Intrinsic and Immune Extrinsic Defects causing Hemolytic Anemia Flashcards
How are inherited anemias classified with examples
Membrane defects:
Hereditary Spherocytosis
Hereditary Elliptocytosis
Hereditary Stomatocytosis
Enzyme defects:
G6PD
Pyruvate Kinase
Globin structure and Synthesis :
Hemoglobinopathies
Thalassemias
How are acquired anemias classified with examples
Immune:
Alloimmune -Transfusion Reactions, Hemolytic Disease of the Newborn
Autoimmune-Warm Antibody, Cold Antibody
Non-immune
Chemical & Physical Agents
Infections
Mechanical
Secondary liver & renal disease
How does normal extravasular hemolysis occur
Macrophage splits RBC into heme/metheme and Fe+ unconjugated bilirubin
-goes into the liver comes out as a bilirubin and urobilinogen in normal amounts into the intestine
-the intestine secretes urobilinogen (also found in fecal) some gets reabsorbed into circulation
-absorbed into the kidney and secreted in urine with negative bilirubin and normal urobilinogen
how does normal intravascular hemolysis occur
What occurs in excessive extravascular hemolysis
excess urobilinogen is found in the feces and urine
many rbs are seperated into many hemes and unconjugated bilirubin
What are intrinsic hemolytic anemias
-defects in RBCS resulting in hemolysis and anemia
-can be divided into abnormalities with RBC membrane, metabolic enzymes and hemoglobin
how is the RBC membrane unique
-shape due to vertical and horizontal interactions between transmembrane and cytoskletal proteins in the plasma membrane
What are the cytoskeletal proteins in the plasma membrane and what is their function
Ankyrin complex
Actin complex
Protein 4.2
α & β Spectrin
G3PD (band 6)
-provide deformability, elasticity and stability to the cell
-defect can change membrane shape and affect elasticity or viscosity of the cytoplasm = hemolysis
how are hereditary membrane causing hemolytic anemia defects classified
Mutations That Alter Membrane Structure
Hereditary Spherocytosis
Hereditary Elliptocytosis/Pyropoikilocytosis
Mutations That Alter Membrane Transport Proteins
Hereditary Stomatocytosis
Hereditary spherocytosis
inheritance pattern
deficient protein
pathophysiology
rbc morph
clinical findings
inheritance pattern -mostly autosomal dominant 25% nondominant
deficient protein
Ankyrin(ANK1)
Band 3 (SLC4A1)
α-Spectrin (SPTA1)
β-Spectrin (SPTB)
Protein 4.2 (EPB42
pathophysiology - protein mutation that disrupts vertical membrane interactions; causing membrane loss and low surface area to volume
rbc morph- spherocytes , polychromasia and microspherocytes
clinical findings - asymp to severe presents as splenomegaly, jaundice, and anemia
What will you see as lab findings in hereditary spherocytosis
indicators of hemolysis
additional testing
decreased hgb
increased mchc
increased rdw
increased Retic
decreased HAP
increased LD
increased BC
eosin 5 binding test Flow cyto
-osmotic fragility test -increased
-SDS page of membrane proteins
Hereditary Elliptocytosis
inheritance pattern
deficient protein
pathophysiology
rbc morph
clinical findings
inheritance pattern - autosomal dominant
deficient protein
α-Spectrin (SPTA1)
β-Spectrin (SPTB)
Protein 4.1 (EPB41)
pathophysiology - protein mutation disrupts horizontal linkages in cytoskeleton, loss of mechanical stability of membrane
rbc morph- elliptocytes , schistos in sever cases
clinical findings - 90% asym however the other 10 show mod - severe anemia
Hereditary Pyropoikilocytosis
inheritance pattern
deficient protein
pathophysiology
rbc morph
clinical findings
inheritance pattern - autosomal recessive
deficient protein
α-Spectrin(SPTA1)
β-Spectrin (SPTB
