Warfarin: Bridging Anticoagulation

suggest the use of bridging in individuals taking warfarin for one of the following conditions

• Embolic stroke or systemic embolic event within the previous three months
• Mechanical mitral valve
• Mechanical aortic valve and additional stroke risk factors
• Atrial fibrillation and very high risk of stroke (eg, CHADS₂ score of 5 or 6, stroke or systemic embolism within the previous 12 weeks)
• Venous thromboembolism (VTE) within the previous three months (preoperative and postoperative bridging)
• Recent coronary stenting (eg, within the previous 12 weeks)
• Previous thromboembolism during interruption of chronic anticoagulation

Other Conditions

• For most other patients on warfarin with atrial fibrillation (ie, for most individuals not included in the list of examples above), we suggest not using bridging anticoagulation.
• avoiding bridging the lower the patient’s baseline thromboembolic risk (eg, lower CHADS₂ or CHA₂DS₂-VASc score and the higher the risk of bleeding.
• This practice is supported by the BRIDGE trial (Bridging Anticoagulation in Patients who Require Temporary Interruption of Warfarin Therapy for an Elective Invasive Procedure or Surgery)
• A potential role for bridging in reducing the risk of "rebound hypercoagulability" has also been proposed; however, this premise is not supported by data from the BRIDGE trial discussed above

Heparin Products

• LMW heparins have similar efficacy compared with unfractionated heparin, are more convenient to use, and generally do not require monitoring
• Heparins can be dosed at prophylactic doses, therapeutic doses, or doses intermediate between the two.
• There are no clinical trial data or practice standards to guide dosing, and clinical judgment is required to determine the appropriate dose for each patient

• Therapeutic dosing
• Therapeutic dosing (also called "full dose") is appropriate for bridging anticoagulation for individuals with a potential arterial thromboembolic source (eg, atrial fibrillation, mechanical heart valve) or VTE within the preceding month.
• enoxaparin, 1 mg/kg subcutaneously twice daily
• Intermediate dosing 
• Intermediate dose anticoagulation may be appropriate for individuals with atrial fibrillation or VTE within the preceding month when bridging is needed but concerns about bleeding are greater.
• enoxaparin, 40 mg twice daily
• Prophylactic dosing 
• Prophylactic dose anticoagulation (also called "low dose") generally is not used for bridging in patients with atrial fibrillation, because there is no evidence that prophylactic dose heparin prevents stroke in this setting.
• This dose level may be reasonable in patients who have had a VTE event between within the preceding 3 to 12 months.
• enoxaparin, 40 mg once daily

Timing of bridging: Preoperative

• initiate heparin bridging three days before a planned procedure (ie, two days after stopping warfarin), when the PT/INR has started to drop below the therapeutic range.
• discontinue LMW heparin 24 hours before the planned surgery or procedure, based on a biologic half-life of most subcutaneous LMW heparins of approximately three to five hours

Timing of bridging: Postoperative

• For those undergoing major surgery or those with a high bleeding risk procedure, therapeutic-dose unfractionated heparin or LMW heparin should be delayed for 48 to 72 hours after hemostasis has been secured
• For most minor procedures associated with a low bleeding risk in which bridging is used (eg, laparoscopic hernia repair), therapeutic-dose unfractionated heparin or LMW heparin can usually be resumed 24 hours after the procedure

Reference

www.uptodate.com

Warfarin: PreOperative Procedure

Discontinuation

• typically discontinue warfarin five days before elective surgery  and, when possible, check the PT/INR on the day before surgery
• If the INR is >1.5, administer low dose oral vitamin K (eg, 1 to 2 mg) to hasten normalization of the PT/INR and recheck the following day.
• proceed with surgery when the INR is ≤1.4. An INR in the normal range is especially important in patients undergoing surgery associated with a high bleeding risk (eg, intracranial, spinal, urologic) or if neuraxial anesthesia is to be used
• This timing of warfarin discontinuation is based on the biological half-life of warfarin (36 to 42 hours) and the observed time for the PT/INR to return to normal after stopping warfarin (eg, two to three days for the INR to fall to below 2.0; four to six days to normalize)
• Normalization of the INR may take longer in patients receiving higher-intensity anticoagulation (INR 2.5 to 3.5), and in elderly individuals
• For a procedure that requires more rapid normalization of the INR, additional interventions may be needed to actively reverse the anticoagulant.
• This discontinuation schedule will produce a period of several days with subtherapeutic anticoagulation. As an example, it is estimated that if warfarin is withheld for five days before surgery and is restarted as soon as possible afterwards, patients would have a subtherapeutic INR for approximately eight days (four days before and four days after surgery)
• Thus, for patients at very high or high thromboembolic risk, bridging may be appropriate.

