Impact of Clinical Pharmacist in an Anticoagulation Management Service in several countries
[Abstract] Objective: To assess the impact of a clinical pharmacist in an anticoagulation management service, and especially on the oral anticoagulation therapy.
Methods: Through four reviewers independently searched the MEDLINE, High Wire, CNKI and Google Scholar databases and using some key words such as “warfarin”, “clinical pharmacist”, or "anticoagulation service", and "patient education" peer-reviewed English, Chinese and French languages articles were identified from January 1, 1979, through October 31, 2008. In-patient pharmacist interventions were selected if they included a control group and objective patient-specific health outcomes; type of intervention, study design, and outcomes such as adverse drug events, medication appropriateness and resource use were abstracted.
Results: Seventy-seven studies met inclusion criteria, including 9 evaluating pharmacists’ participation on rounds, 18 medication reconciliation studies, 19 on drug-specific pharmacist services, and 31 on organization of oral anticoagulation treatment and Anticoagulation service’s setting. Adverse drug events,adverse drug reactions, or medication errors were reduced in 7 of 12 trials that included these outcomes. Medication adherence, knowledge, and appropriateness improved in 7 of 11 studies, while there was shortened hospital length of stay in 9 of 17 trials. No intervention led to worse clinical outcomes and only 1 reported intensive health care use. Improvements in both inpatient and out-patient outcome measurements were observed.
Conclusions:Regardless the country, even if the anticoagulation service’s management is a bit different from one country to another, the addition of clinical pharmacist services in the care of inpatients and outpatients generally resulted in improved care, with no evidence of harm. Interacting with the health care team on patient rounds, interviewing patients, reconciling medications, providing patient discharge counseling, laboratory and clinical monitoring and follow-up all resulted in improved outcomes. Future studies should include multiple sites, larger sample sizes, reproducible interventions, and identification of patient-specific factors that lead to improved outcomes.
The role of clinical pharmacists in the care of hospitalized and non-hospitalized patients has evolved over time, with increased emphasis on collaborative care and patient interaction. CLINICAL PHARMACISTS are uniquely trained in therapeutics and provide comprehensive drug management to patients and providers (includes physicians and additional members of the care team). Pharmacist intervention outcomes include economics, health-related quality of life, patient satisfaction, medication appropriateness, adverse drug events (ADEs), and adverse drug reactions (ADRs). An ADE is defined as “an injury resulting from medical intervention related to a drug,” and an ADR is defined as “an effect that is noxious and unintended and which occurs at doses used in man for prophylaxis, diagnosis, or therapy.”  Generally we get two main types of patients (Inpatient and outpatient) and according to these two categories of patients; the education (service) approach carried out by the pharmacist is quite different in few issues.Anticoagulant medicine prevents harmful blood clots from forming in blood vessels. In primary care, anticoagulants are one of the classes of medicines most commonly associated with fatal medication errors. There are two main types of anticoagulants: (a) oral anticoagulants (Mainly the Warfarin); and (b) anticoagulants that have to be injected or infused (Ex: Heparin). To use anticoagulants safely, patients must have their treatment explained to them by a healthcare professional at the start of the treatment, when they leave hospital and at their first anticoagulant clinic appointment. Written information should always be given and advice should be available throughout the treatment, whenever the patient needs it. However we should acknowledge or notice that all the hospitals don’t have the same standard of the anticoagulation clinic (ACC) or anticoagulation service (ACS). In this article, we will be giving more and deeper information on the Oral anticoagulation (basically on Warfarin).
Concepts about the Anticoagulants
As we noticed above, the anticoagulants are in two main types: oral anticoagulants (Warfarin is the wide common used) and anticoagulants that have to be injected or infused (heparin remains the most common used).The commonest clinical indications for the use of oral anticoagulants are: atrial fibrillation (abnormal beating of the heart that can cause blood pooling and embolus (clot) formation in the small chambers of the heart (atria); the treatment and prevention of deep vein thrombosis and pulmonary embolus (clot formation in the blood vessels in the lungs); and the treatment of patients with mechanical heart valves, where the artificial valves may lead to clot formation. Heparin is used in high doses to treat venous thromboembolism (deep vein thrombosis and pulmonary embolism) and in lower doses for prophylaxis (prevention) of thromboembolism in surgical patients and pregnant women at risk. It is also used in the management of arterial thromboembolism including that associated with unstable angina, myocardial infarction and stroke. 
