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Acute Exceptional Blood Loss Anemia

Acute Exceptional Blood Loss Anemia

Acute Exceptional Blood Loss Anemia


Treatment Protocol Guidelines

The following hyperbaric medicine treatment protocol is based upon the recommendations of the Hyperbaric Oxygen Committee of the Undersea and Hyperbaric Medical Society.  Clinical protocols and/or practice guidelines are systematically developed statements that help physicians, other practitioners, case managers and clients make decisions about appropriate health care for specific clinical circumstances.  

Protocols allow health providers to offer evidence-based, appropriate, standardized diagnostic treatment and care services to patients undergoing hyperbaric oxygen therapy (HBOT). Evidenced-based medicine offers clinicians a way to achieve improved quality, improved patient satisfaction, and reduced costs. This topic covers exceptional blood loss anemias and HBOT. Utilization Review should be initiated when clinical decisions result in deviation from or modification of treatment protocols. This includes any course of treatment at or above the recognized threshold limits. 

Medical Necessity

Medicare.gov defines “medically necessary” as “health-care services or supplies needed to prevent, diagnose, or treat an illness, injury, condition, disease, or its symptoms and that meet accepted standards of medicine.” 

The following condition is NOT a covered indication per the National Coverage Determination (NCD) 20.29. [1] This medical condition shall not be treated adjunctively or primarily by HBOT for reimbursement by the Medicare program as data supporting its use has not been established as medically beneficial. Services deemed treatment for these primary conditions will be denied as Not Reasonable and Necessary.  Some private insurers do cover exceptional blood loss anemias and must be approached on a case by case basis. That said, this is an unusual indication and rarely seen in hyperbaric chambers.  


 Sample Physician Order   | $ ICD-10 Crosswalk  |   Treatment Table   Emergent / Urgent Indication 

  • Patients who have marked blood loss of red blood cell mass by hemorrhage, hemolysis, or aplasia run the risk of lacking adequate oxygen carrying capacity by blood. The more quickly the patient develops anemia, the less tolerant the body is of that insult.[2] Patients may not be able to be transfused for a variety of reasons. Common reasons include refusal of transfusion based on religious beliefs or inability to crossmatch blood for transfusion.
  • The arterial oxygen content primarily relies on hemoglobin concentration, with each gram of hemoglobin able to carry 1.38 ml of oxygen.[2]A small portion of oxygen in the arteries is dissolved in plasma, based on the blood's partial pressure of oxygen (PaO2). The equation for arterial oxygen content is:
      • CaO2= (Hemoglobin concentration x 1.38 ml O2 x %oxygen saturation) + (0.003 x PaO2).
  • In 1959, Dutch surgeon Boerema studied hyperbaric oxygen therapy (HBO) for treating anemia.[3] He drained blood from healthy piglets and replaced it with a plasma-like solution, resulting in a critically low hemoglobin level of 0.4 g/dL. Despite this, when placed in a hyperbaric chamber at 3 atmospheres absolute (ATA) for 45 minutes, the piglets survived. This indicated that under hyperbaric conditions, plasma can hold significantly more oxygen than in standard conditions, as dictated by Henry’s Law. Breathing 100% oxygen under hyperbaric conditions can lead to a PaO2 of over 2000 mmHg. Thus, at 3 ATA, the oxygen in plasma can suffice for the body's oxygen needs.[2]
  • Goals of HBOT
    • Serve as a bridge therapy to allow proper oxygen delivery when hemoglobin drops to critical levels, until underlying pathology is corrected, and/or RBC transfusion becomes available 
    • In subacutely or chronically anemic patients, induce an increase in red blood cell mass [4]
    • We know from early hyperbaric medicine studies that life can be sustained in a hyperbaric chamber without blood  [5] 
    • We also know from basic physiology that the body's end-organs withdraw 5 - 6 volumes percent of oxygen from the blood in order to maintain normal function. 
    • At 3 ATA, breathing 100% oxygenation, there is 6.8 volumes percent oxygen in plasma (assuming normal lung function. 
    • Therefore, life can be theoretically sustained with very low concentrations of hemoglobin (as a lifesaving measure). 
    • The primary pathophysiology in these cases is end-organ oxygen debt.


