Platelet transfusion

Currently, platelet collection and preparation is largely based on apheresis, and to a lesser extent, on preparation of platelet rich plasma, derived from whole blood.

The use of platelet transfusions has steadily increased over time, while there has been a decrease in platelet collections.

Fractionation of a unit of donated whole blood produces a unit of platelet concentrate that should contain at least 5.5 x 1010 platelets, and 4 to 6 such platelet concentrates are typically combined for one platelet transfusion in an adult.

Platelet concentrates can be obtained by the platelet rich plasma technique utilized in the U.S. and the buffy coat method used mainly in Canada and Europe.

No difference in the quality of platelets collected by the varying techniques, when the platelets are stored for up to 7 days.

Platelets are available from 2 sources based on their method of collection: Apheresis derived platelets and whole blood-derived platelets.

Apheresis platelets are collected from a single donor to constitute a transfusion dose, which is equivalent to the pooling of 4-6 donors of whole blood.

2-3 apheresis platelet units can be collected during a single event, with each of these units being considered one adult dose.

Apheresis accounts for 94% of the platelets used foor transfusions and whole blood separation with manual plasma rich  platelets accounts for 6%.

Whole blood-derive platelets are acquired from the platelet concentration part of a whole blood donation, and routinely 4-6 platelet concentrates are pulled together to obtain the typical dose.

Both apheresis platelets and pooled whole blood derived platelets must contain a minimum of 3×10 to the 11th platelets per bag, And they have similar clinical effects and can be used interchangeably.

Apheresis allows for reduction in donor exposures and has the potential of reducing transfusion transmitted infections and incidence of platelet allo-immunization.

The most common clinical applications for platelet transfusions are in hematology, oncology, ICUs, and surgery.

More than 80% of platelet transfusions are adminisered to individuals 50 years of age or older, the very demographic that is expanding in the US.

There are automated and semiautomated platelet rich plasma systems, which can efficiently use all donated whole blood, and increase the capacity to provide sufficient platelets.

Platelet products also contain plasma, some red cells and some white cells.

Platelet transfusions are usually cloudy and yellowish in color, but may occasionally have a pink tone because of the presence of residual red cells.

Platelets are stored at 68° to 75° Fahrenheit, require continuous gentle agitation, and can be stored up to five days.

When received for transfusion, pooled and apheresis platelets expire in less than four hours to avoid bacterial growth, since preparation for transfusion involves pooling, volume reduction and leuko reduction which require entry into the component.

A whole blood platelet concentrate is prepared from whole blood by centrifugation to separate the red cells from the platelet rich plasma.

A second harder centrifugation is used to concentrate the platelets that are then resuspended in 60 ml of residual plasma.

A clinically adequate dose of platelets for an adult consists of four to six platelet concentrates.

Pooled platelets are ABO type compatible, but other types may be substituted.

The average yield of platelets collected by apheresis is approximately 4.2 x 10 to 11th platelets.

Standard dose considered approximately 3 x 10 to the 11th-6×10 to the 11th platelets.

Stored in the blood bank at room temperature 68-75° on the platelet rotator to facilitate oxygen exchange.

Because of the risk of bacterial contamination at 1 per 1000 units, platelets have a shelf life of 5 days, and the day of collection is considered days 0.

All blood collection facilities monoscreen platelets for bacteria by bacterial cultures were assessing bacterial growth by oxygen consumption measurement.

Bacterial contamination of blood components is a significant challenge, especially for platelets because they cannot be stored at sufficiently low temperatures that have a bacteriostatic effect.

Bacterial contamination of blood components may be a result of endogenous bacteria with donors that might Have subclinical infections to include endocarditis, osteomyelitis dental disease or, more commonly related to skin contamination.

During the storage of blood/components bacteria present in the container may increase significantly in numbers up until the time of transfusion.

1 case of platelet related sepsis per 12,000 transfusions.

Bacterial risk associated is high because platelets are stored at 22°C rather than 4°C storage required by red blood cells.

All platelet concentrates are now tested for bacterial contamination.

Culture methods for capable of interdicting approximately 50% of contaminated units, and most of the contaminated units are transfused in the initial storage period before the bacterial load can reach clinical concentrations that have consequences for the recipient.

The rate of bacterial detection in platelet units is approximately 1 and 5000, And the incidence of significant morbidity associated with bacterial E contaminated platelets ranges from 1 in 70,000 118,000.

Bacterial platelet contamination reaction depends on the amount of bacteria present as well as their pathogenicity.

A study in patients with leukemia revealed reactions occurred in 2.2% of transfusions and 22% of individuals, and these reactions include fever, chills, urticaria, dyspnea, bronchospasm and cyanosis.

Up to 20% of patients with thrombocytopenia may become refractory to platelet transfusions.

