Lako S, Daka A, Nurka T, Dedej T, Ostreni V Hematological changes in patients undergoing Coronary Artery Bypass Surgery Lako S, Daka A, Nurka T, Dedej T, Ostreni V

Introduction Major surgery in general and in particular cardiac surgery is a challenge to the hematopoietic system. Trauma of surgery, the use of Cardiopulmonary Bypass (CPB), bleeding (during and after surgery), frequent blood analyses, hemodilution, significant shift of intravascular volume, mechanical trauma of blood cells, therapeutic hypothermia, co-morbidities, the use of anticoagulant and antiplatelet drugs (before, during and after surgery), transfusion of blood products, all cause significant changes in the three major cellular components of the hematopoietic system. Removal of proinflammatory stimuli after surgery, wound closure and the regenerative ability of the bone marrow will ensure a gradual recovery to preoperative values of ​​hematological parameters. Experience and literature have shown that the values ​​of peripheral blood parameters (number, size, function) undergo significant changes during the early phase of the surgery, gradually recovery during the postoperative period and reach the preoperative (baseline) values ​​2-6 months after surgery.

Objectives The purpose of this study was to assess changes in hematological parameters of peripheral blood after cardiac surgery (the count of red blood cell, leukocytes, platelets and the values of haemoglobin, hematocrit), analyzing changes in trend over time until 90 days after cardiac surgery (D+1, D+2, D+3, D+4, D+6, D+14, D+21, D+28, D+90) and comparison with values ​​before surgery (D-1).

Patients and Methods This study involved 164 patients (138 men and 26 women) who underwent CABG surgery at the Department of Cardiac Surgery at the American Hospital, Tirana, Albania, over a period of 2 years spanning January 2011 to December 2012. Patients with primary hematologic disease were not included in this study. Also not included were patients with DIC and HIT II after surgery. Patients were reviewed for their preoperative demographic, clinical (coronary artery disease severity and co-morbidities) and laboratory variables and then followed to record their postoperative data and outcomes. One surgical team operated on all of the patients in this study.

Patients and Methods Day 0 was the day of surgery. Hematological parameters were assessed immediately before surgery (D-1) and after surgery: at the first day (D+1; the second day (D+2), the patient was transferred from the ICU to the ward; the third day (D+3); the fourth day (D+4); the sixth day (D+6), the patient left the hospital; at the end of the second week (D+14), the third week (D+21), the fourth week (D+28) and the twelfth week (D+90). In the American Hospital, to achieve the complete blood count analysis, 4 ml of venous blood was taken by venopuncture technique, by Vacutest REF 13030 K3 EDTA 7.2 mg, and evaluation done on the equipment Sysmex XS-1000i Automated Hematology Analyzer. All the patients included in the study were managed according to the hospital's current policies regarding preoperative preparation, intraoperative surgical and anesthetic management and postoperative care. Packed red blood cells (PRBC) are transfused according to the needs of each patient. At our clinic, blood transfusion was used to maintain Hct > 25% and hemoglobin (Hb) > 8.0 g/dL during cardiac surgery. PRBC were administered to 79.87% of patients. In total, 334 units were transfused. The average number of PRBC units per patient was 2.0 .  

Statistical Methods This prospective cohort study involved consecutive patients who underwent elective or emergency CABG surgery. The data are summarized as the mean ± SD values. The differences between the data were assessed by the Student’s t-test and p values ​​≤ 0.05 were considered statistically significant. Normal values ​​of peripheral blood hematological parameters and their changes towards normal values ​​were evaluated according to WHO criteria. SPSS 20.0 software (IBM, 2011) was used for statistical analysis. Percentage changes of postoperative values, ​​versus preoperative values (D-1) were calculated as follows; [(Preoperative Value – Postoperative Value)/ Preoperative Value ]×100

Patients and Methods The average age of the patients was 61.8 ± 9.0 years (range, 34-82 years). Figure 1 illustrates the patient distribution according to age.

