Pooled Platelet Concentrates Prepared by the Platelet-Rich-Plasma Method and Filtered with Three Different Filters and Stored for 8 Days

Pooled platelet concentrates (PC) prepared by the platelet-rich plasma (PRP) method were filtered with three different filters and stored for 8 days at room temperature. The effect of filtration on leukocyte contamination, platelet concentration, and the in vitro function, morphology, metabolism and activation of platelets were studied. Eight pools of 20 PRP-PC were used, each pool was split into 4 equal volumes; 3 were filtered over a PL50HF, a PL-10A and a Bio P10 filter, the 4 served as a control. After filtration, leukocyte counts exceeded 3×10⁵ in none of the pooled PC. Platelet loss induced by filtration was about 17%. During storage, no differences in pH, PCO₂, and lactate and glucose concentration were found between the filtered and the unfiltered units, nor were any differences observed between filtered and unfiltered pooled PC in aggregation upon stimulation with collagen and/or ADP, adhesion capacity to collagen in flowing blood, nucleotide content of the platelets and nucleobase concentration in the plasma, expression of activation-dependent antigens, or platelet morphology as observed by light microscopy and by the swirling effect. Selective removal of β-thromboglobulin (22%) by the PL50HF filter was observed. Pooled PC prepared by the PRP-method can be filtered and stored for 8 days without detrimental effect on platelet function, metabolism or activation.     

Comparison of Platelet Activation and Membrane Glycoprotein Ib and IIb-IIIa Expression after Filtration through Three Different Leukocyte Removal Filters

We evaluated three filters used for leukocyte removal from platelet concentrates: Imugard IG 500, Pall PL100 and Sepacell PL-10A. Filter performance, platelet activation and expression of membrane glycoproteins Ib and IIb-IIIa were evaluated. Imugard, Pall and Sepacell showed median postfiltration in vitro platelet recoveries of 88, 84 and 80%, and total residual leukocyte counts of 16.1, 7.5 and 0.6 x 10(6)/pool of 8 platelet concentrates, respectively. Mean platelet volume was reduced after filtration with all filters. Postfiltration values of glycoproteins Ib and IIb-IIIa, and of activation markers GMP 140 and gp 53 were not significantly different from prefiltration values. Filtration through Imugard, Pall and Sepacell did not induce significant platelet activation or modifications of platelet membrane glycoproteins Ib and IIb-IIIa.     

Adsorption Filtration of Leukocyte-Reduced Single Donor Platelet Units

The effect of adsorption filtration of leukocyte-reduced single donor platelet (SDP) units collected on a CS-3000+ with a TNX chamber was compared to filtration of SDP units prepared via an isoradial chamber. The leukocyte enumeration technique employed a Nageotte chamber and had a nominal lower detection limit of 0.05 leukocytes/μl (if no cells were seen, the concentration was recorded as 0.01 μl). Although the prefiltration leukocyte content of the TNX units was unexpectedly low (2.4±2.8 times 10⁴ per unit), filtration reduced the leukocyte content further to no greater than 1.7±0.07 times 10³ (p<0.05). (The full extent of the leukocyte removal could not be assessed as no leukocytes were seen in counting any of the 20 filtered TNX units.) The 20 isoradial (control) SDP units achieved similar leukocyte depletion, with a postfiltration leukocyte content of 2.7±2.5 times 10³ (p>0.05, compared to filtered TNX units). Thus while significant leukocyte reduction occurred with adsorption filtration of both control and leukocyte-depleted SDP units, comparison of the relative degree of reduction awaits application of more sensitive leukocyte counting techniques. This study documented, however, that additional leukocyte reduction can be obtained by applying adsorption filtration to SDP units with an already low leukocyte content.     

