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Paul Banaszkiewicz Paul Banaszkiewicz Section Editor, Segment Author
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Section editor: Paul Banaszkiewicz

Segment author:Paul Banaszkiewicz

Document history: 8/7/2019

• Trauma the leading cause of death in the age group ranging between 1 and 44 years

• Among those trauma patients, major haemorrhage is responsible for 30-40% of mortality, with up to half of them dying before arrival to hospital
• With the introduction of Major Trauma Networks there has been a significant improvement in the delivery of trauma care across the UK
• Every MTC has developed a Massive Transfusion Protocol

  • Fluids for major trauma have traditionally been replaced according to the advanced trauma life support protocols.
  • ATLS guidelines have recommended the rapid administration of IV fluids. This involves giving two liters of crystalloids and continuing with packed red blood cells (PRBCs) and fresh frozen plasma (FFP) if there was transient or no response, with the aim of achieving normotension.
  • Increasingly, evidence over the last decade suggests this may be harmful, and trauma resuscitation should be more refined
  • As such hypotension resuscitation, specific early and aggressive reversal of coagulopathy using blood and products, with limited use (or avoidance) of crystalloids has become the mainstay of modern trauma fluid management.

ATLS protocol

ATLS protocols have traditionally provided a classification for haemorrhagic shock that is divided according to the amount of blood loss (Table 1)

Limitations of the protocol include clinical signs might be masked in young fit

individuals with larger physiological reserves, as well as elderly patients on medications such as beta-blockers that manipulate normal physiological responses.

Classification of haemorrhagic shock (ATLS manual American College of Surgeons)

Blood loss (mL)

Up to 750

750–1500

1500–2000

>2000

 

Blood loss (% blood volume)

Up to 15

15–30

30–40

>40

 

Pulse rate (per minute)

<100

100–120

120–140

>140

 

Blood pressure

Normal

Normal

Decreased

Decreased

Pulse pressure (mmHg)

Normal or increased

Decreased

 Decreased

Decreased

 

Respiratory rate (per minute)

14–20

20–30

30–40

>35

 

Urine output (mL/hour)

>30

20–30

 

5–15

Negligible

Central nervous system/mental status

Slightly anxious

Mildly anxious

Anxious/confused

Confused/lethargic

 

Table 1. Classification of haemorrhagic shock (ATLS manual American College of Surgeons)


New methods of shock assessment

Shock index

The shock index is the ratio of heart rate to systolic blood pressure. Birkhahn et al. proved that the shock index was a more useful tool in diagnosing early haemorrhage.

Rope

This is another method of assessment of blood loss. It involves the division of pulse rate by pulse pressure (pulse rate/systolic blood pressure –diastolic blood pressure)

A rope value of less than 3.0 was predictive of patients remaining stable while a rope value of >3.0 was predictive of patients that may go on to develop decompensated haemorrhagic shock.

Pre-hospital care

Interventions in the pre-hospital care of trauma patients has advanced in recent years. Application of pelvic binders based on the mechanism of injury has become routine. In addition the administration of tranexamic acid is becoming more widespread. More complex interventions that include pre-operative blood transfusion.

Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA)

This technique was first described during the Korean War over 50 years ago but lost momentum possibly due to sub-optimal endovascular technology, a poorly understood skill set, or anticipated ineffectiveness. Advancement in endovascular technology means that this technique is being re-evaluated in the trauma setting.

Proposed indications for REBOA include refractory hemorrhagic shock, blunt or penetrating abdominal trauma, pelvic fractures causing pelvic hemorrhage, ruptured abdominal aortic aneurysms, or the crashing trauma patient with no obvious cardiac injury on cardiac ultrasound[1]

Early identification of a patient with major haemorrhage is essential. It is vital to recognize and control haemorrhage as a matter of urgency. Junctional zones such as the groin or axilla respond to direct pressure prior to transfer to theatre for operative control. More distal sources such as a limb can be controlled with a tourniquet

Tourniquets

Two devices are in common use (1) The Combat Application Tourniquet (C-A-T) and (2) Emergency Medical Tourniquet (EMT).

Both work on a principle of applying even circumferential pressure from a hand tightened windlass mechanism.

Common indications for application are:

  • Penetrating trauma from firearms and stabbings
  • High-velocity blast injuries to the limbs
  • Injuries in rural or wilderness areas where resources are limited and transport to definitive care may be difficult or delayed
  • Industrial or farm accidents.

