August 2007 Vol 7 copy.indd ABSTRACT A sickle cell crisis can occur during cardiopulmonary bypass for cardiac surgical procedures in patients with sickle cell hemoglobin, which could lead to hemolysis. There is a dearth of such reports from the Arab world. We hereby present two cases from Oman with subclinical sickle cell crisis during cardiopulmonary bypass. The timely detection and early management resulted in good outcome. The good clinical practice for management of such patients is also discussed. Key words: Sickle cell trait; Cardiopulmonary bypass; Hemolysis; Case report; Oman. Subclinical Sickle Cell Crisis during Cardiopulmonary Bypass Timely detection and early management Raj Gopal Menon,1 *Madan M Maddali,2 Adil Al-Lawati,1 Hilal Al-Sabti3 SULTAN QABOOS UNIVERSITY MEDICAL JOURNAL AUGUST 2007 VOL 7, NO. 2, P. 79-81 SULTAN QABOOS UNIVERSITY© SUBMITTED - 28TH FEBRUARY 2007 1Department of Surgery, Royal Hospital, Muscat, Sultanate of Oman; 2Department of Anesthesia, Royal Hospital, Muscat, Sultanate of Oman; 3Department of Surgery, College of Medicine and Health Sciences, Sultan Qaboos University, P. O. Box 35, Al-Khod 123, Muscat, Sultanate of Oman *To whom correspondence should be addressed. Email: madan@omantel.net.om C A S E R E P O R T وِيَّة الرِئَ بِيَّةٌ لْ ازَةٌ القَ َالسريرية أثناء ا دون املنجلية اخللية أزمة مبكرا وعالجها املناسب في الوقت اكتشافها السبتي علي هالل اللواتي، ايد مادالي، عادل عبد م مادان مانون، راج جوبال اخللية هيموجلوبني ــن م يعانون الذين للمرضى اجلراحية ــب القل لعمليات لْبِيَّةٌ الرِئَوِيَّة القَ ــازَةٌ َا املنجلية أثناء ــة أزمة اخللي حتدث أن ــن ميك ــص: امللخ اخللية أزمة من يعانيان مان عُ من حالتني هنا نقدم العربي. العالم في التقارير هذه من القليل هناك احلمراء. الدم خاليا قد يؤدي إلى حتلل املنجلية مما أيضاً متت . جيدة نتائج إلى مبكر يؤديان ــكل بش الالزم وإجراء ــب املناس الوقت ــاف احلالة في اكتش . لْبِيَّةٌ الرِئَوِيَّة القَ ازَةٌ َا أثناء ــريرية الس دون املنجلية املرضى. هؤالء مثل لعالج اجليدة السريرية املمارسة مناقشة مان عُ حالة، احلمراء، تقرير الدم خاليا الرِئَوِيَّة، حتلل لْبِيَّةٌ ازَةٌ القَ َاملنجلية، ا اخللية الكلمات: سمة مفتاح A SICKLE CELL CRISIS CAN OCCUR IN PATIENTS with sickle cell trait (SCT) under extremely stressfully conditions albeit the incidence is much less than in patients with sickle cell disease (SCD). 1, 2 We report two consecutive cases of SCT who developed subclinical sickle cell crisis during cardiop- ulmonary bypass (CPB) resulting in haemolysis without overt haematuria. Observation of an alteration in the color of the ultrafiltrate and a simultaneous fall in hae- matocrit, as noticed in the intraoperative arterial blood gas analysis report, led to the detection and eventual mitigation of the problem. C A S E R E P O R T S C A SE  A 50-year lady underwent a coronary artery bypass graft (CABG) on CPB under a narcotic based general anesthesia and appropriate life support monitoring. The preoperative haematological results revealed sickle cell trait due to presence of heterozygous haemoglobin S (HbS) of 29.7%. The intraoperative arterial blood gas (ABG), inclusive of those on CPB, showed: pH ranging from 7.37 to 7.4, PaO2: 108 to 154, PaCO2: 34 to 38 and mixed venous saturations were more than 70%; all were suggestive of adequate perfusion. In addition, the tem- perature of the perfusate was maintained above 34OC and nitroglycerine infusion was administered to pre- R A J G O PA L M E N O N , M A D A N M M A D D A L I , A D I L A L - L AWAT I , H I L A L A L -S A B T I 80 vent vasoconstriction. A centrifugal pump was used to minimize blood trauma. Myocardial protection was achieved using cold antegrade blood cardioplegia. However, as soon as the cardioplegia was given, the ultrafiltrate from the hemofilter became bloodstained without obvious