Reduction of blood loss by restoration of platelet levels using fresh autologous blood after cardiopulmonary bypass
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1 Thorx (1972), 27, 410 Reduction of blood loss by restortion of pltelet levels using fresh utologous blood fter crdiopulmonry bypss J G WAGSTAFFE, A D CLARKE, nd P W JACKSON' Deprtments of Crdic Surgery nd Anesthetics, The Royl nfirmry, Mnchester Two methods of tking off two units of blood before bypss, storing it t 40 C, nd giving it fter heprin reversl t the end of bypss re described nd compred When the blood ws tken into cid citrte dextrose before the ptient ws heprinized, the pltelet count incresed by 22,000/mm3 nd blood loss ws reduced by 26-7% ( significnt decrese) Blood, tken fter heprin ws given, gve similr pltelet increse fter retrnsfusion but the resulting decrese in blood loss ws 17 6% ( non-significnt decrese) Neither difficulties nor complictions were noted using the technique in 38 ptients Thrombocytopeni fter open hert surgery is common nd my be ssocited with incresed blood loss During the use of pump oxygentors for crdiopulmonry bypss the whole of the ptient's circulting blood volume is exposed to progressive mechnicl trum which produces chnges in the fctors ffecting cogultion (Rothnie, Normn, Steele, nd Kinmonth, 1960; Kendll nd Lowenstein, 1962; Gns nd Krivit, 1962; Gibbon nd Cmishion, 1964), in prticulr reduction in circulting pltelets Grindon nd Schmidt (1969) perfused with pltelet-poor blood wthout impiring cogultion, but, in our experience, the immedite post-perfusion thrombocytopeni hs been the min cuse of impired cogultion Low pltelet counts of 70,000/mm3 (Couch, 1967) nd 60,000/mm3 (Obermn, 1967) hve been quoted, but, like Khn, Strng, nd Wilson (1968), we regrd levels below 50,000/mm3 s criticl Exposing the whole circulting blood volume to mechnicl trum ppered undesirble Blood ws therefore withdrwn from the ptient before bypss (Dodrill et l, 1957; Hrdesty, Byer, nd Bhnson, 1968) This utologous blood ws lter returned Removl of blood from even the very ill ptient ws considered fesible s these ptients hd n incresed blood volume due to congestive hert filure The purpose of this study ws to evlute the lcorrespond-nce to PWJ, Dept of Anesthetics 410 bove technique by mesuring the pltelet levels nd totl blood loss fter the perfusion Heprin reduces circulting pltelets in vivo (Kirby, 1958) nd in vitro (Perkins, Osborn, nd Gerbode, 1958), but s cid citrte dextrose (ACD) is reported to increse pltelet survivl (Perkins et l, 1958), the effect of using either heprin or ACD s the nticogulnt ws lso investigted METHOD Two groups of ptients operted on by two different surgicl tems were investigted nd compred with their respective control groups The opertions performed in these groups re listed in Tble The opertions performed in both control groups were consecutive cses strting before this study n both study groups ptients were lso consecutive Ptients who hd known preopertive cogultion disorders nd ny ptient who bled due to fulty surgicl hemostsis were excluded from both control nd study groups GROUP 1 (23 ptients) From ech ptient 840 ml of blood ws collected in two 540-ml trnsfusion bottles, ech contining 120 ml of ACD nticogulnt The blood ws tken pproximtely 5 minutes before heprin ws given for bypss, vi 100-cm tube of 4 mm internl dimeter (D) inserted in the right trium nd secured by purse-string suture (Fig 1) n this group the rte of bleeding ws controlled by the rteril nd venous pressures, the systolic rteril pressure not being llowed to fll below 70 mmhg Recovery from the brief period of hypotension occurred when hlf the blood volume withdrwn ws replced with 5 %
