Let's Stop the Bleeding: Preventing Errors with Heparin Therapy

​​​Introduction

A recent medication error that occurred in an Indiana hospital received nationwide publicity when three premature infants died as a result. The infants mistakenly received overdoses of heparin because the wrong strength was used to prepare flush solutions for umbilical lines. The error occurred when heparin 10,000 units/mL, 1 mL vials inadvertently were placed into a unit-based automated dispensing cabinet (ADC) pocket where heparin 10 units/mL, 1 mL vials were normally kept. While nothing can erase the grief experienced by the families and hospital workers in the wake of this tragic incident, it does serve as a reminder of the need to take a closer look at heparin utilization in our facilities.¹

Heparin is an anticoagulant and one of the oldest drugs still in widespread clinical use. When administered, the medication prevents formation of new clots while allowing the body's natural clot lysis mechanism to work normally to break down clots that have previously formed.²

Heparin’s clinical uses include the following:²

• To prevent existing clots from enlarging and then blocking coronary arteries in patients with unstable angina
• To treat (i.e., acutely) and prevent (i.e., prophylactically) deep-vein thrombosis and pulmonary emboli
• To decrease the risk of patients with atrial fibrillation developing blood clots in the left atrium of the heart
• To prevent coagulation as blood passes through an extracorporeal circuit during dialysis
• To maintain the patency of indwelling intravenous catheters

While heparin provides many benefits, this medication can be very dangerous, and errors involving heparin have a heightened risk of significant patient harm. For this reason, heparin is considered a high-alert medication that requires special safeguards to reduce the risk of errors.³

Errors associated with heparin use are as multifaceted as its indications. Common types of errors, with causative factors similar to the case mentioned above, that have been reported to PA-PSRS include wrong-drug errors due to look-alike packaging and names, wrong-dose errors, and the concomitant administration of heparin with other medications that have anticoagulant or antithrombotic effects.

Look-Alike Packaging

Look-alike packaging of heparin and other intravenous (IV) products (e.g., lidocaine, dopamine, hetastarch in sodium chloride [HESPAN]), is a frequent source of medication mix-ups (see Figure 1).

Image provided to PA-PSRS courtesy of a Pennsylvania healthcare facility.

The bags of these other products can be the same size as heparin IV bags and use the same fonts, font sizes, and color schemes. Examples of medication error reports submitted to PA-PSRS include the following:

Nurse was approached by a technician and asked if patient was still on lidocaine. The nurse stated “yes.” The technician then informed the nurse that a heparin bag was hanging on the patient’s IV pump, not lidocaine. The nurse immediately stopped the heparin infusion and drew an aPTT. Lidocaine was restarted per physician order. The patient was not injured.

Staff found dopamine infusing instead of heparin drip.  Bag had been hung approximately 12 hours prior, and half of 250 mL bag was infused.  The doctor was notified, and monitoring was increased.  No harm was noted.

Pharmacy technician mislabeled heparin drip on a pre-mixed bag of lidocaine. Pharmacist did not detect error when checking the medication. Nurse noticed error prior to administering the medication to the patient.

Physician ordered HESPAN 50 mL/hr for 10 hours. Nurse hung heparin 20,000 units in 500 mL, all of which was infused. At this point, aPTT was greater than 100, Hemoglobin was 7.2, and Hematocrit was 21.4. Patient was awake and alert with stable vital signs. The physician ordered protamine.

