Red Blood Cells Flashcards
Anemia Classifications
Size (3) Hemoglobin (2) Shape (2)
Measurements (4)
Normocytic, Microcytic, Macrocytic
Normochromic, Hypochromic
Poikilocytic, Non-Poikilocytic
Mean Cell Volume
Mean Cell Hemoglobin
Mean Cell Hemoglobin Concentration
Red Cell Distribution Width
Acute Blood Loss Compensatory Changes (4)
Increased CFU-E cells (RBC progenitors) Become Reticulocytes (5 days)
Leukocytosis and Thrombocytosis also occur
Hemolytic Anemias
Extravascular (2) Intravascular (6) Unique Characteristics
Extravascular:
Splenomegaly
Caused by decreased RBC deformability
Intravascular:
Hemoglobinemia, Hemoglobinuria
Caused by mechanical injury to normal cells
Also caused by toxins, parasites and complement
Hemolytic Anemias
Common Clinical Features (3) Lab Features (3) Blood Smear (2)
Anemia
Jaundice
Cholelithiasis
Decreased Haptoglobin
Unconjugated bilirubinemia
Hemosiderinuria
Increased normoblasts
Reticulocytosis
Hereditary Spherocytosis
Pathogenesis (3) Diagnosis (2) Presentation (3) Crisis Syndromes (2)
Mutated cell membrane proteins ankyrin and spectrin
Cells become spheroid and less deformable
Spleen traps and destroys RBCs
Increased sensitivity of RBCs to osmotic lysis (osmotic fragility test)
Increased mean cell hemoglobin concentration
Anemia, Splenomegaly, Jaundice
Aplastic Crisis: caused by Parvovirus destruction of RBC progenitors
Hemolytic Crisis: caused by increased splenic RBC destruction
G6PD Deficiency
Pathogenesis (2) Morphology, Presentation (4) Worse Variant
Decreased NADPH causes decreased protection against oxidative stress
ROS cause intra/extravascular hemolysis
Heinz Bodies
Episodic Hemolysis:
Following Infection, Drugs, Fava beans
Mediterranean variant shows worse hemolysis
Sickle Cell Disease
Pathogenesis (4) Blood Smear (3) Complications (4)
Point mutation of beta-globin
Glutamate to Valine substitution creates HbS
Increased MCHC, decreasaed pH and slow blood flow increase sickling
Mononuclear cells phagocytose sickled cells causing extravascular hemolysis
Irreversibly sickled cells
Target cells
Howell-Jolly bodies in RBCs
Autosplenectomy
Priapism
Stroke
Retinopathy
Vaso-Occlusive Sickle Cell Crises
Pathogenesis, Examples with Descriptions
Hand-Foot, Acute Chest (2)
Hypoxic injury and infarction
Hand-Foot Syndrome: bone pain in kids
Acute Chest Pain: caused by lung infection, life threatening
Non-Occlusive Sickle Cell Crisis Descriptions
Sequestration (3) Aplastic
Sequestration Crisis: in kids, entrapment of RBCs in spleen, can cause life threatening shock
Aplastic: Parvovirus B19 RBC progenitor infection
Thalassemia Syndromes
Genetics (4) General Pathogenesis and Presentation
Genetics:
Beta - Point mutations of single Beta-globin gene on Chromosome 11
Alpha - Deletions of a pair of Alpha-globin genes on Chromosome 16
Anemia caused by decreased RBC production and lifespan
Beta-Thalassemia
Pathogenesis (2) Secondary Complication, Blood Smear (4)
Anemia caused by two mechanisms:
Decreased HbA synthesis
Imbalanced alpha-beta synthesis causes membrane damage that decreases RBC survival (EV hemolysis)
Secondary Hemochromatosis from ineffective erythropoiesis
Anisocytosis (varying size)
Poikilocytosis
Hypochromia
Microcytosis
Beta-Thalassemia Major vs Minor Clinical Features (5/2) Lab Values (1/1) Major Treatment (3)