The aim of permissive hypotensive resuscitation is to maintain a palpable radial pulse, which translates to a systolic pressure of between 70 and 80 mmHg, until definitive surgical control

The rational is that the hypotension retains the first clot that forms, which has a better structural integrity, compared with later clot formations that become compromised by the onset of coagulopathy.

In trauma patients the onset of a coagulopathic state is thought to evolve secondary to the initial trauma further contributed by massive haemorrhage or iatrogenic causes such as excessive crystalloid administration

Lethal Triad

With severe exsanguinating haemorrhage a severe pathophysiological derangement associated with hypothermia, coagulopathhy and acidosis can occur. This is known as the lethal triad as mortality rates can reach as high as 90%.

Hypothermia

Hypothermia secondary to trauma is a common occurrence due to the inability of the body to generate heat.

This is secondary to an altered central thermoregulation, blocked shivering response and reduction of metabolic activity at the cellular level.

Resuscitation may further exacerbate hypothermia when using cold intravenous fluids, patient exposure during evaluation or laparotomies

Hypothermia exacerbates coagulopathy by affecting platelet function; the imbalance of thromboxane and prostacyclin reduces the response of platelet activation. Hypothermia also reduces the enzyme activation pathway of the coagulation cascade.

Treatment involves either passive or active measures. Passive warming involves preventing further heat loss by covering the patient and warming the operating or resuscitation room. Active warming involves use of warmed blankets, administrating warmed intravenous fluids or blood and warmed body cavity lavage. 

Metabolic Acidosis

Metabolic acidosis is due to the prolonged inadequate tissue perfusion. . This leads to a change from aerobic to anaerobic cellular metabolism and increased production of lactate. This results in a reduction in pH, which has a negative effect on cardiac contractility.

Treatment of acidosis consists of restoration of the circulation volume to maintain tissue perfusion.

Coagulopathy

Several factors contribute to a coagulopathy following trauma:

(1) Tissue damage, which leads to the exposed endothelium initiating the coagulation cascade and fibrinolysis

(2) Shock

(3) Haemodilution from the shift of cellular and interstitial fluid that is deficient in clotting factors into the plasma, and the administration of intravenous fluid, which also interrupts clot formation and the transfusion of red blood cells,

(4) Inflammation, which interferes in coagulation as it causes monocytes to adhere to platelets, activation of the thrombomodulin-protein C pathway, and the binding of C4b to protein S

(5) Hypothermia

(6) Acidosis

Major haemorrhage is defined as the loss of 100% of total blood volume within 24 hours, loss of 50% within four hours, or the loss of 150mL per minute.

Massive transfusion is defined as transfusion of more than ten units of packed red cells over 24 hours or four units within one hour.

The early administration of fresh frozen plasma and platelets helps to reduce the overall requirement for packed red cell transfusion

There has been a more in recent years towards restricted fluid resuscitation rather than standard fluid resuscitation.

Duke et al[2] reported on a retrospective analysis of 307 patients admitted to a level 1 trauma centre with penetrating torso injuries and a systolic blood pressure of less than 90mmHg who were managed by damage controlled resuscitation and surgery.One group received standard fluid resuscitation(SFR) the other group restricted fluid resuscitation(RFR).The SFR group had a higher intraoperative mortality(32% versus 9%) and  overall mortality rate (37% versus 21%).The higher mortality was attributed to the effect of a large volume of fluid in diluting clotting factors and reducing blood viscosity and the increased blood pressure.RFR was beneficial in that it provided patients with permissive hypotension(systolic blood pressure of 90)until damage control surgery was achieved.

Massive transfusion protocol

The activation criteria for every MTC varies slightly but in general is based on markers of haemodynamic hypovolaemic shock

Antifibrinolytics

The use of tranexamic acid to reduce the amount of bleeding in trauma patients is now well established

The crash 2 study was a randomized prospective multicentre control trial performed in 274 hospitals in 40 countries involving 20,211 patients[3].

Patients were randomized to being given tranexamic acid (TXA) or placebo.

The effect of TXA on death, thromboembolic events and blood transfusion requirements in trauma patients was recorded.

 Administration of TXA was in two doses; 1 g over 1 hour and a further 1 g infused over 8 hours. The data showed that the administration of TXA was a time-critical intervention. Data from the group treated within one hour showed the most dramatic benefit, with the risk of death reduced from 7.7% to 5.3% in the treated group[4].

