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The prevalence of anaemia, hypochromia and microcytosis in preoperative cardiac surgical patients.

SUMMARY

This retrospective study aimed to determine the prevalence of preoperative anaemia, hypochromia and microcytosis in cardiac surgery patients. Data was analysed for 943 patients (over a two-year period) undergoing coronary artery bypass graft, valve or combined coronary artery bypass graft and valve surgery at a tertiary hospital in South Australia. Overall prevalence of preoperative anaemia was 25.2%, greater in males than females (27.6 vs 19.9%, P <0.01). Of patients with preoperative anaemia, 19.3% had reduced red cell indices (mean corpuscular haemoglobin and/or mean corpuscular volume) compared to 4% of patients without anaemia. The proportion of anaemic patients with low red cell indices was significantly higher in women <50 years and 50-65 years, compared to those >65 years of age (P=0.003). Anaemic patients with low red cell indices had lower preoperative haemoglobin than anaemic patients without low red cell indices (median haemoglobin 112 vs 120 g/l, P=0.008). Compared to non-anaemic patients, anaemic patients had higher transfusion rates (79.8 vs 46.4%, P <0.0001), which were greater in those with reduced red cell indices compared to those with normal red cell indices (93.5 vs 76.6%, P=0.01). This study demonstrated a high prevalence of preoperative anaemia, microcytosis and hypochromia in cardiac surgical patients.

Key Words: anaemia, cardiac surgery

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In patients undergoing cardiac surgery, preoperative anaemia increases the likelihood of red cell transfusion (1,2). Both preoperative anaemia and red cell transfusion have been associated with an increased risk of morbidity and mortality (3-11). Iron deficiency is a common cause of anaemia and is readily managed with iron supplementation (oral or intravenous) (12). The importance of identifying and managing preoperative anaemia has been included as a recommendation in the recently released Patient Blood Management (PBM) Guidelines in Australia (Module 2: Perioperative) (13).

While little data exists on the prevalence of anaemia and iron deficiency in Australia, it has been identified as a public health issue by the Australian government and is a component of the national health survey to be implemented during 2011-2013 (14). A national survey conducted in the United States in 2004 found that 11% of men and 10% of women over the age of 65 were anaemic, with iron deficiency accounting for 20% (15).

Iron deficiency anaemia (IDA) may be suspected in individuals with microcytosis, i.e. low mean corpuscular volume (MCV) and/or hypochromia, i.e. low mean corpuscular haemoglobin (MCH). In recent years there has been increasing recognition of the importance of a low MCH without microcytosis as an early indicator of iron deficiency (even in the absence of anaemia) (16,17) While IDA may be both microcytic and hypochromic, hypochromia often precedes the onset of microcytosis.

Iron studies are required to confirm the diagnosis of IDA, with serum ferritin being the most useful test. A ferritin level is an essential starting point in evaluation of anaemia, regardless of red cell indices (12). Baseline iron studies to assess available iron stores have also been incorporated into the recently released national PBM Guidelines--Perioperative (Module 2) (13) in the 'Preoperative haemoglobin assessment and optimisation template' for both anaemic and non-anaemic patients having major surgery in which substantial blood loss is anticipated.

The diagnosis of iron deficiency must prompt assessment for the underlying cause(s), which may be multifactorial. Gastrointestinal blood loss is the most important cause of iron deficiency in men and post-menopausal women (12), and may be due to serious underlying pathology. In cardiac surgery patients, there is a paucity of data on both the prevalence and management of preoperative IDA in Australia.

The aim of this retrospective study was to determine the prevalence of preoperative anaemia, microcytosis and hypochromia in a cohort of patients undergoing cardiac surgery (coronary artery bypass grafting [CABG] or valve surgery) at a major teaching hospital in South Australia (SA).

