JPH09122231A - Hollow thread membrane type white blood cell removing filter device - Google Patents

Abstract

PROBLEM TO BE SOLVED: To increase the white blood cell removing capability without increasing the pressure loss by filling a porous hollow thread membrane with through holes having the average hole diameter of the prescribed value, having the average membrane thickness of the prescribed value, and having the average filtration area/apparent membrane volume of the prescribed value in a container provided with an inlet and an outlet. SOLUTION: A porous hollow thread membrane 2 provided with through holes having the average hole diameter 1-100μm and having the average membrane thickness 0.05-2mm and the average filtration area/apparent membrane volume of the value 3-200cm<2> /cm<3> is filled in a container 1 provided with a liquid inlet 4 and a liquid outlet 6 to form this hollow thread membrane type white blood cell removing filter device. The average hole diameter is the average diameter of fine holes dispersed on the cut surface of an optical cross section of the hollow thread membrane 2, and the average membrane thickness is the average value of the membrane thicknesses measured at ten or more points at random on one hollow thread membrane 2. The average filtration area is the logarithmic average between the total inner area and the total outer area when the hollow thread membrane 2 is typically regarded as a cylinder, and the apparent membrane volume is the sum of the total volume of the membrane base material and the total fine hole volume in the membrane.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a hollow fiber membrane type leukocyte removal filter device for capturing and removing leukocytes from leukocyte suspension. More specifically, the present invention relates to a hollow fiber membrane type leukocyte removal filter device for capturing and removing leukocytes mixed in blood products for transfusion such as whole blood, concentrated red blood cells and concentrated platelets.

[0002]

2. Description of the Related Art In recent years, with the progress of immunology and blood transfusion, component blood transfusion in which only components necessary for treatment of various diseases are concentrated and transfused has been performed from conventional whole blood transfusion. . Various blood products used for component transfusion, namely, erythrocyte concentrate (CRC), platelet concentrate (PC), and platelet poor plasma (PPP), are separated and fractionated by centrifuging whole blood obtained by donation. Be adjusted. However, it has been clarified that a large number of leukocytes are contained in the blood product separated by the centrifugation operation, and the mixed leukocytes induce post-transfusion side effects. Post-transfusion side effects include relatively minor side effects such as headache, nausea, chills, and non-hemolytic fever reaction.
Induction of graft-versus-host reaction (GVHD) in which transfused leukocytes have a lethal effect on the recipient's skin and internal organs, infection by viruses present in leukocytes such as cytomegalovirus infection, alloantigen sensitization, etc. It is known to have serious side effects. In order to prevent such blood transfusion side effects, it is effective to capture and remove leukocytes mixed in the blood product. Usually, blood products used for transfusion such as whole blood and blood products contain 10 ⁷ / ml of white blood cells. In order to prevent relatively minor side effects such as headache, non-hemolytic fever reaction, chills, and nausea, it is necessary to keep the number of white blood cells infused to the recipient in a single blood transfusion to less than 100 million. For this purpose, it is necessary to remove the residual white blood cells contained in the blood product until the residual ratio becomes 10 ^-1 to 10 ^-2 or less. In order to prevent alloantigen sensitization and virus infection, the leukocyte residual rate is 10 ^-4 to 10 ^-5.
It is expected to be prevented by removing up to the following. Methods for removing leukocytes from blood products include gravity centrifugation using the difference in specific gravity of blood and a porous element such as a fibrous medium such as a non-woven fabric or a porous body having three-dimensional continuous pores as a leukocyte-capturing material. The filtering method is broadly classified into two types, and the filtering method is widely used because of its advantages of high leukocyte removal efficiency, simple operation, and low cost.

[0003]

