Clin Hemorheol Microcirc.2017 64(3):977-987

Rheopheresis in vascular diseases

MelindaVass1, Ágnes Diószegi1, Norbert Németh2, Viktória Sógor2, Sándor Baráth3, Eszter Szalai4, László Módis4, Soltész Pál1 

 

University of Debrecen Clinical Center, Department of Internal Medicine, Division of Angiology1

University of Debrecen Clinical Center, Department of Operative Techniques and Surgical Research2

University of Debrecen Clinical Center, Department of Laboratory Medicine3

University of Debrecen Clinical Center, Department of Ophtalmology4  

Corresponding author: Prof. Dr. Pál Soltész

Equal contributed: Dr. Vass Melinda, Dr. Diószegi Agnes

 

Abstract

Rheopheresis is an extracorporal selective double-filtration procedure. In the first part of the treatment the blood is passes through the plasma filter, which separates blood cells from the plasma. Then the plasma flow to a second filter called MONET (Membranefiltration Optimised Novel Extracorporal Treatment). The MONET filter retains high molecular weight proteins such LDL, Lp(a), fibrinogen, α2 macroglobulin, vWF and IgM. Hereby the whole blood and plasma viscosity decrease, improves microcirculation, and has a positive effect on lipid profile as well.

According to ASFA recommendation rheopheresis is a first line treatment in age-related dry macular degeneration and in sudden sensorineural hearing loss. There are other clinical situations in which rheopheresis has been used effectivly. But only few data are available and large clinical trials have not been done in these diseases. In this paper we describe a case history and laboratory findings of a patient who suffers from age related dry macular degeneration and was successfully treated by rheopheresis.

Keywords: rheopheresis, microcirculation, age-related dry macular degeneration, anti-inflammatory effect, haemorheological parameters

 

 

Supplement

During the past few years several novel therapeutic apheresis methods were introduced, One of these new therapeutic procedures is called rheopheresis, which is a 2-step cascade filtration (1). As the first step of the treatment cellular elements are separated from the plasma, then the plasma flows through a special filter which is able to eliminate certain plasma components based on molecular size, or at least it is able to reduce their level significantly (2).

With the help of the MONET filter (Membrane filtration Optimised Novel Extracorporal Treatment) proteins with molecular weights higher than 250-300 kDa can be eliminated from the plasma. LDL, Lp(a), fibrinogen, α2 macroglobulin, vWF and IgM are some of those proteins of high molecular weight which are eliminated this way. The fibrinogen level is also reduced to its half in general (3).

Decrease of Lp (a), vWF and IgM levels as well were observed.The favourable effect of the rheopheresis therapy is resulting from the beneficial changes in levels of these macromolecules. As a result of this, treatment viscosity of the plasma and the whole blood is reduced, the erythrocyte aggregation is moderated and deformability of the erythrocytes is improved (2, 4).

As a consequence of these, microcirculation is improved, and microcirculatory dysfunctions are also alleviated.

Indication range of rheopheresis has been widened during the past few years. Trials were conducted with rheopheresis in different disease groups, however, randomized, prospective clinical trials were only conducted in case of age-related macular degeneration and sensori-neural hearing loss (5,6). Based on double blind, placebo-controlled trials, and 2013 guidelines of the American Society for Apheresis (ASFA), rheopheresis is the recommended as first line therapy in case of dry form of age-related macular degeneration (7).

Firtstly in Hungary rheopheresis was performed in our Department with the indication of dry, age-related macula degeneration. Our patient experienced blurred vision and central visual field loss. Based on the dilated fundus examination, optical coherence tomography (OCT), and fluorescent angiography dry type age-related macula degeneration was diagnosed in the background of his complaints. Between July 2014 and July 2016 the patient received 6 cycles of rheopheresis treatment, altogether for 11 times. No complications or side effects were observed during the course of the therapy.

For efficacy assessment of the rheopheresis treatment we performed laboratory tests and angiological examinations – besides the ophthalmological tests – preceding the treatment cycles, as well as at the end of each therapeutic cycle. According to our assumption, rheopheresis treatment not only works via improvement of viscosity to moderate microcirculatory dysfunction, but it may have other anti-inflammatory effects, and it might decrease the level of endothelial and thrombocyte activating markers. All these beneficial effects may result in improving the endothelial functions.

quotient obtained this way is m/s.