homo or hetero
pathophysiology - spectrin mutation disrupts horizontal linkages in cytoskeleton; severe fragmentation
rbc morph
Elliptocytes, schistocytes, microspherocytes
clinical findings- severe anemia
Overhydrated hereditary stomatocytosis (OHS)
inheritance pattern
deficient protein
pathophysiology
rbc morph
clinical findings
inheritance pattern - autosomal dominant
deficient protein -Rh-associated glycoprotein(RHAG
pathophysiology - protein mutation that causes increased membrane permeability to Na and K
-high intracellular Na causes water influx, increased mcv (high MCV) and low cytoplasmic viscosity (low MCHC)
rbc morph -Stomatocytes, macrocytes
clinical findings - mod to severe hemo anemia
Dehydrated hereditary stomatocytosis (DHS)
inheritance pattern -Autosomal dominant
deficient protein -Piezo-type mechanosensitive ion channel component 1(PIEZO1)
Potassium calcium-activated channel subfamily N member 4 (KCNN4)
pathophysiology - protein mutation that causes increased membrane permeability to K, low intracellular K causes loss of water (low MCV) decreased cell volume, and increased cytoplasmic viscosity (increased MCHC)
rbc morph -Target cells, burr cells, stomatocytes , RBCs with puddled hgb, desiccated cells with spicules
clinical findings- mild to mod anemia , jaundice and splenomegaly
Rh Deficiency Syndrome:
Stomatocyte defect
- absence of Rh membrane protein
-mild to mod hemolytic anemia
-stomatocytes and occ spherocytes
-treat with splenectomy
Acquired Stomatocytosis:
-drying artifact on Wright stained PBS
-acute alcoholism
Red Blood Cell Enzymopathies
-RBCs need anaerobic glycolysis for energy because they dont have mitochondria
-metabolic pathways for RBC are Embden – Meyerhof pathway and the Hexose monophosphate shunt
-Glucose-6-phosphate dehydrogenase (G6PD) &
Pyruvate kinase (PK) are two key pathways
-most common deficiencies resulting in decreased life of cell causing HA
What is G6PD
-protects hemoglobin, protein and lipids from oxidative denaturation
-catalyzes first steps of reaction that helps to detoxify hydrogen peroxide formed from oxygen radicals
-G6PD is the only means of generating NADPH which is required for the detoxification step.
G6PD Deficiency
-x linked
-class I to V with Class V being mild to Class I being chronic and severe.
-when RBC cant make enough NADPH to detoxify hydrogen peroxide during oxidative stress
-Heinz bodies stick to inner membrane of RBC causing irreversible damage
-RBCs with Heinz bodies removed by INTRAvascular hemolysis
Clinical Manifestations of G6PD Deficiency
Drug Induced HA- oxidative stress from malarial or sulfa drugs
Infection Induced HA- common cause of HA linked to generation of H2O2 by phagocytizing WBC
Neonatal Hyperbilirubinemia
-occurs with G6PG dif
-jaundice that occurs after birth is not associated with anemia
Chronic Hereditary Nonspherocytic HA
-chronic form
-ongoing hemolysis that is more extra then INTRAvascular
Laboratory Findings in G6PD Deficiency During a Hemolytic Episode
confirmatory testing
biochem
decreased HAP
Hemoglobinemia present
Hemoglobinuria present
Ansiocytosis
Poikilocytosis
Spherocytosis
Schistocytosis
Bite & blister cells
Supravital staining – Heinz bodies seen
G6PD activity assay – decreased
Genetic testing – detect mutation in G6PD gene
Treatment of G6PD Deficiency
-most HAs are self limiting since new RET have high G6PD than mature RBCs
-stop oxidative agent - stop drug and treat infection
-transfusion
-prevent with screening and avoiding known oxidative agents
Pyruvate Kinase Deficiency
-presents as anemia, jaundice, splenomegaly and gallstones
-neonates - severe anemia
