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C. Cherenfant and U. Umeh
in the setting of NSAIDs or aspirin with simultaneous use of
other medications such as antiplatelets and anticoagulants
due to an increased risk of bleeding [9].
Ticlopidine, clopidogrel, and prasugrel are thienopyridine
derivatives that irreversibly inhibit the P2Y12 component of
ADP receptors on the platelet surface. This prevents the
GPIIb/IIIa receptor complex from activating and
consequently reduces platelet aggregation. Ticagrelor also
has a similar mechanism of binding to the P2Y12 receptor;
however, it is not a thienopyridine derivative, and its binding
is reversible and noncompetitive. Cangrelor selectively and
reversibly binds to the P2Y12 receptor, also preventing
platelet activation and aggregation, but its administration is
intravenous [42].
ASRA recommendations for patients taking these medi-
cations are as follows [9]:
• The recommended time interval between discontinuation
of therapy and neuraxial blockade is 10days for ticlopidine,
5–7days for clopidogrel, 7–10days for prasugrel, 5–7days
for ticagrelor, and 3hours for cangrelor.
• Therapy may be reinstituted 24hours postoperatively for
ticlopidine, clopidogrel and prasugrel (thienopyridine
therapy), and ticagrelor.
• Neuraxial catheters should not be maintained with prasugrel or ticagrelor due to their rapid onset.
• Neuraxial catheters may be maintained for 1–2days with
ticlopidine and clopidogrel, in the setting of no
administration of a loading dose, since these antiplatelets
do not have an immediate antiplatelet effect.
• Remove neuraxial catheter 8hours prior to reinstitution
of cangrelor therapy postoperatively.
• Thienopyridine and ticagrelor therapy may be resumed
immediately after needle placement/catheter removal, if a
loading drug is not given. If a loading dose is administered,
a suggested time interval between catheter removal and
administration is 6hours.
GPIIb/IIIa receptor antagonists include abciximab, epti-
batide, and tiroban. They greatly inhibit platelet aggregation, which impacts the recommendations made with
their involvement in regional anesthesia. For context, after
administration of abciximab, normal platelet aggregation
reoccurs in 24–48 hours, while normalcy occurs 4–8hours
after eptibatide and tiroban [43]. In patients taking these
medications, ASRA suggests avoiding neuraxial procedures
until platelet function has recovered. If these therapies are
given after neuraxial technique, it is recommended to use
drugs that minimize sensory and motor blocking so patient
can be monitored neurologically. No catheter removal time
has been suggested; rather it is recommended to weigh the
risk of spinal bleeding against the benets of antiplatelet
therapy [9].
Cilostazol reversibly inhibits platelet aggregation by
inhibiting phosphodiesterase III.As its bleeding risk effect
on neuraxial block is unknown, it is suggested that cilostazol
be discontinued for 2 days prior to neuraxial anesthesia,
which is based on its elimination half-life. ASRA also
suggests neuraxial catheter removal prior to restarting
therapy, with the rst postoperative dose being administered
6hours after catheter removal [9].
Dipyridamole’s antiplatelet effect is also through inhibition of platelet aggregation. ASRA recommendations are as
follows [9]:
• Discontinue the extended release form 24hours prior to
neuraxial block.
• Remove neuraxial catheters prior to reinstitution of ther-
apy, with suggested administration 6hours after removal.
Herbal Therapy
Examples of herbal remedies that are known to affect hemostasis are garlic, ginseng, and ginkgo. These therapies are
all known to impact platelet aggregation and are therefore
relevant to our discussion [44–46]. Although there are case
reports of neuraxial bleeding following the consumption of
garlic and ginkgo, larger studies have found no difference
in bleeding after surgery among patients on herbal therapy
[47–49]. This gives insight to the ASRA recommendation
which states that herbal medications does not create a level
of risk that will interfere with the performance of neuraxial
block. Among patients on these herbal therapies, there is also
a recommendation against the discontinuation of these medications or avoidance of regional anesthesia [9]. However,
just as there are reservations against neuraxial anesthesia
in patients using dual antiplatelet or antiplatelet and anticoagulant therapy simultaneously, there is a similar discretion
regarding herbs with concurrent anticoagulation use [9].