haematuria. An ABG analysis was im- mediately repeated and showed a haematocrit of 16%. Blood samples for surrogate markers of haemolysis were sent [Table 1]. Even though the urine appeared clear, urinalysis showed presence of haemoglobin. Im- mediately, 2 units of cross-matched blood were add- ed to the pump to increase the haematocrit to 24%. Shortly afterwards, the ultrafiltrate became clear. Fol- lowing this, the surgery was completed uneventfully. The patient did well postoperatively. The preoperative hematology status, values of markers for haemolysis during haemolysis and after transfusion have been tabulated [Table 1]. C A SE 2 A 70 years old gentleman underwent CABG on CPB. Preoperative haematological tests revealed SCT (HbS 30%). Like in Case 1, all precautions were taken to avoid a sickling episode. However, soon after cardio- plegia administration, the haematocrit dropped to 18% and the ultrafiltrate changed its colour without any change in the urine color. After sending blood specimens for identifying markers for haemolysis, two units of cross-matched blood were infused immedi- ately. Soon after, the haematocrit improved to 22% and the ultrafiltrate cleared. The blood investigations are shown in Table 1. D I S C U S S I O N In Oman, the prevalence of SCT is 6% and SCD is 0.9%.3 Patients with sickle cell abnormalities undergo- ing surgery are generally at a greater risk of periop- erative complications such as precipitation of a sickle cell crisis, microvascular occlusion, red cell membrane CASE 1 CASE 2 Parameters Pre- operative During the hemolytic event Post transfusion Post operative (immediately on reaching the ICU) Pre- operative During the hemolytic event Post transfusion Post operative (immediately on reaching the ICU) Hemoglobin [Hb] (g/dl) 11 5.4 8.4 9 11.2 5.8 7.8 9.2 Hematocrit (%) 33 16 24 24 34 18 22 28 Urinalysis Clear Free Hb Trace of RBC Clear Clear Free Hb Clear Clear Total bilirubin [µmol/L] 9.5 12.5 12.1 1 3.5 10.4 13.5 13.9 13.2 Serum haptoglobin (mg/L) Not done 690 900 380 Not done 520 513 360 Serum LDH (IU/L) Not done 298 108 100 Not done 304 104 102 Absolute reticulocyte count 109/L Not done 5 5 5 Not done 3.9 5.9 4.0 Table 1: Hematological values and markers of hemolysis WNL: within normal limits Normal Ranges: Hb: 10.9 – 16.1 g/dl, Hematocrit: 33-46%, Total bilirubin: 3-17 µmol/L, Serum haptoglobin: 360-1950 mg/L, Serum LDH: 95-190 IU/L, Absolute reticulocyte count: 5-200 x 109/ L S U B C L I N I C A L S I C K L E C E L L C R I S I S D U R I N G C A R D I O P U L M O N A R Y B Y PA S S 81 fragility and haemolysis.1, 2 In addition, CPB can cause a sickling crisis due to aortic cross clamping, hypo- thermia, cold crystalloid cardioplegia, haemodilution and low perfusion pressures. As both patients mentioned above were diag- nosed to have SCT by routine sickle cell screen and subsequent haematological investigations, all steps were taken to prevent a haemolytic episode during surgery. However, immediately after cross clamping and cardioplegia administration, the ultra filtrate ap- peared bloodstained in both patients, which indicated haemolysis. The urine remained clear. We suggest that this event was triggered by haemodilution following cardioplegia administration with a precipitous fall in haematocrit. Intraoperatively, it becomes difficult to make an im- mediate diagnosis of a sub-clinical sickling crisis and one has to depend on surrogate markers of haemolysis i.e. total bilirubin, serum lactate dehydrogenase (LDH) serum haptoglobin and absolute reticulocyte counts. The LDH levels were elevated in both patients (normal range: 95-190 IU/L) concurrent with a low haemat- ocrit. Haptoglobin, an acute phase protein, was mildly elevated from the lower range of normalcy and abso- lute