The preoperative demographics and hematological data

1. Results – Red Blood Cells (RBC) Time trends of the average values ​​of RBC (mm3), Standard Deviation (SD), percentage changes of these values ​​versus D-1 (preoperative value taken as the basic value). RBC (mm3) SD RBC (Δ%) D-1 4590609.7 596768.0 D+1 3328628.0 487111.2 -27.5 D+2 3086375.0 387076.5 -32.7 D+3 3050191.0 466538.6 -33.6 D+4 3184870.1 473869.1 -30.6 D+6 3377151.9 437229.4 -26.4 D+14 3575625.0 527160.6 -22.1 D+21 3653428.5 490113.7 -20.4 D+28 4203658.5 589519.9 -8.4 D+90 4790303.0 473117.9 +4.3

1. Results – Red Blood Cells (RBC) Using the paired-sampled t test differences between mean values ​​of variables and those of the first day were analyzed. Values ​​in red indicate a statistically significant difference. Comparison with preoperative values ​​(D-1) ± Standard Deviation (SD) for pairs: D-1, D+1; D-1, D+2; D-1, D+3; D-1, D+4; D-1, D+6; D-1, D+14; D-1, D+21; D-1, D+28; D-1, D+90. RBC (mm3) ± SD P value D-1;D+1 4590609.7 ± 596768.0 3328628.0 ± 487111.2 <0.001 D-1;D+2 458702.5 ± 579690.4 3086375.0 ± 387076.5 D-1;D+3 4581656.0 ± 571287.1 3050191.0 ± 466538.6 D-1;D+4 4572467.5 ± 566213.5 3184870.1 ± 473869.1 D-1;D+6 4591139.2 ± 581806.9 3377151.9 ± 437229.3 D-1;D+14 4510750.0 ± 539901.0 3575625.0 ± 527160.6 D-1;D+21 4440285.7 ± 622875.1 3653428.5 ± 490113.6 D-1;D+28 4521463.4 ± 664291.2 4203658.5 ± 589519.9 0.008 D-1;D+90 4616666.6 ± 457955.1 4790303.0 ± 473117.8 0.045

1. Results – Hemoglobin (Hb) Time trends of the average values ​​of Hemoglobin (gr/dl), Standard Deviation (SD), percentage changes of these values ​​versus D- 1 (preoperative value taken as the basic value). Hemoglobin (gr/dl) SD Hemoglobin (Δ%) D-1 13.4 1.6 D+1 9.8 1.3 -27.2 D+2 9.1 1.0 -32.2 D+3 9.0 1.2 -33.1 D+4 9.3 -30.3 D+6 9.9 -26.2 D+14 10.4 1.4 -22.2 D+21 10.7 -20.4 D+28 11.6 -13.4 D+90 13.1 1.5 -2.2

1. Results – Hemoglobin (Hb) Using the paired-sampled t test differences between mean values ​​of variables and those of the first day were analyzed. Values ​​in red indicate a statistically significant difference. Comparison with preoperative values ​​(D-1) ± Standard Deviation (SD) for pairs: D-1, D+1; D-1, D+2; D-1, D+3; D-1, D+4; D-1, D+6; D-1, D+14; D-1, D+21; D-1, D+28; D-1, D+90; Hemoglobina (gr/dl)±SD P value D-1;D+1 13.4 ± 1.6 9.8 ± 1.3 <0.001 D-1;D+2 9.1 ± 1.0 D-1;D+3 9.0 ± 1.2 D-1;D+4 9.3 ± 1.2 D-1;D+6 13.5 ± 1.6 9.9 ± 1.0 D-1;D+14 13.3 ± 1.6 10.4 ± 1.4 D-1;D+21 13.4 ± 1.7 10.7 ± 1.4 D-1;D+28 13.0 ± 1.9 11.6 ± 1.6 D-1;D+90 13.1 ± 1.5 0.354

