Consensus of the Brazilian association of hematology, hemotherapy and cellular therapy on patient blood management: Preoperative Phase - Preoperative management of the patient's anemia

Benites, Bruno Deltreggia; Leite, Flavia; Soriano, Selma; Silva, Roberto Luiz da; Alves, Susankerle de Oliveira Costa; Rizzo, Silvia Renata Cornélio Parolin; Rabello, Guilherme; Langhi Junior, Dante Mario

doi:10.1016/j.htct.2024.02.006

Bruno Deltreggia Benites

Centro de Hematologia e Hemoterapia da Universidade Estadual de Campinas Hemocentro UNICAMP), Campinas, SP, Brazil

Flavia Leite

Hemocentro de Ribeirão Preto, Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (HCFMRP-USP), Ribeirão Preto, SP, Brazil

Selma Soriano

Hemocentro Coordenador do Estado do Pará (Fundação HEMOPA), Belém, PA, Brazil

Roberto Luiz da Silva

Instituto Brasileiro de Controle do Câncer (IBCC), São Paulo, SP, Brazil

Hospital São Camilo Pompéia, São Paulo, SP, Brazil

Susankerle de Oliveira Costa Alves

Chamberlain University, Chicago, IL, USA

Silvia Renata Cornélio Parolin Rizzo

Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular (ABHH), São Paulo, SP, Brazil

Guilherme Rabello ^⁎⁎ Corresponding author at: Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (Incor - HCFMUSP), São Paulo, SP, Brazil. E-mail address: grabello.inovaincor@fz.org.br (G. Rabello)

Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (Incor - HCFMUSP), São Paulo, SP, Brazil

https://orcid.org/0000-0002-7100-7897

Dante Mario Langhi Junior

Escola Paulista de Medicina, Universidade Federal de São Paulo (EPM UNIFESP), São Paulo, SP, Brazil

⁎ Corresponding author at: Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (Incor - HCFMUSP), São Paulo, SP, Brazil. E-mail address: grabello.inovaincor@fz.org.br (G. Rabello)

Conflicts of interest

The authors declare no conflicts of interest.

Exam	Utility
Complete blood count	Indicates the hemoglobin level (presence or absence of anemia). Allows the evaluation of MCV/ MCH/RDW, which help to identify the type of anemia. Indicates the existence of other cytopenias (leukopenia, thrombocytopenia).	MCV <80 fl (microcytic)	ID, thalassemia, sideroblastic anemia
		MCV 81-95 fl (normocytic)	Chronic disease anemia, combined deficiency (iron + Vitamin B12/folic acid), MDS, hemolytic anemia
		MCV >95 fl (macrocytic)	Vitamin B12/folic acid anemia, alcoholism, cirrhosis, MDS, reticulocytosis (hemolysis) agglutination
Reticulocyte count	When increased, it indicates an attempt by the bone marrow to compensate for the peripheral destruction of red blood cells (hemolytic anemias), that is, erythropoiesis is preserved. A low count suggests impairment of erythropoiesis due to deficiencies: EPO deficiency (CKD), bone marrow failure, hematological neoplasms, among others.
Ferritin	This is the most specific test and best reflects the body iron deposits. It is widely available and standardized. Serum ferritin <15 mcg/L is confirmatory for ID. A value <30 mcg/L has greater sensitivity (92 %) and a similar specificity (98 %) and is most often used. The presence of inflammation causes ferritin (acute phase protein) to increase, interfering with the assessment of ID. Currently, serum ferritin levels <100 mcg/L are accepted to diagnose ID in chronic inflammatory conditions (this level is also commonly recommended in the elderly and post-operatively). For ferritin levels 100-300 mcg/L in the presence of inflammation, it is recommended to use transferrin saturation (<20 %) in conjunction with ferritin to define ID.
Transferrin saturation (TS)	Increased hemolytic anemias, inefficient erythropoiesis, megaloblastic anemia. Increased LDH together with an increase in reticulocytes or indirect bilirubin should raise suspicion of hemolysis.
Haptoglobin	A very sensitive and specific marker for the presence of hemolysis. It binds to free heme and is rapidly removed from circulation, however it is reduced in the presence of hemolysis, including with intramedullary hemolysis observed in megaloblastic anemia. It may be increased in the presence of inflammation, but this increase, in general, is not sufficient to hide hemolysis. It reduces in chronic liver disease.
Direct antiglobuin test (DAT or direct Coombs)	DAT has low predictive value in the absence of hemolysis. That is, it should not be used in the initial investigation of anemia. It should be requested when there are indications that the anemia is hemolytic, with the aim of investigating whether there is an immune component involved in the destruction of the red blood cells.
Bilirubin	This is especially useful to evaluate the presence of a hemolytic component in which there may be an increase in indirect bilirubin.
Vitamin B12 and folic acid measurements	Widely available. Measurement and replacement should be considered in all at-risk patients for these deficiencies (restricted diets, atrophic gastritis, inflammatory bowel disease, etc.) or who will be submitted to procedures with risk of major blood loss.
Others: Renal function, Glycated Hb, CRP, TSH, enzymes and hepatic function	In the presence of anemia, especially when absolute ID has been ruled out as the cause, it is important to evaluate the presence of other comorbidities and inflammation.

