Syllabus (Fourth Edition, 2023)
Topics
i. Understand the pharmacology of blood and its components, including individual factor replacement.
ii. Understand the adverse consequences of blood transfusion, including that of massive blood transfusion and storage lesions.
iii. Understand the process of collection and production of blood and its components.
Topics not covered in previous SAQs
i. Understand the pharmacology of blood and its components, including individual factor replacement.
iii. Understand the process of collection and production of blood and its components.
Learning Objectives for the First Part Examination in Intensive Care Medicine
- This will ensure that trainees, tutors, and examiners can work from a common base.
- All examination questions are based around this Syllabus.
- These learning objectives are designed to outline the minimum level of understanding required for each topic.
- The accompanying texts are recommended on the basis that the material contained within them provides sufficient information for trainees to meet the learning objectives.
- Trainees are strongly encouraged to explore the existing and evolving body of knowledge of the Basic Sciences as they apply to Intensive Care Medicine by reading widely.
- For all sections of the syllabus an understanding of normal physiology and physiology at extremes of age, obesity, pregnancy (including foetal) and disease (particularly critical illness) is expected.
- Similarly, for pharmacology, trainees are expected to understand a drug’s pharmacology in these contexts.
- An understanding of potential toxicity and relevant antidotes is also expected.
Definitions
Throughout the document specific wording has been used under the required abilities to indicate the level of knowledge and understanding expected and a glossary of these terms is provided.
Definitions
| Calculate | Work out or estimate using mathematical principles. |
| Classify | Divide into categories; organise, arrange. |
| Compare and contrast | Examine similarities and differences. |
| Define | Give the precise meaning. |
| Describe | Give a detailed account of. |
| Explain | Make plain. |
| Interpret | Explain the meaning or significance. |
| Outline | Provide a summary of the important points. |
| Relate | Show a connection between. |
| Understand | Appreciate the details of; comprehend. |
SAQs
i. Understand the pharmacology of blood and its components, including individual factor replacement.
2022B 02 – 2019A 03
Compare and contrast fresh frozen plasma and prothrombin complex concentrate.
CICMWrecks Answer
| Fresh Frozen Plasma (FFP) | Prothrombin Complex Concentrate (Prothrombinex) | |
| Intro | Human plasma containing all coagulation factors including the labile plasma coagulation Factors VIII and V | Human plasma derivative containing concentrates of factors II, IX and X (500IU PCC has 500IU of II, IX, X each in a vial) The 3 factor prothrombin complex concentrate available in Australia (4 factor PCC in some European countries) |
| Preparation | Prepared either via: Separation from whole blood Apheresis: Removal of a large volume (typically 800ml) of plasma from a single patient, with return of red cells to the donor. Once collected, it is frozen and rethawed in a water bath prior to use | developed through the process of ion-exchange chromatography from the cryoprecipitate supernatant of large plasma pools and after removal of antithrombin and factor XI |
| Indications | reversal of warfarin anticoagulation (in setting of bleeding or need for invasive procedure) Bleeding and multiple coagulation defects (e.g. DIC with significant PT/PTT elevation) Correction of coagulation defects for which no specific factor is available Transfusion of more than one blood volume with evidence of active bleeding + coagulopathy accepted treatment for patients with thrombotic thrombocytopenic purpura often in conjunction with plasma exchange. Where PCCs are not available | Bleeding and warfarinized Bleeding from factor deficiency (either congenital or due to liver disease, and haemophilia) Prophylaxis |
| Contraindications | Allergy to class/drug ABO incompatibility when you can correct coagulopathy effectively with specific therapy in plasma exchange procedures except for treatment in thrombotic thrombocytopenic purpura treatment of immunodeficiency states | Allergy to class/drug DIC known HIT (Heparin induced thrombocytopenia) patients with haemophilia B if a specific factor IX concentrate is available |
| PC | Dose: 10-15ml/kg will increase factors by ~20-30% Transfuse at least 15 mL/kg at a time (4 units in 70-kg adult) INR >1.5 and needs invasive procedure INR >1.5 and actively bleeding (e.g. massive transfusion protocol, post-bypass surgery) INR of FFP is ~1.6; therefore transfusing for INR <1.7 is not advised | Dose: – 25-50 IU\kg (1 IU\kg of Factor IX raises the Factor IX by 1%) – Dose adjusted based on INR |
| PD – MoA | restores factors II, VII, IX and X in the anticoagulated patient | provision of factors II, IX and X |
| Side Effects | Serious Hemolytic transfusion reactions Febrile non-hemolytic reactions Transfusion-associated circulatory overload (TACO) Transfusion-related acute lung injury (TRALI) Transfusion-associated graft-versus-host disease Anaphylaxis Sepsis Common Headache, paraesthesia Nausea, Pruritus, urticaria | Serious Thromboembolic Events Common Allergy, anaphylaxis phlebitis vomiting, fever rash, urticaria SOB pain thrombocytopenia |
| PK | IV Distributed and metabolized in the same way as endogenous coagulation factors | IV Distributed and metabolized in the same way as endogenous coagulation factors |
| Advantages | cheap | small volume readily available reliable reversal avoids complications of FFP – immune reaction, TRALI, fever, infection risk familiarity cheap |
| Disadvantages | ABO compatibilty a must (but crossmatch before transfusing not) Needs to be thawed – time delay Immune reaction, TRALI, fever, infection risk significant fluid load in patients that are elderly and frail, or have heart failure. | More expensive than FFP May cause thromboembolic complications |
Examiner Comments
2022B 02: 52% of candidates passed this question.