Major Clinical:
Anemia starting 6-9 months after birth (HbA needed)
Growth retardation and death at early age
Enlarged bones
Hepatosplenomegaly
Cardiac failure from hemochromatosis
Minor Clinical:
Usually asymptomatic
Mild anemia
Lab values
Major: Elevated HbF
Minor: Elevated HbA2
Treat Major with Iron chelation and blood transfusions
May cure with hematopoietic stem cell transplant
alpha-Thalassemia
Types with Descriptions
Silent Carrier (2) a-Thalassemia Trait (3) HbH Disease (4) Hydrops Fetalis (4)
Silent Carrier:
Missing one alpha-globin gene
Asymptomatic
Trait:
Missing two alpha-globin genes
Minimal microcytic anemia
If both deleted from one chromosome, can cause symptomatic a-Thalassemia in offspring
HbH Disease: Missing three alpha-globin genes Forms Beta tetramers Tissue hypoxia disproportionate to level of HgB Can cause Sequestration Crisis
Hydrops Fetalis:
Caused by four missing alpha-globin genes
Formation of Hemoglobin Barts (gamma tetramers)
Fetus shows edema, hepatosplenomegaly, pallor
Lifelong chelation and transfusion dependence
Paroxysmal Nocturnal Hemoglobinuria
Genetics (2) Pathogenesis (3) Complications (3) Diagnosis, Treatment
Phosphatidylinositol glycan complementation group A (PIGA) gene mutation
Only hemolytic anemia caused by acquired defect
Mutation causes GPI-linked protein deficiency
RBCs susceptible to lysis via C5b-C9 MAC
Causes intravascular hemolysis
Hemosiderinuria causing iron deficiency Venous thrombosis (leading cause of death) Acute myeloid leukemia or myelodysplastic syndrome
Diagnose with flow cytometry
Treat with Eculizumab
Warm Antibody Immunohemolytic Anemia
Etiologies: Primary/Secondary (3) Pathogenesis (3)
Drug-Induced Mechanisms (2)
Primary idiopathic
Secondary - Lupus, Drugs, Lymphoid neoplasms
IgG coats RBCs
Phagocytes remove membrane, forming spherocytes
Spleen destroys spherocytes
Drug Antigens bind RBCs and are attacked
Drugs induce the production of auto-Abs against RBCs
Cold Agglutinin Immunohemolytic Anemia
Etiologies: Acute (2) Chronic (2) Pathogenesis (3) Presentation (2)
Acute: mycoplasma pneumoniae, mononucleosis
Chronic: idiopathic, lymphoid neoplasms
IgM binds RBCs in cold periphery
C3b deposited on RBCs
Phagocytes destroy RBCs in liver/spleen/BM
Raynaud phenomenon
Cyanosis in extremities
Cold Hemolysin Immunohemolytic Anemia
Etiology, Pathogenesis (2)
Post-Viral infection (in kids)
IgG binds P antigen on RBCs in cold periphery
Once in warm areas, complemented-mediated hemolysis
RBC Trauma Hemolytic Anemia
Etiologies (2) Pathogenesis (2) Blood Smear (4)
Cardiac Valve Prosthetics (artificial mechanical)
Microangiopathic disorders: DIC
Microvascular lesion causing fibrin/platelet deposition
Luminal narrowing increases shear forces on RBCs
Shistocytes (RBC fragments)
Burr cells
Helmet cells
Triangle cells
Megaloblastic Anemias
Etiologies (2) Blood Smear (5)
Vit B12 deficiency
Folate Deficiency
Macro-Ovalocytes Nuclear Hypersegmentation of Neutrophils Hypercellular bone marrow Giant Metamyelocytes Band cells
Normal B12
Metabolism (4) and Functions (4)
Pepsin breaks B12 from natural binding protein
Haptocorrin picks B12 up and carries to SI
Proteases break B12 from Haptocorrin
Intrinsic Factor picks B12 up and sends it to blood in Ileum
Helps synthesize methionine
