Heme/Onc Flashcards
Manifestations of CO poisoning
CO displaces oxygen on hemoglobin
treat with 100% oxygen, possibly in a hyperbaric chamber
AMS
Cherry-red lips
Pulse-ox normal
microcytic anemias
IDA lead poisoning chronic disease sideroblastic thalassemia
normocytic anemias
hemolytic anemia
chronic disease
hypovolemia
macrocytic anemia
folate deficiency
B12 deficiency
liver disease
alcohol abuse
Mean RBC lifespan
120 days
hemolysis
intrinsic- defect intrinsic to cell
extrinsic
H and P:
pale, jaundice, hepatosplenomegaly, brown urine
Labs: decreased H/H increased retic count increased indirect bilirubin increased LDH normal MCV decreased serum haptoglobun
Coombs test for autoimmune abs
Peripheral blood smear:
schistocytes
spherocytes
Burr cells
Types of hemolytic anemia Drug- induced immune mechanical G6PD deficiency
COOMBs test
coomb’s reagent is rabit IgM against human IgG or complement, so that red cells that are bound by auto-immune factors will agglutinate in presence of reagent
direct test looks at patient red cells (reagent mixed with patient RBCs, agglutination- RBCs coated with IgG and complement)
antibodies on the RBCs may be due to warm or cold agglutinins
Warm= IgG (agglutinate at body temp)
Cold= IgM (mycoplasma, EBV), only agglutinate in cold environment
indirect test looks at patient plasmsa: mix serum with type O RBCs, and then with Coombs’ reagent. Agglutination if anti-RBC antibodies in serum
Drug- induced (coombs positive) hemolytic anemia
- PCN
- methyldopa
- quinidine (and quinine)
- cephalosporins
- NSAIDs
Immune hemylotic anemia
warm agglutinins or cold agglutinins
Associations:
EBV, mycoplasma pneumoniae, HIV
Treatment:
avoid cold exposure
steroids
splenectomy
Mechanical hemolytic anemia
turbulent blood flow
prosthetic heart valve
schistocytes
Hereditary spherocytosis
Genetic defect of red cell membranes, resulting in spherical red cells
characteristic findings:
- jaundice and gallstones
- splenomegaly
- anemia with reticulocytosis and increased MCHC (mean corpuscular hemoglobin concentration)
- high incidence of pseudohyperkalemia as RBCs lyse after blood draw and intracellular potassium leaks
- peripheral smear reveals spherocytes
- positive osmotic fragility test
What is the treatment?
- folic acid 1mg daily
- red cell transfucions in cases of extreme anemia
- splenectomy in moderate to severe disease
G6PD deficiency
Spleen Purges Nasty Inclusions From Damaged Cells
G6PD repairs oxidative damage to RBCs. Without it the body is prone to hemolysis
Spleen Purges Nasty Inclusions From Damaged Cells
Sulfonamides Primaquine Nitrofurantoin ING Fava beans Dapsone Chloroquine
PBS:
bite cells
Heinz bodies
Diagnosis:
decreased G6PD activity
fatigue begins within days of ingesting oxidants
Treatment:
antioxidants
transfusions
severer form affects mediterranean patients
milder affects blacks
Why is serum haptoglobin decreased in hemolytic anemia
Why is LDH increased
Haptoglobin binds free hemoglobin in the blood
Haptoglobin-hemoglobin complex is removed from circulation by the spleen
LDH is found inside RBCs
When RBCs lyse, LDH is released into circulation
G6PD
enzyme involved in pentose phosphate pathway
maintains glutathione in RBCs, which is neded to protect RBCs from oxidative damage
deficiency is x- linked recessive non-immune hemolytic anemia
stressors include infection, drugs, fava beans
Iron deficiency anemia
most common anemia
blood loss
poor iron intake
poor iron absorption
acutely, after blood loss the H/H will be normal. H/H won’t drop until after dilution
The new red cells have less iron, so they’re smaller than normal (hypochromic and microcytic with central pallor)
pregnancy
kids can have iron- fortified cereal after 6 months of age due to inadequate intake
history: fatigue, weakness, dyspnea, pica, restelss legs
exam: pallor, tachycardia, tachypnea. angular chelitis, spooning of the nails (concave)
Treatment: iron supplements
determine cause of iron loss
elderly, suspect colon cancer and pursue colonoscopy
Labs:
low serum iron
low serum ferritin
increased TIBC (directly proportional to transferrin), which is the iron transport protein
iron:TIBC ratio is decreased (
