Cryopreserved platelets in bleeding management in remote hospitals: A clinical feasibility study in Sweden

BackgroundBalanced transfusions, including platelets, are critical for bleeding patients to maintain hemostasis. Many rural hospitals have no or limited platelet inventory, with several hours of transport time from larger hospitals. This study aimed to evaluate the feasibility of using cryopreserved platelets that can be stored for years, in remote hospitals with no or limited platelet inventory.Material and methodsThree remote hospitals participated in a prospective study including adult bleeding patients where platelet transfusions were indicated. Cryopreserved platelets were prepared in a university hospital, concentrated in 10 ml, transported on dry ice, and stored at −80°C at the receiving hospital. At request, the concentrated platelet units were thawed and diluted in fresh frozen plasma. The indications, blood transfusion needs, and laboratory parameters pre- and post-transfusion, as well as logistics, such as time from request to transfusion and work efforts in preparing cryopreserved platelets, were evaluated.ResultsTwenty-three bleeding patients were included. Nine patients (39%) were treated for gastrointestinal bleeding, five (22%) for perioperative bleeding, and four (17%) for trauma bleeding. The transfusion needs were 4.9 ± 3.3 red blood cell units, 3.2 ± 2.3 plasma units, and 1.9 ± 2.2 platelet units, whereof cryopreserved were 1.5 ± 1.1 (mean ± SD). One patient had a mild allergic reaction. We could not show the difference in laboratory results between pre- and post-transfusion of the cryopreserved units in the bleeding patients. The mean time from the order of cryopreserved platelets to transfusion was 64 min, with a range from 25 to 180 min.ConclusionCryopreserved platelets in remote hospitals are logistically feasible in the treatment of bleeding. The ability to have platelets in stock reduces the time to platelet transfusion in bleeding patients where the alternative often is many hours delay. Clinical effectiveness and safety previously shown in other studies are supported in this small feasibility study

Storage and transfusion of platelets : In vitro and in vivo studies in healthy volunteers and in allogeneic hemapoetic progenitor cell transplant recipents

Early studies in the 1960´s showed that platelet (PLT) transfusions significantly reduced the incidence of fatal hemorrhages. Together with the advances in the hematology and transplantation field, easily accessible PLTs for transfusion use have resulted in a rapid increase of PLT utilization and a change from therapeutic-i.e., treatment of clinical bleeding- to prophylactic PLT transfusions, despite limited clinical evidence regarding whether a prophylactic PLT transfusion strategy results in a lower morbidity or mortality compared with transfusing patients with early signs of bleeding. About 2 million PLTs are transfused in the United States, 2.9 million in Europe and 40 000 in Sweden with a roughly tenfold increase since 1984. In a 1991 survey in the United States, more than 70% of hospitals reported transfusing PLTs primarily for prophylaxis. Continued increase in demand may result in problems with shortages and difficulties to comply with orders. Several in vitro studies have shown satisfactory quality results for platelets stored for 7 days and even longer. Storage has been limited to 5 days because of the risk of bacterial contamination, with subsequent bacterial increase during storage at room temperature. Provided that contaminating bacteria can be effectively detected or put out of action in platelets, prolonged storage represents one possibility to obtain improved availability, logistical management and decreased outdating. The overall aim of this thesis was to assess the quality of platelets after prolonged storage up to 7 days and to evaluate the consequences of lowering the platelet transfusion trigger for prophylactic transfusion, representing two possible approaches suggested to have impact on the platelet accessibility. In paper I, we showed that a prophylactic platelet transfusion trigger level of 10 instead of 30 x109 platelets/L for allogeneic HPCT recipients considerably reduced the number of PLT transfusions without increasing the incidence of hemorrhagic events. In paper II, recovery and survival in healthy volunteers of PLTs stored for 7 days decreased, but met the suggested criteria. Analyzed in vitro parameters showed acceptable results. Addition of potassium and magnesium to the storage medium indicated higher quality in vitro but this could not be verified by in vivo recovery and survival (paper III). In paper IV, when comparing transfusion in allogeneic HPCT recipients of PLTs stored for 6-7 days vs 1-5 days, a significant lower platelet increment (CCI) and shorter interval between transfusions was noticed with prolonged storage. To have sufficient PLTs of excellent quality in stock at any given time to provide to patients in great need represents a difficult challenge to transfusion services. If prolonged storage results in decreased time between the transfusion and more PLTs are transfused in general the result might not be what was aimed at. In that case it might be wiser to question the need of prophylactic transfusion. Lately it has been proposed that patient selection may be the key to the safety of therapeutic only based platelet transfusion strategy. To conclude, there is a growing need of further randomized, controlled clinical trials to establish the therapeutic approaches that maximizes the quality of patient care in different patient categories while minimizing expenses to transfusion services and the health care system to be able to ensure an adequate PLT supply when really needed