Important for Folate synthesis and then Thymidine
Helps synthesize Succinyl CoA
Important for proper synthesis of neuronal lipids
Pernicious Anemia
Pathogenesis (3) Morphology (2) Complications (2) Clinical Diagnostic Features (4) Treatment
T cell mediated AI damage of gastric epithelium
Triggers formation of auto-Abs
Abs destroy intrinsic factor secreting cells, blocking B12 absorption
Fundic gland atrophy Stomach metaplasia (intestinalization)
Atrophic glossitis (beefy, shiny tongue) Demyelination of dorsal and lateral spinal tracts
Megaloblastic anemia
Leukopenia with hypersegnmentation
Low serum B12
Elevated homocysteine and methymalonic acid
Can treat megaloblastic anemia with Folate supplementation (does not treat demyelination)
Non-Pernicious Anemia Causes of B12 Deficiency (4)
Decreased Pepsin
Ileal resection
Gastrectomy (decreased IF)
Tapeworms
Folate Normal Functions (3) Causes of Deficiency (3) Presentation
Purine synthesis
Converts homocysteine to methionine
dTMP synthesis (Thymidine)
Decreased intake (alcoholics) Increased requirements (pregnancy, cancer, anemias) Impaired utilization (Methotrexate)
Megaloblastic anemia identical to B12 deficiency
Iron Physiology
Distribution (2) Transport, Absorption Regulation (2)
Most iron is in heme and enzymes
About 20% is stored as ferritin
Free iron is toxic, Transferrin used to transport instead
Absorption decreased by hepcidin
In response to elevated intrahepatic iron
Iron Deficiency Anemia
Etiologies (4) Morphology, Clinical Features (4) Labs (4) Associated Syndrome with Presentation (3)
Dietary lack (infants, elderly, impoverished) Impaired absorption (sprue, chronic diarrhea) Increased demand (children, pregnancy) Chronic blood loss (most common)
Hypochromic Microcytic anemia
Koilonychia (spoon nails)
Fatigue
Alopecia
Glossitis
Elevated Total Iron Binding Capacity (TIBC)
Decreased HCT, Ferritin, Hepcidin
Plummer Vinson Syndrome: Esophageal webs, anemia, glossitis
Anemia of Chronic Disease
Etiologies (3) Pathogenesis (3) Labs (6)
Chronic Microbial Infections: osteomyelitis, endocarditis
Chronic Immune Disorders: Rheumatoid Arthritis
Neoplasms
Chronic inflammation causes increased IL-6
IL-6 causes increased hepcidin
Increased hepcidin decreases iron absorption and decreases ferroportin function
Decreased TIBC, serum iron, EPO
Elevated Ferritin, Hepcidin, Macrophage Iron
Aplastic Anemia
Etiologies (5) Pathogenesis (2) Diagnosis, Clinical Features (5) Prognosis
Acquired - Idiopathic Chemicals - Chemo drugs Physical Agents - Viral infections Whole body Irradiation Inherited: Telomerase Defects, Fanconi anemia
Extrinsic immune mediated suppression of marrow progenitors
Intrinsic abnormalities of hematopoietic stem cells
“Dry” bone marrow tap devoid of hematopoietic stem cells (hypocellular)
Pancytopenia: Reticulocytopenia** Macrocytic Normochromic Anemia Petechiae and Ecchymoses (thrombocytopenia) Frequent Infections (neutropenia)
Good prognosis with bone marrow transplant
Pure Red Cell Aplasia
Etiologies (3) Clinical Feature
Thymoma
Large Granular Lymphocytic Leukemia
Parvovirus Infection (can persist if immunocompromised)
Primary bone marrow disorder causing only loss of RBCs
Myelophthisic Anemia
Etiologies (2) Pathogenesis, Blood Smear (2)
Most often from Metastasis
Myeloproliferative disorders