Effects of 3-5 log10 pre-storage leucocyte depletion on red cell storage and metabolism

SUMMARY. A new, in-line high-efficiency 3-5 log₁₀ leucodepletion filter system (Leukotrap° RC system) was used to investigate the effect of pre-storage white cell removal on the quality of AS-3 red cell concentrates stored for 42 d at 4°. Median residual white cell content was 4 × 10⁵ when filtration was performed at 22° within 8 h of phlebotomy ( n = 20) and 3.2 × 10⁴ when filtration was performed at 4° 12-24 h after phlebotomy ( n = 24). None exceeded 1 × 10⁶ WBC per red cell product. Filtration was rapid (median 28 min), and red cell loss averaged (mean ± 1 SD) 6.4 ± 0.7%. In a paired study design, post-transfusion recoveries of 42 d stored red cells in the filtered units averaged 84 ± 6% v 82 ± 8% for unfiltered units ( P < 0.05) and post-storage haemolysis, ATP, osmotic fragility, K+ and pH were significantly ( P < 0.05) better in the filtered units. Reduced glycolytic activity was also observed in the filtered units, and there was a correlation between osmotic fragility, glucose consumption, and lactate produced in standard units that was not present in leucodepleted units. In conclusion, this study suggests that leucodepletion of AS-3 red cell concentrates prior to storage results in better maintenance of the integrity of the red cell membrane with reduced glycolytic activity. There was a modest improvement in post-infusion viability sufficient to offset the filtration-induced loss and to result in an equivalent red cell product.     

Investigation of how different filters affect some biochemical properties of stored platelet concentrates.

The aim of the present study was to investigate how four different filters, i.e. Imugard IG500 (Terumo, Japan), Miropore (Miramed, Italy), Pall P1-100 (Pall, USA) and Sepacell P1-10A (Asahi, Japan) affect some biochemical properties of platelet concentrates. The work was conducted using 42 pairs of platelet concentrates. After 2 days of storage, one of the preparations was filtered and the other served as an unfiltered control. Immediately after filtration, determination of the platelet count, desarginated activated complement factor 3 (C3a des arg) and the extracellular and total concentrations of platelet factor 4 (PF4) and lactate dehydrogenase (LDH) were carried out on both these platelet concentrates. After an additional storage period of 3 d, extracellular concentrations of PF4 and LDH were determined on both concentrates. A significant decrease of extracellular PF4 concentration was found immediately after filtration when Pall P1-100 and Imugard IG500 were used. During the 3-d storage after filtration, the concentrates filtered with Imugard IG500 and Pall P1-100 demonstrated significantly higher platelet lysis as compared to the unfiltered controls. It is concluded that the present work demonstrates storage instability after filtration with Imugard IG500 and Pall P1-100. Therefore, platelet concentrates filtered with these filters would not appear to be suitable for storage.     

Effect of Prestorage Leukocyte Reduction on Proteins of Platelets Obtained by Apheresis

The effect of prestorage leukocyte reduction was evaluated on platelet concentrates (PCs) obtained by apheresis using the ‘surge’ technique. Two hours after collection, the PCs were divided into 2 equal units. One unit was filtered through a Sepacell PL-10a®, producing a filtered PC (FPC). The second unit constituted a non-filtered PC (NFPC). FPCs and NFPCs were stored at room temperature in 1,400-ml CLX® bags on a horizontal agitator up to 7 days. We analyzed platelet samples obtained during storage from NFPCs and FPCs at days 1,3 and 7. The expression of membrane glycoproteins (GP)Ib and GPIIb/IIIa (assessed by flow cytometry), platelet response to thrombin and ristocetin (aggregometry) and global platelet protein pattern (studied by high-resolution two-dimensional gel electrophoresis) remained stable over the 7 days of storage in NFPCs as well as in FPCs. However, in both preparations, the expression of GMP-140 (flow cytometry) progressively increased during storage. Our in vitro study indicates that early leukocyte reduction by filtration of apheresis PCs does not induce modifications in platelet GPs and protein patterns.     

