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Alteration of Coagulation and Selected Clinical Chemistry Parameters in Patients Undergoing Open Heart Surgery Without Transfusions JOHN D. MILAM, M.D., STEPHEN F. AUSTIN, MT(ASCP), ROBERT F. MARTIN, PH.D., ARTHUR S. KEATS, M.D., AND DENTON A. COOLEY, M.D. Milam, John D., Austin, Stephen F., Martin, Robert F., Keats, Arthur S., and Cooley, Denton A.: Alteration of coagulation and selected clinical chemistry parameters in patients undergoing open heart surgery without transfusions. Am J Clin Pathol 76:155-162, 1981. Alteration of coagulation status and certain clinical chemistry laboratory determinations of 75 adult patients undergoing cardiopulmonary bypass procedures for acquired heart disease was studied during and after surgery. None of the patients was given transfusions of blood or blood components. With hemodilution, the mean hematocrit value dropped from 38% to 28% during the procedure. Fibrin degradation products and euglobulin lysis time were transiently abnormal. Factor V diminished somewhat during the procedure, whereas factors VIII and IX increased after surgery. Clottable fibrinogen values decreased slightly, but increased to an abnormally high value at 24 and 48 hours. Mean value of platelet counts decreased from 194,000 to 144,000//xl immediately after surgery. Knowledge of expected deviation of coagulation factors and certain clinical chemistry tests following open heart surgery is helpful in evaluating the status of the postoperative patient. (Key words: Open heart surgery; Cardiopulmonary bypass; Coagulation.) THE PRINCIPLE OBJECTIVE of this investigation was to define subclinical coagulation derangements and to denote certain physiologic changes occurring as a result of open heart surgery (OHS) and/or hemodilution procedures in a comprehensively studied group of 75 patients who did not receive transfusions. Recognition and proper management of aberrant clotting disorders in patients undergoing OHS depends greatly on awareness of usual or expected alterations. Materials and Methods Patients The randomly selected study group consisted of 75 adult patients having OHS for acquired heart disease. Blood transfusion was not clinically indicated or adminReceived October 22, 1980; received revised manuscript and accepted for publication January 20, 1981. Supported in part by the Kleberg Memorial Fund and the Johnson Space Center Fund. Address reprint requests to Dr. Milam: Department of Pathology, St. Luke's Episcopal Hospital, Texas Medical Center, Houston, Texas 77030. Departments of Pathology, Cardiovascular Surgery, and Anesthesiology, St. Luke's Episcopal Hospital and Texas Heart Institute, and the Department of Pathology, Baylor College of Medicine, Houston, Texas istered before, during, or after surgery for any of the patients. The surgical procedures performed were as follows: aortocoronary artery bypasses (two or more), 57; mitral valve resection and aortocoronary artery bypasses, one; mitral valve resection, four; aortic valve resection, 13. The average age was 53 years; the range was 31 to 76 years. Cardiopulmonary Bypass Technic. Anticoagulation was achieved by intravenous administration of sodium heparin solution, 300 units/kg body weight, with an additional 2,500 units added to each liter of priming solution. A disposable bubble oxygenator (Harvey disposable oxygenator, Model H 200)* was utilized, with hemodilution 6 being accomplished by priming with lactated Ringer's (Hartman's) solution—5% dextrose mixture, 20 ml/kg body weight. Other constituents of the extracorporeal circuit included the Sarns roller pump,t Harvey cardiotomy reservoir (Model H-500),* Swank extracorporeal filter (Type CA-100),$ and the Texas Heart Institute custom tubing pack.