Getting Sample Hemolysis Under Control

Hemolysis has been cited as the most common cause of preanalytical error. How can sample hemolysis be avoided? A: Many variables contribute to the ability to obtain a high quality, non-hemolyzed blood sample. Controlling the flow of blood between the vein and the tube is really the basis of a good sample collection. Factors that influence the flow of blood include needle gauge, force of suction, size and quality of the vein, and the device used for collection. Direct transfer into vacutainer tubes will control the flow from the needle into the tube, minimizing hemolysis during transfer. When drawing blood into a syringe, the force of suction should be minimal. A good tip is to pull the syringe back and fill it a bit at a time to control the flow. The same goes for transferring from syringes into collection tubes. Allowing the vacutainer to pull the blood into the tube—rather than pushing—maintains appropriate pressure. How should laboratories examine samples to identify hemolysis? Automated hemolysis index measurements on chemistry analyzers are fast and very reliable at detecting the presence—and relative quantification—of hemoglobin in a sample. Compared to visual examination, automation is more sensitive and reproducible in detecting the presence of hemoglobin and distinguishing it from similar colored interferents, such as bilirubin. Significantly, automation also allows direct electronic communication to the laboratory information system.  How hemolyzed is too hemolyzed? Read more here

Defining Critical Value Lists and Limits: How can labs balance efficiency and patient safety?

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An interview with Christine Schmotzer, MD

Defining Critical Value Lists and Limits: How can labs balance efficiency and patient safety?

Defining, identifying, and rapidly communicating critical values is essential to the quality of care. But as the workload in clinical laboratories continues to increase and physicians face information overload, laboratories are forced to be more efficient without compromising patient safety. In this interview, Christine Schmotzer, MD, discusses how to design a critical value list and steps that labs can take to balance efficiency with patient safety. Schmotzer is the medical director of clinical chemistry at University Hospitals Case Medical Center and an assistant professor of pathology at Case Western Reserve University School of Medicine in Cleveland, Ohio.

Jaime Noguez, PhD, of the Patient Safety Focus editorial board conducted this interview.

Q What is the best strategy for establishing a critical value list and limits?
A Despite the importance of critical values in patient care and the emphasis on effective communication of these results in the past decade, there is no widely accepted guideline for defining which analytes should be on a critical value list and how the ­cutoffs should be assigned. Developing a critical value list remains at the discretion of each institution. In practice, a common group of tests—including glucose, potassium, hemoglobin, hematocrit, and platelets—appear on the critical value list of nearly every institution. The specific values for these commonly covered analytes, as well as other analytes that should be included beyond the common ones, vary considerably between institutions. The best strategy for your lab is to use all available data to guide your decision. This includes published literature, peer comparisons, local institutional data—especially the populations being served—and the local opinion and consensus of clinicians working at your institution.

Ideally, labs would use outcomes literature to determine cutoffs at which a specific analyte value becomes life-threatening if an intervention is not taken. But outcomes literature is limited, due in part to the challenges of obtaining broadly applicable data in varied patient populations. A number of surveys and institutional case studies have been published on this topic emphasizing the institutional variability of critical value lists/cutoffs and the lack of a well-defined mechanism for establishing them (1–4). The availability of these surveys and studies allows laboratories to compare their lists to others and provides insight into whether your institution is over or under-restrictive in critical value calling. Survey data should be transferred with caution as it may not be current, and may not be a suitable match to your patient population. 

Achieving Balance in Critical Value Policies • Optimize critical value limits • Remove tests that do not meet "life-threatening­" criteria • Discontinue repeat calls for select analytes with previous criticals • Discontinue calls to units where "critical" result is expected • Include regular review of critical value ­policies and data in test utilization management committee meetings

Another approach to improving your critical value list is specific peer-to-peer comparisons. Peer comparison can enable a lab to select institutions with a similar patient mix and complexity of population which may lead to critical value lists that are more directly transferrable or comparable to your own institution. Peer comparison has been enabled in the last decade by widespread availability of current institutional critical value lists and cutoffs on the Internet (5–7). These are provided by national labs, university-based labs, and other hospital labs. In general, it is relatively easy to find a peer, either through the Internet or your professional network.

Regardless of your initial approach to data-gathering, developing a critical value list and cutoffs should include discussion among clinicians, nurses, laboratory directors, and staff representing various departments and specialties. It is in this setting that institution-specific practices and needs can be discussed and influence the critical value list. For example, if an institution performs all blood gases at the point-of-care rather than in a decentralized laboratory, it may not need pH or pO2 to be included on a critical value list. Without specific outcomes literature to guide decisions, institutional and personal experience can be solid guides to setting critical value cutoffs that best meet the needs and philosophy of an institution.