2 Reduction of blood loss by rwestortion of pltelet levels 411 TABLE Opertion Study Control ncision' Group 1 ptients Mitrl vlve replcement AT Mitrl vlve resuture - 1 AT Mitrl nd ortic vlve replcements 2 3 MS Aortic vlve replcement 3 2 MS Tetrlogy of Fliot 2 3 MS Ventriculr septl defect - 1 MS Pulmonry stenosis - AT Crdiotomy only 1 MS Totl Group 2 ptients Mitrl vlve replcement 4 10 AT Mitrl vlve replcement with tricuspid vlvuloplsty 2 - AT Mitrl nd tricuspid vlve replcements 1 1 AT Mitrl nd ortic vlve replcements 3 - MS Aortic vlve replcement 2 3 MS Aortic vlve replcement nd mitrl vlvotomy - MS Tetrlogy of Fllot MS Ventriculr septl defect 1 AT Primum tril septl defect 1 - AT Totl AT =ntero-lterl thorcotomy; MS= medin sternotomy 4 mm D TUBE FLOW CONTROLLER 540 ml GROUP FG 1 Method of collection of utologous ACD blood dextrose in 0-18% norml sline, which ws given fter the collection of blood so s to void dilution of the collected blood GROUP 2 (15 ptients) Ten minutes fter giving 3 mg/kg body weight of heprin, 1,080 ml of heprinized blood ws collected into two 540-ml bottles s bypss begn The priming fluid (5% dextrose in 0-18% norml sline) in the venous tube of the extrcorporel circuit ws first displced by the ptient's blood This blood ws then collected vi 12 mm D polycrbonte stright connector with Luer side rm, inserted in the venous tube ner the entry port to the oxygentor Attched to the Luer side rm ws 20 cm length of 4 mm D tube for collection of blood (Fig 2) GROUP 11 FG 2 Method of collection of utologous heprinized blood The collected blood from both groups of ptients ws stored t 40 C until required t the end of bypss Ptients in both study groups received no donor blood before bypss but, to compenste for the volume of blood withdrwn, similr volume of ACD donor blood, sometimes up to five dys old, ws dded to the pump oxygentor prime to mintin sfe operting volume within the Rygg oxygentor during bypss The prime ws buffered with sodium bicrbonte (25 meq/litre) The volume of the priming fluid (5% dextrose in 0-18% norml sline) ws clculted t 20 ml/kg body weight (Cooley, Bell, nd Grondin, 1962) All the perfusions were normothermic except in those cses involving surgery of the ortic vlve in which hypothermi (32 C oesophgel) ws used When the bypss ws completed, intrvenous protmine sulphte ws given to neutrlize circulting heprin, the dose required hving been determined by heprin protmine titrtion (Perkins et l, 1956) The utologous blood ws then returned to the ptient vi drip set connected to the rteril line of the pump oxygentor This drip set ws ttched to the luer side rm of 12 mm D polycrbonte connexion proximl to the rteril pump The introduction of blood t this point of the circuit llowed the stored blood to be wrmed nd filtered before it entered the
3 412 J G Wgstfje, A D Clrke, nd P W Jckson ptient The remining utologous blood in the rteril line ws displced with blood from the oxygentor The infusion time vried from 5 to 15 minutes, being controlled by the centrl venous pressure (CVP) which ws mintined below 20 cm H20 n group 1, clcium gluconte, 10 g per litre of blood, ws given to cover the effect of citrte contined in the ACD utologous blood n group 2, further dose of protmine sulphte, 30 mg/litre, ws lter given to neutrlize the heprin in the utologous blood After ll the utologous blood hd been returned to the ptient stored donor blood ws given to replce overll blood loss (the ge of this blood vried from two to five dys) Seril pltelet counts ccording to the method of Lempert (1935) were mde t the following times: (1) before opertion; (2) t the end of bypss; (3) 10 minutes fter utologous