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Keywords:

  • clinical transfusion;
  • fresh frozen plasma;
  • guidelines;
  • platelets;
  • red cell;
  • transfusion trigger

Abstract

  1. Top of page
  2. Abstract
  3. Methods
  4. Recommendations
  5. Red cells transfusion
  6. Optimizing red cell transfusion in the peri-operative setting
  7. Leucocyte reduction of red cells
  8. Irradiation of blood components (red cells, platelets)
  9. Fresh frozen plasma
  10. Cryoprecipitate transfusion
  11. Disclosures
  12. References

Blood transfusion (which includes FFP, platelets, cryoprecipitate and any other blood-derived product) remains an important modality of treatment across all clinical disciplines. A blood transfusion is deemed appropriate when used in an evidence-based fashion and where the effects of the transfusion are felt to outweigh any potential risks and complications that may arise from the transfusion. In certain cases, it may be the best treatment option available, for example plasma exchange in thrombotic thrombocytopenic purpura. However, blood transfusion can result in acute or delayed complications, as well as the risk of transmission of infectious agents. The inappropriate use of blood and blood products increases the risk of transfusion-related complications and adverse events to recipients. It also contributes to shortages of blood products and the possibility of it not being available when required for other patients in an appropriate setting. It is therefore necessary to reduce the unnecessary transfusions through the appropriate clinical use of blood, avoiding unnecessary transfusions, and use of alternatives to transfusion.


Recommendations

  1. Top of page
  2. Abstract
  3. Methods
  4. Recommendations
  5. Red cells transfusion
  6. Optimizing red cell transfusion in the peri-operative setting
  7. Leucocyte reduction of red cells
  8. Irradiation of blood components (red cells, platelets)
  9. Fresh frozen plasma
  10. Cryoprecipitate transfusion
  11. Disclosures
  12. References

These are based on the current available data; in situations where there is lack of randomized data, published reports or recommendations from previous experiences are used.

Red cells transfusion

  1. Top of page
  2. Abstract
  3. Methods
  4. Recommendations
  5. Red cells transfusion
  6. Optimizing red cell transfusion in the peri-operative setting
  7. Leucocyte reduction of red cells
  8. Irradiation of blood components (red cells, platelets)
  9. Fresh frozen plasma
  10. Cryoprecipitate transfusion
  11. Disclosures
  12. References

The aim of red cell transfusion is to increase oxygen carrying capacity of blood by increasing haemoglobin concentration in patients with acute or chronic anaemia.

The decision to transfuse red cells should be carefully weighed on an individual basis, taking into consideration clinical evaluation of symptoms and haemodynamic status as well as laboratory parameters such as haemoglobin level. It is more relevant to consider the goal of red cell transfusion as the avoidance of tissue hypoxia rather than the correction of a laboratory parameter. In general, patients should not be transfused so as to achieve ‘normal’ haemoglobin (Hb) concentration [1,2]. Packed red cells should generally be provided for allogeneic transfusion where possible [3,4]. Packed red cells are preferred over whole blood to reduce the volume of transfusion and avoid the white cells/plasma that can potentially cause more febrile reaction and HLA sensitization, etc.

Transfusion trigger?

There is no standard fixed trigger for red cell transfusion. The trigger for transfusion should always be evaluated in the context of a multiplicity of factors including rate and amount of blood loss, cardiopulmonary reserve. The rate of development of anaemia is also an important factor.

The risks of transfusion need to be weighed against the perceived benefits as there are risks to every transfusion such as errors from transfusing incorrect blood product, bacterial contamination of blood products, etc.

In general, when haemoglobin is >10 g/dl, there is usually very little indication for red cell transfusion. When haemoglobin is <7 g/dl, red cells transfusion may be beneficial particularly in symptomatic patients or ongoing blood loss is expected [1,2,5–8]. In situations where the haemoglobin is between 7 and 10 g/dl, the decision to transfuse should be guided by clinical signs and symptoms, coexisting medical or surgical problems [1,2,5–8]. The clinician should avoid transfusion if the indication is unclear or there is minimal or weak evidence for benefit. Pre-operative transfusion is rarely required when Hb >10 g/dl and no differences have been found between patients who received transfusions to maintain their Hb >10 g/dl and those who received transfusions only when symptomatic or if Hb is below 8 g/dl [7,10,11,15–17].

Management of transfusion needs during acute blood loss (including trauma and gastrointestinal bleeding)

In acute blood loss, measurement of Hb level can be misleading due to haemoconcentration and therefore, should not be used as the sole indicator of the amount and severity of blood loss.

