Week 23 Anemia Flashcards
Discuss the framework for a ddx of bleeding
Clinically significant bleeding?
Hematologic vs Non-Hematologic?
Hematologic: Platelet vs Factor
Non-Hematologic: Vessel abnormality
Discuss the production of platelets
Hematopoietic stem cell
Common myeloid progenitor
Megakaryoblast
Promegakaryocyte
Megakaryocyte
Thrombocytes (platelets).
What is the growth factor for platelets and where is it produced?
TPO, produced in the liver.
Binds to C-MPL receptor on platelets and megakaryocytes.
If platelets are low, TPO is high - not as much binding to platelets.
Normal platelet count
150-400 x10^9/L
How long does a platelet transfusion last?
A couple of days.
How much of the platelet population is trapped in the spleen at any one time?
1/3
What components are involved in primary hemostasis
Platelets.
Vessel wall.
Von Willebrand factor.
What are the functions of VWF in primary hemostasis?
Aggregate platelets.
Adhere platelets.
(Carries FVIII).
Where is VWF synthesized and stored?
Endothelial cells.
How is VWF released?
Usually constitutively.
Stored VWF can be released ie. by DDAVP.
What is the role of VWF in thrombotic thrombocytic purpura (TTP)?
VWF is made up of multimers (usually this is needed for creating platelet plug). The larger multimers are most adhesive.
Larger multimers are cleaved by ADAMTS13. If this is lacking, large multimers contribute to TTP.
What are the 3 platelet components?
Receptors.
Granules.
Membrane.
What are the 3 important RBC components?
Enzymes.
HBg.
Membrane.
What would happen is a platelet receptor was missing or not working?
No adherance.
No aggregation.
Antiplatelet drugs can detroy receptors.
What are the 2 types of granules in platelets?
Alpha.
Dense: ADP, Serotonin which are platelet agonists.
How do platelets link primary and secondary hemostasis?
Coagulations factors bind to phospholipids on platelets, helping to form a fibrin clot on the platelet plug.
What are the functions of platelets?
ASAP:
Adhesion.
Secretion.
Aggregation.
Procoagulant activity.
Discuss platelet adhesion
Receptors bind collagen and VWF on exposed subendothelium, causing platelet adhesion.
Discuss the secretion role of platelets
Mediators released from granules have important roles in platelet activation, aggregation, and stabilization of platelet plug.
What is important for platelet aggregation?
GP IIb-IIIa receptor.
Binds platelets together through VWF and fibrinogen.
Discuss procoagulant activity of platelets
Platelet membrane activity supports secondary hemostasis and is where coagulation complexes form (Tenase & Prothrombinase).
Formation of the fibrin clot is the endpoint for hemostasis.
Discuss the degrees of thromocytopenia
Very mild: 100-150. Wouldn’t expect to see any bleeding at all.
Mild: 50-100.
Moderate: 30-50. May see nose bleeds.
Severe: 10-30.
Very severe: <10.
Approach to thrombocytopenia
- Blood film to rule out clumping.
Then determine:
Increased consumption or
Decreased production or
Splenic sequestration or
Dilutional.
MOI for Increased platelet consumption
Immune mediated:
Immune thrombocytopenia,
Neonatal alloimmune thrombocytopenia,
Heparin induced throbocytopenia.
Non immune mediated:
Microangiopathic hemolytic anemias (MAHA).
Would a platelet transfusion be effective in a case of increased consumption?
No. Transfused platelets would also be consumed.
MOI for decreased platelet production
Bone marrow normal:
Meds or radiation that suppress marrow,
B12 deficiency.
Bone marrow abnormal:
Bone marrow failure eg MDS,
Bone marrow infiltration eg Lymphoma.
Would a platelet transfusion be effective in a case of decreased platelet production?
Yes.
Discuss splenic sequestration as a cause of thrombocytopenia
Splenomegaly increases the amount of platelets trapped in the spleen.
Tends to be mild-moderate thrombocytopenia.
