This document discusses blood and blood products used in critically ill patients. It summarizes current recommendations for red blood cell transfusion thresholds, risks of transfusion, and alternatives to transfusion such as restrictive transfusion strategies and erythropoietin use. Complications of transfusion discussed include acute and delayed hemolytic reactions, febrile reactions, allergic reactions, infections, and transfusion-related acute lung injury. Platelet and plasma transfusion indications and risks are also summarized.

1. DR IMRAN GAFOOR
DR DINESH RAWAT
FELLOW.DEPT. OF CCEM
SGRH,NEW DELHI
BLOOD & BLOOD PRODUCTS

2. INCIDENCE :
: Anemia has an incidence of 29-37% in critically ill.
: Recent cross-sectoinal analysis showed that,29%
had Hb < normal & 37% required RBC
transfusions.[vincent et al;JAMA-02]
:MOST SIGNIFICANT RISK assoc with anemia is
the harm resulting from decrease in Oxy carrying
capacity & plasma volume.

3. NATURAL HISTORY OF
UNCORRECTED ANEMIA
: Leung et al found ECG changes that may be
indicative of myocardial ischemia in subjects of
isovol hemodilution to a conc. Of Hb 5gm/dl.
[leung et al-anaesthesi. 2000]
:Descriptive studies in pt refusing RBC transfusion
have demonstrated that pt can survive surgical
interventions with Hb as low as 4.5gm/dl.
[spencer et al-Am j surg 1990]

4. : Development of consequences of anemia
depends on pt’s ability to compensate.
: less tolerating group of pt’s are –
a) older
b)severly ill
c) coronary,cerebrovas,resp co-
morbidities

5. :Researches have revealed that increasing degrees of
anemia were associated with a disproportionate
increase in mortality rates in cardiac patients.
[Hebert et al-Am j resp criti care 1997]
:Anemia increases risk of death in patients of significant
cardiac disease.

6. : CURRENT RECOMMENDATIONS –
- except in circumstances of ACS pt can be
transfused for Hb<7gm/dl with a goal of main-
taining levels between 7-9 gm/dl .
- in ACS,increased survival has been demon-
strated with transfusion for Hb<10 gm/dl.

7. [Hebert et al NEJM-1999]
: enrolled 838 patients
: it’s only trial powered adequately to evaluate the
impact of different transfusion strategies on mor-
tality/morbidity of recepients.
: concluded – 30 days mortality rates were signif-
icantly lower with restrictive transfusion strategy
(≤7 gm/dl),who were less acutely ill(APACHE<
20) & among patients < 55 yrs of age.

8. SUBGROUPS OF TRICC TRIAL
Effects of transfusion in pt with cardiovascular d/e :
pt when equally divided in restrictive transfusion &
liberal transfusion groups, study, revealed that
restrictive group required lesser diuretic usage but no
difference in mortality was noted between two groups.

9. SUBGROUPS OF TRICC TRIAL
Effects of transfusion on weaning :
- 82% of pt in restrictive transfusion group were
successfully weaned & extubated compared with
78% in liberal group.
- In pt’s who required > 7 days of ventilation,no
difference in time of successful ventilation b/n two
groups.
- Each additional transfusion was associated with inc-
reased duration of ventilation.

10. QUESTIONS UNANSWERED IN TRICC
TRIAL
? Why liberal strategy group failed to improve
mortality & rates of organ failure in critically
ill ??
Possible explanations :
a) greater no. of allogenic RBC units depressed
host immune responses.
[Hermans j et al circulation 1998]
b) altered microcirculatory flow as consequence
of prolonged storage times.

11. . Pulmonary edema & ARDS were increased in libe-
ral strategy group. Thus further concluding –
“ restrictive RBC transfusion strategy didn’t
adversely affect outcomes related to mechanical
ventilation .
[Hebert pc et al – chest 2001]

12. - Goal directed transfusion triggers :
If fall in Scvo2 < 70% is used as a transfusion
trigger , for increasing Hct > 30%, Rivers et al
concluded that it only led to increased no. of tran-
sfusions with no added survival benefit.
[Rivers et al NEJM 2001]

13. ALTERNATIVES TO TRANSFUSION
- Two most useful approaches in ICU :
1) decrease phlebotomies ,
2) use of erythropoietin .
- Other strategies :
: decreased use of NSAIDS ,
: blood conservation in form of pediatric
test tubes,arterial catheter reinfusion
setups.
: use of tranexamic acid .