As the leukocyte-capturing material to be filled in the leukocyte-removing filter device, a fibrous medium such as a non-woven fabric or a sponge-like structure having a three-dimensional network continuous structure is mainly used. Since the mechanism of removing leukocytes is thought to be mainly due to adhesion, the difference in leukocyte-removing ability of leukocyte-capturing materials made of the same material and having the same surface is said to be caused by the frequency of collision between leukocyte-trapping materials and leukocytes. . Therefore, in order to enhance the leukocyte-removing ability, it is preferable that the surface area of the leukocyte-capturing material to which the leukocytes should adhere is larger because the frequency of collision between the leukocyte-trapping material and the leukocytes is increased. It is large and has a high leukocyte-removing ability. Therefore, when the non-woven fabric is used as the leukocyte-capturing material, the average fiber diameter is 1 to 3 μm.
Ultrafine fibers of about m are mainly used. However, using a conventional nonwoven fabric having such an ultrafine fiber diameter, in order to enhance the leukocyte removal ability per unit volume, the packing density of the nonwoven fabric is increased to substantially increase the amount of the trapping material, or It was necessary to switch to a non-woven fabric with a small fiber diameter. Usually, the upper limit of the packing density is about 0.4 g / cm ³ , and if it is increased more than this, it will be difficult to fill the inside of the container due to the repulsive force of the nonwoven fabric. In this case, the non-woven fabric will be crushed into a film and will no longer function as a capturing material. Therefore, as a method for enhancing leukocyte-removing ability, it is necessary to increase the amount of leukocyte-capturing material within the range of a packing density of 0.4 g / cm ³ or less, or to use a leukocyte-trapping material having a smaller fiber diameter. However, in any of these cases, as the leukocyte-removing ability is improved, the pressure loss at the time of passing the blood product increases, and the processing speed extremely decreases before the expected blood volume is processed. There was a problem of doing.

On the other hand, regarding the sponge-like structure, the bubble point is 0.08 to 0.08 as a leukocyte separating material which does not cause clogging by leukocytes in JP-A-1-224324.
A porous body of 0.3 kg / cm ² is disclosed.
However, as a result of examination by the present inventors, the leukocyte separating material has a residual ratio of leukocytes mixed in blood products of 10 or less.
^{In the} case of using a porous body having a relatively small average pore diameter, which is suitable for reducing to ⁻² to 10 ⁻³ and is necessary for achieving the target leukocyte survival rate of 10 ⁻⁴ in the present invention, It had the following problems. That is, if a porous body having an optimal average pore size is used, it shows equivalent leukocyte-removing ability with a thickness of a fraction of that of non-woven fabric, and can provide a powerful means for achieving miniaturization. However, those exhibiting such a high leukocyte-removing ability have a problem that at the same time, the pressure loss due to the clogging of leukocytes is high, and similarly to the case of using a non-woven fabric having a small fiber diameter, the processing speed of blood is significantly reduced. Had. A nitrocellulose membrane is described in WO94 / 17894 as a leukocyte-capturing material other than the above, but the flat membrane used in the examples has a small effective filtration area per membrane volume due to its structure, and the membrane surface It has a problem that white blood cells are likely to be clogged.
It is an object of the present invention to provide a leukocyte depletion filter which has increased leukocyte depletion capacity per unit volume without increasing pressure loss, and more specifically, whole blood, red blood cell concentrate (CRC), platelet concentrate ( PC), platelet poor plasma (P
PP) and the like to remove leukocytes from leukocyte suspensions in high yield, and the treatment rate does not decrease when treating the leukocyte suspensions, that is, clogging by blood cells and increase in pressure loss are not seen. It is to provide a filter device.

[0005]

The present invention has an average pore size of 1
Having a through-hole of ˜100 μm and an average thickness of 0.05
2 mm, the value of (average filtration area / apparent membrane volume) is 3 to
A hollow fiber membrane-type leukocyte removal filter device in which a porous hollow fiber membrane having a volume of 200 cm ² / cm ³ is filled in a container having an inlet and an outlet for a liquid. With the average pore diameter of the porous hollow fiber membrane in the present invention, the porous body having through-holes is cut perpendicularly to the flow direction of blood, and the diameter is measured for each of the pores dispersed in the entire cross section. When the relationship between the diameter and the number of pores is investigated, it represents the diameter of the circle with the largest number of pores. That is, the pores dispersed on any cut surface of the porous filter have various shapes and diameters, but each pore is converted into a circle having the same area as the cross-sectional area of the pore, and its diameter is Is plotted on the abscissa and the number of pores is plotted on the ordinate, and a graph is generally drawn to approximate a normal distribution. The straight line corresponding to the peak of the curve is the average pore diameter in the present invention. That is, the average pore diameter is an average diameter of pores dispersed on each cut surface, and the average pore diameter on any cut surface is 1 to 100 μm.
Must be within the range. Further, the average pore size on the inlet side and the outlet side of blood means the average pore size of the cut surface at a portion of 0.01 mm or less from the surface of the porous body in the thickness direction of the filter, and the range of 0.01 mm thickness. The average pore size on the surface may be used as the average pore size on the blood inlet side and the average pore size on the blood outlet side, provided that the average pore size does not change. The average pore size is at least three or more cut surfaces including the blood inlet side and the outlet side, photographed with a scanning electron microscope, and the diameters of pores dispersed on the cut surfaces are randomly measured by 1000 or more. Ask.

