CPGL Source

Recommendation

SoR

QoE

Pre-transfusion testing

NT.1. What are the samples required for pre-transfusion testing in neonates?

BSH 2020b

Within the first 4 months, wherever possible, samples from both mother and infant should be obtained for initial ABO and D group determination. The antibody screen should be undertaken on the maternal sample when available. A maternal sample is preferred for antibody testing for the following reasons:

·     If maternal antibody has bound to fetal cells in vivo, the resulting lower concentration of antibody in neonatal plasma could lead to a false negative antibody screen result.

·     It is easier to obtain a sufficiently large sample from the mother to allow for screening and antibody identification if required.

·     Sample collection from the infant exacerbates the anaemia of prematurity.

The maternal sample should be collected within 3 days predelivery or collected post-delivery.

GPS

Red cell transfusion

NR.1. What are the indications and thresholds for transfusion of packed red cells in acute ill neonate without other comorbid conditions?

BSH 2020b

Studies to date support restrictive transfusion thresholds (2B) and suggested Hb thresholds for top-up transfusions are given in Table 1.

*Standard definition of preterm is <37 weeks gestational age at birth but table applies to very preterm neonates (<32 weeks).

†It is accepted that clinicians may use up to 85 g/dl depending on clinical situation.

‡NIPPV, non-invasive positive pressure ventilation.

Table 1 does not include suggested thresholds for moderate to late preterm (≥32 weeks gestational age at birth) or term neonates, as there is little evidence regarding the appropriate thresholds for these groups. Clinicians may consider similar thresholds to those used for preterm babies off oxygen.

Intermediate

Strong

NR.2. What are the indications to transfuse packed red cells in acute ill neonate with neonatal sepsis?

Villeneuve et al 2020 ³¹

Decision of transfusion is based on the clinical status.

For those not requiring cardiopulmonary support or oxygen supply and condition is stable, transfusion is not usually required unless Hb level is below 7g/dl.

GPS

NR.3. What is the volume required for red cell transfusion in neonates?

BSH 2020b

Transfusion volumes of 15 ml/kg are generally recommended for non-bleeding neonates.

Intermediate

weak

BSH 2020b

Repeated small volume ‘red cell transfusions (up to 20 mL/kg) are commonly carried out in preterm babies, mainly to replace losses from repeated blood testing exacerbated by reduced red cell production (‘anaemia of prematurity’).

Intermediate

Strong

NR.4. What are the characteristics of red cells used for exchange transfusion in neonates?

BSH 2020b

-   A specific red cell component for neonatal exchange transfusion, usually group O, and should also be compatible with any maternal antibody.

-   Red cells suitable for neonatal exchange need to be irradiated and ‘fresh’ (before the end of Day 5 following donation, with a 24-h shelf-life post-irradiation in order to reduce the risk of recipient hyperkalaemia. They have a controlled hematocrit 0.5–0.6. They are negative for high-titre anti-A and anti-B antibodies.

-   Exchange blood transfusion (EBT) should not be undertaken with red cells straight from 4°C storage, and an approved blood-warming device can be used to avoid hypothermia. The use of a blood warmer is only appropriate if the infusion is given at a constant rate (warming is not suited to the intermittent bolus nature of a single vessel EBT where the ‘push-pull’ cycle method is used). Blood warming during EBT should not be uncontrolled, e.g., infusion lines exposed to a radiant heater, because of the risk of red cell hemolysis.

GPS

Platelets

NP.1. What are the indications and thresholds for platelet transfusion in neonates?

BSH 2020b

In Preterm neonate

-   For preterm neonates with very severe thrombocytopenia (Platelet count below 25 × 10⁹/l) platelet transfusions should be administered in addition to treating the underlying cause of the thrombocytopenia

Intermediate

Weak

BSH 2020b

In full-term neonate

-   For non-bleeding neonates, platelet transfusions should not be routinely administered if platelet count is ≥ 25 × 10⁹/l.

High

Strong

BSH 2020b

-   If Platelet count < 25× 10⁹/l transfuse in Neonates with no bleeding

-   If Platelet count < 50× 10⁹/l transfuse in Neonates with bleeding, current coagulopathy, before surgery, or infants with FNAIT if previously affected sibling with ICH.

-   If Platelet count < 100× 10⁹/l transfuse in Neonates with major bleeding or requiring major surgery (e.g., neurosurgery)

Intermediate

Intermediate

Intermediate

Weak

Weak

Weak

NNF 2020

In antibody mediated thrombocytopenia

-   In neonatal alloimmune thrombocytopenia (FNAIT), maintaining platelet count > 30 x10⁹/l is strongly recommended.

High

Weak

NNF 2020

In preterm neonate with PDA

-   The routine use of platelet transfusion for PDA closure in thrombocytopenic preterm neonates with PDA is not recommended.

Intermediate

weak

NP.2. What is the dose and rate for platelet transfusion in neonates?

BSH 2020b

Typical transfusion volume: 10–20 ml/kg

Transfusion rate: 10–20 ml/kg/h

GPS

NP.3. Is ABO compatibility required for platelet transfusion in neonates?

BSH 2016b

ABO, Rh matched platelets should be used when available to maximize increments

Intermediate

Weak

BSH 2016b

It is acceptable to use ABO incompatible platelets to reduce wastage. Platelets tested and negative for high titre haemagglutinins and non-group O platelets are associated with a lower risk of haemolysis.

High

Strong

Fresh Frozen Plasma (FFP)

NF.1. What are the therapeutic indications of fresh frozen plasma transfusion (FFP) in neonates?

BSH 2020b

FFP may be of benefit in neonates with clinically significant bleeding (including massive blood loss) or prior to invasive procedures with a risk of significant bleeding, and who have an abnormal coagulation profile, defined as a PT or aPTT significantly above normal gestational and postnatal age-related reference range. (Considering local reference ranges where available).

Intermediate

Weak

BSH 2020b

FFP is appropriate for the early management of severe hereditary protein C deficiency but should not be used in preference to protein C concentrate if this is available.

Intermediate

Strong

BSH 2020b

FFP should be used for the management of severe hereditary protein S deficiency.

Intermediate

Strong

BSH 2020b

Management of DIC, inherited deficiency of clotting factors, vitamin- K deficiency bleeding (prothrombin complex concentrates are preferable to FFP).

Intermediate

Weak

BSH 2018 – ad 2020

If virally inactivated specific clotting factors are not available, pathogen-reduced plasma may be used for factor replacement in congenital coagulation factor deficiency.

High

Weak

NNF 2020

FFP transfusion is preferred over cryoprecipitate in the management of disseminated intravascular coagulation.