14. ERYTHROPOIETIN
* Critical illness is characterized by blunted erythro-
poietin production & response.
[Rodriguez et al –j critical care 2001]
• Anemia in critically ill is result of erythro. gene in-
hibition by inflammatory mediators.
[Jelkmannw et al-j inter cytoki 1998]
• Inflammatory cytokines directly inhibit RBC production
by bone marrow & may produce Fe
metabolism abnormalities.
[Krantz sb et al-Am j med sci 1994]

15. : 300 units / Kg daily for 5 days f/b every
other day till ICU discharge.
• Studies demonstrate that recom. erythro. therapy
in critically ill can decrease RBC transfusion & in-
crease Hb levels.thus consistent with hypothesis
that anemia in critically ill is similar to anemia in
chronic disease pt & characterised by RELATIVE
ERYTHROPOIETIN DEFICIENCY.

16. sHOWEVER due to highcosts,lack of clinical benefit,
& delayed effects(weeks to act),,its use is not reco-
mmended as a blood conservation strategy.
RECOMMENDATIONS (FINK Textbook cri care)-
1) Adopt a transfusion threshold of 7 gm/dl in vol-
resuscitated critically ill adult,child & post op
patients including pt with h/o CAD;septic shock
after initial resuscitation.
2) Aim to maintain Hb between 7-9 gm/dl.

17. 3) Transfuse one unit at a time & measure after
every transfusion.
4) Insufficient evidence regarding transfusion
trigger in ACS & early septic shock(<10gm/dl
might be beneficial)
5) Erythropoietin is not routinely recommended
except in chronic renal failure.

18. NAPOLITAM LM et al (critical care clinic)
2004
* RBC transfusion doesn’t improve tissue oxygen
ation consistently in critically ill & may sometime
result in worsening.
Lack of efficacy related to changes during storage :
- storage time
- increased endothelial adherence of st-
ored RBC
- NO binding of free Hb in stored blood
- donor leucocytes
- host inflammatory response
- decrease RBC deformability
SUGGESTION : conservative RBC transfusion strategy in cr-
itically ill.

19. DOSING & ADMINISTRATION
- Each unit of packed cell~300 ml,given over 2-3hrs
- Each unit increases Hb by 1g/dl or Hct by 3% in
healthy individuals without ongoing blood loss
or destruction,however,it takes 24 hrs for intra-
vascular volume to equlibrate for full effect.
- In emergency O neg RBC can be given.

20. TYPES OF RBC PRODUCTS
WHOLE BLOOD : RBC+platelets+plasma proteins
- indicated in hemorrhage & anemia
- autologous donation prior to surgery
PACKED RBC’S : 200ml of RBC’S + preservatives
- each bag has Hct of 60% & approx
200 mg elemental iron.
GAMMA IRRADIATED : destruction of donor T-lym.
for GVHD prevention in immunocom.,
stem cell recepient.

21. - CMV antibody neg : used in transplant & pregna-
ncy(high risk of CMV complications)
- Leukocyte depleted : in febrile reactions,to avo-
id leucocyte immunization in hema-
tological malignancy.
- Washed RBC’S : washed with NS to remove
donor serum,
-used in IgA def & those at high
risk for anaphylaxis,
- in PNH pt ( to deplete complement)

22. RISKS OF TRANSFUSION :
- UNIFACTORIAL : (transfusion is the cause)
- compatibility/technical errors,
- HIV / hepatitis,
- endotoxemia,
- GVHD.
- OLIGIFACTORIAL: (transfusion + other factors)
- fever
- anaphylactoid reaction
- TRALI
- CMV
- allergies

23. - MULTIFACTORIAL (transfusion as a risk factor):
- ARDS
- MODS
- TRIM(transfusion related immuno-
modulation)
- thrombosis.