ferritin
storage form of iron, low in IDA
elevated in hemochromatosis
increased or elevated in anemia of chronic disease
normal in lead poisoning
increased in sideroblastic anemia
normal in thalassemia
transferrin
protein that transports iron in the blood
high in iron deficiency anemia, when your body wants to bind up iron and transport it where it needs to go
decreased in anemia of chronic disease
normal in lead poisoning
decreased in sideroblastic anemia
normal in thalassemia
Anemia of chronic disease
decreased serum iron
increased or normal ferritin
decreased TIBC
iron:TIBC ratio is normal or high (>18%)
Lead poisoning
serum iron is normal or increased
ferritin and TIBC are normal
Sideroblastic anemia
increased serum iron
increased serum ferritin
decreased TIBC
ringed sideroblasts build up in erythroblast, RBC precursors
seen in the bone marrow
Thalassemia
increased serum iron
normal ferritin
normal transferrin and TIBC
lead poisoning anemia
fatigue, weakness crampy abdominal pain joint pain HA short-term memory loss lead lines on gums peripheral neuropathy
Labs:
decreased MCV
peripheral blood smear: basophilic stippling (basophilic dots, granules of denatured RNA all over the cell) -lead poisoning -thalassemia -alcohol use
no central pallor
Treatment:
adults- EDTA, succimer
children- EDTA, succimer, dimercaprol if severe
Megaloblastic anemia
impaired DNA synthesis B12 deficiency folate deficiency (suspect in elderly with poor nutrition, and alcoholism, drug induced- phenytoin) hypersegmented PMN (more than 6 lobes)
H and P: poor nutrition inflammation of the tongue (glossitis) no neurologic symptoms How do we diagnose folate deficiency anemia?
Just give PO folate supplements anyway
To look at folate levels over time, check RBC folate level
What test gives a measure of RBC folate level over time
RBC folate level
B12 deficiency anemia
pernicious anemia- autoantibodies attack gastric parietal cells in the stomach
so that the body can’t make IF
inadequate B12 intake (vegetarian)
Note: folate insufficiency develops a lot more quickly than B12 deficiency
Resection of the ileum
Bacterial overgrowth
Diphyllobothrium latum infection (fish tapeworm)
H and P peripheral neuropathy paresthesias ataxia loss of vibration sense dementia
labs:
megaloblastic anemia
decreased B12 levels
high serum MMA and homocysteine (intermediate byproducts that build up with B12 is insufficient)
Schilling test (out-dated)
Treatment:
- IM B12
- dietary B12 supplements
- Intranasal B12
Anemia of chronic disease
Anemia in patients with chronic inflammatory states
DM
defect in iron mobilization and utilization
total body iron content is normal
serum iron levels may be low
Treatment:
treat the underlying disorder
supplemental erythropoietin to hgb 11 or 12
Aplastic anemia
pancytopenia from bone marrow failure (leuopenia and thrombocytopenia as well)
Causes: radiation drugs toxins viral infection (EBV, HIV, parvovirus) SCD- parvo B19 aplastic crisis idiopathic congenital
H and P
anemia (weakness, pallor, fatigue)
leukopenia (persistent infections)
thrombocytopenia (poor clotting, easy bruising, petechiae)
Labs: pancytopenia
hypocellularity
IH: fatty infiltration, with aplastic anemia
Treatment:
address underlying cause
bone marrow transplant
worse the older you get
What conditions are associated with schistocytes (fragmented RBCs)
hemolytic anemia
DIC, TTP, HUS
Acanthocytes (spur cells)
abetalipoproteinemia
Echinocytes (burr cells)
uremia, hemolysis
Bite cells
G6PD deficiency
it’s macrophages that bite the Heinz bodies
Basophilic stippling of RBCs
lead poisoning
peripheral neuropathy + ringed sideroblasts
lead poisoning
hypersegmented PMNs
megaloblastic anemia
Heinz bodies (denatured hgb in RBC)
G6PD deficiency
Sideroblastic anemia
anemia due to defects in the heme synthesis pathway
May be inherited (genetic) or acquired (alcohol abuse, INH, lead poison, zinc tox, copperdeficiency)
High RDW
MCV low, hypochromic
sideroblasts are normal nucleated RBC precursors with visible iron granules in their cytoplasm, found in the bone marrow
Ringed sideroblasts, which have iron granules surrounding the nucleus, are NOT normal.
