Consensus of the Brazilian association of hematology, hemotherapy and cellular therapy on patient blood management: Assessment and management of coagulation in the preoperative period

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

doi:10.1016/j.htct.2024.02.005

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

Bruno Deltreggia Benites

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

Roberto Luiz da Silva

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

Hospital São Camilo Pompéia, São Paulo, SP, Brazil

Selma Soriano

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

Susankerle de Oliveira Costa Alves

Chamberlain University, Chicago, IL, USA

Silvia Renata Cornélio Parolin Rizzo

Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular, 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 author declares no conflicts of interest.

Mechanism	Causes
Pseudothrombocytopenia	In vitro platelet aggregation due to ethylenediaminetetraacetic acid (EDTA) in the collection tube
Major platelet consumption	Major active hemorrhage, disseminated intravascular coagulation, sepsis, extracorporeal circulation
Platelet sequestration	Hepatosplenomegaly
Low platelet production	Chemotherapy, radiotherapy, alcohol intoxication (or other drugs), viral infection (human immunodeficiency viruses, hepatitis C virus, cytomegalovirus, Epstein-Barr virus), bone marrow infiltration (leukemia, lymphomas, other tumors), infection, liver disease (reduction of thrombopoietin)
Platelet destruction	Immune thrombocytopenia, immune thrombocytopenia induced by drugs including heparin, thrombotic microangiopathies, post-transfusion purpura, extracorporeal membrane oxygenation, cardiopulmonary bypass

	Clinical condition	Recommended count
Prophylactic indication (without bleeding or just grade 1 bleeding)	Transient bone marrow aplasia secondary to chemotherapy or allogeneic transplantation	≥10 000
	Thrombocytopenia in a patient with aplasia secondary to chemotherapy or allogeneic transplantation without bleeding, but with risk factor^a a consider not performing prophylaxis in autologous transplantations Adapted from Estcourt et al. (2017).2	≥20 000
	Chronic bone marrow aplasia in which platelet count recovery is not expected after intensive drug treatment	≥10 000
	Chronic bone marrow aplasia in which platelet count recovery is not expected	Routine prophylactic transfusion not recommended
	Chronic bone marrow aplasia to prevent recurrence of bleeding ≥ grade 2	Individually evaluate each case
	Bone marrow biopsy and puncture, peripheral catheter insertion, cataract surgery, central venous catheter removal	Routine prophylactic transfusion not recommended
	Chronic stable bone marrow aplasia, platelet function disorder, consumption or destruction (DIC, PTT), immune thrombocytopenia (PTI, HIT, PPT)	prophylactic transfusion is not indicated
	Transient or chronic aplasia with risk factors (critically ill, other associated coagulation disorders, sepsis, antibiotic use)	10 000 - 20 000
	Central venous catheter implantation (guided by ultrasound by experienced team)	>20 000
	Lumbar puncture	≥ 40 000
	Insertion or removal of an epidural catheter	≥80 000
	Major surgery	>50 000
	Percutaneous hepatic biopsy	>50 000
	Neurosurgery or posterior ophthalmic surgery	>100 000
Therapeutic indication	Severe hemorrhage	>50 000
	Polytrauma, brain lesion, CVA	>100 000
	Bleeding grade ≥ 2, not severe	>30 000

Bleeding risk	Examples of procedures
High (greatest bleeding in 30 days >2%)	Any major surgery (duration >45 min) and neuraxial anesthesia. Heart surgery, intracranial, spinal column, oncological surgery, major orthopedic surgery, reconstructive plastic surgery, urological and gastrointestinal surgery (especially with anastomosis), transurethral resection of the prostate gland, bladder or tumor ablation, nephrectomy, renal biopsy, resection of colonic polyps, intestinal resection, percutaneous gastrostomy, endoscopic retrograde cholangiopancreatography and surgeries of organs with much irrigation (kidneys, liver, spleen).
Low to moderate (greatest bleeding in 30 days 0-2%)	Arthroscopy, skin and lymph node biopsy, foot/hand surgery, coronarography, endoscopic procedures with or without biopsy (endoscopy, colonoscopy, bronchoscopy), hysterectomy, cholecystectomy, abdominal herniorrafia, hemorrhoid surgery, epidermal injection
Minimal (greatest bleeding in 30 days = 0%)	Minor dermatologic procedures (basal cell and squamous cell excision, actinic and actinic keratoses and nevi), cataract surgery, minor dental procedures (extractions, restorations, prostheses, endodontics), dental cleaning, pacemaker or cardiac defibrillator implantation