The study found that traexamic acid reduced the risk of death in trauma patients. Most benefit was seen in the group sustaining penetrative trauma.

No increase in thromboembolic events were noted and the risk of adverse events was low. As such the recommendation was that TXA be administered to all severely traumatized patients who have a significant bleeding risk.

 Damage control orthopaedics

The concept of damage control orthopaedics evolved from its use in abdominal surgery. A systematic 3-phase approach was used to disrupt the lethal cascade of events that lead to death by exsanguination.

Phase 1 involved immediate laparotomy to control haemorrhage and contamination. Phase 2 was resuscitation in the ITU with improvement of haemodynamic parameters, correction of coagulation defects and rewarming. Phase 3 consisted of re-operation, removal of abdominal packs, definite repair of abdominal injuries and closure.

This was extended to orthopaedic practice.

Guidelines

The American society of anesthesiologist gave the following evidence based guidelines for blood transfusion in 2006:

  1. A close watch on assessment of blood loss during surgery and assessment of tissue perfusion is to be maintained.
  2. Transfusion is rarely indicated when the haemoglobin concentration is greater than 10 gm/dl, and is almost always indicated when it is less than 6 gm/dl.
  3. For intermediate haemoglobin concentrations (6–10 gm/dl), justifying or requiring RBC transfusion should be based on the patient's risk for complications of inadequate oxygenation.
  4. Use of a single haemoglobin “trigger” for all patients and other approaches that fail to consider all important physiologic and surgical factors affecting oxygenation are not recommended.
  5. When appropriate, preoperative autologous blood donation, intraoperative and postoperative blood recovery, acute normovolemic hemodilution and measures to decrease blood loss (deliberate hypotension and pharmacologic agents) may be beneficial.
  6. The indications for transfusion of autologous RBCs may be more liberal than for allogeneic RBCs because of the lower (but still significant) risks associated with the former.

It is essential to ask “Is blood transfusion necessary in this patient?”

If so, ensure:

Right blood

Right patient

Right time

Right place.

 There is a 10 commandments guide for blood transfusion published in the NHS Blood and Transplant booklet that recommends

  1. Transfusion should only be used when the benefits outweigh the risks and there are no appropriate alternatives.
  2. Results of laboratory tests are not the sole deciding factor for transfusion.
  3. Transfusion decisions should be based on clinical assessment underpinned by evidence-based clinical guidelines.
  4. Not all anaemic patients need transfusion (there is no universal ‘transfusion trigger’).
  5. Discuss the risks, benefits and alternatives to transfusion with the patient and gain their consent.
  6. The reason for transfusion should be documented in the patient’s clinical record.
  7. Timely provision of blood component support in major haemorrhage can improve outcome – good communication and teamwork are essential.
  8. Failure to check patient identity can be fatal. Patients must wear an ID band (or equivalent) with name, date of birth and unique ID number. Confirm identity at every stage of the transfusion process. Patient identifiers on the ID band and blood pack must be identical. Any discrepancy, DO NOT TRANSFUSE.
  9. The patient must be monitored during the transfusion.
  10. Education and training underpin safe transfusion practice.

Blood transfusion is not free from potential complications.

Known viral infection risks include HIV, HBV and HCV and the list of blood borne infections includes syphilis, malaria, coagulase negative Staphylococcus and Yersinia.Although not a true pathogen transmission of Creutzfeldt Jakob disease is also a possible complication

The list of immunological complications include febrile reaction, allergic reaction, direct immune haemolytic reaction, transfusion related acute lung injury and immunomodulation.

The ABO system

There are four main blood groups: A, B, AB and O.

Individuals of blood group O are known as universal donors as their red cells have no A or B antigens. However, their plasma does contain anti-A and anti-B that, if present in high titre, has the potential to haemolyse the red cells of certain non-group O recipients

Transfusion reaction due to ABO incompatibility

Anti-A and/or anti-B in the recipient’s plasma binds to the transfused cells and activates the complement pathway, leading to destruction of the transfused red cells (intravascular haemolysis) and the release of inflammatory cytokines that can cause shock, renal failure and disseminated intravascular coagulation (DIC).

