Anemias Flashcards
What is the cause of hereditary spherocytosis?
Genetic defect that causes abnormal proteins in RBC membrane -> RBC are round -> stuck in spleen red pulp fenestrations
What is the presentation of hereditary spherocytosis?
mild to severe anemia
Jaundice and enlarged spleen
Sometimes gallstones
Sometimes post acute infection
What are the lab findings for hereditary spherocytosis?
Increased Reticulocytes
High MCHC (big indicator)
Low or normal MCV
What is the treatment for hereditary spherocytosis?
Give Folic Acid to all
Transfusions/EPO for severe
Eventually splenectomy after age 5
Give antipneumococcal vaccination
What chromosome is the Alpha Hemoglobin on and how many copies does each person have?
Chromosome 16
4 total copies
What chromosome is the Beta Hemoglobin on and how many copies does each person have?
Chromosome 11
2 total copies
What is haptogen and what does it tell you?
A protein in the blood that binds to free hemoglobin. Low haptogen levels means that there is a lot of free hemoglobin, indicating lysis (esp intracellular)
What smear findings are c/w intravascular hemolytic anemias?
Schistocyte
What smear findings are c/w extravascular hemolytic anemias?
Spherocyte
Which type of hemolytic anemia (intra or extravascular) is associated with loss of iron stores?
Intravascular
What is the pathology of Alpha thalassemia?
Many small pale RBCs. Also excess beta chains that precipitate and damage RBC membranes causing hemolysis in bone marrow and spleen
Who is alpha thalassemia most common for?
Southeast and Chinese descent
How will a person with 1 abnormal alpha globulin gene will present?
Normal (silent carrier). Must do genetic testing
How will a person with 2 abnormal alpha globulin genes present?
Alpha thalassemia minor. HCT is 28-40% and MCV is 60-75 (both a hair low).
How will a person with 3 abnormal alpha globulin genes present?
Hemoglobin H disease. Have HgH (beta 4 tetramers) that have a high affinity for oxygen, and are highly unstable, precipitating as toxic Heinz bodies which predominate in mature red blood cells, leading to premature hemolysis
HCT 22-32
MCV 60-70
How will a person with 4 abnormal alpha globulin genes present?
Die in utero in either 2nd or 3rd trimester, called hydrops fetalis
How would you best describe the RBC of a patient with alpha thalassemia?
Hypochromic microcytic
What is the treatment for alpha thalassemia minima?
None
What is the treatment for alpha thalassemia minor?
Might require transfusions in gross blood loss, surgery, etc
Monitor iron, chelation if necessary
What is the treatment for HbH disease?
Folic acid, 1 mg QD
Avoid iron, oxidative drugs
Transfusion
Splenectomy
Iron monitoring
What is the treatment for hydrops fetalis?
Lethal in utero, termination recommended
What is the cause of beta thalassemias?
Gene point mutations of the beta chain causing reduced synthesis
What is beta+?
Reduced but not absent beta chain synthesis
What is beta0?
absent beta chain synthesis
What will an electrophoresis for beta thalassemia show?
HBA2 and HgF
What is HgF?
Fetal hemoglobin. Made with 2 alphas and 2 gamma chains. Primary until 6 months of age
What is HgA2?
Hemaglobin made with 2 alphas and 2 delta chains
Who is beta thalassemia most common in?
Mediterranean descent
What is the pathology for beta thalassemia?
Causes many small pale RBCs. Alpha chains precipitate and cause RBC membrane damage, hemolysis in the liver and spleen, and damage erythroid precursors therefor preventing production
What are the genotypes for thalassemia minor?
Beta/beta+ or beta/Beta0 (must have one normal copy)
What are the genotypes for thalassemia intermedia?
Beta+/Beta+
What are the genotypes for thalassemia major?
Beta0/beta0 or beta+/beta0
Which beta thalassemia patients require transfussions?
Major are dependent on transfusions. Intermedia need occasional transfusions. Minor should not require transfusions.
What does mod-severe beta thalassemia cause in the bone marrow?
