25
Volume 69 July 1976
521
Clinical Section President Ian Burn FRCS
Meeting 14 November 1975
Cases Postvagotomy Diarrhea Treated with Cholestyramine L S Hill MB (King's College Hospital, London SE5 9RS) and 'N K Maybury FRCS (Middlesex Hospital, London WIP 7PN) (for J R Condon MRCP) (Brook General Hospital, London SE18)
1975). This response strongly suggests that excessive quantities of bile are reaching the colon where they inhibit the ab"sorption of salt, potassium and water, resulting in diarrhoea. Increased fecal concentration of bile acids are reported in patients with postvagotomy diarrhoea (Allan et al. 1973, M South 1975, unpublished) and may therefore be the cause of 'intractable' postvagotomy diarrhoea.
J B, man aged 46 Presented in 1970 with hmmatemesis. Gastro- REFERENCES J G, Gerskowitch V 0 & Russel R J scopy and barium studies showed a duodenal Allan (1973) Gut 14,423-424 ulcer and a deformed duodenal cap. There was Condon J, Robinson V, Suleman M I, Fan V S & McKeown M D (1975) British Journal of Surgery 62, 309-312 intermittent recurrent epigastric pain throughout Faber R G, Parkin J V, Whitfield P & Hobsley M 1972 despite medical treatment and in 1973 vago- (1975) Gut, 6, 343-346 tomy and pyloroplasty were performed. After operation there was severe watery diarrhoea which responded only partially to codeine phosphate. Investigations: Routine blood count (Hb 14.6 g/dl) and indices, serum calcium, phosphorus, alkaline Disseminated Intravascular Coagulation phosphatase, urea and electrolytes and serum Associated with Polycythiemia Rubra Vera creatinine were all normal. Fecal fat 3.3 g/day. Christine A Lee BM MRCP and S Moss MB MRCP Lactose tolerance test normal. D-xylose excretion (for J Fielding FRCP and R Lancaster PhD MRCP) 1.95 g in 5 hours. Gastric emptying time after a (St Mary's Hospital, Harrow Road, London glucose meal labelled with radioactive indium was W9 3RL) within the normal range. Packed cell volume at 5-minute intervals following glucose test meal and Mrs A N, aged 63 the hTmatocrit did not vary, indicating that there Presented with a hemorrhage into the shoulder was no dumping. Gastric function tests showed joint. On examination she was plethoric with that vagotomy was complete, being Faber nega- splenomegaly. Laboratory findings subsequently showed a raised hoemoglobin (22 g/dl) and hemative on insulin testing (Faber et al. 1975). Treatment andprogress: Following treatment with tocrit (68 %). The prothrombin time (PT) and kaolin partial cholestyramine (Questran), 12 g/day in divided doses, diarrhoea was completely controlled. With- thromboplastin time (KPTT) were prolonged due drawal of cholestyramine resulted in recurrence of to a reduction of Factors V and VIII. The red cell diarrhoea within 48 hours. Reinstitution of therapy mass of 59 ml/kg (normal 28-35 ml/kg) and an increased leukocyte alkaline phosphatase conrelieved-diarrhoea within 48 hours. firmed the diagnosis of polycythemia rubra vera (PRV). Other causes of polycythemia were exComment Intractable diarrhoea following vagotomy may cluded: there were no abnormal respiratory respond to cholestyramine, an anion exchange symptoms or signs, the chest X-ray was normal, resin which binds with bile acids (Condon et al. liver function tests were normal and the only
522
Proc. roy. Soc. Med. Volume 69 July 1976 22--,
Haenwgoi
2501 ISO-_I
co
KPTT
504,
s-C PT
t
40-
1000
500300-f 200-
FDPs+ Wnesection P"
* 1
2
3
4
5
6
7
12
13 14
1S 16
Weeks
Fig I Changes in hemoglobin, kaolin partial thromboplastin time (KPTT), prothrombin time (PT) andplatelets in polycythamia rubra vera
abnormality of an intravenous pyelogram was a duplex kidney with a partial double ureter on the right. Fig 1 illustrates the patient's progress. The KPTT and PT were increased when first measured and remained elevated until the patient was venesected. Three weeks after admission the platelets decreased to 175 000/,ul and the fibrin degradation products (FDP) were found to be increased at 80 ,ug/ml (normal 10 ,ug/ml). At this time, there was no clinical evidence of a deep vein thrombosis or any large thrombosis which might have elevated the FDP. These changes reversed spontaneously before therapy. The patient was treated by venesection of 1700 ml which decreased the h2emoglobin concentration and the h2matocrit. Although venesection was associated with an improvement of coagulation abnormalities, the platelet count remained high; it decreased only after 32p therapy when the coagulation factors remained normal and the hmmatocrit fell further to normal values. Discussion The serious symptoms of polycyth2emia rubra vera are thrombotic (Wetherley-Mein 1974) but