The accidental transfusion of ABO-incompatible blood is now classified as a ‘never event’ by the UK Departments of Health

Blood group

 

Antigens on red cells

Antigens in plasma

UK blood donors

O

 

None

anti-A and anti-B

 

A

 

A

anti-B

 

B

 

B

anti-A

 

AB

 

A and B

None

 

Table 2. Distribution of blood group and antibodies


The Rh System

  • There are five main Rh antigens on red cells for which individuals can be positive or negative: C/c, D and E/e.
  • RhD is the most important with around 85% of white Northern Europeans being RhD positive, rising to virtually 100% of people of Chinese origin.
  • Antibodies to RhD (anti-D) are only present in RhD negative individuals who have been transfused with RhD positive red cells or in RhD negative women who have been pregnant with an RhD positive baby.
  • IgG anti-D antibodies can cause acute or delayed haemolytic transfusion reactions when RhD positive red cells are transfused and may cause haemolytic disease of the fetus and newborn.
  • It is important to avoid exposing RhD negative girls and women of childbearing potential to RhD positive red cell transfusions except in extreme emergencies when no other group is immediately available.

Recombinant erythropoietin

This is a hormone synthesized by recombinant DNA technology that mimics the human hematopoietic hormone erythropoietin.

It is mainly used for treating anemia due to chronic renal failure and that occurs during cancer chemotherapy.

Its use is now extended to improve the preoperative hemoglobin in elective orthopedic surgeries. Instead of postoperative transfusion or preoperative autologous blood donation, this hormone directly improves the hemoglobin of the patient

It is anticipated with its use the need for blood transfusion can be reduced

Platelets

  • Platelets are used in the perioperative setting, when a quantitative or qualitative platelet defect is the suspected cause of bleeding
  • Prophylactic platelet transfusion is ineffective and rarely indicated when thrombocytopenia is due to increased platelet destruction (e.g. idiopathic thrombocytopenic purpura)
  • Prophylactic platelet transfusion is rarely indicated in surgical patients with thrombocytopenia due to decreased platelet production when the platelet count > 100 and is usually indicated when the count is <50. The determination of whether patients with intermediate platelet counts (50-100) require therapy should be based on the risk of bleeding.
  • Surgical patients with microvascular bleeding usually require platelet transfusion if the platelet count is < 50 and rarely require therapy if it is >100. With intermediate platelet counts (50–100), the determination should be based on the patient's risk for more significant bleeding, type of surgery and site of operation, e.g. closed space like brain or eye.
  • Platelet transfusion may be indicated despite an apparently adequate platelet count if there is known platelet dysfunction and microvascular bleeding

Fresh frozen plasma

Recommendations for use of FFP include:

  • Urgent reversal of warfarin therapy
  • Correction of known coagulation factor deficiencies for which specific concentrates are unavailable
  • Correction of microvascular bleeding in the presence of elevated (>1.5-times normal) prothrombin time (PT) or partial thromboplastin time (PTT)
  • Correction of microvascular bleeding secondary to coagulation factor deficiency in patients transfused with more than one blood volume and when PT and PTT cannot be obtained in a timely fashion 

Cryoprecipitate

Cryoprecipitate, which contains factor VIII, fibrinogen, fibronectin, von Willebrand's factor (vWF) and factor XIII, is used for the correction of inherited and acquired coagulopathies.

Recommendations for the use of Cryoprecipitate include:

  • Prophylaxis in non bleeding perioperative or peripartum patients with congenital fibrinogen deficiencies or von Willebrand's disease unresponsive to 1-desamino-8-D-arginine vasopressin (DDAVP).
  • Bleeding patients with von Willebrand's disease
  • Correction of microvascular bleeding in massively transfused patients with fibrinogen concentrations less than 80–100 mg/d

Autologous blood transfusion (collection and reinfusion of the patients own red blood cells)[5]

Predeposit autologous donation (PAD)

Background

  • This is the banking of red cell units from a patient before planned surgery.
  • PAD was developed due to concerns regarding viral transmission by donor blood, especially the HIV epidemic of the early 1980s
  • With a red cell storage-life of 35 days at 4°C, most healthy adult patients can donate up to three red cell units before elective surgery. 
  • Patients may be given iron supplements, sometimes with erythropoietin, to prevent anaemia or allow more donations to be collected.
  • Donations for PAD must be performed in a licensed blood establishment, rather than a routine hospital setting.
  • Donations must be processed and tested in the same way as donor blood and are subject to the same requirements for traceability.

