Factors affecting posttransfusion platelet increments, platelet refractoriness, and platelet transfusion intervals in thrombocytopenic patients

Many modern therapies depend on platelet (PLT) transfusion support PLTs have a 4- to 7-day shelf life and are frequently in short supply In order to optimize the inventory PLTs are often transfused

/pdf/platelet-transfusion-the-art-and-science-of-compromise-56ozxfs5xz.pdf

Platelet Transfusion - the Art and Science of Compromise

Transfused platelets (plts) are either pooled random-donor platelet (plt) concentrates or single-donor apheresis plts. When stored for 5 days, all of these products are equally efficacious. A 10,000/microL prophylactic plt transfusion trigger has been documented to be both hemostatically efficacious and cost effective in reducing plt transfusion requirements. The optimal plt dose/transfusion is being evaluated in an ongoing clinical trial. Therapeutic plt transfusions to control or prevent bleeding with trauma or surgical procedures require higher transfusion triggers of 100,000/microL for neurosurgical procedures and between 50,000/microL and 100,000/microL for other invasive procedures or trauma. Leukoreduction has been documented to reduce plt alloimmunization rates, cytomegalovirus (CMV) transmission by transfusion, and febrile transfusion reactions. Whether it reduces immunomodulatory effects of transfusion (i.e., decreases infection rates and cancer recurrence) is still controversial, as is universal leukoreduction. Poor responses to plt transfusions are often multifactorial. For alloimmune plt refractoriness, HLA matching, cross-matching, and identification of the specificity of the patient's antibodies with avoidance of mismatched donor antigens are all equally effective in identifying compatible plts for transfusion. Other causes of poor plt responses are splenomegaly, ABO mismatching, females with 2 or more pregnancies and males, use of heparin or amphotericin, bleeding, fever, graft-vs-host disease (GVHD), and vaso-occlusive disease (VOD).

/pdf/evidence-based-platelet-transfusion-guidelines-nqu7ry81a0.pdf

Evidence-Based Platelet Transfusion Guidelines

Bacterial infection is a major cause of death and long-term morbidity in preterm neonates. Infection rates among neonates undergoing intensive care range from 25% to 50% (Stoll et al, 1996; Cooke et al, 1997; Fanaroff et al, 1998) and, in spite of effective antibiotic therapy, sepsisrelated mortality has remained constant at 15±20% for nearly two decades (Gladstone et al, 1990). The reason for such high sepsis rates and attendant mortality are largely due to the immaturity of bactericidal mechanisms. Clinical evidence of the preterm neonate's immune incompetence is the pattern of bacterial infections which closely parallels that seen in patients with profound neutropenia (Stoll et al, 1996) and the frequent development of neutropenia in response to bacterial sepsis (Engle et al, 1984; Gessler et al, 1995). These two phenomena can be directly related to immaturity of neutrophil function and production.

https://onlinelibrary.wiley.com/doi/pdf/10.1046/j.1365-2141.2000.01992.x

Neutrophil Production and Function in Newborn Infants

Transfusion-associated graft-versus-host disease (TA-GvHD) is a very rare but potentially lethal complication occurring after blood components transfusion� Goal of the article: to analyze the literature describing this complication� TA-GvHD can develop due to several factors: quantity and viability of lymphocytes, contained in the transfused blood component, responsiveness of the patient's immune system to replantation of donor lymphocytes and degree of immunological HLA-homology between the donor and the recipient� History and epidemiology of this fatal syndrome, its pathogenesis, clinical manifestations, diagnostics and therapy have been reviewed� It has been shown that the main prevention techniques include abstaining from blood components transfusion collected from close relatives and using special irradiation modes, suppressing proliferation of the donor's lymphocytes� Conclusion: Doctors performing blood components transfusion should note that post-transfusion reaction development in the variant of graft-versus-host might develop in order to provide timely diagnostics and to start the specific treatment of this complication�

https://onlinelibrary.wiley.com/doi/pdf/10.1046/j.1365-2141.2002.03450.x

Transfusion-associated graft-versus-host disease.

