Kano, Eunice Kazue; Borges, Jessica Bassani; Scomparini, Erika Burim; Curi, Ana Paula; Ribeiro, Eliane

doi:10.1590/1806-9282.63.10.842

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ORIGINAL ARTICLES • Rev. Assoc. Med. Bras. 63 (10) • Out 2017 • https://doi.org/10.1590/1806-9282.63.10.842 copiar

Algoritmos para monitorar o uso de varfarina: resultados do método Delphi

Autoria SCIMAGO INSTITUTIONS RANKINGS

Resumo

A varfarina é o anticoagulante oral mais prescrito. Novos anticoagulantes orais foram recentemente aprovados; porém, o uso é restrito e as técnicas de reversibilidade do efeito anticoagulante ainda são pouco conhecidas. Assim, este estudo propõe o desenvolvimento de um algoritmo para o monitoramento terapêutico de pacientes em uso de varfarina, com base na opinião de médicos que utilizam esse fármaco na prática clínica. O desenvolvimento do algoritmo foi realizado em dois estágios: (i) revisão da literatura e (ii) avaliação do algoritmo por médicos, segundo o método Delphi. Com base na análise dos artigos, dois algoritmos foram desenvolvidos: “Recomendações para o uso de varfarina na terapia anticoagulante” e “Recomendações para o uso de varfarina na terapia anticoagulante: ajuste de dose e controle de sangramento”. Posteriormente, os algoritmos foram analisados por 19 médicos que responderam ao convite e aceitaram participar da pesquisa. Desses, 16 responderam a primeira rodada, 11, a segunda e oito, a terceira. Houve um consenso de 70% ou mais na maioria das questões e 50% para seis questões. Assim, foi possível desenvolver algoritmos para o monitoramento do uso de varfarina por médicos, utilizando o método Delphi. O método proposto é de baixo custo e envolve a participação de médicos especialistas, revelando-se adequado para o fim pretendido. Mais estudos são necessários para validar esses algoritmos, permitindo que eles sejam usados na prática clínica.

Palavras-chave:
técnica Delfos; varfarina; tomada de decisões; conduta do tratamento medicamentoso