The average pore diameter of the porous hollow fiber membrane used in the present invention is preferably in the range of 10 to 100 μm on the inlet side in the liquid filtration direction, more preferably 15 to 75 μm, and most preferably 25 to 50 μm. If the average pore size on the inlet side is less than 10 μm, the pore size is too small, and the flow velocity is likely to be reduced due to clogging by leukocytes and the like on the inlet side surface. On the other hand, if it exceeds 100 μm, the frequency of contact between leukocytes and the membrane surface decreases, and the function of efficient leukocyte removal is not fulfilled. The outlet side in the liquid filtration direction is preferably 1 to 30 μm, more preferably 2 to 20 μm, most preferably 3 μm.
Is in the range of ˜15 μm. If the average pore diameter on the outlet side is less than 1 μm, the pore diameter is too small and the flow velocity is greatly reduced.
On the other hand, if it exceeds 30 μm, white blood cells may leak.

Further, in order to prevent the membrane from being clogged, the structure may be such that the average pore diameter decreases continuously or stepwise in the liquid filtration direction. At this time, the pore size of the inlet side surface of the liquid in the filtering direction is preferably 2 to 50 times, more preferably 3 to 30 times the pore size of the outlet side surface. If it is less than 2 times, the effect of preventing clogging of the membrane is small, while if it exceeds 50 times, the gradient of the pore diameter is too large and the membrane volume of the pore diameter suitable for leukocyte removal is relatively reduced.

The uniform thickness in the present invention is an average value of the thicknesses of one hollow fiber membrane measured at random at 10 points or more, and the average thickness of any hollow fiber membrane in the filter is 0. Must be within the range of .05 to 2 mm. Membrane thickness is an average obtained by cutting the hollow fiber membrane in a direction perpendicular to the hollow fiber axis direction, that is, in the direction parallel to the liquid filtration direction, and randomly measuring 4 or more points each of the inner diameter and the outer diameter of one membrane cross section. It is a value obtained from the value according to the following formula. Average film thickness = average value of film thickness of 10 points or more The average film thickness of the porous hollow fiber membrane used in the present invention is 0.05 to
It is 2 mm, and the more preferable range is 0.1 to 1 mm. If it is less than 0.05 mm, the number of contact between leukocytes and the membrane surface is small, and the possibility of leukocyte leakage increases. On the other hand, when it exceeds 2 mm, the ratio of the filtration area to the apparent membrane volume decreases, and the filtration speed decreases.

The average filtration area (S _av ) of the porous hollow fiber membrane used in the present invention is the total inner area (S ₁ ) and the total outer area (S ₂ ) when the hollow fiber membrane is regarded as a cylinder. Is the logarithmic average of and is calculated by the following equation. The apparent membrane volume is the total volume occupied by the base material of the membrane and the total volume of all pores in the membrane, and is the apparent volume occupied by the membrane. The value of (average filtration area / apparent membrane volume) of the present invention is ³ to 200 cm ² / cm ³ , and a more preferable range is 5 to 100 cm ² / cm ³ . 3 cm ²
If it is less than / cm ³ , the filtration area is small as in the case of the conventional flat plate filter, so that the processing speed may be reduced and clogging may occur. On the other hand, if the membrane exceeds 200 cm ² / cm ³ , the inner and outer diameters of the hollow fiber membrane will be unnecessarily large to secure the membrane thickness necessary for leukocyte removal, making it difficult to manufacture the membrane and the module filled with the membrane. become. The porosity of the porous hollow fiber membrane used in the present invention is preferably 0.40 to 0.95. If the porosity is less than 0.40, the space volume of pores for passing blood is insufficient and clogging by blood cells occurs, and if it exceeds 0.95, the strength of the porous membrane decreases, and the filter medium is no longer used. It is not suitable because it does not fulfill its function.