Peripheral Nerve Blocks
Among patients who are on anticoagulants, the feared consequences of regional anesthesia via peripheral and plexus techniques are bleeding, hematoma formation, and subsequent
neurological effects. There are limited case reports and studies that have evaluated and described the complications of
peripheral nerve and plexus blocks in anticoagulated patients.
Among the data available, profound bleeding has been found
to be the critical complication, when compared to neurological decits. This may be due to bleeding occurring into xed,
noncompressible, deep spaces, at which hemorrhage contributes to patient morbidity [9, 50]. For patients taking antico-
44 Coagulation andRegional Anesthesia
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429
agulants who undergo peripheral or more supercial plexus
blocks, ASRA suggests that the similar guidelines for neuraxial techniques be used. However, for patients undergoing
deep plexus or deep peripheral blocks, it is suggested that the
anesthetic performance, catheter maintenance, and catheter
removal be based on each site and its vascularity, bleeding
consequences, and compressibility. Of note, the lack of more
specic recommendations, like those pertaining to certain
anatomical locations, serves as a reminder for the need of further studies and case reporting in this topic.
Anticoagulation inObstetric Patients
Pregnancy is a state of hypercoagulability. Factors such as
cesarean delivery, increased age, previous thromboembolism, and obesity all increase the preexisting prothrombotic
state. The 6weeks after pregnancy is also associated with
higher rates of thrombosis [51]. These characteristics may
contribute to certain patients beneting from anticoagulation. Since neuraxial anesthesia is a common effective
method of pain management during vaginal and cesarean
delivery, it is important to acknowledge neuraxial anesthetic
management in anticoagulated patients. Heparins are the
main anticoagulant used in pregnancy because they do not
affect fetal development [18, 51–53].
A systematic review of obstetric patients receiving thromboprophylactic dose of UFH or LMWH did not identify a
single case of causally related spinal epidural hematoma
(SEH) [54]. In contrast, a study involving direct oral anticoagulants during pregnancy resulted in miscarriages, fetal
anomalies, and questionable efcacy with a lack of reported
thrombotic or bleeding complication [55]. For parturients,
ASRA suggests similar recommendations regarding anesthetic management amidst heparin use, which we previously
discussed. However, in patients who are taking anticoagulants and require urgent intervention, these guidelines should
be modied as found appropriate, and the risks of general
anesthesia versus neuraxial anesthesia should be assessed
[9]. Overall, the limited data on the implications of anticoagulant use during pregnancy on neuraxial anesthesia and
epidural hematoma incidence serves as a reminder for the
need of more studies [54].
incidence in anticoagulated patients is unknown due to
underreporting [9, 56].
Spinal hematomas are asymptomatic until they begin
to compress the spinal cord, causing neurological symptoms and pain. These neurological consequences include
bladder/bowel dysfunction and most commonly motor and
sensory decits [54, 57, 58]. MRI of the spine is the most
sensitive and specic diagnostic method of spinal hematomas. If paralysis or signicant decits have not occurred,
recovery can occur with conservative management that
often includes close follow-up, frequent neurological
exams, imaging, and coagulation. There have also been
cases with spontaneous resolution of hematomas [57–62].
However, if paralysis occurs, the treatment is rapid surgical decompression of the spinal cord by laminectomy,
evacuation of the hematoma, and coagulation of the bleeding [60–62].
Conclusion
The guidelines provided by the American Society of
Regional Anesthesia and Pain Medicine are based on case
reports, clinical studies, expert opinion, hematology, pharmacological data, and recommendations from other organizations like the European Society of Anaesthesiology.
Although these guidelines are evidence-based reviews, it is
crucial to note that they should not preclude weighing the
risks and benets for each individual patient. In performing
regional anesthesia in patients on hemostasis-altering therapy, it is also important to determine their risk factors and
enhance their coagulation status. Nevertheless, these recommendations are fundamental in aiding to provide safe, quality care to patients while simultaneously decreasing the risk
of adverse events like spinal hematomas. The evidencebased guidelines discussed in this chapter are undoubtedly
advantageous, but are not infallible. It is essential to remember that there is always a need for further studies, data, and
case reporting to establish updated recommendations based
on strengthened evidence.
