Hematology Flashcards
Causes of microcytic anemia (MCV less than 80)
Iron deficiency lead poisoning sideroblastic thalassemia anemia of chronic disease
Causes of normocytic anemia (MCV 80-100)
anemia of chronic disease
hemolytic anemia
hemorrhagic anemia
Causes of microcytic anemia (MCV >100)
Folate deficiency
B12 deficiency
Liver disease
etOH abuse
Iron deficiency anemia
MC overall
Etiology: chronic blood loss (MC), inadequate iron intake, poor iron absorption, pregnancy
Presentation: Fatigue SOB, exercise intolerance, tachypnea Tachycardia - d/t decreased O2 carrying capacity Pallor - conjunctivae, nail beds, palms Ice pica Restless legs syndrome Angular stomatitis (chelitis) Spooning of nails
Dx: Low Hgb and Hct Low MCV Low MCH and MCHC - hypochromic Iron: low iron, low ferritin, high transferrin, low %TIBC
Tx: iron supplements, determine underlying cause
Lead poisoning
Etiology:
Adult - occupation lead exposure
Child - ingestion of dust from lead-based house paint
Presentation:
microcytic anemia -> fatigue, dyspnea, pallor -interferes with heme synthesis
Abd pain and constipation
Joint and muscle pain
HA, irritability, short term memory loss - AMS, neuropathy
Peripheral neuropathy - foot drop, wrist drop
Gingival “lead lines”
Dx:
Low Hgb and Hct, low MCV
High serum lead level
Smear: basophilic stippling - blue
Tx: Eliminate source of exposure Chelation for severe poisoning Adults - EDTA or succimer (DMSA) Children - add dimercaprol
Sideroblastic anemia
Etiologies:
Inherited - defect in heme synthesis pathway
Acquired - etOH abuse, isoniazid (low B6), Zn or Cu toxicity
Presentation:
Microcytic anemia - fatigue, dyspnea, pallor
Dx:
Low Hgb and Hct, low MCV
Bone marrow bx - ringed sideroblasts - nucleated RBC precursors with iron granules encircling the nucleus - blue
Tx: Inherited - vit B6 - pyridoxine Acquired - addressed underlying cause RBC transfusion, epo Chelation - deferoxamine or phlebotomy prn for iron overload
Conditions that shift Hgb-O2 dissociation curve left
Holds onto O2 tightly
Alkalosis low temp low CO2 low 2,3-DPG Hgb F (binds less 2,3-DPG)
Conditions that shift Hgb-O2 dissociation curve right
unloads O2
acidosis high temp High altitude exercise elevated CO2 high 2,3-DPG
Alpha thalassemia
Defect in alpha globin production
MC in African and Asian descent
1 defective allele - minima; asx
2 defective alleles - minor; MC; minimal microcytic anemia
3 defective alleles - Hemoglobin H dz; 4 beta globins, microcytic anemia, chronic hemolysis
4 defective alleles - hydrops fetalis; Hgb Bart’s -4 gamma globins very far left shift of Hgb O2 curve; -> fetal edema and intrauterine death
Beta thalassemia
Defect in beta globin production
MC in Mediterranean descent
1 defective allele - minor; low beta globin, high Hgb A2 (alpha 2, delta 2), minimal anemia “trait”
2 defective alleles - major; absent beta globin; Hgb F (alpha 2 gamma 2) + Hgb A2; severe anemia
Dx and Tx of thalasemias
Dx: \+/- microcytic anemia Normal iron studies Smear: atypical RBC forms - target cells Hemoglobin electrophoresis to confirm
Tx:
Transfusion -> iron overload -> iron chelation (deferoxamine)
Always r/o thalassemia in all microcytic anemia to avoid iron overload
Sickle cell disease
Glu->Val position 6 of Beta globin gene on Chr 11
AR
Heterozygous - trait = asx
Homozygous - disease - form Hgb S
Presentation:
Acidosis, hypoxia, or dehydration -> sickling -> hemolysis and vasooclusion/infarction
Episodes of acute pain - sickle crisis
-triggered by dehydration, infection, hypoxia, trauma, illness
Acute chest syndrome
Stroke
Dactylitis - sickling in fingers
Bone infarction; osteonecrosis of humeral or femoral head
Priapism
Splenic sequestration crisis -> splenic infarcts -> autoinfarct by 3-4 yo
