INTRODUCTION — Disagreements between patients and their clinicians on the choice of therapy remain a challenge in medical practice and can strain the clinician/patient relationship. Few disagreements have drawn as much attention in the medical, legal, and public spheres as the refusal of blood transfusion.
This topic discusses treatment of active bleeding in individuals who decline blood transfusion for any reason. The indications for transfusion, risks of mortality from extremely low hemoglobin levels, and strategies to minimize transfusion in the operating room are discussed separately.
●Transfusion thresholds and indications:
•Red blood cells (RBCs) – (See "Red blood cell transfusion in infants and children: Indications" and "Indications and hemoglobin thresholds for red blood cell transfusion in the adult".)
•Platelets – (See "Platelet transfusion: Indications, ordering, and associated risks", section on 'Indications for platelet transfusion'.)
•Plasma – (See "Clinical use of plasma components", section on 'Indications'.)
•White blood cells (WBCs) – (See "Granulocyte transfusions", section on 'Indications and clinical efficacy'.)
●Mortality risk from severe anemia – (See "Indications and hemoglobin thresholds for red blood cell transfusion in the adult", section on 'Impact of anemia on morbidity and mortality'.)
●Minimizing need for transfusion during surgery – (See "Perioperative blood management: Strategies to minimize transfusions" and "Techniques to reduce blood loss during abdominal or laparoscopic myomectomy".)
COMPONENTS OF SHARED DECISION MAKING
Understand patient beliefs and reasons for declining transfusion — Clinicians occasionally may encounter refusal of transfusion. Sometimes, the refusal is based solely on the perceived risk of the transfusion. Other common reasons include cultural and/or religious beliefs. These vary widely from those who express a desire not to take in someone else's "life force" to those (such as certain Native Americans) who only accept blood from "spiritual relatives."
These views highlight two important principles [1,2]:
●The need for attention to the multiple symbolic associations of blood
●The importance of practicing "cultural humility" in applying culture-based training to specific patients
The approach to understanding the wishes of each patient needs to be broad, without preconceived notions of what is appropriate in a given population [3]. Culture-based training may not provide every answer; each patient must be approached intersectionally, with the understanding that the person's illness experience lies at an unique nexus of religious, political, historical, and cultural forces, all of which may have bearing on the patient's clinical care.
Since it is impossible to generalize, it is helpful to ask patients about specific beliefs when obtaining informed consent for blood components, derivatives, or procedures involving blood. (See 'Be clear about the patient's wishes' below.)
Jehovah's Witnesses — The most well-known reason for declining blood transfusion involves Christians known as Jehovah's Witnesses (JW; Witnesses). There are at least eight million active Witnesses worldwide and over one million in North America. Witnesses are generally pacifists and are not particularly litigious [4].
Witnesses are encouraged to purchase health insurance and avail themselves of modern medical care, with the exception of certain forms of blood transfusion [4]. This aversion to transfusion stems from their interpretation of Biblical scripture (eg, Genesis 9:3,4; Leviticus 7:26,27; 1 Samuel 14:32,33; Acts 15:28,29) [5-7]. Witnesses believe that voluntarily accepting blood transfusion may affect their eternal salvation [8]. Further information about specific reasons that Witnesses do not accept blood transfusion is provided on their website [9].
For Witnesses, the differentiation between acceptable and unacceptable blood fractions may be complex, as outlined in the table (table 1). As a result, it is especially important to gain a clear understanding of the individual patient's wishes. (See 'Components of shared decision making' above.)
General examples of "typical" JW beliefs include the following:
●Devout Witnesses generally will not accept transfusions of whole blood or any of the four major components (red blood cells, platelets, plasma, and white blood cells) [4]. Most devout Witnesses are prepared to die rather than compromise this refusal.
●Devout Witnesses do not consider preoperative autologous blood donation to be an acceptable alternative, due to a belief that blood should not be taken out of the body and stored for any length of time (based on scriptures such as Deuteronomy 12:16). However, if the blood circulates back into the patient (eg, during cardiopulmonary bypass, therapeutic apheresis, or certain intraoperative and postoperative blood salvage systems), this may be acceptable to many Witnesses. (See 'Optimize preprocedure patient preparation' below and "Surgical blood conservation: Preoperative autologous blood donation".)
●Many Witnesses will accept blood plasma derivatives (typically called "subfractions" by Witnesses). This includes immunoglobulins, albumin, coagulation factor concentrates, and recombinant coagulation factors. Albumin naturally crosses the placenta between mother and fetus and is often considered acceptable. The choice is left up to individual discretion and religious conscience; some will accept certain products while others will not (table 1) [4]. An informed discussion with patients may relieve their concern regarding certain plasma derivatives.
In the past, the practice of "disfellowshipping" was applied to unrepentant Witnesses who accepted blood transfusion. However, this policy has become less stringent, since in the act of accepting transfusion itself, patients have already dissociated themselves spiritually from God.
Other reasons for declining transfusion — Patients may decline transfusion for other reasons. Examples include a fear of bloodborne disease such as HIV or a previous experience with a severe transfusion reaction [10].
A different approach should be taken if patients refuse blood for reasons other than religious or cultural beliefs:
●Concern about safety of the blood supply – An understanding of the patient's psychosocial history, along with a careful explanation of the risks and benefits of transfusion particular to their situation may resolve the fear of disease.
The safety of the blood supply is continuously improving; reviewing the present risks should calm many people's fears of life-threatening infection. These risks are summarized in the table (table 2) and discussed in detail separately. (See "Blood donor screening: Medical history" and "Blood donor screening: Laboratory testing" and "Pathogen inactivation of blood products".)
●Previous transfusion reaction – Investigation of a previous transfusion reaction may allay patient fears and provide valuable clinical information. If the patient has had a prior anaphylactic transfusion reaction due to immunoglobulin A (IgA) deficiency or another cause, prevention of future problems begins with establishing the diagnosis. (See "Immunologic transfusion reactions", section on 'Anaphylactic transfusion reactions' and "Selective IgA deficiency: Management and prognosis".)
●Desire to avoid getting blood unless "absolutely necessary" – As patients become more empowered in determining their health care, some might specify that they are only willing to receive blood when at a certain degree of extremis. Thus, they might desire to let their hemoglobin level fall farther than the typical threshold suggested in institutional or published guidelines. In such cases, the patient is not necessarily refusing transfusion as much as desiring to negotiate regarding the transfusion trigger. Many aspects of this topic review will apply to these individuals. However, they should be encouraged to sign the consent for transfusion in case it becomes necessary; they can stipulate their additional restrictions on the consent form.
●Individuals who are highly alloimmunized – Some individuals receiving chronic transfusion can become highly immunized to red blood cell (RBC) alloantigens, and it may be desirable to avoid transfusions when possible to prevent immunologic complications. (See "Transfusion in sickle cell disease: Management of complications including iron overload", section on 'Alloimmunization and hemolysis'.)
Be clear about the patient's wishes — Understanding the needs and perspectives of the individual who declines transfusion is essential to shared decision making [11]. As noted above, it is important to ask the individual about their beliefs and not to assume that all individuals identifying with certain groups (such as Jehovah's Witnesses) share the same beliefs or the same rationales for them. (See 'Understand patient beliefs and reasons for declining transfusion' above.)
There can be substantial variation among individual Witnesses regarding which blood products they will or will not accept. A chart review of obstetric patients found that among 61 self-identified Witnesses who had filled out an advance health care directive, 24 (39 percent) would accept certain blood derivatives [12]. An additional 10 percent indicated they would accept donated RBCs, suggesting that not all who identify themselves as Witnesses would decline RBC transfusion. It is not uncommon for patients who are "studying" with Witnesses to identify themselves as such, even though they have not been baptized. These observations emphasize the importance of clarifying with the patient what they mean when they say that they "do not want blood," to find out which blood "fractions" they are (or are not) willing to accept, and under what circumstances they will or will not accept them. A sample checklist for clinicians obtaining informed consent is provided in the table (table 3).
