blood component therapy

Blood component therapy

Transfusion of specific parts ofblood, rather than whole bloodADVANTAGEOne donated unit can help multiple patients– Conserves resources– Optimal method for transfusing large amounts of a specific component

Major blood components• Blood components are the products derived

from whole blood (or platelet-rich plasma)using the technique of differential centrifugation or apheresis. These include;

• Plasma• Red blood cells• Platelets • Granulocytes

Red blood cell transfusion in adults: Storage, specialized modifications, and infusion

parameters

COLLECTION AND STORAGE PROCEDURES

Preservative solutionscitrate phosphate dextrose (CPD) for 21-day storage CPD-adenine for 35-day storageand the current generation of additive solutions – SAGM that permit storage for 42 days.

Storage temperature stored under refrigeration at controlled temperatures of 1 to 6°C to maintain the viability of the red cells and to prevent the growth of bacteria. When transported between facilities (eg, from a blood collection facility to a hospital or between hospitals), the storage temperature must be maintained at 1 to 10°C.

• studies have shown that red cell units can be maintained outside controlled temperature conditions for up to 60 minutes without either of these adverse effects.

• Freezing to preserve rare RBC units • RBCs frozen in 40 percent glycerol are approved

by the FDA and the AABB for storage at -80ºC for up to 10 years [9]. The use of this product was evaluated in a prospective, randomized trial

EFFECT OF STORAGE CONDITIONS ON TRANSFUSION OUTCOME

• Red cell viability and recovery :• dependent upon the A-P solution used, donor-to-donor

variation, leukoreduction, the amount of mannitol in storage solutions, and storage hematocrit.

• One criterion for FDA licensing of A-P solutions is to measure the 24-hour recovery of autologous radiolabeled red cells in normal subjects after different intervals of storage. The recovery threshold for the percentage of circulating red cells 24 hours following infusion is currently set at 75 percent, with some ongoing discussion about the degree of statistical variation that is allowable.

2,3 BPG concentration :levels in the RBC progressively fall toward 10 percent of normal. As a result, the oxyhemoglobin dissociation curve progressively shifts to the left, resulting in reduced oxygen release by hemoglobin at any given tissue pO2. • It is uncertain whether this abnormality is

physiologically important, even in critically ill patients . Even if it were, the red cell 2,3 BPG concentrations increase to normal within 6 to 24 hours of transfusion, resulting in normalization of oxygen release .

• Potassium leakage :• Plasma potassium concentrations in stored blood increase

approximately 1 mEq/L per day due to passive leakage out of the red cells.Potassium is not actively transported back into the RBC because membrane ATPase is inhibited at 1 to 6°C, the temperature range employed for storage of red cells.

• Loss of one unit of blood through bleeding would result in the loss of 1.5 mEq of potassium (5 mEq/L x 0.3 L of plasma); transfusion of one unit of whole blood or RBC would be expected to provide approximately 10 mEq of potassium, leading to a net gain of 8.5 mEq . There is usually no increase in the serum potassium concentration, since the excess potassium moves into cells

• three clinical settings in which there is an increased risk of transfusion-related hyperkalemia:

• Severe trauma;• prevalence of 29 percent in massively traumatized

patients at a United States military combat support hospital in Iraq.

• Although blood product transfusion plays an important role, other risk factors include

• tissue breakdown with the release of cellular potassium into the extracellular fluid,

• low cardiac output which impairs renal function, • and hypocalcemia which can increase the severity of

the manifestations of hyperkalemia play a role.

• Impaired renal function • Infants and newborns • Irradiated red cells — Red cells that have been

irradiated to prevent graft-versus-host disease leak more potassium than non-irradiated products. As a result, their shelf life is reduced to 28 days

• Ammonia — Plasma ammonia concentrations progressively increase in stored blood, approaching 900 mcg/dL after five to six weeks. It has been suggested that this amount of ammonia may make it undesirable to transfuse large numbers of stored units of blood to a patient with high ammonia levels, and that saline-washed red cells should be used instead

Clinical relevance of storage time

• The Age of Red Blood Cells in Premature Infants (ARIPI) trial

• The Age of Blood Evaluation (ABLE) trial• The Red Cell Storage Duration Study (RECESS).

In each of these trials, outcomes were equivalent in each of the arms.

