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TRANSFUSION PRACTICE

Early changes in hemoglobin and hematocrit levels after packed red


cell transfusion in patients with acute anemia

J.I. Elizalde, J. Clemente,J.L. Marin, J. Pan& B. Aragon, A. Mas, J.M. Piquk, and J. Terh

T
he clinical use of blood components has experi-
BACKGROUND: Equilibration of hemoglobin concentra- enced a sustained increase during the last 50
tion after transfusion has been estimated to take about years.' Up to now, controversy has existed about
24 hours, but some studies have shown that earlier the usefulness of monitoring the effects on hemo-
measurements reflect steady-state values in persons globin (Hb) or hematocrit (Hct) levels of the administration
who have not bled recently.This study was aimed at as- of packed red cells (RBCS).~Although an increase of 10 to 15
sessing the changes over time in hemoglobin concentra- g per L in Hb per unit of blood transfused is e ~ p e c t e dthe
,~
tion after transfusion in acutely anemic patients because time between blood transfusion and reflection of the incre-
of recent bleeding. ments in the blood measurements is unknown. Most text-
STUDY DESIGN AND METHODS: Thirty-two books state that the equilibration of Hb concentration after
normovolemic patients recovering from an acute bleed- transfusion takes about 24 h o u r s , " but
~ ~ there is no evidence
ing episode who were no longer thought to be bleeding supporting this idea. Conversely, some studies conducted in
and who received a 2-unit red cell transfusion were children6 and adults7 have provided data indicating that
studied. At baseline and 15, 30, 60, and 120 minutes measurements performed as early as 15 minutes after the
and 24 hours after transfusion, hemoglobin concentra- end of transfusion reflect steady-state values. However, the
tion and hematocrit values were measured. only study performed in an adult population excluded pa-
RESULTS: The administration of 2 units of packed red tients who had had a recent bleeding episode, even though
cells elicited a 24-hour increase of 22.4 i 6.8 g per L in it is exactly those patients in whom a rapid assessment of the
hemoglobin concentration. Hemoglobin values were not effects of transfusion could help in early detection of recur-
different at any of the defined posttransfusion times. He- rent bleeding. Moreover, in that study, the duration of trans-
matocrit levels experienced similar changes over time. fusion was variable but, in any instance, longer than the
Agreement between 15-minute and 24-hour values was usual time that most centers require to perform the proce-
excellent, as only 6 percent of patients exhibited a clini- dure. In addition, only data related to Hb concentration were
cally significant difference (>6 g/L) between the hemo- a s ~ e s s e dHct
. ~ levels are both rapid and easy to determine,
globin measurements. and they provide clinical information similar to that of Hb
CONCLUSION: Hemoglobin and hematocrit values rap- concentration, with the possibility that the results can even
idly equilibrate after transfusion in normovolemic pa- be obtained at the bedside.
tients who are recovering from an acute bleeding epi-
sode. This fact would allow a rapid assessment of the
effects of transfusion and of the recurrence of bleeding
in patients remaining at risk. ABBREVIATIONS: Hb = hemoglobin; Hct = hematocrit, RBC(s) =
red cell(s).
From the Gastroenterology Department, the Liver Unit, and the
Emergency Laboratory Unit, Hospital Clinic i Provincial, Univer-
sity of Barcelona, Barcelona, Spain.
Supported by Grant FISS 96/0241 from the Fondo de Investi-
gaciones Sanitarias de la Seguridad Social and by Grant FIAP/96-
9105 from Comissionat per a Universitats i Recerca de la Generalitat
de Catalunya (JIE).
Received for publication August 5,1996; revision received Oc-
tober 16,1996,and accepted December 5,1996.
TRANSFUSION 1997;37:573-576.

Volume 37, June 1997 TRANSFUSION 573


ELIZALDE ET AL.