It is not uncommon to find patients who are not Witnesses who initially refuse transfusion out of respect for a family member who is a Witness. Most of these individuals will accept blood in extremis. This reinforces the need for the clinician to have a frank discussion in private about the patient's religious commitment, treatment desires, and the possible outcome of those treatment choices [13]. It also is important at subsequent hospitalizations to ask whether these wishes have changed [14].
Having these discussions with patients and their relatives or caregivers who might be present takes additional time and energy. Nevertheless, clinicians are obliged to provide the best management possible, factoring in the time required to assess the specific preferences of patients and sometimes interacting with their relatives or caregivers. This time also includes educating the patient and family regarding the various options and the possible consequences of their decisions. A thorough understanding of these issues, combined with a precise determination of the patient's wishes, will enable a clinician to outline the most appropriate treatment plan or to refer the patient to a more appropriate colleague when clinically possible.
Discuss contingency plans for life-threatening situations — Many people hold beliefs about the refusal of blood transfusion that they value more than their own lives. Nevertheless, clinicians should direct patients to examine their preferences in light of possible adverse health consequences as well as the possible increased risk of death when they refuse transfusion [15-17]. It is important to ask the patient specifically if their wishes would change in the event that refusal of transfusion is expected to be fatal, as some individuals may allow certain interventions only in such an event.
●Most patients can survive critically low levels of hemoglobin (≤5 g/dL) [15,18,19]. However, there are no clear indicators the patient will die from anemia until it is too late [20]. (See "Indications and hemoglobin thresholds for red blood cell transfusion in the adult", section on 'Impact of anemia on morbidity and mortality'.)
●A retrospective review covering 11 years of data from the Duke University Hospital Center for Blood Conservation calculated that in patients admitted with severe anemia (hemoglobin <8 g/dL) who declined transfusion, mortality increased by 55 percent for each 1 g/dL decrease in nadir hemoglobin (odds ratio [OR] 1.55) [21].
Thus, it is important to have discussions in advance.
Some individuals may be willing to accept transfusion in extremis, and this possibility should be thoroughly explored early during the patient's hospital stay, before the patient's hemoglobin declines to the point that thinking becomes clouded. This prevents the need for the clinician to "second guess" the patient's wishes. It also allows the patient to be explicit about their wishes to whomever may become their health care decision maker (proxy). In addition to a general discussion about the patient's wishes, specific questions should be asked concerning what should occur under the worst-case scenario, namely, the potential for death or morbidity (eg, stroke, myocardial infarction, renal failure) resulting from severe anemia or hypovolemic shock. These advance care directives should be clearly documented and available to all clinicians involved in the patient's care. (See 'Document well, including advance directives' below.)
For emergency care, if there is any doubt in a clinician's mind concerning the wishes of a patient or what is legally appropriate, the prudent course would be to treat according to the accepted standard of care. Once the patient is stabilized, then there will be additional time to investigate more thoroughly.
During the consent process, the clinician must make it clear that the patient will die if bleeding cannot be stopped in a reasonable amount of time and transfusions are declined. Eliminating the option of transfusion may also lead a clinician to proceed more rapidly towards a more aggressive intervention or it may lead the clinician to choose a suboptimal treatment or surgical approach. This may require discussing options that would not be the clinician's first choice if the patient were willing to accept blood products. As an example, a contingency plan may state that a hysterectomy or colectomy might be required, rather than let a patient bleed to death, if the surgeon cannot achieve sufficient hemostasis. A cesarean delivery and/or hysterectomy might be performed earlier during a difficult labor than it would be in an individual who is willing to accept transfusions when needed [22]. In rheumatology or oncology, a second tier treatment might be pursued to avoid a myelosuppressive drug [23,24]. (See 'Reports of successful outcomes' below.)
Some patients may be willing to accept blood products when a licensed physician determines that death is likely without transfusion. In reluctant patients, it may sometimes be useful to suggest an arrangement where blood will not be given unless two independent physicians agree that death is likely without transfusion. In the operative setting, the surgeon and anesthesiologist can fulfill this requirement.
Maintain patient rapport — Respecting the wishes of competent, informed patients who refuse blood transfusion demands high standards of ethics and professionalism [4,25].
Provide advocacy — It may be tempting to engage a patient refusing blood in debate regarding the appropriateness of their decision; however, this casts the clinician into an adversarial role, making it easier for the patient to discount what the clinician is saying and refuse treatments that might otherwise have been acceptable. An alternate approach involves serving as the patient's advocate, with the focus on finding the best possible therapy within the boundaries of the patient's religious beliefs and comfort zone (ie, values and preferences). Except in urgent circumstances, ample time should be set aside for the discussion of transfusion issues. In most cases, this initial discussion should occur in private, as friends or family members may influence the patient's decision [13].
Whether a person accepts a product sometimes depends on how adequately the clinician can explain it in a straightforward and nonjudgmental way. If a patient senses a misleading or condescending discussion, they may choose to reject everything to "stay safe." In these situations involving Witnesses, the JW Hospital Liaison Committee may provide useful patient education and help to establish positive communication between the patient and medical team. Other resources that may be helpful are listed below. (See 'Resources for clinicians' below.)
Minimize distress — Discussion aimed at convincing a Witness to violate personal religious beliefs may cause harm by pressuring the patient to compromise ethical values. A Witness or a family member of a Witness who unwillingly receives a transfusion may consider such transfusion a form of battery (as opposed to something affecting eternal salvation) and suffer the related emotional stress [26]. On the other hand, willing acceptance of a transfusion of blood products may result in the patient being cut off from a broad community of friends and family. In some cases, such rejection may influence the decision more than any personal belief regarding transfusion.
If at all possible, the clinician should confirm the treatment plan with the patient in private (possibly in the presence of another member of the health care team with whom the patient feels comfortable, such as the patient's nurse).
Preserve confidentiality — A Witness who receives a transfusion secretly (without the knowledge of family members, friends, or other members of the congregation) will not be investigated and is unlikely to be discovered unless they admit the fact [27]. As such, a patient may communicate a wish to receive transfusions privately. The clinician should take whatever steps are necessary to ensure complete confidentiality concerning this point, including actions to ensure privacy from family, friends, and even hospital personnel not directly caring for the patient.
An exception to strict privacy might be in the case where the patient refuses transfusion but the family desires it. In this case, the patient might be asked to share their convictions with family members to lessen the pressure on the clinical team to transfuse against patient wishes, should a family member request it [13]. Although this conversation may be initially stressful to the patient, it may reduce stress in the long run.
Document well, including advance directives — Documenting a patient's wishes concerning blood transfusion should be viewed with the same importance as documenting a patient's code status (ie, it should have the same importance as a 'do not resuscitate' [DNR] order). Either one could mean the difference between life and death if any misunderstanding is involved.
It is best if these wishes are documented in an advance care directive; Witnesses are encouraged to carry one on their person. However, standard templates for advance directives may not have sufficient information to cover the acceptance or rejection of many blood product derivatives. The attending clinician(s) should review the written directive personally with the patient and make sure that a copy is placed in the medical record along with a clinical note summarizing patient desires and clarifying anything that may not be clear. (See "Advance care planning and advance directives".)
Some hospitals include this note in the section of the electronic medical record that contains "Urgent Clinical Documents" such as advance directives and code status (resuscitation orders). Inclusion in this section of the chart ensures that the entire health care team will see it, and it may prompt them to review and update it during subsequent hospitalizations.
In many cases, there will not be any written documentation from the patient, and the clinician must discuss the risks and benefits of each blood product, subfraction, or derivative and determine what the patient is comfortable receiving (table 3). (See 'Be clear about the patient's wishes' above.)