Can cause pancytopenia.
MOI:
Congestive (liver cirrhosis),
Infiltrative (lymphoma),
Work hypertrophy (hemolytic anemia).
Which is the most important type of thrombocytopenia in clinical practice?
Increased consumption.
ITP
MAHA
Discuss ITP
The platelet counterpart of autoimmune hemolytic anemia.
COMMON acquired bleeding disorder.
Premature destruction of autoantibody coated platelets in spleen.
Normal blood film with large platelets.
Diagnosis of exclusion.
No autoantibody tests.
Mucosal bleeding.
Primary vs Secondary (drugs, cancer, AI ds)
Treatment of ITP
Acute rescue treatment:
Prednisone or Dexamethasone.
IVIG.
Most respond within a few days but short lived.
Longer term treatment:
Rituximab.
Thrombopoietin receptor agonists.
Steroid sparing immunosupressants.
Spleen TKi.
Splenectomy.
Discuss TTP
Patients look SICK.
LOW HBg & LOW platelets.
Increased retics, LDH, bili.
Low haptoglobin.
Schistocytes.
Clotting and bleeding.
Low ADAMTS13 levels.
VWF multimers bind to vessel walls and platelets leading to:
Vessel occlusion,
Platelet consumption,
Shearing of RBCs
EMERGENCY
MAHA
DAT neg hemolysis with schistocytes.
Thrombocytopenia.
Caused by occlusion of small blood vessels.
Diagnosis of TTP
Neurologic symptoms.
Thrombocytopenia.
MAHA (schitocytes).
Low ADAMTS13 level.
Mortality 90% without treatment so treat is you see MAHA and low platelets, confirm later.
TTP treatment
URGENT PLEX!
Corticosteroids.
Monocolonal Abs.
What investigation must be done for thrombocytopenia?
Blood film to look for schistocytes.
TTP vs ITP
Diagnostic tools for platelet function testing.
Platelet aggregometry.
Discuss qualitative platelet disorders.
Congenital vs acquired (congenital is rare).
Congenital: Glanzmann’s, Grey, Scott.
Acquired - drugs (ASA).
Testing is finicky but available.
Features of congenital platelet disorders
Variable bleeding.
Variable thrombocytopenia.
Variable mode of inheritance.
Some have characteristic morphology.
Some have characteristic aggregometry abnormalities.
Some have other syndromic features.
Discuss MYH9 related disease
Mutation of MYH9 gene which regulates shape, adhesion, migration.
Thrombocytopenia.
Platelet dysfunction.
Autosomal dominant.
Variable bleeding.
Blood film characteristics; Dohle body like, giant platelets.
Normal aggregometry.
Variable additional manifestations.
Treatment: transfusion, DDAVP, tranexamic acid.
Antiplatelet drugs that cause platelet function defects
ASA
Clopidogrel
NSAIDs
Systemic illness that cause platelet function defects
Advanced kidney disease.
Advanced liver disease.
Cardiopulmonary bypass.
Hematologic malignancies that cause platelet function defects
MDS
MPN
Components of yellow marrow
Fat.
Mesenchymal stem cells.
Components of red marrow
Blood cells.
What are the most numerous granulocytes?
Neutrophils.
What are the broad mechanisms of anemia?
Decreased production.
Increase destruction (hemolysis or loss)
What are 3 types of RBC membranopathies
Hereditary spherocytosis.
Hereditary elliptocytosis.
Southeast Asian ovalocytosis.
What are 2 types of RBC enzymopathies?
G6PD deficiency.
Pyruvate kinase deficiency.
What are 2 types of hemoglobinopathies?
Qualitative: sickle cell disease.
Quantitative: thallasemia.
What is the mortality rate of children under 5 with sickle cell disease?
50-90%
What are contributing factors of death d/t sickle cell disease?
Access to diagnosis.
Treatment extremely limited.
Sickle cell trait
Hb AS: 1 normal B-globin allele and 1 mutated B-globin allele.
