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Anemia, Thrombocytopenia, & Blood Transfusions Joel Saltzman MD Hematology/Oncology Fellow Metro Health Medical Center Objectives An overview and approach to the anemic patient. An overview and approach to the thrombocytopenic patient

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anemia thrombocytopenia blood transfusions

Anemia, Thrombocytopenia,& Blood Transfusions

Joel Saltzman MD

Hematology/Oncology Fellow

Metro Health Medical Center

objectives
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
anemia
Anemia
  • A reduction below normal in the concentration of hemoglobin or red blood cells in the blood.
  • Hematocrit (<40% in men,<36% in women)
  • Hemoglobin (13.2g/dl in men, 11.7g/dl in women)
symptoms of anemia
Symptoms of Anemia
  • Nonspecific and reflect tissue hypoxia:
    • Fatigue
    • Dyspnea on exertion
    • Palpatations
    • Headache
    • Confusion, decreased mental acuity
    • Skin pallor
history and physical in anemia
History and Physical in Anemia
  • Duration and onset of symptoms
  • Change in stool habits: Stool Guaiacs in all
  • Splenomegaly?
  • Jaundiced?
components of oxygen delivery
Components of Oxygen Delivery
  • Hemoglobin in red cells
  • Respiration (Hemoglobin levels increase in hypoxic conditions)
  • Circulation (rate increases with anemia)
classification of anemia
Classification of Anemia

Kinetic classification

  • Hypoproliferative
  • Ineffective Erythropoiesis
  • Hemolysis
  • Bleeding

Morphologic classification

  • Microcytic
  • Macrocytic
  • Normocytic
anemia a kinetic perspective
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)
reticulocyte count
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
absolute retic count
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 20’s)
  • Absolute retic/3 (hct <20)
indirect bilirubin a marker of rbc destruction
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
hypoproliferative anemias
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
anemia of chronic disease
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
ineffective erythropoiesis
Ineffective Erythropoiesis
  • B12 and Folate Deficiency
    • Macrocytosis
    • Decreased serum levels
    • Elevated homocysteine level
  • Myelodysplastic Syndromes
    • Qualitative abnormalities of platlets/wbc
    • Bone marrow
hemolysis
Hemolysis
  • Thalassemia
    • Microcytosis
    • RBC count elevated
    • Family history
  • Microangiopathy
    • Smear with schistocytes and RBC fragments
    • HUS/TTP vs. DIC vs. Mechanical Valve
hemolysis cont
Hemolysis (cont.)
  • Autoimmune (warm hemolysis)
    • Spherocytes
    • + Coomb’s test
  • Autoimmune (cold Hemolysis)
    • Polychromasia and reticulocytosis
    • Intravascular hemolysis
    • + cold agglutinins
    • Hemoglobinuria/hemosiderinuria
bleeding
Bleeding
  • Labs directed at site of bleeding and clinical situation
rbc transfusion
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?
risks of rbc transfusion in the usa
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
packed red blood cells
Packed Red Blood Cells
  • 1 unit= 300ml
  • Increment/ unit: HCT: 3% Hb1/g/dl
  • Shelf life of 42 days
  • Frozen in glycerol+up to 10 years for rare blood types and unusual Ab profiles
special rbc s
Special RBC’s
  • 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
hebert et al nejm feb 1999
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
methods hebert et al
Methods: Hebert et. al
  • 838 patients with euvolemia after initial treatment who had hemoglobin concentrations < 9.0g/dl within 72 hours of admission were enrolled
  • 418 pts: Restrictive arm: transfused for hb<7.0
  • 420 pts: Liberal arm: transfused for Hb< 10.0
exclusion criteria
Exclusion Criteria
  • Age <16
  • Inability to receive blood products
  • Active blood loss at time of enrollment
  • Chronic anemia: hb< 9.0 in preceding month
  • Routine cardiac surgery patients
study population
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)
success of treatment

Restrictive Group

Liberal

Group

Average Hemoglobin

8.5+0.7

10.7+0.7

Noncompliance

>48hrs

1.4%

4.3%

# of transfusions

2.6+ 4.1

5.6+ 5.3

Success of treatment
survival curve
Survival curve
  • Survival curve was significantly improved in the following subgroups:
    • Apache<20
    • Age<55
conclusions
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
thrombocytopenia
Thrombocytopenia
  • Defined as a subnormal amount of platelets in the circulating blood
  • Pathophysiology is less well defined
thrombocytopenia differential diagnosis
Thrombocytopenia: Differential Diagnosis
  • Pseudothrombocytopenia
  • Dilutional Thrombocytopenia
  • Decreased Platelet production
  • Increased Platelet Destruction
  • Altered Distribution of Platelets
pseudothrombocytopenia
Pseudothrombocytopenia
  • Considered in patients without evidence of petechiae or ecchymoses
  • Most commonly caused by platelet clumping
    • Happens most frequently with EDTA
    • Associated with autoantibodies
dilutional thrombocytopenia
Dilutional Thrombocytopenia
  • Large quantities of PRBC’s to treat massive hemmorhage
decreased platelet production
Decreased Platelet Production
  • Fanconi’s anemia
  • Paroxysmal Nocturnal Hemoglobinuria
  • Viral infections: rubella, CMV, EBV,HIV
  • Nutritional Deficiencies: B12, Folate, Fe
  • Aplastic Anemia
  • Drugs: thiazides, estrogen, chemotherapy
  • Toxins: alcohol, cocaine
increased destruction
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
increased destruction cont
Increased Destruction (Cont.)
  • ITP
  • HIV associated ITP
  • Drugs: heparin, gold, quinidine,lasix, cephalosporins, pcn, H2 blockers
  • DIC
  • TTP
altered distribution of platelets
Altered Distribution of Platelets
  • Circulating platelet count decreases, but the total platelet count is normal
    • Hypersplenism
    • Leukemia
    • Lymphoma
prophylactic versus therapeutic platelet transfusions
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
factors affecting a patients response to platelet transfusion
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
strategies to improve response to platelet transfusions
Strategies to improve response to platelet transfusions
  • Treat underlying condition
  • Transfuse ABO identical platelets
  • Transfuse platelets <48 hrs in storage
  • Increase platelet dose
  • Select compatible donor
    • Cross match
    • HLA match
platelet transfusions reactions
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