Intermediate

Weak

BSH 2020b

Where indicated, cryoprecipitate may be used if there is persistent hypofibrinogenemia (<1.0 g/L) despite FFP transfusion, or in conjunction with FFP for very low or rapidly falling fibrinogen.

Intermediate

Weak

NF.2. What are the prophylactic indications of fresh frozen plasma transfusion in neonates?

NNF 2020

The routine use of prophylactic FFP in preterm neonates is not recommended.

High

Weak

NNF 2020

Prophylactic FFP is not recommended in non-bleeding neonates receiving therapeutic hypothermia and having deranged coagulation parameters

High

Strong

NNF 2020

Neonates with deranged coagulation parameters and planned for surgical or invasive procedures should receive FFP.

High

Weak

NF.3. What are the indications of fresh frozen plasma transfusion in neonatal emergency?

NNF 2020

FFP 15–20 ml/kg given 8–12 hourly may be used as first line therapy to treat acquired neonatal purpura fulminans in association with protein C or protein S deficiency while the underlying cause is being investigated. The underlying cause should be treated, and it may be helpful to monitor PC/PS levels.

GPS

NF.4. What are the contraindications to plasma transfusion in neonates?

NNF 2020

There is no evidence to support the routine use of FFP to try to correct abnormalities of the coagulation screen alone in non-bleeding neonates.

Intermediate

Weak

NNF 2020

Prophylactic FFP is not recommended in non-bleeding neonates receiving therapeutic hypothermia and having deranged coagulation parameters.

High

Strong

NNF 2020

FFP should not be used in the management of inherited factor deficiencies other than in a few exceptional circumstances where specific factor concentrates are not available.

High

Strong

NNF 2020

FFP should not be used for simple volume replacement or routinely for prevention of intraventricular hemorrhage.

Intermediate

Weak

NNF 2020

FFP should not be used for performing a partial exchange transfusion for polycythemia

GPS

NF.5. What is the dose and rate of plasma transfusion in neonates?

BSH 2018 – ad 2020

For patients who have abnormal clotting tests and other factors (i.e., personal/family bleeding history, drug history, bleeding risk associated with planned procedure or thrombocytopenia) that indicate a significant bleeding risk during a procedure, then a starting dose of 15 ml/ kg of FFP can be considered.

High

Strong

BSH 2018 – ad 2020

For the first 15 minutes: 1 mL/kg/hr.; reassess patient, if well tolerated increase rate as per Physician’s order (this is recommended “test dose, slow rate of infusion”). Usual rate: 10 to 20 mL/kg/hr.

GPS

CPGL Source

Recommendation

SoR

QoE

Packed Red Blood Cells (PRBCs)

I.  Indications

PR.1. What are the indications and thresholds of red cell transfusion in different paediatric diseases?

BSH 2016b

In children with cancer

•  There is insufficient evidence to make recommendations for pre-transfusion Hb thresholds in paediatric haematology/ oncology patients and those undergoing stem cell transplantation.

Intermediate

Weak

•  In children with oncologic diagnoses who are critically ill or at risk for critical illness, and hemodynamically stable, an Hb concentration of 7– 8 g/dl is suggested as a threshold for RBC transfusion.

Intermediate

Weak

BSH 2016b

In children with pure red cell aplasia

•  Patients with chronic anaemia due to red cell aplasia may require an Hb threshold of 8 g/dl.

Intermediate

Weak

BSH 2016a

In children with sickle cell disease

•  Transfusion is recommended and may be lifesaving in acute sickle complications such as splenic sequestration, hepatic sequestration, aplastic crisis and severe acute chest syndrome

High

Strong

BSH 2016a

•  Simple transfusion to steady state haemoglobin concentration is indicated for patients with acute exacerbation of anaemia as a result of aplastic crisis or sequestration crisis.

•  Over-transfusion (to Hb > 8 g/dl) should be avoided in sequestration crises because of the risk of hyperviscosity due to the re-entry of sequestered red cells into the circulation.

High

Strong

BSH 2016a

•  There is no evidence that transfusion shortens the duration of a painful crisis. Transfusion is not recommended in uncomplicated painful crises but should be considered if there is a substantial drop in Hb from baseline (e.g., >2 g/dl or to Hb <5 g/dl), haemodynamic compromise or concern about impending critical organ complications.

High

Weak

BSH 2016a

•  Transfusion should be considered in the unwell patient with acute multi-organ failure, mesenteric syndrome (1C) and patients with severe sepsis (2C).

High

Intermediate

Weak

Weak

BSH 2016a

•  Transfusion is recommended in cases of acute chest syndrome with hypoxia. Transfusion may be given by simple or exchange transfusion depending on clinical severity under the guidance of the specialist haemoglobinopathy team.

High

Strong

BSH 2016a

•  Adults or children with signs or symptoms suggestive of acute ischaemic stroke should be transfused to sickle haemoglobin (HbS) <30% pending further investigation. Those with confirmed stroke due to sickle cell disease should continue regular transfusions indefinitely.

High

Strong

BSH 2016a

•  Transfusion is not recommended to treat steady state anaemia provided that Hb has not fallen over a period of time to symptomatic levels (e.g., with developing chronic kidney disease).

High

Weak

TAXI 2018

In critically ill children admitted to PICU

•  In critically ill children or those at risk for critical illness, who are hemodynamically stable and who have an Hb concentration ≥ 7 g/dl, we recommend not administering a RBC transfusion.

High

Strong

TAXI 2018

•  When deciding to transfuse an individual critically ill child, consider not only the hemoglobin (Hb) concentration, but also the overall clinical context (e.g. symptoms, signs, physiological markers, laboratory results) and the risk, benefits, and alternatives to transfusion.

GPS

TAXI 2018

•  In critically ill children or those at risk for critical illness, we recommend measuring the hemoglobin (Hb) concentration before prescribing each RBC transfusion; knowledge of Hb concentration is not required before RBC transfusion if the patient has life threatening bleeding.

GPS

BSH 2016b

In the preoperative setting

•  A perioperative Hb transfusion threshold of 7 g/dl should be used in stable patients without major co-morbidity or bleeding.

High

Weak

PR.2. What are the definitions and precautions of transfusion with massive blood loss?

BSH 2016b

Massive blood loss (MBL) may be defined as either 80 ml/kg in 24 h, 40 ml/kg in 3 h or 2–3 ml/kg/min.

In clinical practice, haemodynamic changes compatible with hypovolaemia accompanying evidence or suspicion of serious haemorrhage are the usual triggers.