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in the epidural, subdural, or subarachnoid space. However,
bleeding occurs more commonly in the epidural space due to
its venous plexus. Spinal hematomas are rare, and the true
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Iron Overload
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MichaelGodbold andPatrickD.McFarland
45
Anesthetic Implications ofIron Overload
Introduction
Iron overload is dened as excessive levels of circulating
iron in the body. An estimated 16 million Americans have
some form of iron overload with hereditary hemochromatosis being the most common form of iron overload [11]. It is
estimated that 10–14% of the population are a genetic mutation carrier for some form of iron overload [14]. Iron overload affects a variety of organ systems including hepatic,
cardiac, and endocrine. The symptoms of this condition
range from changes in skin pigmentation to severe end-organ
damage including cirrhosis and heart failure. Current treatment options are highly effective at controlling circulating
iron levels. However, if left untreated, iron overload can
progress to cirrhosis and increased morbidity and mortality
associated with anesthesia.
Iron Metabolism
To understand iron overload and other disorders of iron balance, one must study how the body regulates iron metabolism. Iron metabolism is well regulated by specic proteins
and homeostatic mechanisms including the balance between
iron absorption and iron release from cells. Specic proteins
involved in regulating this balance include transferrin, ferritin, ferroportin, and hepcidin, among others. Synthesized in
the liver, transferrin is the primary protein responsible for
iron transport in plasma. The transporter protein binds two
M. Godbold
University of Tennessee Medical Center– Knoxville, Department
of Anesthesiology, Knoxville, TN, USA
P. D. McFarland (
Department of Anesthesiology, University of Tennessee Graduate
School of Medicine, Knoxville, TN, USA
e-mail: pmcfarland@utmck.edu
*)
3+
ferric (Fe
Ferritin functions as a storage protein for iron in cells. A relatively large protein, ferritin has a molecular weight of
440kDa and can store up to 4500 atoms of iron at a time [3].
Additionally, ferritin acts as an acute phase reactant and will
experience elevated levels during times of stress and inammation to protect against oxidative damage. Serum levels of
ferritin are a good surrogate measure for total body iron storage. Roughly 1ng/mL of ferritin equals 10mg of total body
iron [7]. Iron overload is characterized by an elevated ferritin
level in the absence of any confounding infection or
inammation.
Iron exportation from cells into the circulation is accomplished by ferroportin. Ferroportin allows both enterocytes
in the gut to export iron absorbed from diet and macrophages
in circulation to export iron recovered from heme resorption.
The protein hepcidin serves as the main regulator in the negative feedback mechanism ensuring normal iron balance.
Hepcidin prevents iron overload by limiting iron absorption
from diet and iron release from macrophages [13]. The protein’s activity directly correlates with serum ferritin levels; in
other words, when ferritin levels are high, hepcidin activity
is also high, and vice versa. Mutations in hepcidin gene
expression or protein dysfunction result in pathological primary iron overload states.
Normal total body iron levels are 3–4 grams with the
majority found in heme [7]. The element is also found in
iron-containing proteins, such as cytochromes and myoglobin, as well as transferrin-bound in plasma. Iron itself is
insoluble in plasma and would result in toxicity from the
generation of free radicals; however, transferrin acts to counter this effect, providing solubility to transferrin-bound iron.
As such, virtually all iron circulating in plasma is bound to
transferrin [7]. The remainder is mainly stored in the form of
ferritin in organs such as the liver and spleen. Additionally,
there are gender differences with regard to normal iron storage. Due to menstruation, adult women typically experience
lower levels of iron storage as compared to adult men.
) molecules at a time during iron trafcking [7].
