DATA STORIES | DIGITAL HEALTHCARE | KNIME ANALYTICS PLATFORM

Heparin Therapeutic Monitoring and Calculation with KNIME

A codeless solution for adult general cardiovascular, and adult and children’s deep vein thrombosis and peripheral edema

Published in

Low Code for Data Science

6 min readMay 11, 2023

Authors: Sebastian Jaques, Amir Behdani, Micah Buller, Gina Chong, Maria DePonte, ReHanshae Harvey, Dori Leka, and Dayanjan Wijesinghe, Ph.D.

Note. This workflow was developed as partial fulfilment of the 2022 Fall, Introduction to Data Science and Rapid Prototyping elective by the student authors listed above studying at Virginia Commonwealth University School of Pharmacy.

Heparin is an anticoagulant agent widely used in inpatient settings to prevent the formation of blood clots which can develop into deep vein thrombosis (DVT) and pulmonary embolism (PE). The risk for development of DVT and PE is highest in the hospital due to long-term bed rest. Signs and symptoms of DVT include unilateral leg swelling, pain, warmth, redness, palpable cord, and Homan’s sign; whereas, signs and symptoms of PE include cough, chest pain/tightness, shortness of breath, palpitations, hemoptysis, tachypnea, tachycardia, diaphoresis, and extension of neck pain. Heparin dosing is very complicated. The provider has to calculate the initial bolus dose and infusion dose based on the patient’s weight until the maximum dose is reached. From there a patient needs to be monitored closely using the Activated Partial Thromboplastin Time (aPTT) tool to see if a heparin dose adjustment is needed to prevent an adverse event from occurring. For instance, if a supra-therapeutic dose of heparin and sub-therapeutic dose of heparin is given it can cause bleeding and induce clots forming, respectively.

The Importance of Heparin Therapeutic Monitoring

All hospitals have a standardized heparin nomogram that utilizes the Activated Partial Thromboplastin Time (aPTT) to guide heparin dosing to reduce delays in therapy and adverse events. The aPTT is a measure of how long it takes for an individual to form a blood clot. With that being said, there are different heparin nomograms created for specific patient indications. For the sake of simplicity, we focused on creating a clinical calculator based on VCU’s heparin dosing protocol for the adult general cardiovascular (CV), adult DVT/PE, and pediatric DVT/PE.

Therefore, a patient on heparin needs to be monitored closely using the Activated Partial Thromboplastin Time (aPPT).

Use of KNIME in Heparin Calculations

We utilized a free data analytics software called KNIME to create our simple input-output heparin dosing calculator. Our clinical calculator provides the initial bolus dose, initial infusion rate, infusion rate/bolus dose adjustment and time to repeat aPTT measurement for adult general CV, adult DVT/PE and pediatric DVT/PE cases. The goal of developing a heparin dosing calculator is to help ease the burden and stress for the healthcare provider, to reduce dosing errors, and to retrieve a dosing regimen rapidly.

Advantages of our KNIME Workflow in Comparison to our Competitors

There are other clinical calculators available for heparin dosing available online, such as GlobalRPh, Dr. Zad, and Heart Recovery. Unlike our competitors, our calculator is not product specific, available for different patient populations, and offers multiple heparin dosing protocols. We also use an open source free platform, KNIME, which is available for anyone to use. Our competitors’ clinical calculators are most likely written in code, which can not be easily followed or understood by an ordinary person. This poses another advantage of our calculator since we utilize an abstract version of code called nodes. Lastly, our internal workflow is easily accessible to anyone who is interested in learning how we were able to create our calculator, and in return, can be effortlessly modified and applied as a starting point for others to use for their own projects.

KNIME Workflow

Our workflow consists of three main sections, adult general CV, adult DVT/PE, and pediatric DVT/PE heparin dosing, as shown in Figure 1. Each section is broken into two separate components, one for initial bolus and initial infusion rate and the other for adjusted heparin dosing based on the patient’s aPTT.

1. Adult general CV and DVT/PE

We will use the adult general CV calculator as an example. The first component in the workflow (Figure 2) is the interactive board that utilizes the String Input node and two Single Selection Widget node. These nodes allow the user to input patient specific information such as weight and the heparin concentration. Whether the weight is entered in pounds or kilograms, our workflow can convert the value into kilograms to use in the calculation of the initial doses through the Rule Engine Variable node and the “Unit conversion” component. The final portion handles heparin calculations to determine the initial bolus dose and initial infusion rate by using the Math Formula, Rule Engine, Round Double, and Column Filter nodes.

Figure 2. This figure depicts the workflow used to calculate the heparin initial bolus dose and initial infusion rate for adults.

The next component of the workflow, as shown in Figure 3, calculates the post-aPTT dose adjustments. It also allows the user to input the time, current aPTT, concentration of the heparin product used, and current infusion rate which are all merged and sorted based on aPTT. There are 8 different pathways the calculator will follow based on the aPTT entered in seconds: <40, 40–54, 55–69, 70–100, 101–115, 116–130, 131–150, and >150. With a therapeutic aPTT goal between 70–100 seconds. Each pathway will have a different outcome that will provide an adjusted bolus dose, if needed, and notify the provider whether they should stop the infusion, change the rate, and what time to take another measurement, as shown in Figure 4.

For adult DVT/PE dosing, the components are exactly the same. However, there are a couple of differences including the initial bolus and initial infusion values used in the calculations and the aPTT ranges that determine the calculator output

Figure 3. This figure is an overview of the workflow to determine the post-aPTT dose adjustments for adult heparin dosing.

Figure 4. An example of the output text populated when the patient’s measured aPTT is above 150 seconds utilizing our post-aPTT dose adjustment calculator.

2. Pediatric DVT/PE

A similar workflow is utilized for the pediatric DVT/PE initial bolus dose and initial infusion rate yet there is one discrepancy. The initial infusion dose is based on whether the child is less than or greater than one year of age; therefore, an additional String Input node is utilized for the patient’s age, as shown in Figure 5.

Figure 5. This figure depicts the workflow used to calculate the heparin initial bolus dose and initial infusion rate in pediatrics. Noting the additional sting input for patient age.

The aPTT ranges are slightly different from the ones seen in the adult general CV and DVT/PE calculators: <55, 55–69, 70–110, 111–125, 126–140, and >140. The therapeutic aPTT goal is broader at 70–110 seconds. In addition, the aPTT dose adjustments are based on rate change perchange, as shown in Figure 6.

Figure 6. This figure is an overview of the workflow to determine the post-aPTT dose adjustments for pediatric heparin dosing.

The calculator described above as well as other KNIME based workflows related to healthcare can be downloaded from our public Digital Healthcare from the KNIME Community Hub.