developed opportunistic infections consistent with AIDS. The second patient represents an IVDA, seropositive for antibody to HIV, presenting with TTP but no other clinical manifestations of HIV disease. We assume that this patient was seropositive at the time of his first presentation with TTP, as he was a former IVDA, and he denied any risky behavior during the time between diagnosis of TTP and the testing for HIV antibody. These two cases further support a possible association between TTP and HIV infection. Thus, in the current clinical era, it would seem appropriate to examine all patients presenting with TTP for evidence of HIV infection. LEONIDAS C. PLATANIAS, M.D. DINO PAIUSCO, M.D. STEVEN BERNSTEIN, M.D. MANDAKOLATHVR R. MURALI, M.D. State University of New York/ Health Science Center at Brook:; Brooklyn
Veterans
Administration Hospital Brooklyn, New York
1. Byrnes JJ. Moake JL: Thrombotic thrombocytopenit purpura and haemolytic uremia syndrome: evolving concepts of pathogenesis. Clin Haematol 1986: 15: 413-W. 2. Leaf AN. laubenstein U. Raphael B. et aC Thrombotic thrombocytopenic purpura associated wrth human immunodeficiency virus type 1 (HIV-l). Ann Intern Med 1988: 109: 194-197. 3. Nair JMG. Bellevue R. Bertoni M. Dosik H: Thrombotic thrombocytopenic purpura in.patients with the acquired immunodeficiency syndrome (AIOS)-related complex. Ann Intern Med 1988: 109: X9-212. Submitted
April 20. 1989.
and accepted in revised form August 7. 1989
POLYCYTHEMIA SECONDARY TO HEPATIC HEMANGIOMA WITH ABNORMAL SECRETION OF ERYTHROPOIETIN Raised serum concentrations of erythropoietin and presence of erythropoietin activity in extracts of tumoral tissue have been report-
700
December
1989
The American
Journal
ed in a few patients with erythrocytosis associatedwith hepatic tumor [l]. Most frequently, patients have hepatocellular carcinoma. We herein report on a patient with polycythemia related to hepatic hemangioma with elevated serum and tumor tissue erythropoietin concentrations. To our knowledge, this is the fist report in the literature. Case Report. A 37-year-old man was admitted for asymptomatic polycythemia. On examination, blood pressure was 140/90 mm Hg. The left lobe of the liver was enlarged and the spleen and the kidneys were not palpable. The urine was normal. Hematocrit was 55% and hemoglobin was 17 g/dL; white blood cell count was 5,700/mm3, with a normal differential count; platelet count was 275,000/mm3. Prothrombin time, liver enzymes, alpha-fetoprotein and carcinoembryonic antigen were in the normal range. An automated blood chemistry scan was normal. Abdominal computed tomography disclosed a homogeneous hypervascular solid mass,10 cm in diameter, in the left hepatic lobe. The spleen and the kidneys were normal. Serum erythropoietin was 353 mU/mL (normal, 14 mU/mL) (A. Boffa, M.D., Institut National de Transfusion Sanguine, Paris). Selective subhepatic vein catheterization revealed a raised serum erythropoietin level (492 mU/mL). A left hepatic lobectomy was performed 20 months after admission. The right lobe appeared free of disease and no other involvement was evident within the abdomen. Microscopic examination revealed a typical hemangioma. Erythropoietin activity in tumoral extract was 672 mU/g of fresh tissue.Two months later, the hematocrit returned to 36%and the hemoglobin level to 11.2 g/dL. Comments. Erythrocytosis caused by an inappropriate stimulus to e hropoiesis is rarely observed [2r” . About half of the tumors causing olycythemia are renal tumors [2Pbut only 2% to 3% of kidney cell carcinomas are accompanied by this disorder, since benign renal lesions such as cysts and hydronephrosis can also be responsible for erythrocytosis. Among other tumors associated with polycy-
of Medlclne
Volume
87
themia, the most frequent onesare hepatoma. Erythrocytosis occurs in 3%to 12%of patients with hepatocellular carcinoma [3]. Pathogenesisof this paraneoplastic phenomenon is poorly understood [4]. As liver is the site of erythropoietin clearance, hepatic dysfunction could result in increased serum erythropoietin concentrations. Only a small proportion of hepatoma sampleshave seldomshowed an erythropoietic activity. In one case, the tumor extract served as a substrate for the renal erythropoietic factor, perhaps leading to generation of an increased amount of erythropoietin [5]. Other types of hepatic mass can be observed in erythrocytosis: angiosarcoma [4], hamartoma [6], hepatic metastasis of a small renal tumor that secreted erythropoietin. Association of hemangioma with erythrocytosis has not been documented before this time in the literature [7,8]. In our case, we have demonstrated an increased serum erythropoietin concentration related to a hemangioma, producing a biologically active erythropoietin leading to erythrocytosis. As well as other usually involved tumors, hepatic hemangioma should be considered as a possible cause of polycy-themia.
Cimiez
B. TAILLAN F. SANDERSON J.G. FUZIBET H. VINTI A. PESCE P. DUJARDIN Hospital, BP 179 Nice, France
1. Davidson CS: Hepatocellular carcinoma and erythrocytosis. Semin Hematol 1976; 13: 115-119. 2. Balcerzak SP. Eromberg PA: Secondary polycythemia. Semin Hematol 1975; 12: 353-382. 3. Jacobson RJ. Lowenthal MN. Kew MC: Ervthrocvtosis in hepatocellular carcinoma. S Afr Med’J 19%; 53: 658-660. 4. Case records of the Massachusetts General Hospital. Case 20-1979. N Engl J Med 1979: 300: 11481154. 5. Gordon AS, Zaniani ED. Zaluskv R: A oossible mechanism for the erythrocytosis associated with hepatocellular carcinoma in man. Blood 1970: 35: 151-157. 6. Josephs BN, Robbins G, Levine A: Polycythemia secondary to hemartoma of the liver. JAMA 1962; 1979: 867-870. 7. Desaint B. Conrad M. Florent C, Najman A, Levy VG: La polyglobulie au tours des maladies du foie. Ann Gastroenterol Hepatol 1986; 22: 399-404. 8. Naughton BA: Evidence for an erythropoietin stimulating factor in patients with renal and hepatic disease. Acta Haematol 1983; 69: 171-179. Submitted
July 18. 1989.
and accepted
August 7, 1989