A Tool for Deprescribing Antithrombotic Medication in Palliative Cancer Patients: A Retrospective Evaluation

Figures & data

Figure 1. The antithrombotics scheme.

Derived and adapted with permission from Huisman BAA (13).

ACS: Acute Coronary Syndrome; AF: Atrial Fibrillation; BMS: Bare Metal Stent; CVA: CererbroVascular Accident; DES: Drug-Eluting Stent; DVT: Deep Venous Thrombosis; INR: International Normalized Ratio; LMWH: Low-Molecular-Weight Heparin; LVEF: Left Ventricular Ejection Fraction; TAVI: Trans Catheter Valve Implantation; TE: Thrombo Embolism; TIA: Transient Ischemic Attack; PCI: Percutaneous Coronary Intervention.

For the valves, several items should be taken into account to determine if a valve results in high or low risk:

High risk: (items regarding valves): Atrial fibrillation with mechanical heart valve; For biological valves (including TAVI) placed < 3 months ago, Mechanical heart valve in mitral, tricuspidal or pulmonary position; Aortic valve prostheses with additional risk factor in consultation with the surgeon; Heart valve prosthesis (including biological valve) with additional risk factor *; Mechanical heart valve old model: caged ball, tilting disk (Starr-Edwards, Björk-Shiley)

Low risk: (items regarding valves): Mechanical heart valve in aortic position > 3 months ago placed without additional risk factor *; Biological valve > placed 3 months ago.

* Risk factors include: atrial fibrillation, left ventricular ejection fraction< 35%, history of thromboembolism.

Table 1. Patient characteristics.

Variable category		Median (min-max)	Count (N)	%
Gender	F		49	44.1%
	M		62	55.9%
Age		70 (28–92)	111
Location of primary cancer*	Head and neck		12	10.3%
	Digestive tract		60	51.3%
	Respiratory tract		18	15.4%
	Skin		3	2.6%
	Bone, articular cartilage and soft tissues		2	1.7%
	Breast		6	5.1%
	Female genital organs		1	0.9%
	Male genital organs		3	2.6%
	Urinary tract		8	6.8%
	Endocrine glands		2	1.7%
	Central nervous system		2	1.7%
Received oncological treatment	YES		80	72.1%
	NO		31	27.9%
History of major bleeding	YES		31	27.9%
	NO		80	72.1%
History of VTE	YES		46	41.4%
	NO		65	58.6%
n AT reviewed per patient	1		88	79.3%
	2		19	17.1%
	3		4	3.6%
AT groups	DOAC		28	20.4%
	Heparin group (LMWH and heparin)		66	48.2%
	PAI		34	24.8%
	VKA		9	6.6%
AT	Acenocoumarol		8	5.8%
	Acetylsalicylic acid		13	9.5%
	Apixaban		14	10.2%
	Carbasalate calcium		6	4.4%
	Clopidogrel		15	10.9%
	Edoxaban		4	2.9%
	Phenprocoumon		1	0.7%
	Heparin		1	0.7%
	Nadroparin		63	46.0%
	Rivaroxaban		10	7.3%
	Tinzaparin		2	1.5%
Time between first palliative care consultation and time of death in days**	0–15		42	42.0%
	16–30		12	12.0%
	31–45		12	12.0%
	46–60		5	5.0%
	61–75		3	3.0%
	76–90		7	7.0%
	>90		19	19.0%
Time to event		56 days (2–262)	11

F, female, M, male, VTE, venous thromboembolism, AT, antithrombotics. DOAC, direct oral anticoagulant, LMWH, Low-molecular-weight heparin, PAI, platelet aggregation inhibitors, VKA, Vitamin K antagonists. * Location of primary cancer is categorized based on the Dutch Cancer Registry (21). ** Eleven lost to follow-up patients were not included, resulting in n = 100.

Table 2. An overview of antithrombotic use and outcome in all patients experiencing clinical events after consultation with the palliative support team.