1. Results – Hematocrit (Hct) Time trends of the average values ​​of Hematocrit (%), Standard Deviation (SD), percentage changes of these values ​​versus D- 1 (preoperative value taken as the basic value). Hematocrit (%) SD Hematocrit (Δ%) D-1 40.0 4.7 D+1 28.9 3.7 -27.7 D+2 27.0 3.1 -32.4 D+3 26.9 3.5 -32.6 D+4 28.0 -30.0 D+6 29.7 3.2 -25.7 D+14 32.7 -18.2 D+21 33.6 3.6 -15.9 D+28 36.5 4.6 -8.7 D+90 40.8 4.2 +2.1

1. Results – Hematocrit (Hct) Using the paired-sampled t test differences between mean values ​​of variables and those of the first day were analyzed. Values ​​in red indicate a statistically significant difference. Comparison with preoperative values ​​(D-1) ± Standard Deviation (SD) for pairs: D-1, D+1; D-1, D+2; D-1, D+3; D-1, D+4; D-1, D+6; D-1, D+14; D-1, D+21; D-1, D+28; D-1, D+90; Hematocrit (%)±SD P value D-1;D+1 40.0 ± 4.7 28.9 ± 3.7 <0.001 D-1;D+2 27.0 ± 3.1 D-1;D+3 40.0 ± 4.6 26.9 ± 3.5 D-1;D+4 39.9 ± 4.5 28.0 ± 3.7 D-1;D+6 29.7 ± 3.2 D-1;D+14 39.5 ± 4.3 32.7 ± 3.7 D-1;D+21 38.4 ± 4.8 33.6 ± 3.6 D-1;D+28 39.1 ± 5.5 36.5 ± 4.6 0.003 D-1;D+90 39.8 ± 4.3 40.8 ± 4.2 0.169

Results – RBC, Hemglobin, Hematocrit Time trends of the average values ​​of RBC (mm3), Hemoglobin (gr/dl), Hematocrit (%), percentage changes of these values ​​versus D-1 (preoperative value taken as the basic value). RBC (mm3) Hemoglobin (gr/dl) Hematocrit (%) RBC (Δ%) Hemoglobin (Δ%) Hematocrit (Δ%) D-1 4590609.7 13.4 40.0 D+1 3328628.0 9.8 28.9 -27.5 -27.2 -27.7 D+2 3086375.0 9.1 27.0 -32.7 -32.2 -32.4 D+3 3050191.0 9.0 26.9 -33.6 -33.1 -32.6 D+4 3184870.1 9.3 28.0 -30.6 -30.3 -30.0 D+6 3377151.9 9.9 29.7 -26.4 -26.2 -25.7 D+14 3575625.0 10.4 32.7 -22.1 -22.2 -18.2 D+21 3653428.5 10.7 33.6 -20.4 -15.9 D+28 4203658.5 11.6 36.5 -8.4 -13.4 -8.7 D+90 4790303.0 13.1 40.8 +4.3 -2.2 +2.1

Results – RBC, Hemglobin, Hematocrit Time trends of the average values ​​of RBC (mm3), Hemoglobin (gr/dl), Hematocrit (%), percentage changes of these values ​​versus D-1 (preoperative value taken as the basic value). Average values ​​of erythrocytes, hemoglobin and hematocrit declined (normocromic, normocytic anemia), to reach their lower values ​​on day 3 after surgery (-33.6 %, -33.1 %, - 32.6 % respectively from the preoperative value, p<0.001), and then gradually increased to reach normal values ​​after one month and the preoperative values ​​after three months.

