Transfusion Answers

Question 1.

a) There is an incidental finding of a microcytosis - you should identify what this is (although the relatively low MCV is likely to point towards a haemoglobinopathy of some description) - perform iron studies, ferritin and haemoglobinopathy screen. Also check B12/folate levels and coagulation screen (to check for any bleeding tendency as transfusion of red cells will not be possible).

b)

• ascertain what blood products she will accept according to local hospital/trust policy, including use of Jehovah's Witness advocates as needed, and document in notes/obstetric notes. Specifically offer intra-operative cell salvage with a closed loop where LSCS might be considered
• ensure iron, B12 and folate are well replenished through prescribing prior to delivery
• assess any coagulation screen abnormalities and diagnose as appropriate
• discussion with obstetricians with joint clinic to discuss peridelivery plan
• repeat blood tests near delivery at 32-36 weeks to confirm no worsening anaemia
• delivery is possible as per standard obstetric guidelines
• if no further risks during pregnancy for VTE, 1g tranexamic acid at the commencement of labour (IV for 24 hours and oral thereafter).
• actively managed third stage of labour to reduce blood loss, vitamin K/fetal scalp monitoring as per standard obstetric guidelines.

Question 2.

Please note that some hospitals/trusts no longer screen for CMV because of routine leucodepletion at NHSBT and this may not be an option.

a) Irradiated red cells only (for the reason of Hodgkin's and not for HIV which does not require special blood requirements.

b) CMV negative for the duration of the pregnancy; and because of sickle cell should be ABO/Rh, Kell matched as well as HbS negative. Ideally cells should be less than 10 days old if possible.

c) CMV negative as pregnant and Kell negative, note that it is the *woman* who is getting the transfusion, not the neonate. For safety it should be ABO/Rh matched in the context of upcoming IUT to avoid antibody generation which could be deleterious to the fetus.

d) ABO/Rh/K matched, cells less than 10 days old if possible (note not a mandated requirement), plus anti-Jkb negative

e) This is a major mismatch, so continue to use donor group FFP/platelets, ie group A. In terms of Rh group, give RhD products as per the recipient until the transplant blood group switching is complete to the donor type (ie here give RhD- products). Also requires irradiated products +/- CMV negative depending on the serotype.

f) CMV, HbS negative, single donor red cells, ABO/Rh/K matched, crossmatch compatible with maternal plasma. Should be red cells <28 days old in CPDA, with Hct 0.5-0.7. No need for irradiation.

g) Irradiated red cells required (given previous bendamustine, and current autologous transplant). May consider CMV negative if consideration of future allogeneic transplant.

h) Bidirectional mismatch - as this is five days before commencing conditioning - continue to use recipient group (B RhD+). Also requires irradiated +/- CMV negative products.

Question 3.

a) There is a moderate rise in the haemoglobin above the baseline - manual exchange was probably not done correctly in terms of replacement with the same number of red cells in vs number of red cells venesected.

b) either O R2r" K- or O R2R2 K-

c) Differentials:

• - hyperhaemolysis, slightly early for delayed haemolytic transfusion reaction, possibility of ATR as a result of ABO incompatibility. For review of units and blood group given - usual bloods (including repeat G+S, clotting, check for haemoglobinuria and send blood cultures).
• stop transfusion (and contact blood bank to put a stop on further transfusions for this patient)
• steroids (1-2mg/kg prednisolone or methylprednisolone), IVIg and observe, add on haematinics and replace as required; and serial monitoring of FBC (if possible do in as small volumes as possible). Only for transfusion in life-threatening anaemia.

Question 4.

a) 200mg is the approximate amount of iron in one adult unit of packed red cells.

b) Chelation consists of three types:

Desferioxamine - SC/IV

- known effectiveness in multiple situations; but requires SC/IV administration

- ocular and ototoxicity and Yersinia infections - needs annual hearing review and baseline assessment

Deferiprone - oral (three times daily)

- Not parenteral administration but three times daily administration orally is difficult for compliance

- Can cause bone marrow suppression and FBC needed regularly (1-2 weeks), arthropathy, can cause GI upset and rash, zinc deficiency, Baseline renal and liver function required.