Space occupying lesions replace normal bone marrow elements
Leukoerythroblastosis
Teardrop shaped RBCs
Chronic Diseases Associated with Anemia (3)
Chronic Renal Failure
Hepatocellular disease
Hypothyroidism
Polycythemia
Clinical Description (2) Relative vs Absolute
Primary vs Secondary
Abnormally high red blood cell count
Increased Hgb level
Relative: caused by dehydration that decreases plasma volume
Absolute: caused by increased hematopoietic progenitor cells
Primary: Polycythemia vera
EPO-independent growth of RBC progenitors
Secondary: compensatory of pathologic increase in EPO
Excessive Bleeding
Causes (3) and Tests with Descriptions (4)
Increased vessel fragility
Platelet deficiency or dysfunction
Coagulation issues
Prothrombin Time: Extrinsic, Common coagulation paths
Partial Thromboplastin Time: Intrinsic and Common
Platelet counts
Platelet Function Tests: thrombin, vWf tests
Vessel Wall Defects Causing Bleeding
Examples (6)
Infections: meningococcemia
Drug Reactions: hypersensitivity reactions
Collagen Defects: Scurvy, Ehlers Danlos
Immune Complex Deposition: Henoch Schonlein
Hereditary Hemorrhagic Telangiectasia
Perivascular Amyloidosis
Thrombocytopenia Lab Values (3) Causes (4)
<100,000 is thrombocytopenia
<20,000 can cause spontaneous bleeding
Normal PT/PTT
Decreased Production: Bone Marrow defects, HIV
Decreased Platelet Survival: Immune-Mediated, DIC, Thrombotic Microangiopathies
Sequestration: Splenomegaly
Dilution: Blood transfusions
Chronic Immune Thrombocytopenic Purpura
Pathogenesis, BM/Blood Findings (2) Clinical Features (4) Treatment
IgG autoantibodies opsonize membrane glycoproteins IIb/IIa or Ib/IX
Spleen removes opsonized platelets
Increased megakaryocytes
Megathrombocytes in peripheral blood
Petechiae
Ecchymoses
Melena
Hematuria
Glucocorticoids
Acute Immune Thrombocytopenic Purpura
Pathogenesis (2) Clinical Features (2)
IgG autoantibodies opsonize membrane glycoproteins IIb/IIa or Ib/IX
Spleen removes opsonized platelets
Occurs in Kids after viral illness
Spontaneously regresses
Heparin Induced Thrombocytopenia Type I (2) and Type II (4)
Type I
Occurs right after initiation of therapy
Spontaneously resolves
Type II Occurs 5-14 days after heparin started Causes arterial/venous thromboses Caused by auto-Abs to Heparin-PF4 complexes Complexes activate platelets
Thrombotic Thrombocytopenic Purpura
Pathogenesis (2) Clinical Pentad
ADAMTS13 deficiency
vWF multimers accumulate and activate platelets
Fever Thrombocytopenia Microangiopathic Hemolytic Anemia Transient Neurological Defects Renal Failure
Hemolytic Uremic Syndrome Typical Pathogenesis (2) Atypical Pathogenesis (3) Common Pathologic Feature, Presentation (5)
Shiga-like toxin absorbed into circulation
Toxin alters endothelial cells which activates platelets
Atypical HUS
Defects in Complement Factor H, CD46 or Factor I
Both types characterized by excessive activation of complement
Bloody diarrhea followed by: Fever Thrombocytopenia Renal Failure Microangiopathic Hemolytic Anemia
Defective Platelet Function Bleeding
Inherited Etiologies with Examples (3)
Acquired Etiologies (2)
Defective Platelet Adhesion:
Bernard Soulier - glycoprotein Ib-IX defect
Defective Platelet Aggregation:
Glanzmann Thrombasthenia - glycoprotein IIb-IIIa defect
Defective Platelet Secretion (storage pool disorders):