© Springer Nature Switzerland AG 2021
C. S. Scher et al. (eds.), Essentials of Blood Product Management in Anesthesia Practice,
https://doi.org/10.1007/978-3-030-59295-0_45
433
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M. Godbold and P. D. McFarland
Absorption of iron occurs primarily through the gastrointestinal tract. The amount of iron absorbed varies by dietary
intake and rate of gastrointestinal absorption. Gastrointestinal
absorption is almost exclusively regulated by the protein,
hepcidin. Produced by hepatocytes and expressed by the
hepcidin antimicrobial peptide (HAMP) gene, hepcidin is
the primary mechanism for control of iron absorption
through the gastrointestinal tract. Hepcidin binds to the protein ferroportin and causes its internalization and degradation. As described above, ferroportin is the protein
responsible for the transcellular movement of iron within
the GI tract, macrophages, and hepatocytes. Inhibition of
the function of ferroportin results in loss of iron through the
GI tract and low iron states [13].
Homeostatic control of iron absorption through the gastrointestinal tract is primarily regulated through control of
hepcidin production. The primary control of hepcidin production is through iron levels and erythropoietic activity.
High levels of circulatory iron cause an increase in hepcidin
synthesis and subsequently a decrease in iron absorption.
Secondly, increased erythropoietic activity in the bone marrow will cause a decrease in production of hepcidin and
increase circulatory levels of iron. In addition to these two
primary mechanisms of control, hepcidin is also upregulated
in states of inammation, infection, and chronic kidney disease. Conversely, hepcidin is downregulated in states of
hypoxia, hereditary hemochromatosis, and hepatitis C.
Hepcidin also controls iron release from macrophages.
Through phagocytosis, macrophages will resorb heme from
broken-down red blood cells. Depending on the local concentration of hepcidin, macrophages will utilize ferroportin
to release the resorbed iron into the circulation or rely on
ferritin to store iron for later release [9].
Iron loss is not regulated as strictly as iron absorption and
release. Normal iron loss occurs at a rate of about 1–2mg/
day through processes such as sweating and gastrointestinal
excretion [7]. Through diet alone, both adult men and women
can compensate for these daily losses; however, adult women
are more prone to deciency given the additional iron losses
experienced through menstruation. Regarding possible
future pharmacological therapies, some studies have shown
the kidney may contain possible excretory pathways that
could be a drug target to combat iron overload states [2].
Signs andSymptoms ofIron Overload
Iron overload can cause a variety of clinical manifestations.
Complications can be mild, such as in skin hyperpigmentation, or major, such as in advanced end-organ failure. In
hemochromatosis, men are more likely than menstruating
women to show symptoms of iron overload due to a lack of
menses [11]. Ultimately, end-organ failure can be fatal if
enough liver or cardiac damage occurs. The severity of damage is directly related to the degree of iron overload as toxicity results from free iron deposition in organ tissues [
Typical clinical ndings are wide-ranging, depending on the
extent of organ involvement, and include:
• Nonspecic abdominal pain and generalized malaise
• Bronze pigmentation of skin
• Joint pain
• Polyuria and polydipsia secondary to diabetes mellitus
development
• Decreased libido and impotence due to hypogonadism
from pituitary and gonadal involvement
• Abnormal liver function and inammation that can progress to cirrhosis
• Palpitations, dyspnea on exertion, and peripheral edema
secondary to dysrhythmias and cardiomyopathy from cardiac tissue deposition
In the past, iron overload had been referred to as “bronze
diabetes” due to the bronzing of skin from hyperpigmentation and development of diabetes mellitus from free iron
deposition in pancreatic tissue. The lack of specicity of
early signs and symptoms often leads to a delay in diagnosis
once advanced end-organ injury has already occurred [
17].
17].
Etiologies ofIron Overload
The etiology of iron overload can be divided into two main
categories: increased iron intake and increased gastrointestinal absorption. Increased iron intake occurs primarily from
either increased dietary intake or from a need for frequent
blood transfusions. Iatrogenic increases in dietary intake
include oral iron supplementation or intravenous iron
administration. Iron overload resulting from chronic
transfusion- related medical conditions is also called transfusion-associated iron overload. In this patient population, it
is important to evaluate transfusion needs and requirements
as each unit of transfused red blood cells contains roughly
200mg of iron [17]. Transfusion-associated iron overload
commonly results from the following medical conditions:
• Sickle cell disease and other hemolytic anemias
• Myelodysplastic syndromes
• Beta-thalassemia major
• Chemotherapy, bone marrow replacement, or stem cell
transplantation
• Intrinsic RBC and hemoglobin abnormalities
Conditions resulting in increased GI absorption of iron
include hemochromatosis, ineffective erythropoiesis, and
chronic liver disease. Primary hereditary hemochromatosis
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435
is the most common form and results from a mutation in the
HFE gene resulting in decreased production of hepcidin.