Sickle cell disease
Homozygous:
Hb S + Hb S
Compound heterozygous:
Hb S + other mutated B-globin allele
(HbS + B-thalassema or Hb S + Hb C).
What is the mutation in Hb S?
Beta globin has Glu6Val
Pathophysiology of sickle cell disease
Mutation causes sickle cell formation leading to:
Vaso-occlusion - damage to ts/infarcts.
Hemolysis.
Endothelial dysfunction (increased inflammatory markers and coaguability)
Diagnosis of Hb S?
Newborn screen in BC.
Sickle solubility test - cannot distinguish trait from disease so…
**NEED 2 METHODS TO CONFIRM HB S; HPLC AND GEL ELECTROPHORESIS
What is the difference between sickle trait and disease?
Sickle cells in peripheral blood = disease.
Trait = 1 copy of mutation
60% Hb A: 40% Hb S
What is an important complication of sickle cell disease to be aware of?
Acute chest syndrome.
Acute pain events.
What is the quality of life like with sickle cell disease?
Similar to having cancer and being on treatment.
Discuss vaso-occlusive pain crises in sickle cell disease.
Most common reason for ER.
Triggers include:
Stress, weather changes, menses, infection, dehydration.
Prompt treatment essential 30-60 minutes.
Multimodal parenteral analgesia.
Supportive care (fluids/O2).
Monitor secondary complications; acute chest syndrome, thromboembolism, stroke, infection.
What is most important when addressing acute attacks of sickle cell disease?
Believe the patient and treat pain rapidly.
Acute chest syndrome
FEVER + NEW INFILTRATE + NEW RESPIRATORY SIGN OR SYMPTOM.
Lack of blood flow d/t occlusion.
Most common cause of death in sickle cell disease = 25% of all deaths.
Treatment of sickle cell disease
Hydroxyurea - induces HbF
Decreases pain crises, acute chest syndrome, hospitalizations.
Improves life expectancy.
Offered to all patients.
Health maintenance screening
Brain, retina, heart, lungs, abdo, bone density, bloodwork.
Blood transfusion.
High risk for complications.
Include prophylaxis for stroke.
***DO NOT TRANSFUSE UNLESS DISCUSSED WITH HEMATOLOGIST.
Bone marrow transplant.
Only 10% will find appropriate match.
Gene therapy.
Casgevy.
What gene is implicated in HbF?
BCL11A suppresses HbF.
When you knock it out you get high HbF levels.
What is the key mechanism in thalassemia?
Globin chain imbalance.
(Minor)A-thalassemia: prob with an alpha chain. Excess beta chains form soluble tetramers causing hemolysis in blood.
(Minor)B-thalassemia: prob with a beta chain. Excess alpha chains are insoluble tetramers leading to ineffective erythropoiesis and subsequent hemolysis.
Thalassemia intermedia
NTDT: non-transfusion dependen thalassemia.
Thalassemia diagnosis
CBC: microcytosis or microcytic anemia.
Blood film: microcytosis, hypochromia, target cells.
Electrophoresis/HPLC: Cannot rule out a-thalassemia based on protein level testing.
Genetic testing.
4 types of alpha thalassemia
- Silent
- Trait (cis/trans)
- Deletional hemoglobin H or Non-deletional hemoglobin H.
**Hb H = TETRAMERS OF b-GLOBIN - Hemoglobin Bart’s.
**TETRAMERS OF y-GLOBIN
**HYDROPS FETALIS
How are alpha thalassemias differentiated/diagnosed?
Genetic testing
Beta thalassemia
2 beta genes.
Will start manifest after 6 months of age when adult Hb becomes dominant.
Mutations can interact with other beta-globin variants resulting in clinically significant hemoglobinopathies.
**SUSPECT BETA IF INCREASED Hb A2 or Hb F
Treatment for transfusion dependent thalassemia
Transfusion every 3-4 weeks.
Monitor for complications:
anemia, bony remodeling. osteoporosis, organomegaly.
Toxicities, allo antibody formation.
