Bleeding risk scores. CHA2DS2-VASc and HAS-BLED scales. Is it possible to avoid bleeding with long-term use

With an INR of more than 3.5, the risk of bleeding, including intracranial, increases significantly, and with an INR of 2.0-3.0, the risk of bleeding is not higher than with less than 2.0, but there is a therapeutic effect.

To assess the risk of bleeding, risk scales for bleeding in patients receiving anticoagulant therapy have been developed. The most famous and effective in practice is the HAS-BLED (IIa A) scale. A value of 3 or more indicates a high risk of bleeding and requires alertness - IIa B, but this does not rule out oral anticoagulants.

HAS-BLED bleeding risk scale:

When taking oral anticoagulants of vitamin K antagonists, the INR serves as a reference point for the clinical effect. For the prevention of thromboembolic complications in AF without valvular heart disease, the therapeutic range of INR is 2.0-3.0 (the optimal range between efficacy and safety; ideally 2.2-2.3). Maintenance of INR within 1.5-2.5 in elderly patients did not justify itself (the number of strokes increased), therefore, maintenance of INR less than 2.0 is not recommended. When INR>3.5 significantly increases the risk of bleeding, primarily intracranial.

Sensitivity to warfarin is determined by the carriage of the cytochrome P450 2C9 (CYP2C9) gene, which controls the metabolism of warfarin in the liver, and the gene for the vitamin K epoxide reductase complex (VKORC1). They determine the required dose of warfarin and the risk of bleeding. Genotyping of these genes is justified only in patients with a high risk of bleeding. In 2010, the FDA published values ​​for maintenance doses of warfarin depending on the polymorphisms of the above genes.

Separate groups of patients:

