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Anticoagulation by Ancrod for Haemodialysis Br Med J: First Published As 10.1136/Bmj.4.5735.591 on 5 December 1970

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Anticoagulation by Ancrod for Haemodialysis Br Med J: First Published As 10.1136/Bmj.4.5735.591 on 5 December 1970 BRITISH 5 December 1970 MEDICAL JOURNAL 591 Anticoagulation by Ancrod for Haemodialysis Br Med J: first published as 10.1136/bmj.4.5735.591 on 5 December 1970. Downloaded from G. H. HALL,* M.D., B.SC., M.R.C.P.; HAZEL M. HOLMAN,t M.B., D.C.H., D.A.; A. D. B. WEBSTERt M.B., M.R.C.P. British MedicalJournal, 1970, 4, 591-593 Summary: The defibrinating agent ancrod (Arvin) TABLE I.-Anticoagulation Schedules of Two Patients Undergoing Haemo- was used instead of heparin for intermittent dialysis using Heparin and Ancrod haemodialysis. It was an and effective, apparently safe, Time Dose anticoagulant and reduced the deposition of fibrin and Serial Anti- Given Method of No. coagulant Pre- Pre- Post- Administration leucocytes on the Cellophane membrane. Administration dialysis dialysis dialysis was more complicated and urea dialysance was less with ancrod than with heparin. Case 1 1 Heparin 25 units/min. Constant infusion via arterial line 2 .. Heparin 25 units/min. Constant infusion via arterial line Introduction 8 hr. 51 u. In 300 ml. N/S over 3 hr. 4 .. Ancrod { 5 hr. 51 u. In 20 ml. N/S over i hr. An essential condition for successful haemodialysis is the i hr. 25-5 u. In 10 ml. N/S over i hr. maintenance of an flow u. adequate blood through the dialyser. 5 .. Ancrod 4* hr. 51 In 300 ml. N/S over 3 hr. With the Kiil system the blood comes into contact with the { I hr. 51 u. In 20 ml. N/S over i hr. hr. 51 u. In 300 over polyvinyl chloride tubing and cuprophane or Cellophane 6 .. Ancrod { 34 ml. N/S 3 hr. membranes. Without prior anticoagulation blood would clot i hr. 51 u. 51 u1. In 20 ml. N/S over i hr. within 7 .. Ancrod 31 hr. 51 u. In 200 ml. N/S over 2 hr. this system. At present the accepted method of { 1i hr. 51 u. In 20 over i hr. anticoagulation is to use heparin, either by constant infusion ml. N/S 8 hr. 58 u. In 300 ml. N/S over 3 hr. or by intermittent administration. Heparin is a relatively safe 8 .. Ancrod { 4 hr. 58 u. In 20 ml. N/S over i hr. drug and its effect is easily reversed. Complications include I hr. 26 u. In 20 ml. N/S over hr. 5 hr. 58 u. spontaneous haemorrhage, hypersensitivity, alopecia, and more 9 .. Ancrod { In 300 ml. N/S over 4 hr. rarely osteoporosis (Griffith, Nichols, Asher, and Flanagan, 1 hr. 58 u. 58 u.i. In 20 ml. N/S over hr. 1965). Ancrod (Arvin) is prepared from the venom of the 10 . Ancrod 3 hr. 58u. 58u.i. In 200 ml. N/S over 2 hr. Malayan pit viper and produces its anticoagulant effect by 11 . Ancrod 2 hr. 58 u. In 100 ml. N/S over i hr. defibrination (Reid, Thean, Chan, and Baharom, 1963). Case 2 After our experience with ancrod in other clinical contexts 3 .. Heparin 25 units/min. Constant infusion via arterial line we wished to explore its -use in haemodialysis. The following 3a . Heparin 25 units/min. Constant infusion via questions were considered: (1) is arterial line ancrod an effective 3b Heparin 25 units/mmn. Constant infusion via anticoagulant for haemodialysis? (2) what effect does it have arterial line 6 hr. 65 u. In 300 ml. N/S over 3 hr. on dialysance? (3) is fibrin and leucocyte deposition on the 21I hr. 65 u. In 20 ml. N/S over i hr. membrane affected? (4) what untoward side effects occur? 12 . Ancrod 4 During 16 In over http://www.bmj.com/ and (5) can the anticoagulant schedule be simplified by its use dialysis U. 10 ml. N/S i hr. 5* hr. 61 u. In 300 ml. N/S over 3 hr. in place of heparin? 12a . Incrod { 2* hr. 61 U. In 20 ml. N/S over i hr. 1 hr. 30 u. In 20 ml. N/S over i hr. Patients and Methods N/S = Normal saline The effects of heparin and ancrod were compared in four home. He returned twice weekly for this regimen. Before sub- .patients. Case 1: a man aged 22 with chronic nephritis; on sequent dialyses we found that the pre-ancrod fibrinogen level haemodialysis for 30 months; anuric. Case 2: a man aged 35 was still below normal (Fig. 1). We then tried the effect of with chronic nephritis; on haemodialysis for 20 months; giving a dose of ancrod (1 unit per kg.) on some occasions on 25 September 2021 by guest. Protected copyright. unsuccessful cadaver allograft six months previously. Case 3: before the patient-went home, but found that there was no a man aged 49 with polycystic kidneys; on haemodialysis for further reduction in the fibrinogen level on his return. Sub- 12 months. Case 4: a man aged 48 with polycystic kidneys; on sequently we shortened predialysis defibrination time to two haemodialysis for six months; later (three months after trial) died of subarachnoid haemorrhage. H A A A A H A A A A Anticoagulation with heparin was effected by a continuous infusion into the arterial line of the dialyser by roller pump; the total dose in 12 hours averaged 35,000 units. 