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The main indication for the transfusion of plasma is to correct deficiencies of clotting factors, for which a specific concentrate is not available, in patients with active bleeding. The products available are: fresh-frozen plasma (FFP), plasma that has undergone viral inactivation with solvent/detergent treatment (S/D FFP), with methylene blue (MB FFP) or with psoralens, in particular amotosalen (S59) and light1; inactivation technology using riboflavin will soon be available2.
FFP prepared from units of whole blood and that derived from apheresis are therapeutically equivalent in terms of haemostasis and side effects (Grade of recommendation: 1A)4.
FFP contains normal levels of the stable clotting factors, albumin and immunoglobulins. It contains at least 70% of the original coagulant factor VIII and at least similar quantities of the other labile clotting factors and natural inhibitors of coagulation1,3–5.
FFP for clinical use must not contain clinically significant irregular anti-erythrocyte antibodies. In order to increase its safety, FFP can be quarantined for a minimum period of 4 months.
Physiological individual differences in the concentrations of plasma proteins mean that the generic definition of FFP is applied to products that differ notably in quality.
Methylene blue (MB) is a phenothiazine dye with a virucidal effect2,35–40. MB FFP is not a pharmaceutical product, but is derived from the use of an inactivation method applied to single units of plasma.
The content of the biologically active proteins of this product cannot be standardised, so the biological variability of the units remains high.
The potential decrease in the residual infective risk is the same as that for S/D FFP.
The transfusion of FFP is indicated in the following situations (Table I):
Coagulation times in the neonate, which, on average, are longer than those in the adult, are not necessarily related to the risk of bleeding71–74. This is even more the case in premature neonates; thus, abnormal coagulation test results, in the absence of symptoms or haemorrhagic risk, are not an indication for the transfusion of FFP.
FFP is indicated for bleeding caused by vitamin K deficiency and bleeding (or high risk of bleeding) due to DIC. It is also indicated for the treatment of congenital deficiencies of single clotting factors, when the specific concentrate is not available (Grade of recommendation: 2C)4,71–74.
FFP should preferably be ‘safe’, in the sense of having undergone viral inactivation or been quarantined.
For further details, refer to the joint recommendations from the Italian Society of Neonatology and SIMTI72.
FFP must be thawed between 30 °C and 37 °C in a water bath under continuous agitation or with another system able to ensure a controlled temperature. The plasma must be transfused as soon as possible after thawing, but in any case within 24 hours, if stored at 4 ± 2 °C 4,5.
Refer to the product summary sheet for information on the maximum time between the completion of thawing of S/D FFP and starting its transfusion.
FFP must not be refrozen once it has been thawed (Grade of recommendation: 1C+)4.
The recommended therapeutic dose of FFP is 10–15 mL/kg of body weight1,4,43,44,47. The dose of FFP does, however, depend on the clinical situation and laboratory parameters (Grade of recommendation: 1C+)1,4,43,44,47,50, which may justify the administration of higher doses75–77.
Absolute contraindications to the use of FFP are documented intolerance to plasma or its components and congenital deficiency of immunoglobulin A (IgA) in the presence of anti-IgA antibodies4.
Relative contraindications are heart failure and pulmonary oedema.
The transfusion of platelets is indicated for the prophylaxis and treatment of haemorrhage1 in patients with thrombocytopenia or with primary or secondary functional disorders of platelets.
The platelet content differs according to the type of product (see appendix B):
Pools of PC from single units of whole blood and apheretic PC contain about the same amount of platelets; comparative studies have shown that they are therapeutically equivalent, in terms of post-transfusion platelet count increment and haemostatic efficacy, if transfused fresh, and that the incidence of side effects associated with the two types of PCs is similar (Grade of recommendation: 1A)4–8.
Compared to PC from apheresis, PC from a pool expose the recipient to a greater number of donors.
The decision to transfuse PCs must not be based exclusively on the platelet count1. The absolute indication is severe thrombocytopenia together with clinically relevant bleeding. All the other indications are more or less relative and depend on the clinical condition of the patient.
Human platelet antigen (HPA) and/or human leucocyte antigen (HLA)-compatible platelets can be used in the treatment of immunised patients. It is advised not to use apheretic platelets from relatives of the patients, or other HLA-compatible individuals, who could be haematopoietic stem cell donors.
After a validated procedure of leucodepletion, apheretic PCs are an acceptable alternative to cytomegalovirus (CMV)-negative PCs for the prevention of CMV infection.
Prophylactic use of PCs is possible, and sometimes inevitable, in very severe cases of thrombocytopenia. In these cases the currently recommended transfusion threshold is 10,000 platelets/μL in clinically stable patients4,8,9–40, that is, in the absence of all the following clinical conditions4,8,15,17,19–22,26,27,34–36,39,40:
See table III.
In the following circumstances (table III):
The need for PCs, in the presence of thrombocytopenia (platelets < 100,000/μ L) or functional defects (including iatrogenic ones) of platelets, depends on the nature and the site of the bleeding, on the presence or absence of coagulation disorders, ongoing treatments, as well as the clinical condition of the patient (Table IV).
See table VI.
For further details refer to the recommendations issued jointly by the Italian Society of Neonatology and SIMTI52.
The CCI should be > 7,500 at 1 hour and 4,500 at 20–24 hours.
Group O PC can be used for patients with blood groups A, B, and AB only if they are resuspended in additive/preservative solutions, or if negative for high titre anti-A/A,B [critical titre (in a gel-test) of anti-A/A,B: IgM ³ 1:64 and/or IgG ³ 1:256] (Grade of recommendation: 2C+)64–67.
In the case of a transfusion of a RhD-positive PC to a RhD-negative women of childbearing age, 250 UI (50 μg) of anti-D immunoglobulin should be administered, a dose able to cover the transfusion of five therapeutic doses of PC in 6 weeks (Grade of recommendation: 1C)4,8,10.
A low CCI already in the first hour (< 7,500) is often associated with alloimmunisation to leucocyte and platelet antigens. This type of refractoriness can be caused by antibodies against HLA class I antigens (A and B) or against platelet-specific antigens (in particular HPA-1a)44.
A normal CCI at 12 hours and a low one (< 4,500) at 20 – 24 hours is usually related to reduced survival of the platelets as a result of non-immunological causes such as64: fever, sepsis, splenomegaly, administration of amphotericin B, substantial bleeding, DIC.
Patients with a low CCI on two or more occasions fulfil the criteria for a diagnosis of refractoriness to platelet transfusions. These patients should be investigated to identify immunological or non-immunological causes of the refractoriness. The use of ABO-compatible and fresh PCs (produced within less than 2 days of transfusion) is important in order to determine whether the cause of the refractoriness is antibody-mediated; in fact, platelets collected more than 48 hours before transfusion give a reduced post-transfusion yield and have a shortened survival in patients with clinical conditions that are among the non-immunological causes of refractoriness.
The transfusion of HLA-compatible platelets, for patients with refractoriness of an immunological origin, should not be considered a first line strategy because it would be necessary to have at least 1,000 donors of typed apheretic platelets.
The use of transfusion therapy with PCs in the following circumstances: