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BIKHABIKHA
Anemia,
Thrombocytopenia,
& Blood Transfusions
Dr. Rafi Ahmed Ghori
FCPS
Professor Medicine
Liaquat University of Medical & Health Sciences,
Jamshoro
Rafi
BIKHABIKHA
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
Rafi
BIKHABIKHA
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)
Rafi
BIKHABIKHA
Symptoms of Anemia
• Nonspecific and reflect tissue
hypoxia:
– Fatigue
– Dyspnea on exertion
– Palpatations
– Headache
– Confusion, decreased mental acuity
– Skin pallor
Rafi
BIKHABIKHA
History and Physical in Anemia
• Duration and onset of symptoms
• Change in stool habits: Stool
Guaiacs in all
• Splenomegaly?
• Jaundiced?
Rafi
BIKHABIKHA
Components of
Oxygen Delivery
• Hemoglobin in red cells
• Respiration (Hemoglobin levels
increase in hypoxic conditions)
• Circulation (rate increases with
anemia)
Rafi
BIKHABIKHA
Classification of Anemia
Kinetic classification
• Hypoproliferative
• Ineffective Erythropoiesis
• Hemolysis
• Bleeding
Morphologic classification
• Microcytic
• Macrocytic
• Normocytic
Rafi
BIKHABIKHA
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)
Rafi
BIKHABIKHA
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
Rafi
BIKHABIKHA
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)
Rafi
BIKHABIKHA
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
Rafi
BIKHABIKHA
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
Rafi
BIKHABIKHA
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
Rafi
BIKHABIKHA
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
Rafi
BIKHABIKHA
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
Rafi
BIKHABIKHA
Ineffective Erythropoiesis
• B12 and Folate Deficiency
– Macrocytosis
– Decreased serum levels
– Elevated homocysteine level
• Myelodysplastic Syndromes
– Qualitative abnormalities of platlets/wbc
– Bone marrow
Rafi
BIKHABIKHA
Hemolysis
• Thalassemia
– Microcytosis
– RBC count elevated
– Family history
• Microangiopathy
– Smear with schistocytes and RBC
fragments
– HUS/TTP vs. DIC vs. Mechanical Valve
Rafi
BIKHABIKHA
Hemolysis (cont.)
• Autoimmune (warm hemolysis)
– Spherocytes
– + Coomb’s test
• Autoimmune (cold Hemolysis)
– Polychromasia and reticulocytosis
– Intravascular hemolysis
– + cold agglutinins
– Hemoglobinuria/hemosiderinuria
Rafi
BIKHABIKHA
Bleeding
• Labs directed at site of bleeding and
clinical situation
Rafi
BIKHABIKHA
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?
Rafi
BIKHABIKHA
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
Rafi
BIKHABIKHA
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
Rafi
BIKHABIKHA
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
Rafi
BIKHABIKHA
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
Rafi
BIKHABIKHA
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
Rafi
BIKHABIKHA
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
Rafi
BIKHABIKHA
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)
Rafi
BIKHABIKHA
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
Rafi
BIKHABIKHA
Outcome Measures
Restrictive
group
Liberal group
Rate of death at 30
days
18.7% 23.3
Mortality rates 22.2% 28.1
Rafi
BIKHABIKHA
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
Rafi
BIKHABIKHA
Survival curve
• Survival curve was significantly
improved in the following subgroups:
– Apache<20
– Age<55
Rafi
BIKHABIKHA
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
Rafi
BIKHABIKHA
Thrombocytopenia
• Defined as a subnormal amount of
platelets in the circulating blood
• Pathophysiology is less well defined
Rafi
BIKHABIKHA
Thrombocytopenia:
Differential Diagnosis
• Pseudothrombocytopenia
• Dilutional Thrombocytopenia
• Decreased Platelet production
• Increased Platelet Destruction
• Altered Distribution of Platelets
Rafi
BIKHABIKHA
Pseudothrombocytopenia
• Considered in patients without evidence
of petechiae or ecchymoses
• Most commonly caused by platelet
clumping
– Happens most frequently with EDTA
– Associated with autoantibodies
Rafi
BIKHABIKHA
Dilutional Thrombocytopenia
• Large quantities of PRBC’s to treat
massive hemmorhage
Rafi
BIKHABIKHA
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
Rafi
BIKHABIKHA
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
Rafi
BIKHABIKHA
Increased Destruction (Cont.)