300v Anticoagulation (defibrination) by ancrod was performed by the modified method described by Bell, Pitney, and Goodwin E (1968). Initially ancrod (one unit per kilogram body weight) in 300 ml. of normal saline was given slowly over three hours via _ 200 the patient's Silastic A-V shunt. If the fibrinogen level was E then more than 10 mg./100 ml. and the titre above one in four c IV or dilution a second similar dose in 20 ml. of normal saline was 0 given by the same route over 15 minutes, followed by a fur- .' 00 ther half dose if required (Table I). Dialysis was then begun, with no alteration in the usual routine apart from the absence of heparin. At the end of dialysis, which usually took place overnight and lasted about 12 hours, the patient was allowed 0 4 8 12 16 20 24 2aB 8 12 1l 20 24 28 Consultant Physician. September 1968 November 968 tRegistrar in Pathology. Medical Registrar. FIG. 1.-Fibrinogen levels during two trials of ancrod on Case 1. H= Royal Devon and Exeter Hospital, Exeter EXI lPO. Heparin. A Ancrod. BRITISH 592 5 December 1970 Ancrod for Haemodialysis-Hall et al. MEDICAL JOURNAL hours, and this could, if necessary, be shortened still further Results Br Med J: first published as 10.1136/bmj.4.5735.591 on 5 December 1970. Downloaded from to about one hour (A. P. Fletcher, 1968, personal communi- cation). No dialysis had to be discontinued because of clotting in the dialyser, and at no time during defibrination did these The fibrinogen level was estimated by the method of patients experience haemorrhagic effects. In particular, there Stirland (1956), modified by R. D. Eastham (personal commu- were no episodes of spontaneous bruising or nose-bleeds. One nication, 1961). The fibrinogen titre was estimated by the method of Sharp, Warren, Paxton, and Allington (1968). The patient (Case 2), three hours after beginning the first dialysis after defibrination, complained of cramp in the leg containing order of treatment is shown in Table II. Blood flow was kept the shunt. Though the fibrinogen reading was less than 10 mg./ 100 ml., micro-clots were seen in the polyvinyl chloride TABLE II.-Urea Clearance Values During Dialysis. Number of Estimations tubing. A further quarter dose of ancrod (16 units) was Per Dialysis In Parentheses given. The micro-clots disappeared but the leg remained painful, so dialysis was discontinued one hour later. There Urea Clearance (ml./min.) no same was used Case No. were untoward after-effects, and the shunt Heparin Ancrod again for further dialysis. f 84 (10) No significant changes in fibrinogen concentration or titre J 86 (10) were the administration 2 90 (10) observed when using heparin. After L 81 (8) of ancrod the fibrinogen concentrations were reduced to less F 86 (10) than 10 mg./100 ml. and the fibrinogen titres from 0 to 1 in 4 I110 (9) 80 (6) (Fig. 2). 1 ~ .. .. .. g44 (8) 41 (7) Ancrod 128 83 (7) 43(6) Anc rod C 72 (4)! 80 (5) 300- 64- 80 (5) 3 .. .. i I I150 (6) I ~~~~78(2) 32- 76 (6) 7 ( 76 (6) E 67 (5) 8200. 120 (5) l 65 (5) 74 (7) E 8- 4 43 (2) :- 75 (3) cr 4. o 110 (5) 70 (7) 100. .0 Mean urea clearances: Heparin 86 ml./min., Ancrod, 62 ml./min. (P<0 01). 2 protamine LA- Owith N"2 bf6.9 0 a as constant as possible by the use of Watson-Marlow before after before after MHRE roller pump at about 120 ml./min. When heparin was http://www.bmj.com/ used after ancrod refibrination of the patient was achieved by FIG. 2.-Effect of ancrod on fibrinogen concentration and titre. Continuous lines refer to Case 1, and dotted lines to Case 2. Numbers by lines refer to giving antivenom (130 units) and fibrinogen (1.5 g.) intra- serial numbers of dialysis. venously. Samples of arterial and venous blood were taken at intervals during dialysis. At the same time as the sampling, the blood Urea dialysance values with ancrod were significantly less to flow was estimated by the bubble technique. Urea clearances than those with heparin (Table II), according Wilcoxon's sum to means were then calculated by the formula: of ranks test applied the overall of each dialysis (Langley, 1968).
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