Monitor for iron overload - needs chelation.
Treatment for non transfusion dependent thalassemia
Intermittent transfusion as required.
Hemoglobin induction.
Monitor for iron overload.
Monitor for other complications.
Hereditary spherocytosis
Mutations in any of the vertical protein anchors.
Autosomal dominant.
Northern Europeans.
Extravascular hemolysis.
Anemia, jaundice, splenomegaly, reticulocytosis, gallstones, spherocytes on blood film.
Hereditary elliptocytosis
Malaria endemic regions.
Mutation in horizontal protein anchors; spectrin, band 4.1R.
Autosomal dominant.
Asymptomatic.
Severe variant: hereditary pyropoikilocytosis.
Southeast Asian Ovalocytosis
Southeast Asia.
Autosomal dominant.
Band 3 mutations.
G6PD deficiency
G6PD protects RBCs against oxidative damage.
Africa, Asia, Mediterranean, Middle East.
X-linked.
Must reference all new medications.
Heinz bodies
Blister cells.
Bite cells.
Pyruvate Kinase deficiency
Autosomal recessive.
Very rare.
Norther europeans.
Anemia, Fractures, Gallstones
General treatment for membranopathies/enzymopathies
Treat anema.
Support erythropoiesis (Folic acid).
Avoid triggers (G6PD med list).
Monitor for complications.
Splenectomy.
Genetic counselling.
Stages of RBC development
Pluripotent hematopoietic stem cell.
Proerythroblast.
Basophilic erythroblast.
Polychromatophilic erythroblast.
Orthochromatic erythroblast.
Reticulocyte.
Erythrocyte.
Why do RBCs lack nucleus and organelles?
Increase SA, more cells fit into vessels.
Why are RBCs in the shape of a bioconcave disc?
Increase SA,
Proper flow through vessels.
Don’t stick together as much.
How do RBCs get energy
Anaerobic primitive ATP production from glucose.
Functions of RBCs
Transport O2 to tissues.
Remove CO2 to lungs.
Regulate blood pressure by release of NO.
Regulate blood pH via HCO3 & H+.
Clotting.
What are the key cytoskeleton proteins in RBCs?
Spectrin - binds to actin.
Ankyrin - binds Band3 to spectrin.
Protein 4.1 - binds spectrin-actin complex to glycophorin.
What are the key transmembrane proteins in RBCs?
Glycophorin.
Band3.
Discuss the consequence of pyruvate kinase deficiency in RBCs
PK deficiency d/t mutation in the PKLR gene.
Results in hemolytic anemia.
Prevalence 8/1 million.
Requires blood transfusion.
What does excess bilirubin in bile lead to?
Pigment gallstones.
What can occur if RBC destruction and bili production is excessive?
Jaundice.
What causes yellowing in jaundice?
Unconjugated bilirubin.
Normal Hb levels in women?
Men?
W: 120-160
M: 130-170
Why is anemia important as a co-morbidity?
Independent predictor of mortality in
CKD
Malignancy
Heart failure
Geriatric
Also can be early sign of serious disease.
Who is mainly affected by anemia?
Young children.
Pregnant/postpartum women.
Menstruating females.
Signs of severe anemia
Fainting
Chest pain
Angina
Heart attack
Worsening CHF
What factors can help identify the severity and urgency for work-up in anemia?
Time course.
Current clinical context.
Hb levels.
Slightly concerning anemia
Chronic/stable anemia.
Asymptomatic.
Isolated anemia.
Hb >110.
Moderately concerning anemia
Slowly progressive.
Co-existing abnormalities in cell morphology/counts.
Worrisome symptoms/signs.
Asymptomatic.
Hb <110
Majorly concerning anemia
Rapidly progressive.
Symptomatic (Hb rarely >100)
Active bleeding.
Concerning morphologic abnormalities.
Discuss the pathogenesis approach to anemia
Anemia ->
Reticulocyte count ->
Low/normal (decreased production) vs high (blood loss/destruction).
