Alcohol

Some Critical Notices Should Knowing When Using Warfarin

June 30, 2017 Anticoagulant Therapy, Hematology, Laboratory Medicine No comments , , , , , , , , , , , ,

PT/INR and Anticoagulation Status

For the vast majority of patients        , monitoring is done using the prothrombin time with international normalized ratio (PT/INR), which reflects the degree of anticoagulation due to depletion of vitamin K-dependent coagulation. However, attention must be paid that the PT/INR in a patient on warfarin may note reflect the total anticoagulation status of the patient in certain settings:

  • First few day of warfarin initiation

The initial prolongation of the PT/INR during the first one to three days of warfarin initiation does not reflect full anticoagulation, because only the factor with the shortest half-life is initially depleted; other functional vitamin K-dependent factors with longer half-lives (e.g., prothrombin) continues to circulate. The full anticoagulation effect of a VKA generally occurs within approximately one week after the initiation of therapy and results in equilibrium levels of functional factors II, IX, and X at approximately 10 to 35 percent of normal.

  • Liver disease

Individuals with liver disease frequently have abnormalities in routine laboratory tests of coagulation, including prolongation of the PT, INR, and aPTT, along with mild thrombocytopenia, elevated D-dimer, especially when liver synthetic function is more significantly impaired and portal pressures are increased. However, these tests are very poor at predicting the risk of bleeding in individuals with liver disease because they only reflect changes in procoagulant factors.

  • Baseline prolonged PT/INR

Some patients with the antiphospholipid antibody syndrome (APS) have marked fluctuations in the INR that make monitoring of the degree of anticoagulation difficult.

Time in the Therapeutic Range (TTR)

For patients who are stably anticoagulated with a VKA, the percentage of time in the therapeutic range (TTR) is often used as a measure of the quality of anticoagulation control. TTR can be calculated using a variety of methods. The TTR reported depends on the method of calculation as well as the INR range considered “therapeutic.” A TTR of 65 to 70 percent is considered to be a reasonable and achievable degree of INR control in most settings.

Factors Affecting the Dose-Response Relationship Between Warfarin and INR

  • Nutritional status, including vitamin K intake
  • Medication Adherence
  • Genetic variation
  • Drug interactions
  • Smoking and alcohol use
  • Renal, hepatic, and cardiac function
  • Hypermetabolic states

In addition, female sex, increased age, and previous INR instability or hemorrhage have been associated with a greater sensitivity to warfarin and/or an increased risk of bleeding.

Dietary Factors

Vitamin K intake – Individuals anti coagulated with warfarin generally are sensitive to fluctuations in vitamin K intake, and adequate INR control requires close attention to the amount of vitamin K ingested from dietary and other sources. The goal of monitoring vitamin K intake is to maintain a moderate, constant level of intake rather than to eliminate vitamin K from the diet. Specific guidance from anticoagulation clinics may vary, but a general principle is that maintaining a consistent level of vitamin K intake should not interfere with a nutritious diet. Patients taking warfarin may wish to be familiar with possible sources of vitamin K (in order to avoid inconsistency).

Of note, intestinal microflora produce vitamin K2, and one of the ways antibiotics contribute to variability in the prothrombin time/INR is by reducing intestinal vitamin K synthesis.

Cranberry juice and grapefruit juice have very low vitamin K content but have been reported to affect VKA anticoagulation in some studies, and some anticoagulation clinics advise patients to limit their intake to one or two servings (or less) per day.

Medication Adherence

Medication adherence for vitamin K antagonists can be challenging due to the need for frequent monitoring and dose adjustments, dietary restrictions, medication interactions, and, in some cases, use of different medication doses on different days to achieve the optimal weekly intake. Reducing the number of medications prescribed may be helpful, if this can be done safely.

Drug Interactions

A large number of drugs interact with vitamin K antagonists by a variety of mechanisms, and additional interacting drugs continue to be introduced. Determine clinically important drug interactions is challenging because the evidence substantiating claims for some drug is very limited; in other cases, the evidence is strong but the magnitude of effect is small. Patients should be advised to discuss any new medication or over-the-counter supplement with the clinician managing their anticoagulation, and clinicians are advised to confirm whether a clinically important drug-drug interaction has been reported when introducing a new medication in a patient anticoagulated with a VKA.