In medical centers that are less familiar with this patient population, it may be prudent to indicate prominently that the patient has chosen not to receive certain blood products. A brief statement such as "some blood products and related procedures not acceptable per patient preference" might be kept with the documentation of a patient's allergies. This would prompt caregivers to review complete documentation that might be kept in the section of the medical record that contains "Urgent Clinical Documents." Some medical centers find it helpful to flag the front of the patient's physical chart and the patient's identification wristband with "No Blood" in cases where no blood is desired. However, it should be noted that just because the patient has a sticker on the chart or an armband that states "No Blood" does not mean that the patient will not accept certain blood fractions or procedures that manipulate blood; care should be taken so that the team does not assume that "we can’t give anything" whenever that sticker is used.
A mechanism to remind phlebotomists to draw pediatric-size tubes is also important (see 'Reduce blood draws (phlebotomy)' below). In absence of another mechanism, signs above the patient's bed and on the door may help.
The patient's clinical care team – especially nurses – must be made aware of the patient's wishes. Bedside nurses are sometimes left out of these discussions, and this may add to the potential stress from watching their patient die from severe anemia [28]. They are also typically most current on the needs and desires of their patients.
The final agreement between patient and clinician may be complex and should be recorded clearly in the medical record, including any differences in plans for a potentially life-threatening event (see 'Discuss contingency plans for life-threatening situations' above). Some hospitals provide a form specifically for this purpose to be signed by the patient. A checklist (table 3) lists items that the clinician may want to address with patients who are uncomfortable accepting blood transfusion. If there is an advance health care directive in place, then this should be amended to reflect the final agreement. The clinician may also wish to have the patient sign a copy of the clinical note outlining the final agreement.
The patient's family, caregivers, and other support providers should typically be aware of the plan unless the patient feels that his or her decisions (eg, to accept blood in extremis) should remain strictly confidential. (See 'Preserve confidentiality' above.)
In cases where declining transfusion affects a major part of the patient's treatment plan, it is helpful to involve next of kin or other power of attorney to ensure that they understand the patient's wishes and desires. As patients experience severe anemia, they often lose the mental ability to actively make decisions for themselves. A clinician may avoid misunderstandings, resentment, and confusion if this possibility is discussed early in the treatment course with the individuals who may become decision makers in the future.
It has been suggested that members of ancillary services such as pharmacists and blood bank technologists should also be made aware of the patient's wishes [14,29]. However, just as a do not resuscitate (DNR) order can be rescinded by the patient at any time, a patient can change their mind about accepting blood products at any time. In a life-threatening situation, this information is best documented and acted on at the bedside by the clinical team rather than by other individuals; otherwise, there may be a delay in obtaining or administering a life-saving product. This analogy also explains why members of the pharmacy and blood bank generally should not act as product gatekeepers, although they may assist in the patient's care (eg, by drawing smaller blood volumes for laboratory testing or ensuring that hemostatic products are provided as rapidly as possible).
THE ACTIVELY BLEEDING PATIENT
Aggressively treat bleeding — During the surgery, delivery, or other procedure, there should be meticulous attention to hemostasis and technical blood losses (eg, use of hemostatic surgical devices, fibrin glue, and tissue adhesives; controlled hypotension; elevating the surgical field above the rest of the body) [5,30-32]. The clinical team and patient must realize that, in a patient who refuses transfusion, if the bleeding cannot be stopped, the patient will die [4]. An example of the approach to trauma patients is provided separately. (See "Coagulopathy in trauma patients", section on 'Diagnosis' and "Coagulopathy in trauma patients", section on 'Treatment'.)
Anesthesiology considerations for reducing blood loss may include positioning, ventilation mode, local/regional anesthesia, deliberate hypotension or hypothermia, tourniquets as appropriate, and aggressive surgical hemostasis. Cell salvage and acute normovolemic hemodilution (ANH) may be appropriate in patients who qualify [30,33,34]. A continuous circuit may need to be maintained to make this acceptable to some Witnesses [33]. (See "Perioperative blood management: Strategies to minimize transfusions" and "Surgical blood conservation: Acute normovolemic hemodilution".)
Surgical and critical care resuscitation — If it is clear that a competent, well-informed patient declines transfusion (based on documentation or a contemporaneous discussion) and there is significant, acute blood loss, the following may be considered to optimize outcomes [14]. For the most part, these interventions are based on clinical experience with patients in various settings and extrapolated to individuals who decline transfusions. Randomized controlled trials enrolling patients at risk of death from life-threatening anemia are extremely challenging to conduct, both technically and ethically. Therefore, clinicians must rely on information from related studies accompanied by recommendations from experts with experience in the field.
●Maintain hemodynamic stability – Resuscitate as needed with intravenous fluids, pressors, and/or arterial tourniquets as appropriate. Evaluate the possible use of blood conservation techniques such as intraoperative or postoperative cell salvage or acute normovolemic hemodilution if the patient allows them. Some of these blood conservation techniques are acceptable to some Witnesses, as discussed below. (See 'Jehovah's Witnesses' above and "Surgical blood conservation: Acute normovolemic hemodilution".)
●Reduce further blood loss – Use surgical, endoscopic, and radiologic interventions to identify and treat sources of ongoing bleeding. Minimize diagnostic phlebotomy (eg, use pediatric collection tubes, avoid routine collection of multiple tubes). (See 'Minimize blood loss' below and "Surgical blood conservation: Blood salvage".)
●Assess hemostasis and correct coagulopathy – Maintain normothermia and stop medications that inhibit clotting. Obtain laboratory tests such as hemoglobin, coagulation studies such as the prothrombin time (PT), fibrinogen, and platelet count (and/or thromboelastography, if available [35]). If laboratory testing reveals a coagulopathy, additional medications and clotting factor products may be needed, as discussed in the next section. (See 'Medications and clotting factor products' below.)
Medications and clotting factor products — In addition to localized treatment at sites of bleeding, the following medications and clotting factor products may be appropriate:
●Antifibrinolytic agents - Agents such as tranexamic acid (TXA) or epsilon-aminocaproic acid (EACA) are effective in reducing bleeding, especially in mucosal sites [36-38]. Randomized trials in areas such as trauma, hemorrhagic shock, and postpartum hemorrhage have shown significant efficacy and safety in early antifibrinolytic therapy [36,39,40]. (See "Management of bleeding in patients receiving direct oral anticoagulants", section on 'Antifibrinolytics and other pro-hemostatic therapies'.)
●PCCs – Coagulation factor concentrates or recombinant factor products may be used when specific coagulation factors are deficient. These may include one or more of the following products:
•Prothrombin complex concentrates (PCCs, not activated) may be used if the levels of factor II, VII, IX, and/or X (2, 7, 9, and/or 10) are low, or if the patient is receiving an anticoagulant that interferes with these factors (eg, warfarin or a direct factor Xa inhibitor) [41]. While there may be an increased risk of thrombosis, the benefit may outweigh the risk in this population. One retrospective study found no additional risk of thrombosis but suggested that 4-factor PCC use in patients refusing blood transfusion for cardiac surgery did not result in a significant change in "baseline to seven-day postoperative hemoglobin" levels [42]. However, significant differences between the control and PCC groups make it hard to interpret these results. (See "Plasma derivatives and recombinant DNA-produced coagulation factors", section on 'PCCs'.)
•Fibrinogen concentrates or recombinant fibrinogen may be used if the plasma fibrinogen level is low. If these are not available, Cryoprecipitate may be used as a source of fibrinogen, if acceptable to the patient. Many clinicians believe that as long as the fibrinogen concentration is >100 mg/dL (1 g/L), everything is fine with their patient's hemostasis [43]. Randomized controlled trials have yet to fully assess the role of fibrinogen supplementation in critically bleeding patients; however, observational and cohort studies, a meta-analysis, and recommendations from the European Society of Anaesthesiology support our recommendation that a fibrinogen level of >200 mg/dL (2 g/L) may be a reasonable target in severely bleeding patients that cannot receive regular blood products [44-47]. (See "Disorders of fibrinogen", section on 'Fibrinogen concentrate: Dosing and monitoring' and "Disorders of fibrinogen", section on 'Cryoprecipitate and Fresh Frozen Plasma (FFP): Dosing and monitoring'.)