1. planned surgical interventions: with a low risk of thromboembolic complications and the absence of mechanoprosthetic heart valves, it is possible to temporarily cancel vitamin K antagonists with the creation of subtherapeutic anticoagulation (INR<1,5) на срок до 48 часов без перехода на гепарин – IIa C. При приеме варфарина обычно отменяют за 5 дней до операции. В случае же высокого риска тромбэмболических осложнений или наличия механопротезов клапанов сердца временная отмена пероральных антикоагулянтов рекомендована с переходом на терапевтические дозы гепарина или НМГ («терапия моста») – IIa C. После вмешательства возобновление приема антагониста витамина К (в прежней дозе) возможно вечером дня операции при условии полного и успешного гемостаза – IIa B. При этом в случае «терапии моста» на этапе возобновления приема антагониста витамина К время перекреста с гепарином или НМГ должно быть не менее 5 суток. Если операция проводится экстренно, то можно, при необходимости дать небольшие дозы витамина К.
2. CVA or TIA: before starting antithrombotic therapy, it is necessary to make sure that the blood pressure numbers are controlled and to exclude cerebral hemorrhage using CT or MRI - IIa C. bleeding, anticoagulants should not be prescribed - IIa C. With a large size of the focus of ischemic stroke, it is advisable to postpone the appointment of anticoagulants in view of the risk of hemorrhagic transformation of the focus - IIa C. If a patient with AF develops TIA, but stroke is excluded and there is no risk of bleeding, then it is recommended as it is possible to initiate anticoagulants earlier - IIa C. In hemorrhagic stroke, anticoagulants are canceled immediately and prescribed again after a long period of time and in the absence of a high risk of recurrent hemorrhagic stroke.
3. Chronic ischemic heart disease: With a stable course of coronary heart disease (no acute ischemia and no planned TBCA), monotherapy with oral anticoagulants, primarily warfarin, can be used (it is at least as effective as aspirin in the secondary prevention of coronary artery disease, but there is less risk of bleeding than with the combined use of acetylsalicylic acid and clopidogrel; ASPECT-2, WARIS-2 studies) - IIb C. After surgical myocardial revascularization in a patient with AF, the combination of a vitamin K antagonist with one of the antiplatelet agents can be considered, but this is poorly understood - IIb C.
4. PCI: Drug-eluting stents should be avoided if possible, as this would require triple antithrombotic therapy for at least 1 year, and bare-metal stents should be preferred. In this case, triple antiplatelet therapy is required for 1 month, then vitamin K antagonist + clopidogrel for a year - IIa C. In the case of implantation of drug-eluting stents, triple antiplatelet therapy is required for 3-6 months, then vitamin K antagonist + clopidogrel until years after stenting - IIa C. If the patient is planned for TBCA and a high or medium risk of thromboembolism, then the INR values ​​​​should be left in the range of 2.0-3.0, but if possible, radial access should be chosen - IIa C. For primary emergency TBCA and INR more than 2.0, it is better to refrain from taking IIb / IIIa receptor blockers. Triple or dual antithrombotic therapy should be carried out in combination with proton pump or H2-histamine receptor inhibitors and maintain the INR within 2.0-2.5 - IIb C.
5. OKS: in ACS and PCI, triple antiplatelet therapy is required for at least 6 months, then a vitamin K antagonist + clopidogrel or acetylsalicylic acid up to a year after stenting - IIa C. In ACS without PCI, either a combination of a vitamin K antagonist (INR 2, 0-3.0) with acetylsalicylic acid or monotherapy with a vitamin K antagonist with an INR of 2.5-3.5 - IIa C. Approaches to the treatment of ACS against the background of initial therapy with new oral anticoagulants have not been studied, therefore, in this case, a switch to warfarin is recommended. EKV with unstable hemodynamics, inability to control heart rate or persistent ischemia; preferably in / in the introduction of beta-blockers (IC) or non-dihydropyridine AK (IIa C; in the absence of clinical signs of heart failure); in the presence of severe CHF, digoxin (IIb C) and / or amiodarone (IC) can be used.
6. elderly: with age, in terms of preventing thromboembolic complications, the effectiveness of antiplatelet agents decreases, but the effectiveness of oral anticoagulants remains; but in the elderly gradually, despite the continued use of anticoagulants, the risk of stroke and other thromboembolism increases.
7. valve defects: with a combination of defects in the atrioventricular valves, only oral anticoagulants; in the presence of a defect in the mitral valve, it is worth considering its correction separately. The target values ​​of the INR for the mitral valve prosthesis are at least 2.5, for the aortic valve - 2.0 (I B).
8. pregnancy: ECV is possible in all trimesters (the same power charges) - IC; in the first trimester, try to avoid any drugs; beta-blockers are best avoided (fetal growth retardation); in terms of anticoagulant therapy: only at high risk of TE, in the first trimester only heparin or LMWH, VKA only from the 2nd trimester (IC) and canceled a month before delivery (IB); to reduce heart rate, beta-blockers and AK (very carefully in the first trimester) - IIa C; in terms of restoring the rhythm, you can use flecainamide or ibutilide - IIb C; with contraindications to beta-blockers and AK, digoxin - IIb C can be used.
9. postoperative AF: 30% after CABG, 40% after valve surgery, and 50% after combined heart surgery develop AF; effective prophylaxis - beta-blockers and amiodarone also, but less effectively reduce the risk of sotalol and atrial pacing; ACE inhibitors and ARBs, as well as corticosteroids, statins - debatable, sometimes even harmful.
10. CHF: to control heart rate, first of all, beta-blockers - I A. If they are not effective enough, digoxin - I B. Non-dihydropyridine AKs only with intact EF and with ineffective beta-blockers - IIb C. In unstable hemodynamics and low EF, it is recommended to start treatment with amiodarone – I B; in the absence of DPP, an alternative in such cases is digoxin - I C. If there are indications for CRT, decide on ablation of the AV node - IIa B. In severe CHF and unstable hemodynamics, only amiodarone to control the rhythm - I C. Consideration of RFA – IIb B.
11. DPP: in the presence of a combination of symptomatic DPP and AF, RFA is indicated - I A; in socially responsible professions, even with non-symptomatic DPP and AF - I B. In asymptomatic, but clearly manifest forms of DPP and AF, RFA can also be considered (recommended for additional examination of CPES) - I B. In the absence of clear indications against the background of a combination of DPP and AF, RFA can be carried out after an explanatory conversation about possible risks at the request of the patient – ​​IIa B.