Transfusionsstrategi – att ge blod på rätt indikation - I Sverige ges fler blodtransfusioner än i jämförbara länder – restriktiv policy ger inte sämre vårdresultat

During the last decade, the varying use and the lack of consistent indications for blood transfusions have been questioned. Comparisons of liberal and restrictive transfusion policies, most often support a restrictive policy. This has led to an evidence-based approach to optimizing the care of patients who might need transfusion, Patient Blood Management (PBM). There is evidence that both anemia and allogeneic blood transfusions are independently associated with increased morbidity and mortality. In elective surgery it is possible to adapt the three pillars of PBM in a structured way; i.e. optimization of red blood cell mass, reduction of blood loss and bleeding, and optimization of the patient's physiological tolerance towards anemia. These activities should be included in the pre-peri- and postoperative routines, in all surgical units

Cardiac and Vascular Sympathetic Baroreflex Control during Orthostatic Pre-Syncope

We hypothesized that sympathetic baroreflex mediated uncoupling between neural sympathetic discharge pattern and arterial pressure (AP) fluctuations at 0.1 Hz during baroreceptor unloading might promote orthostatic pre-syncope. Ten volunteers (32 +/- 6 years) underwent electrocardiogram, beat-to-beat AP, respiratory activity and muscle sympathetic nerve activity (MSNA) recordings while supine (REST) and during 80 degrees head-up tilt (HUT) followed by -10 mmHg stepwise increase of lower body negative pressure until pre-syncope. Cardiac and sympathetic baroreflex sensitivity were quantified. Spectrum analysis of systolic and diastolic AP (SAP and DAP) and calibrated MSNA (cMSNA) variability assessed the low frequency fluctuations (LF, similar to 0.1 Hz) of SAP, DAP and cMSNA variability. The squared coherence function (K-2) quantified the coupling between cMSNA and DAP in the LF band. Analyses were performed while supine, during asymptomatic HUT (T-1) and at pre-syncope onset (T-2). During T-2 we found that: (1) sympathetic baroreceptor modulation was virtually abolished compared to T-1; (2) a progressive decrease in AP was accompanied by a persistent but chaotic sympathetic firing; (3) coupling between cMSNA and AP series at 0.1 Hz was reduced compared to T-1. A negligible sympathetic baroreceptor modulation during pre-syncope might disrupt sympathetic discharge pattern impairing the capability of vessels to constrict and promote pre-syncope

Frequent platelet donation is associated with lymphopenia and risk of infections : A nationwide cohort study

Background: Recently, plateletpheresis donations using a widely used leukoreduction system (LRS) chamber have been associated with T-cell lymphopenia. However, clinical health consequences of plateletpheresis-associated lymphopenia are still unknown. Study Design and Methods: A nationwide cohort study using the SCANDAT3-S database was conducted with all platelet- and plasmapheresis donors in Sweden between 1996 and 2017. A Cox proportional hazards model, using donations as time-dependent exposures, was used to assess the risk of infections associated with plateletpheresis donations using an LRS chamber. Results: A total of 74 408 apheresis donors were included. Among donors with the same donation frequency, plateletpheresis donors using an LRS chamber were at an increased risk of immunosuppression-related infections and common bacterial infections in a dose-dependent manner. While very frequent donors and infections were rare in absolute terms resulting in wide confidence intervals (CIs), the increased risk was significant starting at one-third or less of the allowed donation frequency in a 10-year exposure window, with hazard ratios reaching 10 or more. No plateletpheresis donors that used an LRS chamber experienced a Pneumocystis jirovecii, aspergillus, disseminated mycobacterial, or cryptococcal infection. In a subcohort (n = 42), donations with LRS were associated with low CD4+ T-cell counts (Pearson's R = -0.41; 95% CI, - 0.63 to -0.12). Conclusion: Frequent plateletpheresis donation using an LRS chamber was associated with CD4+ T-cell lymphopenia and an increased risk of infections. These findings suggest a need to monitor T-lymphocyte counts in frequent platelet donors and to conduct future investigations of long-term donor health and for regulators to consider steps to mitigate lymphodepletion in donors