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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 l.jpg

Anemia, Thrombocytopenia,& Blood Transfusions

Joel Saltzman MD

Hematology/Oncology Fellow

Metro Health Medical Center

Objectives l.jpg

  • 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 l.jpg

  • 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)

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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 20’s)

  • Absolute retic/3 (hct <20)

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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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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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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

Hemolysis l.jpg

  • 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

    • + Coomb’s test

  • Autoimmune (cold Hemolysis)

    • Polychromasia and reticulocytosis

    • Intravascular hemolysis

    • + cold agglutinins

    • Hemoglobinuria/hemosiderinuria

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  • 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 glycerol+up to 10 years for rare blood types and unusual Ab profiles

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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

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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 < 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

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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

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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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Restrictive Group



Average Hemoglobin







# of transfusions

2.6+ 4.1

5.6+ 5.3

Success of treatment

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Survival curve

  • Survival curve was significantly improved in the following subgroups:

    • Apache<20

    • Age<55

Conclusions l.jpg

  • 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 l.jpg

  • 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

Pseudothrombocytopenia l.jpg

  • 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 PRBC’s to treat massive hemmorhage

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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

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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 transfusion

  • Treat underlying condition

  • Transfuse ABO identical platelets

  • Transfuse platelets <48 hrs in storage

  • Increase platelet dose

  • Select compatible donor

    • Cross match

    • HLA match

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Platelet Transfusions Reactions transfusion

  • Febrile nonhemolytic transfusion: caused by patients leucocytes reacting against donor leukocytes

  • Allergic reactions

  • Bacterial contamination: most common blood product with bacterial contamination