-risk of infection by encapsulated bacteria (S. pneumo, H. flu, N. meningitides)
Salmonella osteomyelitis
Parvovirus B19 -> aplastic anemia/crisis
Dx:
Anemia
Smear: sicking of RBCs
Hgb electrophoresis: Hgb S + increased Hgb F
-baby has high Hgb F - asx first 3 mo of life
Skull Xr: “hair on end” appearance from marrow hyperplasia
Tx:
IVF, supplemental O2, opioids during acute pain episodes
Folic acid to optimize marrow production of RBCs
Hydroxyurea to increased Hgb F production
Immunize - pneumococcal, HIB, meningococcal, influenza
ppx PCN until 5 to prevent pneumococcal infection
General features of hemolytic anemia
Presentation:
- fatigue, dyspnea, tachypnea, tachycardia
- Pallor and or jaundice (depending on the type of analysis)
Diagnostic testing for hemolytic anemia
low hemoglobin and hematocrit Normal MCV Elevated indirect bilirubin Elevated LDH Serum haptoglobin low Elevated reticulocyte count Peripheral smear may show should schistocytes, spherocytes, sickle cells, etc
Causes of intrinsic hemolysis
Problem inside RBC
Membrane defects
Enzyme deficiencies
Hemoglobinopathies
Extrinsic hemolysis causes
Microangiopathic anemia
- mechanical destruction of RBCs passing through a obstructed or narrowed small vessels
- examples: DIC or TTP-HUS
- peripheral smear show schistocytes
Macroangiopathic anemia
- mechanical destruction of RBCs due to mechanical forces in large vessels
- examples: prosthetic valves, aortic stenosis
RBC infections - malaria, babesiosis
Autoimmune hemolysis - Ab-mediated
Autoimmune hemolytic anemia - cold agglutinins
Antibodies against RBCs the interact more strongly at low temperatures (4C)
Nearly always IgM
After regularly and infections with EBV or Mycoplasma and some malignancies such as CLL
Circulation to a cold extremity leads to IgM find RBC antigen -> complement fixation -> RBC lysis
Autoimmune hemolytic anemia - warm agglutinins
Antibodies react against RBC antigens at body temperature
Nearly always IgG
Seen in SLE, CLL and non-Hodgkin’s lymphoma malignancies, HIV or EBV, congenital immune abnormalities
Autoimmune hemolytic anemia - drug induced
Drugs induced IgG antibodies that can crossreact with RBCs: Cephalosporins Penicillin Quinidine or quinine NSAIDs Methyldopa
Coombs test
RBC agglutination with the addition of anti-human antibody because RBCs are coated with immunoglobulin or complement proteins
Direct Coombs (DAT) -prepared antibodies are added to a patient RBCs to detect the presence of immunoglobulins already present on the RBCs (using antibody to detect antibody that is already bound)
Indirect Coombs
- patient serum is incubated with normal RBCs to detect the presence of antibodies
- positive when antibodies to foreign RBCs are present - used to test blood prior to transfusion and to screen for maternal antibodies to fetus’ blood
Treatment of autoimmune hemolytic anemia
Warm agglutinins - glucocorticoids, rituximab (against B cells), splenectomy
Cold agglutinins - avoid exposure to cold temperatures
Drug-induced antibodies- stop offending drug
Hereditary spherocytosis
Genetic effect of the red cell membranes and cytoskeleton -> spherical RBCs, no central pallor
Presentation:
Splenomegaly
Hemolysis -> jaundice +/- gallstones
Aplastic anemia following Parvovirus B19 infection
Diagnostic testing:
- anemia with reticulocytosis and increased MCHC
- peripheral smear - spherocytes
- higher incidence of pseudohyperkalemia (rbc’s lyse after blood draw)
- positive osmotic fragility test - rbc’s lyse readily in a hypotonic saline solution
Treatment
Folic acid 1 mg per day
RBC transfusions in cases of extreme anemia
Splenectomy in moderately severe disease -> Howell-Jolly body when no spleen