    A severe drop in red blood cells (RBC) quantity through exsanguination, surgical bleeding, hemolysis, faulty red cell production, or severe RBC functional loss of oxygen-carrying capacity.

    Hyperbaric Criteria

    • Acute onset blood loss anemia, when RBC transfusion is indicated, but not possible (due to patient refusal of transfusion or unavailability of red blood cells for transfusion) [6]
    • Blood loss must be controlled 


    • Comprehensive history (past bleeding, hemolysis or inadequate production)
    • Physical examination
    • Labs: draw or review 
      • Complete Blood Count (CBC), Mean Corpuscular Value (MCV), reticulocyte count   Indent these one level
      • Serum B12, serum folate
      • Electrolytes, urinalysis
      • Arterial Blood Gas (ABG)
    • Chest x-ray: order or review, if indicated
    • Electrocardiogram (ECG)


    • In this diagnosis, hyperbaric oxygen is delivered in a "pulsed" basis. That is, hyperbaric oxygen is delivered at whatever pressure (between 2.0 and 3.0 ATA) that relieves end-organ failure.
    • 2.0 ATA for 90 minutes of oxygen breathing (Table 1)
    • Consider increasing to 2.5-3.0 ATA with air breaks for periods of 3 to 4 hours in cases of persistent end-organ failure.
    • 3 to 4 treatments should be given in 24 hours. The frequency of subsequent hyperbaric treatments should be tailored to the patient's clinical status. 
    • Titrate surface interval (SI) to avert symptoms associated with reoccurring oxygen debt. SI may be lengthened with hematinics (i.e., erythropoietin).
    • Recognize that pulmonary function (due to oxygen toxicity) will rapidly deteriorate the longer patients are exposed to higher ATA pressures of 100% oxygen breathing. This is a tight line in order to preserve life and organ function without permanently damaging the lung tissues.
    • Administer hematinics (i.e., erythropoietin) along with nutritional support to correct protein-energy malnutrition
    • Reinstitute HBOT to treat signs and symptoms of tissue hypoxia and end-organ dysfunction, which may include:
      1. altered mental status
      2. ischemic EKG change
      3. tachycardia & hypotension
      4. ischemic brain syndrome
      5. sprue-like diarrhea from ischemic bowel (chronic diarrhea with substantial weight loss)
      6. diminished urinary output
      7. elevated lactate
      8. metabolic acidosis
      9. abnormal cardiac enzymes
    • HBOT should be tapered to time and frequency of treatment until RBC's have been replaced adequately by patient regeneration or patient accepts transfusion. It is important not to over-treat due to the risk of pulmonary oxygen toxicity.
    • These patients are typically in an inpatient setting receiving critical care; blood pressure (arterial line), central pressures (Swan Ganz), ECG, and urinary output may be monitored as directed
    Treatment Threshold
    Until satisfactory levels of hemoglobin & hematocrit (hematocrit >20%) are reached, patient stable/asymptomatic, or transfusion becomes possible.[7] We suggest internal utilization review/peer review after 20 treatments. External peer review should occur at 30 treatments.
    Refer to the ICD-10 Guideline for the appropriate ICD-10 code
    • A hyperbaric treatment is equivalent in wholesale cost to a unit of packed red blood cells in the Western world.
    • If diabetes mellitus, blood glucose should be checked within an hour prior to treatment and immediately post-HBOT. 
    • This indication is not covered by Medicare but may be covered by commercial carriers. Medicare patients must sign an Advanced Beneficiary Notice (ABN) to receive HBOT.
    Primary Sources: Whelan and Kindwall [8]Weaver [9][10]  



    "Mary P. is a 35 y/o woman who was involved in a motor vehicle accident this morning. She has massive internal bleeding from multiple sites. The surgeons were able to find the bleeders and stop the bleeding, but Mary's hemoglobin level is dangerously low a 2.5 gm/dL. On multiple occasions, she has refused blood transfusion during this admission, knowing that she might die from this decision. She still refuses.

