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)

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Hemoglobin (13.2g/dl in men, 11.7g/dl in women)

Symptoms of Anemia

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Nonspecific and reflect tissue hypoxia:

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Fatigue

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Dyspnea on exertion

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Palpatations

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Headache

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Confusion, decreased mental acuity

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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 • 1/120 th of RBC normally

Absolute Retic count

• Retic counts are reported as a percentage: RBC count x Retic % = Absoulte retic count(normal: 40 60,000/ μl 3 ) • 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/LDH

Ineffective 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

Aplastic anemia

High low Extremely high Normal to 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: • Minor allergic reactions: • Bacterial contamination: 1/100 tx 1/100-1000 tx 1/ 2,500,000 • Viral Hepatitis 1/10,000 • Hemolytic transfusion rxn Fatal: 1/500,000 • Immunosuppression: • HIV infection Unknown 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= 10 8 FNHTR WBCs prevent • Leukocyte-depleted= 10 6 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

Average Hemoglobin Noncompliance >48hrs # of transfusions Restrictive Group Liberal Group 8.5+0.7

1.4% 2.6+ 4.1

10.7+0.7

4.3% 5.6+ 5.3

Outcome Measures

Liberal group Restrictive group Rate of death at 30 days 18.7% Mortality rates 22.2% 23.3

28.1

Complications while in ICU

cardiac MI Pulm edema ARDS restrictive 13.2% 0.7% 5.3% 7.7% Septic shock 9.8% liberal 21.0% 2.9% 10.7% 11.4% 6.9% P value <0.01

0.02

<0.01

0.06

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 10 9 /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