Listed below are a series of key points that are crucial for successful Unfractioned Heparin, Low Molecular Weight Heparin, and Warfarin therapy:

Unfractionated Heparin (Heparin)
Listed below are a series of key points that are crucial for successful therapy:

• Rapid-acting parenteral anticoagulant ².
• Uses: Prophylaxis of DVT/PE (Deep Vein Thrombosis/Pulmonary Embolism), Treatment of DVT/PE, Thrombosis due to atrial fibrillation, and Acute Coronary Syndrome/MI (Myocardial Infarction).
• The prophylaxis dose is 5000 units Subq (Subcutaneous) every 8 – 12 hours. This dose is not high enough to elevate aPTT (Activated Partial Thromboplastin Time) therefore aPTT does not need to be monitored ¹.
• Heparin treatment doses are administered by continuous IV infusion and are based on actual body weight (when calculating the dose do not exceed 100 Kg total body weight).¹ A bolus dose is required to quickly achieve therapeutic level.
• Patient’s aPTT should be monitored every 6 hours for 24 hours and then until stable ¹ . Once the aPTT is stable, it should be monitored once daily. Dose changes should be based on the patient’s aPTT according to the hospital’s Heparin continuous IV infusion algorithm ⁴.
  • In regards to monitoring – a patient’s Heparin Xa levels can be monitored instead of or in addition to their aPTT (as long as staff is trained appropriately)¹.
• Adverse effects of Heparin treatment include: bleeding, thrombocytopenia, osteoporosis (with long-term use), and hyperkalemia.
• Heparin-induced thrombocytopenia (HIT) is a drop in platelets to less than 100,000/mm3 or by greater than 50% ². It is antibody mediated and has a delayed onset of 5-14 days ¹. When a patient experiences HIT, all forms of Heparin should be stopped and the patient should never receive Heparin again. HIT can cause venous and arterial thrombosis and leads to amputation in 25% of cases and death in 25-30% of cases¹.
• Contraindications to the use of Heparin include: History of HIT, Active bleeding, and Hypersensitivity¹.
• The effects of Heparin can be reversed by holding the infusion, transfusions with fresh frozen plasma or whole blood, or protamine¹.

Low Molecular Weight Heparin (Brand Name - Lovenox®)

• Derived from unfractionated Heparin¹.
• Uses: Prophylaxis of DVT/PE, Treatment of DVT/PE, and Acute MI/Unstable Angina ⁸.
• The prophylaxis dose is 40 mg subq daily for patients with normal renal function, or 30 mg subq daily for patients with impaired renal function (CrCl < 30 ml/min).
• The treatment dose is 1 mg/Kg subq BID (twice daily) for patients with normal renal function, or 1 mg/Kg subq daily for patients with impaired renal function (CrCl < 30 ml/min).
• Low molecular weight Heparin does not elevate aPTT. Anti-factor Xa concentrations can be monitored ^{1, 6}.
• Adverse effects include: bleeding, thrombocytopenia, and pain at the injection site.
• Low molecular weight Heparin does carry a black box warning for risk of epidural/spinal hematoma ⁹.
• Contraindications include: History of HIT, Active bleeding, and Hypersensitivity.
• The effects of Heparin can be reversed by holding doses, transfusions with fresh frozen plasma or whole blood, or protamine ⁸.
• The advantages of low molecular weight Heparin over unfractionated Heparin include: longer half-life, lower incidence of HIT, less routine laboratory monitoring, patient can self-administer and can potentially be treated in the outpatient setting ^1,8.
  • When clinically feasible Low Molecular Weight Heparin can be used instead of Heparin. It is safer, and is applicable in the majority of situations in which Heparin is indicated ¹⁰.