GPS

BSH 2016b

Key principles in MBL are:

1     Early recognition of children at risk of MBL using clinical parameters.

2     Education of staff to understand when to activate/trigger the local major haemorrhage protocol.

3     Active resuscitation and control of bleeding.

4     Seek specialist assistance.

5     Rapid provision of O D-negative or group specific red cells.

6     Prescribe all transfused components in ml/kg bodyweight (for children <50 kg) and not as units.

7     Anticipate and treat coagulopathy and thrombocytopenia in trauma with early use of FFP and consideration of platelets and cryoprecipitate in on-going bleeding.

8      Use tranexamic acid in trauma.

9     Avoid hypothermia, hypocalcaemia, acidosis and hyper-kalaemia.

Appropriate aliquots to be transfused are as follow:

-  RBCs 20 ml/kg aliquots (maximum four adult units), D-negative or ABO and D-specific (ideally, cross-matched)

-  Group specific FFP in 20 ml/kg aliquots (maximum four adult units)

-  Platelets in 15–20 ml/kg aliquots (maximum one adult therapeutic dose) to be considered after every 40ml/kg RBCs

-  Cryoprecipitate 10 ml/kg (maximum two pools)

Initial immediate transfusion of 20 ml/kg RBCs should be given (up to four adult units).

There was no difference between early administration of plasma, platelets and RBCs in a 1:1:1 ratio and in a 1:1:2 ratio³². A ratio of at least 1 FFP:2 RBC is recommended in early resuscitation of major haemorrhage (in major trauma clinicians may consider aiming for a ratio of 1 FFP:1 RBC). Platelets and cryoprecipitate must be considered if active bleeding persists after initial resuscitation.

These aliquots should be repeated in recommended ratios as necessary until bleeding is controlled. Ratios should be modified accordingly once laboratory parameters are available.

The therapeutic aims should be Hb 8 g/dl, fibrinogen > 1.5 g/l, PT ratio < 1.5, platelet count > 75x10⁹/l. Careful monitoring for adequacy of resuscitation and for circulatory overload is essential.

GPS

II. Volume and rate of PRBCs transfusion

PR.3. What is the best way of ordering volume of PRBCs in children?

Prescription of blood components for paediatric transfusion should be in millilitres unless there are local risk-assessed protocols for prescribing in units for older children, and the maximum volume should not be greater than prescribed for adults.

High

Weak

PR.4. What is the volume and rate of PRBCs transfusion in in acute ill children?

In a non-bleeding infant or child, it is important to take into account the pre-transfusion Hb in relation to the transfusion threshold, and it is recommended that a post-transfusion Hb no more than 2 g/dl above the threshold be aimed for.

GPS

Transfusion rate 5 ml/kg/h (usual maximum rate: 150 ml/h)

GPS

PR.5. What is the transfusion volume for regular transfusion in transfusion-dependent thalassemia in chronic transfusion program?

TIF 2021*³³

(Desired – actual Hb (g/dl)) x weight (kg) x 3 = ml to be transfused assuming the haematocrit of the unit is 0.58.

GPS

PR.6. What are the standards for PRBCs transfusion in transfusion-dependent thalassemia?

UK Thalassaemia Society clinical standards³⁴

·   Blood must be ABO compatible and antigen negative for any clinically significant antibodies the patient is known to have, or to have had previously identified even if not currently detectable. It should be fully matched for all the Rh antigens and K.

·   Units should be less than 2 weeks old and, in adults, of larger volume where possible.

·   There should be a clear record of patient’s transfusion requirements outlining volume, frequency and target haemoglobin.

·   Transfusions will be given on each occasion in a designated age-appropriate area with suitable facilities, experienced regular named nurses and familiar supervising medical team.

Pre-arranged transfusions should be started within 30 minutes of the patient’s arrival.

GPS

BSH 2016b

Patients with transfusion-dependent anaemia and sickle cell

disease should preferably have extended red cell phenotyping or genotyping (D, C, c, E, e, K, Fya, Fyb, Jka, Jkb, M, N, S and s) prior to transfusion and, as a minimum, red cells should be matched for Rh (D, C, c, E, e) and K antigens.

GPS

Bowden 1995³⁵

Pre-storage leukodepletion of cellular blood products achieving a residual leukocyte count < 5 x 10⁶ per unit allows the reduction of CMV transmission to a level at least equivalent to the transfusion of sero-negative blood components for those patients at major risk of severe CMV transfusion-associated disease.

GPS

Platelets

PP.1. What are the indications for platelet transfusion in infants and children during acute bleeding?

In non-immune thrombocytopenia

BSH 2016b

•  In severe bleeding, maintain the platelet count above 50 ×10⁹ /l. Consider empirical use for the initial management of major haemorrhage.

High

Weak

BSH 2016b

•  In patients with multiple trauma, traumatic brain injury or spontaneous intracerebral haemorrhage, maintain the platelet count above 100 ×10⁹ /l

Intermediate

Weak

BSH 2016b

•  In patients with bleeding that is not considered severe or life-threatening, consider platelet transfusion if the platelet count is below 30 ×10⁹ /l

Intermediate

Weak

In immune thrombocytopenia

BSH 2016b

•  In ITP, consider co-administration of intravenous immunoglobulin in addition to the platelet transfusion

Intermediate

Weak

BSH 2016b

•  In post-transfusion purpura (PTP), intravenous immunoglobulin is the treatment of choice

High

Weak

BSH 2016b

•  Give therapeutic platelet transfusions (more than one dose) to treat serious bleeding

High

Weak

BSH 2016b

•  Only use platelet transfusion prior to a procedure or surgery when other treatment has failed and/or the intervention is urgent. Usual threshold counts may be unachievable or unnecessary and individual case review is required

High

Weak

In Platelet Function Disorders (Congenital)

BSH 2016b

•  If pharmaceutical therapies are contraindicated, ineffective or if there is high risk of bleeding, consider transfusion of platelets. In Glanzmann thrombasthenia, consider human leucocyte antigen (HLA)-matched platelets (2C) where available (GPS).

Intermediate

Weak

In drug- induced Platelet Function Disorders (Acquired)

BSH 2016b

•  Do not use platelet transfusion pre-procedure when antiplatelet agents have not been discontinued

Intermediate

Weak

BSH 2016b

•  Use general haemostatic measures to treat bleeding in patients during treatment with aspirin, P2Y12 antagonists or glycoprotein IIa/IIIb inhibitors. If necessary, consider drug cessation and reversal of the effect of co-prescribed anticoagulants

Intermediate

Weak

BSH 2016b

•  Use TXA to counteract the effect of anti-platelet agents when a risk/benefit assessment would support this

High

Strong

BSH 2016b

•  Consider the use of platelet transfusion as an additional measure to those suggested above for critical bleeding

Intermediate

Weak

PP.2. What are the indications for prophylactic platelet transfusion?