Treatment: Supplement vitamin B6 (pyridoxine) Address underlying cause, stop alcohol Transfusions Erythropoietin Deferoxamine or phlebotomy if patient is iron-overloaded
myelodysplasia with ringed sideroblasts also exists and can progress to acute leukemia
Alpha Thalessemia
alpha thalessemia- defect in alpha globin
more prevalent in patients of African and Asian descent
alpha thalessemia minima: 1 mutated allele, asymptomatic
alpha thal minor or trait: 2 mutated alleles, asymptomatic
HbH disease: 3 mutated alleles a ton of beta globin made of 4 beta globin molecules microcytosis chronic hemolysis
Hemoglobin Bart’s: 4 mutated alleles, incompatible with life
made of 4 gamma globins
hydrops fetalis (leads to death)
Beta thalessemia
defect in beta globin
mediterranean populations
beta thal minior:
- decreased amounts of beta- globin
- minimal anemia
- increased HbA2, made of alpha globin and gamma globin
Beta thal major:
no beta globins at all
HbA2 and HbF
more severe anemia
target cells: central darkening, surrounded by pallor, then more darkening on the outside
thalassemia complications:
iron overload due to transfusions: iron chelator (deferoxamine) for iron overload
rule out thalessemia before starting iron supplements on an anemic patient. Rule out can be done with hemoglobin electrophoresis
How long does HbgF stick around for?
6 months
SCD
H and P sickle cell pain episodes infection hypoxia trauma bone pain/infarction: fish vertebrae (middle infarcts, so the vertebrae get narrow in the center)
osteonecrosis of the femoral head or humoral head
hair on end on skull xray
chest pain
stroke
painful swelling of hands and feet
dyspnea priapism splenomegaly jaundice leg ulcers
labs: anemia sickling HbS increased HbF
Treatment: hydration oxygen analgesics folate longterm management with hydroxyurea, increased HbF avoid triggers, stay healthy
Treatment: pneumococcal vaccine especially if asplenic HiB Meningococcal vaccine hep B vaccine annual flu vaccine
prophylactic penicillin until age 5
Transfusions
Stem cell transplant
Gene therapy
Complications:
- chronic anemia
- pulmonary htn because of occlusion of pulmonary vasculature
- heart failure
- aplastic crisis
- acute chest syndrome (cp, hypoxemia, pulm infiltrates)
- stroke
- osteonecrosis
- autosplenectomy
vaccinate against Hib, pneumococcus, meningococcus, influenza, hep B
- increased risk of infection
- salmonella osteomyelitis
- strep pneumo
- h, influenzae
- meningococcus
- klebsiella
What complication occurs in 10% of patients with sideroblastic anemia?
acute leukemia
Osteomyelitis in a sickle cell patient
salmonella
What can cause lymphopenia without immunodeficiency?
increased cortisol levels
chemotherapy
radiation
lymphoma
What can cause eosinophilia?