Erythroid hyperplasia that leads to chipmunk facies, thin long bones, pathologic fx, and failure to thrive
What is the treatment for beta thalassemia minor?
None, monitor for iron overload
What is the treatment for beta thalassemia intermedia?
Monitor iron
Occasional transfusions
Maybe splenectomy
What is the treatment for beta thalassemia major?
Transfusion dependent
splenectomy
Luspatercept (Reblozyl) (promotes RBC production via TGF-B signaling)
Allogeneic bone marrow transplant is definitive txt
What is the mode of inheritance for sickle cell disease?
Autosomal recessive
What is the cause of sickle cell disease?
SNP in beta chain
Who is sickle cell disease most common in?
African Americans (8% are carriers)
1/400 black children have sickle cell anemia
What is the pathology of sickle cell disease?
Unstable HgS polymerizes causing sickled shaped RBC, RBC cause vasoocclusive episodes
What destroys RBCs in sickle cell disease?
Spleen sequesters and destroys sickled cells
What are triggers for sickle cell disease?
Hypoxemia, acidosis, infection, excessive exercise, abrupt temperature change, anxiety/stress, dehydration
What will the electrophoresis look like for a carrier of sickle cell disease?
HbA and HbS bands
What will the electrophoresis look like for a patient with sickle cell disease?
HbS band and a little bit of HbF
What are Howell-Jolly inclusion bodies?
These are usually single peripheral bodies within red cells representing DNA material. These bodies may be seen in post-splenectomy, megaloblastic anemia, severe hemolysis, and myelophthisic anemia.
How will a patient with sickle cell trait present?
Asymptomatic but might have s/s during physical stress
How will a patient with sickle cell anemia present?
Chronically Ill
Jaundice, pallor, ulcers
Pain, swelling, dactylitis
VC, retinopathy, retinal detachment (cotton wool spots)
Splenomegaly, hepatomegaly, gallstones
Cardiomegaly, hyperdynamic precordium
What is the typical age of onset of sickle cell anemia?
6 months old
What is the definition of a sickle cell crisis?
Ischemic injury to 1+ organs. Sx of pain, fever, tachycardia, tenderness, and anxiety
What is sickle cell treatment?
1 mg folic acid per day
All vaccines
ACEI to prevent kidney damage
Omega 3 fatty acids
Transfusions
Pain management
Antibiotics to prevent infection
Monitor iron
Hydroxyurea (increases HbF levels, causes bone marrow supression)
Crizanlizumab (Adakveo) (MAB agains P-selectin proteins, reduces stickiness)
L-glutamine (Endari) (Reduces oxidative stress)
Allogenic stem cell transplant
What is HOP for sickle cell anemia?
Hydration, Oxygenation, Pain Control
What is a splenic sequestration crisis?
Sickle cell anemia complication where too much blood is sequestered in the spleen, causing rapid splenomegaly and a Hgb drop of >2 g/dL below bsl. Very dangerous and indication for splenectomy.
What is the cause of G6PD deficiency?
X linked recessive mutation in the glucose-6-phosphate dehydrogenase enzyme
Who is G6PD most common in?
African american males
What is the pathology of G6PD?
RBCs are prone to oxidative stress -> Hb denatures and forms Heins bodies-> RBC membrane ruptured -> spleen destroys
Is G6PD inter or extravascular hemolysis?
Both!
Does G6PD have splenomegaly?
No! Spleen only destroys, is not hurt by clots so does not grow
What are the triggers for G6PD?
Antibiotics: sulfa, quinolones, Macrobid
Azo, asprin
Food: fava beans, soy, red wine, beans, blueberries
What are the sx of G6PD?
malaise, weakness, abdominal/lumbar pain, jaundice, dark urine
What is the treatment for G6PD?
Supportive care only
Folic acid
Rarely need transfusions
Do you need to monitor iron in a G6PD patient?
No because only episodic
What is the cause of autoimmune hemolytic anemia?
Antibodies form against RBC surface antigens (IgG). Can be idiopathic or caused by diseases.