Ophthalmological examination determined the best corrected visual acuity of the patient on a logarithmic scale, we took colour photos of the eye fundus (TRC-NW7SF, Topcon, Tokyo, Japan) and we performed an OCT (Zeiss Stratus, Carl Zeiss Meditec, Inc, California USA).

Viscosity of whole blood and the plasma was increased prior to the first treatment, and increased erythrocyte aggregation was also measured, in line with borderline fibrinogen level. It can be observed that by the end of the first therapeutic cycle viscosity of the plasma returned to the normal range, viscosity of the whole blood also decreased significantly, it almost reached the reference range. Erythrocyte aggregation normalized and fibrinogen level also decreased. examination. During the additional therapeutic cycles we observed obtained similar results

Prior to the first therapeutic cycle significantly increased phagocyte activity and increased CD14+/CD16+ cell population ratio were detected. Our results support the hypothetic inflammatory involvement of chorio-capillaries in pathogenesis of AMD. After the first treatment session, as a result of that phagocyte activity and CD14+/CD16+ cell population ratio normalized.

Beneficial effects emerging as a result of rheopheresis therapy may not only be exhibited via enhancing blood flow and improvement of microcirculation. According to our assumption these effects can improve macrocirculation as well. Within the confines of this endothelial dysfunction may be improved, as well as stiffness parameters

Our examinations supported the hypothesis that besides the above mentioned effects of rheopheresis, it may have other vascular and angiological impacts. In line with normalization of viscosity parameters and decreasing the levels of atherogenic lipid fractions, it was proven that rheopheresis has anti-inflammatory effect as well, and it also moderates thrombocyte activation, which has additional beneficial effects too. In addition to all the above mentioned facts, we also found evidence that rheopheresis therapy may improve endothelial functions and stiffness parameters. These effects might have the outmost importance regarding the treatment of vascular diseases developing as a result of atherosclerosis. However, further examinations are needed to discover vascular target points of rheopheresis in details.

 

Figure 1. Picture of the patient’s coloured fundus: before the 1st treatment (on the top), after the 2nd (in the middle), and after the 3rd treatment (below)

 

Based on the examination of the eye fundus, the wasting of the right eye was not aggravated as a result of the therapy, and sub-retinal bleeding of the left eye absorbed completely by the end of the third cycle of therapy.

 

 

Figure 2. OCT image: before the 1st rheoferezis treatment (on the top), after the 2nd treatment (in the middle) and after the 3rd treatment (below)

 

By the end of the therapeutic cycles the contour of the fovea on the right became even, no progression was observed, neither intra-retinal nor sub-retinal fluid was visible on the left eye, and the pigment epithelium abruption also ceased (Figure 2).

 

References

1. Schuff-Werner P Extracorporeal hemorheotherapy with selective plasma protein elimination, Jpn, J Apheresis, 1997, 16;25-30
2. Brunner R1, Widder RA, Walter P, Borberg H, Oette KInt Change in hemorrheological and biochemical parameters following membrane differential filtration. J Artif Organs. 1995 Dec;18(12):794-8
3. J Ringel, MS80 LIPOPROTEIN FILTRATION BY MONET: FIRST CLINICAL APPLICATION IN LDL REMOVAL, Atherosclerosis Supplements, 2010,Volume 11, Issue 2, Page 126
4. Widder RA1, Brunner R, Borberg H, Changes of haemorheological parameters when using plasma exchange, selective adsorption and membrane differential separation. Transfus Sci. 1996 Dec;17(4):505-10
5. Brunner R1, Widder RA, Walter P, Lüke C, Godehardt E, Bartz-Schmidt KU, Heimann K, Borberg H. Influence of membrane differential filtration on the natural course of age-related macular degeneration: a randomized trial. Retina. 2000;20(5):483-91.
6. Pulido JS1; Multicenter Investigation of Rheopheresis for AMD (MIRA-1) Study Group. Multicenter prospective, randomized, double-masked, placebo-controlled study of Rheopheresis to treat nonexudative age-related macular degeneration: interim analysis. ., Trans Am Ophthalmol Soc. 2002;100:85-106; discussion 106-7
7. Carallo C, Loprete A, Mazza G, Bellotti G, de Siena M, Serrao P, Vuoto ES, de  Franceschi MS, Irace C, Gnasso A. Biphasic hemodynamic effects of LDL-apheresis in common carotid artery. Clin HemorheolMicrocirc. 2015;60(3):297-307.