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