§ Systemic normothermia was maintained during surgery. Coronary artery perfusion was not performed. At the end of the procedure, intravenous protamine sulfate (1 mg per 100 units of heparin) was administered to neutralize the heparin. The mean values obtained from the perfusion data of the 75 patients show a mean age of 53 years; weight of patient, 79 kg; flow rate, 3,910 ml/min; perfusion rate, 50 ml/kg/min; and CPB time, 57 min. Fundamental as* William Harvey Research Corporation, Santa Ana, California. t Sarns Manufacturing Company, Ann Arbor, Michigan. t Pioneer Filters Inc., Beaverton, Oregon. § Artificial Organs Division, Travenol Laboratories, Morton Grove, Illinois. 0002-9173/81/0008/0155 $00.90 © American Society of Clinical Pathologists 155 156 MILAM ET AL. A.J.C.P. • August 1981 Table 1. Hematology Data Mean ± Standard Deviation Hemoglobin (g/dl) Preoperative 30 min CPB 1 hour postoperative 24 hours postoperative 48 hours postoperative 13.1 9.2 12.0 11.5 10.2 Hematocrit (%) Preoperative 30 min CPB 1 hour postoperative 24 hours postoperative 48 hours postoperative 38 28 35 34 30 Range of Values Average Percentage Change ± Confidence Interval! Tolerance Limits for Percentage Changet — 10.8-16.6 7.2-11.9 9.3-15.2 9.3-14.7 8.0-13.5 -30.0 -8.6 -12.0 -22.0 ± ± ± ± 1.8 2.3 2.4 2.8 ± 3.8 ± 3.1* ± 3.7* ± 3.5* ± 3.8* 29-50 21-37 26-45 27-45 23-42 -27.6 -8.2 -11.4 -21.1 ± ± ± ± 2.0 2.4 2.6 2.9 -12— 11— 9— 1— 4.4 3.0 4.0 3.8 3.4 ± ± ± ± ± 0.46 0.37* 0.47* 0.43* 0.46* 3.5-5.5 2.3-4.1 2.9-5.1 3.0-4.8 2.6-4.4 -29.8 -9.1 -12.2 -22.1 ± ± ± ± 1.8 2.3 2.4 2.8 -15.1— 9.6 — 6.8— 0.6 — Mean corpuscular volume (cu fj.) Preoperative 30 min CPB 1 hour postoperative 24 hours postoperative 48 hours postoperative 88 90 88 88 89 ± ± ± ± ± 4.6 4.6* 4.6 4.5 4.4 77-98 76-101 77-98 79-96 77-96 2.1 0.3 0.3 0.6 ± ± ± ± 0.6 0.4 0.5 0.6 7— 5 4— 6— -3 -5§ -6§ -5 Mean corpuscular hemoglobin (pg) Preoperative 30 min CPB 1 hour postoperative 24 hours postoperative 48 hours postoperative 30 30 30 30 30 ± 1.5 ± 1.5 ± 1.5 ± 1.5 ±1.6 26-34 25-33 26-33 26-33 26-34 -0.3 0.4 0.2 0.1 ± ± ± ± 0.5 0.5 0.6 0.7 4— 8— 6 6— -4 -8§ -3§ -7§ Mean corpuscular hemoglobin concentration (%) Preoperative 30 min CPB 1 hour postoperative 24 hours postoperative 48 hours postoperative 34 33 34 34 34 ± ± ± ± ± 0.9 0.9* 0.9 0.8 0.9 32-36 31-36 32-36 32-36 32-36 -2.7 -0.1 -0.3 -0.7 ± ± ± ± 0.8 0.6 0.6 0.8 6.6 7.0 11.4 13.5 13.0 ± ± ± ± ± 1.97 2.61 3.98* 3.03* 4.20* 3.3-13.6 2.9-13.7 5.2-23.3 8.4-21.9 5.5-35.9 8.4 76.9 114.8 103.9 ± ± ± ± 10.7 16.6 18.1 18.0 2-40 3-235 5-224 2-58 0.1-52 632.5 980.2 43.4 -13.9 ± 253.0 ± 226.7 ± 52.2 ± 24.8 <25->200 0-100-200 0-100-200 0-100-200 <25->200 -63.2 -63.7 -46.4 36.1 ± 6.8 ± 9.7 ± 10.0 ± 22.3 Erythrocyte count (x 106//xl) Preoperative 30 min CPB 1 hour postoperative 24 hours postoperative 48 hours postoperative ± ± ± ± ± 1.23 0.99* 1.26* 