24. TRANSFUSION RELATED
COMPLICATIONS
A) Acute Hemolytic Transfusion Reactions(AHTR):
- most severe & life threatening,
- IgM against donor major RBC antigen,
- manifes. : fever,dyspnea,tachycardia,
back pain,hypotension,chills,chest pain
pain at infusion sites,lumbosacral pain
- hemoglobinuria may be first sign in se-
dated patient,
- centrifuged blood & reddish plasma co-
nfirms diagnosis.

25. - STOP TRANSFUSION IMMEDIATELY
- Start 5% dextrose with 3 amp soda-bicarb@250
ml/hr.(target UOP 30-50 ml/hr)
- i/v hydrocortisone 100mg stat,
- i/v diphenhydramine 50mg stat,
- Acetaminophen PO 650mg,
- 0.3ml s/c 1:1000 epinephrine,
- Notify blood bank
- Send CBC,coombs test,haptoglobin,LDH,biliru-
- bin,PT/Aptt,fibrinogen.

26. b)Delayed Hemolytic Transfusion Reaction(DHTR):
, -occurs by 1-2 days,can be seen by 10 days
- recipients antibodies against minor donor
RBC antigens produced by anamanestic
response,d/t previous sensitization
- manifesn. : dec Hb,inc indirect bilirubin,
positive direct coombs test
-T/t : compatible PC transfusion.

27. c) Nonhemolytic febrile reactions :
- minimum 1 dec rise in temp,not explained by
pt’s clinical condition(usually within 1Hr)
- most common with platelet transfusion
- maybe due to recepients Ab’s against donor
WBC antigens,
D/d with bacterial contamination(high fever/se-
psis in infection)
- T/t : antipyretics & tramadol for shivering.

28. d) ALLERGIC REACTIONS :
- d/t transfused allergens in donor products,
- may reach anaphylactic proportion in IgA def.
- presents as urticaria,bronchospasm,
- T/t : antihistaminics
e) IRON OVERLOAD :
- each ml of PC contains ~ 1mg elemental iron
- seen in sickle cell d/e,thalassemia,myelodys-
plastic syndromes.
- iron deposited in myocardium,liver,bone-marrow

29. f) Transfusion related acute lung injury(TRALI) :
- due to diffuse neutrophilic activation & ca-
pillary leakage,
- both immune & non immune mechanisms
involved,
- manif. : dyspnea,tachypnea,fever,hypoxia,
B/L pulmonary infiltrates
- picture resembling ARDS (vol overload,
heart failure excluded)
- T/t is supportive as most cases self limiting.

30. g) Bacterial infections :
- commonly yersinia through blood & staph/
strepto/gram neg through platelets/cryopt.
- incidence decreased d/t plastic blood bags,
- hypotension,fever,chills within 3 hrs f/b se-
ptic shock & DIC,
- both pt’s & blood bag’s blood should be cu-
ltured

31. h) Viral infections :
- Hep C,B,A HIV(I,II) HTLV(I,II) CMV
prions,parvovirus B19
- CMV infection in immunocom. Is asympto-
matic but in immunocompromised can lead
to end organ d/e.
i) Others :
malaria ,syphilis,tryp. Cruzi(chagas d/e)

32. j) Transfusion assoc. cardiovascular overload :
-resembles TRALI clinically but responds
to diuretics.
k) GVHD(Graft versus host disease) :
- d/t donor lymphocytes that engraft & then
proliferate in response to stimuln. by fore-
ign antigens,
- seen post transfusion 2-50 days,
- rash,diarrhea,hepatitis,pancytopenia.
- seen in HSCT,neonates,lymphoprol. d/e
- prevention by gamma-irradiation of blood

33. l) Hyperbilirubinemia :
~30% of aged RBC’s don’t survive,
- bilirubin from destroyed RBC’s can lead to un-
conj. Hyperbil. & impaired excretion into bilia-
ry canaliculus leads to conjugated hyperbil.
m) Post transfusion purpura :
-potentially life threatening
- platelet specific alloantibodies develop 5-10
days after transfusion & can cause severe
thrombocytopenia,
-paradoxically recip. Platelets are destroyed