Discuss the MCV approach to anemia
Microcytic <80
Normocytic 80-100
Macrocytic >100
Microcytic anemia
Iron/heme/globin
T Thalassemia
A Anemia of chronic disease
I Iron deficiency
L Lead poisoning
S Sideroblastic anemia
What are the most common causes of microcytic anemia?
Thalassemia trait.
Iron deficiency.
Microcytic anemia workup
Ferritin.
Thalassemia.
CRP.
What is the best test for iron deficiency?
Ferritin.
Low ferritin <15.
Can be elevated in liver disease, inflammation, cancer, infection and heart failure.
TIBC
Maximum amount of iron needed to saturate plasma or serum transferrin.
Serum iron level
Measure of iron in serum, mostly bound to transferrin.
Transferrin saturation
Serum iron/TIBC*100 - % sat.
Tells us how much serum iron is actually bound to transferrin.
What will serum iron be in:
Iron deficiency
Chronic inflammation/malignancy
Thalassemia trait
Iron deficiency: reduced
Chronic inf/malig: reduced
Thalassemia trait: normal
What will TIBC be in:
Iron deficiency
Chronic inflammation/malignancy
Thalassemia trait
Iron deficiency: raised
Chronic inf/malig: reduced
Thalassemia trait: normal
What will serum ferritin be in:
Iron deficiency
Chronic inflammation/malignancy
Thalassemia trait
Iron deficiency: reduced
Chronic inf/malig: raised or normal
Thalassemia trait: normal
Contributing factors to iron deficiency related to inadequate intake
Vegan/vegetarian diet.
Food insecurity/low diversity.
Prolonged breast feeding.
Cow’s milk.
Contributing factors to iron deficiency related to inadequate absorption
Diet with inhibitor of iron absorption.
Inadequate stomach acidification.
Intestinal mucosal dysfuntion.
Gastric surgery.
Obesity.
Contributing factors to iron deficiency related to increased requirements
Growth.
Pregnancy.
Erythropoiesis stimulating agent.
Exercise (elite endurance athletes).
Contributing factors to iron deficiency related to blood loss
GI.
Gynecologic.
GU tract.
Respiratory.
Blood donation/excessive draws.
What should anemia of chronic disease be considered?
Work-up?
Treatment?
Mild microcytosis.
Normal/elevated ferritin (low iron/low TIBC)
CRP
Work-up and treatment of underlying inflammatory condition.
When should thalassemia be considered in an anemic presentation?
Lifelong hx of microcytic anemia.
Family hx.
Elevated RBC.
Severe microcytosis.
Normal red cell width.
Anisopoikilocytosis (variation in size and shape of RBCs)
Target cells.
Hereditary hemorrhagic telangiectasia
Autosomal dominant.
Abnormal blood vessel formation in skin, mucous membranes, lungs, liver, brain.
Results in epistaxis, Gi bleeds, Iron deficiency
Top cause of iron deficiency in North America
BLEEDING
BLEEDING
BLEEDING
ALWAY NEED TO RULE OUT OCCULT/OVERT GI BLEED IN ALL IRON DEFICIENT PATIENTS
Iron deficiency specific to children
Inattention
Poor school performance.
Irritability.
Depression.
Growth retardation.
Cognitive/intellectual impairment.
Breath-holding spells.
Infants:
Poor feeds
Lethary
Failure to thrive
Cardiomegaly
Tachypnea
Causes of iron deficiency in children
Increased requirements d/t growth.
Cow’s mild protein.
Colitis.
Maternal iron deficiency.
Twin-twin transfusion.
Premature.
Inappropriate milk substitutes.
Causes of MEGALOBLASTIC macrocytic anemia
B12 deficiency
Folate deficiency
Drugs that interfere with DNA synthesis.
Congenital.
