Heme Flashcards
inheritance in G6PD
x linked recessive enzymatic disorder
sx G6PD
asx until times of oxidative stress
episodic hemolytic anemia - sx begin 2-4 days after exposure of precipitants - fatigue, pallor, jaundice, dark urine, back or ab pain
may have neonatal jaundice
peripheral smear G6PD
normocytic hemolytic anemia only during crises - schistocytes (bite or fragmented cells) + Heinz bodies are hallmark
smear normal when not in acute stage
Most sensitive test for G6PD
rapid fluorescent spot test - positive if blood spot fails to fluoresce under UV light
Dx IDA
microcytic (MCV) hypochromic (MCHC) anemia
increased RDW
Decreased ferritin < 30
increased TIBC
decreased transferrin saturation (< 20-15%)
decreased serum iron
normal MCHC values
32-36
peripheral smear lead poisoning anemia (plumbism)
microcytic hypochromic anemia w basophilic stippling
ringed sideroblasts on bone marrow
radiographs for plumbism
lead lines - linear hyperdensities at the metaphysical plates in kids
when should you think about thalassemia
microcytic anemia
increased iron or no response to iron replacement therapy
MC cause B12 anemia
pernicious anemia
what type of IBD is more susceptible to B12 deficiency
Crohn disease
Dx B12 deficiency
increased MCV + megaloblastic anemia (macro-ovalocytes and hyperhsegmented neutrophils w > 5 lobes)
decreased serum B12
increased homocysteine
increased methylmalonic acid (MMA)
Dx folate deficiency
Increased MCV + megaloblastic anemia (hyperhsegmented neutrophils, macro-ovalocytes)
decreased serum folate
increased homocysteine
normal methylmalonic acid (MMA)
dx hereditary spherocytosis
hyper chromic microcytosis
spherocytes
increased MCHC
negative Coombs test
tx hereditary spherocytosis
folic acid
splenectomy is curative
PTT measures
1, 2, 5, 8, 9, 11, 12
PT measures
1, 2, 5, 7, 10
MC hereditary bleeding disorder
Von Willebrand disease
sx Von Willebrand dz
prolonged bleeding (oral, uterine, GI)
coagulation studies for von willebrand
normal or prolonged PTT that corrects with mixing study
PT is not affected
PTT and bleeding time prolonged and worse w aspirin
platelet count usually normal
in what subtype of von willebrands are platelets decreased
type 2B
what other factor may be decreased in von willebrand
factor 8
tx von willebrand
Desmopressin
IV Von Willebrand factor with factor 8 (severe)
Inheritance of hemophilia A and B
X linked recessive
dx hemophilia A
low factor 8
prolonged aPTT, normal PT, platelet levels
PTT corrects with mixing studies
tx hemophilia A
factor 8 infusion
desmopressin
dx hemophilia B
low factor 9
prolonged aPTT, normal PT and platelets
prolonged PTT corrects w mixing studies
tx hemophilia B
factor 9 infusion
desmopressin not useful
MC inherited type of hyper coagulability (thrombophilia)
Factor 5 leiden mutation (activated protein C resistance)
Pathophysiology factor 5 leiden
mutated factor 5 is resistant to breakdown by activated protein C
sx factor 5 leiden
increased incidence of DVT, PE, hepatic vain or cerebral vein thrombosis
increased risk of miscarriage, preeclampsia, placental abruption, stillbirth
is factor 5 leiden associated w increased risk of MI or CVA
no
dx factor 5 leiden mutation
activated protein C resistance assay –> if positive, confirm w DNA testing
normal PT and PTT
tx factor 5 leiden mutation
asx - no anticoagulation
severe - indefinite anticoagulation (warfare in direct oral anticoagulant)
Pathophysiology of protein C or S deficiency
proteins C and S are vitamin K dependent anticoagulant proteins produced by the liver that stimulate fibrinolysis and inactivate factors five and 8
decreased protein C or S leads to hyper coagulability
sx protein C or S deficiency
increased incidence of DVT and PE
Warfarin-induced skin necrosis (and pt presenting w this needs to be tested)
purpura fulminan in newborns - red purpuric lesions at pressure points, progresses to painful black eschars
tx protein C or S deficiency
protein C concentrate. indefinite anticoagulation (warfarin or direct oral anticoagulation)
warfarin induced necrosis - D/C, administer IV vitamin K, therapeutic heparin, protein C concentrate or fresh frozen plasma.
