Ifeanyi Egbunike-Chukwuma, PharmD
Clinical Coordinator
Maryland General Hospital
Joseph Norbet Ngwa Nforbi, PharmD Candidate
University of Maryland School of Pharmacy
Kevin A. Schnupp, PharmD, MBA
Director of Pharmacy
Maryland General Hospital
Baltimore, Maryland

Unfractionated heparin (UFH) remains an important parenteral anticoagulant for the treatment of several thrombotic disorders. Studies have demonstrated improved patient outcomes when targeted therapeutic ranges of activated partial thromboplastin time (aPTT) are achieved within 24 hours of therapy initiation.1,2 These therapeutic ranges are best achieved when weight-based heparin protocols (WBHP) are used.3,4

A WBHP was first introduced in our institution in 2008, with one dosing nomogram for all indications and a target aPTT range of 50 to 80 seconds. A medication use evaluation (MUE) conducted in 2009 revealed that therapeutic aPTTs were achieved in only 57% of patients within the first 24 hours of therapy; there was poor physician and nursing compliance with the dosing protocol, primarily due to their lack of familiarity with the WBHP and/or their awareness of their role in dosing and monitoring these patients. In 2012, we revised and implemented a protocol that emphasized a multidisciplinary collaboration between prescribers, nurses, and pharmacists. The components of our WBHP protocol include the following:

  • 2 dosing nomograms, a low-dose nomogram for patients with acute coronary syndrome (ACS), with an aPTT target range of 50 to 70 seconds (printed on green paper), and a high-dose nomogram for patients with other indications, including venous thromboembolism and atrial fibrillation or flutter, with an aPTT target range of 54 to 83 seconds (printed on pink paper);
  • a physician order form;
  • a color-coded heparin dosage calculation form (housed in the pharmacy); and
  • a color-coded weight-based heparin floor sheet (housed in the nursing station) (Figure 1).
image
Figure 1. Components of the weight-based heparin protocol.
ACS, acute coronary syndrome; AF, atrial fibrillation; aPTT, activated partial thromboplastin time; DVT, deep vein thrombosis; PE, pulmonary embolism

Before implementation of the revised protocol, extensive physician, nursing, and pharmacy education was conducted and an online WBHP training course was developed for annual recertification of nurses and training of new nurses.

Weight-Based Heparin Dosing Program

The prescriber initiates the process by using the WBHP order form and defining the indication for therapy. The pharmacist calculates the initial loading dose and maintenance dose based on the patient’s weight using the appropriate color-coded form. For obese patients, a dosing weight (DWT) is calculated using the following formula: ideal body weight (IBW) plus 0.4 times (difference between the actual body weight [ABW] and the IBW). When the patient’s DWT falls between 2 points, for example 70 and 75 kg, the pharmacist will round down to the closest 5 kg. The pharmacist is responsible for verifying that baseline laboratory tests have been ordered before entering the heparin order into the computer. Our pharmacy uses a standard heparin concentration of 25,000 units/500 mL in a 5% dextrose solution (D5W). The protocol requires that 2 nurses verify the pharmacist calculation and the infusion pump setting before initiating the heparin infusion. The nurse also is responsible for verifying the availability of baseline laboratory tests before starting the infusion, and for obtaining the aPTT 6 to 8 hours after any bolus dose or dosage adjustments, and daily once the aPTT is in therapeutic range. The nurse modifies the patient’s heparin doses and infusion rates based on the aPTT, then documents any signs and symptoms of bleeding and other adverse events (AEs) on the appropriate color-coded heparin flow sheet. On a daily basis, the pharmacist reviews the patient’s laboratory values and consults with the nurse to ensure appropriate dosage adjustments are made and AEs are monitored.

Post-Implementation Evaluation

We conducted a post-implementation MUE to determine pharmacist and nursing compliance with the weight-based protocol and to determine the rate at which our patients achieve therapeutic aPTT targets using our current WBHP. We obtained a computer-generated list of all patients prescribed UFH 25,000 units/500 mL from Feb. 1, 2012 to May 31, 2012 and conducted a comprehensive review of the patient’s electronic medical records. Patients were excluded from the study if they received the heparin infusion for less than 24 hours, or if their heparin infusions were prescribed by vascular surgeons with targeted therapeutic ranges outside those recommended by our protocol. Pharmacy compliance with the protocol was determined by evaluating the accuracy of the pharmacy calculation of the bolus and maintenance infusion doses and their use of the appropriate nomogram form, based on the prescriber’s indicated patient diagnosis. Nursing compliance with the protocol was determined based on the nurse’s ability to adhere to the correctly calculated heparin dose; obtain all aPTT levels between 6 and 8 hours following any bolus or dosage adjustments; make appropriate dosage adjustments based on aPTT levels; and document on the dosing form that 2 nurses reviewed and signed off on dosage calculations and adjustments. Data collected include the following: age, gender, height, ABW, calculated IBW and DWT, pharmacy bolus and maintenance doses calculated and administered, and baseline laboratory tests, including complete blood counts, aPTT, and serum creatinine. The aPTT values were evaluated at 3 time points within 24 hours after therapy initiation. The first aPTT was measured 6 to 8 hours after therapy initiation, the second aPTT was measured 6 to 8 hours after dosage adjustment (if applicable), and the third 6 to 8 hours after the dosage adjustment aPTT (if applicable). Additionally, we documented the availability of daily aPTT after therapeutic level was achieved and recorded any AEs from heparin therapy.