• ITP
• HIV associated ITP
• Drugs: heparin, gold, quinidine,lasix,
cephalosporins, pcn, H2 blockers
• DIC
• TTP
Rafi
BIKHABIKHA
Altered Distribution of Platelets
• Circulating platelet count decreases,
but the total platelet count is normal
– Hypersplenism
– Leukemia
– Lymphoma
Rafi
BIKHABIKHA
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
Rafi
BIKHABIKHA
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
Rafi
BIKHABIKHA
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
Rafi
BIKHABIKHA
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
Rafi
BIKHABIKHA

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11..blood transfusion anemia thrombocyt

  • 1. BIKHABIKHA Anemia, Thrombocytopenia, & Blood Transfusions Dr. Rafi Ahmed Ghori FCPS Professor Medicine Liaquat University of Medical & Health Sciences, Jamshoro Rafi
  • 2. BIKHABIKHA 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 Rafi
  • 3. BIKHABIKHA 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) Rafi
  • 4. BIKHABIKHA Symptoms of Anemia • Nonspecific and reflect tissue hypoxia: – Fatigue – Dyspnea on exertion – Palpatations – Headache – Confusion, decreased mental acuity – Skin pallor Rafi
  • 5. BIKHABIKHA History and Physical in Anemia • Duration and onset of symptoms • Change in stool habits: Stool Guaiacs in all • Splenomegaly? • Jaundiced? Rafi
  • 6. BIKHABIKHA Components of Oxygen Delivery • Hemoglobin in red cells • Respiration (Hemoglobin levels increase in hypoxic conditions) • Circulation (rate increases with anemia) Rafi
  • 7. BIKHABIKHA Classification of Anemia Kinetic classification • Hypoproliferative • Ineffective Erythropoiesis • Hemolysis • Bleeding Morphologic classification • Microcytic • Macrocytic • Normocytic Rafi
  • 8. BIKHABIKHA 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) Rafi
  • 9. BIKHABIKHA 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 Rafi
  • 10. BIKHABIKHA 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) Rafi
  • 11. BIKHABIKHA 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 Rafi
  • 12. BIKHABIKHA 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 Rafi
  • 13. BIKHABIKHA 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 Rafi
  • 14. BIKHABIKHA 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 Rafi
  • 15. BIKHABIKHA 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 Rafi
  • 16. BIKHABIKHA Ineffective Erythropoiesis • B12 and Folate Deficiency – Macrocytosis – Decreased serum levels – Elevated homocysteine level • Myelodysplastic Syndromes – Qualitative abnormalities of platlets/wbc – Bone marrow Rafi
  • 17. BIKHABIKHA Hemolysis • Thalassemia – Microcytosis – RBC count elevated – Family history • Microangiopathy – Smear with schistocytes and RBC fragments – HUS/TTP vs. DIC vs. Mechanical Valve Rafi
  • 18. BIKHABIKHA Hemolysis (cont.) • Autoimmune (warm hemolysis) – Spherocytes – + Coomb’s test • Autoimmune (cold Hemolysis) – Polychromasia and reticulocytosis – Intravascular hemolysis – + cold agglutinins – Hemoglobinuria/hemosiderinuria Rafi
  • 19. BIKHABIKHA Bleeding • Labs directed at site of bleeding and clinical situation Rafi
  • 20. BIKHABIKHA 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? Rafi
  • 21. BIKHABIKHA 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 Rafi
  • 22. BIKHABIKHA 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 Rafi
  • 23. BIKHABIKHA 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 Rafi
  • 24. BIKHABIKHA 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 Rafi
  • 25. BIKHABIKHA 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 Rafi
  • 26. BIKHABIKHA 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 Rafi
  • 27. BIKHABIKHA 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) Rafi
  • 28. BIKHABIKHA 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 Rafi
  • 29. BIKHABIKHA Outcome Measures Restrictive group Liberal group Rate of death at 30 days 18.7% 23.3 Mortality rates 22.2% 28.1 Rafi
  • 30. BIKHABIKHA 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 Rafi
  • 31. BIKHABIKHA Survival curve • Survival curve was significantly improved in the following subgroups: – Apache<20 – Age<55 Rafi
  • 32. BIKHABIKHA 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 Rafi
  • 33. BIKHABIKHA Thrombocytopenia • Defined as a subnormal amount of platelets in the circulating blood • Pathophysiology is less well defined Rafi
  • 34. BIKHABIKHA Thrombocytopenia: Differential Diagnosis • Pseudothrombocytopenia • Dilutional Thrombocytopenia • Decreased Platelet production • Increased Platelet Destruction • Altered Distribution of Platelets Rafi
  • 35. BIKHABIKHA Pseudothrombocytopenia • Considered in patients without evidence of petechiae or ecchymoses • Most commonly caused by platelet clumping – Happens most frequently with EDTA – Associated with autoantibodies Rafi
  • 36. BIKHABIKHA Dilutional Thrombocytopenia • Large quantities of PRBC’s to treat massive hemmorhage Rafi
  • 37. BIKHABIKHA 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 Rafi
  • 38. BIKHABIKHA 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 Rafi
  • 39. BIKHABIKHA Increased Destruction (Cont.) • ITP • HIV associated ITP • Drugs: heparin, gold, quinidine,lasix, cephalosporins, pcn, H2 blockers • DIC • TTP Rafi
  • 40. BIKHABIKHA Altered Distribution of Platelets • Circulating platelet count decreases, but the total platelet count is normal – Hypersplenism – Leukemia – Lymphoma Rafi
  • 41. BIKHABIKHA 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 Rafi
  • 42. BIKHABIKHA 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 Rafi
  • 43. BIKHABIKHA 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 Rafi
  • 44. BIKHABIKHA 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 Rafi