Question 21

College Answer

Examine the list of blood or plasma products listed in the table below. Indicate in your answer,
a)  whether crossmatch is essential with the use of each of these products
b)  one major indication for the use of each of these products.

c)  List one contraindication to the use of

i)          Platelet transfusion -ITP . immune thrombocytopenia 
ii)         IV immunoglobulin infusion - Hereditary IgA deficiency

d)  Very briefly, outline the role of erythropoietin in the management of anaemia of critical illness?

Anaemia of critical illness is characterised by blunted EPO production and altered iron metabolism. EPO use has been shown to reduce transfusion requirements, but there in no proven benefit in terms of clinical outcome. A potential benefit may exist in patients who are in ICU for > 1 wk, but data are lacking. Potential side effects include red cell aplasia, EPO resistance, thromboembolic complications and hypertension.

Discussion

his question closely resembles other questions where one is expected to match a blood product with a need for transfusion.

These questions are:

• Question 1 from the second paper of 2012
• Question 24.2 from the second paper of 2010 (this contains a detailed dissection of crossmatching practice)

However, in contrast, this one also demands indications. These can be dug out of the old 2001 NHMRC guidelines, or read about broadly in this article. More modern guidelines are available from the Australian Red Cross Blood Service website, and these were used to construct the list below.

In brief:

The following blood products require a crossmatch:

• Packed red blood cells
• Granulocyte concentrate

The indications are as follows:

• Packed red blood cells
  • Uncontrolled bleeding
  • Symptomatic anaemia
• Platelets
  • Uncomplicated bone marrow failure (<10,000)
  • Bone marrow failure with additional risk factors for bleeding(<20,000)
  • Simple surgical procedures (<50,000)
  • Neurosurgical procedures (<100,000)
• Fresh frozen plasma
  • Replacement of clotting factors in coagulopathy; according to the ARCBS, "You may give fresh frozen plasma to replace labile plasma coagulation factors during massive transfusion, cardiac bypass, liver disease or acute disseminated intravascular coagulation in the presence of bleeding and abnormal coagulation."
  • Replacement of ADAMTS-13 for plasma exchange in TTP
• Cryo precipitate
  • Replacement of factor VIII, fibrinogen, factor XIII, von Willebrand factor and fibronectin.
  • Indicated specifically for the replacement of fibrinogen for the management of low fibrinogen levels or to relpace functionally abnormal fibrinogen
• Prothrombin concentrate
  • Relacement of prothrombin to correct over-anticoagulation with Warfarin
• Granulocyte concentrate
  • The college says "neutropenic sepsis". This is consistent with the UK guidelines. There is little Australia-specific information about this, which is reflected in this policy documentfrom The Alfred in Melbourne (an almost verbatim copy of the UK guidelines).
• Intravenous immunoglobulin
  A good article from 2005 contains a detailed table of indications for IVIG. This table is massive and cannot (should not) be reproduced here. Highlights are as follows:
  • Guillain-Barre syndrome
  • ITP
  • Myasthenia gravis
  • Lambert-Eaton syndrome
  • Autoimmune haemolytic anaemia
  • Streptococcal toxic shock syndrome

As for the contraindications; there would probably be an excellent answer to this question somewhere in an article by Tomičić et al (2014), but it is in Croatian. Fortunately, the authors' native Russian armed him with the ability to discern that "trombocitne transfuzije kontraindicirane" probably means something about the contraindications to platelet transfusion, and from this poor quality translation the belowstated contraindications are derived.

• Contraindication to the use of platelet transfusion include:
  • TTP/HUS -  platelet transfusion makes the organ system failure worse as the organs are clogged with debris; Goel et al (2015) found it increases mortality
  • HITS type II - though Kumar et al (2013) did not find platelets to be all that harmful in HIT patients, and all evidence to support this contraindication seem to come from case reports
  • IgA deficiency is a relative contraindication: IgA-deficient recipients may have anti-IgA antibodies, and platelets transfusion may bring enough IgA with it to cause life-threatening anaphylaxis (Davenport et al, 1992).  It is however possible to collect platelets from IgA-deficient donors or to wash them.
• Contraindication to the use of immunoglobulin  infusion include:
  • IgA deficiency is again a relative contraindication, for the abovementioned reasons. Berger (2013) recommends you still have a try of it to see if it is tolerated. The argument is, the anti-IgA antibodies may not cause anaphylaxis - just an urticarial rash. 
  • Severe decompensated heart failure:  Immunoglobulin is usually given in a reasonably high dose (tens of grams of protein) as a hyperoncotic (10-20%) solution. Even if it were isooncotic, that would be a fairly large volume load. Pulmonary oedema may ensue.
  • Previous severe reactions (for example, stroke, renal falure, haemolytic anaemia) following IV Ig transfusion.

And as for the anaemia of critical illness: there's an excellent article on that from Azare (2008), which is unfortunately paywalled.  In short, this is a condition "hematologically similar to ...chronic anemia, except that the onset is generally sudden". A review by Rodriguez et al (2001) blames inappropriately blunted EPO secretion for this, although this is on the basis of small-scale studies. There also does not seem to be much good from EPO supplementation: Corwin et al (2002) found that though the total transfusion requirements decreased, the mortality did not. This may be another indicator that transfusion according to haemoglobin thresholds is not going to improve mortality. In answer to the college question, one would have to write that the routine use of EPO in the critically ill is not supported by robust evidence and that EPO use is not without its risks.

Sharma, Sanjeev, Poonam Sharma, and Lisa N. Tyler. "Transfusion of blood and blood products: indications and complications." American family physician83.6 (2011): 719.

Massey, Edwin. "CLINICAL GUIDELINES FOR THE USE OF GRANULOCYTE TRANSFUSIONS."

Jolles, S., W. A. C. Sewell, and S. A. Misbah. "Clinical uses of intravenous immunoglobulin." Clinical & Experimental Immunology 142.1 (2005): 1-11.

Tomičić, Maja, Tomislav Vuk, and Željka Hundrić-Hašpl. "Indications and contraindications for platelet transfusions in patients with thrombocytopenia." Liječnički vjesnik 136.3-4 (2014): 0-0.

Goel, Ruchika, et al. "Platelet transfusions in platelet consumptive disorders are associated with arterial thrombosis and in-hospital mortality." Blood (2015): blood-2014.

Kumar, Rohit, Amy Zhou, and Roy E. Smith. "Outcomes Of Platelet Transfusion In Heparin Induced Thrombocytopenia Patients." (2013): 2311-2311.

Davenport, R. D., K. L. Burnie, and R. M. Barr. "Transfusion management of patients with IgA deficiency and anti‐IgA during liver transplantation." Vox sanguinis 63.4 (1992): 247-250.

Hamrock, David J. "Adverse events associated with intravenous immunoglobulin therapy." International immunopharmacology 6.4 (2006): 535-542.

Berger, Melvin. "Adverse effects of IgG therapy." The Journal of Allergy and Clinical Immunology: In Practice 1.6 (2013): 558-566.

Asare, Kwame. "Anemia of critical illness." Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy 28.10 (2008): 1267-1282.

Rodriguez, Robert M., et al. "Nutritional deficiencies and blunted erythropoietin response as causes of the Amemia of critical illness." Journal of critical care 16.1 (2001): 36-41.