Platelet Concentrates Stored in Synthetic Medium after Filtration

Platelet concentrates prepared from pooled buffy coats (BCPC) were stored in Plasma-Lyte A, a glucose-free synthetic medium, after leukocyte depletion by filtration through Pall PL 50, and compared to paired unfiltered BCPC stored in the same medium. Each pair of BCPC units was prepared from a pool of 10 buffy coats split into two identical units. Platelet and leukocyte counts per unit of BCPC were 2.70 +/- 0.19 x 10(11) and 3.8 +/- 2.8 x 10(6) (filtered BCPC), 2.59 +/- 0.27 x 10(11) and 79 +/- 56 x 10(6) (control BCPC), respectively. Filtration procedures did not affect in vitro parameters of platelet quality and function such as osmotic reversal, ATP release and aggregation in response to collagen and ADP during 15-day storage. A similar decrease of platelet membrane glycoprotein Ib and a similar rise of activation markers GMP-140, gp 53 and platelet-bound fibrinogen were observed during storage of filtered and control BCPC. Our study indicates that storage of BCPC after filtration is feasible and that a reduction in leukocyte content by filtration to mean cell counts of less than five millions per unit has probably no effect on platelet storage lesion.     

In vitro Evaluation of a New Filter for Leucocyte Depletion of Platelet Concentrate during Component Preparation

A newly developed filter for prestorage leucocyte depletion of platelet concentrates (PC) was studied. The filter is designed for leucocyte depletion during the preparation of the pool PC from platelet rich buffy coats. In all the leucocyte depleted PC (LD-PC) leucocyte depletion was satisfactory. 19 of 20 units of LD-PC had a leucocyte content below 3times10⁵per PC and 1 contained 8times10⁵leucocytes. The standard PC contained 2.53times10⁸(0.87times10⁸–15.3times10⁸; n = 20) leucocytes per PC (median and range). The quality of the LD-PC was evaluated by measuring platelet activation, platelet morphology, and pre- and poststorage pH. There were no differences in any of the parameters studied.     

Removal of Leukocytes from Blood by Fibre Filtration: A Comparison Study on the Performance of Two Commercially Available Filters

Abstract: Two different kinds of filters suitable for the almost complete removal of leukocytes from blood-cell concentrates were tested. The maximal retention of filter I was 1.9-3.4×10⁹ leukocytes per filter, whereas filter II could retain 3.6–7.8×10⁹ leukocytes per filter before the leukocyte concentration in the filtrate passed the level of 500 leukocytes/μl. The leukocytes, once absorbed by the fibre material, could be released by washing the filters I, whereas the leukocytes were retained by the material of the filters II. No detectable particles were released after the first 100 ml of filtrate during the washing procedure of either kind of filters. From more than 20% of the filters I, more than 500 pg/ml of endotoxin could be released during the prewashing, whereas none of the filters II was contaminated with endotoxin. The filter II released acetic acid which could be completely removed during the prewashing with 250 ml of saline solution. Operation according to the prescribed conditions of 25 filters of both kinds revealed that the residual leukocyte content in the filtrate was more than 0.25 ×10⁹ leukocytes in 8 out of 25 of the filtrates when filters I were used, whereas with all filters II, this content remained lower than 0.1×10⁹ leukocytes per filtrate. It was concluded that only filter II has sufficient capacity to guarantee the removal of 97% of all leukocytes and 90% of the thrombocytes present in 500 ml of fresh human blood.     