Reducing the tendency to form blood clots when taking anticoagulants increases the risk of bleeding. In order to assess their likelihood, a kind of medical calculator is used - the HAS-BLED risk scale.

To prevent undesirable consequences, a complete examination of the patient before the start of therapy, monitoring of the INR index, proper nutrition and accounting for drug interactions is necessary.

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Causes of bleeding when taking anticoagulants

Thromboembolic complications lead to death, development, gangrene of the lower extremities, acute violation of the renal and intestinal circulation.

To prevent these complications, anticoagulant therapy is prescribed for patients after surgery, especially in traumatology and orthopedics, for cancer patients, in the presence of atrial arrhythmia (),. It is also indicated for all patients who have had acute cerebral ischemia or to prevent relapse.

With long-term treatment, Warfarin is most often used, as well as relatively new medicines -,. All of them cause side effects over time, the most common of which is bleeding.

They are more susceptible to patients who have diseases:

• hemophilia or other hereditary coagulopathy (reduced blood clotting);
• congenital hypersensitivity to warfarin or other anticoagulants;
• untreated or insufficiently controlled hypertension;
• operations, childbirth;
• violations of the kidneys or liver with a severe course;
• transferred;
• malignant neoplasms;
• portal hypertension with;
• hyperthyroidism;
• high body temperature;
• viral infections;
• in the stage of decompensation;
• a sharp loss of body weight against the background of the use of drugs;
• ulcerative defect of the mucous membrane of the stomach, duodenum, ulcerative colitis;
• uterine bleeding in menopause;
• smoking cessation.

The risk of bleeding increases with age, if high doses are required and concomitant use of drugs that also reduce blood clotting.

In addition to direct (Heparin, Fraxiparin, Xarelto, Eliquis, Pradaxa), indirect (Sinkumar, Warfarin) anticoagulants, have this property:

• enzymes - Streptokinase, Fibrinolysin;
• - Kordaron,;
• antibiotics - Amoxicillin, Azithromycin, Cefalexin, Norfloxacin, Tetracycline;
• Aspirin, Paracetamol, Indomethacin, Ibuprofen;
• vitamins A, E;
• antiplatelet agents - Curantil, Tiklid,;
• antifungal - Diflucan, Orungal;
• influenza vaccine;
• anabolics;
• steroid, male sex hormones.

Other pharmacological combinations may also have undesirable consequences, therefore, all combinations of medicines, including herbal preparations (ginko, ginger, papaya, garlic), must be agreed with the doctor who prescribed antithrombotic therapy.

It is undesirable for patients to radically change the diet after selecting the desired dose. For example, incorporating cranberries or grapefruit juice, stopping leafy greens and kale, avocados, or green tea can change the state of blood clotting. Most often, bleeding occurs in the first three months of treatment.

For each risk factor present, the patient is assigned one point. The probability of blood loss is estimated as a total positive assessment of such conditions:

• systolic blood pressure above 160 mm Hg. Art.;
• the patient is on permanent hemodialysis (artificial kidney), blood creatinine is above 200 µmol/l, he underwent a kidney transplant;
• there is a chronic liver disease, in the blood test, bilirubin is 2 times higher than the norm, or / and ALT, AST transferases - 3 times;
• there was an acute violation of cerebral hemodynamics, especially the lacunar variant of stroke;
• in the past there was bleeding from an ulcer, hemorrhoids, uterine, pulmonary, renal, or there is anemia of unknown origin;
• INR must be maintained at a level of more than 3;
• age after 65 years;
• prescribed long-term use of other medications that reduce blood clotting;
• the patient abuses alcohol (more than 8 glasses per week).

If the patient scored more than three points, then he is included in the high-risk group, which means that he needs constant and frequent monitoring of INR.

Is it possible to avoid bleeding with long-term use

To prevent hemorrhagic complications of anticoagulant therapy, a thorough examination of patients before prescribing drugs is necessary. It may include:

• gastroduodenoscopy and sigmoidoscopy for diseases of the digestive tract or suspicion of them;
• Ultrasound of the vessels of the head, heart, abdominal organs;
• EEG, with angiography for signs of cerebrovascular accident;
• blood tests: general, hepatic and renal complex, tumor markers, coagulogram;
• examination of the fundus;
• urine and stool tests for occult blood.