What is the presentation of a patient with autoimmune hemolytic anemia?
abrupt rapid onset fatigue, jaundice, splenomegaly
10% mortality
What is the pathology of autoimmune hemolytic anemia?
RBCs tagged by immune system -> spleen macrophages remove part of RBC membrane -> spherocyte forms -> spherocytes get stuck in spleen and then destroyed.
Also complement tags and Kupffer cells in liver destroy
IgM helps facilitate MAC-induced direct intravascular hemolysis
What is warm autoimmune hemolytic anemia?
normal body temperature which is most common
What is cold autoimmune hemolytic anemia?
Only active at colder temps
What is the treatment for autoimmune hemolytic anemia?
Immunosuppression with prednisone (1-2 mg/kg/day) or rituximab
Splenectomy
Might need transfusions
What is the cause of hemolytic disease of the newborn?
Maternal IgG attacks antigens on fetal RBCs. Can cause fetal-maternal hemorrhage
What is the pathology of hemolytic disease of the newborn?
Maternal IgG crosses the placental to fetal circulation and bind fetal RBCs causing hemolysis. Mild to severe anemia in the baby.
What is the most common type of hemolytic disease of the newborn?
anit- ABO antibodies
What is the most severe hemolytic disease of the newborn?
Anti-Rh antibodies
What is the presentation of hemolytic disease of the newborn?
Jaundice
Anemia
Positive Direct Coombs
Hepatomegaly
Splenomegaly
Edema
Heart failure
What maternal labs support hemolytic disease of the newborn?
Mother has negative direct and positive indirect coombs test.
What is the treatment for hemolytic disease of the newborn?
Transfusion (intrauterine or after birth)
Induce labor
Maternal plasma exchange (reduces Ig levels)
What is the prevention for hemolytic disease of the newborn?
RhoGAM for Rh negative mothers if partner is Rh+
What is the cause of Paroxysmal Nocturnal Hemoglobinuria?
Acquired genetic defect leads to lysis of RBCs by complement
Who gets Paroxysmal Nocturnal Hemoglobinuria?
Typically young adults but any age
Equal genders
Not heritable
What is the pathology of Paroxysmal Nocturnal Hemoglobinuria?
MAC forms and destroys RBCs
Free Hb depletes nitric oxide causing esophageal spasms, erectile dysfunction, renal damage, and thrombosis
What is the presentation for Paroxysmal Nocturnal Hemoglobinuria?
Episodic hemoglobinurea in mornings
Might have s/s or thrombosis and anemia
What tests should you order for Paroxysmal Nocturnal Hemoglobinuria?
urine hemosiderine (can still be elevated after episode)
flow cytometry (gold standard)
What is the treatment for Paroxysmal Nocturnal Hemoglobinuria?
Mild- none
Severe - allogeneic hematopoietic stem cell transplant
Eculizumab (C5 MAB)
Transfusion
iron replacement
Corticosteroids (may reduce hemolysis)
What are the stages of blood loss anemia?
- Hypovolemia (organ hypoperfusion, CBC normal)
- Anemia (CBC shows anemia, compensation occurs, resolve hypovolemia)
- Recovery (retics released)
What is the treatment for blood loss anemia?
Stop the bleeding
Transfusion if necessary
Fluid replacement
Might need iron
What is aplastic anemia?
Failure of hemopoietic bone marrow due to suppression of or injury to stem cells
What is the most common cause of aplastic anemia?
Idiopathic autoimmune (causes suppression of hemopoiesis)
What are the causes of aplastic anemia?
Idiopathic autoimmune
Diseases
Toxins- benzene
Medications - chemo
Infections - hepatitis
Others - radiation exposure, pregnancy
What is the pathology of aplastic anemia?
Hypoplasia of hematopoietic bone marrow leads to decrease in all hematopoietic cell lines
What is the treatment for mild aplastic anemia?
