Indications for Transfusion

					Transfusion
BLOOD PRODUCTS
• Blood-cells products
   whole blood
   packed red blood cells
   leukocyte-poor (reduced) red cells
   washed red blood cells
   random-donor platelets concentrates
   single-donor platelets concentrates
   irradiated blood products (red blood cells and
     platelets concentrates)
   FFP
   leukocyte (granulocyte) concentrates
• For over 40 years, decision to transfuse red blood
  cells was based upon the "10/30 rule

• 1988 National Institutes of Health Consensus
  Conference on Perioperative Red Blood Cell
  Transfusions : no single criterion  clinical
  status and O2 delivery should be considered.

• Transfuse erythrocytes must be based upon risks
  of anemia vs risks of transfusion
• The major considerations : degree of
  O2 delivery and compensatory
  mechanisms.

•   DO2 = Cardiac output x arterial O2 content

• Greater CO, right shift O2-Hb dissociation
  curve, and increased O 2 extraction can
  compensate.
• A study : acute reduction in Hb=5
  g/dL : No inadequate O2 delivery
• RBC Tx should initiated when pt develops
  symptoms of anemia (easy fatigue, dyspnea on
  exertion, tachycardia) regardless of anemia.

• Level varies with age and underlying disease.

• Young : until Hct< 20

• significant underlying CVD= Hct = 25-33 %
• Compensatory mechanisms may be
  impaired in critically ill patients

• 838 critically ill pts found no difference in
  mortality between Tx Hb 7-9 or 10-12
Perioperative transfusion
• "restrictive" Tx strategy (<7) and to
  "liberal" strategy (<10)

• Mortality rates were significantly lower
  with restrictive who <55 years but not
  among significant cardiac disease.
• Mortality during hospitalization was
  significantly lower in restrictive
  although 30-day mortality similar.

• At least as effective as, and possibly
  superior, in critically ill, with
  exception of MI and UA
Critically Ill
• Anemia is common in ICU patients.

• 95 % stay > 3 days (> 40% receive PC)

• Pts may receive other blood products to
  manage bleeding.
RED BLOOD CELLS
• Historically to provide clinical benefits
  when the Hb <10 g/dL.

• Adverse outcomes (infection, acute
  respiratory distress, multiple organ
  dysfunction, and death)
• Decision based on :
  volume status, shock or hypoperfusion,
  duration and severity of A, and
  cardiopulmonary status.

• Restrictive approach (< 7 g/dL) as
  effective as liberal approach (<10 g/dL) in
  hemodynamically stable critically ill
  (exceptions of acute MI, UA, or active
  hemorrhage).
Use of supplemental erythropoietin
• Erythropoietin increases erythropoiesis if B12,
  folate, and iron are adequate.

• Preoperatively with EPO with 40,000 units

• EPO postoperatively can increase recovery to
  normal Hb levels.
COLLECTION AND STORAGE
 Transfusion are due to two important
 developments :

• Preservative solutions (long shelf-life)

• Storage bags (permit separation of
  blood components and maintain sterility
  and viability of cells).
Preservative solutions

• CPD for 21-day storage
• CPD-adenine for 35-day storage
• Additive solutions storage for 42 d.
CHOICE OF COMPONENT
• Choice between red cells, whole blood or
  autologous salvaged blood.

• In addition, red cell preparations may be
  leukoreduced, irradiated, or washed.

• Major difference : volume of plasma.
• Chronic anemia should be transfused with
  RBC since volume replacement is not
  required.
• Whole blood : only when with an adult
  who has bled acutely and massively

• And only after 5-7 U of RBC plus
  crystalloids.
PHYSIOLOGIC CHANGES WITH
STORAGE
Red cell viability and recovery

• When stored RBC are transfused, some of cells
  are removed from circulation; as storage
  increases, more cells removed after transfusion.