26
paradoxically it may also present as a bleeding problem. Wasserman & Gilbert (1964) reported that hlemorrhage was the most common complication of surgery in patients with PRV. They also showed in another group of patients with PRV that there was a high incidence of certain coagulation abnormalities in addition to the well-known increase in platelet count, namely an increase in the number of untrapped red cells after clot retraction, a decrease in fibrinogen and an increased prothrombin time. These defects were found in our patient before venesection. The cause for the hemorrhagic diathesis in PRV is not established. It has been suggested that the coagulation defects of PRV may be due to abnormal platelet function but in this patient the coagulation defect was not correlated with the platelet count which increased during venesection while coagulation defects were improving. The combination of abnormalities found in this case, namely the raised FDP, decrease in platelet count and reduction of clotting factors suggest that disseminated intravascular coagulation (DIC) may be a cause of the himorrhagic diathesis. We postulate that hyperviscosity in PRV results in small vessel stagnation and DIC with consumption of clotting factors and platelets. Venesection decreased the hematocrit and resulted in disappearance of the coagulation defects. Such an explanation could resolve the paradox of simultaneous thrombosis and haemorrhage in PRV. REFERENCES Wasserman L R & Gilbert H S (1964) Annals of the New York Academy of Sciences 115, 122 Wetherley-Mein G (1974) In: Blood and its Disorders. Ed. R M Hardisty & D J Weatherall. Blackwell, Oxford; p 1157
Hsemochromatosis and Arthritis Clive Stubbings MB MRCP (for J M Gumpel BM MRCP) (Northwick Park Hospital, Watford Road, Harrow, Middlesex, HAI 3UJ) D B, man aged 56 Presented in January 1971 complaining of pain and stiffness of his right thumb and index finger, with no acute episodes of arthritis. Examination showed thickening and deformity of the 2nd and 3rd metacarpophalangeal joints of the right hand. Investigations: Uric acid 500 ,umol/l, RA latex negative, Hb 15.6 g/dl, ESR 6 mm in 1 hour (Westergren). X-rays of hands showed cystic changes and loss of joint space of 2nd metacarpophalangeal joints of both hands (Fig IA).
Volume 69 July 1976
521
Clinical Section President Ian Burn FRCS
Meeting 14 November 1975
Cases Postvagotomy Diarrhea Treated with Cholestyramine L S Hill MB (King's College Hospital, London SE5 9RS) and 'N K Maybury FRCS (Middlesex Hospital, London WIP 7PN) (for J R Condon MRCP) (Brook General Hospital, London SE18)
1975). This response strongly suggests that excessive quantities of bile are reaching the colon where they inhibit the ab"sorption of salt, potassium and water, resulting in diarrhoea. Increased fecal concentration of bile acids are reported in patients with postvagotomy diarrhoea (Allan et al. 1973, M South 1975, unpublished) and may therefore be the cause of 'intractable' postvagotomy diarrhoea.
J B, man aged 46 Presented in 1970 with hmmatemesis. Gastro- REFERENCES J G, Gerskowitch V 0 & Russel R J scopy and barium studies showed a duodenal Allan (1973) Gut 14,423-424 ulcer and a deformed duodenal cap. There was Condon J, Robinson V, Suleman M I, Fan V S & McKeown M D (1975) British Journal of Surgery 62, 309-312 intermittent recurrent epigastric pain throughout Faber R G, Parkin J V, Whitfield P & Hobsley M 1972 despite medical treatment and in 1973 vago- (1975) Gut, 6, 343-346 tomy and pyloroplasty were performed. After operation there was severe watery diarrhoea which responded only partially to codeine phosphate. Investigations: Routine blood count (Hb 14.6 g/dl) and indices, serum calcium, phosphorus, alkaline Disseminated Intravascular Coagulation phosphatase, urea and electrolytes and serum Associated with Polycythiemia Rubra Vera creatinine were all normal. Fecal fat 3.3 g/day. Christine A Lee BM MRCP and S Moss MB MRCP Lactose tolerance test normal. D-xylose excretion (for J Fielding FRCP and R Lancaster PhD MRCP) 1.95 g in 5 hours. Gastric emptying time after a (St Mary's Hospital, Harrow Road, London glucose meal labelled with radioactive indium was W9 3RL) within the normal range. Packed cell volume at 5-minute intervals following glucose test meal and Mrs A N, aged 63 the hTmatocrit did not vary, indicating that there Presented with a hemorrhage into the shoulder was no dumping. Gastric function tests showed joint. On examination she was plethoric with that vagotomy was complete, being Faber nega- splenomegaly. Laboratory findings subsequently showed a raised