reticulocyte counts remained unchanged proba- bly indicating that the haemolytic process had just be- gun. As soon as the ultrafiltrate became bloodstained, we suspected subclinical haemolysis, despite the fact that there was no obvious haematuria and transfused cross-matched blood to elevate the haematocrit to above 20%. The colour of the ultrafiltrate cleared and serum haptoglobin that was slightly elevated and se- rum LDH levels normalized rapidly indicating a short duration of a sickling related haemolysis. Following a haemolytic episode, surrogate mark- ers (total bilirubin, serum haptoglobin, serum LDH and reticulocyte counts) are usually elevated. The elevation of these markers depends to a large extent on the duration and severity of the episode. Total bi- lirubin, serums LDH and serum haptoglobin are sen- sitive indicators and are elevated earlier than absolute reticulocyte counts. When the surrogate markers are considered individually in both the patients, the total bilirubin was slightly elevated from its preoperative values. Serum haptoglobin levels, though within the normal range, were elevated during the episode com- pared to postoperative values. Serum LDH was ele- vated, but once again normalized postoperatively. It is true that the institution of a cardiopulmonary bypass could derange several biochemical values. At the same time, macroscopic haemolysis and a drop in haemat- ocrit per se are not markers for haemolysis. However, based on an overt change in ultrafiltrate colour that rapidly corrected after elevation of the haematocrit, presence of free haemoglobin in urine and mild ele- vation in some of the haemolytic markers, a working diagnosis of a short-lived subclinical haemolysis was made. The shortcoming in this case report is that we did not measure the surrogate markers for haemolysis pri- or to surgery. This would have provided base line val- ues for confirming the diagnosis and would have aided in identifying any pre-existing problems. Other than total bilirubin, as all the other markers were measured for the first time only intraoperatively, an elevation from their respective normal ranges was taken as di- agnostic criteria. In patients with sickle cell haemoglobin, preopera- tive partial exchange transfusion to achieve a haemat- ocrit of 30% with HbS < 30% has been recommended for major surgery.1 This is done to reduce the overall burden of HbS mass to less than 30% thereby avoiding a sickling episode. As both our patients had base line haemoglobin (Hb) levels above 10gms, no blood trans- fusions were administered preoperatively. In conclusion, in the absence of other triggering factors, a drop in haematocrit during cardiopulmonary bypass in patients with sickle cell alone could lead to a subclinical sickle cell crisis and haemolysis. This might not necessarily be associated with haematuria. In the event of such a crisis being precipitated on CPB and if the cause is deemed to be haemodilution, rapid res- toration of the haematocrit to above 20% would avoid further progress of the crisis. Lastly, a preoperative estimation of all the surrogate markers of haemolysis would aid in identifying any pre-existing problems as well as serve as base line values for identifying periop- erative sickle cell related issues. R E F E R E N C E S 1. Maddali MM, Rajakumar MC, Fahr J, Albahrani MJ, Amna MA. Cardiopulmonary bypass with- out preoperative exchange transfusion in sicklers. Asian Cardiovasc Thorac Ann 2006; 14:51-56. 2. Singh J, Mehta S, Sharma R, Rana SS, Thingnam SK, Dhaliwal RS. Cardiopulmonary bypass in sickle cell dis- ease. Asian Cardiovasc Thorac Ann 2006; 14:445-46. 3. Al Riyami A, Ebrahim GJ. Genetic blood disorders Sur- vey in the Sultanate of Oman. J Tropical Pediatrics 2003; 49:11-20.