ØMechanism of Action:
üWarfarin, the main oral anticoagulant inhibits clotting by limiting hepatic production of the biologically active vitamin K-dependent clotting factors (activated factors II, VII, IX, and X). Normally, the precursors of these factors undergo a carboxylation reaction to be converted to their activated forms. Warfarin, as a vitamin K antagonist, interferes with this reaction. The reduction in the amount and activity of these factors produces the anticoagulant response. However, Warfarin also interferes with production of body’s natural anticoagulants, protein C and protein S, and can therefore sometimes exert a procoagulant response.  Because the anticoagulant response to Warfarin varies among patients, it is standard practice to adjust the its dose and monitoring its effect by measurement of the International Normalized Ratio (INR)
üHeparin produces its major anticoagulant effect by inactivating thrombin and activated factor X (factor Xa) through an antithrombin (AT)-dependent mechanism. It binds to AT through a high-affinity pentasaccharide, which is present on about a third of heparin molecules. For inhibition of thrombin, heparin must bind to both the coagulation enzyme and AT, whereas binding to the enzyme is not required for inhibition of factor Xa. Molecules of heparin with fewer than 18 saccharides lack the chain length to bridge between thrombin and AT and therefore are unable to inhibit thrombin. In contrast, very small heparin fragments containing the pentasaccharide sequence inhibit factor Xa via AT. By inactivating thrombin, heparin not only prevents fibrin formation but also inhibits thrombin-induced activation of platelets and of factors V and VIII. Like every anticoagulant, the anticoagulant effect varies among patients with tromboembolic disorders. It is standard practice to adjust the dose of the heparin and monitor its effect by measurement of the activated thromboplastin time (APTT) or, when very high doses are used, by the activated clotting time (ACT).
ØPharmacokinetics and pharmacodynamics of Warfarin:
üPharmacokinetics: Knowledge of the pharmacokinetics of Warfarin is helpful in understanding the initial response to therapy. Warfarin can be detected in the plasma one hour after oral administration, and peak concentrations occur in two to eight hours. Warfarin is a racemic mixture of stereo isomers, which are 99 percent bound to albumin.  The drug is metabolized in the liver and kidneys, with the subsequent production of inactive metabolites that are excreted in the urine and stool. The half-life of racemic warfarin ranges from 20 to 60 hours. The mean plasma half-life is approximately 40 hours, and the duration of effect is two to five days. Thus, the maximum effect of a dose occurs up to 48 hours after administration, and the effect lingers for the next five days.
üPharmacodynamics: Talking about the pharmacodynamics of warfarin, we should notify and distinguish its anticoagulant activity and the antithrombotic effect.
Anticoagulant activity: The anticoagulant activity of warfarin depends on the clearance of functional clotting factors from the systemic circulation after administration of the dose. The clearance of these clotting factors is determined by their half-lives. The earliest changes in the International Normalized Ratio (INR) are typically noted 24 to 36 hours after a dose of warfarin is administered. These changes are due to the clearance of functional factor VII, which is the vitamin K dependent clotting factor with the shortest half-life (six hours). However, the early changes in the INR are deceptive because they do not actually affect the body's physiologic ability to halt clot expansion or form new thromboses.
Antithrombotic effect: The antithrombotic effect of warfarin, or the inability to expand or form clots, is not present until approximately the fifth day of therapy. This effect depends on the clearance of functional factor II (prothrombin), which has a half-life of approximately 50 hours in patients with normal hepatic function. 
The difference between the antithrombotic and anticoagulant effects of warfarin need to be understood and applied in clinical practice. Because antithrombotic effect depends on the clearance of prothrombin (which may take up to five days), loading doses of warfarin are of limited value. Because warfarin has a long half-life, increases in the INR may not be noted for 24 to 36 hours after administration of the first dose, and maximum anticoagulant effect may not be achieved for 72 to 96 hours.
