EFFECT OF DIASPIRIN CROSSLINKED HEMOGLOBIN (DCLHb HemAssist™) DURING HIGH BLOOD LOSS SURGERY ON SELECTED INDICES OF ORGAN FUNCTION ^*

Figures & data

Table 1. Clinical and Transfusion Data (Mean±SD)

	Control (n=12)	DCLHb™ (n=12)
Age (yr)	65.8±8.9	62.4±8.3
Weight (kg)	86.6±18.1	80.1±20.8
Female (%)	25.0	33.3
History of Cardiovascular Disease (%)^a	41.7	0.0
History of Hypertension (%)	33.0	50.0
History of Chronic Pulmonary Disease (%)	33.3	25.0
Surgery Type
Urologic/Gynecology (%)	83.3	83.3
Orthopedic (%)	8.3	16.7
Other (%)	8.3	0.0
Estimated Blood Loss (ml/kg)	27±13	31±15
DCLHb™ Dose (mg/kg)^*	NA	999±276
Duration of Transfusion (range, min)	5–100	4–50
Blood Products Transfused^b
Autologous RBC (ml/kg)	4.0±4.4	5.7±4.4
Homologous RBC (ml/kg)	14.9±10.6	11.9±10.9
Fresh Frozen Plasma (ml/kg)	1.8±3.1	0.6±2.1
Crystalloid (ml/kg)	170.8±53.0	182.7±64.2
Colloid (ml/kg)	13.4±6.5	11.8±7.3

POD=Postoperative Day; RBC=Red Blood Cells.

^aCoronary artery disease, dysrhythmias.

^bThrough earlier of POD #7 or hospital discharge.

^*Average of 3 infusions.

Table 2. Units PRBC Infused

	DCLHb		Control		P-Value
	Period	Cumulative	Period	Cumulative	Period^a	Cumulative^b
POD 0	1.9±1.2	–	3.4±2.4	–	.06	–
POD 1	0.5±0.5	2.4±1.1	0.3±0.8	3.8±2.8	.22	.26
POD 2–7	1.3±1.2	3.7±1.3	0.7±0.9	4.4±2.7	.23	.68

POD=Postoperative Day.

^aComparing median units within time period.

^bComparing median cumulative units through time period.

Table 3. Laboratory Tests Indicative of Renal and Hepatobiliary Function (Mean, [SD])^#

Test (Reference Ranges)	PRE		POD1^a		POD2		POD3		POD4		POD7		POD14		POD28
	Mean	[SD]	Mean	[SD]	Mean	[SD]	Mean	[SD]	Mean	[SD]	Mean	[SD]	Mean	[SD]	Mean	[SD]
Total Bilirubin, mg/dL (0–1.5)
Control	0.8	[0.24]	1.0†	[0.54]	1.0	[0.35]	0.8	[0.21]	0.8	[0.21]	0.7	[0.23]	0.7	[0.14]	0.7	[0.10]
DCLHb™	0.9	[0.38	2.2‡	[0.57]	1.6	[0.88]	1.0	[0.40]	1.2	[0.67]	1.0	[0.45]	0.7	[0.18]	0.7	[0.16]
Conjugated Bilirubin, mg/Dl (0–0.4)
Control	0.3	[0.26]	0.3†	[0.30]	0.3^#	[0.22]	0.3^#	[0.14]	0.3	[0.19]	0.3	[0.22]	0.2	[0.22]	0.1	[0.6]
DCLHb™	0.2	[0.16]	1.0‡	[0.28]	0.7	[0.48]	0.5	[0.24]	0.4	[0.33]	0.4	[0.27]	0.2	[0.12]	0.1	[0.14]
Unconjugated Bilirubin, mg/dL (0–1.1)
Control	0.5	[0.31]	0.7†	[0.32]	0.7	[0.37]	0.5	[0.21]	0.5	[0.22]	0.5	[0.25]	0.5	[0.23]	0.6	[0.09]
DCLHb™	0.7	[0.42]	1.2‡	[0.28]	0.8	[0.78]	0.5	[0.34]	0.8	[0.48]	0.6	[0.29]	0.5	[0.18]	0.6	[0.22]
GOT/AST, U/L (7–40)
Control	20.4	[5.48]	24.1^#	[10.06	21.8^#	[6.38]	19.3^#	[6.02]	18.5	[8.65]	31.8	[27.97]	22.7	[9.83]	19.2	[6.62]
DCLHb™	19.4	[5.79]	56.0§	[32.79]	52.7	[28.81]	34.1	[17.36]	28.4	[17.95]	28.6	[10.95]	26.6	[16.09]	24.1	[11.33]
GGT, U/L (M: 0–50/F: 0–35)
Control	29.7	[31.08]	13.0	[11.91]	15.2	[15.12]	15.8	[13.50]	22.5	[18.75]	42.3	[35.66]	62.4	[65.02]	38.8	[30.32]
DCLHb™	28.3	[33.82]	3.3^**	[4.93]	18.0	[12.46]	18.7	[11.44]	25.4	[16.16]	52.9	[39.60]	46.5	[26.50]	41.9	[26.20]
Amylase, U/L (0–96)
Control	43.5	[20.24]	147.6^#	[181.46]	111.3	[157.67]	86.6	[88.69]	82.6	[65.90]	71.8	[36.84]	85.3	[46.64]	74.7	[33.92]
DCLHb™	46.2	[19.75]	312.0††	[127.51]	270.2	[389.65]	117.8	[91.21]	102.6	[71.98]	81.6	[51.20]	95.8	[50.08]	101.7	[36.40]
Creatinine, mg/dL (0.7–1.4)
Control	0.9	[0.31]	1.1	[0.42]	1.0	[0.27]	1.0	[0.26]	0.9	[0.23]	1.0	[0.31]	1.1	[0.46]	1.1	[0.34]
DCLHb™	0.8	[0.14]	1.1	[0.23]	1.0	[0.20]	0.9	[0.14]	0.9	[0.14]	0.8	[0.18]	1.0	[0.30]	0.9	[0.20]

Below are the number of patients in whom valid test results were available: †n=11, ‡n=2, §n=7, ^**n=3, ††n=4.