BSH 2016b

In critically ill child

•  Use the platelet count thresholds for reversible bone marrow failure as a general guide for prophylactic platelet transfusion in patients with critical illness in the absence of bleeding or planned procedures.

Intermediate

Weak

BSH 2016b

In autoimmune thrombocytopenia (ITP)

•  Do not use prophylactic platelet transfusions in patients with autoimmune thrombocytopenia

High

Weak

In reversible bone marrow failure (receiving intensive chemotherapy or undergoing allogeneic haematopoietic stem cell transplant (HSCT)

BSH 2016b

•  Give prophylactic platelet transfusions to patients to maintain a platelet count at or above 10 x 10⁹/l

High

Strong

BSH 2016b

•  Use only one adult dose (one unit) routinely for prophylactic platelet transfusions

High

Strong

BSH 2016b

•  Consider increasing the threshold for prophylactic platelet transfusion to between 10 and 20 x 10⁹/l /l in patients judged to have additional risk factors for bleeding. Individual review is required.

Intermediate

Weak

In chronic bone marrow failure (when recovery is not anticipated)

BSH 2016b

•  Use a ‘no prophylactic platelet transfusion’ strategy for asymptomatic patients with chronic bone marrow failure.

Intermediate

Strong

BSH 2016b

•  Give prophylactic platelet transfusions to patients with chronic bone marrow failure receiving intensive treatment.

High

Strong

BSH 2016b

•  Manage patients with chronic bleeding of WHO grade 2 or above individually (see implementation tools) , according to the severity of their symptoms and signs. Consider a strategy of prophylaxis (e.g., twice a week).

Intermediate

Weak

Prior To Procedures or Surgery:

BSH 2016b

•  Do not give platelet transfusions routinely prior to:

-        bone marrow aspirate or trephine biopsy

-        peripherally inserted central catheters (PICCs)

-        traction removal of tunneled CVCs

-        cataract surgery

High

Inter. Inter. Inter.

Weak Weak

Weak

Weak

BSH 2016b

•  Whenever possible use a procedure/equipment associated with the lowest bleeding risk. Apply local measures, such as compression, to reduce the risk of bleeding post-procedure

High

Weak

Prior To Procedures or Surgery

BSH 2016b

Consider performing the following procedures above the platelet count threshold indicated:

BSH 2016b

•  venous central lines (both tunneled and un-tunneled), inserted by experienced staff using ultrasound guidance techniques, when the platelet count is >20 ×10⁹ /l

High

Weak

BSH 2016b

•  lumbar puncture when the platelet count is ≥40 ×10⁹/l.

Inter.

Weak

BSH 2016b

•  insertion/removal of epidural catheter when the platelet count is ≥80 ×10⁹/l.

Inter.

Weak

BSH 2016b

•  major surgery – when the platelet count is >50×10⁹/L

High

Weak

BSH 2016b

•  neurosurgery or ophthalmic surgery involving the posterior segment of the eye when the platelet count is >100×10⁹ /l

High

Weak

BSH 2016b

•  percutaneous liver biopsy when the platelet count is >50 ×10⁹/l. Consider trans-jugular biopsy if the platelet count is below this level

Inter.

Weak

PP.3. What is the dose and rate for platelet transfusion?

BSH 2020b

Typical transfusion volume:

•  10–20 ml/kg for children <15 kg, or a single pack for children ≥15 kg

•  maximum volume 1 pack

Transfusion rate: 10–20 ml/kg/h

GPS

PP.4. What are the contraindications of platelet transfusion?

BSH 2016b

In patients with thrombotic microangiopathies only use platelet transfusions to treat life-threatening bleeding.

High

weak

PP.5. How to avoid/ manage the risks of platelets transfusion?

BSH 2016b

Hospitals should establish a strategy to maximize the transfusion of ABO compatible platelets, especially to patients who require regular platelet support

Intermediate

Strong

BSH 2016b

ABO, Rh matched platelets should be used when available to maximize increments

Intermediate

Weak

BSH 2016b

It is acceptable to use ABO incompatible platelets to reduce wastage. Platelets tested and negative for high titre haemagglutinins and non-group O platelets are associated with a lower risk of haemolysis. Pooled platelets suspended in Platelet Additive Solution (PAS) would also be expected to reduce this risk.

High

Strong

BSH 2016b

RhD negative girls or women of childbearing potential should receive RhD negative platelets. If unavailable, RhD positive platelets can be given with anti-D prophylaxis.

High

Strong

BSH 2016b

For RhD negative boys under 18 years of age, those who already have anti-D antibodies, and transfusion-dependent adults, the platelets of choice are RhD negative. RhD positive platelets should be given if RhD negative platelets are unavailable or to prevent wastage of RhD positive components. Anti-D prophylaxis is not required

High

Strong

BSH 2016b

In patients with a history of allergic transfusion reactions, apart from mild, use platelets suspended in PAS. If reactions continue or are severe, washed platelets (resuspended in 100% PAS) may be required

High

Strong

BSH 2016b

Patients with hypoproliferative thrombocytopenia who are refractory to platelet transfusions and have class I HLA antibodies should receive class I HLA-selected platelet transfusion

Intermediate

Weak

BSH 2016b

Patients with hypoproliferative thrombocytopenia who continue to be refractory to HLA-selected platelet transfusions and have human platelet antigen (HPA) antibodies should receive HPA-selected platelet transfusion

Intermediate

Weak

BSH 2016b

Patients with hypoproliferative thrombocytopenia who are not refractory to platelet transfusion may not receive HLA-selected or HPA-selected platelets

Intermediate

Weak

Fresh Frozen Plasma

PF.1. What are the indications for plasma transfusion during acute bleeding in paediatrics?

BSH 2018 –
ad 2020

Pathogen-reduced plasma may be used for factor replacement in congenital coagulation factor deficiency If virally inactivated specific clotting factors are not available.

High

Weak

BSH 2016b

FFP may be beneficial in children with DIC who have a significant coagulopathy (PT/APTT >1.5 times midpoint of normal range or fibrinogen <1.0 g/l) associated with clinically significant bleeding or prior to invasive procedures

Intermediate

Weak

BSH 2016b

In DIC, cryoprecipitate may be given if the fibrinogen is < 1.0 g/l despite FFP, or in conjunction with FFP for very low or rapidly falling fibrinogen.