Collagen-vascular disease
Atopic diseases (allergies, asthma, Churg-strauss, allergic bronchopulmonary aspergillosis)
Neoplasm
Adrenal insufficiency (Addison disease)
Drugs (NSAIDs, penicillins, cephalosporins)
Acute interstitial nephritis
Parasites (strongyloides, ascaris- loffler eosinophilic pneumonitis) other causes include HIV, hyper IgE syndrome, coccidiomycosis, etc)
Neutropenia
viral infections: viral hepatitis, HIV, EBV
certain drugs
chemotherapy
aplastic anemia
H and P
recurrent infections
Treatment:
G-CSF
GM-CSF
Steroids
How do we manage neutropenic fever? in a cancer patient
admit the patient for observation
culture blood, urine, CSF
broad-spectrum abx
narrow down abx after you’ve isolated an organism
Type 1 hypersensitivity
mediated by IgE antibodies, cross-link antibodies on mast cells
mechanism: degranulation of mast cells
hives, pruritis, bronchospasm, oropharyngeal angioedema, allergic rhinitis, asthma, anaphylaxis
Treatment: antihistamines leukotriene inhibitors bronchodilators corticosteroids
Type II hypersensitivity
mediated by IgM and IgG antibodies directed towards self cells
bind to specific antigens, and activates the complement cascade
examples:
- drug- induced hemolytic anemia
- immune hemolytic anemia
- hemolytic disease of the newborn
- immune thrombocytopenia
- acute rheumatic fever
- Goodpasture syndrome
- Bullous pemphigoid
- Pemphigus vulgaris
- Graves disease
- Myesthenia gravis
Treat:
anti-inflammatories
immunosuppressive agents
plasmapheresis
Type III hypersensitivity
mediated by IgM and IgG immune complexes against soluble antigens (soluble in the blood)
The immune complexes deposit in tissues, and there they initiate complement cascade
Examples:
Arthus reaction
serum sickness
glomerulonephritis
Treatment:
anti-inflammatories
Type IV hypersensitivity
T cells and macrophages
delayed-type hypersensitivity
mechanism:
T cells present antigens to macrophages
examples:
Transplant rejection, contact dermatitis, PPD testing
Treatment: steroids, immunosuppressants
Anaphylaxis SU138
severe type 1 hypersensitivity MCC drugs also, insect stings latex eggs, nuts, seafood
H and P
si/sx 5-50 minutes after exposure
tingling in the skin pruritis chest tightness angioedema (can't breath, can't swallow) syncope tachycardia wheezing urticaria hypotension
treatment: ABCs, intubate if necessary stop the offending agent epinephrine H1/H2 blockers, helps with itching but not airway bronchodilators steroids (maybe) IV fluids if hypotension because you are trying to fill up the vascular space that opens up 2/2 vasodilation
Thrombocytopenia
PLT
Thrombocytopenia may be due to impaired platelet production
drugs infections aplastic anemia folate and B12 deficiency alcohol, toxic to the bone marrow
bone marrow will show reduced or abnormal megakaryocytes
Treatment: stop the offending agent, initiate bone marrow transplant if needed
drugs that cause thrombocytopenia
Heparin, abciximab carbamazepine, phenytoin, valproate cimetidine acyclovir, rifampin sulfonamides (eg sulfasalazine, TMP-SMX) procainamide, quinidine quinine, gold compounds
Splenic sequestration of platelets
splenomegaly
normal one marrow biopsy
Splenectomy can be curitive
HIT
Thrombosis plus thrombocytopenia (sudden decrease in platelet count by at least 50%)
- heparin forms complexes with platelet factor 4
- antibodies against the complex cause platelet activation and aggregation (hypercoagulable thrombopenic state)
- platelets are removed from circulation
Labs:
- serotonin release assay (gold standard, but expensive)
- immunoassay (ELISA) detects platelets
- heparin- induced platelet aggregation assay (specific, but not sensitive)
Treatment: stop heparin, get labs to confirm the diagnosis
anticoagulate with direct thrombin inhibitor like argatroban until PLT gets about 100,000 or so
Then switch to warfarin for 3 months, or direct thrombin inhibitor