SPECIALIZED MODIFICATIONS • Leukoreduced red cells HLA alloimmunization against class I antigens does not

appear to occur if the red cell preparation contains less than 106 leukocytes. There are now numerous commercially available filters that accomplish this degree of leukocyte removal.

• ●Some patients experience febrile transfusion reactions that are due to white cell contamination of the red cell concentrate rather than RBC alloimmunization. In this setting, the time at which the red cells are filtered is important. The red cells should be filtered as close to the collection time as possible, in order to remove intact leukocytes that would otherwise fragment over time, releasing cytokines that are responsible for the febrile response. This requires that leukoreduction filters be used in the blood collecting facility rather than in the hospital blood bank or at the bedside.

• ●Leukoreduction is an effective method to the risk of transfusion-transmitted cytomegalovirus infection. CMV resides in the leukocytes and is removed during leukoreduction.

• Ideally, leukoreduction to eliminate leukocyte debris and leukocyte-generated cytokines would be performed on all cellular components intended for transfusion. This policy of universal leukoreduction is standard practice in many developed countries, while a minority of other countries (including the United States) has yet to require universal leukoreduction as the official standard of care.

Indiations

• Chronically transfused patients• Patients undergoing cardiac surgery• All potential recipients of solid organ or hematopoietic

cell transplants• Patients with solid organ or hematopoietic cell

transplants• Patients with previous febrile nonhemolytic

transfusion reactions• CMV seronegative at-risk patients for whom

seronegative

Irradiated red cells

• In order to avoid the occurrence of graft-versus-host disease (GVHD) in patients who have immune deficiency states, transfused red cells must be subjected to irradiation with at least 25 Gy to prevent the donor T lymphocytes from dividing in the recipient . Irradiation to prevent GVHD is also recommended for red cells collected from relatives entered in directed donation programs. It has become more generally accepted that irradiated red cells should also be used for transfusion in cancer patients immunosuppressed by large doses of chemotherapy

Washed red cells to remove plasma

• Patients with severe or recurrent allergic reactions (eg, hives) associated with red cell transfusion.

• Certain patients with IgA deficiency when IgA deficient donors are not available (although frozen deglycerolized red cells may be the component of choice); patients with IgA deficiency may have circulating anti-IgA antibodies that react with IgA in the donor plasma.

• Washing of RBCs prior to infusion can also be used to reduce the amount of transfused potassium for patients who are at risk for developing hyperkalemia.

Experimental approaches

• Elimination of blood group antigens;— Enzymatic conversion of A, B, and AB red cells to group O has been achieved in vitro via the use of exoglycosidases derived from bacterial sources.Ex vivo generation of red cells — Limited numbers of viable red cells can be generated ex vivo in culture systems from CD34+ hematopoietic stem cells. In a proof-of-principle study, such red cells were fully functional in terms of their deformability, enzyme content, capacity of their hemoglobin to release oxygen, and expression of blood group antigens

INFUSION PARAMETERS • Consent• Venous access • Patient identification • Premedication – The routine use of premedication (eg, acetaminophen

and/or antihistamines) to prevent febrile nonhemolytic or allergic transfusion reactions is not supported by data

• Filters – All RBC units must be transfused through a standard 170 to 200 micron filter (contained as an integral part of a standard infusion set) designed to remove clots and aggregates

• Compatible fluids – only normal saline(0.9%)• Infusion rate – Suggested rates for adults are 1 to 2 mL per minute (60 to 120 mL

per hour) for the first 15 minutes and then as rapidly as tolerated; the complete infusion should not exceed four hours

• Blood warmers – For patients who require blood that is warmed (eg, those at risk of hypothermia or autoimmune cold-induced hemolysis), blood warmers that raise the temperature closer to body temperature are used. These must be calibrated and monitored to avoid heating of the blood cells above 40°C, which will cause hemolysis

Indications and hemoglobin thresholds for red blood cell transfusion in the adult

• we prefer using a restrictive transfusion strategy (ie, giving less blood; transfusing at a lower Hgb level; and aiming for a lower target Hgb level) rather than a liberal transfusion strategy (ie, giving more blood; transfusing at a higher Hgb level). For most hemodynamically stable medical and surgical patients, we suggest considering transfusion at a Hgb of 7 to 8 g/dL

• Major exceptions to the use of a threshold of 7 to 8 g/dL include the following:

●Symptomatic patients may be transfused at higher Hgb levels to treat symptoms. ●Patients with acute coronary syndromes have not been adequately evaluated in clinical trials and may require higher thresholds for transfusion. ●Threshold-based transfusion is not appropriate for patients requiring massive transfusion, such as in the setting of trauma, because it requires waiting for Hgb levels to be reported.