A number of error reports involving premixed heparin and HESPAN have been submitted to the USP-ISMP Medication Errors Reporting Program (MERP).⁴ These reports indicate that look-alike names (i.e., heparin and HESPAN) and manufacturer packaging frequently contribute to the mix-up of these products. Many errors have occurred when nurses have retrieved heparin from an ADC in which heparin and HESPAN were stored, and where both names appeared as choices on the machine’s computer screen. Since HESPAN, a plasma expander, is sometimes used in patients who are actively bleeding, administering heparin instead can be very hazardous. In one event, an intensive care unit nurse mistakenly selected a heparin 25,000 unit/500 mL premixed container instead of HESPAN and administered two bags to a patient who was actively bleeding. The heparin infusion started at 11 p.m. and was repeated at 2 a.m. At 6 a.m., the patient had a bloody stool, and her hemoglobin and hematocrit levels, previously within normal limits, had fallen to 7.3 g/dL and 28%, respectively. These levels led to consideration of a hemorrhagic event, and several hours later, to discovery of the medication error. By that time, the patient had hemorrhaged extensively, and despite attempts to reverse the effects of heparin, she died later that morning.

Stocking Errors

Stocking errors are fairly common with heparin products, as many of the manufactured vials are very similar in appearance, come in a variety of concentrations, and often are stored in close proximity in the pharmacy, making it easy to grab the wrong vial when refilling floor stock requests.⁵ A stocking error contributed to the aforementioned fatal neonatal administration error. The vials looked very similar (see Figure 2). Several nurses requested 10 units/mL vials to prepare an umbilical line flush and were directed to that drawer in the ADC, but they did not notice that the vials contained the wrong concentration of heparin.¹

Image provided courtesy of ISMP.

A variety of heparin stocking errors have been reported to PA-PSRS, including mix-ups between heparin products and with other medications:

A 69-year-old female was admitted for GI bleed. During admission, patient was found to have oozing blood in the area of her sacrum. After being notified, the attending ordered 2.5 mg Vitamin K PO. Patient's last INR was 2.9 and PT 30.6. Staff later identified that heparin 5,000 units/mL was stocked in Pyxis with heparin 100 units/mL flush. Given patient's unexplained bleeding, another set of labs were drawn which found   an INR of 10.9 and aPTT of greater than 160. The attending was notified, and 10 mg Vitamin K was given at 4 a.m., 1 unit FFP at 5 a.m. Pharmacy was notified, and a housewide check of all Pyxis cabinets   was done immediately. Subsequently, patient was treated with additional blood products and returned to a hemodynamically stable state.

RN was asked to obtain epinephrine 1:10,000 and could not locate the medication in the room. RN left the room to procure the medication in the anesthesia workroom. Upon opening the medication cabinet, she chose a vial with “10,000” on the label.  Medication mixed with 4 cc NSS and administered to patient via injector needle. 

After patient left the room, the N.M. [nurse manager] was in the room assisting the staff to look for epinephrine in the medication drawer.  The N.M. noted that Heparin vials were inadvertently placed in the drawer and brought this to the RN's attention.  The RN looked in the sharps box and discovered that she had handed the scrub RN heparin instead of epinephrine.

The staff RN pulled heparin to give to the patient.  Oxytocin was found in the drawer. The vials appeared very similar. The medications were removed from Pyxis and returned to pharmacy.

When the nurse went to retrieve heparin, Benadryl was found in the medication drawer. The nurse found two other vials; they were removed, and pharmacy was notified. The nurse noted both heparin and Benadryl vials are blue and white in color.

Eight vials of Magnesium sulfate were found in drawer with heparin 5,000 units in a Pyxis machine. Six vials magnesium sulfate found in drawer with heparin in a second Pyxis machine. Pharmacy was made aware. The patient did not receive the wrong medication.