    Her EKG shows evidence of global ischemia; her urine output was 5cc in the past hour with hematuria; and her sensorium is waxing and waning. These symptoms are common with massive blood loss. She wishes to have hematinics administered and she is willing to be placed into a hyperbaric chamber with hopes of reversing the ischemia due to lack of red blood cells."

    Physical Exam

    A severe drop in red blood cells (RBC) quantity through exsanguination, surgical bleeding, hemolysis, faulty red cell production, or severe RBC functional loss of oxygen-carrying capacity may result in: 
    • altered mental status
    • ischemic EKG change
    • tachycardia & hypotension
    • ischemic brain syndrome
    • sprue-like diarrhea from ischemic bowel (chronic diarrhea with substantial weight loss)
    • diminished urinary output
    • elevated lactate
    • metabolic acidosis
    • abnormal cardiac enzymes


    • Acute Exceptional Blood Loss Anemia: Refer to ICD-10 Crosswalk 

    Indication for Hyperbaric Oxygen Therapy (HBOT)

    Patients who have marked blood loss of red blood cell mass by hemorrhage, hemolysis, or aplasia run the risk of lacking adequate oxygen-carrying capacity by blood. The more quickly the patient develops the anemia, the less tolerant the body is of that insult.Patients may not be able to be transfused for a variety of reasons. Common reasons include refusal of transfusion on religious grounds or inability to crossmatch blood for transfusion. 

    Blood substitutes are still undergoing randomized clinical trials. No blood substitute is currently recommended for safe use clinically. Pulsed hyperbaric oxygen therapy provides a way to rectify accumulating oxygen debt in exceptional blood loss anemia when transfusion is not possible.  Hyperbaric oxygen is considered adjunctive to pursuing adequate crossmatching, transfusion of red blood cells, and/or use of hematinic agents.

    Hyperbaric Plan

    The patient can be treated initially between 2.0 and 3.0 ATA for up to 3-4 hours, with surface intervals titrated to the re-occurrence of signs and symptoms of oxygen debt. 

    Risk and Benefit of Hyperbaric Oxygen Therapy

    • Please refer to the topic "Documentation: HBO Risks and Benefits"

    Sample Order

    •  See Sample Physician Order


    • 2CFor patients with acute blood loss who cannot receive expeditious red blood cell transfusions, we suggest the use of adjunct HBOT to increase chances of survival of physiologic insult that created profound anemia (Grade 2C). 
      • Rationale: causes of severe anemia include peripartum bleeding events, hemorrhagic diverticulae, multiple trauma, carcinoma of the cervix, hemolysis from a variety of transfusion-related processes, hemolytic anemias, and others. In most cases, the primary common factor is the refusal of blood transfusion due to religious belief.[11][12][13][14] Studies in 1959 showed that piglets with a hematocrit of 0.5% could be kept alive in a hyperbaric chamber at 3ATA, breathing 100% oxygen.[5] With this rationale, and in moribund patients, HBOT has been a course of last resort for those with severe anemias. Because of the rarity of this event, a formal randomized controlled study has not been performed. However, there have been multiple case reports and small series reported in the literature since 1974.[2][4][15][15][16][17][18] The mortality rate for all of the case reports and series is close to 33%.
      • When to begin therapy: In this case, the sooner the patient begins hyperbaric therapy, the better response. If the patient has already sustained multi-system organ failure, the chance of success diminishes. The endpoint of HBOT is when there is hemodynamic stability and no evidence of end-organ (primarily brain, heart, intestines, and kidneys) failure due to low hematocrit.
      • While treatment of severe anemias is a UHMS approved indication, it is not covered by CMS or many of the private insurers.