Smoking and Excess Alcohol

The effect of chronic cigarette smoking on warfarin metabolism was evaluated in a systematic review and that included 13 studies involving over 3000 patients. A meta-analysis of the studies that evaluated warfarin dose requirement found that smoking increased the dose requirement by 12 percent, corresponding to a requirement of 2.26 additional mg of warfarin per week. However, two studies that evaluated the effect of chronic smoking on INR control found equivalent control in smokers and non-smokers.

The mechanisms by which cigarette smoking interacts with warfarin metabolism is by causing enhanced drug clearance through induction of hepatic cytochrome P-450 activity by polycyclic aromatic hydrocarbons in cigarette smoke. Nicotine itself is not thought to alter warfarin metabolism.

The interaction between excess alcohol use and warfarin anticoagulation was evaluated in a case-control study that compared alcohol use in 265 individuals receiving warfarin who had major bleeding with 305 controls from the same cohort receiving warfarin who did not have major bleeding. The risk of major bleeding was increased with moderate to severe alcohol use and with heavy episodic drinking.

Mechanism by which alcohol use interacts with warfarin anticoagulation are many, and the contribution of various factors depends greatly on the amount of intake and the severity of associated liver disease. Excess alcohol consumption may interfere with warfarin metabolism. Severe liver disease may also be associated with coagulopathy, thrombocytopenia, and/or gastrointestinal varices, all of which increase bleeding risk independent of effects on warfarin metabolism.

Comorbidities

The major comorbidities that affect anticoagulation control are hepatic disease, renal dysfunction, and heart failure. In addition, other comorbidities such as metastatic cancer, diabetes, or uncontrolled hyperthyroidism may also play a role.

The liver is the predominant site of warfarin metabolism. It is also the source of the majority of coagulation factors. Thus, liver disease can affect warfarin dosage, INR control, and coagulation in general. Importantly, individuals with severe liver disease are not “auto-anticoagulated,” because they often have a combination of abnormalities that both impair hemostasis and increase thrombotic risk.

Warfarin undergoes partial excretion in the kidney. Patients with kidney disease can receive warfarin, and management is generally similar to the population without renal impairment; however, dose requirement may be lower.

Heart failure has been shown to interfere with INR stabilization.

Acute illnesses may alter anticoagulation through effects on vitamin K intake, VKA metabolism, and medication interactions, especially infections and gastrointestinal illnesses.

Genetic Factors

Genetic polymorphisms have been implicated in altered sensitivity to warfarin and other vitamin K antagonists.

[Clinical Skills] Taking Medication History

April 6, 2016 Clinical Skills, Practice No comments , , ,

1.Ask open-ended questions at the start of the interview and then move to more direct and targeted questions as the interview proceeds.

e.g., to ask the patient to describe any medications taken daily;
e.g., to ask the patient to describe the size, shape, and color of the medication regularly taken (a more direct and targeted question).

2.Avoid asking leading questions, multiple questions, and excessive yes/no questions.

e.g., a leading question such as "Does your tuberculosis medication turn your urine red?" may make the patient think the medication is supposed to turn the urine red and that something is wrong with the patient if his or her urine is not red.

3.Probe for medication-related effects by asking more general questions.

e.g., "How are you tolerating your tuberculosis medications?", "Have you noticed anything different or unusual since you started taking the medication?"

4.Avoid the trap of asking a series of rapid-fire questions without giving the patient time to answer. Give the patient ample time to address each question before asking another question.

5.Getting into a pattern of asking a series of yes/no questions also is very easy, especially toward the end of the interview, when the pharmacist asks specific and targeted questions.

This type of rapid-fire yes/no questions creates one-sided conversations and may diminish the flow of information from patients.

e.g., "Do you take anything for headache?", "Do you take anything for your eyes?", "Do you take anything for your heart?", "Do you take anything for your breathing?", "Do you take anything when you have a cold?", "Have you ever taken penicillin?"

6.Encourage patients to talk about their experience with medications.