adults have severe to compensated
Laboratory Findings in PK Deficiency
biochem
HAP – decreased
BC - increased
Urine urobilinogen - increased
Ansiocytosis
Poikilocytosis
Polychromasia
Burr cells
Confirmatory testing
PK activity assay – decreased
Genetic testing – detect mutation in PK gene
Treatment of PK Deficiency
-supportive treatment and transfusion increase 2,3 BPG which helps to release O2
-splenectomy
-Hematopoietic stem cell transplant (severe disease in children ONLY)
Paroxysmal Nocturnal Hemoglobinuria (PNH)
WHAT DO WE NEED TO KNOW FROM THE CHART
-intravascular HA
-mutation in clonal hematopoietic stem cell that causes RBCs lacking surface markers CD55 and CD59
-55/59 are complement inhibiting proteins so without them the cells cant prevent complement activation resulting in spontaneous and chronic INTRA hemolysis
Laboratory Findings of PNH
HAP - decreased
HGB - increased
BC - increased
Hemoglobinuria - present (dark urine with free HGB in am and clear urine at EOD)
Hemosiderinuria – present
increased RET
pancytopenia
IDA urinary loss of iron
fragments when acute
bone marrow - normo to hypercellular ; erythroid hyperplasia
Confirm with
Ham’s Test
Sugar Water Test
Flow Cytometry
Treatment of PNH
Eculizumab – monoclonal antibody against complement C5 inhibits membrane attack unit and thus complement
supportive therapy - iron therapy
anticoags to treat thrombotic complications
Hematopoietic stem cell transplant (only severe cases)
Immune Hemolytic Anemia
extrinsic defect
-RBC life shortened due to AB mediated mechanisms
-some AB can activate complements
RBCs with ABs or complement are removed by
- Macrophages (extravascular)
- Complement mediated hemolysis (intravascular)
- Combination of extravascular and intravascular processes
Immune hemolytic anemia maybe classified as:
- Autoimmune hemolytic anemia
- Alloimmune hemolytic anemia
- Drug-induced immune hemolytic anemia
What 2 types of antibodies involved in most immune HA:
IgM and IgG
-Igm mediated hemolysis can occur due to both EXTRA and INTRA
-small amounts of IgM on RBC surface cant finish complement activation so RBCs are destroyed by Kupffer cells in the liver (macrophages)
-large amounts of IgM can complete complement and result in INTRA hemolysis
IgG mediated hemolysis is predominantly extravascular and RBCs removed by macrophages in the spleen/liver
Laboratory Findings of Immune HA
increased RET,MCV, WBC and PLT
biochem
HAP decreased
unconjugated bili - increased
plasma HGB increased (INTRA)
Polychromasia
Spherocytes
Possible RBC agglutination
Nucleated RBCs
Fragments
Confirm with DAT
Autoimmune Hemolytic Anemia (AIHA)
-premature RBC destruction and anemia that is caused by autoAB which bind to RBC surface with/out complement activation
-Warm autoimmune hemolytic anemia (WAIHA)
-Cold agglutinin disease
-Paroxysmal cold hemoglobinura
-Mixed AIHA
Warm Autoimmune Hemolytic Anemia (WAIHA)
-most common AIHA
-idiopathic or 2ndary
Immunoglobulin- IgG
Reactivity - 37
Sensitization detected by DAT = IgG or IgG +comple
Complement activation: iffy
Hemolysis - EXTRAvascular
autoAB specificity - Pancreactive
Polychromasia, spherocytes
Treated with
Glucocorticosteroid
Transfusion
Splenectomy
Rituximab
Hematopoietic stem cell transplantation
Cold Agglutinin Disease (CAD)
-IgM autoAB bind to RBCs with blood exposed to cold temps. Bound IgM AB activate complement. At warm temps IgM dissociates but complement stays attached. Hemolysis occurs by hepatic macros
Immunoglobulin- IgM
Reactivity - 4 deg
Sensitization detected by DAT = complement
Complement activation: Yes
Hemolysis - EXTRA and INTRvascular
