Transfusions


PRBC's

  • Transfusion of red blood cells allows for increased oxygen carrying capacity or oxygen content:  CaO2= Hgb(Sat)(1.34) + 0.003(PaO2)
  • Transfusions are not benign and can lead adverse consequences such as transfusion related acute lung injury (TRALI), transfusion associated cardiac overload (TACO), and transfusion-related immune modulation (TRIM)
  • There exist concerns that blood transfusions, although they may improve overall oxygen carrying capacity, could lead to overall worse local oxygen delivery (due to higher viscosity, loss of deformability, increased adhesion to endothelium, abnormal glycolysis, propensity for microcirculatory stasis, generation of cytokines and bioreactive agents in stored RBC's, impaired control of regional blood flow and NO metabolism, etc.)
  • PRBC's experience a "storage lesion" with diminished levels of 2-3 DPG (resulting in a left-shift in the Hb-O2 dissociation curve), decreased RBC deformability, and free Hb which binds nitric oxide which may lead to local vasoconstriction. 75% of PRBC's alive 24 hrs after transfusion for 42 day old blood
  • TRIPICU Study (Lacroix et al, NEJM 2007) demonstrated no difference between Hgb threshold of 7 gm/dl or 9.5 gm/dl in stable critically ill children with those in the <7gm/dL group receiving 54% fewer transfusions
  • While not replicated in the pediatric population yet, there is evidence from adults to suggest that even in patients with septic shock, contrary to EGDT, a Hgb threshold of 7 for transfusion is equivalent to a more liberal threshold of 9 gm/dl (Holst et al, NEJM 2014
  • Unclear what the optimal Hb threshold is for those with cyanotic heart disease (one RCT of 60 children with Glenn/Fontan procedures comparing 9 vs 13 g/dL Hgb thresholds showed no differences in clinical outcomes) 
  • Controversy regarding whether storage time of transfused blood affects outcomes. Pediatric study, Age of Blood in Children in the PICU (ABC-PICU) is ongoing in an attempt to answer this question. Most recently, Lacroix et al demonstrated in the ABLE study no difference in outcomes with fresh vs. standard blood for critically ill adults. 

Interesting Facts

  • 20-30 trillion RBC's circulating in the average adult
  • ~7% of body mass
  • Comprise ~25% of cells in the human body
  • ~1.4 million produced/second
  • ~200 billion produced/day
  • 100-120 day lifespan
  • ~1% of circulating mass replaced/day
  • ~250 kg of RBC's produced over lifetime
Types of PRBC's

  • Standard: Citrate used as anticoagulant (chelates calcium, which is a critical cofactor in the coagulation cascade), stored for up to 42 days. 1 unit volume ~250 ml (diluted with NS before transfusion for total volume of 32 ml)
  • Leukocyte Reduced: PRBC's contain small amount of WBC's, platelet fragments, and coagulation factors that can lead to inflammatory response when transfused. Decreases the cytokines and WBC's in the blood. Also decreases transmission of intracellular viruses (ie CMV)
  • Washed: washed with sterile saline, removes plasma and increases hematocrit, takes about 2 hours, significantly decreased volume. Can be used in patients with severe allergic reactions
  • Irradiated: Kills off WBC's by inducing DNA damage. Decreases the risk of transfusion associated graft vs. host disease. Can damage RBC's and lead to increased free Hb and potassium. Shelf life 28 instead of 42 days.Indicated if patient has cellular immune deficiency to prevent transfusion associated GVHD
When to Transfuse




How to Transfuse

  • 10 cc/kg should raise Hgb level by 2-3 gm/dl. Generally transfused over 2-4 hours. Generally run slowly over first 15 minutes to detect a reaction
  • Often times, if the patient has never received a transfusion before and is unlikely to receive another one (or is a potential transplant candidate) and would not have difficulties with the volume, 15 cc/kg is given to minimize exposures to multiple donors/units of blood

