Pancytopenia and Folate Deficiency in Alcoholics
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Postgraduate Medical Journal (1987) 63, 117-120 Postgrad Med J: first published as 10.1136/pgmj.63.736.117 on 1 February 1987. Downloaded from Pancytopenia and folate deficiency in alcoholics Clive F.M. Weston and Michael J. Hall Department ofMedicine, Bristol Royal Infirmary, Bristol BS2 8HW, UK. Summary: Three alcoholic patients are reported who presented with pancytopenia and macrocytosis due to acute folate deficiency. While folate deficiency is a common finding in alcohol abusers due to abnormalities in diet, intestinal absorption, internal metabolism and excretion, this life-threatening complication has not been well documented. Introduction A low serum or red cell folate is a frequent finding in between 40 and 80 mg/I. Plasma urea was 1.3 mmol/l, chronic alcoholics who may or may not have sodium 138 mmol/l, potassium 2.8 mmol/I and levels megaloblastic anaemia. Although pancytopenia due of serum liver enzymes, calcium and phosphate were to folate deficiency has been reported as a complica- normal. Serum ferritin was greater than 500 (normal tion ofintravenous nutrition and haemodialysis it has range 15-99) ng/ml, vitamin B12 377 (normal range not been well documented in alcoholics with liver 150- 800) ng/I but the red cell folate was unrecordable. Protected by copyright. disease. We report the cases ofthree patients who were The bone marrow was megalobastic. admitted within an 18 month period with severe The patient was resuscitated with broad-spectrum pancytopenia and low or undetectable red cell folate antibiotics, transfusions of blood, platelets and fresh levels. Two of the patients were known alcoholics and frozen plasma, potassium supplements, vitamin B12 the other, who initially denied alcohol ingestion, was injections and oral folic acid, and by the seventh day of later readmitted with alcoholic hepatitis. her stay her haemoglobin was 9.4 g/dl, reticulocyte count 5%, white cell count 10.7 x 109/1 and platelets 268 x 109/1. A dietary assessment and further inves- Case reports tigations were not possible as the patient became uncooperative and discharged herself. Patient 1 She failed to attend out-patient follow-up and was readmitted one year later with a recurrence ofprevious A 37 year old woman was admitted in November 1983 symptoms. She now admitted to an alcohol intake of2 with a three month history of malaise, anorexia and bottles of sherry per day over a period of 15 years. http://pmj.bmj.com/ weight loss. She had become increasingly dyspnoeic There were signs of liver failure with encephalopathy, and had experienced fever, urinary frequency and jaundice and ascites. She was again anaemic with haematuria. Her only drug therapy was amitryptyline haemoglobin of 7.0 g/dl and MCV 117 fl, but there and she claimed only occasional alcohol intake. was neither pancytopaenia nor vitamin B12 or folate On examination she was ill, anaemic with multiple deficiency. Liver function was grossly abnormal with bruises, ulcerated bleeding gums, and oral candidiasis. elevated transaminases, hypoalbuminaemia and Other signs were hepatomegaly, generalized muscle prolonged clotting time. There was no evidence of wasting and a retinal haemorrhage in the right eye. viral hepatitis and auto-antibody screening was on September 29, 2021 by guest. Blood analysis revealed pancytopenia with a negative. A diagnosis of acute alcoholic hepatitis was haemoglobin of4.6 g/dl, white cell count of 1.3 x 109/l, made. The liver failure improved slowly and she and platelets 55 x 109/l. Mean corpuscular volume abstained from further alcohol. (MCV) was 115 fl and nucleated red cells and hyper- Currently the patient remains well, albeit with signs segmented neutrophils were seen. Clotting times were of chronic liver disease and troublesome pains in her abnormal with a prothrombin time of 18 seconds and legs due to peripheral neuropathy. activated partial thromboplastin time of 50 seconds. The concentration offibrin degradation products was Patient 2 Correspondence: C.F.M. Weston, M.B., M.R.C.P. A 26 year old woman was noted to have a Accepted: 10 September 1986 macrocytosis which was demonstrated to be due to ) The Fellowship of Postgraduate Medicine, 1987 118 C.F.M. WESTON & M.J. HALL Postgrad Med J: first published as 10.1136/pgmj.63.736.117 on 1 February 1987. Downloaded from 30- folate deficiency in 1975. In the presence of a normal jejunal biopsy and the absence of a history of alcohol 25 intake this was felt to be due to continuous oral OA0 20 contraceptive therapy. Four years later she was referred to a psychiatrist 0 15 requesting help with a long-term problem of alcohol 4) 10 abuse. At the age of 34 years she was admitted with 5 alcoholic hepatitis (biopsy-proven) and marked peri- 1._ pheral neuropathy. Nerve conduction studies 0 showed a:0 definite peripheral sensory dysfunction. The red cell 0 12 - folate was low at 76JLg/l (normal range 120-650), the 0, haemoglobin was 11.1 g/dl and MCV 111 fl. 10 - She continued to drink heavily and 2 years later, in 8- 1985, was admitted with a three week history of fatigue, dizziness, fever, menorrhagia and epistaxis. 