Heme/Onc Flashcards
Virchow’s triad
- Vessel injury
- venous stasis
- hypercoagulability
Top 5 hereditary RFs for thrombophilia
- Factor V Leiden
- Prothrombin mutation
- Protein C deficiency
- Protein S deficiency
- Antithrombin deficiency
Top 5 acquired RFs for thrombophilia (RR)
- Antiphospholipid Abs (10)
- Active cancer (7)
- Pregnancy (6)
- Estrogen (OCPs/HRT) (4)
- Smoking
Multiple RFs (either hereditary or acquired) have a additive/synergistic effect on RR of first VTE event?
synergistic
What clinical AND laboratory info is necessary to make a dx of Antiphospholipid syndrome?
- Clinical criteria: arterial/venous thrombosis OR pregnancy loss/ recurrent miscarriage
- Labs criteria: (+) APLA test (any of the 3) detected on 2 or occasions separated by at least 12 weeks
Why do you need a (+) APLA test (any of the 3) detected on 2 or occasions separated by at least 12 weeks?
can be falsely elevated d/t dz
MC inherited thrombophilia
Factor V Leiden
Homozygous neonates may present clinically with neonatal purpura fulminans (DIC) w/ these 2 hereditary thrombosis RFs:
- Protein C deficiency
- Protein S deficiency (cofactor for APC)
What effect does warfarin have on activated protein C (APC)? Why?
↓ levels because protein C is dependent on Vitamin K and warfarin is a Vitamin K antagonist
Name the dz based on clinical presentation:
- VTE (may be recurrent) @ unusual sites
- Recurrent thrombosis may occur despite absence of additional RFs
- Some patients are resistant to heparin therapy
antithrombin deficiency
How does the presence of APLAs mess with the following coagulation labs: aPTT, PT, 1:1 mixing study
- aPTT: prolongs aPTT → makes heparin dosing difficult
- PT: may prolong PT → makes warfarin dosing difficult
- 1:1 mix: does NOT correct BUT causes CLOTTING not bleeding (unlike clotting factor deficiency disorders)!!
Do APLAs act as anti- or pro- coagulants?
PROCOAGULANTS!! 1:1 mixing study does NOT correct but causes CLOTTING not bleeding!
What is the initial therapy for tx of VTE (2 components)?
- heparin or LMWH for ~5 days
- Warfarin/coumadin for 3-6 mo.
When should you test for abnormal hypercoagulable states in the clinic?
When results could change management!
- Young age (<45 yo) w/ unprovoked VTE questions regarding need for long term anti-coagulation therapy
- Thrombosis in unusual sites (arterial, upper extremities)
What are the 3 new anti-coagulation drugs that may change the risk/benefit analysis that is currently an issue with warfarin? What is one potential problem with these drugs?
- Dabigatran (Pradaxa)
- Rivaroxaban (Xarelto)
- Apixaban (Eliquis)
NO OD REVERSAL AGENT!!
What are the 3 APLAs?
- Lupus anticoagulant
- Anticardiolipin Abs
- anti-β2GPI Abs
What is the biggest thrombophilia RF contributing to recurrent clotting events
persistent APLAs
What are 4 modifiable RFs that can be addressed during tx of thrombophilia?
- smoking cessation
- maintaining healthy weight
- staying active (lack of immobilization)
- avoiding estrogen/ progesterone
Which 2 hereditary VTE RFs likely need additional RFs in order to provoke thrombosis?
- Protein C deficiency
- Protein S deficiency
What are 3 lab tests we have to test platelet function?
- PFA-100
- Platelet aggregation testing
- Thromboelastography
What is the most important lab test for differentiating b/w a coagulation factor deficiency and a coagulation factor inhibitor?
1:1 mixing study
Does a 1:1 mix study correct if a coagulation factor deficiency or inhibitor is present?
deficiency: 1:1 mix corrects to normal
inhibitor: 1:1 mix does NOT correct to normal
leading cause of renal failure in children worldwide
HUS d/t shiga toxin in E. Coli
What are the 3 requirements for proper RBC prdn. (erythropoiesis)?
