What it is and nursing managementLynda Gaynor

Understand the basic pathophysiology of CAD

An awareness of the clinical manifestations

An awareness of laboratory findings

Understand the Nursing Management of CAD

◦ Patient Education◦ Transfusion support and blood warmer

Cold Agglutinin Disease (CAD) is one of the acquired Autoimmune Haemolytic Anaemias (AIHA). The cold-reacting antibodies can lead to premature destruction of the red blood cells and therefore anaemia.

CAD is rare and has an incidence of 1: 1 000 000 persons.

Predominately found in the female population, and peaks in the seventh decade of life, however can also be found in paediatric populations.

Other conditions are sometimes associated with CAD, and may reflect an underlying malignancy, such as lymphoma, CLL and Waldenstrom's’ Macroglobinuria.

There are primary and secondary causes of CAD, however we will focus on the secondary causes associated CAD.

◦ Secondary causes result from systemic diseases, which can involve infectious processes or lymphoproliferative disorders.

◦ CAD can be transient.

Cold agglutinin antibodies occur naturally in most healthy individuals at low titres. Usually less than 1:64 at 4°celsius.

Pathological cold agglutinins occur at levels greater than 1:1000

The IgM antibody attaches to the surface of the red blood cell and causes them to agglutinate, or clump, at at temperatures below 37°celsius, but maximally at 0-5°celsius.

This may cause acrocyanosis (impaired blood flow) to the digits, ears and nose.

Agglutination of red cells in small vessels

◦ Fixation of the complement to the red blood cell by the cold agglutinin forms the IgM/C3b complement which coats the red blood cell.

◦ When the IgM/C3b complement circulates to warmer parts of the body, the IgM dissociates, however the complement left on the red blood cell can lead to haemolysis by macrophages in the liver. It is this process which causes haemolytic anaemia in CAD.

◦ This is usually self-limited as the complement depletes and so the red blood cell is no longer attractive to the destructive macrophages.

The next slide is a diagram showing the mechanism by which the cold agglutinin, IgM and the complement C3b interact to cause haemolysis….

Cooling of the blood during passage through peripheral vessels allows immunoglobulin M

(IgM) cold agglutinin to bind to erythrocytes, causing agglutination and complement protein 1

(C1) fixation.

Stone M J Blood 2010;116:3119-3120

©2010 by American Society of Hematology

Haemolysis can increase during times of febrile illness as complement levels increase.

Causes of CAD include;◦ Malignancies, viral infections, genetic abnormalities

eg trisomy 3 and 12, liver transplantation, systemic sclerosis, malarial splenomegaly, DPT vaccination, and rarely, patients subjected to hypothermia fir cardiopulmonary bypass surgery.

For CAD related to infections, there is a good prognosis if the infection itself is self-limiting. However CAD associated with viral infections such as HIV has a poorer prognosis due to the underlying nature of the disease.

A poorer prognosis is also associated with CAD associated with malignancy.

◦ Anaemia and related symptoms.

◦ Acrocyanosis – 24%

On exposure to cold ambient temperatures, dark, purple to gray discoloration of the acral (fingers, nose toes and ears) parts of the body may be noted due to agglutination. Upon warming, this discoloration will disappear.

Diagnosis;

◦ Presence of a high titre of cold agglutinins, usually IgM.

◦ Positive Direct Coombs Test (DAT). This test shows the presence of antibodies and complement on the red cell surface.

Avoidance of cold temperatures– this is the single most useful therapy in CAD.

Cytotoxic agents – including cyclophosphamide and chorambucil to reduce the production of antibodies. This is sometimes used in combination with steroids. This aggressive treatment is usually used for patients with an underlying lymphoma.

Rituximab, alone or in combination with fludaribine for patients with severe haemolysis.

Plasmapherisis – as an adjunctive therapy to physically remove IgM antibodies from plasma to reduce haemolysis. However this treatment is short lived and is usually used in situations of severe haemolysis when CAD is due to infection, to prepare the patient for surgery and severe Acrocyanosis.

Transfusion support – Interestingly, the agglutination of the red cells can make it difficult to determine the ABO type, so ideally the patients red cells need to be washed with warm normal saline to remove the IgM antibody in order to determine the blood type.

Transfusion support (cont)◦ The use of a blood warmer is suggested.

Patient Education◦ Educate the patient about the importance keeping

the body warm by wearing appropriate clothing, and the avoidance of cold foods and working in cold areas.

◦ The importance of nutrition, and especially for maintaining an adequate folic acid intake. It may be necessary to refer the patient to a dietitian.

◦ Advice patients how to monitor and support for signs of anaemia.

◦ If patients require cytotoxic/steroid therapy, educate about the symptoms on how to manage side effects.

Transfusion support

◦ When transfusing red cells, the use of a blood warmer is needed if instructed on the “scientific comment” on the MR17AA at Peter Mac.

Blood Warmer

◦ Also refer to Peter Mac Policy on the use of Blood Warmers (Ref 11.1.1.5) including;

The use of a blood warmer must be documented by a registered medical officer

As per the guidelines, nursing documentation in the patient’s medical record should include;

a blood warmer was used, at what temperature and the the inventory number.

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A link is available with more information abouthe blood warmer below this presentation on this wikipage .

Any further questions about the blood warmer, please post/refer to the discussion page on the wiki page….it is a work in progress

Please add any comments, questions,suggestions to the discussion page on the wiki space.

And of course, you can ask me as well!

Hoffbrand, et al 2001 (4th Ed), Ch.5, Essential Haematology, Blackwell Science Pty Ltd, Carlton, Australia

Gertz, M, 2006, Cold Hemolytic Syndrome,American Society for Haematology, pp 19-23.

Berentsen S, 2011, How I manage cold agglutinin disease, Br J of Haematology; pp 153-309.

Wendell et al 2013, Clinical features and treatment of autoimmune hemolytic anemia: Cold Agglutinins, accessed 1st September 013 from www. uptodate.com/contents/clinical-features-and-treatment-of-autoimmune-he

Smeltzer et al 2004, Brunner and Suddarth’stextbook of Medical-Surgical Nursing 10th Ed, pp892-893.

Stone, M 2013, Heating up cold Agglutinins, Inside Blood, 116(17) pp 3119-3120.