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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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10..lymphoma final year
10..lymphoma final year10..lymphoma final year
10..lymphoma final year
 
9..myeloprolef
9..myeloprolef9..myeloprolef
9..myeloprolef
 
7b..bleeding disorder
7b..bleeding disorder7b..bleeding disorder
7b..bleeding disorder
 
6..sickle cell anemia
6..sickle cell anemia6..sickle cell anemia
6..sickle cell anemia
 
5..the thalassaemias
5..the thalassaemias5..the thalassaemias
5..the thalassaemias
 
hemolytic anemia (cell membrane defect)
hemolytic anemia (cell membrane defect)hemolytic anemia (cell membrane defect)
hemolytic anemia (cell membrane defect)
 
hemolytic anemia 1
hemolytic anemia 1hemolytic anemia 1
hemolytic anemia 1
 
4a..hemolytic anemia
4a..hemolytic anemia4a..hemolytic anemia
4a..hemolytic anemia
 
3..rafi ghori megaloblastic anaemia
3..rafi ghori megaloblastic anaemia3..rafi ghori megaloblastic anaemia
3..rafi ghori megaloblastic anaemia
 
1.. introduction to blood
1.. introduction to blood1.. introduction to blood
1.. introduction to blood
 
2..iron deficiency of anemia.2
2..iron deficiency of anemia.22..iron deficiency of anemia.2
2..iron deficiency of anemia.2
 

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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