The clinical decision for blood transfusion depends on the estimation of blood loss, the rate of ongoing blood loss, the haemogloblin level prior to bleeding, evidence of end organ dysfunction and the risk of coronary artery disease. In assessing the need for transfusion, the physician should consider the percentage/volume of blood loss together with risk factors for patient to develop tissue ischaemia [9].

The source of bleeding should be identified early and appropriate action should be taken immediately, including endoscopic or surgical control of bleeding.

Red cells or plasma should not be used as volume expanders [1,7,9] and the initial volume replacement can be with colloids or crystalloids to ensure that the patient is euvolemic. Red cell transfusion is usually required when blood loss is estimated to be at least 30% of the total blood volume.

Optimizing red cell transfusion in the peri-operative setting

  1. Top of page
  2. Abstract
  3. Methods
  4. Recommendations
  5. Red cells transfusion
  6. Optimizing red cell transfusion in the peri-operative setting
  7. Leucocyte reduction of red cells
  8. Irradiation of blood components (red cells, platelets)
  9. Fresh frozen plasma
  10. Cryoprecipitate transfusion
  11. Disclosures
  12. References

Preoperative evaluation should be done in advance to avoid or minimize the need for transfusion. One should aim to identify and correct (where possible) risk factors for bleeding such as medications that can affect coagulopathy (e.g. use of warfarin, clopidogrel, aspirin) and the presence of congenital or acquired blood disorders such as haemophilia, ITP and liver cirrhosis.

Risk factors for organ ischemia (e.g. cardiorespiratory disease) should be identified which may influence the transfusion trigger for red blood cells.

Some useful measures to minimize blood transfusion requirement include:

  • 1
     Screening for unexpected pre-operative thrombocytopenia or an abnormal coagulation profile; if detected, the procedure should be postponed until the cause of the abnormality is identified [12–14]. A careful patient history should be elicited including a previous history of prolonged bleeding after surgery or dental procedure. These should be investigated further to rule out any bleeding diathesis.
  • 2
     All anti-platelet and anticoagulation therapies should be discontinued or reversed before the procedure. Aspirin and clopidogrel should be discontinued at least 7 days prior to planned surgery unless there is a strong contraindication for stopping it [12,13].Vitamin K or another warfarin antagonist should be used for reversal of warfarin to potentially avoid transfusion of FFP [12,13]. The effects of warfarin may last for several days depending on patient response and the administration of reversal agents (e.g. vitamin K, prothrombin complex concentrate, recombinant activated factor VII, or FFP) [13]. On a note of caution, the risk of thrombosis vs. the risk of increased bleeding should always be considered when altering anticoagulation status [13].
  • 3
     Consider administrating prophylactic pharmacologic agents that promote coagulation and minimize blood loss such as tranexamic acid) [13].
  • 4
     Correction of haemoglobin before surgery with measures other than red cell transfusion (e.g. iron replacement or erythropoietin) should be considered where appropriate [1,5,13,14]. Erythropoietin may be administered in anaemic patients to reduce the need for allogeneic blood in selected patient populations (e.g. chronic renal insufficiency, anaemia of chronic disease, refusal of transfusion) [1,5,13,14].
  • 5
     Explore ways to reduce allogeneic blood usage during surgery such as autologous blood donation, intra-operative haemodilution and intra-operative cell salvage [13,14].

Red cell transfusion in management of chronic anaemia

The decision to treat and correct chronic anaemia with red cells is less urgent due to compensatory mechanisms that have time to develop due to the chronicity of the disease process; haemodynamic shifts present in acute anaemia due to fluid depletion are usually not present. Most patients are well compensated at their level of anaemia and do not require red cell transfusion, especially at Hb >7 g/dl [1,2,5–7,14].

The cause of anaemia should therefore be established before red cell transfusion [1,5]. Red cell transfusion should be reserved for patients with significant signs and symptoms requiring medical intervention. In addition, the patient should be transfused to a level just above that needed to ameliorate the symptoms of anaemia [1,2,5–7,14].

Specific pharmacological agents (iron, vitamin B12, folate) should also be used to correct the anaemia to reduce exposure to allogeneic transfusion. Erythropoietin should be considered where indicated (e.g. chronic renal failure, anaemia of chronic illness, haematologic malignancies) [14,18] as it can lessen exposure to allogeneic blood and its attendant risks. Congenital Haemoglobinopathies, such as sickle cell disease, thalassemias are treated according to specific disease-related protocols [1,5].