The present study was done to clarify the following is- Hct levels over time were examined by repeated-measures
sues: first, whether early measurements of Hb after blood ANOVA using a statistical package (Statview 4.5, Abacus
transfusion adequately reflect Hb levels after prolonged Concepts, Berkeley, CA)on a computer (Macintosh LC475,
equilibration periods in patients with acute anemia; second, Apple Computer, Cupertino, CA). Sex, age, weight, body sur-
whether Hct values really do reflect such changes; and third, face area, urine output, creatinine clearance, and the time
whether the calculated increase in Hb (assuming an increase since hemostasis were included in the ANOVA to explore
of 10 g/L of Hblunit of blood) differs clinically from that re- possible confounding effects on Hb equilibration. The
vealed in the observed data. agreement between Hb levels measured at 24 hours and
those measured at 15 minutes or calculated on the basis of
MATERIALS AND METHODS the expected increase in Hb concentration was also as-
Subjects sessed. For that purpose, the mean difference and the stan-
dard deviation of the differences between 15-minute and 24-
Patients on a gastroenterologic general ward or a gastro-
hour Hb concentration data and between expected8 and real
enterologic intensive care unit of a 1000-bed teaching ter-
24-hour Hb values were calculated and compared to the
tiary-care center who were selected to receive a 2-unit trans-
accepted, clinically relevant differences for Hb concentra-
fusion of packed RBCs because of acute blood losses in the
t i ~ nThe
. ~ same approach was used to assess the agreement
previous 5 days were considered for this study. Only patients
between 15-minute and 24-hour Hct values. Significance
whose bleeding was believed to have stopped at least 24
was established at a two-sided p value of 0.05.
hours before the transfusion (as judged by the stabilization
of their Hb levels) were included. A normovolemic state, as
defined by systolic blood pressure higher than 100 torr, right
atrial pressure higher than 2 cm of H,O, heart rate of less RESULTS
than 100 beats per minute, and urine output equal to or From August 1995 to June 1996,35 consecutive patients ful-
greater than 0.5 mL per kg per hour, was also required at the filling the inclusion criteria were included in this study.
time of inclusion. Exclusion criteria included age younger Among them, 23 patients had had an acute gastrointestinal
than 18 years, history of congestive heart failure, current bleeding episode in the previous 5 days, the source of which
renal failure as defined by serum creatinine levels higher was a bleeding peptic ulcer in 10 patients, stress ulcers in 4,
than 2 mg per dL, previous inclusion in the study, or refusal and gastroesophageal varices in 9. In the remaining 12 pa-
to give informed consent.This study was in accordance with tients, transfusion was indicated because of anemia second-
the standards of the Ethics Committee of the Hospital Clinic ary to blood losses during or after surgery. Once included,
i Provincial de Barcelona. two patients experienced recurrence of bleeding, and, in
Transfusion time was adjusted in all cases to 240 min- another, blood transfusion had to be interrupted because of
utes. Hb concentration and Hct values were measured be- the development of a transfusion reaction. Thus, 32 patients
fore and 15 minutes, 30 minutes, 1 hour, 2 hours, and 24 (21 men and 11 women, aged 61 f 3 years) were included in
hours after the end of transfusion. For that purpose, blood the data analysis. At entry, mean arterial blood pressure and
from an arterial or central venous line was drawn into stan- *
heart rate were 81 f 3 torr and 83 2 beats per minute, re-
dard 3-mL heparinized tubes (Vacutainer,Becton Dickinson spectively, for the whole group.
Company, Rutherford, NJ), and complete blood counts were The administration of 2 units of packed RBCs elicited a
measured on automated analyzers (H1 System, Technicon 24-hour increase in Hb concentration of 22.4 f 6.8 g per L, a
Instruments, Tarrytown, NY) by standard laboratory meth- response that was not different (p = 0.2) from that expected
ods within 1 hour of blood extraction. Care was taken to according to the published data (20 f 8 glL). The values of
obtain the samples from the same line in each individual Hb concentration were not different (p = 0.4) when mea-
case. Body surface area was calculated from body weight sured at 15 minutes, 30 minutes, l hour, 2 hours, or 24 hours
and height by using standard nomograms. after the end of transfusion (Fig. 1A). None of the parameters
included in the ANOVA as possible confounding factors (sex,
Statistics age, weight, body surface area, urine output, creatinine
We calculated sample size by taking into account an ex- clearance, and time since hemostasis) were found to influ-
pected increase in Hb concentration of 20 f 8 g per L7 and ence Hb equilibration. Hct levels did show similar changes
by considering as clinically significant those changes in Hb over time after transfusion (Fig. l B ) , with increases of 6.4
concentration greater than 6 g per L.8 With the probability percent (95% CI, 6.1-7.30) at 15 minutes and of 6.8 percent
of a type I error established at a = 0.05, a sample of 32 pa- (95% CI, 6.14-7.40%)at 24 hours.
tients would yield 90-percent power to detect a change of 6 The differences between 15-minute and 24-hour Hb
g per L in the Hb level. concentration data and between expected (determined by
*
Data are presented as mean SD, and, for some analy- adding 20 g/L to the baseline values) and observed 24-hour
ses, 95-percent CIS are also provided. The changes in Hb or Hb values were calculated. The 95-percent CI for these dif-