hoemoglobin (22 g/dl) and hemative on insulin testing (Faber et al. 1975). Treatment andprogress: Following treatment with tocrit (68 %). The prothrombin time (PT) and kaolin partial cholestyramine (Questran), 12 g/day in divided doses, diarrhoea was completely controlled. With- thromboplastin time (KPTT) were prolonged due drawal of cholestyramine resulted in recurrence of to a reduction of Factors V and VIII. The red cell diarrhoea within 48 hours. Reinstitution of therapy mass of 59 ml/kg (normal 28-35 ml/kg) and an increased leukocyte alkaline phosphatase conrelieved-diarrhoea within 48 hours. firmed the diagnosis of polycythemia rubra vera (PRV). Other causes of polycythemia were exComment Intractable diarrhoea following vagotomy may cluded: there were no abnormal respiratory respond to cholestyramine, an anion exchange symptoms or signs, the chest X-ray was normal, resin which binds with bile acids (Condon et al. liver function tests were normal and the only
522
Proc. roy. Soc. Med. Volume 69 July 1976 22--,
Haenwgoi
2501 ISO-_I
co
KPTT
504,
s-C PT
t
40-
1000
500300-f 200-
FDPs+ Wnesection P"
* 1
2
3
4
5
6
7
12
13 14
1S 16
Weeks
Fig I Changes in hemoglobin, kaolin partial thromboplastin time (KPTT), prothrombin time (PT) andplatelets in polycythamia rubra vera
abnormality of an intravenous pyelogram was a duplex kidney with a partial double ureter on the right. Fig 1 illustrates the patient's progress. The KPTT and PT were increased when first measured and remained elevated until the patient was venesected. Three weeks after admission the platelets decreased to 175 000/,ul and the fibrin degradation products (FDP) were found to be increased at 80 ,ug/ml (normal 10 ,ug/ml). At this time, there was no clinical evidence of a deep vein thrombosis or any large thrombosis which might have elevated the FDP. These changes reversed spontaneously before therapy. The patient was treated by venesection of 1700 ml which decreased the h2emoglobin concentration and the h2matocrit. Although venesection was associated with an improvement of coagulation abnormalities, the platelet count remained high; it decreased only after 32p therapy when the coagulation factors remained normal and the hmmatocrit fell further to normal values. Discussion The serious symptoms of polycyth2emia rubra vera are thrombotic (Wetherley-Mein 1974) but
26
paradoxically it may also present as a bleeding problem. Wasserman & Gilbert (1964) reported that hlemorrhage was the most common complication of surgery in patients with PRV. They also showed in another group of patients with PRV that there was a high incidence of certain coagulation abnormalities in addition to the well-known increase in platelet count, namely an increase in the number of untrapped red cells after clot retraction, a decrease in fibrinogen and an increased prothrombin time. These defects were found in our patient before venesection. The cause for the hemorrhagic diathesis in PRV is not established. It has been suggested that the coagulation defects of PRV may be due to abnormal platelet function but in this patient the coagulation defect was not correlated with the platelet count which increased during venesection while coagulation defects were improving. The combination of abnormalities found in this case, namely the raised FDP, decrease in platelet count and reduction of clotting factors suggest that disseminated intravascular coagulation (DIC) may be a cause of the himorrhagic diathesis. We postulate that hyperviscosity in PRV results in small vessel stagnation and DIC with consumption of clotting factors and platelets. Venesection decreased the hematocrit and resulted in disappearance of the coagulation defects. Such an explanation could resolve the paradox of simultaneous thrombosis and haemorrhage in PRV. REFERENCES Wasserman L R & Gilbert H S (1964) Annals of the New York Academy of Sciences 115, 122 Wetherley-Mein G (1974) In: Blood and its Disorders. Ed. R M Hardisty & D J Weatherall. Blackwell, Oxford; p 1157
Hsemochromatosis and Arthritis Clive Stubbings MB MRCP (for J M Gumpel BM MRCP) (Northwick Park Hospital, Watford Road, Harrow, Middlesex, HAI 3UJ) D B, man aged 56 Presented in January 1971 complaining of pain and stiffness of his right thumb and index finger, with no acute episodes of arthritis. Examination showed thickening and deformity of the 2nd and 3rd metacarpophalangeal joints of the right hand. Investigations: Uric acid 500 ,umol/l, RA latex negative, Hb 15.6 g/dl, ESR 6 mm in 1 hour (Westergren). X-rays of hands showed cystic changes and loss of joint space of 2nd metacarpophalangeal joints of both hands (Fig IA).