METHODS

A retrospective analysis of patients admitted for CABG and/or valve surgery at a major SA public teaching hospital over a two-year period (July 2008 to June 2010) was undertaken. Inclusion criteria were patients undergoing elective or urgent CABG, valve or combined CABG and valve procedures. Urgent cases were considered to be patients who required admission but did not require surgery within 24 hours (e.g. with unstable coronary syndromes). Exclusion criteria were emergency procedures (i.e. surgery required within 24 hours of admission).

Data was obtained from a database maintained at the SA Department of Health. This links SA public hospital morbidity datasets with pathology datasets of the statewide pathology service (SA Pathology). The data linkage methodology is described elsewhere (18). Ethics approval was granted by the Royal Adelaide Hospital and SA Department of Health Research Ethics Committees (protocol number 120413). Patients undergoing CABG or valve procedures were identified from the Australian modification of the International Statistical Classification of Diseases (ICD-10_AM).

Demographic data collected included age, gender and procedure (CABG, valve or combined CABG and valve). Laboratory data included haemoglobin (Hb) and red cell indices (MCV and MCH) obtained using an automated analyser (Sysmex XE-2100, Sysmex Corporation, Japan). Laboratory values recorded up to eight weeks preoperatively were included, with those closest to (but prior to) surgery used for analysis. Red cell transfusion data included all red cell units transfused from time of admission to time of hospital discharge. Anaemia in this study was defined as a Hb level below the reference range of the laboratory (SA Pathology) performing the test: Hb <135 g/l for men and Hb <115 g/l for women. Hypochromia was defined as MCH <27 pg and microcytosis as MCV <80 ft.

Statistical analysis

All data are presented as median (interquartile range) or incidence [%, 95% confidence interval]. Continuous variables between the groups were compared with Mann-Whitney test and categorical variables were compared with Pearson's chi-square test. P values <0.05 were considered statistically significant. All statistical analyses were compared with a Statistical Package for Social Sciences 20.0.

RESULTS

A total of 943 patients meeting inclusion criteria were identified from the linked database from a total of 1013 patients undergoing cardiac surgery during the review period. The study cohort consisted of 559 CABG (59.3%), 271 valve (28.7%) and 113 combined valve and CABG (12.0%) patients. Among the valve surgeries, 198 were aortic valves, 48 were mitral valves, one was tricuspid valve and 24 were dual mitral and aortic valves (repair and/ or replacement). The median age of the patients was 67 (interquartile range 57-75) years and 69.6% (656/943) were males. The overall prevalence of preoperative anaemia was 25.2% [22.6-28.1], (238/943). The median age of anaemic patients was 73 (interquartile range 64-78) years compared to 65 years in non-anaemic patients (interquartile range 56-73), P <0.0001. As shown in Table 1, the prevalence of preoperative anaemia was higher in men and in those undergoing combined procedures (CABG and valve).

Red cell indices were available for 941/943 patients. In anaemic patients, hypochromia was more common than microcytosis (19.3 vs 5.9%). Of the patients without preoperative anaemia, 4% were either hypochromic and/or microcytic. Despite this, none of the patients had ferritin or iron studies performed by the statewide pathology service in the preceding eight weeks. In anaemic women compared to anaemic men, rates of hypochromia were 24.6 vs 17.7% (P <0.25) and rates of microcytosis were 12.3 vs 3.9% (P <0.02) respectively. The prevalence of anaemia increased with increasing age, particularly in men. The proportion of anaemic patients with low red cell indices was significantly higher in women <50 years and 50-65 years, compared to those >65 years of age (P=0.003; Figure 1).

The red cell transfusion rate was significantly higher in the anaemic group when compared to the non-anaemic group (79.8 vs 46.4%, P <0.0001). In addition, of the anaemic patients with either hypochromia and/or microcytosis (46/238), a higher proportion were transfused compared to anaemic patients with normal red cell indices (93.5 vs 76.6%, P=0.01). The severity of preoperative anaemia was also significantly different between the two groups, with the median Hb in the anaemic group with normal red cell indices (MCV and MCH) being 120 g/l (110-129 g/l) compared to 112 g/l (105-123) in the anaemic group with low red cell indices (P=0.008). Of the anaemic group with normal red cell indices, 8.9% (17/192) had Hb levels <100 g/l compared to 10.9% (5/46) of the anaemic group with low red cell indices (P=0.67).