Red cell transfusion in critical care setting

Critically ill patients should be maintained at a haemoglobin level between 7 and 9 g/dl [19–21]. Multicentre randomized clinical trials have shown that a restrictive strategy where haemoglobin was kept between 7 and 9 g/dl is as effective as and possibly superior to a liberal strategy where haemoglobin level was kept between 10 and 12 g/dl in critically ill patients [18–20]. There is no evidence to suggest that a higher haemoglobin level could reduce mortality at 30 days. This is both in the paediatric and adult settings.

Transfusion of leucodepleted or irradiated blood products

Platelet transfusions

The normal platelet count ranges around 140–450 × 109/l, although the normal ranges do differ between ethnic groups. Thrombocytopenia does not always correlate with abnormal bleeding; hence the decision for platelet transfusion should not be based on platelet counts alone but should take into consideration the clinical situation of the patient and other risk factors for bleeding. These include fever or sepsis, the presence of other associated coagulopathies, coexistent medical conditions including liver disease and renal failure and the rapidity of fall of the platelet count.

The major risk of platelet transfusion is bacterial contamination (1:10 000). Other risk factors include severe reactions as well as the potentially life-threatening TRALI. There is also the risk of HLA alloimmunization with platelet transfusions [33,34]. Platelet transfusions should be given as close to the procedure as possible for the best haemostatic effect. Platelet count levels should not be used as the only indicator for transfusion and the bleeding time may not be a good indicator for risk of bleeding [33]. The cause of thrombocytopenia should always be established before considering platelet transfusion unless there is life threatening bleeding.

If platelet transfusion is administered in certain conditions such as heparin-induced thrombocytopenia, thrombotic thrombocytopenic purpura or haemolytic uraemic syndrome, there can be possible exacerbation of the clinical situation [13,33,34]. In these conditions, platelet transfusion should only be given after the risks associated with transfusion have been considered and only when the benefits outweigh the risks.

Platelet product is available in two forms: apheresis platelet and the random platelet. Apheresis platelet is prepared from a single donor and contains at least 3·0 × 1011/l platelets suspended in 200–400 ml of plasma. Random platelet is prepared from units of whole blood collected from random donors and contains at least 5·5 × 109/l platelets suspended in 40–70 ml of plasma [35,36].

As ABO antigens are present on platelets, it is preferable to transfuse with ABO compatible platelets [34,37,38]. The concomitant administration of at least 250 IU of anti-D is recommended in case of transfusion of Rh(D) positive platelets to a Rh(D) negative patient to prevent Rh D allo-immunization [39–42]. Apheresis platelets are recommended to prevent HLA alloimmunisation and platelet refractoriness in patients who require prolonged platelet support [43–48].

An adult dose of platelet (1 unit of random donor platelet concentrate/10 kg body weight or one unit of apheresis platelets) should usually raise the platelet count by 20–40 × 109/l, if there are no other concomitant factors [36].

For critically ill patients with thrombocytopenia who are bleeding and where thrombocytopenia is considered as a major contributing factor, platelet transfusion is indicated regardless of the platelet count [49–52]. Platelet transfusion is indicated where platelet count is less than 50 × 109/l. In such patients, a higher platelet threshold should be considered if there is clinical evidence of microvascular haemorrhage [32,53–55]. For certain procedure at important anatomical sites such as intracranial or spinal and eye, the platelet count may need to be kept higher about 100 × 109/l. Platelet transfusion is indicated in patients undergoing cardiopulmonary bypass surgery where bleeding is associated with acquired platelet dysfunction; secondary to the bypass surgery or the presence of anti-platelet agents such as aspirin, ticlopidine or clopidogrel [13,34,56].

Platelet dysfunction can be caused by inherited conditions such as Glansmann’s Thrombasthenia and Bernard Soulier Syndrome. It can also be acquired in renal failure and in use of anti-platelet drugs such as aspirin and clopidogrel [34,57–59]. In these situations, the platelet count is less useful and the decision to transfuse should be based on clinical circumstances. Platelet transfusion should be given in the event of acute life threatening bleeds or just before major surgery. In renal failure and uraemia, the following recommendations should be implemented to avoid platelet transfusion if possible:

  • • 
    Correct the hematocrit to >0·30 [60,61]
  • • 
    Consider the use of desmopressin [34,62,63]
  • • 
    Consider the use of dialysis, which also have haemostatic benefits in this situation [64,65]
  • • 
    Only use platelet transfusions where the above methods are inappropriate or ineffective [34].

In drug-induced platelet dysfunction such as use of aspirin, NSAIDs or anti-platelet drugs, the following recommendations should be followed.