1.16* 1.21* -15.6 9.7 6.7 0.0 — — — — -44.4 -26.8 -30.8 -44.0 -43 -27 -32 -44 -44.6 -27.7 -31.2 -44.8 1 4— 4— 5— 5— -9 -4 -3§ -7 Leukocyte Count (x 103//A1) Preoperative 30 min CPB 1 hour postoperative 24 hours postoperative 48 hours postoperative Plasma hemoglobin (mg/dl) (NV: 0.5-5.0) Preoperative 30 min CPB 1 hour postoperative 24 hours postoperative 48 hours postoperative 9 ± 7.6 47 ± 37.6* 74 ± 47.8* 9 ± 10.1 6 ± 7.2* Serum haptoglobin (mg/dl) (NV: 100-200) Preoperative 30 min CPB 1 hour postoperative 24 hours postoperative 48 hours postoperative 118 38 36 58 137 ± 50.8 ± 27.8* ± 28.6* ± 37.0* ± 48.0* 94.0— - 7 7 . 1 209.5 — - 5 5 . 7 263.6— 11.2§ 247.1— - 3 9 . 2 2,795 — - 3 3 § 3,194- -10 933 — - 8 9 § 342 — - 9 8 0— 50— 50 — 300 — -100 -100§ -100 -83§ Vol. 76 • No. 2 ALTERATION OF COAGULATION DURING OHS 157 Table I.—(continued) Mean ± Standard Deviation Platelet count (xl0 : 7/nl) (NV: 150-400) Preoperative 30 min CPB 1 hour postoperative 24 hours postoperative 48 hours postoperative 194 119 144 156 149 ± ± ± ± ± Range of Values 58.1 45.9* 49.9* 51.1* 48.0* 80-400 44-245 61-310 70-345 73-310 Average Percentage Change ± Confidence Intervalt — -37.0 -23.8 -16.8 -21.2 ± ± ± ± Tolerance Limits for Percentage Changet — 5.8 6.6 7.4 5.8 9^ 29 -* 53 -> 25 - • -83 -76 -64§ -67 NV, normal value. * P < 0.01 versus preoperative mean by paired / test. t See Results section in text. § When distributions are non-Gaussian, a distribution independent tolerance interval (y = 0.99, P = 0.90) is presented. With N = 75, the confidence interval estimates in column 3 will have a confidence level very little different from 0.99, even when departures from normality are significant. pects of hemodilution technics and cardiopulmonary bypass (CPB) are described elsewhere.14 were obtained by specific factor-deficient substrate plasma procedures.2'9,10,21~23 Fibrin degradation products (FDP) semiquantification was determined by tanned erythrocyte hemagglutination inhibition immunoassay (TRCHII)13 and by staphylococcal clumping technic.1 Fibrinogen standards were used to estimate FDP titer. Serum osmolality was determined by freezing point detection,tt and viscosity by water reference.7 Enzyme kinetic reactions were utilized for erythrocyte 2,3-DPG quantitation.18 Laboratory Procedures The following laboratory determinations were obtained prior to heparinization preoperatively, 30 min following onset of CPB, and at one, 24, and 48 hours postoperatively: hemoglobin; hematocrit; erythrocyte count; mean corpuscular volume; mean corpuscular hemoglobin; mean corpuscular hemoglobin concentration; leukocyte count; plasma hemoglobin; serum haptoglobin; platelet count; prothrombin time; activated partial thromboplastin time; fibrinogen; euglobulin lysis time; tanned erythrocyte hemagglutination inhibition immunoassay; staphylococcal clumping test; reptilase time; assays for factors II, V, VII, VIII, IX, and X; total serum protein; arterial blood gases and/?H; serum osmolality; serum viscosity; serum sodium; serum potassium; serum calcium; serum phosphorus; erythrocyte 2,3-diphosphoglycerate (DPG). Basic hematologic parameters were obtained with the Coulter Counter Model S,H and platelet counting was performed by use of calibrated chamber and phase microscopy4 and by an electrical impedance counter.