- bone marrow cells working
- EPO from kidney
- substrate supplies (iron, Vit. B12, folic acid)
define anemia:
low Hb or Hct
Hct = Hb x 3
The severity of anemia ssx depends on what?
speed at which the anemia developed
What does a reticulocyte index (RI) < 2.0 indicate?
inadequate BM response to anemia
What is iron-deficiency testing confounded by in many anemic patients?
inflammation –> ferritin ↑ as an acute-phase reactant → mask low level of ferritin expected in Fe deficiency
Does Vit. B12 or Folate deficiency typically cause neuro ssx w/ (+) hx of AI dz?
B12 deficincy
↑↑ levels of methylmalonate AND homocysteine suggest which type of macrocytic anemia?
B12 deficiency
MCC of anemia in the western world
Fe-deficiency
RBC smear:
hypochromia (pale RBCs)
+ microcytosis (small RBCs) + anisocytosis (RBCs of different sizes)
Fe deficiency anemia (late)
Which racial population is α-thalassemia MC in?
SE asians
Which racial populations is β-thalassemia MC in?
Mediterranean and African
(but has world-wide distribution)
Single nucleotide substitution in β-globin gene on chromosome 11
sickle cell dz
hallmark of sickle cell dz
pain crisis
What tx do β-thalassemia major patients need regularly?
RBC transfusions
RBC smear:
Rouleaux formation
multiple myeloma causing myelodysplastic syndrome
What Hct and Hb levels for men and wome indicate erythrocytosis (polycythemia)?
- women: Hct > 48, Hb > 16.5
- men: Hct > 52, Hb > 18.5
Tx for polycythemia vera
phlebotomy
labs: ↓Fe ↓TIBC (transferrin) ↑ferritin
anemia of chronic dz
inflammation → ↓ Fe transport (transferrin) → ↓Fe release from m∅s
What does transferrin do (Fe metabolism)?
transferring transports Fe in the blood
TIBC is an indirect measure of transferrin
What does ferritin do (Fe metabolism)?
1° Fe storage protein of the body
labs: ↓Fe ↑TIBC (transferrin) ↓ferritin ↓↓ % transferrin saturation (serum Fe/ TIBC)
Fe deficiency anemia
What are the 3 types of venous dz we learned about?
- chronic venous insufficiency (stasis)
- DVT
- Lymphedema
spider/ varicose veins
chronic venous insufficiency
2 Dx tests of chronic venous insufficiency; which is the most sensitive and specific?
Duplex ultrasound
DVT (most sensitive and specific)
In what situation would you use a CT Scan/ MRI to dx chronic venous insufficiency?
May-Thurner Syndrome
Management of chronic venous insufficiency:
- Compression stockings
- Leg elevation
- then surgical options
Gold standard surgical tx of chronic venous insufficiency
saphenous vein ablation
Major complication of DVT requiring catheter directed thrombolysis
phlegmasia
- Cerulea (cyanotic) Dolens- cancer (40%)
- Alba (white) Dolens
What is reperfusion syndrome?
release of inflammatory mediators upon blood flow restoration in DVT
30-40% mortality in ICUs
Cause of chronic DVT (post-thrombotic syndrome)
venous valve dysfunction → chronic leg pain, eczema, swelling, venous ulcers
What is lymphedema?
accumulation of interstitial fluid d/t defective lymphatic drainage
Comme surgery often leading to lymphedema
breast mastectomy
PE:
- edema
- square toes
- Stemmer’s sign: inability fo pinch the skin over the dorsum of the 2nd toe
lymphedema
mainstay tx for lymphedema
compression stockings
blood smear:
PMNs w/ toxic granulations + Dohle bodies
‘toxic’ PMNs → indicative of infectious (reactive) neutrophilia
absolute neutrophil count < 1000
neutropenic fever → hematologic emergency
Why is neutropenic fever a hematologic emergency? Tx?
d/t high risk of gram(+) bacteremia
Tx: empirically tx w/ broad coverage abx
dx pathology:
> 20% blasts in periphery + Auer rods
AML
t(9:22) bcr-abl
CML
peripheral blood smear: smudge cells
SLL/CLL
What can prolong Prothrombin Time (PT)? (3)
- liver dz
- Vitamin K deficiency
- Warfarin**
PT/INR is most sensitive to what coagulation factor?
VII (extrinsic pthwy)
PTT is most sensitive to which coagulation factors?
VIII and IX
MC lymphoma
Diffuse B cell lymphoma (aggressive NHL)
Reed-Sternberg (‘owl eye’) cells
Hodgkins Lymphoma
common ssx for this lymphoma is pruitis (itchyness) w/o rash
Hodgkins