The Anticoagulation Treatment:
In the past few years the number of patients undergoing oral anticoagulant treatment (OAT) has been exponentially increasing all over the world. This is due mainly to the improved knowledge of OAT indications by hospital specialists and general practitioners, to the extension of clinical indications to more elderly patients, and to the establishment of dedicated hospital departments, the Haemostatic and
The goal of maintenance therapy is to achieve a regimen that is simple yet provides therapeutic anticoagulation. Currently, many physicians use drug regimens that appear simple but require differing tablet strengths. These regimens can be confusing to elderly patients who are taking several other medications concurrently and who may confuse tablet colors and strengths. Effective anticoagulation can be achieved using a single tablet strength and alternating fractions or multiples of that tablet on given days of the week rather than on odd or even days
Effective anticoagulation therapy requires systematic, coordinated patient care management through specialized institutes (Anticoagulation Clinic) by prepared anticoagulation therapy providers (Specialist physicians, clinical pharmacists, nurses etc). As the use of anticoagulant therapy has increased in the last few years, the need for advanced educational preparation in patient care management has emerged.
ØThe Anticoagulation Management Service:
The Anticoagulation Clinic (ACs) is designed to help patients manage their anticoagulation medications. Physically, the anticoagulation clinic is located in the hospital pharmacy where the pharmacists are working in conjunction with physicians. Briefly, ACs should provide a series of medical services with the aim of a) determining the appropriate clinical indications for anticoagulant treatment; b) determining the laboratory tests necessary to pharmacological monitoring; c) prescribing the anticoagulation regimen based on the results of the laboratory tests; d) defining the time intervals for regular anticoagulation controls; e) assessing the potential pharmacological interactions; f) taking care of patients undergoing surgical interventions; and g) carrying out education programs for patients and healthcare providers. 
üKey Components to Consider When Developing an Anticoagulation System:
Patient safety committees should consider assessing anticoagulation safety to help define their organization’s needs before an Anticoagulation clinic setting. This self-assessment allows facilities to outline the positive impact that an ACS program will have to provide safer care and maximize patient outcomes. An individualized Anticoagulation management service is based on the organization’s specific needs, resources, and experiences.
These keys components include the following: Define Rationale for ACS Development (Develop a multidisciplinary AMS program committee comprising physicians, pharmacists, nurses, clinical laboratory, and information technology. Evaluate current anticoagulation processes to clearly define the future AMS program development) , Outline Issues Associated with Anticoagulation Medications (Review literature relating to the use of anticoagulation agents and Standardize the use of anticoagulants.) , and Define AMS Scope of Service and Infrastructure (Determine team composition of AMS program, Develop formal anticoagulation competencies for physicians, pharmacists, and nurses to assess baseline and ongoing knowledge about anticoagulation therapy and Develop a well-designed anticoagulation patient and family educational program to help increase compliance and contribute to improved patient outcomes) 
Patients Check in ACs
-Refers patient to physician
The Impact of a Clinical Pharmacist-managed anticoagulation clinic:
The discipline of clinical pharmacy has been involving in the anticoagulation service for over 20 years in developing countries. The role of the clinical pharmacist include providing therapeutic monitoring, warfarin dosage adjustment, triage of warfarin-related and unrelated problems, patient counseling and education, and, co-ordination of the anticoagulation clinic activities. Monitoring parameters include INR, signs and symptoms of hemorrhagic and tromboembolic events, drug-drug interactions, drug-food interactions, drug-disease interactions and patient compliance. The concept of pharmacist managing anticoagulation therapy is not new. Ambulatory care pharmacists have performed this function for years,  with more recent reports supporting pharmacists’ involvement inside of the hospital. Regardless the normal role of the clinical pharmacist at the clinical clinic, we should notice that in every country, the anticoagulation clinic and the practical role of the clinical pharmacist in these units don’t meet the same standard and settings. Therefore the impact of the clinical pharmacist in the ACS is quite different from one nation to another one.