  • • 
    Discontinue drugs with anti-platelet activity where possible. [34]
  • • 
    Consider platelet transfusion in acute bleeding situation

Prophylactic platelet transfusion is recommended: (i) in patients with impaired bone marrow function when platelet count is less than 10 × 109/l and there are no other risk factors. [34,50,66–70], (ii) in patients with impaired bone marrow function when platelet count is less than 20 × 109/l and there are concomitant risk factors (e.g. sepsis, rapid fall of platelet count or coagulation abnormalities) [49,70–78].

The result of the recent PLADO study demonstrated that platelets given at the trigger level of 10 × 109/l did not have a significant effect on the bleeding tendency. The result of TOPPS study in UK which compares the efficacy of prophylactic with no prophylactic transfusion may guide us more on the role of prophylactic platelet transfusions in the future.

Patients with dengue fever who experience a rapid fall in platelet count or have prolonged clotting times, are thought to demonstrate a haemorrhagic state [79,80]. More liberal approach to prophylactic platelet transfusion should be practiced especially if the patient is having bleeding. A transfusion trigger at platelet count of 30 × 109/l is acceptable. Consultation with the haematologist or transfusion specialist is advised in individual cases where bleeding is thought to be a major risk factor [79,80].

Neurosurgical and ophthalmic procedures may benefit from a higher prophylactic platelet transfusion threshold (100 × 109/l) [34].

Leucocyte reduction of red cells

  1. Top of page
  2. Abstract
  3. Methods
  4. Recommendations
  5. Red cells transfusion
  6. Optimizing red cell transfusion in the peri-operative setting
  7. Leucocyte reduction of red cells
  8. Irradiation of blood components (red cells, platelets)
  9. Fresh frozen plasma
  10. Cryoprecipitate transfusion
  11. Disclosures
  12. References

One unit of red blood cells contains ≥108 white cells. The presence of leucocytes provides no benefit but is associated with various adverse effects such as non-haemolytic febrile transfusion reactions, CMV transmission and HLA alloimmunization.

Leuco-reduced red cell components are generally indicated in the following situations [22,23]:

  • 1
     Patients who have developed febrile non-haemolytic transfusion reactions on two or more occasions;
  • 2
     Immuno-compromised CMV-seronegative recipients at risk of CMV transmission via transfusion (where CMV negative blood products are unavailable), including: (i) patients undergoing stem cell transplants and (ii) premature infants and/or infants weighing <1200 g at birth.
  • 3
     Patients who are likely to require regular transfusions of blood and blood components to reduce the rate of human leucocyte (HLA) alloimmunisation

Irradiation of blood components (red cells, platelets)

  1. Top of page
  2. Abstract
  3. Methods
  4. Recommendations
  5. Red cells transfusion
  6. Optimizing red cell transfusion in the peri-operative setting
  7. Leucocyte reduction of red cells
  8. Irradiation of blood components (red cells, platelets)
  9. Fresh frozen plasma
  10. Cryoprecipitate transfusion
  11. Disclosures
  12. References

Transfusion-associated graft-versus-host disease is a rare but usually fatal complication mediated by viable T-lymphocytes in the transfused product. This condition is preventable by gamma irradiation of cellular blood components [23–25].

This is usually not a problem in the majority of individuals.

Irradiated blood and cellular components, however, are indicated in the following situations to prevent the development of this dreaded complication [22,26–31].

  • 1
     Haematopoietic stem cell transplant recipients (autologous or allogenic), from the time of conditioning chemotherapy onwards;
  • 2
     Haematopoietic stem cell transplant donors (autologous or allogenic) would require irradiated blood products during the period from 7 days prior to stem cell harvesting till completion of harvesting;
  • 3
    Intrauterine transfusions;
  • 4
     Neonatal exchange transfusion subsequent to intrauterine transfusions;
  • 5
     Patients currently or previously treated with the following medications: (i) Purine analogue drugs such as Fludarabine, Cladribine, Deoxycoformicin and Clofarabine, (ii) Campath (Alemtuzimab) and (iii) Anti-thymocyte Globulin (ATG)
  • 6
     Patients with suspected or confirmed congenital T-cell immune deficiency disorders;
  • 7
     Recipients of donor units known to be from a first or second degree blood relative;
  • 8
     Human leucocyte antigen (HLA) compatible blood components and
  • 9
    All granulocyte products.