A poor response to platelet transfusion can be due to immune and nonimmune causes, or both.

Immune refractoriness is most likely the result of HLA antibodies and, much less commonly due to antibodies directed against human platelet specific antigens.

The risk of HLA alloimmunization is significantly reduced with the use of leuko-reduced red blood cells and platelets.

Parous women previously exposed to fetal epitopes may elicit prior alloimmunization.

Men and nulliparous women may have HLA alloimmunization due to prior blood transfusion.

Poor responsiveness to platelet transfusion at 10 minutes or 1 hour following transfusion should be evaluated for possible immune causes for refractoriness.

An average sized person receiving an average dose platelets should increase the platelet count by about 15,000/microliters.

Obtained by preparing concentrates from whole blood or by apheresis techniques.

Platelet concentrates from donated units are isolated by the platelet rich plasma method in the U.S. and by the buffy coat method in Europe.

Leukoreduction of platelet transfusion reduces alloimmunization rates.

Leukoreduction of platelet transfusion prevents cytomegalovirus transmission.

Leukoreduction of platelet transfusion reduces in febrile transfusion reactions.

Leukoreduction results in increased costs and a loss of 25% of platelets.

Data suggest that white blood cells contaminating platelet and red blood cell transfusions can possible contribute to increased incidence of postoperative infections and increased risk of metastases in malignancy.

Gamma irradiation of platelets indicated to prevent transfusion related graft versus host disease.

Gamma irradiation utilized in allergenic stem cell transplantation, for patients receiving blood products from related donors and for patients severely immunocompromised.

Four randomized prospective studies comparing prophylactic platelet transfusions for 10,000 vs. 20,000 platelets/microliter revealed no differences in hemorrhagic risk (Schlicter).

Platelet transfusions are indicated for patients with bleeding due to thrombocytopenia or platelet dysfunction or both.

A bleeding time twice the upper normal limit may be an indication for a platelet transfusion in a bleeding patient.

HLA Matched platelets are indicated for patients who are refractory to random donor platelets due to alloimmunization.

Platelet transfusions may be indicated for either a quantitative defect or a qualitative defect.

Patients with ITP should not receive platelet transfusions unless bleeding is significant.

Present recommendation for prophylactic platelet transfusion is 10,000 platelets/microliter.

Prophylactic platelet transfusions recommended for platelet count less than 10,000/mcL in adult patients with therapy induced hypoproliferative thrombocytopenia, less than 20,000/mcL for central venous catheter placement, and less than 50,000/mcL for either diagnostic LP or major elective non-neuraxial surgery.

Common platelet transfusion triggers include less than 10,000/mcL per stable, nonbleeding individuals, and less than 20,000/mcL for febrile patients, 100,000 for neurosurgical patients or patients with ophthalmological bleeding.

Therapeutic platelet transfusion indicated in chronic thrombocytopenia when WHO grade 2 bleeding or greater is present.

WHO bleeding grades grade 0, none, grade 1, petechiae, ecchymoses, occult blood in body secretions, and mild vaginal spotting, grade 2, evidence of gross hemorrhage not requiring red blood cell transfusions, grade 3, hemorrhage requiring transfusion of 1 or more units of red blood cells per day and grade 4, life-threatening hemorrhage with massive bleeding causing hemodynamic compromise or bleeding into a vital organ such as the brain, pericardium, or pulmonary hemorrhage.

WHO bleeding grades 1 and 2 usually related to the degree of thrombocytopenia.

Grade 3,4 WHO bleeding is usually more associated with other conditions in addition to the thrombocytopenia such as uremia, tumor necrosis, presence of medications, the presence of anticoagulants, plasma clotting abnormalities or other underlying disease processes.

With the use of a surgical procedure or following trauma platelet counts of at least 50,000/microL should be maintained, although no clinical studies substantiate these numbers.

Patients with intracranial bleeding or during or following microsurgical procedures should have platelet counts maintained at greater than 100,000/microL.

In patients with platelet counts between 50,000 and 100,000/microL, the decision to utilize platelet transfusion depends on rates of bleeding, the presence of platelet dysfunction, the extent of surgery , the extent of trauma, the ability to control bleeding with local measures and the presence of other coagulation abnormalities.

Refractoriness to transfusion can be immune or non-immune in nature.

Refractory status requires the determination of two serial platelet transfusion responses.

With increasing transfusions there is a progressive decrease in platelet count increments and days to the next transfusion.

There is a logarithmic decrease in platelet response after transfusions with the largest changes occurring with the earliest transfusions.

A and B red cell antigens are expressed on platelets, and ABO incompatible platelets have reduced post transfusion platelet recoveries but normal survivals.

Recipients of ABO incompatible platelets become platelet refractory at higher rate than the ABO compatible recipients, 69% versus 8%, respectively, because of the development of anti-HLA and platelet specific alloantibodies (Carr).