•Activated coagulation factors such as recombinant activated factor VII (rF7a) or activated PCCs (eg, factor eight inhibitor bypassing agent [FEIBA]) have been used to reduce hemorrhage in some individuals with bleeding who are unable to receive blood products. This use is considered off-label, and activated coagulation factor products carry a prothrombotic risk (including venous and arterial thrombosis) [48-52]. In one report of 27 consecutive liver transplants in Jehovah's Witnesses, rF7a as a single-dose infusion at the beginning of the operation was used in 13 patients to augment coagulation [30]. However, meta-analyses have shown an apparent lack of effect regarding bleeding prophylaxis in hepatobiliary surgery using rF7a [53]; an analysis of many pharmacologic interventions suggests that adequate studies have not been done [54,55]. (See "Recombinant factor VIIa: Administration and adverse effects".)
For patients with uremic platelet dysfunction or those receiving anti-platelet drugs, DDAVP and/or cryoprecipitate (if acceptable) may be considered. (See "Uremic platelet dysfunction".)
The specific choice among these pro-hemostatic products is individualized according to the severity and site of bleeding, the patient's hemostatic status (presence of coagulation or platelet dysfunction), and the availability of the product on the hospital formulary. Early involvement of the consulting specialist (eg, hematologist, intensivist, transfusion medicine specialist) is advised. For individuals with severe hepatic dysfunction, a consulting hepatologist may offer additional guidance. (See "Hemostatic abnormalities in patients with liver disease", section on 'Bleeding'.)
Anticoagulant reversal — Anticoagulation increases the severity of bleeding, and a patient who is anticoagulated, hemorrhaging, and refusing blood products is in special peril. Emergency reversal of anticoagulation (if present) is a top priority. This subject is summarized briefly below and discussed in more detail in the linked topic reviews. (See "Reversal of anticoagulation in intracranial hemorrhage", section on 'Reversal strategy for specific anticoagulants'.)
●Warfarin – Warfarin (and other vitamin K antagonists) can be rapidly reversed with a 4-factor prothrombin complex concentrate (PCC). (See "Management of warfarin-associated bleeding or supratherapeutic INR".)
●Direct oral anticoagulants (DOACs) – The DOACs have shorter half-lives than warfarin, and their anticoagulant effect will reverse more rapidly over time (although their half-lives may be prolonged in individuals with renal or hepatic insufficiency). Specific interventions to rapidly reverse their effects and/or to remove the active drugs may also be available and are discussed in detail separately. (See "Management of bleeding in patients receiving direct oral anticoagulants".)
●Heparins – Heparins have a relatively short half-life. Protamine sulfate can be used for reversal (most effective for unfractionated heparin). (See "Heparin and LMW heparin: Dosing and adverse effects", section on 'Urgent reversal (protamine)'.)
Maximize tolerance of anemia
Reduce oxygen demand — When a patient cannot oxygenate vital organs sufficiently, it may be helpful to reduce the need for oxygen (O2) using sedation and mechanical ventilation with pharmacologic paralysis. Case reports have described successful use of these procedures in Witnesses [4,56-59]. Meticulous control of fever is also critical to reduce oxygen demand.
The 1996 American Thoracic Society (ATS) statement on the detection, correction, and prevention of tissue hypoxia, which provides details of these procedures and evidence supporting their efficacy, can be accessed through the ATS website (www.thoracic.org/statements/resources/respiratory-disease-adults/tissue-hypoxia.pdf) [60].
Improve oxygen delivery — Witnesses may accept a number of forms of oxygen adjuncts to improve their oxygen-carrying capacity (table 3). Options are discussed below and may include high-dose supplemental oxygen, hyperbaric oxygen therapy, and alternative oxygen carriers. If anemia is severe, the use of a hemoglobin-based oxygen carrier (HBOC) may be an option for some patients. (See "Oxygen carriers as alternatives to red blood cell transfusion" and "Hyperbaric oxygen therapy".)
Supplemental and hyperbaric oxygen — All severely anemic patients should receive supplemental oxygen that is titrated to respiratory demand. In addition, administration of hyperbaric oxygen (ie, using a hyperbaric chamber) has been described in a number of case reports [61] and summarized in reviews [62,63]. If the patient is placed intermittently in a hyperbaric chamber, plasma itself may aid in carrying dissolved oxygen [62,64]. (See "Hyperbaric oxygen therapy".)
Extracorporeal membrane oxygenation (ECMO) has also been reported as a way to provide short-term oxygenation and cardiovascular support [65]. (See "Extracorporeal membrane oxygenation (ECMO) in adults".)
This approach is most likely to be effective as a temporizing measure in patients for whom bleeding has been stopped and erythropoietin (EPO) and iron have been administered, while waiting for a few days for these therapies to begin raising the hemoglobin level. In contrast, this approach is not a long-term solution for patients with little hope of recovering RBCs.
Blood substitutes (HBOCs) — Patients and providers often inquire about using "artificial blood" such as hemoglobin-based oxygen carriers (HBOCs) and perfluorocarbon emulsion. While HBOCs may not be equivalent in risk to RBCs in randomized trials, many have well-understood risks. If they can be obtained, some clinicians feel that the risk-benefit ratio favors HBOC use in certain individuals with severe anemia who cannot receive transfusions. (See "Oxygen carriers as alternatives to red blood cell transfusion".)
The position of Witnesses with respect to solutions containing human or animal hemoglobin leaves the decision up to the individual [66]. However, some Witnesses will not accept HBOCs, so it is critical to find out in advance if these are acceptable before pursuing them.
While HBOCs have been doggedly pursued, none has yet reached the market in the United States or Europe, despite some having a history of successful use in patients who cannot receive transfusion [67-73].
HBOC-201 (Hemopure) contains bovine hemoglobin and is not approved by the US Food and Drug Administration (FDA).
After discouraging communications from the FDA, several manufacturers abandoned attempts to obtain approval for their blood substitute products [74]. However, a 2019 review concluded that "it is imperative that we reexamine the possibility of using HBOCs when red blood cell transfusion is not an option" [75].
Reports suggest that the risk-benefit ratio changes and can favor HBOC when blood is not an option or is significantly delayed [76,77].
●An analysis from 2020 identified 41 patients treated with HBOC-201 through the expanded access program in the United States from 2014 through 2017 [78]. Ten of these individuals received more than 10 units of the HBOC for severe anemia (mean hemoglobin 3.3 g/dL; range, 1.8 to 4.4 g/dL). In nine cases, the product was used because the patient declined transfusion; the exception was an individual with sickle cell disease for whom compatible blood was not available. Administration occurred two to five days after initial presentation (within 24 hours of signing consent), with an average of 16.2 units of HBOC administered, which was estimated to replace approximately 80 percent of blood volume on average.
All 10 patients survived and were discharged from the hospital, with a mean hemoglobin at the end of treatment of 7.3 g/dL (range, 4.8 to 10 g/dL) [78]. By comparison, the mortality in similar populations not treated with an HBOC was 50 to 75 percent [76]. The authors acknowledged that the remarkable survival rate in these 10 individuals may have been biased towards being healthy enough to receive multiple doses of the product. The most common adverse events were methemoglobinemia requiring treatment with ascorbic acid and/or methylene blue, and elevated blood pressure that required antihypertensive therapy in some cases. Methemoglobinemia had no discernable adverse effects on any of the patients and did not require cessation of HBOC-201 administration. Patient skin and organs can darken or turn yellow but will return to normal once the product is cleared from the circulation.
●A multicenter randomized controlled trial showed no notable difference in mortality and serious adverse events when up to 7 units of HBOC-201 (Hemopure) was used, when compared with allogeneic RBC in non-cardiac surgery patients [79].