Warfarin (Brand Name - Coumadin®)

• Interferes with the hepatic synthesis of vitamin K dependent clotting factors II, VII, IX, and X, as well as endogenous anticoagulant proteins C and S ^{1, 8}.
• Uses: DVT/PE Treatment, DVT/PE Prophylaxis, and Prevention of thromboembolic events with Prosthetic heart valves, Acute MI, Atrial fibrillation, and Inherited clotting disorders.
• The onset of action is 36-72 hours, and full antithrombotic effect may take up to 15 days. Warfarin may even increase the risk of clotting for a few days^1,2. Therefore, when treating a thromboembolic event, Warfarin and Heparin are started simultaneously ¹.
• Warfarin therapy is monitored using the International Normalized Ratio (INR). INR should be monitored daily while in the hospital ^1,8.
• Adverse effects include: bleeding, skin necrosis, and purple toe syndrome.
• Contraindications include: Pregnancy, Active bleeding, and Hypersensitivity.
• Warfarin has numerous interactions with food and drugs.
  • An increased intake of vitamin K (green leafy vegetables) will decrease the effectiveness of Warfarin ^{1, 2, 8, 14}. Smoking, alcohol, phenytoin, rifampin, carbamazepine, and barbiturates will also decrease the effectiveness of Warfarin by increasing its elimination.
  • Drugs such as amiodarone, fluconazole, metronidazole, sulfamethoxazole, cimetidine, ciprofloxacin, clarithromycin, erythromycin, fluoxetine, and grapefruit juice can increase the effects of Warfarin by decreasing the metabolism ^{1, 8}.
  • Aspirin, clopidogrel, and NSAIDs (Non-steroidal anti-inflammatory drugs) can increase the risk of bleeding associated with Warfarin¹.
• Patient education for Warfarin should include: signs and symptoms of bleeding, signs and symptoms of a clot, possible drug interactions, need for consistency in Vitamin K foods, importance of monitoring INR, what to do when a dose is missed, and knowing which strength and color of tablet they use.

The Joint Commission describes heparin treatment as a high-risk treatment due to the complexity of dosing, monitoring, and patient compliance¹². Errors involving anticoagulants have a significantly higher chance of patient mortality. The fact that anticoagulants are typically prescribed to patient populations that are already at a higher risk of potential complications (geriatric and cardiology patients) only adds to the need to reduce preventable medication errors in order to improve the level of patient safety within a health care organization.

Regarding anticoagulant therapy, the most common general causes of errors were wrong dose/quantity, Omission Error, and prescribing errors (these 3 errors accounted for over 60% of the reported errors)¹¹. However, medication errors are usually the products of multiple causes. Potential errors may include:

 Unknown or unrecognized simultaneous use of anticoagulants. For example, Heparin was prescribed during admission and Low Molecular Weight Heparin was prescribed in the emergency department or other outpatient area and continued after admission.
 Patient/Family confusion about the generic and brand names for an anticoagulant. Example being – self-administration of both Heparin and Coumadin ^{1, 9}.
 Accidental stoppage of therapy by the health care provider. This can occur if a dose is held or if a patient forgets to resume their treatment after discharge.
 Accidental mix-ups between vials, container, or bags.
o This could occur between heparin vials and other similar looking vials such as saline or insulin.
o Hospitals have also reported mix-ups between IV bags of heparin and Hespan (hetastarch) ^{9, 11}.

 Failure to obtain an accurate patient weight prior to calculating the dosage. (Estimations of weight are oftentimes surprisingly inaccurate)^{1, 11}.
 Failure to consider renal functions especially when prescribing low molecular weight heparin ^{1, 4}.
 Infusion pump errors when administering IV heparin.
o Forgetting to reset the pump following a bolus dose from the continuous infusion bag ¹³ .

 Forgetting to reduce the standard starting dose for elderly patients¹.
 Patient self-administration errors if required to take different warfarin doses on different days. This is compounded if the dosing instructions given by their health care provider differ from the dosing instructions provided on the medication label ^{1, 8} .
 Calculation errors regarding heparin prescription of the addition of heparin to an electrolyte solution – these can still occur despite the new FDA mandated changes on heparin labeling ⁷ .
 Adjusting warfarin doses often without taking into account the overall trends in INR (Internationalized Normalized Ratio) levels ^13,14.
 Failure to test the most recent lab values prior to prescribing an anticoagulant.
 Drug and/or food interaction – lack of electronic alerts for potential drug interactions and lack of education/alert system to detect food and diet issues ¹ .
 Anticoagulants used concurrently with spinal puncture – this can lead to an increased risk of epidural or spinal hematoma ^{1, 2, 8}.