Demographic Information

  • Age/date of birth
  • Height and weight
  • Race and/or ethnic origin
  • Type of residence
  • Education
  • Occupation
  • Lifestyle

Housing situation (e.g., loarding hourse, private home, apartment, shelter, living on the street)

The people living with the patient (e.g., spouse, young children, elderly relatives, extended family)

The patient's type of work and work schedule (i.e., day shift, night shift, rotating shift schedule, part time, full time)

Dietary Information

  • Dietary restrictions
  • Dietary supplements
  • Dietary stimulants
  • Dietary suppressants

Social Habits

  • Tobacco use

Packs per day/ppd

pack-years/pk-yr (e.g., 2 ppd for 5 years; 10 pk-yr)

  • Alcohol use (Men, women, respectively)

Lifetime abstainer

Former infrequent drinker

Current drinker

Infrequent drinker

Light drinker

Moderate drinker

Heavier drinker

Binge drinker

  • Illicit drug use

Document the duration of use, amount of each agent consumed, frequency of use, and reasons for use of each agent without being judgemental.

Determine the type, quantity, pattern, and duration of alcohol use.

Screen Shot 2016-04-06 at 6.46.32 PMTo assess tobacco use, note at what age the patient first started smoking tobacco and when the patient quit smoking (if applicable). One pack-year is equivalent to smoking one pack of cigarettes daily for 1 year. A 10 pk-yr tobacco history is quivalent to smoking 0.5 ppd for 20 years, 1 ppd for 10 years, or 2 ppd for 5 years.

Illicit drug use may be difficult to ascertain. Obtain this information in a professional, nothreatening, nonjudgmental manner. Do not try to guess which patients are more or less likely to use these agents but probe for this information with every patient. 


Current Prescription Medications

  • Name (proprietary and nonproprietary) and/or description

Dosage form (e.g., tablet, capsule, liquid, topical formulation)

Size, shape, and color of the dosage form

Any words, letters, and numbers on the dosage form that the patient can remember or that can be seen on the dosage form

  • Dose (prescribed and actual, and reason for discrepancy)
  • Dose schedule (routine times patient taking each dose, prescribed and actual, and reason for discrepancy)
  • Reason for taking the medication (including clarification any discrepancies regarding customary uses of medications with the prescriber)
  • Start date (exact date, duration of therapy)
  • Outcome of therapy

Medication Names

Patients may not be able to remember the names of all their medications. If this is the case, obtain a detail description of each medication, including the dosage form (e.g., tablet, capsule, liquid, topical formulation); size, shape, and color of the dosage form; and any words, letters, and numbers on the dosage form that the patient can remember or that can be seen on the dosage form. If the patient cannot remember the dosage of the drug, the pharmacist may be able to identify the drug and/or dosage from other details the patient provides. However, clearly document the patient's description and note that the medication might be a specific product.

Many physicians, nurses, and other health care profesionals typically know the proprietary (trade) name of the medication but are less familiar with the nonproprietary (generic) medication names. Therefore when a patient identifies a medication by the proprietary name, document both the proprietary and nonproprietary names. If the patient identifies a medication by the nonproprietary name, document the nonproprietary name. For combination medications, document the nonproprietary names of all active ingredients in the bombination  product.

Dose Schedule

Obtain the prescribed dosing schedule (e.g., four times a day, two times a day, once a day) and note the routine times the pateint takes each dose. If a discrepancy between the prescribed dosing schedule and the schedule the patient uses is apparent (e.g., the patient is supposed to take the medication four times a day but takes it two times a day), note the discrepancy and try to determine the reason the patient uses the drug differently from the way it is prescribed.

Reason for Taking the Medication and Start Date

Determine when the patient started taking the prescription medication and the reason the pateint gives for taking the medication. Exact dates are important in determining whether an adverse or allergic reaction is a result of a specific medication and whether the prescribed medication is effectively treating or controlling a specific condition. For example, a patient with elevated blood pressure may claim to adhere to his or her blood pressure medication regimen yet still have elevated blood pressure. The decision to continue or discontinue the medication depends on when the patient started the current regimen. The regimen would continue unchanged if the patient has just started the medication the previous week but would need to be changed if the patient had been taking the medication for 2 months. Some pateints may not known the specific reason they are taking their medications because they forgot or misunderstand the reason it has been prescribed. Document the reasons the patient gives for taking the medication and clarify any discrepancies regarding customary uses of medications with the prescriber, not the patient.