The safe and appropriate use of these products in ICU is a key area of critical care practice so a fair bit of detail was required for a pass. Most candidates had a decent understanding of the main constituents of the two products, although few mentioned that FFP may still contain some cells, or that prothrombin concentrates contain heparin. To gain full marks for this section the components and concentration/amounts would need to be accurately described. Production of the two products was generally well understood and articulated. A more comprehensive and specific list of indications than rather than “bleeding” or “coagulopathy” was expected. While using elements of the standard “compare/contrast” pharmacology structure was helpful, rigidly adhering to it, for instance, noting FFP’s “poor oral bioavailability” – did not garner marks. It is important to note that heparin is not reversed by FFP and FFP may in fact increase heparin’s effect. FFP does not cause dilutional coagulopathy, it is the treatment for dilutional coagulopathy. Most candidates recognised the need for ABO matching with FFP but not prothrombin concentrates, however few noted that Rhesus matching is not required. The larger fluid load of FFP in comparison to prothrombin concentrates was well recognised a major drawback of FFP use.
2019A 03: 10% of candidates passed this question.
Very few answers included details on prothrombin complex concentrate which meant it was difficult to score well. Useful headings included preparation and administration, dose, indications and adverse effects. Not many candidates knew the dose of FFP, and few were able to describe the preparation/production of the product. Few candidates knew the factors available from either product. Commonly missed was the need for ABO typing for FFP and that Prothrombin complex concentrate did not require this.
ii. Understand the adverse consequences of blood transfusion, including that of massive blood transfusion and storage lesions.
2020A 03
Outline the potential adverse consequences of blood transfusion.
2017A 16
List the potential problems resulting from blood transfusion and methods used to minimise them.
2013B 13
Outline the adverse consequences of a blood transfusion. (75% of marks)
Define massive blood transfusion and list the adverse consequences associated with a massive blood transfusion. (25% of marks)
CICMWrecks Answer
Adverse Consequences of Blood Transfusion
1. Acute (<24 hours)
1a) Immune-mediated
| Problem | Methods to Minimize | |
|---|---|---|
| Allergic reaction to plasma proteins | mild (urticarial) or severe (anaphylaxis) | Pre-treatment in high risk patients |
| Acute Haemolytic transfusion reaction | incompatibility of donor and recipient blood leads to widespread haemolysis and circulatory collapse | Group and screening |
| Febrile non-haemolytic transfusion reaction (FNHTR) | due to stored cytokines and/or the presence of recipient alloantibodies | Careful monitoring and early cessation of transfusion |
| Transfusion related acute lung injury (TRALI) | noncardiogenic pulmonary oedema caused by HLA antibodies in donor plasma directed against recipient leukocytes or bioactive lipids which accumulate during storage | Careful monitoring and early cessation of transfusion |
1b) Non-immune mediated
| Problem | Methods to Minimize | |
|---|---|---|
| Sepsis | bacterial infections are most common with platelets as they are stored at room temperature | Safe and sterile methods of storage |
| Transfusion Related Circulatory overload (TACO) | fluid overload usually due to rapid or massive transfusion | Careful monitoring and early cessation of transfusion |
| Non-immune mediated haemolysis | Careful monitoring and early cessation of transfusion | |
| Hypothermia | Careful monitoring and early cessation of transfusion | |
| Dilutional coagulopathy | Careful monitoring and early cessation of transfusion |
2. Delayed (>24 hours)
2a) Immune-mediated
| Problem | Methods to Minimize | |
|---|---|---|
| Delayed haemolytic transfusion reaction | Production of anti-donor antibodies post-transfusion May be associated with transfused malaria | Careful monitoring and early cessation of transfusion |
| Transfusion-related immunomodulation (TRIM) | transient immunosuppression in blood recipients which may be due to release of cytokines from donor lymphocytes | Careful monitoring and early cessation of transfusion |
| Alloimmunisation | development of antibodies during exposure to blood products, resulting in an amplified reaction on subsequent exposure Can cause post transfusion thrombocytopenia and purpura | Re-screening every 48-72 hours |
| Transfusion Associated Graft vs. Host Disease | Profound bone marrow aplasia >90% mortality Viable donor T cells implant and attack recipient tissues | Careful monitoring. Re-screening |
2b) Non-immune mediated
| Problem | Methods to Minimize | |
|---|---|---|
| Iron overload | most common in chronically transfused patients | Monitoring of Iron levels |
| Transfusion-related infection | Viral – the risk of HIV, HTLV 1&2 and HCV is <1/1 million. The risk of contracting HBV is slightly higher at 1/500,000. Other – malaria, vCJD, Dengue Fever, West Nile Virus | Pre-screening of donors, screening of collected blood as per local guidelines (different for different areas) |
3. Storage Lesions
A storage lesion refers to the changes that occur to a sample of blood during storage. (Note: Australian Red cross anti-coagulates Whole blood with CPD, but washes and stores Red Cells in SAGM).