The above listed potential causes of medication errors are by no means all-inclusive. The wide range of potential errors helps to highlight the inherent complexity of heparin treatment. In regards to preventing medication errors there are three necessary objectives:
 Design and implement systems that prevent harm and error
 Make all errors that do occur visible to staff
 Design and implement procedures to mitigate patient harm in the event of an error.

The storage, administration, and management of anticoagulants is an interdisciplinary practice (nurses, physicians, pharmacists, dieticians, and case managers are all involved) and therefore any risk reduction strategies require the input of each of the affected
parties.

Storage and Availability:

• All similarly labeled products should be separated and further distinguished.
  • Consider using “TALLman” lettering on shelves, pharmacy labels, and in the electronic health record ¹⁰ . An example would be: HEParin vs. HeSPAN. This can add a visual checkpoint ¹⁰ .
• When available, only oral unit dose products and pre-mixed infusions are used ¹.
  • Standardizing the concentrations will require the pharmacy to prepare and dispense any “out-of-the-ordinary” concentrations.
• Remove high concentration products from the floor stock. Ideally, only flush solutions are available on the floor stock and all other higher concentrations are available on a patient-specific level ^{1, 2, 10, 11}.
  • Note: There is little evidence that Heparin Flushes are more effective than a saline flush for maintaining the patency of peripheral or arterial lines ¹⁰. The use of saline solutions to flush lines is an evidence-based practice and avoids the risk of confusing heparin formulations (as well as avoids the risk of heparin-induced thrombocytopenia) ¹⁰.
• IV solutions should not be mixed outside of the pharmacy (if possible, not at all) ^1,11 . The process of mixing an IV solution is highly error prone.
• Heparin, Low Molecular Weight Heparin, and Warfarin are available in a wide array of concentrations. Minimize the amount of concentrations as much as possible. Reducing the variety of options reduces the potential for error ¹⁰.

Operational Processes:

• The health care organization must have a written and defined anticoagulant management program to individualize the care provided to each patient receiving anticoagulant treatment ¹².
  • Within this program all applicable staff should be routinely educated and tested in order to stay up to date with the latest evidence.
• Implement weight-based heparin protocols. Weight-based heparin protocols are evidenced based ¹.
• Use pre-printed order forms/protocols (or electronic forms) in order to reduce confusion/miscommunication between departments ^1,10.
  • Handwritten order forms are extremely error prone and should be non-existent within an electronic system ^{1, 2}.
• When infusing heparin use programmable pumps that allow for the administration of bolus doses¹. Ideally the pump should have pre-set maximum and minimum parameters ^10,14.
  • With any form of technology it is crucial that the health care teams using the equipment be familiar with and tested on its use.
  • In situations where a smart pump is not available, then administer the bolus infusion with a pharmacy prepared syringe ^{1, 8}.
  • Although smart pumps are a minimum for safe Heparin treatment, they are not a “silver bullet”. They are unable to detect whether the correct bag is hung or if correct protocols have been followed during IV administration ¹⁰. Operational processes must be in place that allow for checks of these crucial steps.
• Avoid Smart Pump Overrides¹⁰. Should a pump need to be overridden, a process must be in place that will allow the health care team to be notified.
• Computer Alerts or Pages for High aPTT levels should be utilized when available. These alerts should be responded to in a pre-designated “timely” manner and should be sent to a decision maker ¹⁰.
• If available, bedside barcoding and electronic prescriber order entry can be implemented to add further checkpoints to the process ⁷.
• Within the electronic medication system, alerts should be placed that will notify health care providers of any drug interactions ⁷.
• Written guidelines should be established regarding hold orders and for heparin reversal therapy ⁷.
• Written guidelines should be established in the event of IV infiltration.
• Administer Warfarin at a pre-determined time that will allow for necessary lab results and analysis.
• With the help of the laboratory department, coagulation test results should be available within 2 hours or less.
• Anticoagulation flow sheets can be utilized in order to quickly understand dosing history and to communicate this information during shift changes, or a change to a new provider.