No Demand (prn) Medications

For as needed (prn, on demand) prescription and nonpresctiption medications, document the possible use as well as the patient's actual use of the medication. Quantification is important; do not accept imprecise descriptive terms. Patients may or may not be able to describe their frequency of use but may be able to describe how often they get the prescription refilled or buy a new supply of nonprescription medication; both given an indirect indication of frequency of use. One approach to quantifying the amount of medication actually consumed by the patient is to inquire how often the patient has to obtain a new supply of the medication.

Past Prescription Medications

  • Name (proprietary and nonproprietary) and/or description

Dosage form (e.g., tablet, capsule, liquid, topical formulation)

Size, shape, and color of the dosage form

Any words, letters, and numbers on the dosage form that the patient can remember or that can be seen on the dosage form

  • Dose (prescribed and actual, and reason for discrepancy)
  • Dose schedule (routine times patient taking each dose, prescribed and actual, and reason for discrepancy)
  • Reason for taking the medication (including clarification any discrepancies regarding customary uses of medications with the prescriber)
  • Start date (exact date, duration of therapy)
  • Stop date (exact date, duration of therapy)
  • Reason for stopping
  • Outcome of therapy

Knowledge of past prescriptions helps the pharmacist understand the medications used, either successfully or unsuccessfully, to treat current and past medical problems; this knowledge guides recommendations regarding new medication regimens. Patients are unlikely to remember all these details for past medications. Document the details the patient can remember; avoid excessive "grilling" of the patient.

Current Nonprescription Medications

  • Name (proprietary and nonproprietary) and/or description

Dosage form (e.g., tablet, capsule, liquid, topical formulation)

Size, shape, and color of the dosage form

Any words, letters, and numbers on the dosage form that the patient can remember or that can be seen on the dosage form

  • Dose (recommended/prescribed and actual, and reason for discrepancy)
  • Dose schedule (routine times patient taking each dose, recommended/prescribed and actual, and reason for discrepancy)
  • Reason for taking the medication (including clarification any discrepancies regarding customary uses of medications with the prescriber)
  • Start date (exact date, duration of therapy)
  • Outcome of therapy

Knowledge of current nonprescription medications allows the pharmacist to determine whether drug interactions may occur between prescribed and self-administered medications, whether the patient is self-medicating to relieve an adverse drug reaction from a prescribed medication or in an attempt to obtain better relief from symptoms than that provided by the prescribed regimen, and whether a nonprescription medication is the cause of a patient's complaint or is exacerbating a concurrent medical condition.

Past Nonprescription Medications

  • Name (proprietary and nonproprietary) and/or description

Dosage form (e.g., tablet, capsule, liquid, topical formulation)

Size, shape, and color of the dosage form

Any words, letters, and numbers on the dosage form that the patient can remember or that can be seen on the dosage form

  • Dose (recommended/prescribed and actual, and reason for discrepancy)
  • Dose schedule (routine times patient taking each dose, recommended/prescribed and actual, and reason for discrepancy)
  • Reason for taking the medication (including clarification any discrepancies regarding customary uses of medications with the prescriber)
  • Start date (exact date, duration of therapy)
  • Stop date (exact date, duration of therapy)
  • Reason for stopping
  • Outcome of therapy

Knowledge of past nonprescription regimens gives the pharmacist insight regarding past medical problems or attempts to treat current medical problems.

Current and Past Complementary and Alternative Medicines

  • Name (proprietary and nonproprietary) and/or description

Dosage form (e.g., tablet, capsule, liquid, topical formulation)

Size, shape, and color of the dosage form

Any words, letters, and numbers on the dosage form that the patient can remember or that can be seen on the dosage form

  • Dose (recommended/prescribed and actual, and reason for discrepancy)
  • Dose schedule (routine times patient taking each dose, recommended/prescribed and actual, and reason for discrepancy)
  • Reason for taking the medication (including clarification any discrepancies regarding customary uses of medications with the prescriber)
  • Start date (exact date, duration of therapy)
  • Stop date (exact date, duration of therapy)
  • Reason for stopping
  • Outcome of therapy

Approximately 7% of Americans take complementary and alternative medicines (e.g., herbal remedies, megavitamins, homeopathic medicine, folk remedies). However, the majority of people do not discuss these therapies with their physicians. Many of these medicines interact with traditional medicines. Some have significant side effects. Therefore, it is important to document the use of these medicines.