Deferasirox - oral (once daily)

- new film coated tablet preparation is much simpler to take - previous preparations required tablet crushing and drinking this with water

- weekly monitoring of renal function for a month, then liver and renal function every three months and for proteinuria. Low risk of cataracts or deafness

Reference:

Killick SB. Iron chelation therapy in low risk myelodysplastic syndrome. BJH (10.1111/bjh.14602)

Question 5.

a) Picture is of a haemolytic episode. Two months out of the initial episode of ABO HDN this will not be a recurrence:

Differentials: enzymopathy - eg G6PD deficiency; PK deficiency possible but less likely given blood film features, hereditary spherocytosis (most likely here given mum's history of splenectomy, the type I diabetes being incidental).

b) While this will depend on the hospital policy, this is generally safe because neonates will not have developed ABO antibodies until past 4 months of age so a reverse grouping is not required. For safety however, given the history of ABO HDN a crossmatch against maternal plasma would be advised (if there is time to do so prior to necessary treatment).

c) Expected results of DAT are negative because of the membrane disorder which is not immune mediated.

• check G6PD levels, parvovirus serology and consider other viral infections which may be a trigger, or bacterial infections if there is any indication of sepsis
• send for EMA binding test, extended red cell phenotyping or genotyping prior to transfusion
• Probable hereditary spherocytosis
• Urgent flying squad blood (O RhD-), at 15ml/kg and recheck Hb after transfusion complete.

Question 6.

a) Cryoprecipitate has fewer factors than FFP in a unit, but is in a more concentrated form and primarily contains: FVIII, VWF, FXIII and fibrinogen and thus should be used when preferentially these are required. It is worth mentioning (as an aside to the question) that if you continuously give cryoprecipitate you should be aware that this will elevate the levels of all these factors and not just the one you wish to replace (elevating FVIII/VWF to high levels may predispose to thrombosis in the non-urgent setting).

b) Patient requires red cells, and likely a pool of platelets in view of the rapid fall (from what is likely to be abnormal), FFP (15ml/kg) for the deranged clotting results and one adult dose of cryoprecipitate to increase fibrinogen levels to >1.0g/L, and recheck post infusion. Offer tranexamic acid 1g IV.

c) Possible alternatives may include PCC (but should not be used as first line treatment and always in conjunction with other blood products), and rFVIla (only in the most extreme and life threatening cases, and only after adequate fibrinogen or platelet replacement (plt >50, fibrinogen >1.5g/L). Fibrinogen concentrates can be given with 25-50mg/kg, but not if fibrinogen is >1.5g/L. FXIII concentrates (even if available) are not recommended.

- there is risk with thrombosis in using PCC and rFVIIa, and caution is indicated.

Recent recommendations on transfusion in haemorrhage:

Godier A et al. Use of factor concentrates for the management of perioperative bleeding: guidance from the SSC of the ISTH. Journal of Thrombosis and Haemostasis 2018; 170-174.

Also suggest review of 2015 guidelines on management of massive haemorrhage.

Question 7.

Please read the BCSH apheresis guideline for more background reading.

a) 4.5 or 5% human albumin - single volume exchange

b) For sickle cell patients, stroke, acute chest syndrome or acute hepatic sequestration. Other indications may be severe sepsis or multi-organ failure. Alternative reasons for non-sickle patients might be to reduce chance of alloantibody formation from a recent RhD incompatible transfusion for emergency reasons.

c) Failure of hydroxycarbamide therapy resulting in increased sickle vaso-occlusive crises; secondary prevention of acute chest syndrome; primary or secondary prevention of strokes, or prior to elective surgery.

d) The peak target for sickle patients should be 30% before exchange.

e) Symptoms include para-oral and finger parasthesiae; treatment would include reducing, slowing or avoiding citrate infusions, and administration of oral or IV calcium replacement.

Question 8.

a) PIFT = platelet immunofluorescence test. This is a flow cytometric test whereby a fluorochrome is labelled with an antibody designed to bind to an antiplatelet antibody (eg an antibody which will bind anti-HPA-1a antibodies). Controls are set up (with unbound sample) and then the platelets are run through a flow cytometry machine.

