The effects of pathogen reduction technology on apheresis platelet concentrates stored in PAS.

BACKGROUND: The impact of pathogen reduction technology (PRT) such as Mirasol, and the effect of platelet additive solutions (PAS) on the activity and hemostatic profile of transfused apheresis platelets remain largely unknown. The aim of this study was to assess the in vitro hemostatic and metabolic profile of Mirasol treated platelets in PAS during a 7-day storage period. MATERIAL AND METHODS: Ten split bags containing apheresis platelets stored in PAS were split into two groups; control platelets (No.=10 units) and PRT-treated platelets (No.=10 units). In vitro evaluation of the platelet components was performed on the 1st, 3rd, 5th, and 7th days of the storage period. Several metabolic parameters including pH, glucose, and lactate levels were evaluated, while assessment of their hemostatic capacity was performed using light transmission aggregometry (LTA) and viscoelastic studies such as rotational thromboelastometry (ROTEM) and thromboelastography (TEG). Last, Annexin V levels were measured though flow cytometry for evaluation of platelet activation. RESULTS: Clot strength, as reflected by the maximum clot firmness (MCF) and the maximum amplitude (MA) parameters of the viscoelastic studies was significantly decreased in the PRT-treated platelets compared to the control platelets (p<0.05). Clot strength based on MCF and MA values was also found to be decreasing over storage time in PRT-treated platelets (p<0.001), while this was not evident in control platelets. Moreover, the comparison between pH, glucose, and lactate levels were indicative of increased metabolic activity in PRT-treated platelets compared to control platelets (p<0.001). Last, Annexin-V was significantly higher in PRT-treated platelets compared to control platelets on the 7th day of the storage period (p<0.001). DISCUSSION: The results of this study indicate that increased PSL induced by PRT treatment leads to a decreased in vitro platelet hemostatic efficacy and increased metabolic activity. However, the clinical impact of these alternations needs further investigation.

Haemostatic profile of riboflavin-treated apheresis platelet concentrates.

BACKGROUND: The haemostatic activity of platelet concentrates (PCs) treated with pathogen reduction technology (PRT) remains a subject of debate. Our aim was to investigate the effect of Mirasol PRT on the haemostatic properties of PCs stored in plasma. MATERIAL AND METHODS: Untreated and Mirasol-treated platelets stored in plasma and derived from ten split double-dose apheresis PCs were evaluated in vitro on days 1, 3 and 5 post collection for functionality, microparticle procoagulation activity (MPA), endogenous thrombin potential (ETP), and haemostatic profile using rotational thromboelastometry (ROTEM). RESULTS: P-selectin expression was significantly higher in Mirasol-treated platelets compared with untreated counterparts on days 3 and 5 (p=0.003 and p=0.002, respectively). Clot strength, as shown by EXTEM maximum clot firmness (MCF), was significantly lower in the Mirasol-treated platelets at all time points (days 1, 3, 5) than in untreated platelets (p=0.009, p<0.001, p<0.001, respectively). There was a considerable increase in MPA over time (p<0.001) and this was significantly higher in the Mirasol-treated platelets on day 5 (p=0.015). A notable acceleration of decrease in ETP values was observed for Mirasol-treated PCs over time (p<0.001), with significant differences between PRT-treated and untreated PCs on days 3 and 5 (p=0.038 and p=0.019, respectively). Clot strength attenuation was significantly associated with pH reduction (p<0.001, Spearman's rho: 0.84), increased microparticle procoagulant activity (p<0.001, Spearman's rho: -0.75), and with decreased ETP (p<0.032, Spearman's rho: 0.41). DISCUSSION: Increased platelet activation induced by PRT treatment leads to a decrease in in vitro haemostatic capacity as seen by reduced clot strength and thrombin generation capacity over time. The clinical relevance of this needs to be investigated.

Treatment of light chain (AL) amyloidosis with the combination of bortezomib and dexamethasone.

BACKGROUND AND OBJECTIVES: High-dose melphalan and autologous stem cell transplantation is currently the treatment of choice for selected patients with AL amyloidosis; however, new treatments are needed for patients who are ineligible for or relapse after this procedure. Bortezomib is a proteasome inhibitor with proven activity in multiple myeloma, and the addition of dexamethasone results in superior outcome. We evaluated the activity and feasibility of the combination of bortezomib and dexamethasone (BD) in patients with AL amyloidosis. DESIGN AND METHODS: Consecutive patients with histologically proven, symptomatic AL amyloidosis were treated with BD. RESULTS: Eighteen patients, including seven who had relapsed or progressed after previous therapies were treated with BD. Eleven (61%) patients had two or more organs involved; kidneys and heart were affected in 14 and 15 patients, respectively. The majority of patients had impaired performance status and high brain natriuretic peptide values; serum creatinine was elevated in six patients. Among evaluable patients, 94% had a hematologic response and 44% a hematologic complete response, including all five patients who had not responded to prior high dose dexamethasone-based treatment and one patient under dialysis. Five patients (28%) had a response in at least one affected organ. Hematologic responses were rapid (median 0.9 months) and median time to organ response was 4 months. Neurotoxicity, fatigue, peripheral edema, constipation and exacerbation of postural hypotension were manageable although necessitated dose adjustment or treatment discontinuation in 11 patients. INTERPRETATION AND CONCLUSIONS: The combination of BD is feasible in patients with AL amyloidosis. Patients achieve a rapid hematologic response and toxicity can be managed with close follow-up and appropriate dose adjustment. This treatment may be a valid option for patients with severe heart or kidney impairment.