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 Table of Contents  
Year : 2018  |  Volume : 3  |  Issue : 2  |  Page : 83-87

Hospital-Acquired anemia: A hazard of hospitalization

Department of Transfusion Medicine, Manipal Hospital, Bengaluru, Karnataka, India

Date of Web Publication24-Oct-2018

Correspondence Address:
Dr. Shivaram Chandrashekar
Department of Transfusion Medicine, Manipal Hospital, Bengaluru, Karnataka
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/GJTM.GJTM_44_18

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How to cite this article:
Chandrashekar S. Hospital-Acquired anemia: A hazard of hospitalization. Glob J Transfus Med 2018;3:83-7

How to cite this URL:
Chandrashekar S. Hospital-Acquired anemia: A hazard of hospitalization. Glob J Transfus Med [serial online] 2018 [cited 2023 Feb 7];3:83-7. Available from: https://www.gjtmonline.com/text.asp?2018/3/2/83/243933

Hospitalization has its own hazards.[1] One could have a reaction to a diagnostic or therapeutic procedure; the surgery or procedure could go horribly wrong or one may develop a reaction to drugs or blood administered as part of treatment. However, the most commonly recognized hazard of hospitalization is an acquired infection what we call as hospital-acquired infection. Another entity that is probably more common but underrecognized or underreported is hospital- or doctor-induced anemia in a hospitalized patient, what we may call as hospital-acquired anemia (HAA).

  Definition Top

HAA is anemia that is directly attributable to hospitalization. HAA is a concept, wherein a patient admitted for medical problems experiences a drop in their red cell count due to the hospitalization.[2] Alternatively, it is a reduction of hemoglobin (Hb) during hospitalization, as compared with the Hb on admission, regardless of the preadmission Hb levels.

  Anemia Top

The World Health Organization defines anemia as a Hb value <12 g/dL in women and <13 g/dL in men. HAA develops as a result of hospitalization in patients who have a normal Hb level on admission and can be categorized[3] as mild (Hb <11.0 g/dL), moderate (Hb 9.1–11.0 g/dL), or severe (Hb <9.0 g/dL).

  Incidence of Hospital-acquired Anemia Top

According to a study[4] in Journal of Hospital Medicine, nearly one-third of hospitalized patients develop HAA and 1.4% develop severe form of HAA characterized by a hematocrit of 27% or less at the time of discharge. Another study[5] showed anemia as a common complication occurring in almost two-thirds of patients admitted to the hospital. Even though anemia of chronic disease was the leading cause, investigational blood loss was also an important contributing factor. HAA has been shown to develop in nearly half of acute myocardial infarction (AMI) hospitalizations,[6] commonly in the absence of documented bleeding, and is associated with poor mortality and morbidity.

  Etiopathogenesis of Hospital-acquired Anemia Top

HAA has a diverse etiology.[7],[8],[9] HAA is mostly similar to anemia of chronic disease, resulting in a reduced life span of red blood cells attributable to a variety of causes. The etiology of HAA is complex [Table 1]. Some of these causes include marrow suppression by inflammatory cytokines, nutritional deficiencies, medical suppression of red blood cell production, surgical and procedural losses, actual bleeding, and more occult losses by phlebotomy. Rarely, HAA could also be the result of hemodilution caused by excessive fluid infusions.
Table 1: Etiology of hospital-acquired anemia

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Several factors other than bleeding might be associated with HAA, including blunted hematopoietic response and phlebotomy. Impaired hematopoiesis, resulting from preexisting and nonmodifiable factors, such as inflammation, chronic renal disease, or congestive heart failure, could impair recovery from even minor blood loss during hospitalization. Diagnostic blood loss has a substantial impact on the occurrence of hospital-acquired anemia, which is also called iatrogenic anemia.

  Clinical Features of Hospital-acquired Anemia Top

HAA is often insidious in onset. Anemia may go unnoticed for days as small incremental decreases in Hb go unnoticed by most clinicians. It may be asymptomatic or masked by symptoms of the underlying disease and when symptoms do develop, they are standard symptoms of anemia attributable to decreased oxygen-carrying capacity such as fatigue, malaise, shortness of breath, headaches, tachycardia, or dizziness. Most anemias are noticed only when the Hb drops to a level where transfusions become necessary.