Plasma

  • Fresh Frozen Plasma (FFP) frozen within 8 hours, taken from single donor. Can be stored up to 1 year after collection
  • Volume 200-250 ml/unit
  • Transfused to correct coagulation factor deficiencies, particularly if active bleeding or before invasive procedures
  • Can also reverse warfarin 
  • FFP unlikely to appreciably correct INR if <1.7 (some teach that the "INR of FFP" is ~1.5
  • Used in a 1:1 ratio with PRBC's for massive transfusion protocols
  • Should be administered empirically in patients who have received more than 1.5X their blood volume (blood volume estimation for infants ~ 80 cc/kg, for children/adolescents ~70-75 cc/kg)
  • Caution for use empirically in patients with liver failure, as although their INR may be elevated, they actually may be hypercoagulable due to initial reductions in protein C and S
  • In general, 30% of normal factor activity is sufficient to achieve hemostasis
  • Can also be used to deliver ATIII to the patient (ie if heparin infusion rate continues to increase to achieve the same ACT goal on ECMO, the patient may be relatively ATIII deficient)
  • In a recent point prevalence study in pediatric intensive care units, the authors found that 1/3 of patients transfused with plasma were not bleeding and had no planned procedure. In addition, plasma transfusion significantly improved INR only in patients with a baseline INR greater than 2.5 (Karam O et al, AJRCC 2015)
How To Transfuse
  • 10-20 cc/kg  of FFP should increase coagulation factors above 30% of normal. Generally given over 30-60 minutes but can be as fast as tolerated
  • Base effectiveness on clinical evidence of oozing or bleeding and repeat coagulation testing
  • AB is universal donor (vs. O negative for PRBC) as there are no antibodies in the plasma and thus can be given in emergent situations

Platelets

  • Thrombocytopenia is common in the pediatric intensive care unit (~25% of patients are thrombocytopenic at some point) and associated with increased mortality (17 vs. 2.5%) (Krishnan, PCCM 2008)
  • Platelet units contain ~ 55 X 109 platelets
  • Irradiation done to reduce risk of transfusion associated graft vs. host reaction
  • Based on adult studies, no difference in bleeding rates between transfusion thresholds of 10,000 vs 20,000 platelets/µl (Slitcher, Transf Med Rev 2004)
  • Threshold of 100,000/µl used for patients on ECMO
  • 10-20,000 for Lumbar puncture
  • Platelets given before invasive procedure generally if platelet count <50,000/µl
  • Volume of 1 unit is about 50-70 ml (apheresis unit is about 200-300 ml with most of the volume, plasma)
  • ABO compatibility not as crucial (although still typically done) and Rh factor still important (as most units contain some RBC's and can cause alloimmunization in Rh negative patients)
How to Transfuse
  • 1-2 platelet units/10 kg but not more than 6 units per transfusion. Given generally over 30-60 minutes but can be given as fast as necessary 
  • For patients <10 kg, 10 cc/kg of pooled or apheresis platelets
  • 1 unit per 10 kg should increase platelet count by 30-50K/µl
  • Posttransfusion platelet count should be 20% higher 10-60 minutes posttransfusion and 10% higher 18-24 hours posttransfusion
  • Failure to increase the platelet count can reflect consumption (ie DIC or HIT), sequestration (ie hepatosplenomegaly), or immune destruction (ie ITP)


Cryoprecipitate

  • Concentrated source of fibrinogen, factor VIII, von Willebrand factor, and factor XIII
  • Used in hypofibrinogenemia, von Willebrand disease, and hemophilia A
How to Transfuse:
  • 1-2 units/10 kg (maximum 12 units) over 30 minutes or ~0.2 units/kg
  • Should raise fibrinogen level 60-100 mg/dL