• This is highly dependent upon solution, donor
  variation, leukoreduction, amount of mannitol in
  storage solutions, and storage hematocrit
• Recovery threshold for circulating
  red cells 24 hours following infusion
  is currently set at 75 %.
2,3 DPG concentration

• After 5-6 weeks of storage, levels fall
  toward 10 %.
• Shifts to the left, reduced O2 release.
Potassium leakage
• One unit of whole blood = 8.5 meq
• At risk : infants, RF (fresher, washed,
  potassium adsorption filter)
Ammonia

• Plasma ammonia increase in stored
  blood, after five to six weeks.
• Saline-washed red cells
Nitric oxide

• Endogenous NO vasodilator that
  determine vascular resistance.
SPECIALIZED RBC
COMPONENTS
Leukoreduced red cells
• Several complications due to leukocytes.

• HLA alloimmunization against class I Ag does not
  appear if < 106 leukocytes.

• Filters (into blood collection sets or after
  collected).
• Febrile transfusion reactions are due to
  WBC contamination.

• Time red cells are filtered is important.
• As close to collection time as possible, to
  remove intact leukocytes (cytokines)
• Rather than bedside.

• Another advantage do not transmit CMV.
• Cannot be implemented because of costs.


• Following patients should receive leukoreduced :

- Chronically transfused patients
- Potential transplant recipients
- previous febrile nonhemolytic transfusion reactions
- CMV seronegative whom seronegative components not
   available
- Cardiac surgery with cardiopulmonary bypass (outcomes).
Irradiated red cells
  Avoid GVHD in immune deficiency states, (25 Gy)
  to prevent donor T lymphocytes.

 Recommended for :
- From relatives donation
- Large doses of chemotherapy
- AIDS.
• Irradiation also induce lesion in RBC
  membrane.
• Reduced red cell viability
• Leakage of potassium

• Irradiated products < 28 days storage
Washed red cells
• To prevent complications with infusion of
  proteins in plasma.

- Severe or recurrent allergic reactions (eg,
   hives)
- IgA deficiency when IgA deficient donors
   are not available (frozen deglycerolized of
   choice)
- Complement-dependent AHA to prevent
   complement infusion.
RBC transfusion indication
1. Whole blood
       • acute hypovolemia (hemorrhagic shock)
       • massive transfusion
       • exchange transfusion in for HA of newborn

2. Red cell concentrate - symptomatic anemia
        • IDA or megaloblastic in elderly with
           angina or CHF
        • hemolytic anemia- rarely, poor tolerated Hb<7g/L

       • hypoproliferative anemia
              - anemia in malignancy
              - anemia after chemotherapy or radiotherapy
              - aplastic anemia, myelodysplastic syndrome, -
               - mylofibrosis, ACD
3. leukocyte-poor (reduced) red cells :
   - Prevent nonhemolytic febrile reactions
    Ab to WBC and plts exposed to
   previous transfusions or pregnancies
  - Prevent sensitization of AA candidate BMT
  - Minimize transmission of viral disease HIV, CMV



4. washed red blood cells
   -With severe allergic reaction following transfusion
   -With paroxysmal nocturnal hemoglobinuria
Chronic anemia-iron overload
• Chronic anemia (BM failure) can lead to
  iron overload.

• Approximately 200 mg of iron are
  delivered per unit of RBC.

• Hemosiderosis can produce (15 to 20
  grams-75 to 100 units).
Clinical and laboratory aspects of
platelet transfusion therapy
• Until late 1960s platelets were largely
  unavailable for transfusion except in fresh
  whole blood.


  Difficulties in preparing of platelets :
• Platelets tended to clump.
• Refrigeration severely reduced survival,
  room temperature increase bacterial
  overgrowth.
Platelet dose
• Random donors consist of units containing 0.55
  to 0.8 x 10(11) platelets.

• Standard dose : one unit per 10 kg of body wt.

• 5-8 units for prophylactic in adults, 4 units for
  children, and 10 units for thrombocytopenia who
  are bleeding, in surgery, or are victims of trauma.