Q Are there any other factors that need to be considered when designing your critical value list?
A While literature review, peer comparisons, and consulting with your physicians are important, assessing your current state, including critical result distribution, call frequency, and reporting logistics can provide insight into opportunities for improving your critical call list and process. Determining the tests leading to the highest number of calls and the units receiving the most calls can lead to valuable insights. For example, we were surprised to find critical vancomycin levels were in our top 10 most called tests. Further exploration led to practice changes to enhance the relationship between time of draw and drug administration, as well as discussion on whether abnormal vancomycin levels met the definition of a critical—immediately life-threatening—value. An important but often overlooked factor in successful critical value policies and procedures is the capabilities of your laboratory information system (LIS) for helping you identify and flag critical results. Many LISs don't have the ability to assign unit-specific flags. For example, clinical consensus at your institution may show that the threshold for critically low potassium can be different for inpatients versus outpatients. If your LIS does not allow for different critical results based on inpatient or outpatient status, the critical result will likely be set at the most conservative cutoff.

Q How can labs improve their critical values notification efficiency without compromising patient safety? Read more here

The Clinical Laboratory's Role in Preventing False-Negative hCG Point-of-Care Results

False negative pregnancy tests in the emergency department (ED) can have serious consequences—including birth defects or loss of pregnancy—if pregnant women are subjected to certain treatments potentially harmful to a fetus. While in vitro device manufacturers and ED clinicians must do their part to help minimize the frequency of false-negative test results, laboratory personnel ultimately are responsible for the accuracy of point-of-care (POC) testing. To minimize false-negative­ qualitative human chorionic gonadotropin (hCG) test results, laboratorians must understand the limitations of POC hCG devices, utilize strategies to investigate results that are inconsistent with the clinical presentation, and recommend alternate testing to help establish a definitive diagnosis. Measurement of hCG represents an analytical challenge, as the range of hCG concentrations associated with normal pregnancy spans from 0 IU/L immediately following conception to approximately 200,000 IU/L by weeks 8 to 10. False-negative urine hCG results could be encountered for a number of different reasons. Negative results are common in very early pregnancy, when hCG concentrations in urine likely are below a device's limit of detection. False-negative results may also occur due to the hook effect, a phenomenon characterized by a pathologically high concentration of intact hCG that saturates all available binding sites and prevents an antibody-hCG-antibody sandwich from forming. In normal pregnancy, intact hCG concentrations are not sufficiently elevated to cause a hook effect. However, intact hCG is not the only variant observed in normal pregnancy, and hCG POC devices may either recognize or interfere with these other variants. One such variant, hCG β core fragment (hCGβcf), is present at 10-fold higher concentrations than intact hCG in urine beginning at around week 6 of pregnancy. As a degradation product formed during renal filtration, hCGβcf is exclusively found in urine. Of particular interest to laboratory personnel, false-negative POC hCG results have been documented in women with high urinary concentrations of hCGβcf. Read more here

Obesity accelerates aging of the liver, researchers find using novel biological aging clock

Using a recently developed biomarker of aging known as an epigenetic clock, researchers have found, for the first time, that obesity greatly accelerates aging of the liver. "Given the obesity epidemic in the Western world, the results of this study are highly relevant for public health," the lead investigator said. 

Read more here

Energy drinks cause heart problems, study suggests

Energy drinks can cause heart problems according to research presented at ESC Congress 2014 today by Professor Milou-Daniel Drici from France.

Professor Drici said: "So-called 'energy drinks' are popular in dance clubs and during physical exercise, with people sometimes consuming a number of drinks one after the other. This situation can lead to a number of adverse conditions including angina, cardiac arrhythmia (irregular heartbeat) and even sudden death."

He added: "Around 96% of these drinks contain caffeine, with a typical 0.25 litre can holding 2 espressos worth of caffeine. Caffeine is one of the most potent agonists of the ryanodine receptors and leads to a massive release of calcium within cardiac cells. This can cause arrhythmias, but also has effects on the heart's abilities to contract and to use oxygen. In addition, 52% of drinks contain taurine, 33% have glucuronolactone and two-thirds contain vitamins."

He added: "Patients with cardiac conditions including catecholaminergic arrhythmias, long QT syndrome and angina should be aware of the potential danger of a large intake of caffeine, which is a stimulant that can exacerbate their condition with possibly fatal consequences."

He concluded: "Patients rarely mention consumption of energy drinks to their doctors unless they are asked. Doctors should warn patients with cardiac conditions about the potential dangers of these drinks and ask young people in particular whether they consume such drinks on a regular basis or through binge drinking."

HEMOZION : New way to diagnose malaria

Red blood cells from a patient infected with Plasmodium falciparum.

Over the past several decades, malaria diagnosis has changed very little. After taking a blood sample from a patient, a technician smears the blood across a glass slide, stains it with a special dye, and looks under a microscope for the Plasmodium parasite, which causes the disease. This approach gives an accurate count of how many parasites are in the blood -- an important measure of disease severity -- but is not ideal because there is potential for human error.