MAIPA = monoclonal antibody-specific immobilisation of platelet antigen. This is essentially an ELISA. An antibody which binds to the platelet glycoprotein in question, whereby the platelets are lysed and the glycoprotein structure remains. The platelet glycoprotein antibody is immobilised onto an ELISA plate using a goat anti-human IgG, then a HRP antibody which binds any anti-HPA antibody (which is designed to cause colour change) is added to the ELISA plate.

b) The most common antibodies in NAIT in Caucasian parents are HPA-1a and HPA -5b antibodies, although in Asians it is HPA-4, so screening must be done for all three.

Management plan (assuming confirmed NAIT):

• test father of baby for HPA antigens, as well as mother.
• monitoring and follow up in specialist obstetric unit
• base treatment on first child's platelet count (likely severe in this case because of clinical history of probable petechiae) - to give IVIg weekly at 1-2g/kg, possibly including steroids
• will need at a time when safe to sample cord blood for baby's platelet count
• delivery will need careful planning, ideally as soon as possible
• peridelivery plan
  • with first baby's platelet count, LSCS preferable; need sampling of baby's platelet count near delivery and needs to be >50x10^9/L for vaginal delivery
  • neuraxial anaesthesia is acceptable as long as mother's plt count and coagulation screen are unremarkable
  • If vaginal delivery: no use of instrumentation (ventouse or forceps), no IM vitamin K or fetal scalp monitoring, urgent cord blood FBC to be sent once delivered and maintain baby's platelets at >20x10^9/L after delivery
  • inform neonatologists of delivery and consider cranial ultrasound at birth to investigate for any haemorrhages
  • inform mother post delivery about risks of recurrence after birth
  • for baby - may need platelets (preferably negative for antibodies as demonstrated by mother) or IVIg, or both. If no HPA-antibody negative platelets, routine platelets will be useful

Question 9.

a) HTC outlines the general policy of the hospital with respect to transfusion - setting standards and audits the current state of the transfusion system and exercises governance.

b) SHOT - national body which investigates haemovigilance (ie clinical risks of transfusion) and issue recommendations. Yearly reports are issued to inform on safety. Hospital transfusion teams send in reports to SHOT for analysis when there has been an error made

c) MHRA - along with regulating medicines, it also regulates the safety of blood component supply and transfusion in the UK. Reporting of errors is mandatory in situations where the blood supply chain is affected (right up to the point of transfusion), as well as planned inspections of the transfusion laboratory at various intervals.

d) NBTC - overall committee which oversees the work of RTCs (regional transfusion committees) and issues guidelines of best practice, service development needs and engages patients and advises NHS and offers training and education. Ten regional transfusion committees sit under the NBTC which in turn oversee the HTCs.

e) SABRE - is the mandatory system for reporting blood safety incidents which is part of the MHRA. (serious adverse blood reactions and events). SHOT reporting is optional (but strongly recommended).

f) Reporting is required to: SABRE (optional to SHOT but should happen), HTC and discussion within the hospital transfusion team, and NHSBT.

Question 10.

a) C+c+D+E-e+

b) A+ platelets should be acceptable alternatives if present (most likely A+ platelets will be available), otherwise AB+ platelets are not routinely available but can be used

c) There aren't many differentials in this case - if not DIC/sepsis and fall in platelet count or medications, it is likely to be PTP with such a sudden fall in the time frame as written in the vignette. The timings of plt count fall are often very similar to HIT (5-10 days) so ensure that the patient has not had any exposure to heparin (more likely from flushing lines rather than thromboprophylaxis in this vignette). As chemotherapy hasn't started it is unlikely to be related to bone marrow suppression, but check other medications such as co-trimoxazole (and others), as well as B12/folate deficiency.

d) Alloantibody formation to platelet antigens, most commonly HPA-1a. Destruction of platelets occurs to both transfused and autologous platelets. Plan is to identify the offending antibody and ensure that future transfusions are appropriately antibody negative. Treatment will involve possible steroids, IVIg, plasmapheresis, with mortality of about 10% and risk of 30% major bleeding. Classically this disorder tends to occur in females who are multiparous or have had pre-sensitation and demonstrate a known history of HPA-antibodies.

(although you shouldn't put this in the answer, you could think of this as being the hyperhaemolysis equivalent in platelets in order to aid learning)