blood trnsfusion; (4) on return to the intensive cre unit; (5) on the first postopertive dy; nd (6) on the second postopertive dy All pltelet counts were mde s routine hemtologicl procedures by n experienced technicin who ws unwre of the nture of the study Mesurement of the totl blood loss ws mesured in millilitres per squre metre (ml/m2); this begn immeditely fter giving the utologous blood nd ws mintined until ll chest drins were removed, s described by Smith et l (1964) Re-explortion of two ptients ws performed, one from ech study group, due to hemothorx These ptients' blood loss figures re included in Tble The pltelet counts nd blood loss dt for the study groups were compred with those for the respective control groups who received only donor ACD blood fter bypss These dt were compred using Student's t test, ccepting P<0 05 s level of significnce RESULTS The men pltelet increses for both groups, due to utologous blood trnsfusion, re shown in Tble n group 1, this improvement over the TABLE MEAN VALUES FOR PLATELET COUNTS BEFORE AND AFTER AUTOLOGOUS BLOOD TRANSFUSON Group 1 Group 2 (840 ml utologous (1080 ml heprinized blood) utologous blood) Y Volume of blood withdrwn 15 % 22'% Study Control Study Control No of ptients Bypss time (min) Pltelets x 10'/mm' End of bypss 56 5± ± l18-7 Rnge (25-85) (34-120) (18-74) (15-83) After utologous blood 82-4 ± ± Rnge (34-134) (21-132) Men pltelet increse 22-1 ± Rnge (3-93) (9-73) Y increse P<001 P<001 control group ws shown by men increse of 22,100+21,500/mm3 fter trnsfusion This represents 36-6% increse when compred with the control group (P<0-01) The men bypss time for the study group ws 16 minutes less thn for the control Similrly, in group 2 the improvement over the control group ws shown by men increse of 26,690+22,800/mm1 fter trnsfusion This represents 57-8 % rise compred with control group (P<0 01) n study group 1, the smllest increse of pltelets in ny one ptient ws 3,000/mm3 nd the highest increse ws 93,000/mm3 Similrly, for study group 2 the lowest increse ws 9,000/mm3 nd the highest ws 73,000/mm3 fter utologous blood trnsfusion The verge blood volumes withdrwn were 15% for group 1 nd 22% for group 2 Figure 3 illustrtes the typicl chnges in rteril nd centrl venous blood pressures during the collection of blood in ptient from study group 1 The brief period of hypotension ws improved by the trnsfusion of 5 % dextrose in 0-18 % norml sline The immedite nd lter effects of utologous blood trnsfusion in both groups re shown in Figures 4 nd 5 The storge time for blood in group 1 verged 15 minutes longer thn in group 2 s this blood ws withdrwn erlier Fresh blood or pltelet concentrtes were not required for ny ptient in either study group - 8E E ' trnsfusion collect with 5% dextrose blood in 0-18% N sline, "~20-0E >u 0- C O0 0 systolic "% - s- _ distolic U Minutes FG 3 Typicl trcing ofbloodpressure nd centrl venous pressure during bleeding in ptient in group 1 BLOOD LOSS The men totl blood loss figures (ml/nm2) from the end of bypss re shown in
4 xu Ji 5- Reduction of blood loss by restortion of pltelet levels 840 ml AC D AUTOLOGOUS BLOOD E200 * STUDY CONTROL A0\ * L0',, 4'- -k FG4Mpltltcutin4pinsistdgru FG 4 1 nd its control sva*9o r e STUDY 200 t CONTROLL 1000,o t tn9 t g * 't 4 Men pltelet counts in 48 ptients in study group 1080 ml HEPARNZED AUTOLOGOUS BLOOD FG 5 Men pltelet counts in 32 ptients in study group 2 nd its control Tble Blood loss in group 1 shows tht the ptient who received utologous ACD blood produced significnt reduction of 26-7% (P<005 one-til Student's t test) s compred with the control figures Blood loss in group 2 shows tht fter trnsfusion with heprinized