Many of these diagnostic methods need to be used regularly during therapy. Regular INR testing is required for all patients, but especially for those at high risk of bleeding. Initially, the study is carried out daily until the indicator stabilizes. Depending on the individual response, it may take 5 to 10 days. Then, an analysis is prescribed once a month for low and moderate risk and weekly for high risk.

Patients need to exclude unwanted drug combinations, alcohol, a sharp change in diet. In addition, there are specific preventive measures when prescribing specific medications.

Aspirin

To prevent bleeding, the use of minimal doses is required, especially for elderly patients, in the presence of smoking, digestive disorders, peptic ulcer or gastritis, and a history of pancreatitis. It is not recommended to simultaneously prescribe other anti-inflammatory drugs with Aspirin.

Patients who have diseases of the stomach or intestines, as well as an increased likelihood of their occurrence, are prescribed:

• drugs that reduce the acidity of gastric juice (proton pump inhibitors) - Nexium or Lancid;
• gastroscopic and microbiological control of cure in the presence of peptic ulcer;
• tablets of acetylsalicylic acid with an acid-resistant shell (Aspirincardio, Thrombo Ass) or containing magnesium hydroxide (Cardiomagnyl, Magnikor).

With the risk of cerebral hemorrhage, the main emphasis is on maintaining blood pressure in the range of 130-140 / 85-90 mm Hg. Art.

warfarin

The international normalized ratio remains the most important indicator for determining the effect and safety of drug therapy. When it is increased to 4 units, the probability of developing a hemorrhagic stroke increases by about 5 times. The second criterion is the time when the INR is elevated, it should not be allowed to exceed the therapeutic range (2 - 3 units) for most of the course of treatment.

One of the contraindications to prescribing the drug is the impossibility of regular measurement of INR. In the absence of outside control, Warfarin is not recommended for patients who can forget about the dose taken (dementia, encephalopathy) and drink more than required.

It should also be borne in mind that it is extremely important for this medication to exclude the replacement of one trade name with another. There was evidence that when changing Warfarin Nycomed to a generic Warfarex or Warfarin from another manufacturer, as well as from a generic drug to the original INR, you need to select it again.

New drugs

Xarelto, Eliquis and Pradaxa have proven to be fairly safe medicines. With their use, intracranial bleeding, massive and moderate hemorrhages occurred less frequently, but when using high doses, the risk of gastrointestinal hemorrhage was higher, especially in elderly patients. Therefore, before the age of 65, it is less dangerous to prescribe new anticoagulants, and later - Warfarin.

Anticoagulants slow down the blood clotting activity, so one of the main side effects of their use is bleeding. They often appear at the beginning of therapy when selecting the desired dose. To assess the risk of this complication, a special scale is used. It includes the most significant causes of bleeding. There are also individual underlying diseases, drug interactions that need to be taken into account during treatment.

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With thrombophlebitis and against embolism, Xarelto is prescribed, indications for the use of which include certain pathologies of the heart. The method of using the tablets is chosen by the doctor. Side effects of the drug may occur with prolonged use.

CHA2 DS2 -VASc

Thromboembolic complications risk assessment scale in patients with atrial fibrillation/flutter

Prevention of thromboembolic complications in patients with atrial fibrillation/flutter

Note: * With mechanical prosthetic heart valves, the target INR may be higher.

CHADS2

Stroke risk score in patients with atrial fibrillation/flutter

Prepared by I.S. Yavelov

Bleeding risk score: high risk with score ≥ 3

The Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Guidelines for the management of atrial fibrillation. European Heart Journal. Published online: August 29, 2010 doi:10.1093/eurheartj/ehq278

Use of anticoagulants for stroke prevention in non-valvular AF

Sum of scores on the CHADS2 scale ≥2

Use CHA2 DS2 VASC

The Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC).