Forty-three consecutive patients previously unexposed to platelets and undergoing treatment for acute leukaemia or autografting for relapsed Hodgkin's lymphoma were randomized to receive transfused platelets of either their own ABO group (OG) or of a major mismatched group (MMG). The 26 evaluable patients were equally distributed between the two study groups. Nine of 13 (69%) MMG patients became refractory with a median onset at transfusion 7 (15 d), compared with only one of 13 (8%) OG patients (P = 0.001). Refractoriness was associated with the formation of high titre isoagglutinins, anti-HLA and platelet specific antibodies. In one patient refractoriness appeared to be due to high titre isoagglutinins alone. Six other patients developed an increase in isoagglutinin titre sufficient to adversely affect platelet increments. Patients receiving ABO-mismatched platelets had a higher incidence of anti-HLA antibodies (5 v. 1) and platelet specific antibodies (4 v. 1). ABO-mismatched platelets transfused prior to the onset of refractoriness resulted in increments similar to those achieved by ABO-matched platelets. The study demonstrates that ABO-mismatched platelets are as effective as matched platelets in patients with low titre isoagglutinins requiring only few transfusions. However, the greater incidence of early refractoriness induced in MMG patients indicates that ABO-mismatched platelets should not be given to patients with marrow failure requiring long-term support.

Transfusion of ABO-mismatched platelets leads to early platelet refractoriness.

Abnormal FcRIII Expression by Neutrophils From Very Preterm Neonates

We have previously described reduced expression of the Fcγ receptor type III on the cell membrane (M-FcRIH) of neutrophils from very preterm neo- nates To investigate the mechanism underlying this reduced receptor expression, we have measured neutrophil- derived soluble FcRIII (S-FcRIII) in the plasma of fetuses and neonates from 19 wk gestation S-FcRIII in fetal plasma and in preterm neonates born before 32 wk gestation was consistently low [mean 136 ± 12% (mean adult S-FcRIII = 100%, range 30–240%)] In utero, S-FcRIII starts to rise from 33 wk and increases more than 4-fold to reach adult levels by term S-FcRIII measured sequentially in preterm infants born as early as 24 wk of gestation showed a rapid postnatal increase to reach adult levels within 3 wk of birth The changes in S-FcRIII paralleled changes in M-FcRIII expression on the cell surface These observations point to a reduced rate of FcRIII production by fetal neutrophils as opposed to an increase in receptor release The parallel increase in S-FcRIII and M-FcRIII suggests that there may be a programmed activation of FcRIII synthesis within individual cells late in the 3rd trimester of fetal development In addition, FcRIII production may be switched on early by preterm birth

/pdf/changes-in-plasma-fcriii-demonstrate-increasing-receptor-45144qhrjo.pdf

Changes in plasma FcRIII demonstrate increasing receptor production during late pregnancy and after preterm birth.

Platelet concentrates stored for up to 5 days at room temperature or irradiated with 15 Gy immediately prior to transfusion were evaluated for their ability to increase the platelet count in thrombocytopenic patients. Platelets irradiated with a dose of 15 Gy immediately prior to transfusion achieved corrected increments (CI) at 1 and 20 h after transfusion no different from those achieved by non-irradiated platelets. Storage for 5 days reduced the mean 1-hour CI to 5.7 compared with a mean of 12.3 achieved by platelets transfused after only 1-day storage (p = 0.008). Similarly, the frequency of a repeat transfusion being indicated within 24 h increased with increasing storage time (p = 0.005).

Clinical evaluation of the effects of storage time and irradiation on transfused platelets.

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Transfusion of ABO-mismatched platelets leads to early platelet refractoriness.

Abnormal FcRIII Expression by Neutrophils From Very Preterm Neonates

Changes in plasma FcRIII demonstrate increasing receptor production during late pregnancy and after preterm birth.

Clinical evaluation of the effects of storage time and irradiation on transfused platelets.