574 TRANSFUSION Volume 37,June 1997


TRANSFUSION MONITORING IN ACUTE ANEMIA

groups include a drop in the Hb level in the definition of


rebleeding, because other signs, such as changes in heart
rate or blood pressure, may be delayed, absent, or attributed
to intercurrent condition^.*^-'^ Moreover, external bleeding
may not occur in several situations, including some duode-
nal ulcers in which monitoring of gastric aspirates is useless.
The measurement of Hb or Hct levels two or three times a
day is generally used to monitor patients who are at risk for
rebleeding, as a way of detecting clinically unsuspected re-
currences, and a rapid assessment of the effects of blood
Baseline 15 rnin 30 min 60 rnin 120 rnin 24 hours
transfusion in these patients could be of great importance
in their monitoring.
Even though more than 12 million units of packed RBCs
are transfused annually in the United States,I4there is still a
considerable amount of confusion about the best way to
monitor the effects of this therapy tool. For instance, there
is no reason to explain why many centers delay the measure-
ment of Hb levels for up to 24 hours after transfusion. Re-
cently, an equilibration study has shown that the platelet
counts 10 and 60 minutes after platelet transfusion are
equivalent,I5 which enables investigators to decrease the
time that patients spend in the clinic. Similarly, some data
have been provided, demonstrating that the equilibration
Baseline 15 rnin 30 min 60 rnin 120 rnin 24 hours rate following packed RBC administration in patients with-
Time out recent bleeding is very fast, because measurements per-
Fig. 1. A) Hb concentrationat baseline and at various intervals
formed as early as 15 minutes after transfusion really do
after the transfusion of 2 units of packed RBCs. Results are ex-
reflect steady-state values.’
pressed as mean i 1 SD. B) Hct values at baseline and at vari-
The main aim of the present study was to assess
ous intervals after the transfusion of 2 packed RBC units. Re-
whether the changes over time in Hb concentration after
sults are expressed as mean f 1 SD.
RBC transfusion in acutely anemic patients were similar to
those reported in patients with chronic anemia. With that
purpose, patients who had been rendered anemic because
of a recent bleeding episode and who were selected to re-
ferences were -9.26 to 14.02 g per L for expected and ob-
ceive a 2-unit packed RBC transfusion were included. Be-
served 24-hour Hb values, and -5.94 to 7.86 g per L for 15-
cause an equilibration study requires a steady state, only
minute and 24-hour Hb concentrations. The last figure com-
patients who had stopped bleeding at least 24 hours earlier
pares favorably with the previous, and with the generally
and were normovolemic at the moment of inclusion were
accepted significant change in Hb level, which is between
considered. Our results disclose that Hb measurements per-
6.6 and 10 g per L.8 Moreover, the difference between ex-
formed as early as 15 minutes after the end of transfusion
pected and observed 24-hour Hb values was less than 6.6 g
in acutely anemic patients reflect the effect of transfusion
per L in 62.5 percent of cases; the difference was less than
on Hb concentration, because the values are not different
6.6 g per L in 93.8 percent when 24-hour values were plot-
from those obtained at 24 hours. This result cannot be as-
ted against 15-minute data (p = 0.006). Similarly, the agree-
cribed to a long transfusion time, as all patients were trans-
ment between Hct values obtained at 15 minutes and 24
fused at the usual rate employed in the clinical practice for
hours after transfusion was excellent, as 94 and 75 percent
patients without hypovolemic shock or cardiac or renal fail-
of patients exhibited a difference equal to or less than 2 and
ure. Moreover, in nearly 40 percent of patients, the 24-hour
1 percent, respectively, between the determinations.
increase in Hb differed by 6.6 g per L or more from the ex-
pected increase, according to a theoretical 10 g per L in-
DISCUSSION crease per unit of blood.3This result points out the need to
Gastrointestinal bleeding is a medical emergency in which monitor the effects of transfusion, as response variability
prompt and timely intervention may be 1ife-saving.IORecur- exists among patients. In this study, no factor was identified
rence of bleeding, which has been identified as one of the as being responsible for such variability, but this was not in
major determinants of a fatal outcome, usually constitutes the scope of the study and such a determination would
an indication for surgical or endoscopic treatment. Most probably require a larger number of patients. The difference