autoAB specificity - I (most), i (some), Pr (rare)
presence of agglutination
hemoglobinuria
treatment - self limiting if mild
severe : transfusion, supportive care, rituxmab, plasmapheresis
Paroxysmal Cold Hemoglobinuria (PCH)
-caused by Anti P; with autoAB bind to P Ag on rbcs in cold temps and PARTIALLY activates complement but FULLY activated complement at warm temps = INTRAvascular hemolysis
seen in children after VIRAL resp infection
Immunoglobulin- IgG
Reactivity - 4 deg
Sensitization detected by DAT = complement
Complement activation: Yes
Hemolysis - INTRvascular
autoAB specificity - P
Polychromasia, spherocytes, schistocytes, NRBCs, ansiocytes, poikilocytosis; hemoglobinuria; Anti-P positive
treatment
self limiting if mild
if anemia is life threatening then transfusion until better
Mixed-Type Autoimmune HA
Immunoglobulin- IgG + IgM
Reactivity - 4 -37 deg
Sensitization detected by DAT = complement and IgG
Complement activation: Yes
Hemolysis - INTR and EXTRA vascular
autoAB specificity - Panreactive
pt has both IgG and IgM autoantibodies
What are the two types of Alloimmune Hemolytic Anemia
Hemolytic Transfusion Reactions (donor cells are destroyed by AB in the recipient)
Hemolytic Disease of the Fetus and Newborn (HDFN)
Two types of Hemolytic Transfusion Reactions
acute and delayed
Acute Hemolytic Transfusion Reactions (AHTR)
-min - hours after transfusion
-most common cause accidental transfusion of ABO incompatible
-IgM AB to donor cells causes complement activated INTRAvascular Hemolysis and coag activation
HAP and DC decreased
Delayed Hemolytic Transfusion Reactions (DHTR)
-days or weeks after transfusion
-pt was exposed to AG previosly and AB from that exposure was below detetable amounts
-exposure to same AG caused alloAB to increase and bind to transfused RBS = EXTRAvascular
Signs DHTR has occurred:
Inadequate posttransfusion increase in hemoglobin
Positive DAT – IgG/complement
Morphologic evidence of hemolysis – polychromasia, spherocytes etc
Increase in serum unconjugated bilirubin
What are the two types of HDFN
Rh and ABO HDFN
RH- mom (-) baby (+)
-IgG alloAB from mom cross through placenta and binds to fetal cells
-these cells are removed by macros in spleen causing anemia -EXTRAVAS
-to compensate -erythroid hyperplasia occurs in fetal bone marrow and extramedullary erythropoiesis in fetal organs
-severe in utero anemia can lead to edema and death
Treatment of Rh HDFN
ABO HDFN
(Rh HDFN)
Before birth: intrauterine transfusion
After birth: exchange transfusion and phototherapy
low HAP, high unconjugated Bil- severe jaundice, DAT pos, poly and NRBC
(ABO HDFN)
Milder than Rh HDFN because A and B antigens are poorly developed on the newborn RBCs. Other cells in the body have A and B AG so it reduces the # of maternal AB at fetal RBC
-asymp and DAT is weak por or neg
-poly and sphero
Drug-Induced Hemolytic Anemia (DIIHA)
Drugs such as antimicrobials, anti-inflammatory drugs, anti-neoplastic drugs
-decrease in HGB after giving a drug , clinical evidence of extra/intra hemo, DAT post
Extravas caused when AB binds to drug that is attached to RBC or if drug stimulates autoAB to RBC with membrane AG
INTRAvasc occurs when RBC with membrane protein + drug is bound to AB
Two general types of antibodies implicated in drug induced immune hemolytic anemia:
-Drug DEPENdant so
AB that only react with drug treated cells or ABs that only react in the presence of the drug
Drug INDEpendant
treatment
-stop giving drug
-severe = transfusion or plasma exchange and avoid the drug
Non-Immune Hemolytic Anemia
Conditions that causes physical or mechanical injury to the RBCs.