Improved leucoreduction of red blood cell units prepared after a 24-h hold with the platelet-rich plasma method using newly developed filters

Background and Objectives  A previous study indicated that the extension of whole blood (WB) storage from 8 to 24 h at 20–24 °C before the processing of platelet-rich plasma (PRP)-depleted red blood cell (RBC) units had a negative effect on the efficacy of leucoreduction filters. In this study, we further characterized the phenomenon and tested the leucoreduction capacity of two newly developed filters.
Materials and Methods  Whole blood was stored at 20–24 °C and processed at 4-h intervals between 8 and 24 h postcollection. Components were leucoreduced before storage. Efficacy of novel filters to leucoreduce 24-h-hold PRP-depleted RBC units was also evaluated.
Results  Using a conventional filter, the mean residual white blood cell (WBC) counts in leucoreduced PRP-depleted RBCs were comparable in units prepared within 12 h from collection but gradually increased upon extended preprocessing storage from 0·36 ± 0·03 at 12 h to 0·46 ± 0·21, 0·76 ± 0·54 and 1·72 ± 1·76 × 10⁶ per unit at 16, 20 and 24 h, respectively. However, the mean residual WBC content in 24-h-hold RBCs was reduced to 0·60 ± 0·39 × 10⁶ and 0·46 ± 0·13 × 10⁶ per units using RC2D and the prototypes B-1582 rev B filters, respectively.
Conclusion  For PRP-depleted RBC units, the extension of the WB room temperature storage from 8 to 24 h before processing is likely to require the introduction of newly developed filters having an increased leucoreduction capacity in order to meet the maximal residual WBC guideline in the RBCs.     

A Comparative Study of Platelets Stored in Polyvinyl Chloride Containers Plasticised with Butyryl Trihexyl Citrate or Triethylhexyl Trimellitate

Platelet concentrates (PCs), stored for 5 days in PL 2209, a new polyvinyl chloride (PVC) storage container plasticised with butyryl trihexyl citrate, were compared with those stored in PL 1240, a PVC platelet container plasticised with triethylhexyl trimellitate. In part 1 of the study, pooled platelet-rich plasma (PRP) was aliquoted into each type of pack and pH, pCO₂, pO₂, hypotonic shock response, aggregation responses, lactate, glucose and ATP concentrations, and lactate dehydrogenase and β-thromboglobulin release were compared at days 1, 3 and 5. In part 2, 12 volunteers gave a unit of blood on two separate occasions and PCs produced by the PRP method were stored in PL 2209 or PL 1240 for 5 days before autologous reinfusion of a ¹¹¹In-labelled sample. In vitro results demonstrated that PL 2209 was more gas permeable than PL 1240. In part 2 of the study, at day 5, pCO₂ was 3.13±0.62 versus 5.14±0.69 (p<0.001), whilst pO₂ was not significantly different for PL 2209 versus PL 1240, respectively. pH was better maintained in PL 2209 than in PL 1240 (7.38±0.13 vs. 7.24±0.10, respectively, p<0.01) after storage for 5 days. These results were confirmed by those from part 1. In vivo data were similar for PC stored in the two plastics with a multiple-hit recovey of 40.9±12.1% for PL 2209 and 37.4±11.3% for PL 1240, and a multiple-hit survival of 4.89±1.20 days and 5.28±2.06 days for PL 2209 and PL 1240, respectively. γ-Camera imaging of volunteers showed similar biodistribution of radiolabeled platelets stored in each container. These results demonstrate that PL 2209 is a suitable container for storage of PCs for 5 days.     

Evaluation of Apheresis Platelet Concentrates Collected with a Reduced (30-ml) Collection Chamber with Resuspension and Storage in a Synthetic Medium

