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Anemia, Thrombocytopenia,

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Title: Anemia, Thrombocytopenia,


1
Anemia, Thrombocytopenia, Blood Transfusions
  • Joel Saltzman MD
  • Hematology/Oncology Fellow
  • Metro Health Medical Center

2
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

3
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)

4
Symptoms of Anemia
  • Nonspecific and reflect tissue hypoxia
  • Fatigue
  • Dyspnea on exertion
  • Palpatations
  • Headache
  • Confusion, decreased mental acuity
  • Skin pallor

5
History and Physical in Anemia
  • Duration and onset of symptoms
  • Change in stool habits Stool Guaiacs in all
  • Splenomegaly?
  • Jaundiced?

6
Components of Oxygen Delivery
  • Hemoglobin in red cells
  • Respiration (Hemoglobin levels increase in
    hypoxic conditions)
  • Circulation (rate increases with anemia)

7
Classification of Anemia
  • Kinetic classification
  • Hypoproliferative
  • Ineffective Erythropoiesis
  • Hemolysis
  • Bleeding
  • Morphologic classification
  • Microcytic
  • Macrocytic
  • Normocytic

8
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)

9
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

10
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)

11
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

12
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
13
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

14
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
15
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

16
Ineffective Erythropoiesis
  • B12 and Folate Deficiency
  • Macrocytosis
  • Decreased serum levels
  • Elevated homocysteine level
  • Myelodysplastic Syndromes
  • Qualitative abnormalities of platlets/wbc
  • Bone marrow

17
Hemolysis
  • Thalassemia
  • Microcytosis
  • RBC count elevated
  • Family history
  • Microangiopathy
  • Smear with schistocytes and RBC fragments
  • HUS/TTP vs. DIC vs. Mechanical Valve

18
Hemolysis (cont.)
  • Autoimmune (warm hemolysis)
  • Spherocytes
  • Coombs test
  • Autoimmune (cold Hemolysis)
  • Polychromasia and reticulocytosis
  • Intravascular hemolysis
  • cold agglutinins
  • Hemoglobinuria/hemosiderinuria

19
Bleeding
  • Labs directed at site of bleeding and clinical
    situation

20
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?

21
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

22
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

23
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

24
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

25
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

26
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

27
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)

28
Success of treatment
29
Outcome Measures
Restrictive group Liberal group
Rate of death at 30 days 18.7 23.3
Mortality rates 22.2 28.1
30
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
31
Survival curve
  • Survival curve was significantly improved in the
    following subgroups
  • Apachelt20
  • Agelt55

32
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

33
Thrombocytopenia
  • Defined as a subnormal amount of platelets in the
    circulating blood
  • Pathophysiology is less well defined

34
Thrombocytopenia Differential Diagnosis
  • Pseudothrombocytopenia
  • Dilutional Thrombocytopenia
  • Decreased Platelet production
  • Increased Platelet Destruction
  • Altered Distribution of Platelets

35
Pseudothrombocytopenia
  • Considered in patients without evidence of
    petechiae or ecchymoses
  • Most commonly caused by platelet clumping
  • Happens most frequently with EDTA
  • Associated with autoantibodies

36
Dilutional Thrombocytopenia
  • Large quantities of PRBCs to treat massive
    hemmorhage

37
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

38
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

39
Increased Destruction (Cont.)
  • ITP
  • HIV associated ITP
  • Drugs heparin, gold, quinidine,lasix,
    cephalosporins, pcn, H2 blockers
  • DIC
  • TTP

40
Altered Distribution of Platelets
  • Circulating platelet count decreases, but the
    total platelet count is normal
  • Hypersplenism
  • Leukemia
  • Lymphoma

41
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

42
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

43
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

44
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
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