thrombophilia Flashcards
arterial thrombosis accounts for what fraction of deaths in the US
1/3
if there are platelets and vessel wall injury, what type of thrombosis is it?
arterial thrombosis
due to adhesion, activation and then aggregation of platelets
vessel wall abnormalities can result from ?
how?
- trauma/injury
- infection - may induce release of procoagulants from endothelial cells
- inflammation - endothelial cell damage due to multiple etiologies - activated leukocytes, chemokine release, TNF, etc
what are some abnormalities of blood vessels that could happen
- vessel injury/trauma
- atherosclerosis
what is the primary form of venous thrombosis?
deep vein thrombosis (DVT)
DVTs can subsequently embolize to ?
the lungs = pulmonary embolism (PE)
venous thrombosis is most commonly caused by ?
activation of coagulation cascade, due to stasis or hypercoagulability
can be due to heritable or acquired causes
why are DVTs most commonly found in the lower leg/calf?
further away from the heart
veins more prone to stasis bc can’t contract as strong as arteries
some abnormalities that can affect blood flow/stasis (8)
- a-fib
- LVD
- immobility (severe)
- vessel obstruction
- hyperviscosity (ex. polycythemia vera)
- sickle cell anemia
- heart valve disease/replacement (usually mitral)
- indwelling catheters (ex. PIC, femoral)
abnormalities of circulating coagulation proteins/hypercoagulation (6)
- protein C/S deficiency
- activated protein C resistance
- antithrombin (AT) deficiency
- antiphospholipid antibodies
- malignancy (tumor cell procoagulants)
- high dose estrogen therapy/pregnancy (BCs too)
differences between arterial vs venous thrombosis
- started differently and follow distinct pathways
- contribution of hypercoagulability to arterial thrombus formation is not well defined
- common risk factors - age, smoking, obesity, DM, HTN, HLP
- may both be triggered by inflammatory pathways
causes of venous thromboembolism
- inherited thrombophilia
- acquired disorders
6 inherited thrombophilia that can cause venous thromboembolism
- factor V Leiden mutation
- prothrombin gene mutation
- protein S def.
- protein C def.
- antithrombin (AT) def.
- dysfibrinogenemia (rare)
acquired disorders that can cause venous thromboembolism (18)
- malignancy
- presence of central venous catheter
- surgery
- trauma
- pregnancy
- OCs
- hormone replacement therapy
- estrogen meds - tamoxifen, bevacizumab, thalidomide, lenalidoide
- immobilization
- CHF
- antiphospholipid antibody syndrome
- myeloproliferative disorders
- paroxysmal nocturnal hemoglobinuria
- inflammatory bowel disease
- nephrotic syndrome
- marked leukocytosis in acute leukemia
- sickle cella nemia
- HIV/AIDS
what is the MC inherited thrombophilia
favtor V Leiden
factor V Leiden is a risk factor for what types of thrombosis?
cerebral, mesenteric, and portal vein thrombosis
factor V Leiden is most commonly seen in what demographic
white ppl
women who are FV Leiden carriers are more likely to clot if ?
they take OC
what circulates in the plasma as an inactive cofactor and is activated by thrombin?
FV
turns into Va, serving as a cofactor in conversion of prothrombin to thrombin
what are the mechanisms of FV Leiden hypercoagulability
- increased coagulation
- decreased anticoagulation
a vitamin K-dependent protein that is the precursor of thrombin, made in the liver and circulates with a half-life of 3-5d
prothrombin
(prothrombin gene mutation)
what disorder can cause purpura fulminans neonatalis, widespread venous thrombosis, and skin necrosis
protein C def
1-9% of pts with venous thrombosis have ?
protein C def
pts with protein C deficiency are at risk for ?
warfarin-induced skin necrosis
how do you treat a pt with protein C deficiency with warfarin-induced skin necrosis?
- stop warfarin
- start vit. K + heparin + protein C concentrate/FFP
(if labs are normal with warfarin, most likely protein c deficieincy)
pts with heterozygous protein C def with show what lab values? homozygous?
hetero - normal PT and aPTT
homo - abnormal coagulation tests consistent with DIC
any disorder associated with vit. K deficiency may result in protein C def, including ? (5)
- warfarin use
- liver disease
- malnutrition
- DIC
- nephrotic syndrome
what is a cofactor for activated protein C
protein S