Volume 37, June 1997 TRANSFUSION 575


ELIZALDE ET AL.

between 15-minute and 24-hour Hb values was greater than 8. Wintrobe MM. Clinical hematology. 8th ed. Philadelphia: Lea &
6.6 g per L in only 6 percent of patients. This finding chal- Febiger, 1981:8.
lenges the generalized concept that equilibration of blood 9. Bland JM, Altman DG. Statistical methods for assessing agree-
Hb concentration after transfusion requires a long time in ment between two methods of clinical measurement. Lancet
acutely anemic patients with recent bleeding. 19861~307- 10.
Hb concentration is generally preferred to Hct measure- 10. Panos MZ, Walt RP. Current management of bleeding peptic
ment in assessing the extent of anemia, because it is mea- u1cer.A review. Drugs 1993;46:269-80.
sured directly, not calculated.8 However, determination of 11. Turner IB, Jones M, Piper DW. Factors influencing mortality
the Hct value is a cheaper and easier procedure.16This study from bleeding peptic ulcers. Scand J Gastroenterol
suggests that Hct values could be as useful as Hb measure- 1991;26:661-6.
ments at monitoring the effects of RBC transfusion. How- 12. Zimmerman J, Siguencia J, Tsvang E, et al. Predictors of mortal-
ever, a larger number of patients would be necessary to con- ity in patients admitted to hospital for acute upper gastrointes-
firm this assessment. tinal hemorrhage. Scand J Gastroenterol1995;30:327-31.
In summary, the results of the present study confirm 13. Rockall TA, Logan RF, Devlin HB, Northfield TC. Variation in
previous work showing that Hb concentration rapidly equili- outcome after upper gastrointestinal haemorrhage. The Na-
brates after a 2-unit packed RBC transfusion and extends tional Audit of Acute Upper Gastrointestinal Haemorrhage.
this concept to patientswith acute anemia, even when trans- Lancet 1995;346:346-50.
fusion time is as short as that usually employed in the clini- 14. Surgenor DM, Wallace EL, Hao ES, Chapman RH. Collection
cal practice. and transfusion of blood in the United States, 1982-1988.
N Engl J Med 1990;322:1646-51.
ACKNOWLEDGMENTS 15. O’Connell B, Lee EJ, Schiffer CA. The value of 10-minute post-
The authors thank the nursing staff of the Gastroenterology and transfusion platelet counts. Transfusion 1988;28:66-7.
Liver Intensive Care Units. They are also indebted to Maite Gueto for 16. Jiranek GC, Kozarek RA. A cost-effective approach to the pa-
secretarial support. tient with peptic ulcer bleeding. Surg Clin North Am
1996;76:83-103.

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