In an error reported to the MERP, a physician asked for heparin 2,000 units during a procedure. The nurse retrieved 2 vials of heparin from an ADC that was supposed to be stocked with 1,000 units/mL, 1 mL vials. But a pharmacy technician had accidentally stocked the cabinet with look-alike vials of heparin 10,000 units/mL, 1 mL vials. The patient received heparin 20,000 units, but the nurse quickly noticed the mistake, and the patient received protamine sulfate with no resulting harm. In the pharmacy, the 10,000 units/mL concentration was stored next to the 1,000 units/mL concentration, and a pharmacist had not checked the heparin before the technician restocked the cabinet. ⁵

Concomitant Therapies

Other tragic errors occur when low molecular weight heparin products, such as Fragmin (dalteparin sodium), Lovenox (enoxaparin sodium), and Innohep (tinzaparin sodium), are inadvertently initiated in patients that are concurrently being administered heparin infusions or vice versa. Many of these errors result from poor communication of a patient’s medication regimen to caregivers. Many times, low molecular weight heparin is prescribed and administered in the emergency department (ED). Consequently, those orders are rarely communicated to the pharmacy or screened for safety.⁶ Additionally, breakdowns in the medication reconciliation process can leave personnel on the nursing unit without knowledge of what was administered in the ED.

Reports of concomitant heparin and low molecular weight heparin products submitted to PA-PSRS include the following:

Patient was given LOVENOX in the ED. A verbal order for a heparin drip was received, and the drip was started. Labs were obtained, and there were no signs of bleeding.

Patient was ordered and received one dose of FRAGMIN at 1,200. Another physician, unaware of FRAGMIN therapy, ordered weight-based heparin protocol at 1,500. Patient received bolus of heparin, and drip was administered for three hours before the error was discovered.

Order for LOVENOX was received by pharmacy. Some hours later the  pharmacy received heparin protocol dose adjustment order. Pharmacist called to ask why heparin was still infusing since it was discontinued. Nursing had not seen the discontinue order.

In a case reported to the MERP, a hospitalized 86-year-old woman with a history of atrial fibrillation was prescribed Lovenox (enoxaparin) 60 mg every 12 hours subcutaneously by her cardiologist. On the following day, warfarin was added to the drug regimen. Later in the week, a gastroenterologist recommended a colonoscopy to rule out colorectal cancer. Warfarin was discontinued, and a heparin infusion was ordered. However, enoxaparin administration continued every 12 hours, and the heparin order was never faxed to the pharmacy. To administer the bolus and begin the infusion, the nurse borrowed a vial of heparin and a premixed solution that the pharmacy had dispensed for another patient. Several hours later, the patient’s aPTT was above the therapeutic range. The heparin infusion was decreased, but by the next morning, the patient’s aPTT was still elevated, her hemoglobin and hematocrit had dropped, and she exhibited evidence of internal bleeding. Heparin and enoxaparin were discontinued immediately, but the patient died despite aggressive treatment. ⁶

Potential Solutions

The case reports in this article and many others that have been reported to PA-PSRS emphasize that heparin is a high-alert medication that is prescribed, dispensed, and administered via error-prone processes.  To protect patients who are at risk for an adverse outcome if an error occurs, this high-alert medication warrants unique handling.

The following strategies may help reduce the incidence of heparin-related errors: ^1,4-6

Reviewing the medication record. It is important for prescribers, pharmacists, and nurses to consider recent drug therapy before ordering, dispensing, and administering any anticoagulants or antithrombotic agents. Protocols, guidelines, and standard order forms can feature prominent reminders to asses all drug therapy (including medications administered in the ED) and avoid unintentional use of more than one anticoagulant in a patient.

Improving access to information. Instituting a process for immediate communication with the pharmacy, upon a patient’s admission to the hospital, of all medications administered in the ED or other outpatient settings will enable pharmacy to enter the medications into the pharmacy computer system and screen for duplicate therapy or interactions with medications prescribed upon admission.

Testing computer systems.  Testing both computerized prescriber order entry systems and pharmacy computer systems can help to ensure that staff are alerted when heparin and low molecular weight heparin products are ordered on the same patient.

Segregating look-alike products.  Store products with look-alike packaging in different locations in pharmacies, patient care units, and other settings. Use shelf stickers to help locate the product that has been moved.

Reducing similarity of containers.Assess packaging of all heparin products to identify any possibility for confusion. Remedy problems by repackaging medications, affixing auxiliary labels to products, or switching manufacturers to improve distinction and clarity of labeling and packaging.