Intermediate

Weak

BSH 2016b

Prophylactic FFP should not be administered to non-bleeding children with minor prolongation of the prothrombin time (2B)/ activated partial thromboplastin time including prior to surgery, although it may be considered for surgery to critical sites (2C)

Intermediate

Intermediate

Strong

Weak

BSH 2016b

Prophylactic cryoprecipitate should not be routinely administered to non-bleeding children with decreased fibrinogen including prior to surgery. It may be considered for fibrinogen <1g/l for surgery at risk of significant bleeding or to critical sites.

High

Weak

BSH 2016b

FFP should not be used in the management of inherited factor deficiencies other than in a few exceptional circumstances where specific factor concentrates are not available.

High

Weak

BSH 2016b

Urgent plasma exchange with solvent detergent fresh frozen plasma (SD FFP) is indicated for thrombotic thrombocytopenic purpura (TTP) (1B) and some forms of atypical hemolytic uremic sundrome (HUS) (2C).

High

Intermediate

Strong

Weak

PF.2. What is the dose/ frequency for plasma transfusion during acute bleeding in paediatrics?

BSH 2016b

The recommended therapeutic dose of FFP is 10-15 mL/kg of body weight given 8–12 hourly depending on the clinical situation and laboratory parameters

High

Weak

PF.3. What is the best choice of blood group for plasma transfusion?

BSH 2018 –
ad 2020

Plasma of donors with identical ABO blood group to the recipient should be used as the first choice.

If this is not possible, ABO non-identical but compatible plasma is acceptable if it has ‘low-titre’ anti-A or anti-B activity.

High

Strong

BSH 2018 –
ad 2020

Group O plasma should only be given to group O patients.

High

Strong

BSH 2018 –
ad 2020

Fresh frozen plasma and cryoprecipitate of any RhD group may be transfused. If RhD positive plasma is given to an RhD negative individual, no anti-D prophylaxis is required.

High

Strong

MO.1. What are the indications and dose for irradiation of cellular blood components?

BSH 2020a

-  Gamma- or X-irradiation of blood components, by validated systems, is the recommended procedure to prevent TA-GvHD.

-  The minimum dose achieved in the irradiation volume should be 25 Gy, with no part receiving >50 Gy.

High

High

Strong

Strong

BSH 2020a

In Intrauterine transfusion and neonatal transfusion

-  Red cells for neonatal exchange blood transfusion (EBT) should be irradiated.

High

Weak

BSH 2020a

-  Routine irradiation of red cells for transfusion to preterm or term infants (other than for EBT) is not required unless there has been a previous intrauterine transfusion (IUT), in which case irradiated components should be administered until 6 months after the expected delivery date (40 weeks gestation).

Intermediate

Weak

BSH 2020a

-  Routine irradiation of platelet transfusions for preterm or term infants is not required unless there has been a previous IUT, in which case irradiated components should be administered until 6 months after the expected delivery date (40 weeks gestation).

Intermediate

Weak

BSH 2020a

In first and second-degree relative

-  All transfusions of cellular components and fresh plasma from first- or second-degree relatives should be irradiated, even if the patient is immunocompetent. All HLA-selected components should be irradiated even if the patient is immunocompetent.

High

Strong

BSH 2020a

In immunodeficiency

-   All severe congenital T-lymphocyte immunodeficiency syndromes with significant qualitative or quantitative T-lymphocyte deficiency should be considered as indications for irradiation of cellular blood components.

High

Strong

BSH 2020a

-   Once a diagnosis of severe T-lymphocyte immunodeficiency has been suspected, irradiated components should be given while further diagnostic tests are being undertaken.

High

Weak

-   There is no indication for irradiation of cellular blood components for infants or children with temporary defects of T-lymphocyte function as the result of a viral infection. There is also no indication for irradiation of cellular blood components for adults or children who are HIV-antibody positive or who have acquired immune deficiency syndrome (AIDS).

High

Strong

BSH 2020a

In Haematopoietic stem cell transplant (HSCT)

-   All recipients of allogeneic HSCT should receive irradiated blood components from the time of initiation of conditioning chemo/ radiotherapy. The recommendation applies for all conditions where HSCT is indicated regardless of the underlying diagnosis.

Irradiated components should be continued until all of the following criteria are met:

1.   >6 months have elapsed since the transplant date

2.   The lymphocyte count is >1x 10⁹/l

3.   The patient is free of active chronic GvHD

4.   The patient is off all immunosuppression

High

Strong

-   If chronic GvHD is present or continued immunosuppressive treatment is required, irradiated blood components should be given indefinitely.

Intermediate

Weak

-   Allogeneic cellular blood components transfused to bone marrow and peripheral blood stem cell donors of all ages within 7 days prior to or during the harvest should also be irradiated.

Intermediate

Weak

-   Patients undergoing bone marrow or peripheral blood stem cell collections for future autologous re-infusion should receive irradiated cellular blood components for 7 days prior to and during the bone marrow/stem cell harvest to prevent the collection of viable allogeneic T lymphocytes, which can potentially withstand cryopreservation.

High

Weak

-   All patients undergoing autologous stem cell transplant (ASCT) irrespective of underlying diagnosis or indication for this treatment should receive irradiated cellular blood components from initiation of conditioning chemo/radiotherapy until 3 months post-transplant (6 months if total body irradiation was used in conditioning) unless conditioning, disease or previous treatment determine indefinite duration, for example previous diagnosis of Hodgkin lymphoma (HL) or previous purine analogue treatment.

High

Weak

BSH 2020a

In aplastic anaemia

-   For patients with aplastic anaemia, transfusion of irradiated cellular components is not routinely recommended, except for HLA-selected platelets, transfusion of granulocytes, donations from first- or second- degree relatives, or planned relevant treatment (e.g. ATG, alemtuzumab, HSCT).

High

Strong

BSH 2020a

In Hodgkin lymphoma (HL)

-   All adults and children with HL at any stage of the disease should have irradiated red cells and platelets indefinitely.

Intermediate

Weak

BSH 2020a

Medications

-   All patients treated with purine analogue drugs (fludarabine, cladribine, bendamustine and pentostatin) should receive irradiated blood components indefinitely.

Intermediate

Weak

-   Patients with haematological diagnosis treated with alemtuzumab should receive irradiated components.

Intermediate

Weak

-   Patients with aplastic anaemia undergoing treatment with ATG or alemtuzumab should receive irradiated blood components.

Intermediate

Weak

-   Patients receiving ATG or other T-lymphocyte-depleting serotherapy for rare types of immune dysfunction conditions should receive irradiated blood components.