Use of bridging preoperatively

• generally reserve bridging for individuals considered at very high or high risk of thromboembolism (eg, recent stroke, mechanical heart valve, CHA₂DS₂-VASc score of 7 or 8, CHADS₂ score of 5 or 6) if they require interruption of warfarin
• In these cases, the bridging agent (eg, therapeutic dose subcutaneous low molecular weight [LMW] heparin) is started three days before surgery
• A bridging agent may also be appropriate if there is a prolonged period during which the patient cannot take oral medications (eg, postoperative ileus).

Restarting warfarin and postoperative bridging

• resume warfarin 12 to 24 hours after surgery, typically the evening of the day of surgery or the evening of the day after surgery, assuming there were no unexpected surgical issues that would increase bleeding risk and the patient is taking adequate oral fluids
• use the same dose the patient was receiving preoperatively
• After warfarin is restarted in the perioperative setting, it takes 5 to 10 days to attain a full anticoagulant effect as measured by an INR above 2.0.
• Thus, treat individuals at very high risk and some individuals with a high risk of thromboembolism with a heparin bridging agent during this period.

Reference:

www.uptodate.com

Statins: Cost Effectiveness of Splitting Doses

• In the United States, some major drug plan insurers have implemented tablet-splitting programs that target statins.
• Tablet splitting has been shown to reduce prescription costs substantially without negatively affecting laboratory outcomes or compliance
• In addition, patients have found tablet splitting to be simple and acceptable

Supporting Evidence

• A retrospective chart review of total cholesterol and LDL cholesterol values of patients instructed to split simvastatin or atorvastatin between January 1999 and November 2000
• The overall results for this review demonstrated no statistically significant increase in total cholesterol and LDL cholesterol concentrations. Total cholesterol and LDL cholesterol values actually decreased from presplitting to postsplitting, p = 0.017 and p = 0.003, respectively.

Manufacturers Recommendations

• No information provided on tablet splitting
• Most drug companies oppose pill-splitting. They say it can be dangerous. But studies to date have not shown any adverse impact on health on the drugs listed safe to be split

Not To be Split

• combination medications such as Liptruzet (atorvastatin/ezetimibe), Advicor (lovastatin/niacin) or Vytorin (simvastatin/ezetimibe)
• time-release drugs, such as Altoprev (lovastatin sustained-release tablets), or Lescol XL (fluvastatin sustained-release tablets)

Ways to Split

• don’t use a knife—studies show doing so can result in unequal halves. Instead, get a pill splitter device.
• A good practice is to split your pills one at a time, and take the second half as your next dose

References:

1. https://www.consumerreports.org/cro/news/2014/03/is-it-safe-to-split-my-statin-cholesterol-drug-to-save-money/index.htm
2. https://www.ncbi.nlm.nih.gov/pubmed/11847935
3. Dormuth CR, Schneeweiss S, Brookhart AM, Carney G, Bassett K, Adams S, Wright JM. Open Med 2008;2(3):5–13
4. January 1, 2006 University of Michigan Prescription Drug Plan

Needle Stick Injury: HIV Prophylaxis

Risk of seroconversion

• Deep injury (odds ratio [OR] 15)
• A device visibly contaminated with the patient's blood (OR 6.2)
• Needle placement in a vein or artery (OR 4.3)
• Terminal illness in the source patient (OR 5.6)
• The majority of cases were injured by a hollow bore as opposed to a solid needle

Initial actions following exposure

• immediate cleansing of the exposed site.
• Small wounds and punctures may be cleansed with an antiseptic such as an alcohol-based hand hygiene agent, since alcohol is virucidal to HIV, hepatitis B virus (HBV), and hepatitis C virus (HCV).
• Other antiseptics such as iodophors, chloroxylenol (PCMX) and chlorhexidine (CHG) also inactivate HIV