• Symptomatic patient — In some randomized trials of transfusion thresholds, symptoms of anemia were an indication for transfusion regardless of whether the Hgb was above the prescribed threshold

• Acute coronary syndrome — The optimal transfusion threshold in the setting of acute coronary syndromes (ACS; ie, acute MI, unstable angina) remains unresolved . Our practice in patients with ACS is to transfuse when Hgb is <8 g/dL and to consider transfusion when the Hgb is between 8 and 10 g/dL. If the patient has ongoing ischemia or other symptoms, we maintain the Hgb ≥10 g/dL. In a stable, asymptomatic patient, it is unknown when to transfuse, although we tend to maintain a higher Hgb level using clinical judgment based on evaluating the patient's symptoms and underlying condition.

• Asymptomatic hospitalized patient — As described above, for most hemodynamically stable medical and surgical patients, we suggest considering transfusion at a Hgb of 7 to 8 g/dL. Some patients will remain asymptomatic from anemia at lower Hgb levels; conversely transfusion at higher Hgb levels is often appropriate for symptomatic patients and in the setting of an acute coronary syndrome

• Heart failure — Anemia and heart failure (HF) often coexist for a variety of reasons (eg, cytokine changes, dilutional anemia, medical therapy for HF). Many experts consider anemia to be a surrogate marker for poor prognosis in individuals with HF, rather than a therapeutic target.

• Trauma/massive transfusion — Use of massive transfusion in the critically ill, hemodynamically unstable patient cannot be guided by Hgb levels alone and often cannot await interval measurements of Hgb

• Trauma/massive transfusion: — Use of massive transfusion in the critically ill, hemodynamically unstable patient cannot be guided by Hgb levels alone and often cannot await interval measurements of Hgb.

• Intensive care unit/septic shock — Restrictive transfusion appears to be safe in medical patients in an intensive care unit (ICU), with the possible exception of patients with ischemic heart disease/acute coronary syndrome.

• Acute bleeding Acute bleeding is an especially challenging clinical setting in which to evaluate red cell transfusion thresholds. For patients with massive bleeding or who are hemodynamically unstable, transfusion should be guided by the pace of the bleeding and the ability to stop the bleeding, rather than by the Hgb. Therefore, the use of transfusion in acutely hemorrhaging patients cannot be based on thresholds

• Non-cardiac surgery — Results of a randomized trial in patients undergoing hip surgery suggest that it is reasonable to use a lower threshold restrictive strategy of 8g/dL for patients who have undergone surgery, in the absence of symptoms of anemia, even in elderly patients with underlying cardiovascular disease or cardiovascular risk.

• Cardiac surgery — Transfusion thresholds in cardiac surgery have been evaluated in several randomized trials. Together, data from these trials suggest that a restrictive transfusion strategy with a Hgb threshold of 7.5 to 8 g/dL appears to be reasonable in patients undergoing cardiac surgery with cardiopulmonary bypass.

• Chronic kidney disease ; targeting Hgb levels in the range of 10.0 to 11.5 g/dL

• There are two major groups of oncology patients for whom transfusion may be indicated:

• Patients undergoing myelosuppressive chemotherapy

• patients with terminal cancer receiving palliative care

Platelets

• Platelet collection;• There are two ways that platelets can be collected:

by isolation from a unit of donated blood, or by apheresis from a donor in the blood bank.

• ●Pooled platelets – A single unit of platelets can be isolated from every unit of donated blood, by centrifuging the blood within the closed collection system to separate the platelets from the red blood cells (RBC).

• The number of platelets per unit varies according to the platelet count of the donor; a yield of 7 x 1010platelets is typical . Since this number is inadequate to raise the platelet count in an adult recipient, four to six units are pooled to allow transfusion of 3 to 4 x 1011 platelets per transfusion . These are called whole blood-derived or random donor pooled platelets

• Advantages of pooled platelets include lower cost and ease of collection and processing (a separate donation procedure and pheresis equipment are not required). The major disadvantage is recipient exposure to multiple donors in a single transfusion and logistic issues related to bacterial testing.