The material of the porous hollow fiber membrane used in the present invention is not particularly limited as long as it does not easily damage useful components in the filtered liquid other than leukocytes, and various materials can be used. Examples thereof include organic polymers, inorganic polymers and metals. Among them, organic polymers are preferable materials because they are excellent in workability such as cutting. As the organic polymer, for example, polyurethane, polyacrylonitrile, polyvinyl alcohol, polyvinyl acetal, polyester, polyamide, polystyrene, polysulfone, cellulose, cellulose acetate, polyethylene, polypropylene, polyvinyl fluoride, polyvinylidene fluoride,
Polytrifluorochlorovinyl, vinylidene fluoride-tetrafluoroethylene copolymer, polyether sulfone, poly (meth) acrylate, butadiene-acrylonitrile copolymer, polyether-polyamide block copolymer, ethylene-vinyl alcohol copolymer However, the material of the porous hollow fiber membrane of the present invention is not limited to the above examples.

Further, the porous hollow fiber membrane used in the present invention may be produced by a known method, and specifically, the foam decomposition method, the solvent vaporization method, the gas mixing method, the chemical reaction method, the elution method,
Examples thereof include a sponge-like structure manufacturing method such as a sintering method, a stretching opening method, and the like, and secondary processing such as heat treatment or swelling with an appropriate liquid may be performed. The surface of the porous hollow fiber membrane used in the present invention preferably has a basic or acidic functional group. The adhesiveness of leukocytes to polymer materials is influenced by the surface properties of the polymer materials, and not only leukocytes but blood cells generally have a negative charge on the cell surface. Therefore, it is known that a polymer material having a positive charge on the surface is generally effective for capturing and removing leukocytes (W
O / 05812). On the contrary, a surface having a negative charge is also effective for capturing leukocytes. An electrostatic repulsive force acts between the originally negatively charged cell and an acidic functional group that also has a negative charge, and it seems that the amount of cell adhesion may decrease, but It is suspected that certain proteins contained in plasma adhere faster than they contact the negatively charged material surface, and that the mediation of this protein promotes adhesion of leukocytes. It is also effective to smoothly filter the leukocyte suspension or to introduce a hydrophilic functional group such as a hydroxyl group or a polyethylene oxide chain in order to reduce damage or non-specific adsorption to cells other than leukocytes. . In order to contain the above-mentioned functional group on the film surface, a polymer having the above-mentioned functional group or the like may be used as a film material, or may be used as a mixture with another material. It is also preferable to introduce the above-mentioned functional group by graft polymerization, coating, chemical treatment with alkali, acid or the like, surface modification such as plasma treatment.

In the hollow fiber membrane type leukocyte removal filter device of the present invention, a filter for removing aggregates in the leukocyte suspension may be interposed between the liquid inlet and the leukocyte removal porous hollow fiber membrane. . Further, a circuit incorporating a filter for removing agglomerates such as a mesh chamber may be connected to the inlet of the filter device for use. If a large number of aggregates are present in the leukocyte suspension, clogging is likely to occur during filtration. Therefore, it is necessary to remove the aggregates when filtering such a liquid. Examples of filters used for this purpose include porous membranes, non-woven fabrics, woven fabrics, meshes, filter papers and membrane filters. The hollow fiber membrane type leukocyte depletion filter device of the present invention may be used by connecting it to a container containing leukocyte suspension immediately before use, and may be used in advance at the liquid inlet and / or liquid outlet of the device such as a blood bag. A system in which a container is connected may be assembled and a leukocyte suspension may be injected into the system for use. Further, liquids such as physiological saline, blood anticoagulants, and red blood cell preservatives may be present in the filter device in advance. Further, the filtration direction of this device can be either from the inside to the outside or from the outside to the inside of the hollow fiber membrane. When filtering from the inside to the outside, there is an advantage that the entire membrane area can be effectively used because the liquid flows evenly through the membrane due to the liquid flow in the membrane, whichever direction the device is used. On the other hand, when filtering from the outside to the inside, there is an advantage that clogging due to the removed white blood cells is unlikely to occur.

The leukocyte suspension referred to in the present invention includes whole blood, concentrated red blood cells, washed red blood cells, leukocyte-removed red blood cells, thawed red blood cell concentrate, red blood cell preparation of thawed red blood cell suspension, platelet poor plasma, platelet rich plasma, fresh frozen plasma. , Fresh liquid plasma,
Examples include plasma preparations of cryoprecipitate, concentrated platelets, buffy coat, buffy coat-removed blood, and the like. The hollow fiber membrane type leukocyte removal filter device of the present invention will be described in detail based on the following examples.