34. - Platelet transfusion is ineffective rather IVIG 2g/
kg over 2-5 days is recommended.
n) Imunomodulation :
- transfusion induced immunosupp. has been
implicated in post op infections,cancer recu,
non-hodgkins lymphoma,
- but clinically proven only in AML pt undergoi-
ng chemo[slichter et al hemato basic princip]
- leukoreduction decreases immunomodulation

35. PLATELETS
- Spontaneous bleeding doesn’t occur unless plt
count falls below 5000-10,000/µl.
- For majority of invasive procedures plt count of
30-50K/µl will be adequate.
- For high risk procedures (neurological/opthalmo-
logical) ASA & amer coll of pathologists recomm-
end count of 1L/µl.
- In massively hemorrhaging patient factors deficit
correction along with platelets is required if<50k/
µ/L & if there is microvascular bleed <1L/µL

36. Thrombocytopathy(dysfunctional platelets) :seen in
- liver/kidney d/e
- sepsis,malignancy
- trauma,obs. complications
- extra corporeal circulation,some medications.
requires higher platelet count to achieve
hemostasis
-

37. - Treating cause abates thrombocytopenia;therap-
ies which might be helpful :
- dialysis & desmopressin in renal failure
- rewarming in hypothermic trauma pt
- correction of acidosis.
- Platelet transfusion not needed in :
- 1) ITP
- 2) post transfusion purpura
- Instead IVIG needed

38. - Relatively contraindicated in TTP/HUS.
- Amount : 3-4 units of pooled random donor platel-
ts is adequate.
- Survival : ~3 – 5 days in room temp.
- Plt units have to be stored in room temp. as plts
loose shape & release their granular contents if
refrigerated.
APHERESIS :contains equivalent of 4-8 units of
whole blood platelets.

39. - Also has 200-400 ml plasma,
- For pts who have become refractory to random
donor platelets d/t alloimmunization.
- PLATELET & HEMATOCRIT :platelet function &
interaction with subendothelial tissue declines at
lower hematocrits.In thrombocytoenic & thrombo-
cytopathic pt’s;transfusion to higher Hct is better.
[Valeri c r et al –transfusion 2001]

40. GRANULOCYTES
- Used in profound & prolonged neutropenia
secondary to marrow suppression.
- Collected by : 1) filtration leukapheresis
- 2) continuous flow centrifugation
- Usefulness is doubted d/t :
1) inability to collect sufficient cells
2) early development of allo-immuniz.

41. FRESH FROZEN PLASMA (FFP)
- 1 unit of FFP is plasma taken from one unit of
whole blood,
- approx. 200-250 ml in volume,
- No leukocytes ,so,no risk of CMV/GVHD,
- Indicated in hemorrhaging pt as well as coagula-
tion factor defeciencies condn.(massive transf-
usion,DIC,liver d/e,cardiac bypass surgery)
- Never used for volume expansion or isolated
factor deficiencies(VIII/IX)

42. - Usually there is an increase of 1.6 times normal
PT/aPTT before clinically imp factor def. exists
(which is ~20% reduction in normal factor conc.)
- THUS- FFP is indicated when PT/aPTT ratio(re-
ference midrange normal ÷ actual) > 1.5 times.
- Dose : 10-15 ml/Kg recommended
- In a 70 kg adult male :
1 unit FFP increases most factors ~ 2.5%
4 “ “ “ “ “ ~ 10%

43. CRYOPRECIPITATE
contains fibrinogen,v-Wfactor,VIII,XIII,fibronectin,
- conc. of fibrinogen in cryo > 10 times of FFP
Indications : 1) DIC, along with FFP
2) isolated hypofibrinogenemia(<100-
mg/dl)
3) platelet dysfunction not responding
to DDAVP/dialysis.
Dose : ~ one bag / 10 kg body weight

44. FIBRINOGEN CONCENTRATE
 RiaSTAP : heat treated,lyophilized fibrinogen
powder.
- made from pooled human plasma.
RECOMBINANT FACTOR VIIa :
- popularized as ‘panhemostatic agent’
- but evidence outside hemophilia setting is
lacking,
- no decrease in mortality + increased risk
of thromboembolism