    1/06/2024Updated the Background section, reviewed literature
    6/4/2019Added section 'Clinical Evidence and Recommendations'
    5/5/2019Added section on 'Documentation'
    Official reprint from WoundReference® woundreference.com ©2024 Wound Reference, Inc. All Rights Reserved
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    NOTE: This is a controlled document. This document is not a substitute for proper training, experience, and exercising of professional judgment. While every effort has been made to ensure the accuracy of the contents, neither the authors nor the Wound Reference, Inc. give any guarantee as to the accuracy of the information contained in them nor accept any liability, with respect to loss, damage, injury or expense arising from any such errors or omissions in the contents of the work.


    1. CMS. National Coverage Determination (NCD) for Hyperbaric Oxygen Therapy (20.29) . 2017;.
    2. Van Meter KW. The effect of hyperbaric oxygen on severe anemia. Undersea & hyperbaric medicine : journal of the Undersea and Hyperbaric Medical Society, In.... 2012;volume 39(5):937-42.
    3. BOEREMA I, MEYNE NG, BRUMMELKAMP WH, BOUMA S, MENSCH MH, KAMERMANS F, STERN HANF M, van AALDEREN et al. [Life without blood]. Nederlands tijdschrift voor geneeskunde. 1960;volume 104():949-54.
    4. Weiskopf RB, Beliaev AM, Shander A, Guinn NR, Cap AP, Ness PM, Silverman TA et al. Addressing the unmet need of life-threatening anemia with hemoglobin-based oxygen carriers. Transfusion. 2017;volume 57(1):207-214.
    5. Harry T. Whelan, Eric Kindwall et al. Hyperbaric Medicine Practice 4th Edition Best Publishing Company. 2017;.
    6. Weaver L . "Hyperbaric Oxygen Therapy Indications” Best Publishing Company, North Palm Beach, FL . 2014;volume 469(13th Edition,):.
    7. Keith W. Van Meter, MD et al. Undersea and Hyperbaric Medical Society, Hyperbaric Oxygen Indications, 13th edition: Severe Anemia . 2014;.
    8. McLoughlin PL, Cope TM, Harrison JC et al. Hyperbaric oxygen therapy in the management of severe acute anaemia in a Jehovah's witness. Anaesthesia. 1999;volume 54(9):891-5.
    9. Bell MD. The use of hyperbaric oxygen in the management of sever anaemia in a Jehovah's Witness. Anaesthesia. 2000;volume 55(3):293-4.
    10. Graffeo C, Dishong W et al. Severe blood loss anemia in a Jehovah's Witness treated with adjunctive hyperbaric oxygen therapy. The American journal of emergency medicine. 2013;volume 31(4):756.e3-4.
    11. Thenuwara K, Thomas J, Ibsen M, Ituk U, Choi K, Nickel E, Goodheart MJ et al. Use of hyperbaric oxygen therapy and PEGylated carboxyhemoglobin bovine in a Jehovah's Witness with life-threatening anemia following postpartum hemorrhage. International journal of obstetric anesthesia. 2017;volume 29():73-80.
    12. Hart GB. Exceptional blood loss anemia. Treatment with hyperbaric oxygen. JAMA. 1974;volume 228(8):1028-9.
    13. Greensmith JE. Hyperbaric oxygen reverses organ dysfunction in severe anemia. Anesthesiology. 2000;volume 93(4):1149-52.
    14. Dische S, Hewitt HB et al. Carcinoma of cervix with severe anaemia: treatment by radiotherapy without blood transfusion using hyperbaric oxygen. The British journal of radiology. 1972;volume 45(539):848-50.
    15. Van Meter KW. A systematic review of the application of hyperbaric oxygen in the treatment of severe anemia: an evidence-based approach. Undersea & hyperbaric medicine : journal of the Undersea and Hyperbaric Medical Society, In.... 2005;volume 32(1):61-83.
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