Ask the patient follow-up questions to clarify why the patient is taking the alternative medicine. For example, if a patient states that he or she is taking an alternative medicine to boost the immune system, ask the patient whether anyone has ever told the patient that he or she has a weakened immune system and whether the patient gets more infections than most people.

Medication Allergies

  • Drug name (proprietary and nonproprietary) and/or description

Dosage form (e.g., tablet, capsule, liquid, topical formulation)

Size, shape, and color of the dosage form

Any words, letters, and numbers on the dosage form that the patient can remember or that can be seen on the dosage form

  • Dose (recommended/prescribed and actual, and reason for discrepancy)
  • Date of reaction
  • Description of reaction
  • Treatment for the raction

Many physicians, nurses, and other health care professionals as well as patients may be unable to differentiate between a drug allergy and an adverse drug reaction. But it is very important to try to distinguish between the two reactions. Once a medication allergy is documented for a patient, it is highly unlikely that the patient will receive the medication or a similar medication again. If the reaction was a manageable or acceptable adverse reaction rather than an allergic reaction, however, the patient may be unnecessarily denied access to potentially useful medications. The term allergy indicates hypersensitivity to specific substances. Drug-induced allergic reactions include anaphylaxis, contact dermatitis, and serum sickness.

A useful first step is to ask patients whether they are allergic to any medications and then probe for the details of the problem, depending on the response. Ask patients if they have ever experienced rashes or breathing problems after taking any medications. Patients may not correlate a rash with an allergy, so it is important to probe for these details.

After a medication has been identified as the cause of an allergic reaction, ask the patient to provide details regarding the time or date of the allergic reaction and any interventions instituted to manage the reaction, and inquire whether the patient has received the medication since first experiencing the allergic reaction. Ask whether medications in similar drug classes have been taken without the occurrence of a similar reaction (i.e., “Have you taken any antibiotics since you found out you were allergic to penicillin?”).

Adverse Drug Reactions

  • Drug name (proprietary and nonproprietary) and/or description

Dosage form (e.g., tablet, capsule, liquid, topical formulation)

Size, shape, and color of the dosage form

Any words, letters, and numbers on the dosage form that the patient can remember or that can be seen on the dosage form

  • Dose (recommended/prescribed and actual, and reason for discrepancy)
  • Date of reaction
  • Description of reaction
  • Treatment for the raction

Ask patients whether they have ever taken a medication they would rather not take again. This question often elicits specific descriptions of adverse reactions the patient has experienced.


Immunizations

  • Name of vaccines
  • Date each vaccine was administered

Vaccinations are important for the health of individuals and the public. The CDC immunization recommendations are complex and difficult for an individual patient to understand.

Adherence

One of the goals of the medication history interview is to determine whether the patient is adherent to prescribed or recommended medication regimens. Knowledge regarding patient adherence is useful in evaluating the effectiveness of prescribed or recommended medication regimens. Medications may be ineffective if the patient does not comply with the prescribed or recommended regimen. Nonadherence may result in additional diagnostic evaluations, procedures, hospitalizations, and unnecessary combination medication regimens.

Adherence is difficult to determine through direct questioning. Patients know they are supposed to take their prescribed and/or recommended medications. When confronted by an authority figure, patients most likely will say they are adherent even if they are not. Therefore evaluate the patient's adherence by gentle probing throughout the interview. Clues about adherence may be obtained through patient descriptions of how they take their prescribed medications. Many patients can describe their medication routines in detail; other patients may not be able to describe any sort of routine or even recall the color or shape of the medication. Patients who can convincingly describe their medication routines are more likely to be adherent than patients who can provide only vague and general descriptions of their medications and routines.

Sympathetic confrontation may help the pharmacist obtain information regarding patient adherence. Patients are more likely to be truthful when describing their difficulties with complying with the medication regimen if the pharmacist acknowledges that the dosage regimen is complex and difficult to follow and that taking medication regularly is hard. Remain nonjudgmental when assessing patient adherence; this attitude encourages the patient to trust the pharmacist and tell the truth about adherence to prescribed medication regimens.