Intermediate

Weak

-   Treatment of patients with rituximab is not an indication for use of irradiated cellular blood components unless this is indicated for a different reason (underlying diagnosis, type of component or previous treatment).

High

Strong

BSH 2020a

In solid organ transplantation (SOT)

-   Use of irradiated cellular blood components is not indicated for patients undergoing solid organ transplantation (SOT) who have received alemtuzumab or ATG as induction therapy or for treatment of graft rejection.

High

Strong

MO.2. What are the indications for use of washed PRBCs?

BSH 2012

For patients with recurrent febrile reactions, it is recommended to use a trial of premedication with oral paracetamol given one hour before the reaction is anticipated (or non-steroidal anti-inflammatory drugs in patients with predominant chills or rigors - but an assessment of the risks of medication against the severity of reaction should be made in each case). Patients who continue to react should have a trial of washed blood components.

Intermediate

Weak

Handbook of transfusion medicine³⁶

Patients with recurrent or severe allergic or febrile reactions to red cells, and severely IgA-deficient patients with anti-IgA antibodies for whom red cells from an IgA-deficient donor are not available.

GPS

MO.3. What are the indications to give leukofiltered blood components in neonates?

NNF 2020

Provision of CMV safe blood for transfusion in preterm neonates by using CMV seronegative donors or leukoreduction or a combination of both is strongly recommended.

High

Weak

NNF 2020

For intrauterine transfusions use of CMV negative and leuco-depleted packed red blood cell is strongly recommended.

High

Weak

MO.4. What are the characteristics of plasma transfusion and its storage?

BSH 2018 – ad 2020

Plasma of donors with identical ABO blood group to the recipient should be used as the first choice. If this is not possible, ABO non-identical but compatible plasma is acceptable if it has ‘low-titre’ anti-A or anti-B activity.

High

Strong

BSH 2018 – ad 2020

Group O plasma should only be given to group O patients

High

Strong

BSH 2018 – ad 2020

FFP and cryoprecipitate of any RhD group may be transfused. If RhD positive plasma is given to an RhD negative individual, no anti-D prophylaxis is required.

High

Strong

BSH 2018 – ad 2020

Once thawed, standard FFP or methylene blue treated FFP (MBFFP) may be stored at 2-4°C in an approved temperature-controlled blood storage refrigerator before administration to the patient, as long as the infusion is completed within 24 hours of thawing.

Intermediate

Strong

BSH 2018 – ad 2020

Transfusion of FFP should be completed within 4 hours of issue out of a controlled temperature environment.

Intermediate

Strong

BSH 2018 – ad 2020

Pre-thawed FFP that is out of a controlled temperature environment 2-4°C) can be accepted back into temperature- controlled storage if this occurs on one occasion only of less than 30 min).

Intermediate

Strong

Source

Recommendations

Quality of evidence

Level of recommendations

TR.1. How to diagnose acute transfusion reaction (ATR)?

BSH 2012

All patients should be transfused in clinical areas where they can be directly observed, and where staff are trained in the administration of blood components and the management of transfused patients, including the emergency treatment of anaphylaxis.

High

Weak

BSH 2012

The recognition and immediate management of ATR should be incorporated into local transfusion policies and there should be mandatory transfusion training requirements for all clinical and laboratory staff involved in the transfusion process.

Intermediate

Weak

BSH 2012

If a patient develops new symptoms or signs during a transfusion, this should be stopped temporarily, but venous access maintained. Identification details should be checked between the patient, their identity band and the compatibility label of the blood component. Perform visual inspection of the component and assess the patient with standard observations.

High

Weak

BSH 2012

Standard observations during blood components administration include the patient’s pulse rate, blood pressure, temperature and respiratory rate should be monitored and abnormal clinical features, such as fever, rashes or angioedema, frequently assessed.

Symptoms and signs of acute transfusion reactions include:

·      Fever and related inflammatory symptoms or signs, such as chills, rigors, myalgia, nausea or vomiting.

·      Cutaneous symptoms and signs including urticaria (hives), other skin rashes and pruritus.

·      Angioedema (localized oedema of the subcutaneous or submucosal tissues), which may be preceded by tingling.

·      Respiratory symptoms and signs including dyspnoea, stridor, wheeze and hypoxia.

·      Hypotension.

·      Pain.

·      Severe anxiety or ‘feeling of impending doom’.

·      Bleeding diathesis with acute onset.

GPS

BSH 2012

If a patient develops sustained febrile symptoms or signs of moderate severity (temperature ≥39°C OR a rise of ≥2°C from baseline AND/OR systemic symptoms, such as chills, rigors, myalgia, nausea or vomiting), bacterial contamination or a haemolytic reaction should be considered.

High

Weak

BSH 2012

Patients should be asked to report symptoms that develop within 24 h of completion of the transfusion.

Intermediate

Weak

BSH 2012

If a patient being transfused for haemorrhage develops hypotension, careful clinical risk assessment is required. If the hypotension is caused by haemorrhage, continuation of the transfusion may be lifesaving. In contrast, if the blood component is considered the most likely cause of hypotension, the transfusion must be stopped or switched to an alternative component and appropriate management and investigation commenced.

High

Weak

TR.2. How to treat Acute transfusion reactions?

BSH 2012

Initial treatment of ATR is not dependent on classification but should be directed by symptoms and signs. Treatment of severe reactions should not be delayed until the results of investigations are available.

High

Weak

BSH 2012

For patients with mild reactions, such as pyrexia (temperature of ≥ 38°C AND rise of 1–2°C from baseline), and/or pruritus or rash but WITHOUT other features, the transfusion may be continued with appropriate treatment and direct observation.

Intermediate

Strong

BSH 2012

Patients with mild isolated febrile reactions may be treated with oral paracetamol (500–1000 mg in adults). Patients with mild allergic reactions may be managed by slowing the transfusion and treatment with an antihistamine.

Intermediate

Weak

BSH 2012

Anaphylaxis should be treated with intramuscular adrenaline (epinephrine). Patients who are thrombocytopenic or who have deranged coagulation should also receive IM adrenaline if they have an anaphylactic reaction.

High

Strong

BSH 2012

Shock/severe hypotension associated with wheeze or stridor

·      For children over 12 years, administer IM adrenaline: 0.5 ml of 1:1000 adrenaline (500 lg) into the anterolateral aspect of the middle third of the thigh.

·      For children between 6 and 12 years give 0.3 ml of 1:1000 IM adrenaline (300 lg).

·      For children <6 years give 0.15 ml of 1:1000 IM adrenaline (150 lg).