^aNumber of valid test results reduced by Hgb interference

^#Statistically significant P<0.05.

Table 4. Hematological and Coagulation Data (Mean, [SD])

Test (Reference Ranges)	PRE		POD1		POD2		POD3		POD4		POD7		POD14		POD28
	Mean	[SD]	Mean	[SD]	Mean	[SD]	Mean	[SD]	Mean	[SD]	Mean	[SD]	Mean	[SD]	Mean	[SD]
HGB, gm/dL (M:13.5–17.5/F:12.0–16.0)
Control	10.7	[1.4]	8.7	[0.7]	8.7	[0.8]	8.7	[0.9]	8.8	[1.2]	9.5^#	[0.6]	10.1	[1.2]	11.2	[1.2]
DCLHb™	11.1	[1.8]	8.8	[0.6]	8.8	[0.9]	8.6	[1.1]	9.3	[1.5]	10.4	[1.1]	10.8^*	[1.1]	11.8	[1.1]
HCT, % (M:40.0–52.0/F:37.0–47.0)
Control	32	[3.8]	26	[1.8]	26	[2.4]	26	[2.8]	27	[3.5]	29	[2.2]	32	[3.9]	35	[3.6]
DCLHb™	33	[4.4]	25	[2.5]	26	[3.1]	26	[3.7]	28	[4.8]	32	[3.5]	34^*	[3.4]	37	[3.0]
SpO2, %
Control	98.7	[2.4	95.9	[3.5]	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA
DCLHb™	99.2	[1.2]	95.2^*	[3.6]	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA
WBC, K/μL (4.0–11.0)
Control	6.6	[2.3]	12.0	[2.7]	11.3	[1.6]	9.3	[2.0]	8.2	[2.4]	9.2	[3.0]	8.7	[2.9]	7.3	[2.8]
DCLHb™	6.3	[1.2]	12.7	[3.9]	14.8	[5.3]	12.5	[4.5]	10.3	[3.6]	10.6	[4.0]	9.2^*	[2.9]	7.9	[2.7]
Platelets, K/μL (150–400)
Control	235	[87.3]	162	[60.9]	166	[56.3]	170	[56.8]	203	[64.5]	311	[95.4]	500	[160]	319	[136]
DCLHb™	227	[58.9]	150	[49.2]	157	[50.2]	164	[54.3]	194	[53.4]	298	[86.2]	491^a	[162]	343	[84.2]
PT, sec (8.8–13.3)
Control	11.7	[0.9]	12.9^#	[1.1]	12.3^#	[1.2]	12.2	[1.3]	11.9	[1.5]	11.8	[1.3]	11.3	[0.8]	11.2	[0.8]
DCLHb™	11.6	[1.0]	11.6	[1.2]	11.1	[1.0]	11.3	[1.0]	11.5	[1.2]	14.1	[8.3]	12.1	[2.6]	12.5	[3.2]
APTT, sec. (21.5–32.5)
Control	27.6	[2.1]	27.2^b	[1.8]	25.5	[2.0]	24.9	[2.6]	25.0	[2.0]	25.0	[2.1]	27.3	[2.0]	26.8	[2.3]
DCLHb™	27.4	[3.6]	26.0	[3.5]	24.1	[3.3]	24.7	[2.5]	24.9	[2.6]	27.6	[10.6]	26.7	[3.1]	28.5	[3.6]

^an=10.

^bExcludes 1 anticoagulated patient.

^#Statistically Significant, P<0.05.

Figure 1. Creatinine clearance before and after transfusion displayed with boxplots and raw data points. Boxplot detail: top and bottom are 75th and 25th percentiles, horizontal line in middle is median, ‘+’ is mean.

Figure 2. Individual 28-day laboratory profile for each patient in the PRBC and DCLHb groups (A) AST, (B) LDH, (C) amylase. On POD1 data points for amylase are severely reduced because of hemoglobin interference with the assay method. The bold lines represent median values. ULN=upper limit of normal range. Median for DCLHb higher than for PRBC in hours: a) 1–3; b) 1–4; and c) 1–2 (P<0.05 Wilcoxon rank sum tests).

Figure 3. Mean systolic BP (±SD) during the first 72 hours after transfusion of DCLHb or PRBC. Median for DCLHb higher than for PRBC in hours: a) 1–30; b) 1–24; and c) 1–30. (P<0.05 Wilcoxon rank sum tests).

Table 5. Maximum Blood Pressure Increase (mmHg, mean±SD [Median]) within 1 Hour After First Transfusion

	PRBC (n=12)	DCLHb (n=12)	P Value^a
Systolic	12±23 [5]	36±32 [38]	0.043
Diastolic	6±13 [2]	23±13 [26]	0.006
Mean	8±17 [2]	31±22 [32]	0.018

^aGroups compared on median maximum increase (Wilcoxon Rank Sum test).

Figure 4. Individual BP profiles during the first 24 hours after transfusion: (A) systolic, (B) diastolic, and (C) MAP. The bold lines represent median values. BP=blood pressure; MAP=mean arterial pressure. Median for DCLHb higher than for PRBC in hours: a) 1–30; b) 1–24; and c) 1–30. (P<0.05 Wilcoxon rank sum tests).