●The South African experience (where Hemopure is approved for use) has been positive; a comprehensive review of 336 patients receiving the product found no pattern of HBOC-attributable significant adverse events. However, 5 percent of patients experienced a transient elevation in blood pressure greater than 30 mm Hg, all resolving after reducing the infusion rate or with treatment using standard medications. There were no deaths attributed as "probably" or "definitely" linked to the product [75].
Despite lack of routine availability of HBOCs, there are several expanded access ("compassionate use") protocols that can be used to provide certain products such as HBOC-201 (Hemopure) to patients in the United States with life-threatening anemia for whom blood is not an option. These products and mechanisms to obtain them are discussed in detail separately. (See "Oxygen carriers as alternatives to red blood cell transfusion", section on 'Resources and processes for obtaining OCs in the United States'.)
OTHER INTERVENTIONS — All patients should benefit from a patient blood management (PBM) program that seeks to minimize blood loss, optimize hematopoiesis, maximize tolerance of anemia, and thus avoid unnecessary transfusions [80-84]. (See 'Importance of a hospital-wide policy to address blood product refusal' below.)
PBM programs are likely to benefit from a close and continuing consultation among hematologists, intensivists, surgeons, anesthesiologists, and transfusion medicine specialists, as well as the patient care team and the patient decision maker [30,85,86]. Some centers report that a comprehensive PBM program results in similar or better outcomes in patients who decline blood transfusion at equivalent or lower costs [87]. (See "Perioperative blood management: Strategies to minimize transfusions".)
Use of the interventions described below may entail taking risks that would not be taken in an individual willing to accept transfusion. Individuals who decline transfusion should be informed of these risks (see 'Components of shared decision making' above). However, it should also be noted that refusing transfusion does not intrinsically justify taking these risks. As an example, the use of erythropoietin (EPO) in a patient with a hemoglobin in the normal range who is preparing for a surgery with little expected blood loss and would decline blood transfusion has an unfavorable risk-to-benefit ratio, while it might be considered favorable in a patient with a low hemoglobin who is facing a procedure with the potential of significant blood loss.
Minimize blood loss — Major sources of blood loss include diagnostic phlebotomies and bleeding (surgical, traumatic, or due to a bleeding lesion).
Reduce blood draws (phlebotomy) — Studies have found mean daily phlebotomy losses in medical-surgical intensive care units (ICUs) of approximately 29 to 41 mL/day [88,89]. Practices that have been recommended to reduce these losses include decreased testing, small-volume sampling (eg, use of pediatric blood collection tubes), closed sampling circuits, and point-of-care micro-testing [14,88]. It is estimated that four times more blood is discarded after testing by laboratories than is transfused into patients [90]. As noted above, the need for pediatric collection tubes should be documented in such a way that the information is easily accessible to phlebotomists and others involved in the patient's care. (See 'Document well, including advance directives' above.)
Delaying the performance of less important procedures that may lead to bleeding (eg, peripherally inserted central catheter (PICC) placement, Swan-Ganz catheterization) is also an option.
Minimize bleeding risk — General practices directed at reducing bleeding risk include close attention to the degree of anticoagulation (if employed), correcting coagulopathy and/or treating severe thrombocytopenia (eg, platelet count <50,000/microL) if acceptable, and minimizing use of agents with antiplatelet activity (eg, aspirin, nonsteroidal antiinflammatory agents, clopidogrel).
●The use of hormonal therapy in menstruating women to reduce menstrual blood loss may also be appropriate. (See "Hormonal contraception for suppression of menstruation".)
●Surgical interventions to reduce bleeding risk may be appropriate for some individuals. Risk-benefit calculations for patients who decline blood transfusions may be different from those in patients willing to accept transfusions. In some cases, an intervention may be performed earlier in the clinical course of a patient who refuses transfusions than it would be in a patient who would accept transfusions, as a means of preventing more serious bleeding. Examples of changing treatment plans include the following:
•Some obstetricians might consider a cesarean delivery sooner in patients with abnormal labor progression. (See "Labor: Overview of normal and abnormal progression".)
•Some obstetricians might have a lower threshold for performing a hysterectomy in the presence of potentially life-threatening postpartum hemorrhage. (See "Postpartum hemorrhage: Management approaches requiring laparotomy", section on 'Role of hysterectomy'.)
•Some oncologists might choose an alternative chemotherapy regimen (or alternative dosing) that is less likely to suppress the bone marrow rather than using the treatment of choice. This might also affect specialists such as rheumatologists, nephrologists, and neurologists. (See "Causes of anemia in patients with cancer", section on 'Anemia from effects of cancer treatment'.)
Optimize red blood cell production — Production of new blood cells requires iron, folate, vitamin B12, other trace nutrients, erythropoietin (EPO), and a functioning bone marrow. Although the effects may take days to weeks to work, one or more of the following vitamins, minerals, or EPO may be given if indicated:
Iron/folic acid/vitamin B12 — For patients who are deficient in iron, folate, or vitamin B12, these should be provided. Compared with oral iron formulations, intravenous iron formulations are equally effective and have the advantage of allowing the entire dose to be delivered in one or a few infusions, shortening the time to full repletion. Folic acid and vitamin B12 can also be administered parenterally if there are any concerns about oral absorption. (See "Treatment of iron deficiency anemia in adults", section on 'Intravenous iron' and "Treatment of vitamin B12 and folate deficiencies", section on 'Treatment of vitamin B12 deficiency' and "Treatment of vitamin B12 and folate deficiencies", section on 'Treatment of folate deficiency'.)
Erythropoiesis-stimulating agents (ESAs/EPO) — Erythropoietic (EPO) levels may be low in individuals with renal insufficiency and/or chronic inflammatory states. Administration of high-dose EPO is recommended for patients who cannot receive transfusions who have normal EPO production and significant anemia, regardless of the cause [14,91,92].
The use of recombinant human erythropoietin (rhEPO) and iron is acceptable to most Witnesses. The onset of action of rhEPO is at least four to six days, provided that the patient has sufficient stores of vitamin B12, folate, and iron [82,93,94]. A full response may take up to two weeks. Thus, the use of EPO should be discussed early in treatment planning [14].
Case reports have described EPO administration as a component of successful management of individuals with severe bleeding who would not accept blood transfusions, especially in critical situations where bleeding has been stopped but the hemoglobin is very low [56,93,95-97]. While not always cost-effective in patients for whom allogeneic transfusion is an option, using rhEPO in Witnesses to increase the hemoglobin level and allow acute normovolemic hemodilution (ANH) and/or other blood conservation techniques has been viewed as a prudent measure [30,94]. (See "Surgical blood conservation: Acute normovolemic hemodilution".)
Clinicians should be aware of Boxed Warnings from the US Food and Drug Administration (FDA) regarding erythropoiesis-stimulating agents (ESAs) such as EPO and an increased risk of thrombosis and increased mortality or tumor progression in some individuals with cancer [98].
●Thrombosis risk – The concern regarding thrombosis was originally raised in individuals with chronic kidney disease for whom ESAs were used to raise the hemoglobin level into the normal or near-normal range [99]. This increased risk of thrombosis must be balanced with the risk of a patient bleeding to death during surgery or in the intensive care unit. Also, in critical situations where a patient has a low hemoglobin, the goal is to provide a safe hemoglobin level rather than to normalize the value. A safe hemoglobin level is one that will provide a buffer for potential blood loss due to recurrent bleeding (eg, menses, recurrent GI bleed) or planned surgery. This level must be determined on a case-by-case basis.
●ESA considerations in individuals with cancer – This subject is discussed separately. (See "Role of erythropoiesis-stimulating agents in the treatment of anemia in patients with cancer".)
