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Hemolytic Anemias (Inherited and Acquired)

Terms in this set (56)

4 Basic Concepts of Hemolytic Anemias
-RBC Destruction is INCREASED
-Bone Marrow Compensation Occurs (INCREASED RBC Production)
-Bone Marrow RBC Production can INCREASE around 7 Fold
-Some patients have Hemolysis WITHOUT Anemia
3 Components Determining RBC Lifespan
-Membrane Cytoskeleton
-ATP-Generating Pathway
-Hemoglobin
Each day, ̴ 1% of the red cell mass dies and is replaced by...
-Reticulocytes
Haptoglobin Function
-binds free Hemoglobin that is released into the blood stream as a result of Hemolysis.
-thus, if Hemolysis is occuring, free Haptoglobin will be DECREASED on Lab Results
Laboratory Features of Hemolysis (2 Factors)
-Signs of RBC Destruction
-Signs of Accelerated Erythropoiesis
Signs of RBC Destruction (5 Signs)
↑ indirect bilirubin
↑ LDH (Lactate Dehydrogenase)
↓ haptoglobin
↑ plasma hemoglobin
↑ urine hemoglobin
Signs of Accelerated Erythropoiesis (3 Signs)
↑ reticulocytes
blood smear
bone marrow erythroid hyperplasia
Hemolysis Phenotypes
-Jaundice (due to Bilirubin)
-Red Plasma
Inherited Hemolysis Disorders
-RBC membrane disorders
-hereditary spherocytosis
-hereditary elliptocytosis
-RBC enzyme disorders
-G6PD deficiency
-PK deficiency
-RBC hemoglobin disorders
-sickle cell disease
-thalassemia
Acquired Hemolysis Disorders
-Immune-related
-auto-immune hemolysis
-hemolytic disease of the newborn
-transfusion reaction
-Non-immune-related
-infection (malaria, clostridia)
-red cell fragmentation
-TTP
-HUS
-DIC
-prosthetic heart valve
-Other disorders
-PNH
-severe liver disease
-hypophosphatemia
Two Anemias due to Cytoskeletal Defects
-Hereditary Spherocytosis
-Hereditary Elliptocytosis
Hereditary Spherocytosis Genetic Inheritance
-Autosomal Dominant (so positive family history)
-WHITE PEOPLE!
Hereditary Spherocytosis Clinical Features (3)
-Splenomegaly
-Jaundice
-Aplastic Episodes (Parvovirus B19)
Hereditary Spherocytosis Labs
-Osmotic Fragility Test! HS Cells will Hemolyze faster when incubated with Saline Dilutions
Hereditary Spherocytosis Treatment
-Splenectomy
-Folate
G6PD Deficiency Genetics, Resistance, and Pathway
-X-Linked
-relative resistance to Malaria
-key enzyme in the Hexose Monophosphate Shunt
Two Subtypes of G6PD Deficiency
-Congenital non-spherocytic hemolytic anemia
-Occurs in the absence of oxidant stresses
-patients have very low activity levels of G6PD
-Acute, acquired hemolytic anemia
-Precipitated by oxidant stresses-infection, drugs (sulfa), fava beans
-G6PD-deficient hemolysis results in precipitation of denatured globin within the red cell (Heinz bodies)
G6PD Deficiency Mnemonic
"Stress makes me eat bites of Fava Beans with Heinz Ketchup"
-Oxidative Stress
-Bite Cells
-Fava Beans
-Heinz Bodies
G6PD Deficiency Diagnosis
-blood smears shows RBCs with Heinz Bodies and Bite Cells
Two Types of Red Cell Hemoglobin Disorders that cause Hemolysis
-Hemoglobinopathies: qualitative disorders of hemoglobin
-Thalassemias: quantitative disorders of hemoglobin
Sickle Cell Disease Genetics and Phenotypes
-Autosomal recessive
-No phenotype in newborns
-Chronic hemolytic anemia
-Vaso-occlusion
-Pneumococcal infections and sepsis
-Chronic inflammatory state
-Organ damage
Sickle Cell Disease Common Phenotypes
-BLACK PEOPLE