	Oral	Intravenous
Posology and administration	Easy to administer but requires daily use for long periods	Requires an infusion center, some formulations have the possibility of singe infusions
Absorption	Reduced in inflammatory conditions	Not influenced by inflammation
Gastrointestinal tract effects	Epigastralgia, heart burn, nauseas, intestinal constipation	Rare
Other side effects	Alterations in skin color	Reactions at injection site, headaches, hypophosphatemia with some formulations
Therapeutic response	Limited by the side effects and situations of limited absorption	Faster recovery of Hb levels and iron stocks
Access to patients	Widespread availability, low cost	High-dose formulations with higher cost and necessity of infusion center

Iron salt	Presentation	Concentration of elementary iron
Iron sulfate (20 % of elementary iron)	200 mg Tablets/Capsules	40 mg
	400 mg Tablets/Capsules	60 mg
	500 mg Tablets/Capsules	100 mg
	125 mg/mL drops	25 mg/mL
Iron III hydroxide polymaltose complex (30 % of elementary iron)	435 mg Tablets	123 mg
	330 mg chewable Tablets	100 mg
	330 mg/mL solution	100 mg/mL
	182 mg/mL drops	50 mg/mL
Iron glycinate chelate (20 % of elementary iron)	150 mg Tablets	30 mg
	300 mg Tablets	60 mg
	500 mg chewable Tablets	100 mg
	250 mg/mL drops	50 mg/mL
Iron carbonyl (33 % of elementary iron)	400 mg Tablets	120 mg

	Saccharate ferric hydroxide	Ferric carboxymattose	Ferric derisomaltosis
Presentation (ampule)	100 mg/5 mL	500 mg/10 mL	500 mg/5 mL and 1000 mg/10 mL
Maximum dose per infusion	200 mg	20 mg/kg or 1000 mg	20 mg/kg
Dilution (solution)	0.9 % saline solution	Pure or 0.9 % saline solution	Pure or 0.9 % saline solution
Maximum dilution	1 mg of iron/mL	2 mg of iron/mL	25 mg/mL
Time of infusion	100 mg ≥15 min 200 mg ≥30 min	≥15 min	≥15 min
Necessity of test dose	No	No	No
Pediatric use^* ⁎ Maximum dose of 3 mg of elementary iron/kg per dose. Do not exceed a total dose of 500 mg.	Yes	No	No
Use during gestation^⁎⁎ ⁎⁎ Use from the second trimester of gestation.	Yes	Yes	Yes

Hb (g/dL)	Body weight: 35-70 Kg	Body weight: >70 Kg
<10	1500 mg	2000 mg
≥ 10	1000 mg	1500 mg

Hb (g/dL)	Body weight: <50 Kg	Body weight: 50-70 Kg	Body weight: >70 Kg
<10	500 mg	1500 mg	2000 mg
≥ 10	500 mg	1000 mg	1500 mg

[1] ⁎ Corresponding author at: Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (Incor - HCFMUSP), São Paulo, SP, Brazil. E-mail address: grabello.inovaincor@fz.org.br (G. Rabello)

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Consensus of the Brazilian association of hematology, hemotherapy and cellular therapy on patient blood management: Preoperative Phase - Preoperative management of the patient's anemia

Abstract