General:

• A nutritional consultation is necessary for patients receiving Warfarin ^{1, 7}.
  • Partnership with the patient and their loved ones is necessary in order to reduce adverse drug reactions.
• Outpatient warfarin services should be established in order to work with and educate patients in regards to their therapy.
• Basic (Low-Level Literacy) pamphlets should be available to patients receiving anticoagulants⁷.
  • Bilingual options should also be available as needed.

The above listed ideas are evidenced based suggestions for process improvements. As with any healthcare process it is crucial to create a process that is backed by evidence, streamlined, has necessary checkpoints, and is constantly being improved.

Anticoagulants are a necessary treatment option for many patients; however, due to errors within systems, preventable medication errors continue to occur. In recent years the management of anticoagulants has been brought to the forefront of medication error discussion and health care providers are tasked with aiming for an increasingly lower occurrence rate.

1. Anticoagulant Toolkit: Reducing Adverse Drug Events &amp; Potential Adverse Drug Events with Unfractionated Heparin, Low Molecular Weight Heparins, and Warfarin. (2008). Purdue University Indianapolis, IN.
2. Baglin, T, Barrowcliffe, TW, Cohen, A, & Greaves, M. (2006). Guidelines on the Use and Monitoring of Heparin. British Journal of Haematology. Vol. 133, Issue 1.
3. Budnitz, et al. (2006). National Surveillance of Emergency Department Visits for Outpatient Adverse Drug Events. JAMA, 295(15):1585‐1866.
4. Dager, William, Gosselin, Robert, Raschke, Robert, &amp; Vanderveen, Tim. (2009). Heparin: Improving Treatment and Reducing Risk of Harm (Clinical, Laboratory and Safety Challenges). Patient Safety &amp; Quality Healthcare, Jan/Feb (20-27).
5. Ebell, Mark. (2005). Evidence-Based Initiation of Warfarin (Coumadin). American Family Physician, Feb 15:71(4):763-765.
6. Fanikos J, et al. (2004). Medication Errors Associated with Anticoagulant Therapy in the Hospital. American Journal of Cardiology, August 15:94:532‐5.
7. High-Alert Medication Feature: Anticoagulant Safety Takes Center Stage in 2007. (2007). Institute for Safe Medication Practice. Retrieved from: https://www.ismp.org/newsletters/acutecare/articles/20070111.asp
8. How-to Guide: Prevent Harm from High-Alert Medications. (2012). Institute for Healthcare Improvement. Cambridge, MA.
9. Let&#39;s Stop the Bleeding: Preventing Errors with Heparin Therapy. (2006). PA PSRS Patient Safety Advisory. Dec 3(4):31. Retrieved From: http://patientsafetyauthority.org/ADVISORIES/AdvisoryLibrary/2006/Dec3%284%29/Pages/31.aspx
10. Meisel, Steven. (2009). A Systematic Approach to Improving Anticoagulation Safety. Carefusion Center for Safety and Clinical Excellence. March 13-14, San Diego, CA.

11. Piazza, Gregory, Nguyen, Thanh, Cios, Deborah, et.al. (2011) Anticoagulation-associated Adverse Drug Events. The American Journal of Medicine. 124(12). doi:10.1016/j.amjmed.2011.06.009. Retrieved from: http://www.wapatientsafety.org/downloads/1202_Anticoagulation_Associated_Drug_Events.pdf
12. Sentinel Event Alert: Preventing Errors Relating to Commonly Used Anticoagulants. (2008). The Joint Commission. Issue 41. Retrieved from: http://www.jointcommission.org/assets/1/18/SEA_41.PDF
13. Vanderveen, Tim. (2009). Pooled Data from Smart IV Pumps: Review of Heparin Averted Errors and Variability. Carefusion Center for Safety and Clinical Excellence. March 13-14, San Diego, CA.
14. Winterstein, et al. (2002). Identifying Clinically Significant Preventable Adverse Drug Events through a Hospital’s Database of Adverse Drug Reaction Reports. American Journal of Health‐System Pharmacy, 59 (18): 1742‐1749.