anemia, thrombocytopenia, & blood transfusions joel saltzman md hematology/oncology fellow metro...
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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
• An overview of blood transfusions with an evidence based approach
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
• Nonspecific and reflect tissue hypoxia:– Fatigue– Dyspnea on exertion– Palpatations– Headache – Confusion, decreased mental acuity– Skin pallor
History and Physical in Anemia
• Duration and onset of symptoms
• Change in stool habits: Stool Guaiacs in all
• Splenomegaly?
• Jaundiced?
Components of Oxygen Delivery
• Hemoglobin in red cells
• Respiration (Hemoglobin levels increase in hypoxic conditions)
• Circulation (rate increases with anemia)
Classification of Anemia
Kinetic classification• Hypoproliferative• Ineffective Erythropoiesis • Hemolysis• Bleeding
Morphologic classification• Microcytic• Macrocytic• Normocytic
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
• 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
• 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
• 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
Anemia
Low Retic count & Normal Bili/LDH
Hypoproliferative Anemia
High Retic count & High Bili/LDH
Hemolytic Anemia
Low Retic count & High Bili/LDHIneffective Erythropoiesis
High Retic count & normal Bili/LDH
Blood Loss
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
Lab Evaluation of Hypoproliferative Anemias
Fe TIBC Ferritin
Fe Deficiency low High(>300) low
Anemia of Chronic Dx
low low Normal to high
Aplastic anemia High Extremely high
Normal to high
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
• B12 and Folate Deficiency– Macrocytosis– Decreased serum levels– Elevated homocysteine level
• Myelodysplastic Syndromes– Qualitative abnormalities of platlets/wbc– Bone marrow
Hemolysis
• Thalassemia– Microcytosis– RBC count elevated– Family history
• Microangiopathy– Smear with schistocytes and RBC
fragments– HUS/TTP vs. DIC vs. Mechanical Valve
Hemolysis (cont.)
• Autoimmune (warm hemolysis)– Spherocytes– + Coomb’s test
• Autoimmune (cold Hemolysis)– Polychromasia and reticulocytosis– Intravascular hemolysis– + cold agglutinins– Hemoglobinuria/hemosiderinuria
Bleeding
• Labs directed at site of bleeding and clinical situation
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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
4.3%1.4%Noncompliance>48hrs
5.6+ 5.32.6+ 4.1# of transfusions
10.7+0.78.5+0.7Average Hemoglobin
Liberal Group
Restrictive Group
Outcome Measures
Restrictivegroup
Liberal group
Rate of death at 30 days
18.7% 23.3
Mortality rates 22.2% 28.1
Complications while in ICU
restrictive liberal P value
cardiac 13.2% 21.0% <0.01
MI 0.7% 2.9% 0.02
Pulm edema 5.3% 10.7% <0.01
ARDS 7.7% 11.4% 0.06
Septic shock 9.8% 6.9% 0.13
Survival curve
• Survival curve was significantly improved in the following subgroups: – Apache<20– Age<55
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
• Defined as a subnormal amount of platelets in the circulating blood
• Pathophysiology is less well defined
Thrombocytopenia: Differential Diagnosis
• Pseudothrombocytopenia
• Dilutional Thrombocytopenia
• Decreased Platelet production
• Increased Platelet Destruction
• Altered Distribution of Platelets
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
• Large quantities of PRBC’s to treat massive hemmorhage
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
• 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.)
• ITP
• HIV associated ITP
• Drugs: heparin, gold, quinidine,lasix, cephalosporins, pcn, H2 blockers
• DIC
• TTP
Altered Distribution of Platelets
• Circulating platelet count decreases, but the total platelet count is normal– Hypersplenism– Leukemia– Lymphoma
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
• 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
• 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
• Febrile nonhemolytic transfusion: caused by patients leucocytes reacting against donor leukocytes
• Allergic reactions
• Bacterial contamination: most common blood product with bacterial contamination