  Patients at Risk: Clinical Conditions Contributing to Hospital-acquired Anemia Top

Even though anemia of chronic disease is the leading cause of HAA, investigational blood loss is also an important contributing factor. Patients already suffering from chronic anemia such as patients with chronic infection (tuberculosis, HIV), chronic inflammation (rheumatoid arthritis and inflammatory bowel disease), chronic renal failure, chronic liver disease, or neoplasms like Hodgkin's lymphoma are more likely to develop HAA. Sepsis secondary to infections may cause bone marrow suppression leading to anemia. Likewise, acute hemorrhage resulting from surgery or trauma also predispose to HAA. Bedside invasive procedures may also contribute to blood loss anemia. Hemodilution and coagulopathy secondary to the treatment of massive blood loss are other causes of HAA. However, in all these conditions, although the hospital contributes and probably exacerbates the existing anemia, this may not be always preventable as the anemia is secondary to existing illnesses in the patient. Patients in renal failure who already have suppressed erythropoiesis and who are subjected to repeated phlebotomy for various laboratory tests are at risk for HAA [Table 2]. A study[8] has shown that HAA is more prevalent in older patients and those who have more comorbidities, including hypertension, heart failure, peripheral arterial disease, or renal and liver disease.
Table 2: Clinical conditions causing anemia

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  Drug-induced Anemias Top

Drug-induced anemias form an important group of HAA. Common drugs causing drug-induced immune hemolytic anemia (DIIHA) are antimicrobials[10] (e.g., cefotetan, ceftriaxone, and piperacillin), which are associated with drug-dependent antibodies. The most common drug to cause AIHA is fludarabine. Various drugs used to treat the underlying condition of the patient themselves have been implicated to cause anemia. A study[11] has implicated antibiotics such as cephalosporins, penicillin and/or penicillin derivatives, nonsteroidal anti-inflammatory drugs (NSAIDs), and the antimalarials, quinine and/or quinidine, in causing anemia in a hospitalized patient. It is therefore important to consider DIIHA when a patient serologically presents as either warm- or cold-type AIHA. Finding out which drug is causing the problem and stopping that drug is the first approach to therapy. Bite cell hemolytic anemia[12] is a variant of drug-related hemolysis usually associated with methemoglobinemia and Heinz body inclusions in red blood cells secondary to oxidant drug injury. A peripheral smear is an important but often forgotten diagnostic tool in addition to DAT in the investigation of drug-induced hemolytic anemia which could be an important cause of HAA.

  Reducing Blood Loss to Reduce Hospital-acquired Anemia Top

Surgery is the most frequent cause of a medical blood loss of 20% or more of a patient's total blood volume. High-risk surgeries involving the liver, heart, blood vessels, or trauma are a major determinant of hospital blood loss. Extreme losses result in not only anemia but also other morbidities and even death. Surgery-related blood loss varies greatly according to the type of surgery, patient comorbidities, and technical factors. Surgical advances in technology and technique, including vessel-sealing devices and gels, minimally invasive surgical techniques, and cell salvage devices and techniques, all help in reducing blood loss and thereby HAA.

HAA shows a linear relationship with blood loss during hospitalization, leading to higher risk of death or readmission, even after adjusting for other important factors.[13] Both chronic anemias, present at the time of hospitalization, and HAA, that develops later during hospitalization in patients with a normal Hb level at admission, are associated with greater mortality and morbidity in patients with AMI.[14] Better understanding of how HAA can be prevented, and whether its prevention can improve patient outcomes is needed.

  Phlebotomy Losses: the Contribution of Diagnostic Blood Sampling to Hospital-acquired Anemia Top

Phlebotomy losses for laboratory investigations have been shown to be an important contributory factor in causing iatrogenic anemia or HAA. The first study[15] to identify blood loss from diagnostic phlebotomy as independently predictive of HAA was a 2011 study by Salisbury et al. This study showed that 20% of patients without anemia on admission developed moderate or severe anemia during admission. The mean phlebotomy volume was higher in patients with HAA than in those without anemia. For each 50 mL of blood drawn, the risk of moderate-to-severe anemia rose by 18%, suggesting that phlebotomy volume could alter the incidence of HAA.