Testing for HIV 

• Baseline and follow-up serologic testing for HIV should be performed in all HCP exposed to HIV to see if seroconversion occurred.
• The majority of individuals who seroconvert will do so within the first three months.
• Testing should be performed even among those who receive PEP

Post Exposure Prophylaxis

• offer post-exposure prophylaxis (PEP) using a three-drug regimen to healthcare personnel (HCP) with a percutaneous, mucous membrane, or nonintact skin exposure to body fluids of concern (eg, blood or blood tinged fluids) if the source patient is, or is suspected to be, HIV-infected
• PEP should be discontinued if testing shows that the source patient is HIV-negative, unless there is concern that the source is acutely infected with HIV
• If the HIV status of the source patient is unknown, offer PEP while awaiting HIV testing if the source has risk factors for HIV infection (eg, injection drug users, men who have sex with men) or symptoms suggesting HIV infection.
• If the source patient is unknown, do not administer PEP unless the exposure occurred in a setting where exposure to HIV is likely (eg, a needlestick from a sharps container in an HIV clinic

Timing 

• PEP should be initiated as soon as possible.
• The goal is to start within one to two hours (or earlier) after exposure, often using a "starter pack" with appropriate drugs that are immediately available.
•  It is likely that a delay in initiating PEP can reduce efficacy
• For most HCP, we do not initiate PEP if more than 72 hours have elapsed after the initial exposure; PEP is likely to be less effective when administered after that period of time.
•  However, we offer three-drug PEP after a longer interval to patients with a very high-risk exposure (eg, sharps injuries from a needle that was in an artery or vein of an HIV-infected source patient).
• For such HCP, The United States Public Health Services suggests that PEP can be offered up to one week after the exposure

Selection of antiretroviral therapy

• Tenofovir-emtricitabine (300/200 mg once daily) plus raltegravir (400 mg twice daily)
• Tenofovir-emtricitabine (300/200 mg once daily) plus dolutegravir (50 mg once daily)

PEP during pregnancy

•  For pregnant HCP who have an occupational exposure to HIV and choose to initiate post-exposure prophylaxis (PEP), we typically use the same regimen as noted above, namely tenofovir-emtricitabine (available as Truvada) plus raltegravir

Duration of therapy 

• The recommended duration of PEP is four weeks because a course of zidovudine for this duration appeared protective in some studies; however, the optimal duration of PEP is unknown
• PEP should be discontinued if testing shows that the source patient is HIV-negative

Reference:

www.uptodate.com

Types of Hemodialysis

PERITONEAL DIALYSIS

 Continuous ambulatory peritoneal dialysis (CAPD)

• Manual PD is termed continuous ambulatory peritoneal dialysis (CAPD)
• standard CAPD regimen consisting of 4-5, 2-L exchanges/day (Figure 1). The procedure involves the infusion of the solution (approximately 10 min), a dwell period (3-6 hours) and drainage of the dialysate (10 - 20 min)
• Due to variation in patient size and body composition, they might not be able to achieve enough solute clearance per day with the standard CAPD prescription. They may thus require more, frequent exchanges or larger infusion volumes
• The simplicity of CAPD, its low cost, and the associated freedom from machines made CAPD a very popular form of chronic PD. In addition, CAPD can maintain a steady physiological state, control fluid volume and blood pressure in most patients 

Intermittent peritoneal dialysis (IPD)

• IPD is an automated peritoneal dialysis
• generally consists of frequent, short cycles performed over 8 - 10 hours per session, three times weekly
• If IPD is practiced on a nightly basis only, it is referred to as nocturnal IPD (NIPD)
• NIPD is mostly reserved for patients with high solute transport and limited ultrafiltration, since the short cycles of NIPD can achieve better ultrafiltration than the longer cycles of CAPD or CCPD. The total volume of dialysis fluid exchanged per treatment ranges between 8 L and 12 L

References:

1. http://advancedrenaleducation.com/content/modalities-therapy-1
2. www.uptodate.com