Other forms of hemochromatosis include juvenile (which
results from a mutation in the hemojuvelin gene) and neonatal hemochromatosis, which is normally not compatible with
life. Anemias which result from ineffective erythropoiesis
include thalassemias, sideroblastic anemias, and other inherited anemias. Ineffective erythropoiesis results in the destruction of RBC precursors, which subsequently increases
overall erythropoietic activity, decreases hepcidin production, and increases circulatory iron.
Another way to classify iron overload is primary (genetic)
versus secondary (acquired). Any intrinsic deciency in the
normal iron regulatory pathway resulting in excess iron
burden is characterized as primary iron overload. Primary
iron overload includes rare genetic disorders, such as
hereditary hemochromatosis, hypotransferrinemia, and
aceruloplasminemia. With low levels of transferrin available
to transport iron, hypotransferrinemia results in excess iron
storage in various organs. Ceruloplasmin is involved in the
iron exportation and transportation pathway. Ceruloplasmin
works with ferroportin and transferrin to process iron during
exportation and transportation, respectively. Its absence
results in inefcient iron recycling in the liver and excess
iron accumulation. Hereditary hemochromatosis is
described above.
Any extrinsic insult resulting in excess iron burden is
characterized as secondary iron overload. Secondary iron
overload includes chronic transfusion-related medical conditions as well as increased ingestion and excess intravenous
administration of iron.
Laboratory Tests andDiagnostic Imaging
The diagnosis of iron overload is conrmed with two blood
tests, ferritin level and transferrin saturation (TSAT). As previously described, ferritin correlates directly with the total
amount of iron in the body. Elevated ferritin levels are 200–
300μg/L for men and 150–200μg/L for women. Iron overload is dened as ferritin levels greater than 1000μg/L [17].
Of note, ferritin is considered an acute phase reactant and
can be elevated in non-iron overload states. Therefore, a
transferrin saturation is also needed to conrm the diagnosis
of iron overload. Transferrin saturation is calculated as serum
iron divided by total iron-binding capacity. A normal TSAT
ranges from 20% to 50%, and iron overload is conrmed
with a TSAT greater than 50% [5].
In severe cases of iron overload, end-organ damage must
also be considered when determining necessary diagnostic
imaging. To evaluate iron content in the body, magnetic reso-
nance imaging (MRI) is recommended over computed
tomography (CT) as the latter has limited sensitivity [
Individuals with signs or symptoms of cirrhosis should have
appropriate liver function testing. Cardiac evaluation with
electrocardiogram (ECG), echocardiography (ECHO), or
even cardiac MRI is also warranted in some circumstances.
As always, clinical characteristics of the patient will dictate
further cardiac and hepatic workup.
17].
Iron Overload Complications
Complications due to iron overload are often encountered
given the difculty in recognizing the condition. Early signs
and symptoms are nonspecic, and clinical manifestations
can range from skin hyperpigmentation and joint pain to
fatal end-organ disease. The liver is iron’s primary storage
site, and hepatocytes commonly experience cell death in iron
overload states. Reactive oxygen species from toxic iron levels result in oxidative damage which can have cancer- causing
effects [5]. Additionally, hepatoportal brosis can result
from oxidative damage which can progress to cirrhosis and
even hepatocellular carcinoma [4]. Some studies have shown
patients dependent on blood transfusions can develop portal
brosis and cirrhosis within 2–10years if the disease is left
untreated [8].