Transfusion of ABO incompatible platelets increase anti-HLA and platelet specific antibodies and also stimulates the recipients immune systems to make other alloantibodies.

Providing ABO-compatible platelets achieves the best post-transfusion platelet increments and reduces the incidence of all immune platelet refractoriness.

In the presence of platelet alloimmunization selecting HLA compatible donors, selecting antigen compatible apheresis donors and cross-matching platelets for compatible platelets are the three types of management available.

In patients who are refractory to platelet transfusions who have anti-HLA or anti-human platelet antigen antibodies requires identifying the antibody specificity and providing antigen-negative platelets.

If patients have anti-HLA antibodies HLA matched platelets with a matching of HLA class I antigens, specifically the A and B loci can be provided.

In patients with anti-human platelet antigen (anti-HPA) antibodies and refractoriness to platelet transfusions HPA-matched platelets can be provided..

In platelet refractoriness crossmatched-compatible platelets can be performed and compatible platelets can be found that lack the antigen or antigens to which the patient has formed antibodies.

Randomized trials comparing low dose to hogh dose platelet transfusion indicated that both doses prevent bleeding to a similar degree (Tinmouth A, Heddle NM).

In a randomized trial of hospitalized patients undergoing hematopoietic stem cell transplantation or chemotherapy for hematologic cancers or solid tumors to receive prophylactic platelet transfusions at a low dose, medium dose, or high dose ( 1.1×10 to the 11th, 2.2×10 to the 11th or 4.4×10 to 11 platelets per square meter of body surface area, respectively) when morning platelet counts were 10,000 per cubic millimeter or lower:the incidences of higher grades of bleeding was similar among the three groups, the median number of platelets transfused was significantly lower in the low dose group, but the median number of platelet transfusions given was significantly higher in that group and bleeding occurred on 25% of the study days on which morning platelet counts were 5000 per cubic millimeter or lower as compared with 17% of study days on which platelet counts with 6000 to 80,000 per cubic millimeter-at doses. Between 1.1×10 to the 11th and 4.4×10 to 11 platelets per square meter, the number of platelets in the prophylactic transfusion group had no effect on the incidence of bleeding (Slichter SJ).

Median platelet increment after platelet transfusion in the low dose group was 10,000 per cubic ml, 19,000 in the medium dose group and 38,000 in the high dose group: larger doses give higher increments and longer intervals until the next transfusion (Schlicter S et al).

Post transfusion platelet increments are higher in patients who receive apheresis platelets, ABO-identical platelets, and platelets stored 3 days compared with those of 4-5 days.

The status of the spleen has a greatest impact on post-transfusion platelet increments: Splenectomized patients have a greatest increments, whereas patients with a palpable spleen have lower platelet increments and shorter time to their next platelet transfusion.

Post-transfusion platelet increments are lower in patients with increased weight and height, with co-dministration of heparin, amphotericin, the presence of bleeding, fever, and infection.

1 unit of platelets should increase the platelet count by 35-40,000/microliters as measured within 1 hour following the transfusion.

Refractoriness to platelet transfusion is defined as the failure to achieve a 1 hour posttransfusion platelet increments of 11,000/microliters on 2 consecutive transfusions.

Transfusing ABO-incompatible platelets may negatively impact the posttransfusion platelet increment.

Platelet transfusion refractoriness has two categories: Non-immune-mediated and immune-mediated.

Approximately two thirds of platelet refractoriness related to nonimmune factors and 1/5 comprise nonimmune and immune causes.

Immune-mediated platelet refractoriness is due to alloantibody formation against the HLA system, the HPA (human platelet antigens), or both.

Alloimmunization risks to the HLA and the HPA system include prior transfusions, pregnancy, and transplantation.

Leuko-reduction and ultraviolet B irradiation are equally effective in preventing antibody-mediated platelet refractoriness.

All platelets collected and transfused today are leuko-reduced.

Use of prophylactic platelet transfusions is standard of care to reduce the risk of clinically significant bleeding in hypoproliferative thrombocytopenia.

PLADO Trial data suggest that platelet counts, hematocrits, coagulation factors, and clinical treatment categories may all predict increased risk of bleeding.

In the presence of thrombocytopenia, hematocrit levels are inversely associated with risk of bleeding.

Analysis of coagulation assays demonstrated an increased overall risk for bleeding for patients with abnormal INR and aPTT.

There is an increased bleeding risk in patients with hypoproliferative thrombocytopenia treated with chemotherapy or allogeneic transplant vs patients undergoing autologous SCT.

Increased overall risk with hypoproliferative thrombocytopenia and bleeding correlates with profoundly low platelet counts (≤5 × 109/L), hematocrit of ≤25%, INR >1.2, and aPTT >30 seconds.

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