Recommendations

  • Given the current remote risk of viral transfusion-transmitted infection by donor blood in developed countries, the rationale, safety and cost-effectiveness of routine PAD has been severely questioned
  • The procedure is now rarely performed in the UK

Indications

The BCSH (British Committee for standards in haematology) guideline on PAD only recommends its use in ‘exceptional circumstances’, such as:

  • Patients with rare blood groups or multiple blood group antibodies where compatible allogeneic (donor) blood is difficult to obtain.
  • Patients at serious psychiatric risk because of anxiety about exposure to donor blood.
  • Patients who refuse to consent to donor blood transfusion but will accept PAD.
  • Children undergoing scoliosis surgery (in practice, most specialist units now use other blood conservation measures).

PAD should only be considered in surgery with a significant likelihood of requiring transfusion, operation dates must be guaranteed and the patient’s ability to donate safely must be assessed by a ‘competent clinician’, usually a transfusion medicine specialist.

Definition

This is the collection and reinfusion of blood spilled during surgery.

Equipment

Commercially available, largely automated devices are available for ICS and are widely used in hospitals for both elective and emergency surgery with significant blood loss and in the management of major traumatic or obstetric haemorrhage.

The machines must always be used and maintained according to the manufacturer’s instructions by appropriately trained staff.

A 2010 Cochrane Collaboration review of randomised trials of ICS, mainly in cardiac and orthopaedic surgery, showed a 20% reduction in donor blood exposure (an average saving of 0.7 units per patient).

For further information about clinical indications and use of ICS please refer to the UK Cell Salvage Action Group (UKCSAG) website (http://www.transfusionguidelines.org.uk/Index.aspx? Publication=BBT&Section=22&pageid=7507).

Protocol

Blood lost into the surgical field is filtered to remove particulate matter and aspirated into a collection reservoir where it is anticoagulated with heparin or citrate. 

If sufficient blood is collected and the patient loses sufficient blood to require transfusion, the salvaged blood can be centrifuged and washed in a closed, automated system.

Red cells suspended in sterile saline solution are produced, which must be transfused to the patient within 4 hours of processing.

The reinfusion bag should be labelled in the operating theatre

The transfusion should be prescribed, documented and the patient monitored in the same way as for any transfusion.

Patients undergoing elective procedures where ICS may be used should give informed consent after provision of relevant information.

Indications for ICS in adults and children

These include:

  • Surgery where the anticipated blood loss is >20% of the patient’s estimated blood volume.
  • Elective or emergency surgery in patients with risk factors for bleeding (including high-risk Caesarean section) or low preoperative Hb concentration.
  • Major haemorrhage.
  • Patients with rare blood groups or multiple blood group antibodies for whom it may be difficult to provide donor blood.
  • Patients who do not accept donor blood transfusions but are prepared to accept, and consent to, ICS (this includes most Jehovah’s Witnesses).

Contra-indications

  • ICS should not be used when bowel contents contaminate the operation site and blood should not be aspirated from bacterially infected surgical fields.
  • Due to concerns about cancer cell reinfusion and spread, manufacturers do not recommend ICS in patients having surgery for malignant disease. However, extensive clinical experience suggests this is not a significant risk although it is recommended to reinfuse the red cells through a leucodepletion filter.

Obstetric use

  • ICS is widely used in women at high risk of postpartum haemorrhage during Caesarean section and in the management of major obstetric haemorrhage
  • PCS is mainly used in orthopaedic procedures, especially after knee or hip replacement and in correction of scoliosis.
  • Blood is collected from wound drains and then either filtered or washed in an automated system before reinfusion to the patient.
  • The simple filtration systems for reinfusion of unwashed red cells are mainly used when expected blood losses are between 500 and 1000 mL. With these infusion volumes concerns about adverse effects on blood coagulation have not been confirmed in routine practice.
  • Clinical staff must be trained and competency assessed to use the device, accurately document the collection and label the pack at the bedside.
  • Collection of salvaged blood must be completed within the manufacturer’s specified time (usually 6 hours) and the reinfusion must be monitored and documented in the same way as donor transfusions.
  • PCS is relatively cheap, has the potential to reduce exposure to donor blood and is acceptable to most Jehovah’s Witnesses.
  • In ANH several units of blood are collected into standard blood donation packs immediately before surgery (usually in the operating room) and the patient’s blood volume is maintained by the simultaneous infusion of crystalloid or colloid fluids.
  • The blood is stored in the operating theatre at room temperature and reinfused at the end of surgery or if significant bleeding occurs.
  • ANH is most often used in cardiac bypass surgery where the immediate postoperative transfusion of ‘fresh whole blood’ containing platelets and clotting factors is seen as an advantage.
  • Reported hazards of ANH include fluid overload, cardiac ischemia and wrong blood into patient errors.

