Are transfusion alternatives – namely, intravenous iron, erythropoietin stimulating agents, prothrombin complex concentrates, and fibrinogen concentrates – efficacious and safe in the perioperative setting?

We will search MEDLINE via PubMed, The Cochrane Library, and CINAHL (Cumulative Index to Nursing and Allied Health Literature). The search strategy will include only terms relating to transfusion alternatives, and will be restricted to the English language and publications between July 1997 and July 2012. Additional studies will be identified by manually searching the reference lists of eligible studies and review articles.

We will include randomized trials and non-randomized studies with a comparator group to assess the beneficial and harmful effects of fibrinogen concentrates, prothrombin complex concentrates, intravenous iron formulations, and erythropoietin stimulating agents (ESA).

We are interested in efficacy outcomes (hematological parameters, clinical outcomes) and safety outcomes concerning the use of transfusion alternatives to address conditions predisposing to-, or traditionally treated by-, blood component transfusion. Such conditions include perioperative anemia, dilutional coagulopathy, use of oral anticoagulation, and/or acquired states of fibrinogen deficiency.

Inclusion: Adults with anemia in the perioperative setting, or adults who are bleeding due to use of oral anticoagulation and/or acquired states of fibrinogen deficiency in the perioperative setting.

Exclusion: Adolescents (under 18 years of age) and congenital bleeding disorders; the use of Erythroid Stimulating Agents or Hematinics solely for the purpose of managing anemia of chronic kidney disease; the use of ESA or Hematinics solely for the purpose of pre-operative autologous donation.

1. For bleeding in the perioperative setting due to acquired states of fibrinogen deficiency, we will be reviewing the efficacy and safety outcomes of fibrinogen concentrate products.

2. For bleeding in the perioperative setting due to use of oral anticoagulation or dilutional coagulopathy, we will be reviewing the efficacy and safety outcomes of prothrombin complex concentrate products (also known as factor IX concentrates) in reversing anticoagulation.

3. For perioperative anemia, we will be reviewing the efficacy and safety outcomes of intravenous iron formulations and erythropoietin stimulating agents.

1. When study design is suitable, fibrinogen concentrates may be compared to cryoprecipitate or FFP.

2. When study design is suitable, prothrombin complex concentrates may be compared to FFP and vitamin K.

3. When study design is suitable, intravenous iron formulations and erythropoietin stimulating agents may be compared to either placebo or red cell transfusion.

Anemia or bleeding in the perioperative setting.

Primary outcomes

Efficacy Outcomes:

1. Hematological parameters

a. Fibrinogen Concentrate

i. clot firmness

ii. fibrinogen level

iii. dosing formula

b. Prothrombin Complex Concentrates:

i. complete or partial INR reversal

ii. dosing formula

iii. time to INR reversal

c. IV Iron and ESA

i. hemoglobin or hematocrit response

ii. iron profile response

iii. dosing formula

2.Clinical outcomes:

a. Fibrinogen concentrate

i. bleeding or blood loss

ii. need for blood transfusions

b. Prothrombin Complex Concentrate

i. Bleeding or blood loss

ii. need for blood transfusions

c. IV Iron and ESA

i. need for blood transfusions

Safety Outcomes:

1. Fibrinogen concentrate

a. Thrombotic events

b. Other adverse events

2. Prothrombin Complex Concentrates

a. Thrombotic events

b. Other adverse events

3. IV Iron and ESA

a. Thrombotic events

b. Other adverse events

Secondary outcomes

None.

Titles and/or abstracts of studies retrieved using the search strategy and those from additional sources will be screened independently by two review authors to identify studies that potentially meet the inclusion criteria outlined above. The full text of these potentially eligible studies will be retrieved and independently assessed for eligibility by two review team members. Any disagreement between them over the eligibility of particular studies will be resolved through discussion with a third reviewer.

Two reviewers will independently assess the risk of bias of randomized and non-randomized studies using the Cochrane risk of bias tool: sequence generation, allocation concealment, blinding, completeness of outcome data, selective outcome reporting, and other sources of bias including funding. Disagreements between the review authors over the risk of bias in particular studies will be resolved by discussion, with involvement of a third review author where necessary.

No meta-analysis is planned; instead, we will provide a narrative synthesis of characteristics of included studies (randomized and non-randomized trials) as well as the efficacy and safety outcomes for each of the transfusion alternatives

None Planned

A paper will be submitted to a leading journal in this field.

Minh-Ha Tran

UC Irvine Medical Center

101 The City Dr S

Building 1, Room 3003

Orange, CA 92868

minhhat1@uci.edu

UC Irvine Medical Center

www.healthaffairs.uci.edu

Dr Minh-Ha Tran, UC Irvine Medical Center
Dr David Lin, UC Irvine Medical Center
Ms Linda Murphy, UC Irvine Medical Center

03 July 2012

30 September 2012

No funding sources.

None known

English

United States of America

Subject indexing assigned by CRD

Blood Component Transfusion; Blood Transfusion; Humans; Perioperative Care

09 July 2012

23 July 2012