The Pre-brief
Treating severe anemia is something many of us are no strangers to. While most patients can be crossmatched and receive blood transfusions, certain circumstances change care such that simply transfusing blood is not an option. Among patients refusing transfusion of blood products, religious grounds tend to be the most common reason. Other infrequent circumstances include refusal for fear of infection transmission or patients with rare blood types or antibodies for whom suitable blood products may not be available at a given hospital. As has become an obvious recurring theme in my posts, enter hyperbaric oxygen therapy (HBOT). HBOT is a Centers for Medicare and Medicaid Services (CMS) approved therapy for severe anemia, which can be considered a bridge therapy when standard packed red blood cell (PRBC) transfusion is not an option.
Death, taxes, and the laws of physics
According to Henry’s gas law, gases (oxygen in this case) are predictably driven into the solution at higher ambient pressure as occurs during HBOT. As illustrated in the figure below, the arterial oxygen content is the sum of oxygen bound to hemoglobin and oxygen dissolved in plasma. In normobaric (sea level) conditions, oxygen dissolved in plasma plays a near negligible role in the total oxygen content, as modifications to PaO2 are somewhat limited. Add 2 atmospheres (2 ATA = 1520 mmHg) of ambient pressure with HBOT, however, and PaO2 suddenly plays a much greater role in the same equation. During an HBOT treatment at 3.0 ATA (common treatment pressure for emergency dives), PaO2’s as high as 2000 mmHg can be measured!
To explore this same phenomenon in an animal study in 1959, Boerema exposed pigs to 3.0 ATA with 100% inspired O2 (identical conditions to HBOT), and exsanguinated the pigs to hemoglobin felt to be incompatible with life (0.4-0.6 g/dL). Blood volume was replaced with a dextran/dextrose/Ringers’ lactate solution such that any meaningful tissue oxygenation would have to occur from oxygen dissolved in the solution. Amazingly, the pigs survived, demonstrating that in the near-absence of hemoglobin-bound oxygen, tissue oxygenation can be accomplished with oxygen dissolved in the plasma. Subsequent, less extreme studies in animal models of severe anemia have demonstrated similar effects from HBOT.
Treating human
Whether from severe blood loss, hemolytic conditions, or aplastic conditions, a significant drop in hemoglobin results in inadequate oxygen-carrying capacity of blood and an oxygen debt at the tissue level. The more quickly blood loss occurs, the more poorly it is tolerated by the patient. Oxygen debt correlates directly with morbidity and mortality with a four-hour cumulative oxygen debt of greater than 33L/m2 being uniformly fatal in cases of severe hemorrhage.
Surgical or medical hemorrhage control or treatments directed toward the underlying condition are the obvious priorities. Three or even four times daily treatment with HBOT, can help to significantly mitigate cumulative oxygen debt and can be an instrumental bridge to more definitive therapy in cases where blood transfusion is refused or unavailable. Case series in humans support the use of HBOT as a bridge therapy for patients with severe anemia. Patients treated with HBOT for severe anemia routinely feel subjective improvement in symptoms with near immediacy on arrival to treatment pressure. Too much HBOT does come with consequences of oxygen toxicity, so a minimum four-hour surface interval must be heeded between HBOT treatments.
Other adjunctive treatments for a ‘bloodless’ approach to treating anemia include hematopoietic growth factors, vitamin and mineral supplementation (Iron, vitamin B12, folate, vitamin K), and artificial oxygen carriers (perfluorocarbons, bovine-derived hemopure). Some patients refusing PRBC’s will accept blood factors such as Von Willebrand factor or PCC, or plasma-derived fractions such as albumin, cryoprecipitate, or immunoglobulin. Collectively, this long and by no means an exhaustive list of potential alternative therapies should be carefully considered on a case-by-case basis in severely anemic patients refusing a blood transfusion. In addition, a simple call and discussion with the nearest HBOT facility should be considered.
The Debrief
- Addressing the underlying cause (i.e. hemorrhage control in trauma) is still the first priority in the severely anemic patient
- HBOT can be a bridge or temporizing measure in cases where blood transfusion is refused or otherwise not an option
- Given the dramatic change in PaO2 in hyperbaric conditions, oxygen dissolved in plasma plays a much greater role in affecting total arterial oxygen content when compared to normobaric conditions
- HBOT is one of MANY adjunctive and alternative treatment options which can be considered for severe anemia in the patient refusing or unable to receive blood transfusion
References
- BOEREMA I, MEYNE NG, BRUMMELKAMP WH, BOUMA S, MENSCH MH, KAMERMANS F, STERN HANF M, van AALDEREN. [Life without blood]. Ned Tijdschr Geneeskd. 1960 May 7;104:949-54. Dutch. PMID: 13802034.
- Chander, Y., Misra, R. N., & Rai, R. (1999). HYPERBARIC OXYGEN THERAPY [HBOT]. Medical journal, Armed Forces India, 55(2), 89–90. https://doi.org/10.1016/S0377-1237(17)30257-5
- Choudhury R. (2018). Hypoxia and hyperbaric oxygen therapy: a review. International journal of general medicine, 11, 431–442. https://doi.org/10.2147/IJGM.S172460
- Leach, R. M., Rees, P. J., & Wilmshurst, P. (1998). Hyperbaric oxygen therapy. BMJ (Clinical research ed.), 317(7166), 1140–1143. https://doi.org/10.1136/bmj.317.7166.1140
- Scharman, CD, Shatzel, JJ, Kim, E, DeLoughery, TG. Treatment of individuals who cannot receive blood products for religious or other reasons. Am J Hematol. 2017; 92: 1370– 1381. https://doi.org/10.1002/ajh.2488
- Van Meter, K. W. (2019). Severe Anemia. In R. Moon (Ed.), Undersea and Hyperbaric Medical Society Hyperbaric Oxygen Therapy Indications (14th ed., pp. 293–300). Best Publishing Company.