Reducing access. Limit the concentrations of heparin products stored in patient areas. Whenever possible, allow only one concentration for bolus doses, and use pre-filled syringes for all heparin flushes. Avoid stocking items on nursing units that require further preparation by nurses before administration.

Conducting independent double-checks. Having an independent double-check of heparin products before they leave the pharmacy can prevent mistakes. Consider having a pharmacist (or a technician, if necessary) check all products pulled for restocking of ADCs before they leave the pharmacy. In addition, many facilities have instituted a double-check by nursing staff before heparin administration.

Implementing bar-code technology. Bar-code technology can be employed for selecting and stocking medications in ADCs and before administering medications to patients. Bar-coding is valuable for bedside scanning to confirm the accuracy of the patient, drug and dose of medication.

Even if these problems with heparin use are not obvious in your facility today, every facility can proactively anticipate and focus on problems with heparin use by discussing heparin errors that have happened at other facilities and incorporating the risk reduction strategies presented above.

Notes

1. Institute for Safe Medication Practices (ISMP). Infant heparin flush overdose. Medication Safety Alert! 2006 Sep 21; 11(19):1-2.
2. Micromedex® Healthcare Series, Thomson Micromedex, Greenwood Village, Colorado (Edition expires [2006 Dec 31]).
3. Institute for Safe Medication Practices (ISMP). ISMP’s list of high alert medications. Medication Safety Alert! 2003 Dec 18 [cited 2006 Nov 15]. Available from Internet: http://www.ismp.org/Tools/highalertmedications.pdf.
4. Institute for Safe Medication Practices (ISMP). Hespan and heparin mix-ups—reduce the risk by using generic name and product. Medication Safety Alert! 1999 Sep 8;4(18):1.
5. Institute for Safe Medication Practices (ISMP). Heparin mix-ups. Medication Safety Alert! 2003 Aug 21;8(17):1.
6. Institute for Safe Medication Practices (ISMP). Hazard alert! action needed to avert fatal errors form concomitant use of heparin products. Medication Safety Alert! 2001 Feb 21;6(4):1-2.

Supplemental Material

Self-Assessment Questions

The following questions about this article may be useful for internal education and assessment. You may use the following examples or come up with your own.

1. Heparin’s mechanism of action allows the medication to break down clots that have already formed.
1. True
2. False
2. Heparin’s clinical uses include which of the following?
1. To prevent existing clots from enlarging and then blocking coronary arteries in patients with unstable angina.
2. To treat (i.e., acutely) and prevent (i.e., prophylactically) deep-vein thrombosis and pulmonary emboli.
3. To decrease the risk of patients with atrial fibrillation developing blood clots in the left atrium of the heart.
4. To prevent coagulation as blood passes through an extracorporeal circuit during dialysis.
5. All of the above
3. Which medications have the potential to be mixed-up with heparin products (i.e., due to look-alike packaging) and be mistakenly administered to your patient?
1. Lidocaine
2. Dopamine
3. Hetastarch
4. All of the above
4. Tragic errors have occurred when which one of the following have been concomitantly administered with heparin?
1. cephalosporins
2. anti-psychotics
3. corticosteroids
4. low molecular weight heparins (LMWHs)
5. Strategies that will help to prevent medication errors associated with heparin include all EXCEPT which one of the following?
1. Considering recent drug therapy before ordering any anticoagulants or antithrombotic agents.
2. Assume that computerized prescriber order entry systems and pharmacy computer systems will provide alerts when heparin and low molecular weight heparin products are ordered on the same patient.
3. Developing protocols, guidelines, and standard order forms that feature prominent reminders to assess all drug therapy (including medications administered in the emergency department) and avoiding concomitant use when indicated.
4. Upon a patient’s admission to the hospital, communicating with the pharmacy about all medications administered in the emergency department or other outpatient settings.