[0014]

【Example】

Example 1 Hydroxyethyl methacrylate (HE) was added to a polyethylene porous hollow fiber membrane obtained by an elution method.
MA) and dimethylaminoethyl methacrylate (D
A polymer consisting of M) (DM content in the polymer was 30 mol%) was impregnated as a 0.5% ethanol solution, and the solution was drained and dried with hot air at 60 ° C. for 16 hours to obtain a coating film. A hollow fiber membrane type leukocyte removal filter as shown in FIG. 1 was prepared by filling 34 hollow cylinders 1 made of polycarbonate having liquid inlet 4 and outlet 6 with the hollow fiber membranes 2 and fixing both ends with urethane adhesive. Was produced. The coated porous hollow fiber membrane used here had an effective length of 15 cm, a membrane thickness of 0.4 mm (membrane outer shape average value 1.1 mm, membrane inner diameter average value 0.3 mm), average pore diameter 5.2 μm, and apparent membrane volume 4.
It was 5 cm ³ . 28 ml of CP in 200 ml of blood
Platelet-rich plasma was removed from 228 ml of whole blood prepared by adding D by centrifugation within 8 hours after blood collection.
The red blood cell preparation (hematocrit 61%) prepared in a blood bag and stored in a blood bag at 4 ° C. for 15 days was allowed to reach room temperature (23 ° C.), and then the above-mentioned white blood cells to which a blood transfer tube 8 incorporating a mesh chamber 7 was connected. It was filtered with a filter device. At the time of filtration, the blood transfer bag 8 containing the mesh chamber 7 is connected to the blood supply bag 9 containing the red blood cell preparation, and further blood is introduced inside the hollow fiber membrane 2 and filtered toward the outside. The leukocyte removal filter device was connected, and the blood collection bag 10 was connected to the outlet 6. At this time, the head from the lower end of the supply bag 9 to the upper end of the blood collection bag 10 is set to 1.0 m,
The head was filtered.

Red blood cell preparation before filtration (hereinafter referred to as original solution)
Also, the volume of the recovered liquid, hematocrit, and the number of white blood cells were measured to obtain the red blood cell recovery rate and the white blood cell removal rate. Red blood cell recovery rate = (recovered liquid liquid x recovered liquid hematocrit)
/ (Source solution volume x source solution hematocrit) x 100 (%) Leukocyte residual rate = (1-recovered solution leukocyte concentration / source solution leukocyte concentration) x 100 (%) The volumes of the source solution and the recovered solution are Specific gravity is 1.
The value was divided by 075. The white blood cell concentration was measured by the following method. Determination of white blood cell concentration of original solution: The original solution diluted 10 times with Turk's solution was injected into a Bürkertürk's hemocytometer, and white blood cells present in 4 large sections were counted using an optical microscope. Was set to n ₁ . Original liquid leukocyte concentration = n ₁ × 0.25 × 10 ⁵ (cells / ml) Measurement of recovered liquid leukocyte concentration: 5 in the bag containing the recovered liquid
% Ficoll 400 DL EBSS solution (hereinafter referred to as Ficoll solution) was added while shaking and mixing the same volume as the collection solution, and the collection bag was fixed on the plasma separation stand.
Let stand for minutes. After leaving still, the supernatant was gently recovered so as not to disturb the sedimented red blood cell layer, and then Ficoll solution was again added to the same volume recovery bag as before, and the same operation was repeated. Corning the supernatant collected by two operations 2
Dispense into 4 tubes of 5350, 840 xg, 15
After centrifuging for a minute, the supernatant was discarded with an aspirator, taking care not to suck up the precipitate. 200 for each centrifuge tube
ml of hemolyzed blood (1.145% ammonium oxalate physiological saline) was added and mixed by shaking. Immediately, 468 × g,
After centrifuging for 10 minutes, the supernatant was discarded with an aspirator while paying the same attention as above. Collect the four precipitates in a 15-ml centrifuge tube, add hemolyzate to make the total volume 15 ml, then leave at room temperature for 10 minutes, centrifuge at 468 xg for 10 minutes, and leave 0.5 ml containing the precipitate. The supernatant was carefully discarded. The solution containing the precipitate was thoroughly stirred to give a single cell suspension, and 50 μl of a fluorescent staining solution (69.9 mg / 1 accridine orange solution) was added and further stirred. This solution was injected into six modified Neubauer-type hemocytometers, and white blood cells present in the large section 108 were counted using an epi-illumination fluorescence microscope. The white blood cell concentration of the recovered liquid was calculated from the count value n ₂ by the following equation. Recovered liquid leukocyte concentration _{= (n 2/108 × 10} 4 × 0.55
/0.55)/recovered liquid volume (pieces / ml) The underlined portion from the recovered liquid finally uses 0.1%.
The white blood cell concentration (cells / ml) in a liquid concentrated to 55 ml (hereinafter referred to as a concentrated liquid), and the volume of the concentrated liquid was 0.
The white blood cell count is calculated by multiplying by 55 ml. The reason for further dividing by 0.55 is that the recovery rate when leukocytes are recovered using Ficoll solution is 55%. As a result, the red blood cell recovery rate was 95%, the white blood cell removal rate was 99.9%, and the filtration time was 15 minutes.