DISCUSSION

The principal finding of this study was the high prevalence of preoperative anaemia (25.2%) in our cohort of cardiac surgery patients. International studies have reported rates ranging from 6-54% (19-24); this broad range may relate to differences in (i) timing of blood tests before angiography and surgery, (ii) age, (iii) gender, (iv) comorbidity level and (v) Hb values used to define anaemia in the cohorts studied. Using the World Health Organization definition of anaemia (Hb <130 in men and <120 g/l in women), the overall prevalence of anaemia was similar to that using the laboratory reference ranges (25.2 vs 22.3%).

Preoperative anaemia is independently associated with adverse outcomes after cardiac surgery, including increased morbidity and mortality (4,5,20,23,25). In one cohort of cardiac surgery patients, iron deficiency was associated with a significant increase in fatigue postoperatively, which may have a negative impact on postoperative rehabilitation (24). Munoz et al cited age, chronic kidney disease, consumption of proton pump inhibitors and diuretics as independent risk factors for the presence of preoperative anaemia in elective cardiac surgery patients (21). Furthermore, Karski et al found that inpatient angiography close to time of surgery contributed to anaemia (22).

In our cohort, approximately 20% of anaemic patients were hypochromic and/or microcytic, suggesting a significant proportion may have been iron deficient. The prevalence of reduced red cell indices was similar in a study of cardiothoracic and orthopaedic surgical patients published by Grey et al (26). Piednoir et al (24) found an absolute iron deficiency rate of 37% in their cohort using a biological iron profile; they suggest iron deficiency in cardiac surgery patients appears to be greater than that seen in the general population. They also found a greater proportion of female cardiac surgery patients to be iron deficient compared to male counterparts even when post menopausal (24). This is consistent with our data showing higher rates of reduced red cell indices in anaemic women both <50 years and between 50 and 65 years compared to older anaemic women and men. Population studies have also shown a higher prevalence of iron deficiency in postmenopausal women compared with men, consistent with women emerging from the premenopausal years with lower iron stores due to previous menstrual losses and pregnancy (27).

The most important cause of iron deficiency in men and post-menopausal women is gastrointestinal blood loss. Other causes include malabsorption due to gastrointestinal mucosal disorders (e.g. coeliac disease), impaired gastric acid secretion and gastric/ intestinal bypass procedures (12). Under-recognition of the prevalence and importance of preoperative iron deficiency is likely to have contributed to the lack of serum ferritin or iron studies in our cohort. The most important differential diagnoses of microcytic and/or hypochromic red cell indices are thalassaemia trait and anaemia of chronic disease. Anaemia in both of these settings may be exacerbated by co-existing iron deficiency, which requires serum ferritin or iron studies to assess iron stores. A comprehensive clinical update on diagnosis and evaluation of IDA in the Australian context was published in 2010 (12).

Oral iron is generally considered first-line therapy for most patients with iron deficiency anaemia; however the intravenous (IV) route is being increasingly used to provide rapid iron repletion when this is clinically important, such as when there is a short time to non-deferrable surgery associated with substantial blood loss (13). A recent study of cardiac surgery patients without preoperative anaemia showed that IV and oral iron supplementation was ineffective in correcting anaemia after cardiopulmonary bypass and did not reduce blood transfusion (28). These findings cannot be extrapolated to patients with preoperative anaemia due to iron deficiency, where there are more likely to be therapeutic benefits to iron repletion; thus, more work is required in this area.