In general, our approach to the use of ESAs agrees with the Society of Thoracic Surgeons and Society of Cardiovascular Anesthesiologists [100]. We believe it is reasonable to use preoperative rhEPO plus iron for patients undergoing elective surgery who are at high risk for postoperative anemia. A decision to use rhEPO must take into account the risk of thrombotic cardiovascular events that was demonstrated in patients with renal failure; chronic use of rhEPO is typically avoided to reduce this risk. Oral iron may be used in a preoperative setting when time permits; however, in the perioperative and intensive care setting, intravenous iron allows for a greater rate of erythropoiesis [94].
The FDA-approved dose for epoetin alfa to reduce the need for allogeneic red cell transfusion in patients undergoing elective, noncardiac, nonvascular surgery is based on the time interval before surgery [98]:
●If at least three weeks before surgery, give 600 units/kg subcutaneously once per week, for a total of four doses (the last dose is given the day of surgery). For a 70 kg patient, each dose would be approximately 40,000 units.
●If less than three weeks before surgery, give 300 units/kg subcutaneously once per day for a total of 15 daily doses, starting 10 days before surgery and continuing through post-op day 4. For a 70 kg patient, each dose would be approximately 20,000 units.
Published reports of the off-label use of ESAs in Witnesses show widely divergent dose regimens [101]. Both standardized and weight-based dosing have been used. Most clinicians administer rhEPO at least three times per week for one to two weeks, along with intravenous iron; approximately half also give vitamin B12 and folic acid. It is reasonable to round doses up to the nearest vial size (eg, 20,000 units for rhEPO) to avoid waste. Darbepoetin alfa is similar to epoetin alfa but has been modified so that it has a half-life that is three times greater; it has not been as widely used as epoetin alfa in this population.
Clinical experience with ESAs in Witnesses is illustrated in the following examples:
●A published protocol from a Korean bloodless surgery program for moderate-risk operations (<500 mL expected blood loss) used rhEPO intravenously at 200 units per kg three times per week or subcutaneous darbepoetin at 240 mcg once per week in the weeks preceding surgery, with the duration of treatment determined by the preoperative hemoglobin level [102]. In this protocol, preoperative screening tests included a complete blood count (CBC) with differential and blood smear review, iron, total iron-binding capacity (TIBC), ferritin, reticulocyte count, and total bilirubin. If there was macrocytosis (mean corpuscular volume [MCV] >95 fL), folate and vitamin B12 levels were also ordered and these vitamins replaced if deficient. If the ferritin was <200 mg/dL, iron (intravenous or oral) was administered. The authors commented that the 3 percent mortality at their institution with anemic patients undergoing bloodless surgery was far lower than that in other series, although it is not clear how much (if any) of this benefit was due to the use of ESAs.
●A "severe anemia protocol" for JW patients outlined in a 2014 document described the use of EPO and iron in individuals with symptomatic critical anemia with the hemoglobin <7 g/dL [73]. EPO (40,000 units) daily is given until the hemoglobin is >7 g/dL. Iron sucrose (100 mg) is given daily for 10 days, along with vitamin C, vitamin B12, and folate.
●A 2018 retrospective observational study in Witnesses encompassing over 10,000 admissions suggested that "low-dose" EPO (<600 units per kg per week) was not effective in shortening the duration of anemia, decreasing morbidity, or increasing survival [103]. The authors' recommendation was that if EPO is used, it should be given at doses >600 units per kg per week (eg, for a 70 kg patient, >42,000 units per week).
If bone marrow dysfunction is present, the best approach depends on the underlying disorder, which may require additional evaluations to properly diagnose. (See "Aplastic anemia: Pathogenesis, clinical manifestations, and diagnosis" and "Treatment of aplastic anemia in adults".)
Optimize preprocedure patient preparation — In addition to the blood management principles discussed above, certain preprocedure interventions may be helpful for obstetric patients and those undergoing surgery or invasive procedures. For certain procedures, it may be advisable to refer the patient to a center that routinely cares for patients who do not accept blood transfusions, especially if there is any doubt as to whether the procedure may be performed safely without blood.
Ideally, individuals who will not accept transfusion and are undergoing elective surgery with the potential for clinically significant blood loss should have testing with a CBC (and in some cases a ferritin level) approximately four to six weeks before the procedure to allow identification and treatment of iron deficiency or iron deficiency anemia prior to surgery [14,104]. (See "Causes and diagnosis of iron deficiency and iron deficiency anemia in adults" and "Treatment of iron deficiency anemia in adults".)
This model has been formulated into a useful algorithm for preoperative/preprocedural patient optimization based on the risk of significant blood loss [14,105]. However, these guidelines should not supersede the clinical judgment of the clinicians caring for the patient.
An optimization algorithm from Johns Hopkins hospital was tested prospectively on 48 patients and resulted in a median hemoglobin increase of 2.3 g/dL [106]. All patients who had surgery were alive 30 days later, and there were no thromboembolic complications associated with use of EPO.
A German hospital with frequent surgery on JWs (approximately 100 surgeries on JWs annually) retrospectively analyzed severely anemic JW surgical patients over an 11-year period and concluded that, "Given optimal management, JW patients can undergo major surgery without an excessive risk of death" [34].
A guideline for estimating bleeding risk is presented in the table (table 4) and a separate topic review. (See "Perioperative management of patients receiving anticoagulants", section on 'Estimating procedural bleeding risk'.)
Four to six weeks in advance of the procedure, patient wishes regarding transfusion are documented and appropriate blood work is drawn based on anticipated blood loss:
●Minimal risk – For minimal anticipated blood loss, obtain a CBC and proceed to the surgery/intervention if no anemia (or only minimal anemia) is present.
●Intermediate risk – For intermediate risk of clinically significant blood loss, obtain a CBC and ferritin level. If the ferritin is <100 ng/mL, give intravenous iron (eg, 1 gram of low molecular weight iron dextran or equivalent). Preprocedure erythropoietin (EPO) may be appropriate, and/or an intraoperative antifibrinolytic agent such as tranexamic acid or aminocaproic acid. (See 'Erythropoiesis-stimulating agents (ESAs/EPO)' above and 'Optimize red blood cell production' above.)
●High risk – For high risk of clinically significant blood loss, obtain a CBC and ferritin level; test for vitamin B12 deficiency if the patient history or CBC results suggest a potential deficiency. If the ferritin is <100 ng/mL, give intravenous iron. If vitamin B12 deficiency is present, give one dose of intramuscular vitamin B12 and supplement with folic acid if needed (see "Clinical manifestations and diagnosis of vitamin B12 and folate deficiency"). Preoperative EPO and/or an intraoperative antifibrinolytic agent may be appropriate.
Postoperative considerations — Postoperatively, it is appropriate to minimize the number of blood draws and the amount of blood drawn, as discussed above, as well as to provide supplemental iron if the ferritin level remains low. EPO may also be used in selected individuals who may not have received it previously and/or who have severe anemia. It is also very important that patient handoffs are timely and complete; they must include the patient wishes concerning blood, along with the treatment plan [11]. (See 'Reduce blood draws (phlebotomy)' above and "Treatment of iron deficiency anemia in adults" and 'Erythropoiesis-stimulating agents (ESAs/EPO)' above.)
Appropriate prophylaxis should be considered for venous thromboembolism (VTE) in most patients; refusal of blood transfusion is not a reason to avoid VTE prophylaxis. Conversely, however, anticoagulation or antiplatelet therapy that is inappropriate or no longer needed should be discontinued. Agents to provide prophylaxis against gastrointestinal (GI) bleeding should be used if indicated. (See "Prevention of venous thromboembolic disease in adult nonorthopedic surgical patients" and "Prevention of venous thromboembolism in adults undergoing hip fracture repair or hip or knee replacement" and "Stress ulcers in the intensive care unit: Diagnosis, management, and prevention", section on 'Prophylaxis'.)