caused by abnormalities in the vasculature of the heart, large blood vessels, venoms, drugs and burns
Microangiopathic Hemolytic Anemia (MAHA)
niha
-RBC fragmentation and thrombocytopenia
-fragmentation due to INTRAvascular shearing of RBC membranes as they pass through partially blocked thrombi. When the RBCs rip they reseal and Spleen removes the fragments . Produces helmet cells and microspherocytes
↓ hemoglobin level
↑ reticulocyte count
↑ serum unconjugated bilirubin
↓ serum haptoglobin
↑ urine urobilinogen
If fragmentation is so sever that INTRA hemolysis occurs it can cause hemoglobinemia, hemoglobinuria and marked Hap decrease
4 main MAHAs:
TTP
HUS
HELLP syndrome
DIC
Thrombotic Thrombocytopenic Purpura (TTP)
MAHA
NIHA
MAHA characterized by the abrupt appearance of microangiopathic anemia
-elevated LD, neurological problems- possible ischemia , renal failure
- deficiency of protease ADAMTS13
- ADAMTS13 cuts long VWF multimers
- Deficiency means long VWF multimers will bind and activate PLTs, resulting in PLT aggregation, this leads to blockage of microvasculature
-causing severe thrombocytopenia , ischemia in the brain and HA as the RBC rupture as they pass through thrombi
Hemoglobinuria - extensive intravascular HA
Urinary casts (protein, RBCs)
↑↑↑ serum LD- marked
↑ serum unconjugated bilirubin several days AFTER ha
↓ serum haptoglobin
Normal PT/PTT
↓↓↓ ADAMTS13
LOW Plts
schisto
COAG results in RI which differentiates from DIC
Treatment of TTP
Idiopathic TTP:
Plasma exchange (replacement therapy)-Removal of the autoantibody against ADAMTS
Corticosteroids -Suppresses autoimmune response
splenectomy
Rituximab-Represses autoantibody response in pts with relapsing ttp
-inhibition of VWF binding to platelets
Secondary TTP:
Treat primary disease the above doesnt work
Support patient
Poor prognosis
Inherited TTP:
FFP-infusions of fresh frozen plasma to supply deficient ADAMTS
Hemolytic Uremia Syndrome (HUS)
Known as Hamburger Disease
shiga toxin producing ecoli or shigella
-produces the Shiga toxin preceded by acute gastroenteritis and bloody diarrhea. Most common cause is eating improperly cooked meat mostly in kids .
-the toxin is absorbed from the intestines into the plasma, the toxins have an affinity to receptors on cells in the brain and plasma. so the toxin enters the cell, inhibits protein synthesis causes injury and apoptosis
.
Shiga Toxin + Cytokines (as aresult of infection) – Induces changes in endothelial cells which are prothrombotic, including expression of TF (Tissue Factor) and secretion of lots of long VWF multimers
-the damage to the endothelial cell causes narrowing of small RBCs exacerbated by platelet activation and thrombi formation = blockage in microvasculature = acute renal failure
-no treatment only supportive care
shisto, poly and NRBC, marked increase in LD and TBIL/BC , casts (renal failure)
coag tests in RI diff from DIC
HELLP Syndrome
-severe pregnancy complication occurring in PREEC .
-Mom develops high BP to the point that it causes damage to organs that leads to poor perfusion and hypoxia
-release of anti-angiogenic proteins from placenta that bind and inactivate placental cells causing maternal endothelial cell dysfunction, platelet activation and fibrin deposition in the liver . Placenta suffers vascular insufficiency
anemia
shistos
high LD (hepatic necrosis and hemolysis)
high aspartate aminotransferase (AST
liver issues)
The higher the platelet count the greater the risk
pt/ptt are in RI diffs from DIC
-treat: fetus delivery, supportive care, electrolyte balance and seizure prevention
HELLP:
-Hemolysis
-Elevated liver enzymes
-Low PLT counts
Disseminated Intravascular Coagulation (DIC)
systematic activation of the hemostatic system causing fibrin thrombi formation throughout the microvasculature. This results in organ damage and eventually bleeding
signs of intravascular hemolysis (shish and poly), anemia and thrombocytopenia
PT/PTT prolonged, decreased fibrinogen level and increased D-dimer.