It is not surprising that our data showed that all patients with preoperative anaemia had significantly greater transfusion rates than those without anaemia. This is consistent with previous studies (1,2). Risk models have been developed to predict transfusion rate in cardiac surgery, with a recently published scoring system nominating the following variables as predictors of transfusion: age >67 years; weight <60 kg for females and <85 kg for males; preoperative haematocrit; female gender; and complex surgery (29).

It is interesting to note that the transfusion rate for anaemic patients with reduced red cell indices was significantly greater than anaemic patients with normal red cell indices. While this may be explained by a significantly lower mean Hb level preoperatively, it is possible that reduced erythropoiesis due to iron deficiency in the postoperative period may be a contributing factor. This may be consistent with Piednoir et al's finding that iron deficiency was associated with higher transfusion volumes, even in patients without preoperative anaemia (24).

The term 'patient blood management' refers to the management and preservation of patients' own blood to reduce or avoid the need for transfusion (13). PBM optimises the use of donor blood and reduces risks associated with transfusion. The national PBM Guidelines--Perioperative (Module 2), contain a preoperative Hb assessment and optimisation template for patients undergoing major surgery where substantial blood loss is anticipated. This is particularly relevant to the cardiac surgical population and we have recently introduced this into our preoperative workup. This template includes routine preoperative blood tests with full blood count, iron studies, C reactive protein and renal function. The template provides guidance for the management of preoperative anaemia depending on laboratory results (in particular the serum ferritin result) and clinical assessment.

In the setting of cardiac surgery, given that it is largely non-deferrable, the nature and timing of investigation of iron deficiency is a significant issue. Loor et al suggest that reversible causes of anaemia, such as gastrointestinal bleeding, should be ruled out and addressed prior to cardiac surgery, with elective surgery delayed to allow correction of anaemia wherever possible (30). However, many patients with critical cardiac disease may not tolerate deferral of surgery nor invasive gastrointestinal investigations. An alternative strategy is to provide IV iron repletion preoperatively and defer invasive gastrointestinal investigations until after cardiac surgery, but there is no current guidance on this issue and further studies are needed to define the optimal approach in different patient groups.

Another unanswered question is the effect of preoperative iron repletion (oral or IV) in patients with IDA detected prior to cardiac surgery on important outcomes, including thrombotic risk. The safety of perioperative erythropoiesis stimulating agents has not been established as studies to date have been underpowered to assess a difference in thrombotic vascular events (31,32).

The limitations of our findings include the fact that it was a retrospective study, where patients were identified according to the Australian modification of the International Statistical Classification of Diseases (ICD-10_AM). The underlying type of anaemia was not confirmed as serum ferritin or iron studies were not available, and other causes such as chronic disease, chronic kidney disease and vitamin B12 deficiency could not be evaluated. Multivariate analysis of transfusion data was not performed. The strengths of this study are the large sample of patients and minimal selection bias, and that the prevalence of microcytosis and hypochromia has not been widely explored previously.

In conclusion, this study has demonstrated the high prevalence of anaemia, microcytosis and hypochromia in cardiac surgery patients. Anaemia, and in particular IDA, represents a modifiable risk factor that can be assessed and managed preoperatively using published algorithms as part of a comprehensive PBM program that also addresses the other key pillars of reducing blood loss and optimising the patient's tolerance of anaemia. Importantly, future research should include prospective studies to determine the aetiology of preoperative anaemia in cardiac surgery patients, including the prevalence of iron deficiency. The effect of treatment of pre operative anaemia, and specifically iron deficiency, on clinically important outcomes also needs to be investigated.

Caption: Figure 1: Prevalence of preoperative anaemia (Hb <135 g/l for men and Hb <115 g/l for women) and low red cell indices in anaemic patients with age and gender. MCH=mean corpuscular haemoglobin, MCV=mean corpuscular volume, CI=confidence interval.

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(28.) Garrido-Martin P, Nassar-Mansur MI, de la Llana-Ducros R, Virgos-Aller TM, Fortunez PM, Avalos-Pinto R et al. The effect of intravenous and oral iron administration on perioperative anaemia and transfusion requirements in patients undergoing elective cardiac surgery: a randomized clinical trial. Interact Cardiovasc Thorac Surg 2012; 15:1013-1018.