REPORTS OF SUCCESSFUL OUTCOMES — A number of case reports have described successful outcomes in patients with serious medical and surgical conditions who were treated without transfusion, although serious risk exists:
●Surgical conditions:
•Aortic dissection, ruptured abdominal aortic aneurysm [107,108]
•Cardiothoracic surgery and/or cardiopulmonary bypass [32,109-119]
•Cardiac left ventricular assist device [120]
•Substernal goiter [121]
•Transcatheter aortic valve replacement [122,123]
•Organ transplantation (eg, liver, kidney, pancreas) [30,124-126]
•Liver resection [127]
•Trauma [67,128]
•Genitourinary/urologic surgery [70]
•Otolaryngology [129]
•Necrotizing fasciitis [130]
•Orthopedic surgery [131,132]
●Obstetric conditions [133]:
•Postpartum hemorrhage [134]
•Obstetric emergencies (eg, placenta accreta, placenta percreta, uterine rupture) [95,135-138].
•Laparoscopic hysterectomy of massive myomatous uterus [17].
•Specific interventions related to uterine fibroid surgery are discussed separately. (See "Techniques to reduce blood loss during abdominal or laparoscopic myomectomy".)
●Medical conditions:
•Gastrointestinal (GI) bleeding [139]
•Hematologic malignancies (including those requiring hematopoietic cell transplantation [HCT]) [140-148]
•Solid organ tumors [64,149,150]
•Hemorrhagic shock [72,95,151,152]
•Severe autoimmune hemolytic anemia [153,154]
•Severe iron deficiency anemia (hemoglobin 2.4 g/dL) [155]
•Thrombotic thrombocytopenic purpura (TTP) [156-159]
•Nephrology [160]
•Extracorporeal membrane oxygenation (ECMO) [161]
•Red cell aplasia (treated with a hemoglobin-based oxygen carrier) [162]
•Severe pancreatitis (treated by interventional radiology) [163]
IMPORTANCE OF A HOSPITAL-WIDE POLICY TO ADDRESS BLOOD PRODUCT REFUSAL — A hospital-wide policy for addressing refusal of blood transfusion may provide important clinical guidance, especially in an emergency situation when there may not be sufficient time to address the many complex issues that arise. The policy should address emergency situations where patient desires have not been adequately established (eg, a trauma victim presenting to an emergency department or a pediatric patient with acute life-threatening anemia) [129].
Many Jehovah's Witnesses carry "Durable Power of Attorney" documents on their person that detail their wishes (or they make their wishes known in the medical record or to a family member) [31]. However, this information may not be immediately available in an emergency situation such as a trauma, acute bleeding event, or obstetric emergency.
The clinician should follow the patient's wishes. However, if there is any doubt in a clinician's mind concerning the wishes of a patient or what is legally appropriate, the prudent course in an emergency would be to treat according to the accepted standard of care. This would be without regard to special requests of parents on behalf of their children or relatives on behalf of incapacitated adults until reliable legal documentation (as judged by the treating clinician) is available. The treating clinician also must be able to leave the patient's bedside to review any new documentation (this is sometimes not possible until after the patient is stabilized) [164,165].
Patients who refuse transfusion are not usually refusing all care, and it is incumbent on the clinicians caring for the patient to maintain respect and open communication with the patient and/or family as much as possible, even in the emergency setting [166]. It is also worthwhile to confirm from the medical record and/or the patient (if awake and coherent) that specific plans have been discussed regarding their wishes in the event of life-threatening hemorrhage and that these plans are being followed. This is discussed in more detail above. (See 'Components of shared decision making' above and 'Discuss contingency plans for life-threatening situations' above.)
ETHICAL AND LEGAL ISSUES
Competence and informed consent — Many hospitals have an ethics committee that can provide consultation and a risk management group that can give advice for legal protection; however, when dealing with an adult Jehovah's Witness who is competent to make an informed decision, involvement of these groups is rarely needed. Court cases have upheld the validity of advance directives, even when a patient later loses decisional competency due to mental illness and still refuses blood [25,167,168].
One study of South American physician attitudes found that only 128 of 564 cardiologists surveyed (23 percent) would be willing to commit to not performing blood transfusion under any circumstance for patients who refuse such transfusion [169]. Nevertheless, in most countries, the right of a competent adult to refuse consent for medical treatment is well accepted by the majority of clinicians, and a number of legal cases have dealt specifically with Witnesses. Additional legal and ethical issues related to informed consent are discussed separately. (See "Informed procedural consent".)
Children, newborns, and fetuses — Conflicts may emerge between the guardians of a child below the legal age of consent and clinicians attempting to provide the best possible medical care. As minor children cannot legally give informed consent, it is the duty of the clinician to seek legal intervention in cases where the child is placed at "clear and substantial" risk by parental decisions [170]. Candid discussion about the clinician's obligation before the law may help parents understand that the clinician may have no alternative than to transfuse in a life-threatening situation. In such situations, prompt consultation with legal specialists is recommended to clarify the laws of a particular state, province, or country.
Whenever possible, adolescents should be involved in the decision-making process. Situations may arise in which the adolescent may reject a transfusion that is acceptable to his or her guardians. In the United States, individual states have differing criteria for the age of majority (independent choice), and minor patients may be emancipated by the courts or through such events as marriage.
Specific variations regarding pediatric transfusion and the competency of children have been published in some countries:
●Japan [171]
●Great Britain [172]
●Canada [155]
In the event of an acute, life-threatening situation that requires blood transfusion, a court order is not needed to transfuse a minor child in the United States and many other countries. In some settings, a court order allowing transfusion of a minor child is obtained in anticipation of a possible need. Although transfusing the child may be legally supportable, it does not mean that a transfusion must be given. Transfusing against the will of the parents and/or child may have psychological consequences.
If a court order to allow transfusion is sought or the clinician is legally bound to provide transfusions, they should communicate in a straightforward way with both the guardian and child (if old enough) to explain the situation and the intention to transfuse. Criteria that will be used to make the decision to transfuse and the use of transfusion as a last resort should also be clearly communicated. This will be helpful to the guardian in understanding the legal reality faced when conscience forbids consenting to a transfusion and a court order is sought.
Although the courts may overrule parental decision regarding transfusion, parents still have the legal right to be informed about their child's condition and the desire to be involved in other medical decisions. The clinician should remain sensitive to the possible feelings of guilt or distress that may be present in the young patient and family, despite a court order. The health care team should not underestimate the child's awareness and concerns about receiving blood transfusion.
If a court order becomes necessary, it should not be written in a way that classifies the parents as negligent and removes the child totally from parental custody. As an example, the judge can "authorize" the treatment requested by the clinician, avoiding the harsher term "order" [4]. If transfusion is authorized by a judge, a JW family will not be considered to be acting against church teaching by allowing transfusion, since the official position of the faith on this point is that "Christians agree with laws or court actions to prevent child abuse or neglect." Additional information on this difficult subject is available on the Jehovah's Witnesses website, section on medical information for clinicians (www.jw.org/en/medical-library/).
In the case of a fetus, it has been accepted in courts that the mother has control over her own body. This suggests that she can legally refuse transfusion of herself. However, when a mother's life will likely be lost unless transfused, leaving behind a healthy newborn, the father or a designated guardian should be available to care for the child. If no parent or guardian will be available to care for the newborn after the mother's death, the question has been raised as to whether the transfusion should be given to save the life of the infant's sole caregiver. This controversial possibility must be weighed carefully by the hospital ethics committee and in the court system, which differs greatly from state to state in the United States [137]. The case of a pregnant woman carrying a fetus that needs transfusion before birth to save its life is also legally and ethically controversial and should be approached similarly.
Requests from family members — The possibility of legal entanglement from individuals other than guardians or health care decision makers may be a concern. Witnesses are not, as a group, litigious; however, other family members who are not practicing Witnesses may have strong feelings about watching a loved one die after declining blood transfusion.