Traumatic Cardiac Hemolytic Anemia
-caused by prosthetic cardiac valves with turbulent blood flow around the implant
-mild and compensated by the bone marrow
-surgical replacement if anemia is severe enough
-fragments due to mechanical fragmentation of rbcs
↑ reticulocytes
Normal platelet count
↑ serum unconjugated bilirubin
↑ plasma hemoglobin
↓ serum haptoglobin
Hemoglobinuria in severe hemolysis
Hemosiderinuria & ↓ serum ferritin (with chronic hemoglobinuria due to urinary loss of iron)
-may need prosthesis replacement
Hemolytic Anemia Cause by Infectious Agents - MALARIA
caused by five different species of Plasmodium
Malaria impacts human genomes
P. vivax – Asia and South and Central America, but it also occurs in Southeast Asia, Oceania, and the Middle East.P .Vivax needs Duffy antigen to invade RBCs
-West African populations lacks duffy antigen – resistance
P. ovale-West Africa and India
P. malariae- East Africa and India. Malaria selects for G6PD deficient individuals
P. falciparum-sub-Saharan Africa, Saudi Arabia, Haiti, and the Dominican Republic. Asia, Southeast Asia, the Philippines, Indonesia, and South America.
P. knowlesi – less common
how does malaria cause anemia
check slides for asexual and sexual cycles
-caused by bite from infected mosquito
malaria causes anemia by direct lysis after release of merozoites from RBCs and Destruction of infected and non infected RBC in spleen. Malaria parasite sheds protein that bind to cells of non infected RBCs to get them removed by the spleen
Falciparum is lethal - infected RBC adhere to endothelial cells in organs like brain causing cerebral malaria, decreases O2 delivery
extent of the parasitemia & severity of disease is determined by the ability of parasite to invade RBC
P. vivaxandP. ovale- only invade reticulocytes
P. malariae- only invade older RBCs
P. falciparum – invade RBCs of all ages
Clinical & Laboratory Findings of Malaria
mild
cyclic fever with neutropenia with monocytosis , chills and rigor
Severe
Metabolic acidosis
↓ serum glucose
↑ serum lactate
↑ serum creatinine
↓ hemoglobin level
Hemoglobinuria
Hyperparasitemia
-must review PBS 2 thick (detect parasite) and 2 thin (speciate and calculate parasitemia)
-2 samples in 24 hours 8 -12 hours apart to be be negative (malaria life cycle as part of its development is in the liver want to catch them when growing in the blood hence the second sample )
-wrights stain - look for INTRA/EXTRA vac form
parasitemia is calculated by counting how many RBCs have malarial parasites in them (500-300 rbc) and showed as a %
Key Morphological Differences Between HumanPlasmodiumSpecies in Blood Smears
falciparum
many RUBY rings, delicate rings
no trophozoites or schizonts
cresent-shaped banana gametocytes
vivax
enlarged erythrocyte
Schüffner’s dots
‘ameboid’ trophozoite
ovale
similar toP. vivax
compact trophozoite
fewer merozoites in schizont
elongated erythrocyte
malariae
compact parasite in older RBCs
merozoites in rosette
stage
Trophozoites – Large, ameboid with stippling (“like freckles on the cell”)
-Schizonts – Contains multiple merozoites
Other Test for Diagnosis of Malaria & Treatment
Rapid Antigen Test
Detect Plasmodium antigen
Low sensitivity if low # of parasites
Molecular- based Test (PCR)
-detection and speciation of parasites
-Good for low parasitemia levels, low sensitivity , mixed levels - PHL
Serology
Detects antibodies only
May not be current infection
Artemisinin-based combination therapies (ACTs) - drugs that work in all life cycles
Chloroquine phosphate -stops parasite from making toxic heme metabolite when metabolizing hgb (G6PD individuals cannot take this since it promotes oxidative stress trigger HA)
Hemolytic Anemia Cause by Infectious Agents -Babesiosis
a tick-transmitted disease caused by intraerythrocytic protozoan Babesia
-Host: Cattle, Deer, Rodents
-Incidental Hosts: Humans by injection of sporozoites via blood meal by infected ticks
endemic to US and Europe
-chills, sweats, anorexia, juandice, leukopenia, no resp flu symptoms
Increased Risk of Severe Disease:
Immunodeficiency, Immunosuppressant drugs, HIV
-look on slide from wrights stain
-morph is similar to falciparum but there are extracellular merozoites, rings are vacuolated with no pigment production, merozoite tetrad formation = Maltese cross formation
-send to PHL for PCR
-Filariasis
brugia malayi
-filarial larvae enters skin, microfilariae are released into blood at night since they are nocturnal.