polycythemia vera
overproduction of all 3 hematopoietic myeloid stem cell lines
polycythemia vera is caused by what mutation
JAK2
sx polycythemia vera
pruritus esp after a hot shower or bath
epistaxis
bleeding
DVT, TIA
hepatosplenomegaly
facial plethora (flushing)
engorged retinal veins
MC childhood malignancy
acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL)
peaks 2-5 years
sx ALL/LBL
pancytopenia - fever and infections, bleeding, hepatomegaly or splenogemaly
lymphadenopathy
dx ALL/LBL
WBC 5000-100,000, anemia, thrombocytopenia
bone marrow aspiration: hyper cellular w > 20% blasts (definitive)
MC form of leukemia in adults
chronic lymphocytic leukemia/small lymphocytic lymphoma
Pathophysiology chronic lymphocytic leukemia/small lymphocytic lymphoma
clonal proliferation of morphologically mature but immunologically and functionally incompetent B cells
sx chronic lymphocytic leukemia/small lymphocytic lymphoma
usually asx
pancytopenia - fatigue, anemia, increased infections (neutropenia), bleeding
lymphadenopathy**
splenomegaly
dx chronic lymphocytic leukemia/small lymphocytic lymphoma
lymphocytosis
absolute lymphocytosis >/= 5,000/mcL - small, well differentiated, normal and mature-appearing lymphocytes
scattered “smudge cells”
hypogammaglobulinemia (decreased IgG, IgA, IgM)
MC acute leukemia in adults
acute myeloid leukemia
dx acute myeloid leukemia
normocytic normochromic anemia w normal or decreased reticulocytes
circulating myeloblasts
>/= 20% myeloblasts
auer rods (pink/red rod-like granular structures in the cytoplasm)
Pathophysiology of chronic myelogenous leukemia
uncontrolled production of mature and maturing granulocytes (predominantly neutrophils)
fusion of BCR (on chromosome 22) and ABL1(on chromosome 9) = BCR-ABL2 fusion
translocation btwn chromosomes 9 and 22 = Philadelphia chromosome
sx chronic myelogenous leukemia
pruritus after hot bath/shower
splenomegaly
dx chronic myelogenous leukemia
leukocytosis with granulocytic cells (basophilia, neutrophilic, and eosinophilia)
decreased leukocyte alkaline phosphatase score
fluorescence in situ hybridization (FISH) - genetic testing for Philadelphia chromosome
hodgkin lymphoma
B cell malignancy
ages commonly affected Hodgkin lymphoma
peaks at 20 years and then again > 50
RF hodgkin lymphoma
epstein-barr virus
immunosuppression
smoking
Caucasian
MC type of Hodgkin lymphoma
nodular sclerosing - female predominance
which type of Hodgkin lymphoma is associated w Epstein Barr virus
mixed cellularity
which type of Hodgkin lymphoma has the best prognosis
lymphocyte rich/predominant
which type of Hodgkin lymphoma has the worst prognosis
lymphocyte depleted
sx hodgkin lymphoma
painless lymphadenopathy - ETOH ingestion may induce lymph node pain (cervical and supraclavicular)
hepatomegaly, splenomegaly
night sweats, weight loss, Pet-Ebstein fever (cyclical fever)
dx hodgkin lymphoma
excision whole lymph node biopsy - Reed-Sternberg cells - large cells w bi or multilines nuclei (owl eye appearance) and inclusions in nucleoli
infections associated w non-hodgkin lymphoma
epstein barr
HIV
HHV 8
H pylori
thrombotic thrombocytopenic purpura is due to
ADAMTS 13 deficiency –> leads to large vWF multimers that cause small vessel thrombosis
sx TTP
thrombocytopenia - mucocutaneous bleeding (epistaxis, bleeding gums, petechiae, purpura)
microangiopathic hemolytic anemia - anemia, jaundice, schistocytes, splenomegaly
neuro sx - HA, visual changes, confusion, somnolence, seizures
Fever (rare)
Kidney dysfunction - AKI uncommon
dx TTP
thrombocytopenia w normal coagulation studies
tx TTP
plasma exchange
glucocorticoids and/or Rituximab If no response
RF hemolytic uremic syndrome (HUS)
predominantly seen in kids < 5 with a recent hx of gastroenteritis
sx HUS
prodromal diarrheal illness (bloody, N/V) 5-10 days before renal manifestations (oliguria, hematuria)
thrombocytopenia (bleeding)
microangiopathic hemolytic anemia - splenomegaly
renal dysfunction - uremia (elevated BUN)
dx HUS
thrombocytopenia with normal coagulation studies (PT, PTT, fibrinogen)
hemolysis - schistocytes etc
Increased BUN and creatinine
positive stool culture or detectable antibody to Shiga toxin
tx HUS
supportive
if severe - plasmapheresis
what agents are avoided in tx of HUS
antibiotics and anti-motility agents bc they may worsen the condition
causes of DIC
infections - bacterial sepsis MC
malignancies
OB - pre-eclampsia
massive tissue injury and trauma
sx DIC
oozing from venipuncture sites, catheters, drains, extensive bruising, bleeding from multiple sites
thrombosis - gangrene or multi-organ dysfunction
dx DIC
decreased fibrinogen (widespread activation of clotting cascade)
prolonged PT and activated PTT
increased INR
elevated fibrin and D dimer
peripheral smear - thrombocytopenia, fragmented RBCs, schistocytes
Pathophysiology immune thrombocytopenic purpura
autoantibodies against platelets, leading to splenic destruction of platelets
sx ITP
mucocuteanous bleeding
not associated w splenomegaly**
dx ITP
isolated thrombocytopenia
normal coagulation studies
bone marrow: megakaryocytes (large sized platelets)
tx ITP
glucocorticoids or IVIG or anti-D
Rituximab or TPO receptor agonist or splenectomy if refractory