** Plasma hemoglobin was measured by methodology based on peroxidase activity of hemoglobin, with ortho-tolidine being the oxidized substrate.3 Haptoglobin semiquantitative determinations were performed by buffered agar gel electrophoresis of the patients' sera with known quantities of added hemoglobin. Ortho-tolidine was used to stain the hemoglobin bands.19Prothrombin time,21 activated partial thromboplastin time (PTT),1215 clottable fibrinogen,20 euglobulin lysis time,511 and reptilase time8 were determined by established technics. Coagulation factor assays II Coulter.Electronics, Hialeah, Florida. ** Clay Adams Ultra-Flo 100 Whole Blood Counter Model No. 2510, Clay Adams, Parsippany, New Jersey. Results A summary of hematology, coagulation, and chemistry data appears in Tables 1-3, respectively. In the tables, column one lists the sample arithmetic mean and standard deviation. An asterisk indicates that the mean value is significantly different from the preoperative mean at the 99% confidence level (P < 0.01) by the paired t test. Column two lists the range of the individual observations. For the 75-value sample, this corresponds to a distribution independent tolerance interval,? = 0.99, P = 0.9017 (with 99% confidence, at least 90% of a patient population having OHS under the conditions described should have values within this interval). Column three lists the average percentage change from the preoperative value. The 99% confidencelimits from the mean are obtained by performing the indicated addition/subtraction17 (for example, with 99% confidence, the true average percentage decrease in hemoglobin at 30 min CPB would be between 28.2% and 31.8%). To emphasize individual patient variation in percentage change from the preoperative value, column four lists statistical tolerance limits, y = 0.99, P = 0.9517 (for example, with 99% confidence, at least 95% of a patient population having OHS under the conditions described should have a 30 min CPB hemot t Fiske Osmatic-Automatic Osmometer Model 130, Fiske Associates, Inc. Uxbridge, Massachusetts. 158 MILAM EI AL. A.J.C.P. • August 1981 Table 2. Coagulation Data Mean ± Standard Deviation Prothrombin time (sec) (NV: 12-15) Preoperative 30 min CPB 1 hour postoperative 24 hours postoperative 48 hours postoperative Activated partial thromboplastin time (sec) (NV: 24-40) Preoperative 30 min CPB 1 hour postoperative 24 hours postoperative 48 hours postoperative Fibrinogen (mg/dl) (NV: 200-400) Preoperative 30 min CPB 1 hour postoperative 24 hours postoperative 48 hours postoperative 12 ± 0.9 — 14 ± 1.5* 12 ± 1.0* 12 ± 0.8 35 ± 5.5 — 33 ± 5.2* 33 ± 4.2* 33 ± 4.0* 282 176 237 411 557 ± ± ± ± ± 76.2 46.8* 61.5* 85.6* 103.8* Euglobulin lysis time (min) (NV: 60) Preoperative 30 min CPB 1 hour postoperative 24 hours postoperative 48 hours postoperative >60 31 ± 19* >60 >60 >60 Tanned erythrocyte hemagglutination inhibition immunoassay (/xg/ml) (NV: 2-10) Preoperative 1 hour postoperative 24 hours postoperative 48 hours postoperative 3 7 14 16 ± ± ± ± Staphylococcal clumping test (/xg/ml) (NV: 2-10) Preoperative 1 hour postoperative 24 hours postoperative 48 hours postoperative 1 4 4 5 Reptilase time (sec) (NV: 18-22) Preoperative 30 min CPB 1 hour postoperative 24 hours postoperative 48 hours postoperative Range of Values 9-14 29->300 11-17 10-15 10-14 24-51 >300 22-50 25-51 26-42 163-573 91-336 124-479 255-620 275-798 Average Percentage Change ± Confidence Intervalt Tolerance Limits for Percentage Changet — — — 19.2 ± 3.2 7.2 ± 2.9 2.3 ± 2.4 44-> - 6 30-* -16 22 ^ - 1 7 — "— - 4 . 