·      Adrenaline is repeated, if necessary, at 5-min intervals according to blood pressure, pulse and respiratory function under the direction of appropriately trained clinicians.

·       Supportive care of anaphylaxis includes:

-      Rapid fluid challenge of 500–1000 ml crystalloid.

-      Administration of 10 mg of chlorphenamine IM or by slow intravenous (IV) injection following initial resuscitation.

-      Administration of 200 mg of hydrocortisone IM or by slow IV injection following initial resuscitation.

-      If the patient has continuing symptoms of asthma or wheeze, inhaled or intravenous bronchodilator therapy should be considered.

GPS

BSH 2012

Shock/severe hypotension without clinical signs of anaphylaxis or fluid overload:

-  Consider ABO incompatibility or bacterial contamination.
Both require supportive care with fluid resuscitation, expert evaluation for inotropic, renal and/or respiratory support, and blood component therapy for disseminated intravascular coagulation with bleeding.

-  If bacterial contamination is suspected, take blood cultures from the patient (peripheral vein and through central line, if present) and start broad-spectrum IV antibiotics (the local regimen for patients with neutropenic sepsis would be appropriate). Immediately notify the transfusion laboratory staff and haematologist to arrange culture of the implicated unit/units and contact the blood service so that any other components from the implicated donation can be recalled and quarantined.

GPS

BSH 2012

Severe dyspnea without shock.

-   Consider transfusion-related acute lung injury (TRALI) or transfusion-associated circulatory overload (TACO). Ensure the airway is patent and high-flow oxygen therapy started while urgent expert medical assessment is obtained. Initial investigation should include chest X-ray and oxygen saturation.

-  Primary treatment of TRALI is ventilatory support

GPS

TR.3. What are the laboratory investigations done for acute transfusion reactions?

BSH 2012

In all moderate and severe transfusion reactions, standard investigations, including full blood count, renal and liver function tests and assessment of the urine for haemoglobin should be performed.

Intermediate

Weak

BSH 2012

If febrile symptoms of moderate severity are sustained, implicated units should be returned to the laboratory for further investigation, the blood service contacted immediately so that associated components from the implicated donation can be withdrawn and the patient sampled for repeat compatibility and culture.

High

Weak

BSH 2012

Patients who have experienced moderate or severe allergic reactions should have IgA levels measured.

Patients with IgA deficiency diagnosed after an ATR should be discussed with an allergist or immunologist regarding future management.

Intermediate

Weak

TR.4. What is the subsequent management of recurrent reactions?

BSH 2012

For patients with recurrent febrile reactions, it is recommended to give a trial of premedication with oral paracetamol one hour before the reaction is anticipated (or non-steroidal anti-inflammatory drugs in patients with predominant chills or rigors - but an assessment of the risks of medication against the severity of reaction should be made in each case). Patients who continue to react should have a trial of washed blood components.

Intermediate

Weak

BSH 2012

For recurrent mild allergic reactions, there is no evidence to support routine prophylaxis with antihistamines or steroids. Alternative causes, such as allergy to drugs or latex gloves, should be excluded.

Intermediate

Weak

BSH 2012

For patients with recurrent moderate or severe allergic reactions, other than those in which the patient is IgA-deficient, options for further transfusion include:

•  Use of directly monitored transfusion of standard components in a clinical area with resuscitation facilities. Consider antihistamine prophylaxis (although the evidence for efficacy is low, the risks are also low). This may be the only option when further transfusion is urgent and withholding blood is a greater risk.

•  Transfusion of washed red cells or platelets.

•  The use of pooled solvent detergent treated FFP when there are recurrent allergic reactions to FFP in patients undergoing plasma exchange.

Intermediate

Intermediate

Intermediate

Weak

Weak

Strong

BSH 2012

Patients with confirmed IgA deficiency and a history of reaction to blood should be transfused with components from IgA-deficient donors (first choice) or washed red cells (second choice) if time allows.

High

Weak

BSH 2012

Life-saving transfusion should not be denied or delayed if these are not immediately available but the facilities and skills to manage severe allergic reactions must be present.

High

Weak

TR.5. Do transfusion reactions need to be reported?

BSH 2012

All transfusion reactions except mild febrile and/or allergic reactions must be reported to appropriate regulatory and haemovigilance organizations and should also be reviewed within the hospital.

High

Weak

High 

We are very confident that the true effect lies close to that of the estimate of the effect.

Moderate

We are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.

Low                

Our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect.

Very Low           

We have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of the effect.

Strong  

The desirable effects of an intervention clearly outweigh the undesirable effects (or vice versa), so most patients should receive the recommended course of action.

Conditional

There is uncertainty about the trade-offs. The clinician and patient need to discuss the patient's values and preferences, and the decision should be individualized.

Indication

Platelet threshold (x10³/µl)

Prior To Procedures or Surgery*

·     Major surgery or invasive procedure, no active bleeding

< 50

·     Venous central lines (both tunneled and un-tunneled) **

<20

·     Lumbar puncture

< 40

·     Insertion/removal of epidural catheter

< 80

·     Major surgery

<50

·     Neurosurgery or ophthalmic surgery involving the posterior segment of the eye

<100

·     Percutaneous liver biopsy***

<50

In critically ill child and reversible bone marrow failure

<10

In critically ill child and reversible bone marrow failure with additional risk factors for bleeding****

<20

In Stable, non-bleeding child

<10

Indications

Dose of cryoprecipitate

Fibrinogen Replacement

·   Cryoprecipitate can be used for fibrinogen replacement in fibrinogen disorders (congenital afibrinogenemia or dysfibrinogenemia)

·   Dose: 1 unit of cryoprecipitate per 5 kg patient weight will increase fibrinogen by about 100 mg/dL

·   Number of bags = 0.2 x weight (kg) to provide about 100 mg/dL fibrinogen.

Factor XIII Replacement

·   1 unit of cryoprecipitate per 5kg patient weight will provide 10 U/kg of factor XIII.

·   Number of bags =0.2 x weight (kg).

·   Factor XIII has a long half-life and can usually be dosed every 3-6 weeks.

Factor VIII Replacement

·   Dosing depends on patient factor VIII (8) level and requires routine monitoring of factor VIII (8) to determine appropriate dose.

·   Dosing should be repeated every 8-12 hours but will vary with each patient.

·   Post-surgery or major trauma replacement may be required for up to 10 days to maintain hemostasis.

·   Dosing also depends on Plasma Volume (PV) which is a fraction of Total Blood Volume (TBV).