6- On examination she was anaemic with bruising, 0)E haematuria and rectal bleeding. There was tender 0 4 hepatomegaly but no ascites. She was pyrexial with a I tachycardia and hypotension with a postural drop in 2 blood pressure. There was evidence of a proximal 0 I myopathy and peripheral neuropathy. x0) 18 Blood analysis revealed a haemoglobin of 4.0 g/dl, X white cell count of 3.7 x 109/1, platelets 15 x 109/1, 14 0 MCV 152 fl, with many nucleated red cells and hyper- 0 Protected by copyright. segmented neutrophils. Plasma potassium was x= 10 3.9 mmol/l (but fell to 2.2 mmol/l on folic acid 6 therapy) albumin was 25 g/l, bilirubin 25 ymol/l, 0C._ aspartate aminotransferase (AST) 71 IU/l fasting tri- 2 glycerides 3.38 mmol/I and cholesterol 3.34 mmol/l. 700 Serum ferritin was 1560 ng/ml, vitamin B12 190 ng/l and red cell folate was undetectable. 0 600 Treatment was with antibiotics, platelet and blood 0 500 transfusions, oral folic acid and vitamin B12 injections. 400 A reticulocyte count of 28% was achieved 10 days 300 after admission, with a white cell count of 16 x 109/1 200 and platelets of 246 x 109/l (see Figure 1). Jejunal biopsy, small bowel barium follow-through 100 and gastroscopy were normal and liver biopsy confir- http://pmj.bmj.com/ med changes characteristic of alcohol abuse. 0 5 10 15 20 Time (days) Patient 3 Figure 1 Progress of patient number 2 (see text). In 1981 a 54 year old Hungarian man developed a left ileo-femoral vein thrombosis and was coincidentally found to have a macrocytosis and red cell folate of and soon developed a confusional state. When he 91 fig/l. He denied alcohol intake and a jejunal biopsy recovered he was noted to have a tremor, a peripheral on September 29, 2021 by guest. was normal. After 3 months treatment with folic acid neuropathy and poor short-term memory. the MCV had fallen from 112 to 102 fl and He was admitted in 1985 with a four week history of haemoglobin had risen from 16.3 to 20.2 g/dl with a malaise, weakness, anorexia, weight loss and diarr- packed cell volume of0.61. There were abnormal liver hoea. On examination he was pale, thin and apyrexial function tests and although he continued to deny with a resting tachycardia and mild ankle oedema. alcohol abuse a random serum ethanol level was There was tender hepatomegaly and a peripheral 173 mg/100 ml. A bone marrow biopsy demonstrated neuropathy with absent knee and ankle jerks. Occult increased stainable iron and many abnormal blood was detected in the faeces and blood analysis sideroblasts. It was lelt he had 'stress' polycythaemia revealed haemoglobin 6.7 g/dl, white cell count and required venesections. 1.8 x 109/l, platelets 24 x 109/l and, MCV 134 fl. Two years later he was admitted with a lung abscess Serum potassium was 2.5 mmol/l, urea 3.2 mmol/l, PANCYTOPENIA AND FOLATE DEFICIENCY IN ALCOHOLICS 119 Postgrad Med J: first published as 10.1136/pgmj.63.736.117 on 1 February 1987. Downloaded from albumin 27 g/l, AST 44 IU/1, fasting triglycerides ethanol. The gradual fall in serum folate seen in 1.79 mmol/l and cholesterol 3.03 mmol/l. Serum normal subjects on folate-deficient diets is greatly ferritin was 195 ng/ml, vitamin B12 371 ng/l and red cell accelerated on ingestion of alcohol and is associated folate was low at 77 jug/I. An ultrasound of the with megaloblastic marrow changes within 10 days. abdomen showed an echogenic probably cirrhotic These reverse on stopping the alcohol and it has been liver, moderate ascites and gallstones within a shrun- suggested that there is a reversible sequestration of ken, thick-walled gall bladder, and normal sized folate within hepatocytes and acute interruption ofthe spleen. enterohepatic circulation of methyltetrahydrofolate.5 Treatment was with intramuscular vitamin B12 and However, the physiological significance of this distur- oral folic acid and a reticulocyte count of 18.0% was bance of intestinal folic acid metabolism is probably achieved by day 7, and 22% on day 10, by which time very small,6 certainly when compared with the his white cell count had returned to 4.9 x 109/1 and documented increase in urinary folate loss following platelets to 197 x 109/1.