Tor Hervig

Background: Blood products are frequently exposed to room temperature or higher for longer periods than permitted by policy. We aimed to investigate if this resulted in a measurable effect on common quality parameters and viscoelastic hemostatic function of cold stored CPDA‐1 whole blood.Study Design and Methods: 450 ml of whole blood from 16 O Rh(D) positive donors was collected in 63 ml of CPDA‐1 and stored cold. Eights bags were exposed to five weekly 4‐h long transient temperature changes to 28°C. Eight bags were stored continuously at 4°C as a control. Samples were collected at baseline on day 1, after the first cycle on day 1 and weekly before each subsequent cycle (day 7, 14, 21, 28 and 35). Hemolysis, hematological parameters, pH, glucose, lactate, potassium, thromboelastography, INR, APTT, fibrinogen, and factor VIII were measured.Results: CPDA‐1 whole blood repeatedly exposed to 28°C did not show reduced quality compared to the control group on day 35. Two units in the test group had hemolysis of 1.1% and 1.2%, and two in the control group hemolysis of 0.8%. Remaining thromboelastography clot strength (MA) on day 35 was 51.7 mm (44.8, 58.6) in the test group and 46.1 (41.6, 50.6) in the control group (p = .023). Platelet count was better preserved in the test group (166.7 [137.8, 195.6] vs. 117.8 [90.3, 145.2], p = .018). One sample in the test group was positive for Cutibacterium acnes on day 35 + 6.Conclusion: Hemolysis findings warrant further investigation. Other indicators of quality were not negatively affected.

08.11.2021: Noe å lære av - En kvinne seint i 20-årene ble innlagt med brystsmerter og pustevansker.

Thrombosomes are trehalose‐stabilized, freeze‐dried group O platelets with a 3‐year shelf life. They can be stockpiled, rapidly reconstituted, and infused regardless of the recipient's blood type. Thrombosomes thus represent a potential alternative platelet transfusion strategy. The present study assessed the safety and potential early signals of efficacy of Thrombosomes in bleeding thrombocytopenic patients. We performed an open‐label, phase 1 study of single doses of allogeneic Thrombosomes at three dose levels in three cohorts, each consisting of eight patients who had hematologic malignancies, thrombocytopenia, and bleeding. Adverse events, dose‐limiting toxicities (DLTs), World Health Organization (WHO) bleeding scores, and hematology values were assessed. No DLTs were reported. The median age was 59 years (24–71). Most patients had AML (58%) or ALL (29%), followed by MDS (8%) and myeloproliferative neoplasm (4%). The WHO scores of 22 patients who were actively bleeding at a total of 27 sites at baseline either improved (n = 17 [63%]) or stabilized (n = 10 [37%]) through day 6. Twenty‐four hours after infusion, 12 patients (50%) had a clinically significant platelet count increase. Of eight patients who received no platelet transfusions for 6 days after Thrombosomes infusion, 5 had a clinically significant increase in platelet count of ≥5000 platelets/μL and 2 had platelet count normalization. Thrombosomes doses up to 3.78 × 10⁸ particles/kg demonstrated safety in 24 bleeding, thrombocytopenic patients with hematological malignancies. Thrombosomes may represent an alternative to conventional platelets to treat bleeding. A phase 2 clinical trial in a similar patient population is underway.

Background There is a global increase in whole blood usage and at the same time, emerging pathogens give cause for pathogen reduction technology (PRT). The Mirasol PRT has shown promising results for plasma and platelet concentrate products. Treatment of whole blood with subsequent platelet survival and recovery analysis would be of global value. Study Design and Methods A two-arm, open-label laboratory study was performed with 40 whole blood collections in four groups: non-leukoreduced non-PRT-treated, non-leukoreduced PRT-treated, leukoreduced non-PRT-treated, and leukoreduced PRT-treated. Leukoreduction and/or PRT-treatment was performed on the day of collection, then all WB units were stored at room temperature for 24 h. Sampling was performed after hold-time and after 24-h storage in RT. If PRT-treatment or leukoreduction, samples were also taken subsequently after treatment. Thirteen healthy volunteer blood donors completed the in vivo study per protocol. All WB units were non-leukoreduced and PRT-treated. Radioactive labeling of platelets from RT-stored, PRT-treated whole blood, sampling of subjects, recovery, and survival calculations were performed according to the Biomedical Excellence for Safer Transfusion Collaborative protocol. Results In vitro characteristics show that PRT-treatment leads to increased levels of hemolysis, potassium, and lactate, while there are decreased levels of glucose, FVIII, and fibrinogen after 24 h of storage. All values are within requirements for WB. In vivo recovery and survival of platelets were 85.4% and 81.3% of untreated fresh control, respectively. Conclusions PRT-treatment moderately reduces whole blood quality but is well within the limits of international guidelines. Recovery and survival of platelets are satisfactory after Mirasol treatment.

Platelets can modulate cancer through budding of platelet microparticles (PMPs) that can transfer a plethora of bioactive molecules to cancer cells upon internalization. In acute myelogenous leukemia (AML) this can induce chemoresistance, partially through a decrease in cell activity. Here we investigated if the internalization of PMPs protected the monocytic AML cell line, THP-1, from apoptosis by decreasing the initial cellular damage inflicted by treatment with daunorubicin, or via direct modulation of the apoptotic response. We examined whether PMPs could protect against apoptosis after treatment with a selection of inducers, primarily associated with either the intrinsic or the extrinsic apoptotic pathway, and protection was restricted to the agents targeting intrinsic apoptosis. Furthermore, levels of daunorubicin-induced DNA damage, assessed by measuring gH2AX, were reduced in both 2N and 4N cells after PMP co-incubation. Measuring different BCL2-family proteins before and after treatment with daunorubicin revealed that PMPs downregulated the pro-apoptotic PUMA protein. Thus, our findings indicated that PMPs may protect AML cells against apoptosis by reducing DNA damage both dependent and independent of cell cycle phase, and via direct modulation of the intrinsic apoptotic pathway by downregulating PUMA. These findings further support the clinical relevance of platelets and PMPs in AML.