Sickle Cell Disease Diagnosis and Treatment
-Hemoglobin Electrophoresis
-Treatment with Hydroxyurea and Hydration
CLINICAL CONSEQUENCES OF VASO-OCCLUSION
Bone infarction
Visceral infarction-stroke, abdominal
pain , chest pain
Asplenia
Vision loss
Leg ulcers
Renal dysfunction
Priapism
Thalassemia General Characteristics
-Globin chain imbalance leads to chronic hemolysis
-Microcytic hypochromic anemia
-Normal or increased iron stores
-Kinetics-ineffective erythropoiesis
-Splenomegaly
-Cooley's anemia (β-thal-major)
.....Transfusion dependent
.....Transfusion-induced iron overload
Alpha vs Beta Thalassemias
-α-thalassemias: decreased α-chain synthesis
due to α-chain deletions
-β-thalassemias: decreased β-chain synthesis due to multiple mutations (not exonic)
-alpha is diagnosed usually through gene panel, beta is diagnosed with Hemoglobin Electrophoresis
Key Give-Away for Beta Thalassemia
-VERY INCREASED HbA2 and INCREASED HbF
Thalassemia Therapy
-Folate
-Splenectomy
-Transfusion
-Iron chelation
-Bone marrow transplantation
Beta Thalassemia Major Pathogenesis
Classifications of Immune Mediated Hemolytic Anemias
-Isoimmune (alloimmune)
.....acute transfusion reaction
.....delayed transfusion reaction
.....isoimmune hemolytic disease of newborns
(mothers are Rh-; fathers and infants are Rh+)
-Autoimmune
.....caused by cold-active antibodies
.....caused by warm-active antibodies
.....idiopathic
.....drug-induced
.....secondary to other diseases (lupus, lymphoma)
Cold Agglutinin Autoimmune Hemolytic Anemia
-IgM antibodies (usually "cold")
-INTRAVASCULAR destruction
-complement fixing
-"cold weather is MMMiserable"
-reaction doesn't happen in vivo, but happens in blood smear due to being at room temperature.
Warm Agglutinin Autoimmune Hemolytic Anemia
-IgG antibodies (usually "warm")
-Fc receptor mediated
-EXTRAVASCULAR destruction
-some IgG Ab's fix complement
-"warm weather is Great"
-Antibody-coated cells cleared by Fc-
receptors (macrophages)
-no agglutination, SPHEROCYTES and RETICULOCYTES INSTEAD!
Autoimmunity results from a loss of...
...self-tolerance leading to immune reactions to self-antigens
Triggers of Autoimmunity
genetic risks, infection (viral, bacterial), inflammation
Drugs Associated with Warm Agglutinin Autoimmune Hemolytic Anemia
-antibiotics (high dose Penicillin!)
Laboratory findings for Warm Agglutinin
-Direct Coombs' test positive for IgG, rarely positive for complement
-Patient's serum will react in indirect Coombs' test with
red cells coated with drug
Diseases Associated with Warm Autoimmune Antibodies
Treatment for Autoimmune Hemolytic Anemia
-Folic Acid
-Prednisone
-Splenectomy
-IVIG
-Rituximab
-Immunosuppression
Coomb's Negative Hemolytic Anemia (4 Types)
-Infection
-Paroxysmal Nocturnal Hemoglobinuria (PNH)
-Severe Liver Disease
-Hypophosphatemia
Microorganisms that cause Hemolysis
-Protozoa (Malaria, Babesiosis, Trypanosomiasis, Leishmaniasis)
-Bacteria (Bartonella, Clostridium)
-Spirochetes (Borrelia)
Paroxysmal Nocturnal Hemoglobinuria (PNH)
-Coombs Negative
-associated with a stem cell (bone marrow) abnormality in which abnormal clones of hematopoietic cells expand with deficient glycosylphosphatidylinositol (GPI) membrane anchors.
-Two GPI-anchored proteins inhibit complement activation on red cells; their deficiency leads to excessive complement mediated hemolysis.