Causes of NON-MEGALOBLASTIC macrocytic anemia
Liver disease
EtOH
Hypothyroidism
Multiple myeloma
COPD
MDS
HIV
Discuss an approach to macrocytic anemia
Abnormal DNA:
B12/folate deficiency
Drugs
Membrane lipids:
Liver disease
EtOH
Unknown:
Hypothyroid
Multiple myeloma
MDS
Increase reticulocytes:
Hemolysis
Marrow stress/recovery
Work-up for macrocytic anemia
High retics - hemolysis/bleeding
Liver enzymes
B12
TSH
SPEP/UPEP if all normal and still concerned.
Reticulocytes in normocytic anemia
Help us determine marrow status.
Use absolute retics.
Increased:
Bleeding/hemolysis
Premature release from marrow
Low or “inappropriately normal”:
Extrinsic (B12, iron, folate)
EPO/androgen deficiency
Suppression d/t inflammation
Intrinsic marrow disorder
Normocytic screening
High retics:
Ferritin
Urinalysis
GI investigations
Total/direct bili
LDH
DAT
Haptoglobin
Low retics:
Ferritin
Creatinine
B12
TSH
CRP
Marrow screen
Testing for normocytic anemia
Retics High:
Bleeding
Bili
LDH
Haptoglobin
DAT
Smear
Retics Low:
B12
Ferritin
CRP
Creatinine
What is the key membrane transporter of iron in the body?
What does it transport and where?
Ferroportin transports Fe2+ (ferrous iron) directly across membranes, including GI epithelial cells into the bloodstream.
What is the major carrier of iron in the blood and how does it do this?
Transferrin is the major carrier. Converts Fe2+ to Fe3+ (ferric iron) and transports to other parts of the body.
What is the major form of stored iron?
How is iron stored?
Where is it largely stored?
Ferritin is the major storage form of iron.
Binds Fe3+ (ferric).
Liver.
Examples of common causes of blood loss causing iron deficiency
Menorrhagia
GI/GU cancers
IBD
What is the major cause of iron deficiency?
Blood loss.
Why is blood loss the major cause of iron deficiency?
Hb is a major reservoir of iron.
Loss of blood/Hb will significantly affect storage/circulating iron which will be needed to replace lost iron.
What is the most important test for iron deficiency and why?
Ferritin.
It represents the tipping point from uncomplicated iron loss to iron deficiency causing anemia.
When do you have a cause of anemia through iron deficiency?
When ferritin/serum ferritin becomes very low.
What does the liver produce in response to inflammation/physiologic stress or iron overload?
Hepcidin, a regulator of iron.
What does hepcidin do?
Causes internalization/removal of ferroportin transporters.
Without ferroportin, iron accumulates in the GI tract, Liver, Macrophages in spleen.
Decreases tranferrin synthesis.
How does hepcidin/inflammation affect iron tests?
Serum iron decreases - less Fe2+ transported d/t less ferroportin.
Serum ferritin increases - Iron stuck in macophages/liver.
Saturation is normal/increased - Both serum iron and total serum transferrin are reduced so saturation doesnt change.
Functional iron deficiency
Anemia of chronic disease.
Iron is present but not available to make Hb because it is stored d/t hepcidin.
Microcytic hypochromic anemia
Fatigue, SOB, pallor
2 main causes of iron overload
Hemochromatosis (mutations in hepcidin pathway).
Chronic transfusion/increased RBC turnover.
What is the most notable consequence of iron overload?
Liver and cardiac dysfunction.
What is the result of B12 or folate deficiency?
Impaired DNS synthesis leading to slower maturation of RBCs.
Slower maturation leads to larger size of RBCs.
How long does B12 deficiency take to show up?
Folate?
B12 stores last 2-3 years.
Folate stores last 2-4 months.
Discuss the recycling of iron
RBC ingested by macrophages in spleen.
In the macrophage Hb is broken down to release Fe2+.
Fe2+ is released into blood via ferroportin or stored in macrophage via ferritin.
How do drugs induce cytopenias?
Decreased production.
Increased destruction/loss.
Which lymphocyte count is important in leukocytopenia?
Neutrophils
Which lymphocyte count is important in leukocytosis?