[0016]

[Comparative Example 1] The same volume as the apparent membrane volume of Example 1 (4.5
cm ³ ), a container having an effective filtration portion, and a polyvinyl formal (PVF) flat plate-shaped porous body (effective filtration area 9 cm ² , thickness 5 mm) having an average pore diameter of 5.4 μm, which was coated in the same manner as in Example 1, were placed. Filled. The same blood circuit as in Example 1 was connected to this filter, and the same red blood cell preparation was filtered. As a result, the leukocyte removal rate was 99.9%, but clogging occurred during filtration and filtration stopped. The red blood cell recovery rate was 58%.

[0017]

Comparative Example 2 The same volume as the apparent membrane volume of Example 1 (4.5
(cm ³ ), a container having an effective filtration portion was filled with a polyethylene terephthalate (PET) non-woven fabric having an average pore diameter of 5.1 μm and having the same coating as in Example 1 (filling density 0.29 g / cm ³ , filling thickness). 5 mm). The same blood circuit as in Example 1 was connected to this filter, and the same red blood cell preparation was filtered. As a result, the leukocyte removal rate was 99.9%.
However, similar to Comparative Example 1, clogging occurred during the filtration and the filtration stopped. At this time, the red blood cell recovery rate was 76%.

[0018]

[Comparative Example 3] Since clogging occurred in Comparative Example 2, a non-woven fabric having a larger average pore diameter than Comparative Example 2 was used.
A polyethylene terephthalate (PET) non-woven fabric having an average pore diameter of 9.2 μm coated with the same coating as in Example 1 was filled in a container having an effective filtration part having the same volume (4.5 cm ³ ) as the apparent membrane volume. (Packing density 0.2
5 g / cm ³ , filling thickness 5 mm). The same blood circuit as in Example 1 was connected to this filter, and the same red blood cell preparation was filtered. As a result, the red blood cell recovery rate was 96%, the white blood cell removal rate was 99.7%, and the filtration time was 36 minutes. Table 1 shows the results of Examples and Comparative Examples.

[0019]

[Table 1]

[0020]

EFFECT OF THE INVENTION By using the hollow fiber membrane type leukocyte removal filter device of the present invention, leukocytes can be rapidly filtered from leukocyte suspension without lowering the filtration flow rate, clogging, etc. It is possible to achieve the rate.

[Brief description of the drawings]

FIG. 1 shows an example of the hollow fiber membrane type leukocyte removal filter device of the present invention, and is a schematic view of the device of the present invention shown in Examples.

[Explanation of symbols] 1 cylindrical container 2 porous hollow fiber membrane 3 adhesive 4 liquid inlet 5 cap 6 liquid outlet 7 mesh chamber 8 blood transfer tube 9 blood supply bag 10 blood collection bag

Claims (1)

[Claims] 1. A through hole having an average pore diameter of 1 to 100 μm, an average membrane thickness of 0.05 to 2 mm, and a value of (average filtration area / apparent membrane volume) of ³ to 200 cm ² / cm ³ . A hollow fiber membrane-type leukocyte removal filter device in which a container having a liquid inlet and an outlet is filled with a porous hollow fiber membrane.