ØImpact of the Clinical Pharmacist in ACS in
Some others studies have showed that evaluation of pharmacist-led ACS have gone beyond the assessment of clinical outcomes to consider economic impacts. One of these studies found that “if pharmacist-managed warfarin were available for all Medicare patients who received Warfarin therapy in U.S. hospitals, we could expect 9,862 fewer deaths, 1,120,699 fewer patients-days ,and $
ØImpact of the Clinical Pharmacist in ACS in
Therefore from above, we widely notice like in The US, the clinical pharmacist has a great impact in the anticoagulation clinic in
ØImpact of the Clinical Pharmacist in ACS in
In Asia the concept of the Anticoagulation Clinic has not been widely developed as it is in the
By all measures, the pharmacist-managed anticoagulation clinic was a success to the point that the Korean Society of Hospital Pharmacists (KSHP) and Korean colleges of pharmacy took a special interest in the pharmacist-managed anticoagulation clinic.
Management of warfarin therapy in Chinese patients has been challenging because Chinese patients are reported to be more sensitive to the anticoagulation effect of warfarin and require a 40–50% lower maintenance dose of the drug when compared with Europeans . The incidence of major bleeding increased sharply as INR rose from 2.4 to
After two years of study ( November 2002 – June 2004) the pharmacist-managed anticoagulation service was more effective and less costly than the physician-managed service in achieving target anticoagulation control for Chinese patients on warfarin therapy. The patients in the pharmacist-managed group showed a significantly higher overall patient satisfaction score compared with that of the physician-managed group, attributed to the improved satisfaction scores in technical quality, interpersonal manner, communication, time spent and accessibility. In addition, the pharmacist conducted telephone follow-up for selected patients with difficult INR control or adherence issues between their clinic visits and a phone line was available for accessing pharmacist consultation.  In the present study, the Chinese patients in the pharmacist-managed group spent more time in the therapeutic and the expanded therapeutic INR ranges when compared with those in the physician-managed group and the difference achieved statistical significance. The pharmacist-managed anticoagulation service was more effective and less costly than the physician-managed service in achieving target anticoagulation control for Chinese patients on warfarin therapy.
Recent years have seen an increase in interest in the management of oral anticoagulants. However, the risk of therapy with oral anticoagulatants is high because of the following factors: the narrow therapeutic range of the anticoagulants, patient characteristics and the variable quality of care depending on the management system. Under-anticoagulation can result in thrombosis which can be life threatening. Equally over-anticoagulation can result in haemorrhage (bleeding) which can be fatal and outweigh the benefits of preventing the thrombosis (Fitzmaurice and Murray, 2002). Anticoagulation Clinic Service provides a vital resource for physicians, clinical pharmacist, multi-specialty clinics and patients. The key to the successful Anticoagulation Clinic Service is defining an integrated business model which maximizes the utilization of existing resources, coordinates institutional strengths and acknowledges opportunities for both revenue generation and cost savings as a background of escalating patient satisfaction. Several studies surveyed the impact of the type of anticoagulation management on effective patient outcome. Numerous articles and abstracts have been published related the impact of pharmacist-managed anticoagulation services. Pharmacists have served a vital role in managing and monitoring anticoagulation therapy since the 1970s. Pharmacist managed clinics have been shown to decrease warfarin-related hospital admissions and major thromboembolic events.
Involvement of pharmacists in anticoagulant therapy is an accepted part of pharmacy practice in many countries. In the clinical pharmacist-managed anticoagulation clinic, patients have been provided intense education; the clinical pharmacists checked the patients’ adherence more thoroughly and, as a drug expert, provided extra attention to the potential warfarin-drug and warfarin-herb interactions at each clinic visit. Moreover, the pharmacist also conducted telephone follow-up. Evaluations of pharmacist-led ACS have also gone beyond the assessment of clinical outcomes to consider economic impacts. The role of pharmacists was shown to have both financial and quality benefits to the Anticoagulation Clinic and to the hospital.
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