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
From Valentine SL et al, PCCM 2018
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. 1 unit is ~250ml (some considerable variability). Hence, if 10-15 cc/kg is >~250 cc, one would generally transfuse 1 unit (unless actively losing blood and clinically would need more than a single unit).
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
Platelets can be "pooled" or "apheresis." Pooled come from many donors and are more easily collected whereas apheresis come from single donors and have the ability to HLA match.
Irradiation done to reduce risk of transfusion associated graft vs. host reaction (ie immunosupressed patient)
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 often 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 (i.e. for an adult a "5 pack" is generally sufficient). 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
Often given when fibrinogen <150 (actively bleeding) or <100 mg/dl
TEG Interpretation
Courtesy of Richard Pierce, MD
Courtesy of Richard Pierce, MD
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
UM Massive Transfusion Protocol
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
Changes blood products from a PULL (i.e. medical team asking for it from the blood bank) to a PUSH (blood bank actively sending out units to the medical team)
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.