•   Infusion of 6 units of random donor to adult with
    BSA 2.0 raises the platelet 30,000/µL at one hour.
Single donor platelets
• Apheresis technology, permits collection
  of multiple units of plts from single donor.

• An individual can donate twice per week.

• Donors are allowed to donate only 24
  times in a year.
BACTERIAL CONTAMINATION
• One important factor : duration of
  storage.
• Much lower for ≤4 days (1.8 vs 11.9)
INDICATIONS FOR PLATELET
TRANSFUSION
• Chemotherapy
• Aplastic anemia.

• Accelerated platelet consumption (AIDS,
  sepsis, DIC)

• Cardiopulmonary bypass
• Surgery with drugs impair platelet
  function.
• Platelet transfusion should be
  avoided in TTP/HUS.

• Worsening neurologic symptoms
  and ARF (expanding thrombi).

• Similar considerations : HIT.
Hypoproductive thrombocytopenia

• Thrombocytopenia due to chemotherapy
  or aplastic anemia managed prophylactic.

• 6 U plt or one plateletpheresis twice
  weekly.
• Surgical bleeding does not occur until < 50,000
  /microL

• Spontaneous bleeding < 10,000/microL
Recommendation

• Threshold of 5000-10,000/microL with
  no or only "dry" bleeding.
• More aggressive therapy : active bleeding
  >38ºC or prior to minor surgery

• 20,000/microL in infection or other risk
  factors for bleeding
• 50,000/microL with active bleeding or prior
  to an invasive procedure.
Immune thrombocytopenia

• While platelet transfusions not indicated routine
  management, they may be utilized in those with
  significant clinical bleeding.
Platelet function disorders
• Congenital or Acquired

• Common congenital abn : mild, bleeding only in
  surgery, respond to desmopressin.

• More severe (Glanzmann) may require large
  numbers of platelets.

• Recombinant factor VIIa may reduce need for plt.
Cardiopulmonary bypass surgery
• Cardiopulmonary bypass : destruction of
  platelets & function impaired.

• Not transfuse prophylactically

• If bleeding excessively, consider platelet
  transfusions.
Drug-induced platelet dysfunction
• Aspirin , IIb/IIIa inhibitors clopidogrel, and
  ticlopidine

• When surgery is required (bypass),
  bleeding can become a serious problem.

• Transfusions to treat surgical bleeding.
EXPECTED AND OBSERVED INCREASE
IN PLATELET COUNTS


• Increase in platelet count is maximal at 1
  hour post-transfusion.

• Linear decrease, which returns to baseline
  at 72 hours.
• Adult with BSA of 2 m², 6 units should raise
  platelet count by 25,000/microL.

• "refractoriness" defined as corrected platelet
  count increment of less than 5000

• Two or more platelet transfusions
• Causes for platelet refractoriness : fever,
  sepsis, bleeding, splenomegaly, DIC,
  drugs, alloimmunization, and ABO
  mismatch
• Splenomegaly a cause for poor
  responses to platelet transfusion.

• Normal : 1/3 of plts are sequestered.

• In extreme splenomegaly, 90%
• Alloimmune platelet refractoriness : Ab to
  Ag on transfused platelets.
• Almost always against HLA Class I
  (HLA-A and HLA- B)
• Platelet recovery: 10 minutes to one hour
  following transfusion.
• Platelet survival: 18 to 24 hours post-Tx.
• Rise of at least 5000/microL /U or 30,000
  when transfusing apheresis.

• Platelet survival : sufficient in about 3 d
Two patterns :

1. Normal increment at one hour, return to
   baseline within 24 : sepsis, BMT, DIC, and
   bleeding and medications.

2. Little or no increment in platelet count :
   alloimmunization.
MANAGEMENT OF THE ALLOIMMUNIZED
PATIENT

• HLA-matched platelets
• Crossmatch-compatible platelets
• Ab specificity method (identify HLA
 specificities Ab in patient's plasma)

• Antibodies to platelet specific
  antigens
• ABO matched platelets
PREVENTION OF ALLOIMMUNIZATION


• Prevent alloimmunization to HLA Class I
  Ag : leukocyte reduced blood components
• ABO matching of platelets and recipients
  is not essential, but is preferred.