All of them.
Polychromasia
Reticulocystosis.
Tells us the mechanism of anemia is RBC loss/destruction.
In what condition can we see a drug induced oxidant hemolysis?
G6PD deficiency.
Reduced glutathione leads to
oxidized Hb (Heinz bodies) resulting in
Hemolysis with bite and blister cells.
How can abs induce anemia?
Antibiotics like Ceftriaxone induce immune mediated hemolytic anemia.
How can DOACs induce anemia?
Worsen bleeds such as GI from gastric ulcers.
What are other drugs that can cause drug induced hemolytic anemias?
Cephalosporins
Penicillins
Diagnosis drug induced hemolytic anemias
Recognize the drug culprit.
Anemia coincides with starting the drug.
Positive DAT
Spherocytes.
Heparin induced thrombycytopenia
Dangerous!
Platelet factor 4 released from platelets.
Heparin binds to PF4 -> neoepitope
IgG binds to neoepitope -> ternary complex.
Ternary complex binds to platelets -> platelet clearance -> thrombocytopenia and activation (strong clotting tendency).
Diagnosis of HIT
Clinicopathologic diagnosis.
Immunoassays have potential for false positives.
Platelet activation assay used, but only available in Hamilton.
Use 4T score.
Discuss the 4T scoring system for HIT
Thrombocytopenia
Timing of fall in platelets
Thrombosis
oTher cause for thrombocytopenia not evident.
Score of 0-3, testing not indicated.
4-5 intermediate - test
6-8 hight - test
Discuss drug induced thrombocytopenia (DITP)
ITP can be drug induced.
Tends to occur under 2 weeks of starting drug.
Associated with severe isolated thrombocytopenia.
Discuss drug induced myelosuppression
Chemotherapy common culprit.
Predictable!
Blood counts have expected nadir, then recover.
Usually pancytopenia.
MAHA
Hemolytic anemia + schistocytes + thrombocytopenia!!
Mechanisms for drug induced RBC destruction or loss
Oxidant hemolysis
Immune hemolytic anemia
Worsened bleeding
Mechanisms of drug induced thrombocytopenia
Heparin induced thrombocytopenia.
Immune thrombycytopenia (ITP)
Thrombotic microangiopathy.
Bone marrow suppression.
Drug induced pancytopenia
NO DRUGS cause pancytopenia via destruction.
Occur via decreased production - myelosuppression.
Oral iron supplements
Usually adequate, good first step.
150 mg Fe daily w/Vit C
Poor absorption.
GI side effects.
DON’T OVERLOAD
When to consider IV iron
Gi intolerance
Severe deficiency
CKS with EPO stimulants.
Common - iron sucrose
Iron isomaltoside more effecient.
B12 supplements
Oral, IM, nasal, sublingual.
IM for pernicious anemia (absorption is impaired).
High dose oral can overcome impaired absorption; 1-2 mg daily, load w/first dose IM.
Folic acid supplements
1mg PO daily.
Also used for hemolytic anemia and pregnancy.
Must check and treat coexisting B12 deficiency.
EPO stimulating agents
SC or IV
Used in CKD
May be used in MDS, chemotherapy induced anemia, prior to elective surgery, JWs.
EPO stimulating agents in CKD
Hb <100
Target Hb 100-115.
Must ensure iron stores are good.
TPO receptor agonists
Used for ITP but expensive.
GCS factor
Post chemotherapy.
Some cases of febrile neutropenia.
Prior to stem cell collection/transplant.
How do you describe anemia?
Based on MCV.
Always describe other blood counts.
What is the criteria for hemolysis?
Reticulocytosis
Increased LDH
Increased unconjugated bilirubin
Decreased haptoglobin
Unconjugated vs conjugated bilirubin
Unconjugated (indirect) bilirubin is bound to albumin in the blood.
Conjugated (direct) bilirubin secreted into the bile.
Unconjugated = total - direct.
Hemoglobin is broken down in to unconjugated bilirubin - a result of hemolysis.