2. Results – White Blood Cells (WBC) Time trends of the average values ​​of WBC (mm3), Standard Deviation (SD), percentage changes of these values ​​versus D-1 (preoperative value taken as the basic value). WBC (mm3) SD WBC (Δ%) D-1 8305.7 2207.5 D+1 13912.3 4086.6 +67.5 D+2 14509.5 4205.9 +74.7 D+3 12317.7 3838.9 +48.3 D+4 11227.7 3720.1 +35.1 D+6 11893.5 3439.5 +43.2 D+14 11155.6 3278.3 +34.3 D+21 9744.4 3105.4 +17.3 D+28 8506.3 1899.0 +2.4 D+90 7796.3 2143.1 -6.1

2. Results – White Blood Cells (WBC) Using the paired-sampled t test differences between mean values ​​of variables and those of the first day were analyzed. Values ​​in red indicate a statistically significant difference. Comparison with preoperative values ​​(D-1) ± Standard Deviation (SD) for pairs: D-1, D+1; D-1, D+2; D-1, D+3; D-1, D+4; D-1, D+6; D-1, D+14; D-1, D+21; D-1, D+28; D-1, D+90. WBC (mm3)± SD P value D-1;D+1 8305.7 ± 2207.5 13912.3 ± 4086.6 <0.001 D-1;D+2 8283.9 ± 2185.9 14509.5 ± 4205.9 D-1;D+3 8270.1 ± 2187.4 12317.7 ± 3838.9 D-1;D+4 8238.1 ± 2188.0 11227.7 ± 3720.1 D-1;D+6 8291.9 ± 2197.4 11893.5 ± 3439.5 D-1;D+14 8243.6 ± 2342.4 11155.6 ± 3278.3 D-1;D+21 8584.4 ± 2134.5 9744.4 ± 3105.4 D-1;D+28 7922.4 ± 1779.7 8506.3 ± 1899.0 0.093 D-1;D+90 7593.6 ± 1955.3 7796.3 ± 2143.1 0.551

2. Results – White Blood Cells, Neutrophils and Lymphocytes The average values ​​neutrophils increased rapidly (neutrophil leukocytosis) to achieve the highest value on day 2 after surgery, while the average value of lymphocytes decreased quickly to achieve lower value ​​on day 1 after surgery (+127.1 %, -52.4 % respectively from the preoperative value, p<0.001). Once these values were reached, the average values of neutrophiles was reduced gradually and the average value of lymphocytes increased gradually to reach the normal levels on day 21 and the preoperative values on day 28.

2. Results – White Blood Cells, Neutrophils and Lymphocytes The average values ​​of leukocytes and neutrophils increased rapidly (neutrophil leukocytosis) to achieve the highest value on day 2 after surgery, while the average value of lymphocytes decreased quickly to achieve lower value ​​on day 1 after surgery (+74.7 %, +127.1 %, -52.4 % respectively from the preoperative value, p<0.001). Once these values were reached, the average values of leukocytes and neutrophiles were reduced gradually and the average value of lymphocytes increased gradually to reach the normal levels on day 21 and the preoperative values on day 28.

3. Results – Platelets Time trends of the average values ​​of Platelets (mm3), Standard Deviation (SD), percentage changes of these values ​​versus D-1 (preoperative value taken as the basic value). Platelets (mm3) SD Platelets (Δ%) D-1 230920.7 65064.7 D+1 180792.6 67375.4 -21.7 D+2 169956.2 66796.4 -26.4 D+3 171762.8 66144.8 -25.6 D+4 208928.5 76582.7 -9.5 D+6 283528.6 94593.9 +22.8 D+14 463762.5 143604.0 +100.8 D+21 413181.8 159701.1 +78.9 D+28 307200.0 85383.3 +33.0 D+90 275514.3 113725.7 +19.3

3. Results – Platelets Using the paired-sampled t test differences between mean values ​​of variables and those of the first day were analyzed. Values ​​in red indicate a statistically significant difference. Comparison with preoperative values ​​(D-1) ± Standard Deviation (SD) for pairs: D-1, D+1; D-1, D+2; D-1, D+3; D-1, D+4; D- 1, D+6; D-1, D+14; D-1, D+21; D-1, D+28; D-1, D+90. Platelets (mm3)± SD P value D-1;D+1 230920.7 ± 65064.7 180792.6 ± 67375.4 <0.001 D-1;D+2 231500.0 ± 65251.9 169956.2 ± 66796.4 D-1;D+3 230000.0 ± 64825.3 171762.8 ± 66144.8 D-1;D+4 229298.7 ± 64603.9 208928.5 ± 76582.7 D-1;D+6 230407.6 ± 65032.0 283528.6 ± 94593.9 D-1;D+14 225775.0 ± 64342.0 463762.5 ± 143604.0 D-1;D+21 221393.9 ± 64390.3 413181.8 ± 159701.1 D-1;D+28 220325.0 ± 50468.2 307200.0 ± 85383.3 D-1;D+90 241400.0 ± 72491.4 275514.3 ± 113725.7 0.098