Complications

Immediate Reactions
  • Occur immediately or within 6 hours of end of transfusion
  • Nonhemolytic febrile reactions
    • Most common benign reaction
    • Fever, chills, headache, nausea, emesis
    • Mediated by pyrogenic substances in the blood product or recipient antibodies reacting to donor leukocyte
  • Anaphylaxis
  • Isolated Hypotension
  • Bacterial contamination
    • More common with platelets (stored at 20-24 C)
  • Hemolytic Reaction
    • Lysis of RBC's due to incompatibility between donor and recipient
    • Usually due to human error with resulting ABO mismatch (ie unit meant for another patient)
    • Fever, chills, hemoglobinuria, diffuse pain, hypotension, shock, DIC
    • Tx: Stop transfusion immediately, supportive care, inform blood bank
  • Transfusion Related Acute Lung Injury (TRALI)
    • Theory is that antibodies in donor plasma react with recipient WBC antigens, leading to immune activation
    • Diagnosis: Within 6 hours of transfusion, new ALI (P:F <300) and no temporal relationship to other risk factor. Anti HLA or neutrophil Ab's in donor plasma highly suggestive but absence of Ab does not exclude TRALI 
    • Tx: Stop transfusion, supportive care (oxygen, mechanical ventilation, vasoactive infusions), report reaction to blood bank so they can test and remove donor's other units
    • Usually resolves within 96 hours
    • Mortality rate of ~6%
  • Transfusion Associated Circulatory Overload (TACO)
    • Pulmonary edema second to heart failure
    • Respiratory distress, hypoxemia, tachycardia
    • Tx: Stop transfusion, supportive care with oxygen, diruetics
    • Slow transfusion (ie over 4 hours) may prevent TACO in at risk patients
Delayed Reactions
  • Transfusion Associated Graft Vs. Host Disease
    • lymphocytes from donor infused into immunocompromised patient unable to reject them. Donor WBC then attacks recipient's tissue
    • Symptoms: Rash, diarrhea, fever, elevated LFT's 8-10 days after transfusion
    • Mortality 90%
    • Prevention: Use irradiated blood in immunocompromised patients
  • Delayed hemolytic reaction
    • Due to recipient alloantibodies reacting with donor RBC's
    • Occur 3 days to 2 weeks after transfusion
    • Symptoms: anemia, jaundice
From: Weinstein, American Society of Hematology, 2012 Clinical Practice Guide on Red Blood Cell Transfusion

Massive Transfusion

  • Used for massive (>30 cc/kg) and uncontrolled bleeding
  • Uses 1:1:1 ratio of PRBC:FFP:Platelets which has been shown to improve mortality and decrease length of stay
  • Otherwise, with massive transfusion, can get:
    • Coagulopathy
    • Dilutional thrombocytopenia
    • Hypothermia
    • Citrate toxicity, leading to hypocalcemia
    • Hyperkalemia

Massive Transfusion Pediatric Protocol- University of Michigan


References

1) J. Lacroix, P.C. Hébert, J.H. Hutchison, et al.: Transfusion strategies for patients in pediatric intensive care units. N Engl J Med. 356:1609-1619 2007
2) J. Cholette, J. Rubenstein, K. Powers: Cyanotic children undergoing open heart surgery do not appear to benefit from higher hemoglobin levels: Results of a restrictive v liberal RBC transfusion strategy. Crit Care Med. 37:A434 2009
3) Holland LL, Brooks JP. Toward rational fresh frozen plasma transfusion: Theeffect of plasma transfusion on coagulation test results. Am J Clin Pathol. 2006 Jul;126(1):133-9.
4) J. Krishnan, W. Morrison, S. Simone, A. Ackerman:Implications of thrombocytopenia and platelet course on pediatric intensive care unit outcomes. Pediatr Crit Care Med. 9:502-505 2008
5) .S.J. Slitchter: Relationship between platelet count and bleeding risk in thrombocytopenic patients. Transf Med Rev. 18:153-167 2004
6.  Lacroix J, Hébert PC, Fergusson DA, Tinmouth A, Cook DJ, Marshall JC, Clayton L, McIntyre L, Callum J, Turgeon AF, Blajchman MA, Walsh TS, Stanworth SJ, Campbell H, Capellier G, Tiberghien P, Bardiaux L, van de Watering L, van der Meer NJ, Sabri E, Vo D; ABLE Investigators and the Canadian Critical Care Trials Group. Age of Transfused Blood in Critically Ill Adults. N Engl J Med. 2015 Mar 17.PubMed PMID: 25776801.