•

●Apheresis (single donor) platelets

• Platelets can also be collected from volunteer donors in the blood bank, in a one- to two-hour pheresis procedure. Platelets and some white blood cells are removed, and red blood cells and plasma are returned to the donor. A typical apheresis platelet unit provides the equivalent of six or more units of platelets from whole blood (ie, 3 to 6 x 1011 platelets) [2]. In larger donors with high platelet counts, up to three units can be collected in one session. These are called apheresis or single donor platelets.

Advantages of single donor platelets are exposure of the recipient to a single donor rather than multiple donors, and the ability to match donor and recipient characteristics such as HLA type, cytomegalovirus (CMV) status, and blood type for certain recipients

• PLATELET STORAGE AND PATHOGEN REDUCTION — Platelets are stored at room temperature, because cold induces clustering of von Willebrand factor receptors on the platelet surface and morphological changes of the platelets, leading to enhanced clearance by hepatic macrophages and reduced platelet survival in the recipient [3-6].

• All cells are more metabolically active at room temperature, so platelets are stored in bags that allow oxygen and carbon dioxide gas exchange. Citrate is included to prevent clotting and maintain proper pH, and dextrose is added as an energy source

INDICATIONS FOR PLATELET TRANSFUSION

• Actively bleeding patient — Actively bleeding patients with thrombocytopenia should be transfused with platelets immediately to keep platelet counts above50,000/microL in most bleeding situations, and above 100,000/microL if there is disseminated intravascular coagulation or central nervous system bleeding.

• Preparation for an invasive procedure — Platelets are transfused in preparation for an invasive procedure if the thrombocytopenia is severe and the risks of bleeding are deemed high. Most of the data used to determine bleeding risk come from retrospective studies of patients who are afebrile and have thrombocytopenia but not coagulopathy. Typical platelet count thresholds that are used for some common procedures are as follows:

L

Prevention of spontaneous bleeding

• We use prophylactic platelet transfusion to prevent spontaneous bleeding in most afebrile patients with platelet counts below 10,000/microL due to bone marrow suppression. We use higher thresholds (ie, 30,000/microL) in patients who are febrile or septic. Patients with acute promyelocytic leukemia (APL) have a coexisting coagulopathy, and we use a platelet transfusion threshold of 30,000 to 50,000/microL for them.

• Patients with platelet consumption disorders (eg, immune thrombocytopenia [ITP], disseminated intravascular coagulation) and platelet function disorders are typically transfused only for bleeding or, in some cases, invasive procedures. Platelets should not be withheld in bleeding patients with these conditions due to fear of "fueling the fire" of thrombus formation.

ORDERING PLATELETS

• Dose — A standard dose of platelets for prophylactic therapy in adults is approximately one random donor unit per 10 kg of body weight, which translates to four to six units of pooled platelets or one apheresis unit, both providing approximately 3 to 4 x 1011 platelets. A standard pediatric dose is 5 to 10 mL/kg. For prophylactic transfusion there is generally no reason to transfuse platelets more often than once a day. This platelet dosing is expected to raise the platelet count by approximately30,000/microL within 10 minutes of the infusion

Advantages of apheresis platelets

• Apheresis platelets have the advantages of limiting the recipient exposure to a single donor, which potentially reduces the possibility of infection and alloimmunization; some centers use apheresis platelets exclusively. Many believe it is logistically easier to perform bacterial testing on apheresis platelets compared with pooled platelets.

• Use of apheresis platelets also permits transfusion of platelets from specific donors selected based on HLA matching or platelet cross-matching, CMV status, and ABO group. Patients with confirmed immune mediated platelet refractoriness due to anti-HLA antibodies should receive HLA-matched platelets or platelets negative for the corresponding antigen(s) or cross-match compatible platelets; in other cases, either pooled and apheresis platelets can be used

Leukoreduction and Irradiation• Leukoreduction — Leukoreduction removes most of the

contaminating white blood cells (WBC) from the platelet transfusion . In some centers leukoreduction is standard practice. In other centers, leukoreduction is used for the following indications:

●Reduction of HLA alloimmunization●Reduction of CMV transmission●Reduction of transfusion-associated immunomodulation●Reduction of lung injury during and after cardiopulmonary bypass●Reduction of febrile nonhemolytic transfusion reactions (FNHTR)Irradiation — Platelet irradiation is used to prevent ta-GVHD,

• Irradiation — Platelet irradiation is used to prevent GVHD, in which contaminating WBCs attack host tissues and cause serious, even fatal, outcomes in both immunosuppressed and some immunocompetent individuals. Irradiation is not a substitute for leukoreduction, because lymphocytes inactivated by irradiation still express human leukocyte antigens (HLA) on their surfaces and can elicit an anti-HLA antibody response from the host. Irradiation is also inadequate to kill pathogens such as bacteria and viruses. Irradiation is used for the following indications

●Immunosuppression or imminent immunosuppression from hematopoietic cell transplant, solid organ transplant, and cytotoxic chemotherapy.●Congenital immunodeficiency (eg, DiGeorge syndrome, Wiskott-Aldrich syndrome, Leiner's disease, 5” nucleotidase deficiency). ●Fludarabine therapy.●Hodgkin lymphoma and other hematologic malignancies.●Neonatal exchange transfusion.●Premature, low birth weight neonates. ●Intrauterine transfusion.

• CMV — Some CMV seronegative transfusion recipients (eg, immunosuppressed patients) are at greater risk of adverse outcomes from receiving CMV-contaminated blood products than the general population. The AABB (formerly the American Association of Blood Banks) considers transfusion of platelets from CMV negative donors to be equivalent to leukoreduction in reducing this risk

• ABO, Rh, and HLA matching — Platelets express ABO antigens on their surface, as well as HLA class I antigens. They do not express Rh or HLA class II antigens.

• ABO and HLA compatible platelets appear to cause a greater platelet count increment in the recipient, and they can be used to improve responses in patients who have become refractory to platelet transfusion due to alloimmunization

• Although platelets do not express Rh antigens, platelet products contain small numbers of red blood cells (RBCs), which could be Rh incompatible with the recipient. Thus, when women of childbearing age receive a platelet transfusion, platelets from an Rh- donor are given to an Rh- recipient to prevent alloimmunization and hemolytic disease of the newborn.

• Infusion rate — For an average sized adult, six units of pooled platelets or one apheresis unit of platelets is transfused over approximately 20 to 30 minutes. Patients at risk for transfusion associated circulatory overload (TACO) can be transfused at a slower rate

• PLATELET COUNT INCREMENT — Following a platelet transfusion, the platelet count should rise, with a peak at 10 minutes to one hour and a gradual decline over 72 hours. A general rule of thumb is that transfusion of six units of pooled platelets or one apheresis unit should increase the platelet count by approximately 30,000/microLin an adult of average size

• Refractoriness to platelet transfusion can be separated into non-immune and immune causes (

• Approximately two-thirds of refractory episodes are due to non-immune causes, such as sepsis, fever, bleeding, splenomegaly, disseminated intravascular coagulation (DIC), hepatic sinusoidal obstruction syndrome (hepatic veno-occlusive disease), graft-versus-host disease (GVHD) and medications

• Twenty percent of cases have a combination of both immune and non-immune causes.

• Immune causes account for the remaining minority of cases and include alloimmunization to human leukocyte antigen (HLA) and/or platelet-specific antigens.

• DIAGNOSTIC APPROACH — Refractoriness to platelet transfusion is defined in this review as a platelet count response significantly less than expected to two or more platelet transfusions.

• Measuring response to platelet transfusion — Our pragmatic approach is to accept an immediate (within one hour) post-transfusion platelet count increment of>10,000/microL as an acceptable response. Our experience suggests that when evaluating a patient for refractoriness to platelet transfusion, a failure to achieve this cut-off of 10,000/microL on more than one occasion will truly define alloimmune refractoriness.

• The corrected count increment (CCI) has also been used to measure the response to platelet transfusion based on a platelet count obtained 10 minutes to one hour post-transfusion:

• CCI = [PPI x BSA (m2)] x 1011/ number of platelets transfused

• Pattern for non-alloimmune causes — A normal increment at one hour following transfusion (normal platelet recovery), with return to the baseline count within 24 hours (reduced platelet survival), is typical of the shortening of platelet survival seen with sepsis, following hematopoietic cell transplantation, disseminated intravascular coagulation (DIC), and possibly in bleeding patients and those taking medications that interfere with platelet survival. This type of pattern is not consistent with alloimmunization.