Remove the underlying cause if possible
Transfusions, antimicrobials
mild- bone marrow growth factors:
Mulitlineage = eltrombopag (Promacta)
Erythropoeitic: EPO, darbepoetin
Myeloid = filgrastim, sargamostim
What is the treatment for severe aplastic anemia?
Bone marrow transplant (<40 yo w/ sibling HLA-matched donor)
Immunosuppression:
Equine antithymocyte globulin (ATG) and cyclosporin
Steroids (to reduce ATG side effects)
+/- eltrombopag (Promacta)
What is the MOA of epoetin/darbepoetin?
Human EPO made via recombinant DNA stimulates the division and differentiation of erythroid precursors. Increase Hb and Hct in 2-6 weeks
What is the indication for epoetin/darbepoetin?
Anemia due to CKD, chemotherapy, or myelodysplasia
What are the CI for EPO?
Uncontrolled HTN, pure red cell aplasia after EPO tx
What are the BBW for EPO?
Many due to clotting including stroke and DVT, cancer, death
What are common SE for EPO?
HTN, thrombosis
What monitoring needs to be done for EPO?
Iron levels, Hb, BP
What is sideroblastic anemia?
Anemia disorders caused by abnormalities in heme synthesis and mitochondrial fuction
What is the etiology for sideroblastic anemia?
Decreased Hb synthesis due to reduced ability to synthesize heme because of impaired ability to incorporate iron into protoporphyrin IX
What is the cause of sideroblastic anemia?
Inherited
MC- X linked
Autosomal recessive
Mitochondrial inherited
Acquired (most common)
Alcoholism
Lead poisoning
Copper deficiency
Chronic infection/inflammation
Medications (isoniazid, linezolid, chloramphenicol)
What are the sx of sideroblastic anemia?
Anemia sx - fatigue, tachy, dizzy, DOE, palps
Very unspecific and might have infections and bruising
How do you diagnose sideroblastic anemia?
Must do a bone marrow aspirate for erythroid hyperplasia and a prussian blue stain that shows ringed sideroblasts
What is the treatment for sideroblastic anemia?
Transfusions if severe
Correct underlying cause
B6 and B1 for congenital
What is the most common cause of anemia worldwide?
Iron deficiency anemia
What is normal iron dietary requirement?
10-15 mg per day to end up with 1 mg absorbed
What is Heme iron?
Iron found in meat, only 10-20% can be absorbed
What is non-heme iron?
Iron found in meat and veggies. 1-5% can be absorbed
What environment is iron best absorbed in?
Acidic environments, so avoid PPI
What is ferroportin?
Major iron transporter that releases iron from cells
What is hepcidin?
Promotes ferroportin breakdown to inhibit iron release.
How much iron do we lose a day through the skin/mucosa?
1 mg
How much iron do we lose a day through the skin/mucosa?
1 mg
What are the causes of iron deficiency anemia?
Diet
Increased requirements (preg, growth)
Chronic blood loss (menorrhagia, GI, donation)
Decreased absorption
Iron sequestration
What is the presentation of Iron deficiency anemia?
Anemia - fatigue, tachy, dizziness, DOE, palp
Severe - Plummer - Vinson Syndrome (esophageal webs)
Pica
Neuro - RLS, neurodevelopmental delay
What is the treatment for Iron deficiency anemia?
325 mg ferrous sulfate TID for 6 months
With OJ/vitamin C
When should you follow up with a patient with Iron deficiency anemia?
3 weeks shows half improvement in Hct, fixed in 2 months
Retic rise in 4-7 days, peak in 1-1.5 weeks
When would you use parenteral treatment for Iron deficiency anemia?
Cant tolerate oral or anemia is refractory to it
What is the cause of anemias of chronic disease?
Proinflammatory cytokines cause increased hepcidin which causes decreased iron absorption and availability
Are anemias of chronic disease macro or microcytic?
Normo (75%) or microcytic (25%)
How do you tell the difference between iron deficiency anemia and anemias of chronic disease?
Normal ferritin levels. anemias of chronic disease have normal ferritin levels because there is iron stored, it is just not used
What is anemia of chronic kidney disease caused by?
