Pathy's Principles and Practice of Geriatric Medicine. Группа авторов

and thrombotic disease is the commonest cause of hospital admission, disability, and death in patients over 50 in the developed world.

      The incidence of a first acute VTE, defined as DVT and/or PE, rises exponentially with age, ranging from approximately 1 per 10,000 subjects age 25–30 to a rate of nearly 8 per 1000 in the population 85 and older.¹⁸ Overall, >60% of all VTE events occur in people ≥65.¹⁹

      Several factors could explain the higher incidence of thromboembolism in the elderly:

      1 Increased prevalence in the elderly of cancer, stroke, heart failure, recent myocardial infarction, severe infection, diabetes mellitus, obesity, chronic obstructive pulmonary disease, inflammatory bowel disease, frailty, hospitalization, nursing home residence, immobilization, and history of VTE, all of which are considered risk factors for VTE.¹ Elderly patients are more likely to have cancer‐related VTE than younger patients.

      2 Atrial fibrillation (AF) is the most common arrhythmia in our daily clinical practice, affecting 4.5 million people in Europe and approximately 33.5 million people globally.²⁰ Estimates suggest a significant increase in AF incidence with age from 4.1/1000 under age 75 to 26.3/1000 in people older than 75.²¹ In the same way, its prevalence rises from 0.1% in people under 55 to 9% of those older than 80. Due to the increase in life expectancy, the number of elderly people over 80 with NVAF will increase fourfold by 2050; therefore, this group will represent over 50% of total patients with this arrhythmia, and the stroke risk will increase 25–36% in elderly individuals between 80 and 89.²¹

      3 Age‐related endothelial dysfunction and alterations in platelet function may contribute to the increased risk of VTE in the elderly.²² The levels of several plasma components (fibrinogen, factor VII, factor VIII, D‐dimer, and homocysteine) increase with age, although it is unclear whether this has a clinically meaningful impact on the risk of VTE.²²

      4 Hyperglycaemia is associated with enhanced thrombin formation in patients with diabetes or cardiovascular disease, which are more common in older people, increasing the risk of thromboembolic events.²³

The elderly are more prone to haemorrhage

      Bleeding risk is the antithrombotic treatment most important complication, so this requires us to personalize decision‐making, especially in elderly patients with multimorbidity, geriatric syndromes, frailty, or disability. Due to the higher prevalence of comorbid diseases, drug interactions, and age‐related conditions, the risk of anticoagulation‐related major and clinically relevant non‐major bleeding is increased in patients 65 and older versus younger patients. Schulman has comprehensively summarized the increasing body of evidence indicating that age is an independent risk factor for major bleeding in patients receiving oral anticoagulant therapy, with an average twofold increase.²⁴

      Increased age also appears to be a risk factor specifically for intracranial haemorrhage. Age ≥75 is associated with at least a two‐fold increase in intracranial haemorrhage risk due to high‐risk conditions such as cerebral amyloid microangiopathy and leukoaraiosis.^25,26

Several scores were developed to help measure bleeding risk in AF²⁷, with no intention of contraindicating oral anticoagulation but rather to modify it with our intervention to increase the anticoagulation therapy’s security profile. The most widespread is the HAS‐BLED score, which includes different determinants, all of which can be modified except age. Other scores, like HEMORR2AGES, add aspects that are included in the Comprehensive Geriatric Assessment (CGA), such as falls and cognitive impairment, which are usually assessed and managed by a geriatrician. The ATRIA Bleeding Risk Score takes into account five parameters and stratifies the bleeding risk into three levels.^28,29 The ORBIT risk score proposes five determinants: age, anaemia, previous bleeding episodes, renal impairment, and antiplatelet therapy. It demonstrates similar discrimination with better sizing than HAS‐BLED and ATRIA scores, according to the ROCKET‐AF trial.³⁰ The ABC‐bleeding score includes age, previous bleeding episodes, and three serum biomarkers (haemoglobin, troponin T, and GDF‐15 or cystatin C/creatinine clearance) and obtains more appropriate results than HAS‐BLED and ORBIT, according to the ARISTOTLE and RE‐LY trials²⁸; but the biomarkers are not standardized, and there is no defined cut‐off point (class IIb indication) (Table 25.1). The results of a recent study suggest that the bleeding risk assessment tools with high sensitivity should be used for AF patients at high risk of bleeding, and bleeding risk assessment tools with high specificity should be used for patients at low risk of bleeding.³¹

Anticoagulant response differs in the elderly

VKAs such as warfarin have been the treatment of choice in past decades when chronic anticoagulation was needed. However, coumarin therapy is complex, especially in the elderly, due to factors such as wide variation in the dosage among patients, multiple drug and food interactions, and bleeding complications. Several studies have shown that older individuals have increased sensitivity to its anticoagulant effect.³² Froom et al. indicated that for every 10‐year increase in age, there was a 15% increase in the risk of International Normalized Ratio (INR) values ≥5 and that elderly age was associated with increased maximum INR value, decreased minimum value, decreased weekly warfarin dose, and increased number of tests per year to evaluate INR.³³ It seems that oral anticoagulant requirements decline^33,34 with age. In another paper, Schwartz reported that individuals ≥75 presented 50% variability in the daily warfarin dose compared to those <35 for an equivalent INR,³⁵ as Routledge had proposed before.³²

Table 25.1 Characteristics of bleeding risk assessment tools.

Assessment tools	Descriptions and scores	Defined cut‐off values	Advantages (A) and disadvantages (D)
HAS‐BLED	Hypertension, abnormal renal/liver function (1 point each), stroke, bleeding history or predisposition, labile INR, elderly drugs/alcohol concomitantly (1 point each); maximum 9 points.	0‐2; >=3	Simple and easy to operate; balanced predictive sensitivity and specificity (A)
HEMORR2AGES	Liver/renal disease, ETOH abuse, malignancy, age >75, low platelet count or function, rebleeding risk, uncontrolled hypertension, anaemia, genetic factors (CYP2C9), risk of fall or stroke; 1 point for each risk factor present and 2 points for previous bleed.	0–1; >=2	Including geriatric syndromes such as risk of fall and cognitive impairment (A) More complex, with conventional genetic polymorphisms testing limiting its clinical application (D).
ATRIA	Anaemia (3); severe renal disease (GFR <30 ml/min) (3); age >=75 (2); any prior bleeding (1); diagnosed hypertension (1). Maximum 10 points.	<4; >=4	High specificity (A).
ORBIT	Age ≥75 (1); abnormal haemoglobin/hematocrit (2); bleeding history (2); insufficient kidney function (GFR <60 ml/min/1.73 m2) (1); treatment with antiplatelets (1). Maximum 7 points.	<3; >=3	High specificity. Similar discrimination with better sizing than HAS‐BLED and ATRIA scores, according to ROCKET‐AF trial (A).
ABC bleeding	Age (y); biomarkers (growth differentiation factor‐15, high‐sensitivity cardiac troponin T, haemoglobin), previous bleeding.	1%, 1–2%, and >2% risk for bleeding