• Pattern for alloimmune causes — Little or no increment in platelet count (reduced platelet recovery), even within one hour of transfusion, is seen with alloimmunization. In general, a poor platelet increment should be demonstrated after at least two transfusions before entertaining the diagnosis of refractoriness secondary to alloimmunization

• MANAGEMENT OF THE ALLOIMMUNIZED PATIENT:• HLA-matched platelets • HLA-antigen negative "compatible" platelets • Crossmatch-compatible platelets • HPA antibodies against platelets • ABO matched platelets • Matched at HLA and ABO compatible: 76 percent

successful platelet transfusions• Matched at HLA and ABO incompatible or mismatched

at HLA and ABO compatible: 67 percent successful• Mismatched at HLA and ABO incompatible: 46 percent

successful

• Treatment of active bleeding — The acute management of bleeding in patients who have alloimmune platelet refractoriness can be difficult. The most dangerous complications are intrapulmonary or intracranial hemorrhage

●Antifibrinolytic agents ●Intravenous immune globulin ●Splenectomy ●Recombinant human factor VIIa - Anecdotal success has been reported using recombinant factor VIIa to arrest bleeding in an HLA alloimmunized thrombocytopenic patient refractory to transfusion with cross-match compatible platelets. While this represents an off-label use of this product, it may be a reasonable option as a temporary measure and/or last resort●Glucocorticoids : not usefull

Clinical therapy with plasma derived components

plasma products:●Fresh Frozen Plasma (FFP) ●Plasma Frozen Within 24 Hours After Phlebotomy (PF24) ●Thawed Plasma● Liquid Plasma ●Solvent/Detergent Plasma (S/D Plasma) ●Plasma Cryoprecipitate Reduced

Fresh frozen plasma

• frozen to -18 to -30°C within eight hours of collection

• usable for one year from the date of collection.

• Standard FFP units derived from a single unit of whole blood have a volume of approximately 200 to 250 mL;

• "FFP contains all of the coagulation factors and other proteins present in the original unit of blood, slightly diluted by the citrate-containing anticoagulant solution used to collect the blood.

Plasma Frozen Within 24 Hours After Phlebotomy (PF24)

frozen within 24 hours of collection (rather than eight hours for FFP) is a licensed product called PF24, or Frozen Plasma.

PF24 maintains all the clotting factors at the same levels as in FFP, except that factor VIII levels are in the range of 65 to 80 percent of normal and protein C is decreased.

Thawed Plasma

• Thawing – slow heating of FFP for refrigeration at 1 to 6°C reduces the expiration time to 5 days.

• stability of clotting factors other than factors V and VIII in Thawed Plasma is normal

• advantage • available for immediate use• a substantial reduction in the wastage of FFP or PF24

thawed for use and discarded when not transfused within the first 24 hours for rare blood groups AB

• Disadvantage:• Thawed Plasma should not be used as a predominant

source of either factor V or factor VIII, • its usefulness and safety in neonates is not yet known.

Solvent/Detergent-Treated Plasma (S/D Plasma)

• Treatment of pooled plasma prior to freezing with a solvent and a nonionic detergent inactivates a number of viruses with lipid envelopes, including HIV, hepatitis B virus, and hepatitis C virus.

• Non-lipid-enveloped viruses (eg, hepatitis A virus, parvovirus B19) are not inactivated by this process, nor are prions.

• The Solvent/Detergent (S/D) method is similar to that used to inactivate viruses in immune globulin and coagulation factors.

• S/D Plasma has similar levels of most clotting factors and similar hemostatic properties as standard FFP

Plasma Cryoprecipitate Reduced

• Plasma Cryoprecipitate Reduced is the plasma remaining after Cryoprecipitate has been removed. This product is also referred to as "Cryo-Poor Plasma.“

• Uses: • as plasma replacement in some patients with thrombotic

thrombocytopenic purpura.

• vitamin K deficiency or correction of major bleeding in the setting of warfarin anticoagulation because the removal of Cryoprecipitate from plasma does not deplete the vitamin K-dependent clotting factors

Indications of plasma

• Congenital Factor Deficiency• Invasive Procedure or Trauma (e.g. factor XI

Deficiency)• Emergency Warfarin Reversal– VitK

antagonists(INR>2)• Microvascular bleeding and elevated PT/PTT• Massive transfusions.