Recently, the CS-3000® Plus Blood Cell Separator with the TNX-6 platelet separation chamber insert has been furnished with a small-volume (30-ml) collection chamber. In this study, a platelet synthetic medium containing glucose and bicarbonate (PSM) was used for resuspension and storage of this highly concentrated platelet product. Eighteen donors participated in a paired study design where each participant donated platelets on two occasions, once following collection in a standard chamber with resuspension and storage in plasma and once following collection in the new chamber with resuspension and storage in PSM. Substantially higher total platelet counts were obtained using platelets collected in the small chamber and stored in PSM as compared to control (4.4±0.9times10¹¹ vs. 3.5±0.9times10¹¹ platelets, p<0.01 by paired t test). After 5 days of storage, PSM-stored platelets demonstrated higher ATP levels, less lactate dehydrogenase in the supernatant and increased lactate production with resulting lower pH at day 5 of storage (6.94±0.15 vs. 7.08±0.09, p<0.05). There were no statistically significant differences of the survival by multiple-hit estimation of PSM-stored as compared to plasma-stored platelets as determined by ¹¹¹In labeling and infusion. A slight decrease in the initial percent recovery with the additive-suspended as compared to suspended plasma cells was noted: 50±8 versus 54±9%, respectively (p<0.05). In conclusion, the CS-3000 Plus/TNX-6 apheresis system with a new reduced-volume collection chamber and an additive solution provides a plasma-poor and highly concentrated platelet product with satisfactory in vivo viability and in vitro functional characteristics after 5 days of storage.     

Size dependent platelet subpopulations: relationship of platelet volume to ultrastructure, enzymatic activity, and function

A method for the separation of platelets on the basis of their size has been developed using counterflow centrifugation. Platelets were separated, free of plasma proteins and other cells, into seven subpopulations. The smallest-sized platelets, designated as Fraction 1, had a mean platelet volume (MPV) of 3.94 ± 0.60 μm³ (SD). Each successive fraction had a progressively larger MPV. The MPV for the largest-sized platelets, designated Fraction 7, was 8.19 ± 0.64 μm³. The MPV for the original platelets prior to fractionation was 6.57 ± 0.61 μm³. The mean density of Fraction 1 platelets was 1.067 ± 0.002 g/cm³, while Fraction 7 had a mean density of 1.072 ± 0.001 g/cm³. Transmission electron microscopy demonstrated that Fraction 1 had 4.3 ± 0.9 dense bodies per platelet, and Fraction 7 had 12.6 ± 2.4 dense bodies per platelet. Platelet LDH activity showed that the Fraction 1 platelets had 4.77 ± 0.92 iu per 10¹⁰ platelets; Fraction 7 platelets had 14.88 ± 1.23 iu per 10¹⁰ platelets. The LDH activity in the platelets before separation into subpopulations was 9.47 ± 1.45 iu per 10¹⁰ platelets.     

Increased number of peripheral blood CD34+ cells in lithium-treated patients

Eight adult patients with bipolar disorder were prospectively examined to find whether lithium carbonate increased their peripheral blood CD34⁺ haemopoietic stem cells. Following lithium therapy for 3–4 weeks their neutrophil counts increased by a mean of 88% (from 4625 ± 1350 × 10⁹/l, mean ± SD pretreatment, to a peak of 8300 ± 3910 × 10⁹/l). Concommitantly, there was a significant increment in their CD34⁺ cells (from 0.11 ± 0.01% to a peak of 0.18 ± 0.08%). There was a significant correlation between the rise in neutrophil count and that of the CD34⁺ cells ( r  = 0.795, P  = 0.019). Lithium therapy may be used to mobilize peripheral blood CD34⁺ cells for marrow transplantation.     

Combined negative and positive selection of mobilized CD34+ blood cells

We tested four negative and two positive selection methods for separation of CD34⁺ cells from mobilized blood cells, and analysed fold-enrichment, purity and recovery of CD34⁺ cells after selection procedures. The elimination of mature CD34⁻ cells was achieved by adhesion to nylon-wool fibre (5.9 ± 1.0 mean fold-enrichment and 65.2 ± 2.3 mean recovery of CD34⁺ cells). Standard or modified Ficoll-Hypaque and Percoll density gradients, as well as phagocytosis with magnetic beads, were less effective in eliminating CD34⁻ cells, both purity and fold-enrichment of CD34⁺ cells being lower than those obtained with separation by nylon-wool. Both positive selection methods tested, Ceprate and MiniMacs System, generated highly purified CD34⁺ cell populations ranging from 80% to 90%. The recovery of CD34⁺ cells was optimal with MiniMacs (77.9±3.6) and low with Ceprate (28.8±2.8). Based on these results, in two large-scale experiments we combined nylon-wool fibre and MiniMacs System in a two-step separation procedure obtaining a 36.9±2.6 mean fold-enrichment and a 50.5±0.3 mean recovery of CD34⁺ cells. In this way we achieved optimal enrichment and recovery of CD34⁺ cells, with a substantial saving of cost compared to either selection method alone.     