1 ± 4.8 - 3 . 7 ± 4.2 - 3 . 6 ± 4.3 -37.2 -15.2 50.3 106.0 ± ± ± ± 2.5 3.5 9.5 15.5 34 ->• - 4 2 42 -> -33§ 31-> - 3 8 -17-* 15 -* 146-> 229-> -57 -44§ -13§ -17 >60 6->60 21->60 >60 >60 — — — — 2.5 6.8* 36.8* 37.4* 0-10 0-40 0-320 0-320 — — — — ± ± ± ± 1.6 5.1* 3.8* 4.9* 0-10 0-20 0-20 0-20 — — — 20 27 22 19 19 ± ± ± ± ± 1.9 6.4* 3.3* 2.0* 1.5* 17-26 18-59 16-31 16-25 16-24 Factor II (%) (NV: 70-130) Preoperative 1 hour postoperative 24 hours postoperative 48 hours postoperative 81 71 74 80 ± ± ± ± 14.2 13.3* 12.1* 14.4 56-119 46-113 53-109 55-113 -12.6 ± 2.5 - 7 . 4 ± 3.3 - 1 . 0 ± 3.6 7 ^ -32 19-* -34 28 - • - 3 0 Factor V (%) (NV: 70-130) Preoperative 1 hour postoperative 24 hours postoperative 48 hours postoperative 88 61 84 100 ± ± ± ± 15.7 14.8* 15.9* 17.3* 52-132 26-96 40-130 56-150 -30.3 ± 4.1 - 4 . 5 ± 4.2 15.0 ± 5.9 2 ^ -63 29-> - 3 8 62 -* - 3 2 94 79 55 73 ± ± ± ± 31.2 24.4* 22.7* 22.7* 31-200 28-164 21-142 31-164 -15.8 ± 3.8 -40.1 ± 5.6 -19.4 ± 7.1 14 -* - 4 6 5 ^ -85 37 - • - 7 6 Factor VII (%) (NV: 70-130) Preoperative 1 hour postoperative 24 hours postoperative 48 hours postoperative 34.7 10.6 -2.5 -3.9 ± ± ± ± — — — — 7.2 3.2 2.7 2.8 115-> 36-» 19-» 18 -> -1§ -15 -24 -26 ALTERATION OF COAGULATION DURING OHS Vol. 76 • No. 2 Table Mean ± Standard Deviation 159 2.—(continued) Range of Values Average Percentage Change ± Confidence Intervalt Factor VIII (%) (NV: 70-130) Preoperative 1 hour postoperative 24 hours postoperative 48 hours postoperative 89 120 159 173 ± ± ± ± 42.0 58.7* 72.6* 75.1* 37-280 33-340 55-400 42-416 44.7 ± 22.7 96.5 ± 30.0 111.2 ± 27.9 Factor IX (%) (NV: 70-130) Preoperative 1 hour postoperative 24 hours postoperative 48 hours postoperative 77 87 93 111 ± ± ± ± 25.3 26.8* 31.0* 45.2* 31-151 34-193 35-192 24-313 19.7 ± 10.4 30.7 ± 14.9 56.9 ± 21.9 83 71 • 71 73 ± ± ± ± 18.7 15.8* 16.6* 16.9* 43-126 39-109 35-122 35-109 Factor X (%) (NV: 70-130) Preoperative 1 hour postoperative 24 hours postoperative 48 hours postoperative -' — — — -14.1 ± 2.9 - 1 2 . 9 ± 3.7 -11.1 ± 4.9 Tolerance Limits for Percentage Changet — 390— -59§ 266 — -64§ 334 — 111 — 103 — - 6 3 149 — - 8 8 231 — -118 — 9— -37 22 — -39§ 28 — - 5 0 NV, normal value. * P < 0.01 versus preoperative mean by paired I test. t See Results section in text. § When distributions are non-Gaussian, a distribution independent tolerance interval (y = 0.99, P = 0.90) is presented. With N = 75, the confidence interval estimates in column 3 will have a confidence level very little different from 0.99, even when departures from normality are significant. globin value that is from 15.6% to 44.4% lower than the preoperative hemoglobin value). nism by which peripheral blood platelet counts diminish is not always clearly apparent. Utilization, sequestration, premature destruction due to physical damage, and heparin effect are very tenable considerations. Plasma hemoglobin increases to a mean level of 74 mg/dl after surgery and rapidly diminishes during the next two days. Plasma hemoglobin rise is principally attributed to aspiration of blood from the pericardial sac and return of blood to the oxygenator. 