A research team from the Singapore-MIT Alliance for Research and Technology (SMART) has now come up with a possible alternative.The researchers have devised a way to use magnetic resonance relaxometry (MRR), a close cousin of magnetic resonance imaging (MRI), to detect a parasitic waste product in the blood of infected patients 

The new SMART system detects a parasitic waste product called hemozoin. When the parasites infect red blood cells, they feed on the nutrient-rich hemoglobin carried by the cells. As hemoglobin breaks down, it releases iron, which can be toxic, so the parasite converts the iron into hemozoin -- a weakly paramagnetic crystallite.

Those crystals interfere with the normal magnetic spins of hydrogen atoms. When exposed to a powerful magnetic field, hydrogen atoms align their spins in the same direction. When a second, smaller field perturbs the atoms, they should all change their spins in synchrony -- but if another magnetic particle, such as hemozoin, is present, this synchrony is disrupted through a process called relaxation. The more magnetic particles are present, the more quickly the synchrony is disrupted.

Hemozoin crystals are produced in all four stages of malaria infection, including the earliest stages, and are generated by all known species of the Plasmodium parasite. Also, the amount of hemozoin can reveal how severe the infection is, or whether it is responding to treatment. There are a lot of scenarios where you want to see the number, rather than a yes or no answer.

In this paper, the researchers showed that they could detect Plasmodium falciparum, the most dangerous form of the parasite, in blood cells grown in the lab. They also detected the parasite in red blood cells from mice infected with Plasmodium berghei.

The researchers are launching a company to make this technology available at an affordable price. The team is also running field tests in Southeast Asia and is exploring powering the device on solar energy, an important consideration for poor rural areas.

Journal Reference:

1. Weng Kung Peng, Tian Fook Kong, Chee Sheng Ng, Lan Chen, Yongxue Huang, Ali Asgar S Bhagat, Nam-Trung Nguyen, Peter Rainer Preiser, Jongyoon Han. Micromagnetic resonance relaxometry for rapid label-free malaria diagnosis. Nature Medicine, 2014; DOI: 10.1038/nm.3622

Leading Ebola researcher says there's an effective treatment for Ebola

A leading U.S. Ebola researcher from the University of Texas Medical Branch at Galveston has gone on record stating that a blend of three monoclonal antibodies can completely protect monkeys against a lethal dose of Ebola virus up to 5 days after infection, at a time when the disease is severe.

Thomas Geisbert, professor of microbiology and immunology, has written an editorial for Nature discussing advances in Ebola treatment research. The filoviruses known as Ebola virus and Marburg virus are among the most deadly of pathogens, with fatality rates of up to 90 percent.

Since the discovery of Ebola in 1976, researchers have been actively working on treatments to combat infection. Studies over the past decade have uncovered three treatments that offer partial protection for monkeys against Ebola when given within an hour of virus exposure. One of these treatments, a VSV-based vaccine was used in 2009 to treat a laboratory worker in Germany shortly after she was accidentally stuck with a needle possibly contaminated by an Ebola-infected animal.

Further advances have been made that can completely protect monkeys against Ebola using small 'interfering' RNAs and various combinations of antibodies. But these treatments need to be given within two days of Ebola exposure.

"So although these approaches are highly important and can be used to treat known exposures, the need for treatments that can protect at later times after infection was paramount," said Geisbert.
Further research led to a cocktail of monoclonal antibodies that protected 43% of monkeys when given as late as five days after Ebola exposure, at a time when the clinical signs of the disease are showing.

The new study from Qui and colleagues at MAPP Biopharmaceutical Inc. used ZMAPP to treat monkeys given a lethal dose of Ebola. All of the animals survived and did not show any evidence of the virus in their systems 21 days after infection, even after receiving the treatment 5 days after infection. They also showed that ZMAPP inhibits replication of the Ebola virus in cell culture.

ZMAPP has been used to treat several patients on compassionate grounds. Of these, two US healthcare workers have recovered, although but whether ZMAPP had any effect is unknown, as 45% of patients in this outbreak survive without treatment. There were also two patients treated with ZMAPP who did not survive, but this may be because the treatment was started too late in the disease course.

"The diversity of strains and species of the Ebola and Marburg filoviruses is an obstacle for all candidate treatments," said Geisbert. "Treatments that may protect against one species of Ebola will probably not protect against a different species of the virus, and may not protect against a different strain within the species."

Although we certainly need treatments for filovirus infections, the most effective way to manage and control future outbreaks might be through vaccines, some of which have been designed to protect against multiple species and strains. During outbreaks, single-injection vaccines are needed to ensure rapid use and protection. At least five preventative vaccines have been reported to completely protect monkeys against Ebola and Marburg infection. But only the VSV-based vaccines have been shown to complete protect monkeys against Ebola after a single injection.

"Antibody therapies and several other strategies should be included in the arsenal of interventions for controlling future Ebola outbreaks," said Geisbert. "Although ZMAPP in particular has been administered for compassionate use, the next crucial step will be to formally assess its safety and effectiveness."

Journal Reference:

1. Thomas W. Geisbert. Medical research: Ebola therapy protects severely ill monkeys. Nature, 2014; DOI: 10.1038/nature13746