Cytokines in Platelet Concentrates Prepared from Pooled Buffy Coats

Platelet concentrates (PC) prepared from pooled buffy coat (BC-PC) contain a variable number of leukocytes from different donors. We questioned whether storage of BC-PC can lead to a lymphocyte activation in the sense of a mixed lymphocyte reaction. BC-PC were prepared from four ABO-identical buffy coats and we undertook leukocyte analyses and measurement of different cytokines on days 1, 3 and 5 of PC storage (n = 72). Cytokine content was also determined in freshly prepared plasma (n = 48) and PC prepared by thrombapheresis (SD-PC) (n = 12). As control, we studied lymphoproliferation of pooled peripheral blood mononuclear cells from four individuals in 10 mixed lymphocyte cultures (MLCs) under optimal conditions. In the BC-PC, whole blood count and lymphocyte analysis showed a mean leukocyte contamination of 64±28 times 10⁶ per unit with a proportion of lymphocytes of 66.7±13%. In the MLC, levels of interleukin-2 (IL-2) and interferon-γ (IFN-γ) were increased on day 3 and 5 of storage (p<0.001). In a proportion of BC-PC, tumor necrosis factor-α (72.2%) and IL-2 (43.1%) were detectable immediately after preparation, whereas IFN-γ (4.2%), interleukin-1β (4.2%) and interleukin-8 (11.1%) were only found in some BC-PC. In all cases, initial values of cytokines did not increase during storage. Cytokine measurement in FFP and SD-PC showed similar results. The study demonstrates that cytokines are detectable in a variety of blood products immediately after preparation. Levels of cytokines did not increase in the preparations. BC-PC can be stored for up to 5 days without any signs of lymphocyte activation.     

Low Level Hepatitis B Viremia Detected by Polymerase Chain Reaction Accompanies the Absence of HBe Antigenemia and Hepatitis in Hepatitis B Virus Carriers

Objectives: Because outcome of antiviral treatment in patients with chronic hepatitis (CH) B is difficult to predict, we compared the severity of hepatitis with serum hepatitis B virus (HBV) DNA concentration. Methods: We studied 40 HBV carriers with distinct stages of chronic infection, 32 HBe antigen (HBeAg) -negative or low-grade positive carriers whose HBV strains did not contain a point mutation at nucleotide 1896, 37 HbeAg-negative carriers with or without hepatitis, and 51 HBeAg-positive CH patients treated with interferon. Serum HBV DNA concentration was measured by the end-point dilution method using a polymerase chain reaction (PCR). The point mutation at nucleotide 1896 was detected by restriction fragment length polymorphism with PCR. Results: Among the stages of chronic HBV infection, the serum HBV DNA concentration was lowest (10^{0.67 ± 0.71} copies/μl) in HbeAg-negative asymptomatic carriers. A low-level viremia (10^{2.10 ± 1.45} copies/μl) of HBV strains without the mutation at nucleotide 1896 was associated with an HBeAg-negative state. In HBeAg-negative carriers, the serum HBV DNA concentration in those without hepatitis was significantly lower than in those with hepatitis (10^{1.00 ± 0.89} vs 10^{3.31 ± 1.25} copies/μl, p < 0.0001); 20 of 21 asymptomatic carriers had an HBV DNA concentration below 10² copies/μl. Patients with serum HBV DNA concentrations below 10¹ copies/μl at the end of interferon treatment maintained normal serum alanine aminotransferase concentrations. Conclusions: A serum HBV DNA concentration below 10¹ copies/μl is an important goal for successful treatment of CH-B. PCR is necessary to assess such low-level viremias.     