Findings

Eighty-eight patients met the inclusion criteria for this study. Sixteen patients received heparin for ACS; 72 patients were treated for pulmonary embolism, deep venous thrombosis, or atrial fibrillation or flutter. The mean age of the patients in the study was 63.1 years, mean ABW was 87.3 kg, mean height was 73 inches, and mean DWT was 73.3 kg. Forty-nine (55.7%) of the patients were obese, and required calculation of their heparin DWT. Mean serum creatinine of the patients was 2.6 mg/dL (range, 0.48-9.9). The mean loading dose given to the patients was 5,400 units (range, 3,000-10,000 units) and mean maintenance infusion was 1,100 units per hour (range, 500-2,250 units/hour). The mean number of days of heparin therapy was 4.4 days (range, 2-16 days).

Table 1. Pharmacy and Nursing Compliance To the Weight-Based Heparin Protocol
Provider Compliance Measure N Percent
Pharmacy Use of correct color-coded dosing nomogram 88/88 100
Availability of baseline laboratory tests 88/88 100
Correct bolus and maintenance dose calculation 87/88 98.9
Nursing 2 nurses review pharmacy dosing calculation 88/88 100
Nursing adherence to calculated doses 88/88 100
aPTT obtained within 6-8 h post bolus or dosage adjustments 116/176a 73.9
Daily aPTT after therapeutic target is achieved 42/88 47.7
Appropriate dosage adjustments made and documented in response to aPTT value 81/88 92
aPTT, activated partial thromboplastin time
a176 aPTT levels were available.

Pharmacy and nursing compliance with the WBHP is outlined in Table 1. The pharmacist used the appropriate color-coded nomogram based on the prescriber’s indicated diagnosis 100% of the time, and accurately calculated the loading and maintenance dose 98.9% of the time. One patient received a slightly higher dose than indicated because the patient’s weight was between 2 reference points and the pharmacist rounded up the weight. Nursing compliance with the protocol was as follows: 2 nurses acknowledged review of the pharmacist calculation by signing the dosing form 73.9% of the time; aPTT was obtained appropriately within 6 to 8 hours post bolus or dosage adjustment 66% of the time, and daily aPTT was obtained in only 47.8% of the patients once the patient achieved therapeutic aPTT. However, nurses adjusted doses appropriately based on the nomogram in response to aPTT levels 92% of the time. Seventy-two (81.8%) of our patients achieved therapeutic aPTT within 24 hours (Figure 2). Thirty-one (35.2%) achieved therapeutic aPTT within 6 to 8 hours after initiation of therapy, another 16 (18.2%) achieved therapeutic aPTT following one dosage adjustment, and another 25 (28.4%) achieved therapeutic aPTT following a second dosage adjustment.

image
Figure 2. Distribution of patients’ aPTT values in therapeutic range.
aPTT, activated partial thromboplastin time

Our protocol called for calculation of a DWT; hence, we evaluated how well obese and nonobese patients attained aPPT target within 24 hours of initiation of therapy. Obese patients achieved therapeutic aPTT within 24 hours of initiation of therapy at a higher rate than nonobese patients (85.7% vs. 76.9%; Figure 2). Few patients experienced AEs. One patient experienced a minor nosebleed. This patient was on warfarin therapy; however, his aPTT was 31.4 seconds and his international normalized ratio was 1.23. Heparin was not discontinued in this patient. One patient experienced a significant 25% drop in hematocrit (40.2% to 30.3%) and a 6.3 g/dL drop in hemoglobin (16.8 to 10.5 g/dL), which led to discontinuation of therapy.

Conclusion

Approximately 82% of our patients achieved therapeutic aPTT within 24 hours. Two areas of improvement identified nurses obtaining aPTT levels within 6 to 8 hours of each dosage adjustment and daily once the patient attains therapeutic aPTT. This problem was addressed in 2 ways: targeted nursing education and an expanded pharmacist role in daily monitoring of patients on WBHP. Because our institution has a pharmacy-managed anticoagulation program, a clinical pharmacist reviews all patients on WBHP and contacts the patient’s nurse to order an aPTT if it has not already been done. In February 2013, an audit of nursing compliance with aPTT draws revealed a 100% compliance with availability of daily aPTT once a patient had achieved therapeutic aPTT.

References

  1. Hull RD, Raskob GE, Brant RF, Pineo GF, Valentine KA. Relation between the time to achieve the lower limit of the aPTT therapeutic range and recurrent venous thromboembolism during heparin treatment for deep vein thrombosis. Arch Intern Med. 1997;157:2562-2568.
  2. Hirsch J, Bauer KA, Donati MB, et al. Parenteral anticoagulants: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th ed). Chest. 2008;133(6 suppl):141s-159s.
  3. Schaefer DC, Hufnagle J, Williams, L. Rapid heparin anticoagulation: use of a weight-based nomogram. Am Fam Physician. 1996;54(8):2517-2521.
  4. Raschke RA, Reilly BM, Guidry JR, et al. The weight-based heparin dosing nomogram compared with “standard care” nomogram. A randomized controlled trial. Ann Intern Med. 1993;119(9):874-881.