Excess iron burden can also signicantly impact the myocardium. In fact, even small concentrations of free iron are
toxic to cardiac cells [17]. Often, cardiac insult occurs only
after the liver has experienced injury. The most frequent cardiac complication encountered with iron overload is congestive cardiomyopathy, although pericarditis and dysrhythmias
can occur [10]. Furthermore, in advanced disease, sudden
cardiac death has been reported [6]. Like other involved
organs, the extent of cardiac injury directly correlates with
the amount of free iron deposition in organ tissue. Studies
have shown worsened outcomes with ferritin levels greater
than 1000μg/L [12]. Again, given the lack of specicity of
early signs and symptoms, disease is often advanced once
cardiac complications occur. When iron levels reach critical
levels, systolic dysfunction eventually follows as well as the
potential rapid deterioration of clinical status.
Other organ systems can be affected as well, including the
endocrine system and the hypothalamic-pituitary-adrenal
(HPA) axis. As previously mentioned, diabetes mellitus
results from pancreatic dysfunction due to iron deposition
and subsequent oxidative damage. Also, the development of
hypocalcemia and its associated complications can occur
due to parathyroid involvement. Free iron deposition in the
pituitary gland can result in a wide array of symptoms, such
as infertility and growth failure [5].
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M. Godbold and P. D. McFarland
Perioperative Implications
In patients susceptible to chronic iron overload, one must
carefully assess the degree of end-organ involvement prior to
proceeding to the operating theatre. As always, preoperative
cardiac risk stratication and optimization of medical comorbidities should occur to guide intraoperative anesthetic
management and to minimize risk of perioperative complications. As mentioned above, the nonspecic early manifestations of iron overload necessitate vigilance in screening
at-risk patients who have yet to showcase advanced disease.
Screening is accomplished with serum ferritin and transferrin saturation levels. A long-term study of hemochromatosis
patients showed no change in survival if development of cirrhosis was avoided. Therefore, careful management of these
patients includes early diagnosis of iron overload and continued attempts to reduce iron levels and prevent the life-shortening consequence of cirrhosis [1].
When advanced end-organ injury presents, one must
assess the impact such injury will have on anesthetic management. Pharmacodynamic effects from advanced liver disease should be considered when selecting anesthetic agents
as alterations in drug metabolism and protein binding may be
observed. Additionally, altered hemostasis may result as
platelets and coagulation factors become affected. In this
patient population, a restrictive transfusion management
strategy is prudent given the nature of chronic iron overload
and the additional iron burden present in transfused blood
units as well as to limit the other associated risks of a liberal
transfusion strategy [15]. Cardiac involvement may warrant
additional testing such as electrocardiogram to assess baseline rhythm and echocardiography to assess cardiac anatomy
and systolic function. Decompensated heart failure and
unstable dysrhythmias should be managed and optimized
prior to proceeding with elective surgery.
Chronic iron overload is often treated with iron chelators
or therapeutic phlebotomy. Iron chelation therapy has specically been shown to benet patients with transfusiondependent anemia [16]. The anesthesia provider must
consider the adverse effects of these medications during the
perioperative period. Iron chelators, such as deferasirox and
deferoxamine, can affect the cytochrome P450 drugmetabolism pathway, potentially affecting perioperative dosing of anesthetic medications [18]. Also, therapeutic
phlebotomy schedules should be investigated, and appropriate cell counts assessed, to ensure adequate oxygen delivery
to organ tissues.
Summary
Iron overload is an uncommon disease process that results
in specic anesthesia-related implications. The homeo-
static regulation of iron levels in the body is achieved
through a complex process involving the liver, GI tract,
and circulating hemoglobin. This chapter reviewed the
roles that transferrin, ferritin, ferroportin, and hepcidin
have in the metabolism and regulation of iron levels.
Symptoms of iron overload vary greatly from mild abdominal pain to severe end-organ damage including liver and
cardiac failure. Because of the wide range of symptoms, a
high clinical suspicion is necessary to make the diagnosis
of iron overload. This diagnosis is achieved through two
blood tests, ferritin level and transferrin saturation (TSAT).
Further testing is focused on identifying the primary cause
of iron overload and assessing any end-organ damage if
present. Hereditary etiologies of iron overload include
hemochromatosis, hypotransferrinemia, and
aceruloplasminemia. Secondary causes of iron overload
include transfusion-associated iron overload and excessive
supplemental administration.