·   Number of bags = [Desired activity (%) – Current activity (%)] x PV / 80

N.B: PV (mL) = TBV x (1-Hct), TBV (mL) = 70 mL/kg x weight (kg)

Von Willebrand Factor Replacement

·   Dosing of 1 unit per 10 kg patient weight will usually be enough to control bleeding.

·   Number of bags = 0.1 x weight (kg)

·   Repeat dosing may be required every 8-12 hours for up to 3 days followed by once daily dosing.

·   Follow clinically to adjust dosing and with appropriate lab studies available at your institution.

BASIC INFORMATION

Title/subtitle

1

Identify the report as an adaptation of practice guideline(s), that is include "guideline adaptation", "adapting", "adapted guideline/recommendation(s)", or similar terminology in the title/subtitle.

☒ Yes

☐ No

☐ Unclear

2

Describe the topic/focus/scope of the adapted guideline.

☒ Yes

☐ No

☐ Unclear

Cover/first page

3

Report the respective dates of publication and the literature search of the adapted guideline.

☒ Yes

☐ No

☐ Unclear

4

Describe the developer and country/region of the adapted guideline.

☒ Yes

☐ No

☐ Unclear

Executive summary/abstract

5

Provide a summary of the recommendations contained in the adapted guideline.

☒ Yes

☐ No

☐ Unclear

Abbreviations and acronyms

6

Define key terms and provide a list of abbreviations and acronyms (if applicable).

☒ Yes

☐ No

☐ Unclear

Contact information of the guideline adaptation group

7

Report the contact information of the developer of the adapted guideline.

☒ Yes

☐ No

☐ Unclear

SCOPE

Source guideline(s)

8

Report the name and year of publication of the source guideline(s), provide the citation(s), and whether source authors were contacted.

☒ Yes

☐ No

☐ Unclear

Brief description of the health problem(s)

9

Provide the basic epidemiological information about the problem (including the associated burden), health systems relevant issues, and note any relevant differences compared to the source guideline(s).

☒ Yes

☐ No

☐ Unclear

Aim(s) and specific objectives

10

Describe the aim(s) of the adapted guideline and specific objectives, and note any relevant differences compared to the source guideline(s).

☒ Yes

☐ No

☐ Unclear

Target population(s)

11

Describe the target population(s) and subgroup(s) (if applicable) to which the recommendation(s) is addressed in the adapted guideline, and note any relevant differences compared to the source guideline(s).

☒ Yes

☐ No

☐ Unclear

End-users and settings

12

Describe the intended target users of the adapted guideline, and note any relevant differences compared to the source guideline(s).

☒ Yes

☐ No

☐ Unclear

13

Describe the setting(s) for which the adapted guideline is intended, and note any relevant differences compared to the source guideline(s).

☒ Yes

☐ No

☐ Unclear

RIGOR OF DEVELOPMENT

Guideline adaptation group

14

List all contributors to the guideline adaptation process and describe their selection process and responsibilities.

☒ Yes

☐ No

☐ Unclear

Adaptation framework/methodology

15

Report which framework or methodology was used in the guideline adaptation process.

☒ Yes

☐ No

☐ Unclear

Source guideline(s)

16

Describe how the specific source guideline(s) was(were) selected.

☒ Yes

☐ No

☐ Unclear

Key questions

17

State the key questions of the adapted guideline using a structured format, such as PICO (population, intervention, comparator, and outcome), or another format as appropriate.

☒ Yes

☐ No

☐ Unclear

18

Describe how the key questions were developed/modified, and/or prioritized.

☐ Yes

☒ No

☐ Unclear

Source recommendation(s)

19

Describe how the recommendation(s) from the source guideline(s) was(were) assessed with respect to the evidence considered for the different criteria, the judgements and considerations made by the original panel.

☐ Yes

☒ No

☐ Unclear

Evidence synthesis

20

Indicate whether the adapted recommendation(s) is/are based on existing evidence from the source guideline(s), and/or additional evidence.

☐ Yes

☒ No

☐ Unclear

21

If new research evidence was used, describe how it was identified and assessed.

☐ Yes

☒ No

☐ Unclear

NA

Assessment of the certainty of the body of evidence and strength of recommendation

22

Describe the approach used to assess the certainty/quality of the body/ies of evidence and the strength of recommendations in the adapted guideline and note any differences (if applicable) compared to the source guideline(s).

☐ Yes

☒ No

☐ Unclear

NA

Decision-making processes

23

Describe the processes used by the guideline adaptation group to make decisions, particularly the formulation of recommendations.

☒ Yes

☐ No

☐ Unclear

RECOMMENDATIONS

Recommendations

24

Report recommendations and indicate whether they were adapted, adopted, or de novo.

☒ Yes

☐ No

☐ Unclear

25

Indicate the direction and strength of the recommendations and the certainty/quality of the supporting evidence and note any differences compared to the source recommendations(s) (if applicable).

☒ Yes

☐ No

☐ Unclear

26

Present separate recommendations for important subgroups if the evidence suggests important differences in factors influencing recommendations and note any differences compared to the source recommendations(s) (If applicable).

☒ Yes

☐ No

☐ Unclear

Rationale/explanation for recommendations

27

Describe the criteria/factors that were considered to formulate the recommendations or note any relevant differences compared to the source guideline(s) (if applicable).

☒ Yes

☐ No

☐ Unclear

EXTERNAL REVIEW AND QUALITY ASSURANCE

External review

28

Indicate whether the adapted guideline underwent an independent external review. If yes, describe the process.

☒ Yes

☐ No

☐ Unclear

Organizational approval

29

Indicate whether the adapted guideline obtained organizational approval. If yes, describe the process.

☒ Yes

☐ No

☐ Unclear

SNS  & NEBMC

FUNDING, DECLARATION, AND MANAGEMENT OF INTEREST

Funding source(s) and funder role(s)

30

Report all sources of funding for the adapted guideline and source guideline(s), and the role of the funders.

☒ Yes

☐ No

☐ Unclear

Declaration and management of interests

31

Report all conflicts of interest of the adapted and the source guideline(s) panels, and how they were evaluated and managed.

☒ Yes

☐ No

☐ Unclear

OTHER INFORMATION

Implementation

32

Describe the potential barriers and strategies for implementing the recommendations (if applicable).

☒ Yes

☐ No

☐ Unclear

Update

33

Briefly describe the strategy for updating the adapted guideline (if applicable).

☒ Yes

☐ No

☐ Unclear

Limitations and suggestions for further research

34

Describe the challenges of the adaptation process, the limitations of the evidence, and provide suggestions for future research.

☐ Yes

☒ No

☐ Unclear

--