Estimates for average daily diagnostic blood loss in hospitalized patients ranges from approximately 12 mL/day in general medicine wards to 40–50 mL/day in intensive care units (ICU).[16] ICU patients with an indwelling catheter can lose up to 900 mL of blood during their hospital stay. This degree of phlebotomy-associated blood loss occurs most often in patients with long-term ventilation, coagulation disorders, or those who have undergone surgery.

  Arguments Against Blood Loss as a Cause of Hospital-acquired Anemia Top

Another paper[17] has argued that the association between diagnostic blood loss and HAA could be the results of more test being performed in patients with anemia rather than higher volumes being drawn. Clearly, patients with low Hb concentrations are more ill, and therefore, more likely to undergo diagnostic blood drawing than patients with higher Hb concentrations, first because they are more ill and second because they spend more days in the hospital. Most studies do not adjust the diagnostic blood loss with the duration of hospital stay. It takes at least 10 days of daily 53-mL blood sampling in a 65.4-kg female with no marrow synthesis for anemia to develop. Hence, diagnostic blood sampling alone may not be a major cause of HAA.

  Phlebotomy Losses in Medical Setting Top

Phlebotomy is associated with changes in Hb and hematocrit levels for patients admitted to the internal medicine service[18] and can contribute to anemia. This anemia may have significant consequences, especially for patients with cardiorespiratory diseases. Knowing the expected changes in Hb and hematocrit due to diagnostic phlebotomy will help guide the investigation of anemia in hospitalized patients.

  Phlebotomy Losses in Intensive Care Setting Top

Depending on the number of days in the ICU, the majority of critically ill patients develop anemia.[19] Nosocomial anemia has been associated with increased mortality rate, increase in length of ICU stay, and also need for blood transfusion. A study[20] has noted that of all patients admitted to ICU 76.9% developed nosocomial anemia and the mortality rate in these patients who developed nosocomial anemia was as high as 86.7%. More than half the patients had a length of ICU stay beyond 5 days but <10 days. However, only 12.3% of patients needed a blood transfusion which could mean that the anemia was mild or went unrecognized.

  Phlebotomy Losses in Renal Patients Top

Phlebotomy losses contribute to anemia in renal patients.[21] This is over and above the suppression of erythropoiesis induced by the nonfunctional kidneys. A study on renal patients has shown that phlebotomy losses were highest in the 1st week (mean of 76.8 mL), declining in subsequent weeks. Samples were taken for biochemistry (38%), full blood counts (36%), transfusion (13%), and others (13%). Forty-six percent of patients received transfusions.

  Phlebotomy Losses in New Born Top

Blood loss attributable to laboratory testing has been shown to be the primary cause of anemia among preterm infants during the first few weeks of life. Phlebotomy losses exacerbate the anemia of prematurity already present in many preterm infants. The clinical factors[22] associated with greater phlebotomy overdraw are collection in blood containers without fill lines, lighter weight infants and critically ill infants being cared for in the neonatal ICUs. A significant variation in blood overdraw among individual phlebotomists has also been demonstrated showing the need for better and continued training. Another contributory factor is the workshift. There was significantly greater overdraw for blood samples obtained during the evening shift, compared with the day shift.

  Phlebotomy Volumes Versus Development of Hospital-acquired Anemia Top

Most patients admitted to ICUs have a battery of tests performed on admission and on a daily basis. Tests for biochemical parameters include Renal function tests (RFT), Liver function tests (LFT), and serum electrolytes involve 3–4 ml of blood. Tests for hematology parameters such as complete blood count (CBC) involve 3–4 ml of blood. Tests for coagulation such as prothrombin time (PT)/partial thromboplastin time (PTT) are done on patients on anticoagulation and this involves another 3–4 ml of blood. Blood culture studies if warranted involve a loss of 10–20 ml of blood. In addition to being repeated daily, these tests may be repeated more often in some patients such as those with massive blood loss, DIC, and AIHA leading to further red cell loses. Volume of blood lost by phlebotomy is in most instances, more than the volume needed by the current-day machines for performing the tests. A study by Salisbury et al. has shown that for each 50 mL of blood drawn, the risk of moderate-to-severe anemia rises by 18%, suggesting that phlebotomy volume could alter the incidence of HAA. The volume of phlebotomy is a strong predictor of drop in Hb and hematocrit after adjusting for other predictors. On an average, every 100 mL of phlebotomy is associated with a decrease in Hb and hematocrit of 7.0 g/L and 1.9%, respectively.[17]

Resource utilization and HAA is common and associated with increased mortality and resource utilization.[23] Mean length of stay (LOS) has been shown to be progressively higher in patients who developed HAA. One study showed that the LOS nearly doubled (1.86 fold) with HAA. Total hospital charges also showed a 1.8-fold rise in patients who developed HAA.