PNH Clinical Manifestations
-INTRAVASCULAR
-Hemoglobinuria
-Iron-deficiency anemia
-Jaundice
-Thrombosis
-Abnormal bone marrow- leukopenia and thrombocytopenia may occur
PNH Therapy and Treatment
-Inhibit complement activation- eculizumab
-Red cell transfusion
-Thrombosis prophylaxis and treatment
-Treat bone marrow failure, if present
Laboratory Test to diagnose PNH?
-Flow Cytometry of CD55 and CD59
Liver Disease and Anemia
-Mild-to-moderate liver disease causes target red cells
-Severe liver disease is associated with acanthocytes (spur cells)
-Hemolysis is mostly seen in severe liver disease due to increased red cell fragility.
Hypophosphatemia and Hemolysis
-seen in patients receiving prolonged antacid therapy, parenteral nutrition without phosphorus supplementation, and starvation or alcoholism
-Hypophosphatemia depletes red cell phosphorus and ATP, leading to rigid, non-deformable red cells
Red Cell Fragmentation Syndromes are characterized by...
-Shistocytes!
Common Red Cell Fragmentation Syndromes
-Prosthetic heart valves
-Thrombotic thrombocytopenic purpura (TTP)
-Hemolytic - uremic syndrome (HUS)
-Malignant hypertension
-Disseminated intravascular coagulation (DIC)
Thrombotic Thrombocytopenic Purpura (TTP) Diagnosis
-absent ADAMTS13.
-Hemolysis due to Red Cell Fragmentation
Mechanisms of Red Cell Fragmentation
-DIC: Fibrin Strands
-TTP: Platelet Thrombi
-Prosthetic Heart Valves: Abnormal Shear
-Malignant Hypertension: Abnormal Shear
Case #1
-History: Upper Respiratory Infection, Cough, 3 Weeks of Extreme Weakness and Dark Urine
-Physical: Jaundice, Pallor, Tachycardia, Rales
-Labs: Down Hct, Up RC, Up Bilirubin
-Diagnosis? Tests? Rx?
-Diagnosis: Hemolysis (possibly Coagglutinin)
-Tests: Indirect Bilirubin, Coombs Test
-Rx: treat underlying cause and transfusion if needed
Case #2
-History: Rheumatic Mitral Stenosis, On Penicillin IV for S. viridans infection. After three weeks, develops...
-Physical: Weakness, Pallor, Jaundice, Tachycardia
-Labs: Down Hct, Up RC, Up Bilirubin
-Diagnosis? Tests? Rx?
-Diagnosis: Drug Induced Warm Antibody
-Tests: Indirect Bilirubin, Coombs Test
-Rx: supportive, transfusion
Case #3
-History: Migratory Arthralgias for 2 Years, ANA (Antinuclear Antibody, in systemic autoimmune disease), Rapid Onset Weakness
-Physical: Pallor, Jaundice, Tachycardia
-Labs: Down Hct, Up RC, Up Bilirubin
-Diagnosis? Tests? Rx?
-Diagnosis: Lupus (Immune Hemolytic Anemia)
-Tests: Indirect Bilirubin, Coombs Test
-Rx: treat underlying cause, high dose steroids for lupus
Case #4
-History: life long history of sporadic jaundice and anemia, OTHER FAMILY MEMBERS AFFECTED
-Physical: Pallor, Jaundice, Tachycardia
-Labs: Down Hct, Up RC, Up Bilirubin
-Diagnosis? Tests? Rx?
-Diagnosis: Hereditary Spherocytosis (Family History)
-Tests: Indirect Bilirubin, Coombs Test (negative), Osmotic Fragility
-Rx: Splenectomy, Folic Acid
Case #5
-History: anemia and jaundice starting ̴6 months after birth, other family members are affected
-Physical: Pallor, Jaundice, Stunted Growth
-Labs: Down Hct, Up RC, Up Bilirubin
-Diagnosis? Tests? Rx?
-Diagnosis: Sickle Cell Anemia
-Tests: Hb Electrophoresis
-Rx: Hydroxyurea
Strategy to Evaluate Hemolytic Anemia
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