• Rh- women of childbearing age should
  receive only Rh- plts, unless none
  available.

• In Rh+ : platelets with a dose IVIG.
 Platelet transfusion-indication
1. Temporary thrombocytopenia after radio- chemotherapy

      • platelet count below 5 G/L
      • platelet count 6-10 G/L and:
               - minor hemorrhagic (petechiae , ecchymoses)
               - fever >38oC
      • platelet count 11-20 G/L
               - coexisting deficiency of coagulation factors
               - heparin administration
               - before lumbar puncture and BMB
      • platelet count above 20G/L
               - hemorrhagic diathesis
               - before invasive procedure
Platelet transfusion-indication

2. Bleeding with functional platelet abnormality
3. After massive transfusion(RBC) and
   thrombocytopenia
4. Cardiac surgery with extracorporeal circulation
Plasma preparations
• FFP separated from freshly blood and
  frozen.

• Once thawed must be used within 24 h
  (factor V and VIII begin to decline).

• FFP : deficiencies of any factor (volume)

• FFP needs to be ABO-compatible but does
  not require crossmatching or Rh typing.
• Liquid plasma is prepared from previously
  stored whole blood.

• Rarely used (low levels of factor V and
  VIII) but has some utility if coagulopathy
  from other factors.
Indications for plasma transfusions
1.   Congenital or acquired factor def (II, V, VII, X, XI,
     or XIII) with hemorrhage

2. Urgent reversal of warfarin effect

3. Microvascular hemorrhage in prolonged PT, aPTT

4. Plasma exchange for TTP

Initial dose: 15 mL/kg
Contraindication to plasma
transfusions
- Volume expander or as a nutritional supplement
- As albumin supplementation
- Correction of hypogammaglobulinemia
- Hemophilia or von Willebrand disease
- Treat bleeding alone
- prolonged PT or PTT alone
Cryoprecipitate
• Cryoprecipitate is collected by thawing
  FFP at 4ºC and collecting white
  precipitate.

• Rich in : vWF, VIII, XIII, and fibrinogen.

• Chief advantage : factors replaced with a
  much smaller volume than FFP.
Indications for cryoprecipitate

•   Hemophilia A
•   von Willebrand disease
•   Fibrinogen deficiency
•   Dysfibrinogenemia
•   Factor XIII deficiency
•   Uremic platelet dysfunction
Cryo-poor plasma
• coumadin overdose
• vitamin K deficiency
• plasma exchange in TTP-HUS
Factor concentrates
• Contain large amounts factors with
  recombinant or from thousands of donors.

• Indication : hemophilia A and B
Granulocyte transfusions
1. Granulocyte count <0,5 G/L
2. Documented sepsis (especially
  Gram-)
3. Fail to respond to appropriate
  antibiotics within 48h
Indications for albumin
1. Acute volume expansion in
   - Chronic Alb depletion (protein-losing enteropathy
   with edema resistant to diuretics)
   - Hypovolemia shock

2. Long-term replacement, as in extensive burns
Clinical use of intravenous
immunoglobulin
I. Immunodeficiencies

  1. Primary
  2. Secondary
        - malignancies; MM, CL
        - protein-losing enteropathy
        - nephrotic syndrome
        - pediatric AIDS
        - post-BMT
II. Nonifectious

  1. Proven benefit
       - Kawasaki sx
       - ITP
       - Guillain-Barre
       - Dermatomyositis

  2. Probable benefit
       - immune neutropenia
       - AIHA
       - myastenia gravis

  3. Possible benefit
       - anticardiolipin Ab sx
       - toxic shock syndrome