Low EPO
What is the presentation of anemia of chronic kidney disease?
CKD patient with normocytic normochromic anemia. Will have normal iron studies. Can have a secondary iron or folate deficiency.
What is anemia of endocrine disorders caused by?
Low EPO
What is the presentation of anemia of endocrine disorders?
Non-CKD patient with normocytic normochromic anemia. Seen with Throid, Testosterone, and cortisol disorders
What is the cause of anemia of chronic liver disease?
Cholesterol in RBC membrane causes shortened RBC survival and inadequate EPO secretion to compensate
What is the presentation of anemia of chronic liver disease?
Macrocytic anemia in alcoholics
What is the cause of anemia of starvation?
Decreased protein intake causes decreased metabolism which causes decreased EPO production
What causes anemia in the elderly?
Resistance to EPO
Decreased EPO
Chronic low level inflammation
What is the treatment for anemias of chronic disease?
Give EPO
Correct underlying cause
Transfusions
What does B-12 do in the body?
Converts methylmalonyl-CoA to succinyl-CoA
Converts homocysteine to methionine
Both are for DNA synthesis esp in erythroid precursors
What does vitamin B-12 come from?
animal based and fortified foods
How much vitamin B-12 do we absorb a day? Use a day?
5 mg, need 3-5 mg
What is intrinsic factor?
A protein released by parietal cells in the stomach that binds to B-12 to help with absorption in the ileum
Where is B-12 stored?
Liver
What are the causes of B-12 deficiency?
Diet
Low intrinsic factor (pernicious anemia, gastric surgery)
Pancreatic insufficiency
Transcobalamin II deficiency (inherited)
Medications (metformin, PPI, Cochicine)
Competition for B-12 (blind loop syndrome, tapeworms)
Decreased absorption of B12 (small bowel resection, Crohn’s)
What is the presentation for B-12 deficiency?
moderate to severe anemia with insidious onset
Anorexia, nausea, glossitis, angular cheilitis, fatigue, neuropathy
How do you test for pernicious anemia?
Anti-parietal cell antibodies and Gastrin levels, both must be elevated as these are non-specific
How do you treat B-12 deficiency?
IM cyanocobalamin to start
Can switch to oral or sublingual once deficit has been corrected
Give forever unless diet changes possible
Also give Folic Acid
What monitoring should you do for B-12 deficiency?
CBC and B12 levels every 3-6 months
What is the role of folate in the body?
Coenzyme for conversion of homocystine to methionine
What are sources of folate?
Fruit and veggies
Citrus and green leafy veggies
What is the daily absorption and utilization of folate?
125 mcg/day and 50-100 mcg/day
What is the most common cause of folate deficiency?
Diet
What are the causes of folate deficiency?
Diet
Increased folate requirement (preg, chronic hemolytic anemia, exfoliative skin disease)
Inhibition of reduction to active form (methotrexate)
Excess folate loss (hemodialysis)
Decreased absorption of folate (tropical sprue, B-12 deficiency, Medications)
What is the presentation of folate deficiency?
Just like B-12 but no neuro sx
What is the treatment for folate deficiency?
1-5 mg folate daily for 4+ months
Rule out B-12
What do folate deficient MTFHR patient’s need?
Levomethyfolate (L-methylfolate) which is the active form. Others can take it but it’s expensive
What are myeloproliferative disorders?
Diverse group of disorders categorized by excess growth of one or more hematopoietic stem cell lines which causes competition with erythroid precursors
What is polycythemia vera?
All hematopoietic cells are over produced
What is essential thromocytosis?
Excessive platelet production
What is Myelofibrosis?
Excessive collagen or fibrous tissue in marrow
What is Chronic Myelogenous leukemia?
Excessive granulocyte production
What is the typical presentation of myeloproliferative disorders?
Fatigue, weight loss, night sweats
Splenomegaly, hepatomegaly, abd pain, early satiety
Pallor, bruising, petechiae, bleeding, superficial vein thrombosis
What is the treatment for myeloproliferative disorders?
Myelosuppression