| Problem | Methods to Minimize | |
|---|---|---|
| Physical changes | Reduction in the viability of RBCs due to shape changes and reduced deformability Formation of microaggregates | Careful monitoring and usage of products within a specified period |
| Hyperkalaemia | plasma K can be >20 at 28 days in stored blood due to inactivation of the red cell Na/K ATPase pump. | Careful monitoring and usage of products within a specified period |
| High citrate load | can lead to hypocalcaemia and alkalosis (less or nil in SAGM) | Use of SAGM for storage |
| Reduction in 2,3-BPG | causes left shift of the oxygen/haemoglobin dissociation curve (less in CPDA1) | Use of CPDA1 |
| Renal impairment | Due to Increase in free haemoglobin from cell lysis | Routine monitoring of renal function and careful monitoring during transfusion |
Massive Transfusion
- Replacement of >1 blood volume in 24 hours
- 50% of blood volume in 4 hours
Adverse consequences of massive transfusion
| Problem | Methods to Minimize | |
|---|---|---|
| Hypothermia | Cooled products | Appropriately re-warm products. Use of blood warmers |
| Poor O2 delivery | Depletion of 2,3 DPG in PRBC | |
Haemostatic abnormalities | Dilutional coagulopathy | Monitor coagulation profile at appropriate intervals during massive transfusions. Use of appropriate factors like FFPs, Cryoprecipitate during massive transfusions |
| Hypocalcaemia | Consumption with coagulopathy and bound to citrate added to transfused units | Monitor and replace calcium as necessary |
| Hypomagnesaemia | Bound to citrate in transfused units | Monitor and replace magnesium as necessary |
| Citrate toxicity | Citrate is added to stored units as an anticoagulant | Monitor for acidosis during massive transfusions |
| Lactic acidosis | Hyperlactataemia due to anaerobic metabolism in stored units | Monitor for acidosis during massive transfusions |
| Hyperkalaemia | Potassium migrates from stored erythrocytes into plasma whilst in storage | Careful monitoring and usage of products within a specified period |
| Air embolism | Inadvertent infusion | Careful monitoring, use of transfusion sets with air vents, filters |
JC / Sakurai 2019
Examiner Comments
2020A 03: 43% of candidates passed this question.
As only an outline was asked for, a brief statement about each complication was sufficient. Better answers were structured using a classification of: Acute Immunological, Acute Non Immunological, Delayed Immunological and Delayed Non-immunological. Examples of expected detail would include the following:
E.g. Bacterial infection – a statement outlining the incidence of bacterial infection, a common causative organism or why bacterial infections are more commonly associated with platelet transfusions than red cells would have scored the marks allocated to ‘bacterial infection’.
E.g. Acute Haemolytic Transfusion Reaction – a statement about red cells being destroyed due to incompatibility of antigen on transfused cells with antibody of the recipient and an approximate incidence scored the marks allocated to AHTR.
An excellent resource is the Australian Red Cross transfusion website as listed in the suggested reading section of the syllabus
2017A 16: 53% of candidates passed this question.
This question required a broad answer. It was generally well answered. Those candidates who scored well had a good structure to their answers e.g. grouping potential electrolyte disturbances together, and infectious risks together etc. and including methods used to minimise these risks in appropriate detail.
2013B 13: 17 candidates passed (63.3%).
In general this question was well answered; however candidates often had difficulty differentiating specifically for a massive blood transfusion (defined as replacement of circulating volume in 24 hours, or greater than 4 units blood transfused in 1 hour of continuing blood loss, or loss of 50% circulating volume in 3 hours). Responses to the first part of the question generally lacked depth. It is suggested that candidates take a systematic approach (e.g. use of categories such as immune, infectious, storage, etc.) when answering these type of questions. Candidates are reminded that when asked to “outline”, that the expectation for them to include a description that reflects understanding, and not just “dotpoints”.
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