These patients should avoid heparin
Immune thrombocytopenia
anti-platelet antibodies
platelet count
TTP-HUS
thrombotic thrombocytic purpura and hemolytic uremic syndrome
deficiency of metalloprotease, leading to excessive platelet aggregation
associated with E.COli O157:H7
HUS triad:
hemolysis,
uremia,
thrombocytopenia
TTP pentad: hemolysis, uremia, thrombocytopenia neurologic sequelae fever
Fever, Anemia, Thrombocytopenia, Renal, Neuro symptoms (FAT RN)
all features do not have to be present at once
Treatment:
steroids
plasmapheresis
FFP
Antiphospholipid syndrome
antiphospholipids against specific phospholipids, increasing risk of thrombocytopenia and hypercoagulability
seen in
pregnancy
lupus
other autoimmune diseases
HELLP syndrome
sequelae of eclampsia/pre-eclampsia
HELLP: Hemolysis Elevated Liver enzymes Low Platelets (Hypertension)
Treat by inducing labor, and delivering the baby
vWF disease
autosomal dominant deficiency of vWF and sometimes factor 8
MC inherited bleeding disorder
vWF is released into local circulation from endothelial cells
1. It helps platelets adhere to vessel walls and crosslink with one another
2. it stabilizes factor VIII
This is important for formation of fibrin clot
Labs:
increased PTT due to factor 8 dysfunction
increased BT
decreasd RISTOCETIN COFACTOR activity
decreased vWF antigen
normal platelet count, platelets are normal too, they just won’t work
H and P:
easy bruising
mucosal bleeding
menorrhagia
Tx:
Desmopressin (induces vWF secretion), first-line for acute bleeding
Cryoprecipitate or factor VIII concentrates for severe or refractory bleeding
OCP for menorrhagia
avoid aspirin and other platelet inhibitors
What are the only 2 factors not synthesized by the liver
vWF
factor 8
these remain at normal levels even when there is liver failure
Vitamin K deficiency
10,9,7,2,c,s
poor intake (green leafy vegetables)
malabsorption
eradication of gut flora that produce vitamin K
H and P: easy bruising mucosal bleeding melena hematuria delayed clot formation macrohemorrhage
Labs:
increased PT, INR
Treatment:
PO or IM vit K
FFP for acute bleeding
RF:
ESRD
Hemophilia B (factor 9) “Benign”
Hemophilia A “Eight”
H and P uncontrolled bleeding that is spontaneous, following minimal trauma, after surgery hemarthrosis IM bleeding GI and GU bleeding
This is a macrohemorrhage, fibrin clot issue
Labs:
increasd PTT
normal PT
normal BT
Treatment: Hemophilia A- give factor VIII Hemophilia B- give factor IX Desmopressin can induce factor VIII release Transfusions may be needed
Complications: hemophilia can lead to death from severe uncontrolled bleeding
Disseminated intravascular coagulation SU 141
excess clotting leads to hypocoagulability
STOP Making Thrombi Sepsis Trauma OB complications Pancreaitis Malignancy Transfusions
H and P uncontrolled bleeding hemoptysis jaundice distal cyanosis hypotension especially with sepsis
Labs: decreased platelets increased bleeding time increased PT increased PTT everything is messed up decreasd fibrinogen (all being used up) increased D-dimer
Schistocytes
Treatment:
treat the underlying cause
if platelets are diminished, replace platelets
If PT and PTT are increased, give FFP or cryoprecipitate
+/- heparin
Hypercoagulable states
due to coag cascade defects
Factor V Leiden mutation (most common)
Antithrombin deficiency
Protein C deficiency
Protein S deficiency
Prothrombin gene mutation (prothrombin G20219A)
Screen if patient has recurrent DVT or fhx of DVT
anticoagulate for life only if they’ve had thrombotic event(s)
What’s the teratment for vWF disease?
DDAVP
for severe bleeding, cryoprecipitate or factor VIII concentrates
OCPs
avoid aspirin and other platelet inhibitors
most common mutation leading to venous thrombosis in white patients?
factor V Leiden mutation
How do we treat the hemotologic infection known as sepsis?