The denomination of Jehovah’s Witnesses was founded as a Bible study group in the USA in 1869 by the American Charles Taze Russell. The number of members is growing; Denmark has about 14,000 Jehovah’s Witnesses, while there are over 7 million globally.

Members of this religion do not accept blood transfusions, a stand based on passages from the Bible, such as this from Leviticus: (xvii) "As for any man who eats any sort of blood, I shall certainly set my face against the soul that is eating the blood, and I shall indeed cut him off from among his people."

Blood transfusion is interpreted as the eating of blood, and Jehovah's Witnesses believe that all hope of eternal life will be lost if transfusion is accepted[6].

The ban against transfusion includes whole blood as well as its components, erythrocytes, white blood cells, platelets and plasma. However, there is some variation within the religious group, with some members accepting components such as albumin, recombinant human erythropoietin and immunoglobulin. This must be discussed with each individual patient in order to apply his/her personal choice[7].

Autologous transfusion of packed red blood cells is not accepted by Jehovah’s Witnesses, as this blood has been removed from the body. Strategies involving a cell saver, in which a patient’s own blood is continuously infused while it is collected and, therefore, stays in contact with the patient’s vascular system, are accepted by some Jehovah’s Witnesses

These restrictions present ethical and clinical challenges to surgeons who look after seriously injured Jehovah’s Witnesses and have prompt a search for alternatives to blood.

The situation in which a patient refuses a treatment and could die in a potentially “treatable” situation creates an ethical dilemma for the health care professional.

However, when a patient makes an informed choice, the health care professional must respect the patient’s wish. Not adhering to a known refusal puts the health care professional at risk of legal prosecution.

 Management of a low Hb in Jehovahs witness patient

Strategies to manage a significantly low haemoglobin include

  • Sedation and paralysis to decrease metabolism
  • Mechanical ventilation with a high oxygen fraction to maximise oxygen uptake
  • Asinotropes/vasopressors to support the circulation
  • Antifibrinolytics and minimisation of “routine” blood sampling

The patient usually requires admission to ITU

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Further Reading

  • 1. Joint United Kingdom (UK) Blood Transfusion and Tissue Transplantation Services Professional Advisory Committee http://www.transfusionguidelines.org/red-book/latest-updates. This is comprehensive website that deals with blood transfusion practices and guidelines in the UK.It is well written, informative, regularly updated and has a specific section on the devoted to the red transfusion handbook.

References

  • 1. Stannard, A., J.L. Eliason, and T.E. Rasmussen, Resuscitative endovascular balloon occlusion of the aorta (REBOA) as an adjunct for hemorrhagic shock. Journal of Trauma and Acute Care Surgery, 2011. 71(6): p. 1869-1872.
  • 2. Duke, M.D., et al., Restrictive fluid resuscitation in combination with damage control resuscitation: time for adaptation. Journal of Trauma and Acute Care Surgery, 2012. 73(3): p. 674-678.
  • 3. Collaborators, C.The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised controlled trial. The Lancet, 2011. 377(9771): p. 1096-1101. e2.
  • 4. Brousil, J., D. Forward, and C. Moran, (ii) Resuscitation of the adult trauma victim. Orthopaedics and Trauma, 2015. 29(6): p. 350-358.
  • 5. Joint United Kingdom (UK) Blood Transfusion and Tissue Transplantation Services Professional Advisory Committee; Available from: http://www.transfusionguidelines.org/transfusion-handbook/6-alternatives-and-adjuncts-to-blood-transfusion/6-1-autologous-blood-transfusion-collection-and-reinfusion-of-the-patient-s-own-red-blood-cells.
  • 6. Busuttil, D. and A. Copplestone, Management of blood loss in Jehovah's Witnesses. BMJ: British Medical Journal, 1995. 311(7013): p. 1115.
  • 7. Lorentzen, K., B. Kjær, and J. Jørgensen, Supportive treatment of severe anaemia in a Jehovah's Witness with severe trauma. Blood Transfus, 2013. 11(3): p. 452-453.