Questions	First Round
Questions	Response	Amount (%) (responses/doctors)	Consensus (> 70%)
1. What is the initial dose of warfarin for an adult outpatient who has never taken warfarin and whose desirable INR range for therapy is between 2 and 3?	5 mg/day	94% (15/16)	Yes
	2.5 mg/day	06% (16/01)	Yes
2. And for those patients in poor nutritional status, the elderly, patients with liver disease or those at high risk of bleeding?	2.5 mg/day	75% (12/16)	Yes
	2.0 mg/day	13% (02/16)
	5 mg/day	06% (16/01)
	I would not use	06% (16/01)
3. Is there any difference in the initial dose of warfarin between inpatients and outpatients?	No	75% (12/16)	Yes
	Yes	25% (04/16)	Yes
^* * Questions contained in the questionnaire of the second round. 4. After how many days from taking the initial dose should the first INR testing be done to assess the patient?	5 days	50% (08/16)	No
	3 days	25% (04/16)
	7 days	25% (04/16)
^* * Questions contained in the questionnaire of the second round. 5. What should be the frequency of INR monitoring until the desired range is reached?	weekly	63% (10/16)	No
	every 2-3 days	31% (05/16)
	Daily	06% (16/01)
^* * Questions contained in the questionnaire of the second round. 6. Is there a preferable period in a day to collect blood for INR testing?	Yes, morning.	56% (09/16)	No
	No	44% (07/16)	No
7. What should be the frequency for monitoring of INR after reaching the therapeutic range?	monthly	81% (13/16)	Yes
	every 6 weeks	13% (02/16)
	weekly	06% (16/01)
8. When should dose adjustment be done?	If INR is out of the therapeutic range, after 4-6 days from the beginning of therapy.	75% (12/16)	Yes
	If INR is out of the therapeutic range, in two consecutive measurements;	44% (07/16)
	If after 3 days using warfarin, the patient has not yet reached the expected INR range	06% (16/01)
^ Questions contained in the questionnaire of the third round. 9. Which INR ranges would determine an action for changing the dose?	INR ≤ 1.5/1.5 < INR ≤ 1.8/ 1.9 ≤ INR < 3.2/ 3.2 ≤ INR < 5.0/INR ≥ 5.0	25% (04/16)	Yes
	1.0 ≤ INR <2.0/ 3.0 < INR < 6.0/ 6.0 ≤ INR < 10.0/ 10.0 ≤ INR ≤ 18.0/ INR > 18.0	69% (11/16)
	INR ≤ 1.5/1.51 ≤ INR ≤1.99/ 2.0 ≤ INR ≤ 3.0/ 3.01 ≤ INR < 3.99/ 4.0 ≤ INR ≤ 4.99/5.0 ≤ INR ≤ 8.99/ INR ≥ 9.0	13% (02/16)
	other	25% (04/16)
	No answer	13% (02/16)
Questions 10 to 16 refer to an outpatient whose therapeutic INR range is between 2 and 3, and in none of the cases the patient has shown evidence of hemorrhage.
^* * Questions contained in the questionnaire of the second round. 10. If a patient shows an INR lower than or equal to 1.5; what would the dose adjustment be?	Increase 20%	38% (06/16)	No
	Increase 33%	31% (05/16)
	Double the dose	06% (16/01)
	other	25% (04/16)
10a. After how many days would you reassess patient status?	5-7 days	100% (16/16)	Yes
^* * Questions contained in the questionnaire of the second round. 11. What if 1.5 ≤ INR ≤ 1.8?	Increase 15%	38% (06/16)	No
	Increase 10%	31% (05/16)
	Recollect after a week	06% (16/01)
	Other	25% (04/16)
11a. After how many days would you reassess patient status?	5 to 7 days	88% (14/16)	Yes
11a. After how many days would you reassess patient status?	14 days	13% (02/16)	Yes
12. What if 1.8 ≤ INR ≤ 3.2?	Do not change the dose	81% (13/16)	Yes
12. What if 1.8 ≤ INR ≤ 3.2?	Reduce the dose by 25%	13% (02/16)	Yes
^* * Questions contained in the questionnaire of the second round. 12a. After how many days would you reassess patient status?	7-10 days	44% (07/16)	No
	30 days	44% (07/16)
	other	13% (02/16)
^* * Questions contained in the questionnaire of the second round. 13. What if 3.2 ≤ INR <4.9?	Discontinue the next dose and reintroduce warfarin at a weekly dose reduced by 10 -20%.	50% (08/16)	No
	Discontinue the next dose and reintroduce warfarin at a weekly dose reduced by 33%.	44% (07/16)
	Discontinue for three days and reintroduce warfarin at a dose reduced by 25-50%.	06% (16/01)
13a. After how many days would you reassess patient status?	5-7 Days	88% (14/16)	Yes
	2-5 days	06% (16/01)
	14 days	06% (16/01)