45. CONCENTRATED ALBUMIN :
severe hypoalbuminemic states with compli-
cating hypovolemia:.
ANTI-THROMBIN CONCENTRATES :
- used in anti-thrombin deficiency thrombophilia
GAMMA-GLOBULINS :
- in hypogammaglobulinemia,
- in high doses in autoimmune diseases

46. - SPECIFIC IMMUNOGLOBULINS :
- for prophylaxis in rhesus,tetanus,zoster,
Hep B.

47. TRANSFUSION IN MASSIVE
ACUTE HEMORRHAGE
- Pathophysiology of coagulopathy in actively blee-
ding should be viewed in context of primary/initi-
ating event(which may be d/t trauma,hypoxia,
hemorrhage,hypothermia),followed by,second-
ary insult in resuscitated patient(d/t stored blood
transfusion,hemodilution,continuing hypoxia)
- Recent focus in managing a bleeding patient is
avoiding massive transfusion coagulopthy which
leads to triad of death i.e. coagulopathy,acidosis
& hypothermia.

48. - Lab parameters co-relate poorly with clinical
evidence of hemostatic failure.
- Rather global tests of hemostatic plug formation
& stability, such as, thromboelastography(TEG),
thrombin generation tests,clot waveform analysis
are more clinically relevant.

49. CRASH-2 TRIAL : EFFECT OF TRANEXAMIC ACID
ON DEATH,VASC. OCCLUSIVE EVENTS & BLOOD
TRANSFUSION IN TRAUMA PATIENTS.
- Early administration of tranexamic acid,an antifibrinolytic
agent,to trauma patients,with or at risk of significant bleeding
reduces the risk of death from hemorrhage with no apparent
increase in fatal or non-fatal vascular occlusive events.(with no
stastically significant difference in transfusion requirements)
- DOSAGE : 1gm loading dose in 10 mins f/b infusion
of 1gm over 8hrs.
[lancet- 2010]

50. BLOOD STORAGE LESIONS & POTENTIAL
CLINICAL CONSEQUENCES
- The storage lesions progressively increase until the time of
expiry & extent of these changes depend on specific blood
components,preservative medium,container,storage
time,storage condns.
- Quantative deficiencies may result in reduced RBC
survival & thus excessive donor exposures.
- Qualitative deficiencies leads to decrease membrane
flexibility which impairs microcirculation hemodynamics.
-

51. - Decreased 2,3-DPG decreases Hb’s oxygen affinity thus
impairing oxygen unloading.
- transfusion leads to increased unconjugated
hyperbilirubinimia ,neutrophilia,saturation of serum Fe.
- Biologically active lipids in stored blood leads to ALI.
- Blood transfusion is risk factor for post injury multi-organ
failure & ARDS.
- Many of these changes can be minimised by pre-storage
leukoreduction

52. HAZARDS OF RAPID BLOOD
TRANSFUSION
- CITRATE TOXICITY :
- pt responds to citrate by removal of citrate &
mobilization of ionized calcium.
- toxicity seen when > 500 ml transfused in 5 min
- citrate metabolism impaired by hypotension,
hypovolemia,hypothermia,liver d/e
- toxicity potentiated by alkalosis,hyperkalemia,
hypothermia,cardiac d/e

53. - But,a well perfused warm,adult pt with normal
liver tests can tolerate without Ca replacement.
ACID-BASE/ELECTROLYTE CHANGES :
- acidity of stored blood is d/t citric acid of anticoagulant
+ lactic acid of storage
- Citrate is metabolised to bicarbonate & thus
leads to metabolic alkalosis after transfusion.
- acid base status of recepients is predominantly
determined by tissue perfusion.

54. - High potassium levels in stored blood is harmless
expect in acute renal failure.In contrast after 24hr
hypokalemia can ensue.(transfused cells attaini-
ng electrolyte balance in donor plasma)
- high sodium content in FFP/whole blood
mandates caution in patients having disordered
salt water handling.