16 Serum haptoglobin steadily falls to a mean low level of 25-50 mg/ dl hemoglobin-binding capacity, but rises in the first and second day postoperatively and is roughly inversely related to the level of plasma hemoglobin. Discussion Blood-formed Elements The initial and immediate intraoperative drop in hemoglobin, hematocrit, erythrocyte count, as well as certain other blood-formed elements, and clinical chemistry measurements reflect the effects of hemodilution with crystalloid solutions. The mean hemoglobin and hematocrit values at 30 min following onset of CPB were 9.2 g/dl and 28%, respectively, and when using the previously described systems, represent highly satisfactory levels for perfusion. Postoperatively, the mild and even moderately anemic states do not justify homologous blood transfusion unless other definite clinical indications exist. At 48 hours, the mean hemoglobin and hematocrit values of the group not receiving transfusions were 10.2 g/dl and 30%; respectively. Erythrocyte indices remained essentially unchanged. The mean total leukocyte count increased during surgery and continued to rise, with the highest mean count at 24 hours (13,500//xl). Platelet count fell from a normal range to a mean level of 119,000/^1 during surgery and 144,000/jtxl one hour after closure. Considerable variation occurred in individual cases, and postoperative levels of 61,000 and 73,000/ju.l did not necessarily predispose hemorrhage requiring blood transfusion. There is typically a slight drop in platelet count between 24 and 48 hours. The exact mecha- Coagulation Fibrin split products (TRCHII and staphylococcal clumping test) rise immediately after median sternotomy, virtually a routine procedure in open heart surgery, and gradually increase during the next two days. The PTT and prothrombin times exhibit marked prolongation during CPB owing to heparin effect; however, these tests are unsuitable for heparin monitoring during CPB. Following heparin neutralization, the mean activated PTT returns to normal values, and the mean prothrombin time is slightly longer than mean preoperative level, which may be attributed largely to factor V reduction. Alteration of mean factors II, V, VII, VIII, IX, and X assays may be compared with changes in total serum protein for estimating changes secondary to hemodilution and blood loss as opposed to utilization. Total serum protein drops from the base- 160 A.J.C.P. • August 1981 MILAM ET AL. table 3. Blood Chemistry Data Mean ± Standard Deviation Range of Values Average Percentage Change ± Confidence Intervalt Total Serum Protein (g/dl) (NV: 6.0-7.8) Preoperative 30 min CPB 1 hour postoperative 24 hours postoperative 48 hours postoperative 5.8 3.9 5.1 5.5 5.4 ± 0.58 ± 0.39* ± 0.58* ± 0.36* ± 0.38* 4.6-7.3 2.9-4.8 3.8-6.9 4.7-6.8 4.7-6.5 Arterial blood gases (pH) Preoperative 30 min CPB 1 hour postoperative 24 hours postoperative 48 hours postoperative 7.44 7.37 7.36 7.42 7.46 ± 0.07 ± 0.05* ± 0.06* ± 0.04 ± 0.04 7.29-7.69 7.24-7.49 7.19-7.50 7.34-7.52 7.37-7.55 -1.0 -1.0 -0.2 0.2 P 0l (mm Hg) Preoperative 30 min CPB 1 hour postoperative 24 hours postoperative 48 hours postoperative 178 169 198 91 69 62-308 62-309 62-308 35-183 28-165 3.4 18.1 -44.5 -57.9 PCOa (mm Hg) Preoperative 30 min CPB 1 