Platelet concentrates produced from whole blood using the Atreus processing system

Background  The Atreus 2C+ system automates whole blood (WB) processing into a red cell concentrate, plasma and buffy coat (BC) suitable for platelet concentrate (PC) manufacture. This study compared the quality of PC made from BC using the Atreus, with those made by a manual method.
Study design and methods  WB was collected into Atreus disposables or standard bottom and top processing packs and held without active cooling for 26 h at 22 ± 2°C before processing, either with the Atreus, or using a centrifuge and press. BC were rested for 3 h and then 4 BC were pooled with one unit of plasma, mixed, centrifuged and pressed to make a pooled PC. The PC were analysed for quality markers to day 9 of storage.
Results  Platelet quality was good in both Atreus 2C+ derived PC and control units throughout storage. Metabolic markers (pH, ATP and HSR) and activation markers (CD62P, sCD62P, annexin V binding, microparticles, GP IIb/IIIa) did not differ between the Atreus and control units. Atreus-derived PC had significantly lower platelet yields (302 ± 59 × 10⁹ platelets/unit; mean ± standard deviation, n  = 8) than control PC (411 ± 76 × 10⁹ platelets/unit; P  < 0·01), but met the UK guidelines for platelet yield
Conclusion  From these in vitro data, PC produced from buffy coats prepared using the Atreus appear suitable for clinical use, and WB may be held at ambient temperature overnight without the use of active cooling devices. Optimizing the secondary processing conditions to handle Atreus 2C+ derived BC may increase the platelet yield.     

The effects of leukaemia inhibitory factor on platelet function

Summary Leukaemia inhibitory factor (LIF) is able to promote megakaryocytopoiesis in vitro and elevate platelet counts in vivo , and is a potential new therapeutic agent for the treatment of thrombocytopenia. To determine whether platelets released under conditions of LIF-stimulated megakaryocytopoiesis have intact function, we compared aggregation responses of platelets from mice with constitutively elevated LIF levels (FD/LIF mice) and mice injected with recombinant murine LIF (rmLIF mice) with their respective control mice. We report that ex vivo platelet aggregability and thromboxane B₂ release were intact in the LIF-treated mice, and were significantly enhanced in some situations. LIF-treated mice also had significantly increased platelet counts (FD/LIF mice: 1302 ± 173 × 10⁹/1 compared to 1012 ± 99 × 10⁹/1 for FD mice; rmLIF mice: 1460 ± 193 × 10⁹/1 compared to 985 ± 67 × 10⁹/1 for FCS/NS mice), increased platelet volumes and elevated plasma fibrinogen and calcium levels. The platelet hyperreactivity seen in the LIF-treated mice is likely to reflect the larger platelet volumes and/or the effect of plasma components such as fibrinogen, elevated levels of which were due to the concomitant action of LIF as a stimulant of acute phase protein synthesis.     

Interferon increases serum thrombopoietin in patients with chronic hepatitis C

We measured serum thrombopoietin (TPO) in chronic hepatitis C treated with interferon (IFN). The platelet count before the therapy was 161.9 ×10⁹ ± 64.1 × 10⁹/l, which decreased to 116.3 × 10⁹ ±  48.4 × 10⁹/l 1 week after IFN therapy ( P  <0.01). On the other hand, serum TPO increased from 1.96 ± 0.60 fmol/ml to 2.68 ± 0.69 fmol/ml ( P  < 0.02). Contrary to a recent report that serum TPO was not altered in liver cirrhosis, these data indicate that serum TPO was increased in chronic hepatitis C in response to thrombocytopenia by IFN therapy.