utologous blood reduction of 176% ws produced, which TABLE MEAN VALUES FOR BLOOD LOSS (ml/m2) AFTER AUTO- LOGOUS BLOOD TRANSFUSON Group 1 Group 2 Study Control Study Control No of ptients Surfce re 231 1X Totlbloodloss 1748± Rnge Men reduction %Decrese 26-7 P< P>0-1 (1 til test) (1 til test) One ptient from ech group ws re-explored due to hemothorx ws not significnt (P>0 1, one-til Student's t test) s compred with figures for blood loss in control ptients in group 2 DSCUSSON 413 This investigtion ws begun becuse we were concerned bout the high blood loss often ssocited with pltelet counts below 50,000/mm3 The ccepted tretment of postopertive hemorrhge ssocited with low pltelet count is by the trnsfusion of fresh blood (Obermn, 1967) or pltelet concentrtes (Woods, Tswell, Kirklin, nd Owen, 1967) As method of reducing these demnds on the trnsfusion service, utologous blood ws used in similr mnner to tht described by Hrdesty et l (1968) n group 2 of our series, our results confirm their work using heprin s the nticogulnt Our methods differed in tht smller volumes were collected nd stored in glss bottles t 4' C to increse pltelet survivl (Goldstein, Bunker, nd McGovern, 1964) n group 1 of our series, when ACD utologous blood ws used, the improvement in blood loss becme significnt (P<0 05) We feel it is importnt not to return the utologous blood until fter the protmine sulphte hs neutrlized the circulting heprin nd is seen to be effective by the production of visible clots This reduces the loss of the trnsfused utologous blood from the sites of hemorrhge During the trnsfusion the CVP ws incresed but ws not llowed to rise bove 20 cm H20 to prevent circultory overlod n our study these methods for rising the pltelet count did not produce s high n increse s tht produced by the trnsfusion of pltelet concentrtes, described by Woods et l (1967), who extrcted donor pltelets from up to 8 units of blood collected on the morning of the opertion We feel tht our method is s effective in reducing blood loss nd hs the virtue of simplicity nd of supplying utologous pltelets, nd possibly other cogultion fctors Figures 4 nd 5 illustrte tht the immedite increses in the men pltelet count in both study groups were mintined t higher level thn in the control groups up to the second postopertive dy t is interesting to note tht in group 1 the men pltelet count 10 minutes fter the utologous blood hd been given ws higher thn fter surgery ws completed After bypss nd heprin reversl the utiliztion of pltelets should be t its pek, nd this my suggest tht pltelets stored in ACD blood re immeditely more effective thn those stored in heprin
5 414 J G WgstfJe, A D Clrke, nd P W Jckson The men bypss time in study group 1 ws reduced by 16 minutes nd this ws chieved without mking ny chnges in surgicl technique between the control nd study groups n this group the mjority of opertions were for mitrl vlve replcement nd the reduced bypss time cn probbly be explined by incresed experience However, in study group 2, the reson for incresed bypss time is tht some opertions for replcement of the mitrl vlve re ccompnied by either ortic or tricuspid vlve surgery The greter prt of the decrese in pltelets occurs within 15 minutes fter bypss begins Further but smll reductions continue to occur until the pltelet count becomes stbilized bout 30 minutes fter the strt of bypss (Kendll nd Lowenstein, 1962) Therefore we did not nticipte ny improvement in the pltelet count in study group 1 due to reducing the men bypss time to 68 minutes s compred with the control group men bypss time of 84 minutes On the other hnd, prolonged bypss time is likely to ffect other clotting fctors