About You – Lorrca – Functional RBC Analysis

Lorrca for Research

The Lorrca is currently used in a wide range of research applications and appeared already in hundreds of scientific papers. The Lorrca is a functional Red Blood Cell analyzer capable of automated measurement of various red blood cell (RBC) phenomena by analysis of their rheological behaviour. The technique accurately measures RBC deformability as a function of shear stress, osmolality and oxygen pressure, which should be standard in the haematology laboratory.

The Lorrca provides:

One platform for several applications
High quality data
Flexibility

See below the Research Fields that are currently served by the Lorrca platform:

Deformability of different sub-populations of the RBC’s

When measuring the deformability, the obtained deformability curve shows the mean deformability of all RBC’s present in the sample. By adjusting the gain of the CCD camera (the electronic diaphragm), it is possible to detect the deformability of sub-populations of the RBC’s. This can be refined to the percentage of RBC’s with this decreased deformability, e.g. in sickle cell disease: the percentage of irreversibly sickled cells.

Enzyme deficiencies

Different pathways in which the RBC’s receive their metabolic needs are identified. The hereditary enzyme deficiencies of these pathways can cause non-spherocytic anaemia, of which glucose-6-phosphate dehydrogenase (G6PD) is the most common deficiency. In G6PD deficient individuals RBC deformability was found to be significantly impaired. Carriers have two RBC populations present in their blood: one with and one without G6PD activity, there is evidence that these RBC’s differ in their deformability, this can be further investigated.

Malaria infection

Regarding the instrument’s value in clinical pathology, it was demonstrated that in Malaria Tropicana the mean RBC deformability (mainly of non-parasitized RBC) is the most important predictor of, and most probably a contributor to, mortality. The Lorrca determined the threshold at which complete blood transfusion is the only lifesaving treatment possible. Above this threshold, oral medication is still an adequate treatment. Below this threshold, without intervention, the mortality-rate is up to a 100%.

Immunosuppressive therapy

Cyclosporin is an increasingly popular drug in immunosuppressive treatment, especially after organ transplantation. Unfortunately, serious adverse reactions, like nephrotoxicity, can occur which are possibly dose related. It is suggested that this slow, but continuously increasing, RBC rigidification plays a role in the early pathogenesis of the adverse nephrotoxic complications frequently associated with this immunosuppressive regimen. Therefore, regular screening on a loss of RBC deformability and eventually subsequent intervention by lowering the dose or by changing to another drug, could prevent irreversible nephrotic damage

Lorrca platform measuring a broad spectrum of RBC disorders

Application of Lorrca Measurements in Disease and Research Field

Lorrca for Hospitals

Among the methods proposed for the diagnosis of hemolytic anaemias, ektacytometry is certainly one of the most interesting due to its versatility, being able to discriminate diﬀerent defects by a single analysis and his repeatability and reproducibility, enabling an easy standardization in specialized laboratories, as recently reported by other groups.

Ektacytometry can detect with high sensitivity multiple changes in cellular properties, obtaining information that by conventional methods would require several diﬀerent types of measurements. Several studies have shown that the Osmoscan analysis represents a useful and feasible ﬁrst step screening test for specialized centres involved in the diagnosis of hemolytic anaemias.

The Lorrca Oxygenscan is the only method that will be able to measure the “Point of Sickling”, quantitatively indicating the severity of SCD patients. Based on this information see the positioning of Lorrca in the workflow on the right.

Lorrca for Pharma

Sickle Cell Disease

More than 20 million individuals are living with sickle cell disease (SCD) world-wide. Sickle cell disease, a rare, genetically inherited condition, which affects haemoglobin, the protein in red blood cells that carries oxygen throughout the body.

Healthy RBC are small and flexible, and they have the ability to flow throughout capillaries, the smallest veins in the body. In patients with sickle cell disease, RBC that express the mutant, the sickle form, of haemoglobin (HbSS) polymerizes to form fibers that make RBC less flexible and sickled under low oxygen conditions in the peripheral capillaries.

These sickled blood cells are stiff and angular, and they may get stuck on one another or other cells in the blood leading to occlusion or blockage of vessels in micro capillary beds. Sickled blood cells also become damaged as they collide with the blood vessel walls, further activating immune cells and making them and the vessel wall “stickier”.

Sickle cell disease damages many organs in patients including the lungs, kidneys, brain, liver, spleen and results in daily pain for patients and progressively, frequent hospitalizations.

SCA treatment

Very little has changed in the treatment of this disease over the last several decades. The only approved drug for its treatment is a re-purposed chemotherapy agent called hydroxyurea. While hydroxyurea has been shown to reduce the signs and symptoms of sickle cell disease, achieving correct dosing of this drug is complex and requires patients endure life-long monitoring on a monthly basis, as a hydroxyurea regimen has the potential to cause neutropenia. Furthermore, concerns continue to exist about its potential impact on fertility with sickle cell disease, potential genetic toxicity to foetuses and potential cancer-causing effects.

There has been a recent explosion in the interest among investigators in both the hematologic academic community and in the pharmaceutical industry to develop new treatments for sickle cell disease, as indicated by the large number of active clinical protocols (see clinicaltrials.gov).

New drug development as well as trials of existing compounds have targeted one or more pathophysiologic factors in an effort to improve the overall prognosis of SCD as well as to reduce or treat its cardinal manifestation, vaso-occlusion.

Given the diversity of therapeutic targets and pharmacokinetics of potential drugs, trials of new therapies have focused on a variety of different outcomes, including prevention of SCD events (such as the frequency of both VOC and acute chest syndrome (ACS). Unfortunately, these end points occur at highly variable time points among patients, so that achievement of statistically signiﬁcant differences has been quite challenging. The Lorrca Oxygenscan provides a parameter that is independent from the patient-reported outcome but is indicating the severity of the disease.

The Lorrca provides:

Faster Time to market for therapeutic development program(s)
Reducing Risk & Costs
Individual Patient stratification

Lorrca for Research