Anemia, Thrombocytopenia,

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Anemia, Thrombocytopenia, Blood Transfusions

• Joel Saltzman MD
• Hematology/Oncology Fellow
• Metro Health Medical Center

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Objectives

• An overview and approach to the anemic patient.
• An overview and approach to the thrombocytopenic
  patient
• An overview of blood transfusions with an
  evidence based approach

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Anemia

• A reduction below normal in the concentration of
  hemoglobin or red blood cells in the blood.
• Hematocrit (lt40 in men,lt36 in women)
• Hemoglobin (13.2g/dl in men, 11.7g/dl in women)

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Symptoms of Anemia

• Nonspecific and reflect tissue hypoxia
• Fatigue
• Dyspnea on exertion
• Palpatations
• Headache
• Confusion, decreased mental acuity
• Skin pallor

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History and Physical in Anemia

• Duration and onset of symptoms
• Change in stool habits Stool Guaiacs in all
• Splenomegaly?
• Jaundiced?

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Components of Oxygen Delivery

• Hemoglobin in red cells
• Respiration (Hemoglobin levels increase in
  hypoxic conditions)
• Circulation (rate increases with anemia)

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Classification of Anemia

• Kinetic classification
• Hypoproliferative
• Ineffective Erythropoiesis
• Hemolysis
• Bleeding
• Morphologic classification
• Microcytic
• Macrocytic
• Normocytic

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Anemia A Kinetic Perspective

• Erythrocytes in circulation represent a dynamic
  equilibrium between production and destruction of
  red cells
• In response to acute anemia (ie blood loss) the
  healthy marrow is capable of producing
  erythrocytes 6-8 times the normal rate (mediated
  through erythropoietin)

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Reticulocyte Count

• Is required in the evaluation of all patients
  with anemia as it is a simple measure of
  production
• Young RBC that still contains a small amount of
  RNA
• Normally take 1 day for reticulocyte to mature.
  Under influence of epo takes 2-3 days
• 1/120th of RBC normally

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Absolute Retic count

• Retic counts are reported as a percentage RBC
  count x Retic Absoulte retic count(normal
  40-60,000/µl3)
• Absolute Retic counts need to be corrected for
  early release ( If polychromasia is present)
• Absolute retic/2 (for hct in mid 20s)
• Absolute retic/3 (hct lt20)

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Indirect Bilirubin a marker of RBC destruction

• 80 of normal Bilirubin production is a result of
  the degradation of hemoglobin
• In the absence of liver disease Indirect
  Bilirubin is an excellent indicator of RBC
  destruction
• LDH and Haptoglobin are other markers

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Anemia
Low Retic count Normal Bili/LDH Hypoproliferative Anemia High Retic count High Bili/LDH Hemolytic Anemia
Low Retic count High Bili/LDH Ineffective Erythropoiesis High Retic count normal Bili/LDH Blood Loss
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Hypoproliferative Anemias

• Iron deficiency anemia
• Anemia of chronic disease
• Aplastic anemia and pure red cell aplasia
• Lead poisoning
• Myelophthistic anemias (marrow replaced by
  non-marrow elements)
• Renal Disease
• Thyroid disease
• Nutritional defieciency

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Lab Evaluation of Hypoproliferative Anemias
Fe TIBC Ferritin
Fe Deficiency low High(gt300) low
Anemia of Chronic Dx low low Normal to high
Aplastic anemia High Extremely high Normal to high
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Anemia of Chronic Disease

• Excessive cytokine release (aka, infections,
  inflammation , and cancer)
• Pathophysiology
• Decreased RBC lifespan
• Direct inhibition of RBC progenitors
• Relative reduction in EPO levels
• Decreased availability of Iron

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Ineffective Erythropoiesis

• B12 and Folate Deficiency
• Macrocytosis
• Decreased serum levels
• Elevated homocysteine level
• Myelodysplastic Syndromes
• Qualitative abnormalities of platlets/wbc
• Bone marrow

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Hemolysis

• Thalassemia
• Microcytosis
• RBC count elevated
• Family history
• Microangiopathy
• Smear with schistocytes and RBC fragments
• HUS/TTP vs. DIC vs. Mechanical Valve

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Hemolysis (cont.)

• Autoimmune (warm hemolysis)
• Spherocytes
• Coombs test
• Autoimmune (cold Hemolysis)
• Polychromasia and reticulocytosis
• Intravascular hemolysis
• cold agglutinins
• Hemoglobinuria/hemosiderinuria

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Bleeding

• Labs directed at site of bleeding and clinical
  situation

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RBC Transfusion

• What is the best strategy for transfusion in a
  hospitalized patient population?
• Is a liberal strategy better than a restrictive
  strategy in the critically ill patients?
• What are the risks of transfusion?