Guidelines for the management of atrial fibrillation. European Heart Journal. Published online: August 29, 2010

Shows better results than standard bleeding risk scores that are based on clinical risk factors only. As is known, the benefit of using oral anticoagulants (OACs) in AF is based on a balance between a reduced risk of ischemic stroke and an increased risk of major bleeding. At the moment, to assess the risk of bleeding against the background of OAC, the most commonly used scale is HAS-BLED that takes into account clinical risk factors. However, in recent years, information has been received that some biomarkers can provide additional information about the risk of bleeding in patients with AF, so it would be reasonable to assume that our ability to predict these complications would improve if these variables were included in the model. The new scale for assessing the risk of bleeding was called ABC (from the English words "age", "biomarkers" and clinical history). It has been able to demonstrate higher sensitivity and appropriateness scores than the popular HAS-BLED and ORBIT clinical scales, so it has good prospects as a tool to inform clinical decisions about anticoagulation in patients with AF. The research on this new scale was published in the June 4, 2016 issue of the Lancet.

This study was carried out by a team of scientists from Uppsala University in Sweden with financial support from Bristol-Myers Squibb, Pfizer, Boehringer Ingelheim and Roche Diagnostics. The scientists included in the new model those of the available biomarkers that seemed to them to have the highest predictive value in assessing the risk of bleeding in AF. These included differentiating growth factor-15 (GDF-15), which is a marker of oxidative stress; troponin T, determined by highly sensitive assay methods (hs-TnT), which is a marker of myocardial damage; used to assess kidney function cystatin C or estimated glomerular filtration rate (eGFR), as well as markers of anemia (hemoglobin or hematocrit). The model also included clinical risk factors and the level of the N-terminal fragment of the precursor of brain natriuretic peptide type B (NT-proBNP), which was used as a biomarker for stroke risk.

Initially, the new risk score was validated in a large cohort of patients who participated in the ARISTOLE study (Apixaban for Reduction in Stroke and other Thromboembolic Events in Atrial Fibrillation), in which patients received either apixaban (Eliquis, manufactured by Bristol-Myers Squibb/Pfizer) or warfarin. Biomarker data were available for a total of 14,537 ARISTOLE participants. Major bleeding occurred in 662 people.

Additional Information: Even short-term use of NSAIDs in patients with atrial fibrillation on anticoagulants increases the risk of bleeding

Using the new ABC Bleeding Risk Scale, the researchers found that the strongest predictors of major bleeding in ARISTOLE participants were GDF-15, hemoglobin, hs-TnT, age, and previous bleeding history. These five variables were included in a new, revised version of the ABC model, whose ability to predict major bleeding risk was compared with that of the HAS-BLED score and the newer ORBIT score. The so-called c-index was 0.68 for the ABC scale (its value of 1.0 corresponds to the ideal resolution of the model, and the value of 0.5 is considered poor and approximately corresponds to the predictive value of a coin toss). The HAS-BLED score had a c-index of 0.61, while the ORBIT score had a c-index of 0.65. Differences between both of these scales and the ABC scale were significant :P<0,001 для шкалы HAS-BLED и P=0,0008 для шкалы ORBIT. Шкала ABC демонстрировала равные результаты у пациентов, которые получали в рамках исследования апиксабан или варфарин, и никаких значимых взаимодействий с эффектами тестировавшихся препаратов обнаружить не удалось.

The investigators then moved on to external validation of their results using biomarker data from the RE-LY study (Randomized Evaluation of Long-term Anticoagulation Therapy), in which AF patients received either dabigatran (Pradaxa, manufacturer Boehringer Ingelheim) or warfarin. Archival biomarker blood samples were available for 8468 patients, with 463 major bleeding events reported during the study. In the RE-LY study population, the new ABC scale also demonstrated a higher c-index than two competing scales: for ABC, the c-index was 0.71, for the HAS-BLED scale - 0.62, for the ORBIT scale - 0.68 (differences were highly significant :P<0,0001 и P=0,0016, соответственно). Шкала ABC также превосходила шкалы HAS-BLED и ORBIT с точки зрения способности прогнозировать внутричерепные кровоизлияния: значения c-индекса для трех шкал составили 0,66, 0,58 и 0,60, соответственно). Внешняя валидизация является важным шагом при подтверждении ценности новых шкал, и, таким образом, шкала ABC успешно справилась с этим этапом, превзойдя конкурентные шкалы.