  Strategies to Reduce Phlebotomy Losses Top

Like in the neonates, in adults too, the contribution of diagnostic blood sampling to HAA depends on multiple factors. The determinants of Hb are rate of production in the marrow, the nutritional status which determines availability of iron, B12, folic acid, proteins for hemoglobin synthesis, volume of circulating blood, and the rate of red cell senescence. Coene et al. strategy to reduce diagnostic blood loss comprised the use of low-volume blood collection tubes and standardization of methods for blood collection from central lines and for glucose measurements. Implementation of this strategy was associated with a considerable reduction in total daily diagnostic blood loss, that is, of 25%. Common sense tells us that if we can do CBC, one of the most commonly performed tests, with 1 ml of blood collected in a microtainer from a baby, we do not need 3–4 ml in adult patients for the same test.

However, in contrast to chronic anemia, HAA can potentially be prevented by implementing strategies to reduce blood loss in high-risk patients. HAA seems to be multifactorial and commonly develops in the absence of bleeding. It is important to manage losses by optimizing the frequency and volume of blood drawn for diagnostic laboratory tests. Re-look at the quantity of blood needed for various tests, use of vacutainers with line markings, training of phlebotomists, ICU nurses, and neonatal nurses in phlebotomy may help in limiting red cells loss, thereby preventing HAA. Phlebotomists need to consolidate requests from multiple treating doctors in sick patients, so that number of phlebotomies and consequently the volumes drawn are also limited. The practice of drawing an extra sample “just in case, it is needed later for some test” to avoid pricking the patient again may not be a good practice. Good coordination between various laboratories such as hematology, biochemistry, and coagulation is essential to minimize phlebotomy losses [Table 3].
Table 3: Suggested strategies to prevent iatrogenic blood loss

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  Conclusion Top

HAA is a fairly common condition resulting from myriad causes ranging from surgical blood loss to medical suppression of erythropoiesis to drug-induced hemolysis. It is important to recognize and prevent or minimize this problem as it is associated with poor patient outcomes and increased hospital resource utilization. Preventing HAA demands a team approach, the team consisting of the phlebotomists, the ward, and the clinical laboratory and the blood center together with cooperation from the treating physician(s). Chronic phlebotomy-associated blood loss can lead to anemia or exacerbate the existing anemia, and hence it must be regulated using all possible approaches outlined above. Laboratories can help limit diagnostic blood loss by implementing strategies that reduce the amount of blood required for testing and encourage appropriate test ordering. Blood centers and surgery departments should encourage blood-sparing techniques. Improvements in these areas increase patient safety by reducing the risk of iatrogenic anemia as well as the need for blood transfusion.[2]