hour postoperative 24 hours postoperative 48 hours postoperative 36 38 37 36 34 15-52 28-52 27-62 26-72 22-43 11.3 5.7 4.1 -1.7 ± ± ± ± ± 54.4 61.8 64.8 35.0* 26.0* ± 6.7 ± 4.9* ± 6.7 ± 6.5 ± 4.7 -32.0 -11.4 -4.5 -6.3 ± ± ± ± Tolerance Limits for Percentage Changet 2.2 3.0 2.6 2.8 -14.4 12.416.015.8- -49.5 -35.3 -25.1 -28.5 0.3 0.3 0.3 0.3 1.411.271.512.94- -3.38 -3.27 -2.71§ -2.46 2481251716- -72§ -89 -106 -81§ ±7.7 ± 7.2 ± 8.7 ± 8.2 89858363- -25§ -36§ -38§ -67 ± ± ± ± 16.2 13.4 7.8 5.9 Osmolality (serum) (mOsm/1) (NV: 280-295) Preoperative 30 min CPB 1 hour postoperative 24 hours postoperative 48 hours postoperative 299 315 306 282 275 ± ± ± ± ± 9.8 11.7* 10.7* 10.4* 7.7* 263-320 287-374 269-330 241-316 249-291 5.6 2.7 -5.4 -7.8 ± ± ± ± 1.2 1.0 1.2 1.0 141070- -4§ -5 -11§ -16 Viscosity (serum) (times water) (NV: 1.4-1.8) Preoperative 30 min CPB 1 hour postoperative 24 hours postoperative 48 hours postoperative 1.5 1.4 1.4 1.4 1.4 ± 0.23 ± 0.30* ± 0.24* ± 0.21 ± 0.18 1.2-2.4 1.1-3.3 1.2-2.4 1.1-2.4 1.3-2.3 -6.7 -3.4 -2.1 -1.1 ± ± ± ± 2.5 1.8 3.1 3.0 8.3-> 8.3-• 21.4 -* 25.0 -» -23.5§ -13.3§ -23.5§ -18.8§ Sodium (serum) (mEq/1) Preoperative 30 min CPB 1 hour postoperative 24 hours postoperative 48 hours postoperative 139 132 137 138 135 ± 3.2 ± 4.0* ± 3.6* ± 3.3 ± 3.7* 131-147 123-140 128-144 130-144 126-142 -5.2 -1.2 -0.6 -3.0 ± ± ± ± 0.9 0.9 0.9 0.9 2^> 6^ 7^ 4-> Potassium (serum) (mEq/1) Preoperative 30 min CPB 1 hour postoperative 24 hours postoperative 48 hours postoperative 3.7 4.6 4.2 4.1 4.0 ± ± ± ± ± 0.41 0.76* 0.51* 0.31* 0.33* 2.2-4.5 3.0-6.5 3.0-5.7 3.5-5.3 3.2-4.8 25.0 14.1 11.7 8.5 ± 7.4 ± 6.4 ±4.7 ± 4.8 84.4 -» 65.0 -> 40.7^ 47.0 — -34.4 -36.8 -20.0§ -30.0 Calcium (serum) (mg/dl) Preoperative 30 min CPB 1 hour postoperative 24 hours postoperative 48 hours postoperative 8.5 7.5 8.6 8.4 8.2 ± ± ± ± ± 0.43 0.78* 0.63 0.79 0.42* 7.7-10.2 6.2-10.8 6.9-10.7 7.3-14.2 7.0-9.0 •11.8 1.0 -1.3 -3.7 ± ± ± ± 10.9-> 20.4 — 23.3 -» 12.0 -^ -34.5 -18.5 -25.8 -19.4 2.8 2.4 3.1 2.0 -12 -8 -8 -11 Vol. 76 • No. 2 ALTERATION OF COAGULATION DURING OHS 161 Table 3.—(continued) Mean ± Standard Deviation Range of Values Average Percentage Change ± Confidence Intervalt Phosphorus (serum) (mg/dl) Preoperative 30 min CPB 1 hours postoperative 24 hours postoperative 48 hours postoperative 3.0 2.5 1.8 2.9 2.2 ± ± ± ± ± 0.50 0.57* 0.67* 0.52 0.55* 1.7-4.1 0.6-3.8 0.4-3.5 1.8-4.5 1.2-5.1 -17.4 -41.5 -2.7 -26.0 Erythrocyte 2,3-diphosphoglycerate (nmol/ml RBC) Preoperative 30 min CPB 1 hour postoperative 24 hours postoperative 48 hours postoperative 5.1 4.9 4.9 4.7 5.3 ± ± ± ± ± 0.89 0.84 0.82 0.82* 0.96 3.0-7.8 3.1-7.7 2.9-8.1 2.9-7.1 3.1-8.8 -2.2 -1.9 -6.7 5.8 NV, normal value. * P < 0.01 versus preoperative mean by paired I test. t See Results section in text. § When distributions are non-Gaussian, a distribution independent tolerance interval line value of 5.8 g/dl to 3.9 g/dl at 30 min after initiation of CPB and to 5.1 g/dl one hour after surgery. The aforementioned values represents reductions of 33% at 30 min pump time and 12% one hour after surgery. At one hour after surgery, the greatest reduction in coagulation factors was observed with factor V (31% decrease). At one hour, factor II was reduced by 12%, factor VII by 16%, factor X by 14%, and fibrinogen by 16%, as related to