(29.) Ranucci M, Castelvecchio S, Frigiola A, Scolletta S, Giomarelli P, Biagioli B. Predicting transfusions in cardiac surgery: the easier, the better: the Transfusion Risk and Clinical Knowledge score. Vox Sang 2009; 96:324-332.

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(31.) Canadian Orthopedic Perioperative Erythropoietin Study Group. Effectiveness of perioperative recombinant human erythropoietin in elective hip replacement. Lancet 1993; 341:1227-1232.

(32.) Faris PM, Ritter MA, Abels RI. The effects of recombinant human erythropoietin on perioperative transfusion requirements in patients having a major orthopaedic operation. The American Erythropoietin Study Group. J Bone Joint Surg Am 1996; 78:62-72.

O. DAVID *, R. SINHA ([dagger]), K. ROBINSON ([double dagger]), D. CARDONE ([section])

Royal Adelaide Hospital, Department of Anaesthesia, Adelaide, South Australia, Australia

* BM, BS, Registrar.

([dagger]) MB, BS, Senior Information Analyst, Blood, Organ and Tissue Programs, SA Health and Associate Lecturer, Faculty of Health Sciences, Flinders University.

([double dagger]) MB, BS, FRACR FRCPA, Haematologist, Australian Red Cross Blood Service and Clinical Lead, BloodSafe Program, SA Health.

([section]) MB, BS, FANZCA, Staff Specialist, Department of Anaesthesia, Royal Adelaide Hospital and Senior Clinical Lecturer, Faculty of Acute Care Medicine, University of Adelaide.

Address for correspondence: Dr D. Cardone. Email: david.cardone@ health.sa.gov.au

Accepted for publication on March 17, 2013.

Table 1
Preoperative anaemia (Hb <135 g/l for men and Hb <115 g/l for women)
rates by gender, type of surgery and red cell indices (MCH and MCV) *

                               Preop anaemia,       No preop anaemia,
                               n=238                n=705

Age (Median, IQR)              73(64-78)            65 (56-73)

Gender, % (95% CI)

  Male                         27.6 (24.3-31.1)     72.4 (68.9-75.7)

  Female                       19.9 (15.7-24.9)     80.1 (75.1-84.3)

Surgery type, %, (95% CI)

  CABG and valve               38.1 (29.6-47.3)     61.9 (52.7-70.4)

  CABG                         24.0 (20.6-27.7)     76.1 (72.3-79.4)

  Valve                        22.5 (17.9-27.9)     77.5 (72.2-82.1)

Red cell indices, % (95% CI)

  MCH <27 pg                   19.3 (14.8-24.8)     3.8 (2.7-5.5)

  MCV <80 fl                   5.9 (3.5-9.6)        1.9 (1.0-3.1)

  MCH <27 pg and/              19.3 (14.8-24.8)     4.0 (2.8-5.7)
  or MCV <80 fl

                               P value

Age (Median, IQR)              0.0001

Gender, % (95% CI)             0.01

  Male

  Female

Surgery type, %, (95% CI)      0.003

  CABG and valve

  CABG

  Valve

Red cell indices, % (95% CI)

  MCH <27 pg                   <0.0001

  MCV <80 fl                   0.001

  MCH <27 pg and/              <0.0001
  or MCV <80 fl

* Red cell indices were not available for two non-anaemic patients.
IQR = interquartile range, CI = confidence interval, CABG = coronary
artery bypass grafting, MCH = mean corpuscular haemoglobin, MCV =
mean corpuscular volume.
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Title Annotation:Original Papers
Author:David, O.; Sinha, R.; Robinson, K.; Cardone, D.
Publication:Anaesthesia and Intensive Care
Article Type:Clinical report
Geographic Code:8AUST
Date:May 1, 2013
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