  References Top

Schimmel EM. The hazards of hospitalization 1964. Qual Saf Health Care 2003;12:58-63.  Back to cited text no. 1
Noguez J. Tackling Hospital-Acquired Anemia. Available from: https://www.aacc.org/publications/cln/articles/2016/april/tackling_hospital-acquired-anemia-lab-based-interventions-to-reduce-diagnostic-blood-loss. [Last accessed on 2018 Oct 12].  Back to cited text no. 2
Ahmed AH. Prevention and management of hospital-acquired anemia. Hosp Med Clin 2014;3:e71-84.  Back to cited text no. 3
Makam AN, Nguyen OK, Clark C, Halm EA. Incidence, predictors, and outcomes of hospital-acquired anemia. J Hosp Med 2017;12:317-22.  Back to cited text no. 4
Wong P, Intragumtornchai T. Hospital-acquired anemia. J Med Assoc Thai 2006;89:63-7.  Back to cited text no. 5
Salisbury AC, Alexander KP, Reid KJ, Masoudi FA, Rathore SS, Wang TY, et al. Incidence, correlates, and outcomes of acute, hospital-acquired anemia in patients with acute myocardial infarction. Circ Cardiovasc Qual Outcomes 2010;3:337-46.  Back to cited text no. 6
Martin ND, Scantling D. Hospital-acquired anemia: A contemporary review of etiologies and prevention strategies. J Infus Nurs 2015;38:330-8.  Back to cited text no. 7
Jelkmann W. Proinflammatory cytokines lowering erythropoietin production. J Interferon Cytokine Res 1998;18:555-9.  Back to cited text no. 8
Anand IS. Anemia and chronic heart failure implications and treatment options. J Am Coll Cardiol 2008;52:501-11.  Back to cited text no. 9
Johnson ST, Fueger JT, Gottschall JL. One center's experience: The serology and drugs associated with drug-induced immune hemolytic anemia – A new paradigm. Transfusion 2007;47:697-702.  Back to cited text no. 10
Garratty G. Immune hemolytic anemia associated with drug therapy. Blood Rev 2010;24:143-50.  Back to cited text no. 11
Yoo D, Lessin LS. Drug-associated “bite cell” hemolytic anemia. Am J Med 1992;92:243-8.  Back to cited text no. 12
Wu WC, Rathore SS, Wang Y, Radford MJ, Krumholz HM. Blood transfusion in elderly patients with acute myocardial infarction. N Engl J Med 2001;345:1230-6.  Back to cited text no. 13
Nikolsky E, Aymong ED, Halkin A, Grines CL, Cox DA, Garcia E, et al. Impact of anemia in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention: Analysis from the controlled abciximab and device investigation to lower late angioplasty complications (CADILLAC) trial. J Am Coll Cardiol 2004;44:547-53.  Back to cited text no. 14
Salisbury AC, Reid KJ, Alexander KP, Masoudi FA, Lai SM, Chan PS, et al. Diagnostic blood loss from phlebotomy and hospital-acquired anemia during acute myocardial infarction. Arch Intern Med 2011;171:1646-53.  Back to cited text no. 15
Smoller BR, Kruskall MS. Phlebotomy for diagnostic laboratory tests in adults. Pattern of use and effect on transfusion requirements. N Engl J Med 1986;314:1233-5.  Back to cited text no. 16
van der Bom JG, Cannegieter SC. Hospital-acquired anemia: The contribution of diagnostic blood loss. J Thromb Haemost 2015;13:1157-9.  Back to cited text no. 17
Thavendiranathan P, Bagai A, Ebidia A, Detsky AS, Choudhry NK. Do blood tests cause anemia in hospitalized patients? The effect of diagnostic phlebotomy on hemoglobin and hematocrit levels. J Gen Intern Med 2005;20:520-4.  Back to cited text no. 18
Walsh TS, Saleh EE. Anaemia during critical illness. Br J Anaesth 2006;97:278-91.  Back to cited text no. 19
El-Soussi AH, Asfour HI, Raffat FA. Factors contributing to nosocomial anemia. J Nurs Health Sci 2016;5:31-44. Available from: https://www.pdfs.semanticscholar.org/06e6/633796474d1091054fd57d50638e19e91a14.pdf/. [Last accessed on 2018 Oct 12].  Back to cited text no. 20
Pabla L, Watkins E, Doughty HA. A study of blood loss from phlebotomy in renal medical inpatients. Transfus Med 2009;19:309-14.  Back to cited text no. 21
Lin JC, Strauss RG, Kulhavy JC, Johnson KJ, Zimmerman MB, Cress GA, et al. Phlebotomy overdraw in the neonatal intensive care nursery. Pediatrics 2000;106:E19  Back to cited text no. 22
Koch CG, Li L, Sun Z, Hixson ED, Tang A, Phillips SC, et al. Hospital-acquired anemia: Prevalence, outcomes, and healthcare implications. J Hosp Med 2013;8:506-12.  Back to cited text no. 23


  [Table 1], [Table 2], [Table 3]


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Incidence of Hos...
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Patients at Risk...
Drug-induced Anemias
Reducing Blood L...
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