Risk category	Mechanical heart valve	Atrial fibrillation	Venous thromboembolism (VTE)
High	- Mechanical mitral valve - Cage valve or mitral/aortic tilting disc - Stroke or transient ischemic attack <3 months	- CHADS2 (score 5 or 6) - CHA2DS2VASC (score 7) - Stroke or transient ischemic attack <3 months - Rheumatic valve disease	- Protein C, S or antithrombin deficiency - Antiphospholipid antibodies - Multiple thrombophilias - Active oncological disease^a
Moderate	- Bi-leaflet aortic valve prosthesis with higher risk factors for stroke^b	- CHADS2 (score 3 or 4) - CHA2DS2VAS^C (score 5 or 6)	- VTE in the last 3-12 months - Recurrent VTE - Non-severe thrombophilia - Active or recent oncological disease
Low	- Bi-leaflet aortic valve prosthesis without higher risk factors for stroke^b	- CHADS2 (score 0-2) - CHA2DS2VAS^C (score 1-4)	- VTE more than 12 months previously

VTE risk	Type of OAC	High bleeding risk	Minimal bleeding risk
High	VKA	Interrupt warfarin and consider bridge with LMWH according to clinical judgment and evidence^a,b	Do not interrupt anticoagulation therapy
	DOAC	Interrupt DOAC. Bridge with LMWH not recommended
Intermediate	VKA	Consider suspending warfarin without bridge with LMWH based on clinical judgment and evidence^a,b
	DOAC	Interrupt DOAC. Bridge with LMWH not recommended
Low	VKA	Interrupt warfarin. No necessity to bridge with LMWH
	DOAC	Interrupt DOAC. Bridge with LMWH not recommended

Preoperative day	Warfarin	LMWH	INR
D-10 to d-7	Suspend drug	Without heparin	Assess INR, renal function, complete blood count
D-6 to d-5	Dose suspended	Without heparin
D-4	Dose suspended	Without heparin
D-3	Dose suspended	Start therapeutic dose
D-2	Dose suspended	Maintain therapeutic dose
D-1	Dose suspended	Last dose at least 24 h before the planned surgery time (50% of the daily dose)	Assess INR: - if <1.5 proceed with surgery - If <1.8 and >1.5 consider VKA VO (1.0-2.5 mg)
D0	Dose suspended	Without heparin
D + 1	Restart habitual dose	Restart if procedure low-risk for bleeding
D + 2 to D + 3	Maintain habitual dose	Restart if procedure high-risk for bleeding
D + 4	Maintain habitual dose	Suspend LMWH when INR >1.9	Assess INR
D + 7 to D + 10	Maintain habitual dose		Assess INR

	Renal function	Suspension (no of days before the surgery		Reintroduction (hours after surgery)
		Surgical risk of bleeding		Surgical risk of bleeding
	Creatinine clearance (mL/min)	Low	High^a	Low	High
Dabigatran	>50	2	3
	30-50	3	4-5
Rivaroxaban	>50	2	3
	30-50	2	3
	15-29.9^c	Individualize	Individualize	24 h	48-72 h^b
Apixaban	>50	2	3
	30-50	2	3
Edoxaban	15-29.9	Individualize	Individualize
	>50	2	3

[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: Assessment and management of coagulation in the preoperative period

Abstract