^* * Questions contained in the questionnaire of the second round. 14. What if 5.0 ≤ INR <9.0, with no evidence of bleeding	Discontinue warfarin and assess the need to give vitamin K orally (2-4 mg). After 24 hours, if there is no more risk of bleeding, reintroduce warfarin with reduction of 15% in the weekly dose.	38% (6/16)	No
	Discontinue the next three doses and then restart the treatment at a dose 33% lower	38% (6/16)
	Discontinue the next dose and then restart the treatment at lower doses until reach the therapeutic INR	06% (16/01)
	Discontinue until desirable INR and reintroduce at reduced dose	06% (16/01)
	Discontinue until desirable INR, reassess in 2-3 days, and reintroduce at reduced dose	06% (16/01)
	Discontinue warfarin and assess the need to give vitamin K orally (2-4 mg). After 24 hours, if there is no more risk of bleeding, reintroduce warfarin with reduction of 50% in the weekly dose.	06% (16/01)
^* * Questions contained in the questionnaire of the second round. 14a. After how many days would you reassess patient status?	3-7 days	56% (9/16)	No
	2 days	25% (04/16)
	24 hours	13% (02/16)
	No answer	06% (16/01)
15. And if INR > 10.0, with no evidence of bleeding?	Discontinue warfarin until INR reduction and give 5 to 10 mg of vitamin K orally.	75% (12/16)	Yes
15. And if INR > 10.0, with no evidence of bleeding?	Other	31% (05/16)	Yes
^* * Questions contained in the questionnaire of the second round. 15a. After how long would you reassess patient status?	24 hours	69% (11/16)	No
	Every 2 Days	31% (05/16)	No
16. In case there is evidence of minor bleeding, what is the dose of vitamin K?	Discontinue warfarin, give vitamin K 10mg and, if necessary, supplement with fresh plasma or prothrombin concentrate.	94% (15/16)	Yes
	Discontinue warfarin, give vitamin K, and restart later	06% (16/01)	Yes
16a. After how many days would you reassess patient status?	12 hours	75% (12/16)	Yes
16a. After how many days would you reassess patient status?	24 hours	25% (04/16)	Yes
The question below refers to the case of a patient showing evidences of major bleeding:
17. Sugiro: How would you manage warfarin therapy?	Discontinue warfarin, give prothrombin complex and vitamin K 10mg 75% (12/16)		Yes
17. Sugiro: How would you manage warfarin therapy?	other	25% (04/16)	Yes
17a. After how long should the patient be reassessed?	12 hours	81% (13/16)	Yes
17a. After how long should the patient be reassessed?	1 day	19% (3/16)	Yes
The question below refers to the case of a patient experiencing life-threatening bleeding: 18. Sugiro: How would you manage warfarin therapy?	Discontinue warfarin, give prothrombin complex and vitamin K 10mg	75% (12/16)	Yes
	Other	25% (04/16)	Yes
18a. After how many days would you reassess patient status?	12 hours	81% (13/16)	Yes
18a. After how many days would you reassess patient status?	1 day	19% (3/16)	Yes
Questions	Second Round
Questions	Response	Amount (%) (responses/doctors)	Consensus (> 70%)
^ Questions contained in the questionnaire of the third round. 1. How many days after taking the initial dose should the first INR testing be done to assess the patient?	3 days	27% (3/11)	No
	5 days	55% (6/11)
	1 week	18% (2/11)
^ Questions contained in the questionnaire of the third round. 2. What should be the frequency of INR monitoring until the desired range is reached?	Every 2-3 days	36% (4/11)	No
	Weekly	64% (7/11)	No
^ Questions contained in the questionnaire of the third round. 3. Is there a preferable period within the day to collect blood for INR testing?	Yes, morning	36% (4/11)	No
	No	64% (7/11)	No
4. When should dose adjustment be done (tick all possible alternatives)?	If the INR is out of therapeutic range after 4-6 days from the beginning of the therapy.	100% (11/11)	Yes
The following questions refer to an outpatient whose therapeutic INR range is between 2 and 3, and in none of the cases the patient shows evidence of hemorrhage.
^ Questions contained in the questionnaire of the third round. 5. If a patient shows INR lower than 1.5, which would be the dose adjustment?	Increase by 20%	27% (3/11)	No
	Double the daily dose	9% (1/11)
	Increase by 33%	55% (6/11)
	Other	9% (1/11)