initial values, and the changes are comparable to total serum protein reduction. The euglobulin lysis time shortens and becomes transiently abnormal during the procedure, but at one hour following CPB and thereafter, the euglobulin lysis time is normal. The mean reptilase time increases during CPB and returns to baseline values at 24 hours. Factor VIII is significantly increased postoperatively, probably as a result of stress. The serum osmolality increased and serum viscosity decreased during CPB and in the early postoperative period as a result of hemodilution with crystalloid solutions. The serum calcium drop during surgery is also attributed to dilution effect. Postoperative fall in serum phosphorus is regarded as secondary to carbohydrate (glucose) load of the hemodilution crystalloid fluid. The erythrocyte 2,3DPG levels varied slightly during the study period. Electrolytes, arterial blood gases, and pH determinations reflect physiologic balance with good oxygenation perioperatively. The data presented demonstrate that there is mild hemolysis and alteration of FDP titer, platelet count, and euglobulin lysis time during CPB. Heparin is routinely administered in significant doses prior to CPB — ± ± ± ± — ± ± ± ± Tolerance Limits for Percentage Changet — 4.6 5.4 6.7 6.0 19.4— 1.8— 63.0— 21.6- 5.3 5.1 6.2 7.0 38.5— 56.4— 35.9— 61.4— — -54.1 -84.7 -34.3§ -73.5 -46.8§ -38.58 -39.68 -49.8 (-y = 0.99, P = 0.90) is presented. With N = 75, the confidence interval estimates in column 3 will have a confidence level very little different from 0.99, even when departures from normality are significant. to aid in preventing clotting intravascularly and in the extracorporeal circuit. Nonetheless, there is an expected rise in FDP during open heart surgery, probably due largely to formation of microthrombi, which are not known to be clinically significant. The immediate rise in FDP after median sternotomy is believed by us to be secondary to bone marrow embolization. In other studies24 we have demonstrated evidence of bone marrow embolization during the rapid sawing of the sternum. The procedure is the most conventional thoracotomy approach for OHS and is generally performed before heparinization. Bone marrow particles possessing thromboplastin activity may predispose microthrombi formation. Transient abnormal euglobulin lysis time indicated that plasmin production may reflect a compensatory mechanism or direct activation of the fibrinolytic system. Acknowledgments. Delia Barrientes and Dona Jones provided assistance in the preparation of this manuscript. Kathy McMillan and Susan Stansberry provided technical assistance. References 1. Allington MJ: Fibrinogen and fibrin degradation products and the clumping of staphylococci by serum. Br J Haematol 13: 550-567, 1967 2. Bachmann F, Duckert F, Geiger M, et al: Differentiation of the factor VII complex. Studies on the Stuart-Prower factor. Thromb Diath Haemorrh 1:169-194, 1957 3. Beau AF: A method for hemoglobin in serum and urine. Am J Clin Pathol 38:111-112, 1962 4. Brecher G, Schneiderman M, Cronkite EP: The reproducibility and constancy of the platelet count. Am J Clin Pathol 23: 15-26, 1953 5. Buckell M: The effect of citrate on euglobulin methods of estimating fibrinolytic activity. 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