Patient Case	AT group	MB history	VTE history	Stop/start/continue	Scheme adherence	Clinical event
1	PAI, LMWH^a	Not present	Not present	CONTINUED	NO	Major bleeding unspecified primary site
3	LMWH^a	Present	Not present	CONTINUED	NO	Pulmonary hemorrhage*
4	PAI, LMWH^a	Present	Not present	CONTINUED	NO	Hemothorax
7	DOAC	Present	Present	CONTINUED	NO	Deep vein thrombosis
5	PAI	Present	Not present	CONTINUED	YES	Hemorrhagic shock
6	LMWH^a	Not present	Not present	STOPPED	YES	Severe symptomatic hematemesis
2	PAI	Not present	Not present	CONTINUED	YES	Deep vein thrombosis
8	LMWH^a	Present	Not present	STOPPED	YES	Pulmonary embolism
9	LMWH^b, DOAC**	Not present	Present	CONTINUED	YES	Pulmonary embolism
10	LMWH^a	Not present	Not present	STOPPED	YES	Pulmonary embolism
11	LMWH^b, DOAC**	Not present	Not present	CONTINUED	YES	Pulmonary embolism

AT, antithrombotics, MB, Major Bleeding, VTE, venous thromboembolism, DOAC, direct oral anticoagulant, LMWH, Low-molecular-weight heparin, PAI, platelet aggregation inhibitors.

Scheme adherence refers to the use of antithrombotics conform (indicated with “YES”) or non-conform (indicated with “NO”) the antithrombotics scheme.

*Clinical event stated as the cause of death.

**Medication not used simultaneously.

^a Prophylactic dose of LMWH.

^b Therapeutic dose of LMWH.

Table

Variables	Definitions
Coagulation disorder	The occurrence of thrombocytopenia, renal/liver failure or unstable INR.
Contra-indication for the use of AT due to clinical condition	Contra-indications such as frequent falls, frailty, bedriddenness, inability to swallow, unconsciousness and palliative sedation (13).
Liver failure	Child-Pugh score C or indication “liver failure” in the patients’ files.
Localization of primary cancer	Categorized conform the “Dutch Cancer Registry” (21).
Major bleeding	Defined as fatal bleeding, and/or symptomatic bleeding in a critical organ or bleeding causing a fall in hemoglobin level of at least 20 g/L or leading to transfusion of two or more units of blood cells (22).
Renal failure	EGFR <30 known before most recent palliative consultation or indication “renal failure” in the patients’ files.
Thrombocytopenia	Consistent values below 100 x10^9/L or indication “thrombocytopenia” in the patients’ files.
Variables needed to calculate CHA2DS2-VASc score	Defined conform to CHA2DS2-VASc score (14).
Variables needed to calculate HAS-BLED score	Defined conform to HAS-BLED score (15).
VTE	The occurrence of a venous thromboembolism event requiring medical intervention of which the event is clearly stated in patient files. VTE includes deep vein thrombosis (DVT) and pulmonary embolisms (PE). Excluding cerebral events.

AT, antithrombotics, INR, International normalized ratio, VTE, venous thromboembolism, EGFR, Estimated Glomerular Filtration Rate.

Huisman BAA. Optimizing care at the end of life: decision-making on medication with an emphasis on antithrombotics. PhD thesis. Vrije Universiteit Amsterdam. 2022. ISBN 9789464236927.

 Google Scholar

Integraal Kanker Centrum Nederland (IKNL) Code N. Tumorindeling. 2022. Available from: https://iknl.nl/nkr/registratie/tumorindeling. Accessed September 2022.

 Google Scholar

Schulman S, Kearon C, Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost. 2005;3(4):692–4. doi:10.1111/j.1538-7836.2005.01204.x.

 PubMed Web of Science ®Google Scholar

Lip GYH, Nieuwlaat R, Pisters R, Lane DA, Crijns HJGM. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the Euro Heart Survey on atrial fibrillation. Chest. 2010;137(2):263–72. doi:10.1378/chest.09-1584.

 PubMed Web of Science ®Google Scholar

Pisters R, Lane DA, Nieuwlaat R, De Vos CB, Crijns HJGM, Lip GYH. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the euro heart survey. Chest. 2010;138(5):1093–100. doi:10.1378/chest.10-0134.

 PubMed Web of Science ®Google Scholar

Data availability statement

Based on the data use policy of Amsterdam UMC and reasonable request, the dataset is available by sending an email message to the corresponding author.