- secure the airway, give oxygen
- give IV fluids
- Give vasopressors (NE is choice)
- Colloid can help bulk up intravascular volume
- If the pressors aren’t working, consider adrenal insufficiency and glucocorticoids as treatment
- Broad spectrum antibiotics initially. Avoid antibiotics before culturing to avoid false negative cultures
- glycemic control between 140 and 180. If you gave glucocorticoids or the patient has DM, consider giving insulin
Malaria medications
chloroquine primaquine quinine atovaquone/proguanil mefloquine
Abnormal T cells fighting off infected B cells
Infectious mononucleosis
Downey cells
Teenagers and young adults get this infection
90-95% of adults are seropositive
symptoms appear 2-5 weeks after infection
H and P: 3-6 months of fatigue sore throat malaise lymphadenopathy- posterior primarily splenomegaly fever tonsillar exudates
can have comorbid strep throat
Labs: positive heterophil abs positive Epstein-Barr serology elevated LFTs hemolytic anemia thrombocytopenia increased lymphocytes
Tx:
supportive care
self- limited
reassurance
there is no antiviral medication available
NSAIDs or acetaminophen for fever, sore throat, malaise
Encourage rest and plenty of fluids
Return to sport (risk of splenic rupture)
-may return gradually to noncontact sports 3 weeks after symptom onset
-may return gradually to contact sports 4 weeks after symptom onset
Steroids only helpful if impending airway compromise due to enlarged tonsils or if life- threatening sequelae develop (fulminant liver failure, hemolytic anemia, thrombocytopenia)
Complications: splenic rupture aplastic anemia DIC HUS-TTP
SIRS criteria
38.390
RR>20
12,00010% bandemia
Acute phase HIV presentation
“acute retroviral syndrome”
fever, myalgias, fatigue HA sore throat rash lymphadenopathy mucosal ulcers persistent high fevers
What does latent phase HIV look like?
several years without symptoms while the virus is destroying lymphocytes
Late phase HIV (AIDS)
opportunistic infections AIDS-defining illnesses weight loss night sweats neurological changes recurrent/unusual infections
wasting syndrome
CD410% of baseline
H and P:
chronic diarrhea
weakness
fever
Tx: HIV meds and supportive care, antiretroviral therapy, appetite stimulants (megestrol)
AIDS dementia
CD4 may be over 200
intellectual decline, ataxia, apathy due to virus. Treat with antiretroviral therapy
diagnosis: cerebral atrophy on CT or MRI
Bacterial pneumonia
streptococcus pneumoniae
haemophilus influenzae
nocardia
severe symptoms:
productive cough
high fever
hypoxia
diagnosis: sputum gram stain, lobar consolidation on CR, diffuse, nodular infiltrates on CXR
Treatment: pathogen specific
Candida esophagitis
an AIDS- defining illness
CD4
Pneumocystis jirovecii pneumonia
CD4 35 mmHg
Tuberculosis
also AIDS- defining
CD4
Histoplasmosis
CD4
Toxoplasmosis
AIDS- defining
H and :
HA, confusion, fever, focal neurological symptoms, seizures
Dx:multiple ring- enhancing lesions on CT or MRI
Tx:
pyrimethamine + sulfadiazine+ leucovorin
or pyrimethamine + clindamycin
Lymphomas (esp CNS or non-Hodgkin)
CD4
Progressive multifocal leukoencephalopathy (JC virus)
a demyelinating disease
CD4
Cryptococcal meningitis
CD4
CMV
CD4
Mycobacterium avium intracellulare complex (MAC)
CD4
HIV screening
In what way do we capture all the true positives and then weed out the false positives
99% sensitive for HIV antibodies
If positive, then repeat ELISA is performed
Preliminary positive= both screening tests were positive
Confirm with specific western blot to screen out false positive
HIV screening tests:CD4 count, significance
tracks disease progression
clinical improvement during HIV treatment- how is HIV affecting the immune system?
HIV viral load, significance
measures viral replication in the blood
PCR- amount of virus in a sample of blood
how useful is the antiretroviral regimen
may show evidence of acute infection prior to ab response
What combination of drugs do you give for HIV prevention after a needle stick?
emtricitabine+ tenofovir+raltegravir