Irradiated blood and cellular components are also recommended in the following situations provided this does not cause a clinically significant delay in the red cell transfusion [22,26–31]:

  • 1
    Patients with Hodgkin’s disease;
  • 2
    Neonates undergoing exchange transfusion
  • 3
     Patients with newly diagnosed aplastic anaemia who are likely to undergo a bone marrow transplant.

Fresh frozen plasma

  1. Top of page
  2. Abstract
  3. Methods
  4. Recommendations
  5. Red cells transfusion
  6. Optimizing red cell transfusion in the peri-operative setting
  7. Leucocyte reduction of red cells
  8. Irradiation of blood components (red cells, platelets)
  9. Fresh frozen plasma
  10. Cryoprecipitate transfusion
  11. Disclosures
  12. References

Fresh frozen plasma is prepared either from whole blood donations or from plasma collected by apheresis and contains near-normal plasma levels of coagulation factors, albumin and immunoglobulins [81]. Its use should be limited to the replacement of coagulation factors and there are limited situations where this becomes necessary [82]. The availability of factor concentrate replacement is virally treated and is safer than FFP as factor replacement.

Routine and timely tests for coagulopathy such as the prothrombin time (PT) or international normalized ratio (INR), activated partial thromboplastin time (aPTT) platelet counts and fibrinogen level as well as haemoglobin/haematocrit should be obtained to guide decisions on plasma transfusion [54]. These results should be integrated with a thorough assessment of the patient’s clinical condition and the presence or risk of bleeding. Abnormal PT/INR or aPTT results should not be the sole reason for transfusing plasma as they do not correlate well with bleeding risk and only a small proportion of patients with abnormal results will experience bleeding manifestations [83–85]. All attempts must be made to identify the underlying cause of a coagulopathy and manage this appropriately together with efforts to correct such abnormality with plasma transfusion if necessary.

A comprehensive personal and family history of bleeding is the best pre-operative screen for bleeding in surgical patients. In the event that pre-operative PT and PTT tests are performed and found to be abnormal, its significance should be carefully considered and if necessary, further discussed with a haematologist.

Fresh frozen plasma is recommended for massive blood transfusion, especially with evidence of microvascular bleeding and associated with significant (>1·5× midpoint of normal range) abnormalities in prothrombin time (PT) and activated partial thromboplastin time (APTT). When PT and APTT cannot be obtained in a timely fashion, it is reasonable to give FFP after replacement of one blood volume while waiting for results [86].

If immediate reversal of warfarin effect is required, intravenous vitamin K should be concurrently given for sustained reversal of warfarin effect [87,88]. FFP is also indicated in acute disseminated intravascular coagulation (DIC) associated with microvascular bleeding and abnormal coagulation profile [89,90] and bleeding due to coagulopathy associated with chronic liver diseases. For plasma exchange in thrombotic thrombocytopenic purpura (TTP) and haemolytic uraemic syndrome (HUS), FFP is indicated as the medium for replacement. Cryosupernatant may also be considered as an alternative [91–93]. FFP is also indicated for bleeding associated with clotting factors deficiency if no alternative processed products or specific factor concentrates are available [2,90].

The recommended dose for FFP is 10–15 ml/kg body weight [90]. It is always useful to have FFP administration guided by coagulation screens. If necessary, these should be repeated and more FFP given, depending on the clinical situation [90].

Cryoprecipitate transfusion

  1. Top of page
  2. Abstract
  3. Methods
  4. Recommendations
  5. Red cells transfusion
  6. Optimizing red cell transfusion in the peri-operative setting
  7. Leucocyte reduction of red cells
  8. Irradiation of blood components (red cells, platelets)
  9. Fresh frozen plasma
  10. Cryoprecipitate transfusion
  11. Disclosures
  12. References

Cryoprecipitate is rich in factor VIII, von Willebrand factor, factor XIII and fibrinogen [1]. Use of cryoprecipitate is considered appropriate when there is bleeding associated with hypofibrinogenaemia (fibrinogen level <1·0 gm/l) in conditions such as massive transfusion, DIC, open heart surgery, factor XIII (when factor XIII concentrate is not available) etc.

In the management of hypofibrinogenaemia, 1 unit/5 kg body weight – equivalent to 10 units for an average size adult – should be administered. Further therapy should be guided by fibrinogen levels [90,94–96].

References

  1. Top of page
  2. Abstract
  3. Methods
  4. Recommendations
  5. Red cells transfusion
  6. Optimizing red cell transfusion in the peri-operative setting
  7. Leucocyte reduction of red cells
  8. Irradiation of blood components (red cells, platelets)
  9. Fresh frozen plasma
  10. Cryoprecipitate transfusion
  11. Disclosures
  12. References