nd so my increse postopertive blood loss The longer bypss times in study group 2 s compred with the control (Tble ) could hve bised the results nd my explin the smller reduction in blood loss fter heprinized utologous blood in group 2 s compred with group 1 (Tble ) n our study the use of utologous blood by these simple techniques hs rised pltelet counts from criticl to cceptble post-bypss levels At times it my not be possible to collect blood into ACD s in group 1, due, for exmple, to low circulting blood volume or poor crdic output n these circumstnces it my be preferble to use the method described for group 2 We re indebted to Mr H F M Bssett nd Mr K Bloor for their co-opertion in llowing us to study their ptients We re grteful for the digrms produced by the Deprtment of Medicl llustrtion, Mnchester Royl nfirmry We should like to extend our grtitude to Dr J E Mclver for dvice nd ssistnce, to Miss J Bottomley for technicl ssistnce, to Mr E Moss for vluble ssistnce with the ssessment of dt, nd to Mrs Alcock for secretril ssistnce REFERENCES Cooley, D A, Bell, A C, nd Grondin, P (1962) Openhert opertions with disposble oxygentors, 5 per cent dextrose prime, nd normothermi Surgery, 52, 713 Couch, N P (1967) The role of the blood bnk in crdic surgery n Crdic Surgery, p 54, edited by J C Normn Meredith Publishing Compny, New York, nd Butterworth, London Dodrill, F D, Mrshll, N, Nyboer, J, Hughes, C H, Derbyshire, A J, nd Sterns, A B (1957) The use of the hert-lung pprtus in humn crdic surgery J thorc Surg, 33, 60 Gns, H, nd Krivit, W (1962) Problems in hemostsis during open hert surgery V On the chnges in the blood clotting mechnism during crdiopulmonry bypss procedures Ann Surg, 155, 353 Gibbon, J H, nd Cmishion, R C (1964) Problems in hemostsis with extrcorporel pprtus Ann N Y Acd Sci, 115 (Art 1), 195 Goldstein, R, Bunker, J P, nd McGovern, J J (1964) The effect of storge of whole blood nd nticogulnts upon certin cogultion fctors Ann N Y Acd Sci, 115 (Art 1), 422 Grindon, A J, nd Schmidt, P J (1969) Pltelet-poor blood in open-hert surgery New Engl J Med, 280, 1337 Hrdesty, R L, Byer, W L, nd Bhnson, H T (1968) A technique for the use of utologous fresh blood during open-hert surgery J thorc crdiovsc Surg, 56, 683 Khn, D R, Strng, R H, nd Wilson, W S (1968) Clinicl Aspects of Operble Hert Disese, p 57 Appleton-Century-Crofts, New York (Division of Meredith Corportion) Kendll, A G, nd Lowenstein, L (1962) Altertions in blood cogultion nd hemostsis during extrcorporel circultion; prt 1 Cnd med Ass J, 87, 786 Kirby, C K (1958) Discussion on blood chnges n Extrcorporel Circultion, edited by J G Allen, p 264 Thoms, Springfield, llinois Lempert, H (1935) A modified technique for the enumertion of blood pltelets Lncet, 1, 151 Obermn, H A (1967) The indictions for trnsfusion of freshly drwn blood J Amer med Ass, 199, 93 Perkins, H A, Osborn, J J, nd Gerbode, F (1958) The effect of heprin on the pltelet count in vitro, with prticulr reference to the collection of blood for extrcorporel circultion Amer J clin Pth, 30, 397, Hurt, R, nd Gerbode, E F (1956) Neutrliztion of heprin in vivo with protmine A simple method of estimting the required dose J Lb clin Med, 48, 223 Rothnie, N G, Normn, A G, Steele, M, nd Kinmonth, J B (1960) Chnges in blood-cogultion due to perfusion for crdic surgery Brit J Surg, 48, 272 Smith, B, Omeri, M A, Melrose, D G, Bentll, H H, nd Allwork, S (1964) Blood-loss fter crdiopulmonry bypss Lncet, 2, 273 Woods, J E, Tswell, H F, Kirklin, J W, nd Owen, C A (1967) The trnsfusion of pltelet concentrtes in ptients undergoing hert surgery Myo Clin Proc, 42, 318
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