The anesthetic management of a patient with iron overload should focus on addressing the degree of iron overload
through laboratory testing as well as determining the cause
of iron overload. Ultimately, assessing end-organ damage
is the primary concern of the anesthesiologist. Thorough
evaluations of the hepatic, cardiac, and hematologic systems are warranted and must be completed prior to conducting an anesthetic on a patient with iron overload
syndrome.
References
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Blood Product Management
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inDeveloping Countries
KyleGress, KarinaCharipova, MitchellC.Fuller, IvanUrits,
andAlanDavidKaye
46
Introduction: Understanding theProblem
Transfusion of blood and blood products is not only critical
in life-threatening emergencies but also facilitates management of acute and chronic conditions in routine patient care
[1]. In developing countries (DGCs) such as those in subSaharan Africa, the greatest need for transfusions is in children with malaria-related anemia and women with obstetric
hemorrhage [1, 2]. These clinical scenarios are associated
with a mortality index of up to 25.5% [2]. Although the
World Health Organization (WHO) included fresh frozen
plasma, platelets, red blood cells, and whole blood on its
Model List of Essential Medicines in 2019, many DGCs lack
reliable access to these products [3].
Adequate blood product management requires a stable
supply, a standardized procedure for processing and testing,
and appropriate clinical and laboratory skills for use of products [1]. The problem faced by most DGCs can be broken
down into three basic components: insufcient supply,
excess demand, and inadequate quality of available supply.
K. Gress · K. Charipova
Georgetown Medical School, Department of Anesthesiology,
Washington, DC, USA
e-mail: klg93@georgetown.edu
M. C. Fuller (
Froedtert Hospital, Medical College of Wisconsin,
Milwaukee, WI, USA
e-mail: mfuller@mcw.edu
I. Urits
Beth Israel Deaconess Medical Center Harvard Medical School,
Boston, MA, USA
A. D. Kaye
Department of Anesthesiology and Pharmacology, Toxicology, and
Neurosciences, Louisiana State University School of MedicineShreveport, Shreveport, LA, USA
LSU Health Shreveport School of Medicine,
New Orleans, LA, USA
Tulane School of Medicine, New Orleans, LA, USA
e-mail: akaye@lsuhsc.edu
*)
This problem is further complicated by the issue of cost. It
has been shown that international organizations such as the
Red Cross cannot permanently fund blood transfusion systems and that this responsibility belongs to national authorities [4]. In sub-Saharan Africa many countries have utilized
external funding to establish national blood management
services, but few have been able to convert to reliable selfsufcient systems [1].
Compared to developed countries, DGCs lack voluntary
non-remunerated blood donors that are essential to maintaining adequate supply [5]. Due to a combination of infectionrelated apprehension and local and cultural beliefs, these
countries rely heavily on replacement donations [5, 6]. Even
so, proportions of repeat donors are low, resulting in an
unstable supply of blood and a severe lack of plasma derivatives since very few DGCs have the fractionation plants
required for their production [5]. The shortage of donors in
DGCs is compounded by unindicated transfusion and a large
volume of discarded blood [5]. Blood should be transfused
only when clinically appropriate. Unfortunately, most clinical transfusion guidelines rely on formal assessments such as
quality-assured hemoglobin measurements [1]. In places
where these services are unavailable, clinicians rely solely
on clinical judgment which, when faulty, can result in the
transfusion of a unit of blood that costs 40 times more than
an accurate hemoglobin test [1]. Despite the fact that the
majority of transfusion-related research has focused heavily
on preventing transfusion-transmitted infections rather than
addressing blood shortage, the scope for increasing supply
by reducing unnecessary transfusion is likely substantial [1].
Quality of available blood products in DGCs has beneted substantially from increased awareness of the human
immunodeciency virus (HIV), but efforts to improve testing for other transfusion-transmissible infectious agents are
still warranted [5]. Recent data have shown that transfusionassociated infection rates in sub-Saharan Africa remain
astronomically higher than those in high-income countries,
with risk of HIV, hepatitis B (HBV), and hepatitis C (HCV)
© Springer Nature Switzerland AG 2021
C. S. Scher et al. (eds.), Essentials of Blood Product Management in Anesthesia Practice,
https://doi.org/10.1007/978-3-030-59295-0_46
439
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