The only indication for Liquid Plasma is the initial treatment of patients who are undergoing massive transfusion because of life-threatening trauma/hemorrhages.Use of plasma infusion for congenital TTP (Upshaw-Shulman syndrome) and therapeutic plasma exchange for TTP due to an acquired inhbitor of of ADAMTS13use of S/D Plasma in liver transplantation

Plasma products should not be used as a source of protein or nutrients, or as a volume expander, because other plasma derivatives (eg, albumin, intravenous immunoglobulin) and/or solutions

(eg, crystalloid) can provide the needed components with a lower risk of plasma-related

complications (eg, infection, immunologic reaction, volume overload)

Cryoprecipitate . If a unit of FFP is allowed to thaw for 24 hours at 4ºC, a milky flocculum consisting of several cold insoluble globulins can be separated from the liquid plasma. These cryoprecipitable proteins include fibrinogen (factor I), antihemophilic factor (factor VIII), fibrin stabilizing factor (factor XIII) and von Willebrand factor (vWF), including the larger von Willebrand factor multimers thought to be important in the pathogenesis of thrombotic thrombocytopenic purpura (TTP).This cryoprecipitate, in a volume of 10 to 15 mL, is then refrozen at -18ºC for use up to one year. The residual cryoprecipitate-poor plasma can be frozen for transfusion (previously used for the treatment of TTP during plasma exchange therapy) or sent for further manufacture into albumin and gamma globulin.

Cryoprecipitate is useful for the replacement of fibrinogen and the treatment of uremic

bleeding in appropriate circumstances

Granulocyte transfusions

• INDICATIONS AND CLINICAL EFFICACY• MINIMAL CRITERIA● Absolute neutrophil count <500 cells/microL, except in the case of chronic granulomatous disease ●Evidence of bacterial or fungal infection (ie, clinical symptoms of infection, positive cultures, pathological diagnosis of infection from biopsies, radiographic evidence of pneumonia).●Unresponsiveness to antimicrobial treatment for at least 48 hours (except in extreme circumstances with life-threatening infection)

Neutropenia from chemotherapy or transplantation

• Most common indication• But• A Cochrane meta-analysis of eight randomized clinical

trials concluded that the available evidence was insufficient to either support or refute the generalized use of GTX therapy in the most common neutropenic patient populations (ie, myeloablative chemotherapy with or without hematopoietic stem cell support)

• Randomized, controlled clinical trial in patients with severe neutropenia was unable to accrue sufficient numbers of patients to detect a benefit

Aplastic anemia

• The only definitive cure is stem cell transplantation, but before it can be initiated, infection must be controlled. When bacterial or fungal infection is unresponsive to maximal antibiotic and/or antifungal therapy, GTX should be considered

Chronic granulomatous disease

• GTX has been used in patients who continue to deteriorate under maximum antimicrobial therapy. A number of small studies and case reports have documented the success of GTX in treating patients with chronic granulomatous disease with invasive aspergillosis

Neonatal sepsis

• Neonates with sepsis may become neutropenic due to an immature granulopoietic system. This population may also benefit from GTX. Three studies compared survival rates of septic neonates receiving GTX versus no transfusion or intravenous immune globulin (IVIG) therapy alone . They concluded that there may be some survival benefit with GTX. However, a Cochrane meta-analysis of randomized and quasi-randomized studies on the use of GTX to treat neonatal neutropenic sepsis concluded that there is still insufficient evidence for its benefit in this patient population

Prophylactic GTX

• Prophylactic GTX remains controversial due to the potential adverse effects of GTX

• A more recent trial, reported in 2006, demonstrated that the percent of patients developing fevers and the number of days of intravenous antibiotic use were significantly less in the GTX group, although there were no significant differences in length of hospitalization or 100-day survival.

DONOR ISSUES

• With the introduction of granulocyte colony stimulating factor (G-CSF) and corticosteroid-stimulated granulocyte collection, it is now possible to collect enough granulocytes from a single donor to produce a substantial increment in ANC in a neutropenic patient.

