DSA: RBC Disorders Flashcards
essentials of diagnosis (EOD) for iron deficiency anemia?
- if serrum ferritin is < 12 ng or less than 30
- caused by bleeding unless proved otherwise*
- responds to iron therapy
Tx of iron deficiency anemia
identification of the cause
-especially if it’s occult blood loss
EOD for anemia of chronic disease
- mild or moderate normocytic or microcytic anemia
- normal or increased ferritin and normal or reduced transferrin
- underlying chronic disease
- there’s usually inflammation going on… hepcidin gets released… no iron comes in
what helps us distinguish anemia of chronic disease from iron deficiency anemia?
look at the serum ferritin
- if that is high, then we have plenty of iron
- if low, iron deficiency
is treatment OF THE ANEMIA necessary for management of anemia of chronic disease?
no
-just address the condition causing the anemia of chronic disease
EOD for thalassemias
- microcytosis disproportionate to the degre of anemia
- family hx
- lifelong personal history of microcytic anemia
- normal or elevated RBC count
- abnormal rbc morphology with microcytes, hypochromia, acanthocytes, and target cells
- in beta-thalassemia, elevated levels of hbg A2 or F
what is thalassemia?
reduction in synth of globin chains
- hemoglobin= heme + globin
- Heme= Fe + porphoryn
what is MCH?
mean corpuscular hemoglobin
-it’s low in thalassemias
what region of the world are alpha thalassemias seen in a lot?
SE asia and China
Who does Beta thalassemia affect the most
mediterranean ppl
Alpha thalassemia trait
-mild anemias
-low MCV
-normal iron and reticulocyte count
-
Hemoglobin H disease
- more marked anemia
- low MCV
- microcytosis
- reticulocytes elevated
- electrophoresis will show a fast migrating HbH
Beta thalassemia minor
- in contrast to alpha thalassemia, there is basophilic stippling
- elevation in HbA2
Beta thalassemia intermedia
- elevated reticulocyte count
- basophilic stippling
- there can be lots of HbF
- similar to minor
Beta thalassemia major
- sever anemia
- poikilocytosis and whatnot, basophilic stippling
- nucleated RBC’s
- very little HbA
- predominant is HbF
What should we give people that have to get a lot of transfusions?
iron chelators
-or else everyone else’s iron will get into them
What is the tx of choice for B thalassemia major and the only available cure?
stem cell transplantation
EOD for Vit B12 deficiency
- macrocytic anemia
- megaloblastic blood smear: macro-ovalocytes and hypersegmented neutrophils
- low serum vitamin B12 level
What makes Vit B12 deficiency a little unique from folate deficieny?
there are neuro symptoms
-because methylmalonic acid builds up
if we find not a lot of B12 in the blood, what confirmatory test can we do to make sure that it’s B12 deficiency?
methylmalonic acid or homocysteine
-if high, we got b12 deficiency
How do we tell iron deficiency apart from thalassemia minor?
- thalassemia pts have a lower MCV and a more abnormal peripheral smear and usually reticulocytosis
- look at the freakin iron studies
how is the diagnosis of alpha thalassemia madE?
by exclusion
-there is no change in proportion of the normal adult hemoglobin species
how is B12 decifiency treated?
with parenteral therapy
-means inject it into them
EOD for folic acid deficiency
- macrocytic anemia
- megaloblastic blood spmear
- reduced folic acid levels in rbc’s or serum
- NORMAL B12 LEVELS
What should always be measured if folic acid deficiency is suspected?
vitamin B12
What kind of patients will get folic acid deficiency?
alcoholics!!!
how is folic acid deficiency treated?
with daily oral folic acid
-reticulocytosis will happen and everything will be back to normal
EOD for Paroxysmal Nocturnal Hemoglobinuria
- episodic hemoglobinuria
- thrombosis is common
- suspect in confusing cases of hemolytic anemia or pancytopenia
- flow cytometry demonstrates deficiencies of CD55 and CD59
What happens in PNH?
- RBCs get destroyed by complement
- the Hb binds up NO… vasospasm
- reddish brown urine in the morning
- drop in blood pH while sleeping facilitates hemolysis
lab findings in PNH?
-high serum LD
tx of PNH
- no intervention
- if it’s that bad and you find out they have aplastic anemia, just do stem cell transplantation
- ecluzimab binds C5 and helps
EOD for G6PD deficiency
- X linked recessive disorder seen commonly in american Black men
- Episodic hemolysis in response to oxidant drugs or infection
- bite cells and blister cells on the peripheral blood smear
- reduced levels of G6PD between hemolytic episodes
What does G6PD normally do?
it’s an antioxidant… so without it our RBC get destroyed by oxidants…
is G6PD self limited?
yeah
-unless you’re mediterranean
What does the peripheral blood smear look like with G6PD defiency?
bite cells
-HEINZ BODIES!= denatured hemoglobin
EOD for sickle cell anemia
- recurrent pain episodes
- family hx and lifelong hx of hemolytic anemia
- irreversibly sickled cells on peripheral blood smear
- Hemoglobin S is the major hemoglobin seen on electrophoresis
which kind of hemoglobin retards the sickling process?