Defective TxA2 and ADP release
Aspirin/MSAID induced
Uremia
Clotting Factor Deficiencies
Clinical Features (2)
Most Common Inherited Deficiencies (3)
Acquired Deficiencies (2)
Large Post-traumatic ecchymoses or hematomas
Prolonged bleeding after any laceration
Factor VIII (hemophilia A) Factor IX (hemophilia B) von Willebrand Factor
Vitamin K Deficiency (impaired II, VII, IX, X and Protein C)
Disseminated Intravascular Coagulation
von Willebrand Disease
Presentation (3) Lab Values (2)
Type 1 (2) Type 2 (2) Type 3 (3)
Mucosal bleeding
Excessive wound bleeding
Menorrhagia
Prolonged PTT and Bleed Time
Reduced ristocetin cofactor activity
Type 1: Autosomal dominant point mutations
Mild deficiency in vWF
Type 2: Missense mutations cause defective multimer formation
Type 3: Autosomal recessive deletions/frameshift
Very low vWF and severe bleeding
Hemophilia A
Pathogenesis (3) Lab Value, Diagnosis, Clinical Features (3)
X linked recessive Factor VIII mutations
X inversion causes most severe deficiency
May develop antibodies to Factor VIII
Prolonged PTT
Factor VIII assays
Most common cause of life threatening bleeding
Spontaneous hemorrhage
Hemarthroses
Hemophilia B (Christmas Disease) Pathogenesis, Lab Value, Diagnosis, Clinical Features (2)
X linked recessive Factor IX mutations
Prolonged PTT
Factor IX assays
Spontaneous hemorrhage
Hemarthroses
Disseminated Intravascular Coagulation
Etiologies (4) Pathogenesis (2) Complications (5) Lab Values (4) Associated Syndromes (2)
Obstetric complications
Sepsis (endotoxins)
Malignancies
Major trauma
Release of tissue factor that combines with Factor VII
Endothelial cell injury which increases tissue factor and decreases anticoagulant thrombomodulin
Hypoxia (fibrin deposition) Microangiopathic hemolytic anemia (fibrin deposition) Hemorrhage (platelets consumed) Widespread thrombi in organs Bilateral renal cortical necrosis
Prolonged PT and PTT
Low fibrinogen
Elevated D Dimer
Waterhouse Friderichsen Syndrome (N meningitidis)
Kasabach-Merritt Syndrome (giant hemangiomas)
Febrile Non-hemolytic Reaction
Etiology, Clinical Features (3) Pathogenesis
Most common adverse reaction to blood transfusion
Fever
Chills
Dyspnea
Caused by inflammation from donor leukocytes
Blood Transfusion Allergic Reactions Associated Deficiency (2) Urticaria (2)
IgA deficiency predisposes reaction
Caused by IgG-mediated reaction to donor IgA
Urticarial reaction seen if IgE recognizes allergens in donor blood
Responds to antihistamines
Hemolytic Transfusion Reactions
Acute: Pathogenesis (2) and Presentation (5) Test
Delayed: Pathogenesis (2) Prognosis
Acute
IgM mediated complement attack on donor RBCs
Caused by ABO incompatibility
Fever, shaking, chills, flank pain (severe causes DIC)
(+) Coombs test
Delayed
IgG mediated attack on previously sensitized Ags
Sensitized from prior blood transfusions
Complement activation can be fatal
Transfusion Related Acute Lung Injury
Pathogenesis (3) Clinical Features (4)
Two Hit Hypothesis:
Primer causes sequestered, sensitized neutrophils in lung microvasculature
Neutrophils activated by MHC I Abs in donor blood
More likely with donations containing high levels of Abs such as fresh frozen plasma and platelets
Sudden onset respiratory failure
Diffuse bilateral lung infiltrates
Hypoxemia
Hypotension