• Donor selection :• community donors and directed donors, such as

family members and friends of the patient• One study has suggested that there may be

benefit to utilizing community donors rather than directed donors [26]. The authors found that the time interval between the request for granulocytes and transfusion was significantly less in patients receiving granulocytes collected from community donors. These patients also benefited from higher ANC increments than those receiving donations from relatives

• Donor qualifications :• ABO and Rh matched to the recipient. Due to the

difficulties of separating the granulocyte layer and red blood cell (RBC) layer during the apheresis collection procedure, granulocyte concentrates are usually heavily contaminated with RBCs

• Tested negative for all blood transfusion-associated infectious disease markers within 30 days of granulocyte donation.

• No history of allergies to steroids or starch.• A history of hypertension, diabetes,

gastrointestinal ulcers, glaucoma, tuberculosis, or any fungal infections may be a contraindication to steroid administration.

Donor stimulation

• Although the standard dose of dexamethasone is 8 mg, there is variation in the dose of G-CSF across studies, ranging from 200 to 600 mcg. One study compared the efficacy of an 8 mg dexamethasone dose with either 450 or 600 mcg of G-CSF [51]. The granulocyte yields and side effects were comparable with both regimens. From an economic perspective, the lower G-CSF dose results in significant cost savings for the blood center

ADMINISTRATION OF THE TRANSFUSION AND DETERMINING RESPONSE

• Administration — We use premedication with acetaminophen (500 mg) and diphenhydramine (25 mg) to prevent or minimize transfusion reactions, which are more likely for granulocyte transfusion (GTX) than for transfusion of red blood cells.

• Granulocytes should only be transfused through a standard blood administration set containing a filter with a pore size of 170 microns. Transfusion should start slowly (eg, 2 mL/min), with close monitoring of vital signs, oxygen saturation, and signs and symptoms of complications

• If no transfusion reaction is observed, the infusion rate can be increased to a rate as fast as the patient can tolerate, but care must be taken to avoid circulatory overload in elderly patients. The product should be transfused in two to four hours.

• If the patient develops signs and symptoms of a transfusion reaction, the infusion should be stopped temporarily. The IV line should be kept open with normal saline, but the granulocyte product should not be discarded. The blood bank should be notified, the patient should be evaluated by a physician

• Determining recipient response :• The post-transfusion ANC increment can be

quite large in patients receiving granulocytes from granulocyte colony stimulating factor (G-CSF)- and corticosteroid-stimulated donors

• patients should be monitored for changes in signs and symptoms of the underlying infection by using microbial culture and imaging studies, as appropriate

• Criteria for stopping granulocyte transfusions●The clinical infection has been resolved based on clinical signs/symptoms, and laboratory/radiological test results.●The patient's ANC is above 500 for three days without GTX, which is a sign of bone marrow recovery.●The patient's clinical condition has worsened (ie, poor response to GTX), and the treatment plan has changed to palliative care with patient and family consent

COMPLICATIONS

• Transfusion reaction rates are higher in granulocyte transfusion (GTX) compared with red blood cell (RBC) transfusion, with 25 to 50 percent having mild to moderate reaction

• There is a 1 percent incidence of severe complication

• Pulmonary adverse reaction:• Moderate to severe pulmonary adverse reactions can

occur during GTX. Symptoms include varying degrees of cough, dyspnea, hypoxia, and changes on the chest radiographs:

• 5%• Transfusion-associated GVHD :• Transfusion-associated graft-versus-host disease (ta-

GVHD) is caused by viable functional donor lymphocytes present in granulocyte concentrates, which may mount an immunologic attack against the recipient. Although usually occurring in immunodeficient patients, ta-GVHD can develop in the presence of intact immunity

• We routinely irradiate our granulocyte concentrates with 2500 to 3000 rads prior to transfusion in order to eliminate this risk. This irradiation does not interfere with granulocyte function

Alloimmunization

• Alloimmunization is another potential risk of GTX.

• A retrospective review indicated that 17 percent of patients with severe aplastic anemia developed HLA antibodies during the course of GTX, and that patients with detectable HLA antibodies had lower post-GTX white blood cell increments

Infection

• Transfusion-transmitted diseases are just as important a consideration in GTX as with the use of any other blood transfusion. This is especially true of granulocytes, which must be transfused as soon as possible after collection, before completion of infectious disease testing