-in mosquito they develop into larvae in the gut and then come up to the proboscis
-thread like worms that live in human lymphatic system = elephantiasis with hardening and thickening of the skin
-doesnt cause HA only damage to lymphatic system
-can be diagnosed after identification and blood needs to be collected at night to see the microfilariae
-microfilarae will appear on edge of smear, serpentine in shape and will not stain uniformly unlike debris. extracellular
-absolute eosinophilia
-treat with Diethylcarbamazine (DEC) – kills the microfilariae & some adult worms only on active infections but not for lymphedema
Hemolytic Anemia Cause by Infectious Agents
Clostridial Sepsis
Clostridium perfringens is commonly found in raw meat and poultry
-Can produce toxins that hydrolyze RBC membranes
-can trigger DIC or renal failure
-causes food poisoning if meat isnt cooked properly
-sepsis is rare complication that causes INTRAvas hemolysis with dark plasma and urine (hemoglobinuria)
-↓↓↓ hematocrit
Spherocytes, microspherocytes, toxic changes in neuts
-grave prognosis , needs transfusions, ABtics, fluid management
Hemolytic Anemia Caused by Other RBC Injury
drugs and chemicals
-drugs and chemicals can cause oxidative denaturation from hgb forming methemoglobin and heinz bodies
Heavy Metals: Copper & Lead
Shortened red cell survival
Usually N/N
Basophilic stippling without any other RBC abnormalities
PBS:
Heinz bodies (supravital stain)
Bite & Blister cells (Wright stain
Hemolytic Anemia Caused by Other RBC Injury
Extensive Burns (Thermal Injury)
Fragments
Spherocytes
Microspherocytes
RBC fragmentation & budding
-cleared by spleen in 24hours
-also seen when blood warmer malfunctions causing blood to overheat prior to transfusion or malfunctioning dialysis machine
What are the Three mechanisms thought to produce antibodies as a result of drug exposure:
A. Drug Adsorption – Pt produces an IgG AB to drug, Drug binds to RBCs. Anti-IgG drug will bind to the drug. Extravascular hemolysis occurs because AB is IgG bound to RBC
B. Drug-RBC Membrane Protein Immunogenic Complex – Drug binds loosely to RBC membrane to form Drug-RBC complex that is immunogenic (really gets a response). IgM/ IgG antibody binds to complex activating complement. Acute intravascular hemolysis occurs.
C. RBC Autoantibody Induction – Drug induces patient to form warm IgG autoantibody against RBCs. Extravascular hemolysis, mediated by splenic macrophages (indistinguishable from WAIHA)
three types of TTP
Idiopathic – autoantibody to ADAMTS13 inhibit its activity SEVERE
Secondary – conditions which lower ADAMTS13 synthesis , trauma, pregnancy , SO SO
Inherited form – Mutations to ADAMTS13 gene present in childhood and can reappear if child is stressed, has trauma or is pregnant SEVERE
Differentiate between HUS and TTP
Check patient history (ex. Ingestion of raw meat)
-HUS has more renal failure features (ex. Elevated blood urea, creatinine levels, CASTS in urine)
-HUS has mild-moderate thrombocytopenia; TTP has severe thrombocytopenia
-Shiga toxin testing in microbiology (E. coli, Shigella)
-ADAMTS13 assay
Hemolytic Anemia Caused by Other RBC Injury
venoms
can induce HA
disrupt cell membrane
Alter rbc membrane
initiate DIC