It should also be noted that the new scale also assessed the risk of bleeding equally well in various subgroups of patients with AF and even proved to be able to accurately predict the risk in patients with low HAS-BLED and ORBIT scores.

Answering the question about the availability of a new scale for real practical application, the authors of the work reported that highly sensitive methods for determining troponin are already available in many countries of the world, and in June 2016. Roche plans to launch a new GDF-15 biomarker kit. As for the complexity of calculations, the authors do not consider this a significant problem: doctors are already actively using nomograms, electronic calculators or mobile applications to determine such frequently used parameters as, for example, creatinine clearance or GRACE score, so, given the practical value of the scale ABC, most likely, similar auxiliary tools will quickly appear for it too.

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HAS-BLED scale

The HAS-BLED score is a simple and reliable clinical tool for assessing the risk of major bleeding within 1 year. Major bleeding refers to: any intracranial hemorrhage, bleeding requiring hospitalization, or accompanied by a decrease in hemoglobin > 2 g/l, or requiring blood transfusion.

The scale was created on the basis of a real cohort consisting of 3978 patients with atrial fibrillation.

The bleeding risk score was introduced by R. Pister et al. in 2010 and was named HAS-BLED as an acronym:

— Hypertension - hypertension (systolic blood pressure > 160 mmHg);

— Abnormal renal/liver function - impaired renal function- 1 point (chronic dialysis, or serum creatinine > 200 µmol/l, or a history of kidney transplantation) and/orliver dysfunction- 1 point (chronic liver disease or functional disorders: bilirubin > 2× upper limit of normal, or elevated aspartate aminotransferase/alanine aminotransferase/alkaline phosphatase > 3× upper limit of normal);

— Stroke - stroke;

— Bleeding history or predisposition - history of bleeding and / or predisposition to them (eg, hemorrhagic diathesis, anemia);

— Labile international normalized ratio (INR)— labile international normalized ratio< 60 % (an indicator of the blood coagulation system, calculated when determining the prothrombin time, the indicator was introduced for uniformity in assessing the effect of anticoagulants on the prothrombin time and correcting the prescription of anticoagulant doses);

— Elderly - age (> 65 years old);

— Drugs/alcohol concomitantly (eg, anticoagulants and non-steroidal anti-inflammatory drugs)— 1 point and/or alcohol- 1 point.

1 point is assigned for each item, the result is a simple sum of points. The maximum number of points on the scale is 9.

The effectiveness of any antithrombotic treatment must be balanced against the risk of major bleeding, especially intracerebral bleeding, which is often fatal. Therefore, the risk of bleeding should be assessed before prescribing anticoagulants in patients with atrial fibrillation.

Patients at high risk of bleeding (HAS-BLED score > 3) should undergo regular clinical evaluation after initiation of oral anticoagulant therapy.

The HAS-BLED scale has been included in the European and Canadian recommendations for the treatment of atrial fibrillation since 2010. The score has been validated in various independent cohorts and correlates well with the risk of intracerebral hemorrhage.

Bibliography

1. Pisters R., Lane D.A., Nieuwlaat R., de Vos C.B., Crijns H.J., Lip G.Y. 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 Nov. - 138(5). — 1093-100.

2. Authors/Task Force Members, Camm A.J., Lip G.Y., De Caterina R. et al. 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: An update of the 2010 ESC Guidelines for the management of atrial fibrillation. Developed with the special contribution of the European Heart Rhythm Association // Eur. Heart J. - 2012 Nov. - 33(21). — 2719-47.

3. Lip G.Y., Frison L., Halperin J.L., Lane D.A. Comparative validation of a novel risk score for predicting bleeding risk in anticoagulated patients with atrial fibrillation: the HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly) score / / J. Am. Coll. cardiol. - 2011 Jan 11. - 57(2). — 173-80.