HbF
What do sickled cells lead to?
hemolysis
- ATP to ADP
- NK cells go there and pulmonary inflammation happens
- free hemoglobin takes up NO… pulmonary htn
tx of sickle cell anemia
allogeneic hematopoietic stem cell transplantation is performed before the onset of significant end-organ damage… 80% success
- hydroxyurea
- supportive care is the mainstay of tx 1
EOD for autoimmune hemolytic anemia
- acquired hemolytic anemia caused by IgG autoantibody
- spherocytes and reticulocytosis on peripheral blood smear
- antiglobulin (Coombs) test
is there intra or extra vascular hemolysis in AI hemolytic anemia?
extravascular
-RBC’s get coated with IgG, eaten up by Macs… spleen and liver enlarged
tx of AI hemolytic anemia?
- prednisone
- give incompatible blood? might as well
- Rituximab (CD20 ab…
- splenectomy if prednisone doesn’t work
EOD for cold agglutinin disease
- increased reticulocytes on peripheral blood smear
- antiglobulin (Coombs) test positive only for COMPLEMENT
- positive cold agglutinin titer
clinical findings for cold agglutinin disease
-mottled or numb fingers
-episodic hemoglobinuria in response to exposure to cold
-reticulocytosis
-
tx of cold agglutinin disease
- avoid exposure to cold!
- Rituximab is tx of choice
- RBC’s should be transfused through an in-line blood warmer
EOD for aplastic anemia
- pancytopenia
- no abnormal hematopoietic cells seen in blood or bone marrow
- hypocellular bone marrow
- reticulocytopenia will be there as well
What should definitely NOT be present in aplastic anemia?
hepatosplenomegaly
-it makes sense b/c there’s no freakin cells
what other things could get confused with aplastic anemia?
- hypocellular forms of myelodysplasia or acute leukemia
- look at the marrow, above has mutations and blasts and stuff
tx of aplastic anemia
- supportive care with EPO or filgrastim
- bone marrow transplantation if severe (neturophils less than 500, platelets less than 20,000, retics less than 1%, and bone marrow cellularity less than 20%)
- immunosuppression
what do we need to know about parvovirus?
- it gets erythrocyte precursor cells
- in IC ppl, pure RBC aplasia
- in adults, molecular mimicry to human cytokeratin and TF’s engaged in Hematopoiesis
- in preggo: hydrops fetalis!
- look for IgM antibodies
- RT-PCR is the optimal test
- in IC ppl, give them IVIG
Acute intermittent porphyria EOD
- unexplained abdominal crisis, generally in young women
- acute peripheral or central nervous system dysfunction; recurrent psychiatric illnesses
- hyponatremia
- porphobilinogen in the urine during an attack
Where is the mutation in AIP?
HMBS
-auto dominant
What is AIP caused by?
partial deficiency of hydroxymethylbilane synthase activity
-leads to increased excretion of aminolevulinic acid and porphobilinogen in the urine
What happens with the Urine in AIP people?
it’s normal when freshly voided but turns dark upon standing in light and air
tx of AIP?
-high carbohydrate diet
Porphyria Cutanea Tarda EOD
- noninflammatory blisters on sun-exposed sites, especially the dorsal surfaces of the hands
- hypertrichosis, skin fragility
- associated liver disease
- elevated urine porphyrins
What does porhpyria cutanea tarda look like?
- bilstering and fragility of the skin of the dorsal surfaces of the hands
- facial hypertrichosis and hyperpigmentation are common
What else can happen with the skin lesions of this?
- can be from dialysis or certain meds
- then it’s called, pseudoporphyria
- the biopsy looks the same as porphyria cutanea tarda, but the urine porphyrins are normal
Polycythemial Vera EOD
- JAK2 (V617F) Mutation
- increased RBC mass
- splenomegaly
- normal arterial oxygen saturation
- usually elevated WBC count and platelet count
what cell lines does PCV overproduce
- All three hematopoietic stem cell lines
- but most prominently RBC’s
What is Erythroid production independent of in PCV?
erythropoietin
-so the serum EPO will be low
What do we need to distringuish PCV from?
increased RBC count from costricted plasma volume
-spurious erythrocytosis
What symptoms will PCV present with?
- headache
- dizziness
- tinnitus
- blurred vision*
- fatigue
- pruritis after warm bath
What is the hallmark lab value for PCV?
hematocrit above 54% in males or 51% in females
What do we confirm a diagnosis of PCV with?
JAK2 mutation
What is secreted by WBC’s that leads to increased Vitamin B12 levels in PCV?
transcobalamin III
What does marked elevation of WBC’s make us think of?
CML
What does marked elevation of platelets make us think of ?
ET
What is there’s abnormal RBC morphology and nucleated RBS in the peripheral blood?
Myelofibrosis
What is the tx of choice for PCV?
phlebotomy
- if problematic, hydroxyurea
- if resistant to hydroxyurea, give ruxolitinib
What is the major cause of morbidity and morality in PCV?
arterial thrombosis
Over time, what can PCV convert to?
myelofibrosis or CML