^ Questions contained in the questionnaire of the third round. 6. What if 1.5 ≤ INR ≤1,8	Increase by 15%	64% (7/11)	No
	Increase by 25%	36% (4/11)	No
7. After how many days would you reassess the status of a patient showing 1.9 ≤ INR ≤ 3.4?	7-14 days	73% (8/11)	Yes
	30 days	27% (3/11)	Yes
^ Questions contained in the questionnaire of the third round. 8. What if 3.4 ≤ INR ≤ 5.0	Suspend the next dose and reintroduce warfarin with a weekly dose reduced by 10-20%	55% (6/11)	No
	Suspend the next dose and reintroduce warfarin with a weekly dose reduced by 33%	45% (5/11)	No
^ Questions contained in the questionnaire of the third round. 9. What if 5.0 ≤ INR ≤ 9.0 with patient under risk to develop hemorrhage in the next 30 days?	Discontinue treatment for the 3 next doses and then restart therapy at a dose 33% lower	45% (5/11)	No
	Discontinue warfarin treatment and assess the need for oral administration of vitamin K (2-4 mg). After 24 hours, if there is no more risk of bleeding, reintroduce warfarin with 15% reduction	45% (5/11)
	Other	9% (1/11)
^ Questions contained in the questionnaire of the third round. 9a. After how many days would you reassess patient status?	24h	55% (6/11)	No
	2 days	9% (1/11)
	3-7 days	36% (4/11)
10. What if 9.0 ≤ INR ≤ 20.0?	Discontinue warfarin therapy until reduction of INR. Reintroduce therapy at low-dose of warfarin and restart dose titration. If required, give vitamin K (5-10mg)	73% (8/11)	Yes
10. What if 9.0 ≤ INR ≤ 20.0?	Other	27% (3/11)	Yes
^ Questions contained in the questionnaire of the third round. 10a. After how many days would you reassess patient status?	Daily	64% (7/11)	No
	Every 2 Days	36% (4/11)	No
Questions	Third Round
Questions	Response	Amount (%) (responses/doctors)	Consensus (> 70%)
1. Is there a preferable period during the day to collect blood for INR testing?	Yes, morning	50% (4/8)	No
	No, but always in the same period	50% (4/8)	No
Questions 2 to 5 refer to an outpatient whose therapeutic INR range is between 2 and 3, and in none of the cases the patient shows evidence of hemorrhage.
2. If a patient shows INR lower than 1.5, which would be the dose adjustment?	Increase by 20%	38% (3/8)	No
	Increase by 33%	62% (5/8)	No
3. What if 1.5 ≤ INR ≤1.8	Increase by 15%	38% (3/8)	No
	Increase by 25%	50% (4/8)
	Other	12% (1/8)
4. What if 3.2 ≤ INR ≤ 4.9	Suspend the next dose and reintroduce warfarin with a weekly dose reduced by 10-20%	62% (5/8)	No
	Suspend the next dose and reintroduce warfarin with a weekly dose reduced by 33%	25% (2/8)
	Other	12% (1/8)
5. What if 5.0 ≤ INR ≤ 9.0 with no evidences of bleeding?	Discontinue the next 3 doses and then restart the therapy at a dose 33% lower	50% (4/8)	No
	Discontinue warfarin treatment and assess the need for oral administration of vitamin K (1-2 mg). After 24 hours, if there is no more risk of bleeding, reintroduce warfarin with 15% reduction	38% (3/8)
	Other	12% (1/8)
6. In case there is evidence of bleeding, classified as minor, what should the management be?	Suspend the next dose, give vitamin K according to INR (1-2 mg for INR> 4.5; p 1-2,5mg/5.0 <INR <9.0; 2,5-5,0mg for INR> = 9.0), monitor, and repeat if necessary, the dose of vitamin K, and restart warfarin therapy	50% (4/8)	No
	Discontinue and give vitamin K 1-2 mg, monitor, and repeat if necessary vitamin K, and restart therapy	38% (3/8)
	Other	12% (1/8)
7. In case there is evidence of bleeding, classified as minor, what should the management be?	Discontinue, give 5-10mg of vitamin K by slow intravenous infusion plus 25-50U/kg of prothrombin complex concentrate or 15ml/kg of fresh plasma, and reassess	100% (8/8)	Yes
8. In case there is evidence of a life-threatening bleeding, what should the management be?	Discontinue, give 10mg of vitamin K by slow intravenous infusion and 25-50U/kg of prothrombin complex concentrate OR 150 to 300 ml of fresh plasma, and reassess	75% (6/8)	Yes
	Discontinue, give 10mg of vitamin K by slow intravenous infusion, 25-50U/kg of prothrombin complex concentrate and 15ml/kg of fresh plasma, and reassess	25% (2/8)	Yes

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