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Risks of RBC Transfusion in the USA

• Febrile non-hemolytic RXN 1/100 tx
• Minor allergic reactions 1/100-1000 tx
• Bacterial contamination 1/ 2,500,000
• Viral Hepatitis 1/10,000
• Hemolytic transfusion rxn Fatal 1/500,000
• Immunosuppression Unknown
• HIV infection 1/500,000

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Packed Red Blood Cells

• 1 unit 300ml
• Increment/ unit HCT 3 Hb1/g/dl
• Shelf life of 42 days
• Frozen in glycerolup to 10 years for rare blood
  types and unusual Ab profiles

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Special RBCs

• Leukocyte-reduced 108 WBCs prevent FNHTR
• Leukocyte-depleted 106 WBCs prevent
  alloimmunization and CMV transmission
• Washed plasma proteins removed to prevent
  allergic reaction
• Irradiated lymphocytes unable to divide,
  prevents GVHD

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Hebert et. al, NEJM, Feb 1999

• A multicenter randomized, controlled clinical
  trial of transfusion requirements in critical
  care
• Designed to compare a restrictive vs. a liberal
  strategy for blood transfusions in critically ill
  patients

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Methods Hebert et. al

• 838 patients with euvolemia after initial
  treatment who had hemoglobin concentrations lt
  9.0g/dl within 72 hours of admission were
  enrolled
• 418 pts Restrictive arm transfused for hblt7.0
• 420 pts Liberal arm transfused for Hblt 10.0

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Exclusion Criteria

• Age lt16
• Inability to receive blood products
• Active blood loss at time of enrollment
• Chronic anemia hblt 9.0 in preceding month
• Routine cardiac surgery patients

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Study population

• 6451 were assessed for eligibility
• Consent rate was 41
• No significant differences were noted between the
  two groups
• Average apache score was 21(hospital mortality of
  40 for nonoperative patients or 29 for post-op
  pts)

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Success of treatment
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Outcome Measures
Restrictive group Liberal group
Rate of death at 30 days 18.7 23.3
Mortality rates 22.2 28.1
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Complications while in ICU
restrictive liberal P value
cardiac 13.2 21.0 lt0.01
MI 0.7 2.9 0.02
Pulm edema 5.3 10.7 lt0.01
ARDS 7.7 11.4 0.06
Septic shock 9.8 6.9 0.13
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Survival curve

• Survival curve was significantly improved in the
  following subgroups
• Apachelt20
• Agelt55

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Conclusions

• A restrictive approach to blood transfusions is
  as least as effective if not more effective than
  a more liberal approach
• This is especially true in a healthier, younger
  population

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Thrombocytopenia

• Defined as a subnormal amount of platelets in the
  circulating blood
• Pathophysiology is less well defined

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Thrombocytopenia Differential Diagnosis

• Pseudothrombocytopenia
• Dilutional Thrombocytopenia
• Decreased Platelet production
• Increased Platelet Destruction
• Altered Distribution of Platelets

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Pseudothrombocytopenia

• Considered in patients without evidence of
  petechiae or ecchymoses
• Most commonly caused by platelet clumping
• Happens most frequently with EDTA
• Associated with autoantibodies

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Dilutional Thrombocytopenia

• Large quantities of PRBCs to treat massive
  hemmorhage

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Decreased Platelet Production

• Fanconis anemia
• Paroxysmal Nocturnal Hemoglobinuria
• Viral infections rubella, CMV, EBV,HIV
• Nutritional Deficiencies B12, Folate, Fe
• Aplastic Anemia
• Drugs thiazides, estrogen, chemotherapy
• Toxins alcohol, cocaine

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Increased Destruction

• Most common cause of thrombocytopenia
• Leads to stimulation of thrombopoiesis and thus
  an increase in the number, size and rate of
  maturation of the precursor megakaryocytes
• Increased consumption with intravascular thrombi
  or damaged endothelial surfaces

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Increased Destruction (Cont.)

• ITP
• HIV associated ITP
• Drugs heparin, gold, quinidine,lasix,
  cephalosporins, pcn, H2 blockers
• DIC
• TTP

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Altered Distribution of Platelets

• Circulating platelet count decreases, but the
  total platelet count is normal
• Hypersplenism
• Leukemia
• Lymphoma

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Prophylactic Versus Therapeutic Platelet
Transfusions

• Platelet transfusions for active bleeding much
  more common on surgical and cardiology services
• Prophylactic transfusions most common on hem/onc
  services
• 10 x 109/L has become the standard clinical
  practice on hem/onc services

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Factors affecting a patients response to platelet
transfusion

• Clinical situation Fever, sepsis, splenomegaly,
  Bleeding, DIC
• Patient alloimunization, underlying disease,
  drugs (IVIG, Ampho B)
• Length of time platelets stored
• 15 of patients who require multiple transfusions
  become refractory

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Strategies to improve response to platelet
transfusions

• Treat underlying condition
• Transfuse ABO identical platelets
• Transfuse platelets lt48 hrs in storage
• Increase platelet dose
• Select compatible donor
• Cross match
• HLA match

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Platelet Transfusions Reactions

• Febrile nonhemolytic transfusion caused by
  patients leucocytes reacting against donor
  leukocytes
• Allergic reactions
• Bacterial contamination most common blood
  product with bacterial contamination