If family members or friends strongly disagree with the patient's decision to accept or refuse blood products, the clinician may be asked to provide additional explanation. In such cases, it may be wise to involve the medical center's ethics committee, legal department, and risk management group to balance the need between protecting confidentiality and providing effective communication of the treatment plan and its rationale. If the patient consents to a group meeting to discuss care with all of the concerned parties, this may have the best chance of diffusing the tension [13].
The decision-making process becomes complicated when the patient is incapacitated and the health care agent must balance the needs for patient autonomy and preservation of life (beneficence). Typically, a health care agent cannot override the patient's autonomy if it is known what the patient would have wanted in a given situation and the information is documented (see 'Document well, including advance directives' above). Autonomy should be understood as simple competence, not rationality [173]. In a perfect world, a truly informed consent process would enable a clinician to know precisely what the patient would have wanted under any set of circumstances. Nevertheless, in the real world, the clinician must sometimes need to determine if the consent was given under some sort of duress (even religious pressure might count), and whether the patient had a grasp of the gravity and scope of the decision made. Either of these might move the balance from autonomy toward beneficence, allowing the clinician to honor the request of the health care agent to transfuse [174,175].
Effect on members of the treatment team — Clinicians should be prepared, insofar as it is possible, for the psychological strain that may accompany a seemingly preventable death. This may involve sorrow and/or anger over losing a patient who they feel could have been saved. In certain cases, this has been seen to lead to psychological disturbance that might have been avoided with appropriate counseling and support [4,134]. Providers must be prepared to seek emotional support, if necessary, both for themselves and other team members including nursing staff.
Hospitals that establish bloodless medicine and surgery programs should be prepared to provide support to the health care delivery team members. Although rare, despite a solid legal foundation, there may also be the stress of threatened litigation from the patient and/or family members who do not share the same views about transfusion as the patient. Respecting the wishes of competent, informed patients who refuse blood requires high standards of ethics and professionalism [4,25].
Declining to provide care — Some clinicians may not be comfortable with a patient's choices or may question their ability to care for the patient without providing transfusions [176]. In this case, the clinician may need to consider referring non-emergency patients to another competent provider. In this instance, the patient is also under an obligation to respect the conscience of the health care provider.
Withdrawal from such a case does not constitute malpractice if the clinician arranges for transfer of a non-emergency patient to another caregiver. The patient and family members, as well as the receiving clinician, should understand the reason for the transfer. Other caregivers who may be directly involved (eg, anesthesiologists, intensivists, nurses) should be aware of the patient's decision to refuse blood products, be capable of providing the alternative care necessary, and willing to accept the possible consequences.
RESOURCES FOR CLINICIANS — A number of resources are available to support the decision-making process in patients declining transfusion, including other clinicians who have had experience in similar situations.
●Transfusion medicine specialists are available for consultation at major centers, particularly those with blood conservation programs.
●Many larger cities have a Hospital Liaison Committee of Jehovah's Witnesses (JW; Witnesses) that is capable of addressing patient questions, helping clinicians to obtain pertinent medical literature, and putting them in touch with clinicians experienced in their specific situations.
A local representative may be identified using one of the following methods:
•In the United States, call (718) 560-4300
•Outside the United States, call (718) 560-4700
•Email – HIS@jw.org
•Website – www.jw.org/en/medical-library/
●A number of review articles are available that discuss management of specific clinical scenarios [4,8,11,80,102,142,177,178].
●The Society for the Advancement of Blood Management (www.sabm.org; membership required for access) and the Association for the Advancement of Blood & Biotherapies (www.aabb.org), which are not affiliated with the JW faith, provide information about patient blood management programs.
●The Network for the Advancement of Blood Management, Haemostasis, and Thrombosis (www.nataonline.com) provides information and articles from the literature.
●Englewood Health(www.englewoodhealth.org) provides information about bloodless surgery and has a referral line that offers phone consultation for physicians with their bloodless medicine providers at (888) 766-2566.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Transfusion and patient blood management".)
SUMMARY AND RECOMMENDATIONS
●Reasons for declining – Shared decision-making can ensure that the needs and wishes of the patient are considered when they decline transfusions. Jehovah's Witnesses (JW; Witnesses) avail themselves of modern medical care, with the exception of certain forms of blood transfusion. Acceptable and unacceptable blood components and purified fractions can vary among Witnesses (table 1). Less common reasons include concerns about the safety of the blood supply and previous severe transfusion reactions. (See 'Understand patient beliefs and reasons for declining transfusion' above.)
●How to discuss – Discussions should address the patient's wishes in the event of a life-threatening situation (if they would likely die without transfusion). A sample checklist is provided (table 3). The clinician should seek to understand, develop good rapport, provide non-adversarial support, serve as the patient's advocate, preserve confidentiality, and carefully document the patient's wishes. (See 'Be clear about the patient's wishes' above and 'Discuss contingency plans for life-threatening situations' above and 'Maintain patient rapport' above.)
●How to document – Patient desires concerning transfusions have the same life-or-death importance as code status. A brief statement such as "some blood products are not acceptable per patient preference" might be kept with the documentation of a patient's allergies to prompt caregivers to review complete documentation kept with "Urgent Clinical Documents." (See 'Discuss contingency plans for life-threatening situations' above and 'Document well, including advance directives' above.)
●Emergencies – In an emergency, if there is any doubt concerning the patient's wishes or legal considerations, the prudent course is to follow the accepted standard of care. However, if a competent, well-informed patient wishes not to receive transfusion, care should be focused on other lifesaving interventions. (See 'The actively bleeding patient' above and 'Reports of successful outcomes' above.)
●PBM – The principles of patient blood management (PBM) focus on reducing blood transfusion via the following areas:
•Reducing blood loss – Aggressive treatment of bleeding, meticulous surgical technique, correction of coagulopathy, attention to medications. Minimize blood loss by reducing phlebotomies (eg, using pediatric collection tubes). (See 'Aggressively treat bleeding' above and 'Minimize blood loss' above.)
•Increasing red blood cell production – Provide supplemental iron, vitamin B12, and folic acid if needed. Erythropoietin (EPO) may be used with iron in patients at high risk for postoperative anemia or those who are undergoing preoperative autologous blood donation, if acceptable to the patient. (See 'Optimize red blood cell production' above.)
•Maximizing oxygenation – Maximize tolerance of anemia by reducing oxygen demand (control fever, use sedation) and providing supplemental oxygen as needed. A "blood substitute" such as a hemoglobin-based oxygen carrier (HBOC) may be obtained via compassionate-use. (See 'Maximize tolerance of anemia' above.)
A hospital-wide policy for addressing refusal of blood transfusion may provide important guidance. (See 'Importance of a hospital-wide policy to address blood product refusal' above.)
●Elective interventions – Obstetric patients and those undergoing elective procedures may benefit from preoperative testing and possible treatment with EPO (and iron, vitamin B12, and folate if needed). Autologous cell salvage and/or acute normovolemic hemodilution (ANH) may also be used. It may be advisable to refer the patient to a center that routinely cares for patients who decline blood transfusions. (See 'Optimize preprocedure patient preparation' above.)
●Ethical considerations – A number of ethical and legal issues may arise. Minor children cannot legally give informed consent, and the clinician must seek legal intervention when a child is placed at "clear and substantial" risk by parental/caregiver decisions. In an acute life-threatening emergency, clinicians should not wait for legal intervention; they should transfuse according to standard of care. This also applies to adults for whom there is insufficient documentation to determine their preferences. A clinician may decline to provide care for a nonemergency patient who refuses blood transfusion if they arrange transfer to another caregiver. (See 'Ethical and legal issues' above.)
●Resources – Resources include transfusion medicine specialists, the Jehovah's Witness Hospital Liaison Committee, and publications from various societies. (See 'Resources for clinicians' above.)
ACKNOWLEDGMENT — The UpToDate editorial staff gratefully acknowledges the extensive contributions of Arthur J. Silvergleid, MD, to earlier versions of this and many other topic reviews.