3. Results – Platelets The average platelet count decreased gradually to reach the lowest value on day 2 after surgery (-26.4 % from the preoperative value, p<0.001), after which gradually increased up to +100.8 % of the preoperative value on day 14 (p<0.001), and then gradually decreased to reach normal values ​​on day 21 and preoperative values ​​after three months. Increased Tpo levels after surgery, resulting from enhanced Tpo production under the influence of IL-6 or other inflammatory cytokines, are involved in an enhanced thrombocytopoiesis. Postoperative thrombocytosis, is diagnosed around the 6th postoperative day, reaches its peak 2 weeks postoperatively. Postoperative thrombocytosis is a potentially dangerous complication, with an increased risk for vein graft occlusion*. *Christenson, JanT, Fran&ccedil ois Simonet, and Martin Schmuziger. "Postoperative Thrombocytosis after Coronary Artery Bypass Grafting: A Potential Danger even after Hospital Discharge." Medical Principles and Practice 8.2 (1999): 145-155.

4. Results – RBC, WBC, Platelets Time trends of the average values ​​of RBC (mm3), WBC (mm3), Platelets (mm3), percentage changes of these values ​​versus D-1 (preoperative value taken as the basic value). RBC (mm3) WBC (mm3) Platelets (mm3) RBC (Δ%) WBC (Δ%) Platelets (Δ%) D-1 4590609.7 8305.7 230920.7 D+1 3328628.0 13912.3 180792.6 -27.5 +67.5 -21.7 D+2 3086375.0 14509.5 169956.2 -32.7 +74.7 -26.4 D+3 3050191.0 12317.7 171762.8 -33.6 +48.3 -25.6 D+4 3184870.1 11227.7 208928.5 -30.6 +35.1 -9.5 D+6 3377151.9 11893.5 283528.6 +43.2 +22.8 D+14 3575625.0 11155.6 463762.5 -22.1 +34.3 +100.8 D+21 3653428.5 9744.4 413181.8 -20.4 +17.3 +78.9 D+28 4203658.5 8506.3 307200.0 -8.4 +2.4 +33.0 D+90 4790303.0 7796.3 275514.3 +4.3 -6.1 +19.3

4. Results – RBC, WBC, Platelets All the three peripheral blood cells parameters undergo changes after CABG. Erythrocytes get to their lower average value in D+3 (-33.6 % from the preoperative value); in D+2 leukocytes get to their higher average value (+74.7 % from the preoperative value), and the platelets to their lower average value (-26.4 % from the preoperative value). Leukocytes regain their normal level in D+21, erythrocytes and platelets regain their normal level in D+28. All three elements recover totally in their preoperative levels within three months (D+90).

Conclusions Systematic assessment of peripheral blood hematologic parameters after cardiac surgery is important for the assessment of their changes, detection and correction of the causes. Analysis of complete blood count (CBC) is easily obtained and realized at low cost. We found that the average values ​​of the three peripheral blood cells parameters, undergo mild to moderate changes after CABG and return gradually to normal and preoperative values ​​after 1-3 months from surgery, when the compensatory function of the bone marrow is preserved and there are no post surgery complications associated with continuous consumption or loss of peripheral blood cellular elements. Our study shows that in open-heart surgery a stable model of response of the erythrocytes, leukocytes and the platelets happens. Analysis of change over time in the average values of the hematological parameters can be predicted according to the median curve constructed by a cardio surgeon, cardiologist, hematologist, anesthesiologist or transfusiologist.

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