9. Hypercoagulable States Flashcards
under normal conditions, vascular endothelium is procoag or anticoag?
anticoag
perturbing the endothelium (injury, inflammation) converts it from what to what?
from anticoag to procoag
subendothelium is procoag or anticoag?
procoag. injury will expose this.
the first step in primary hemostasis is vasoconstriction. what causes this?
adrenergic activity, epinephrnie
definition of thrombus?
intravascular mass of fibrin + blood cells. endo product of primary and secondary hemostasis
thrombosis: definition?
act of forming a thrombus. may be physiologic of pathologic
define hypercoagulable state
thrombosis that occurs in circumstances under which you’d not usually expect thrombosis. due to excessive activation of blood coagulation (inc thrombogenic factors, decr anticoag factors)
what are the three things in Virchow’s Triad?
- blood vessel wall damage
- altered blood flow (stasis)
- altered blood composition (hypercoagulability)
which of the Virchow’s triad components is most relevant for arterial thrombosis?
vessel injury. arteries are strong, can withstand injury. and very little stasis
which of the Virchow’s triad components is most relevant for venous thrombosis?
stasis, composition. vessel injury is less impt
major problems from venous thrombosis?
- DVT
- Pulm Embolism
why does stasis lead to thrombosis?
hypoxic vascular endothelium will become procoagulant.
VTE: men vs women? young vs old?
men > women
incidence doubles with each 10 yr inc in age
define thrombophilia
hereditary or acquired predisposition to venous thromboembolism (VTE)
describe, in general, the VTE risk factor model
everyone has an intrinsic risk for thrombosis, from Genes and Acquired Risk Factors. then environment can make it worse, prophylaxis can make it less likely to get a thrombus
what are some environmental/situational risk factors for VTE?
pregnancy, surgery (wound healing), illness (inflammation), immobilization, trauma, air travel
what are some genetic risks for thrombosis?
anticoag deficiencies, Factor V leiden, prothrombin 20210A, Non-Type O blood type
what are some acquired risk factors for thrombosis?
age, cancer, obesity, hormone treatments, smoking
how does obesity contribute to a pro-thrombotic state?
incr FVIII due to inflammatory cytokines from adipose tissue
how does pregnancy contribute to a pro-thrombotic state?
incr procoag factors (FVIII, vWF)
decr anticoag factors (protein S)
what are two hematologic disorders that contribute to a pro-thrombotic state?
myeloproliferative disorders, PNH
what are antiphospholipid antibodies (APA)?
autoantibodies directed against protein of phospholipid, plasma proteins that usually bind to phospholipids (ie, PS/PE on platelet surface)
what can trigger APA?
meds, infections, another autoimmune disorder
what is lupus anticoagulant? what does it do?
badly-named antibody. interferes with prothrombinase complex binding to phospholipid surface of platelet. somehow triggers thrombosis (we don’t know how)
lupus anticoagulant: will it correct in a mixing study?
no, it is an antibody
what are the requirements for Antiphospholipid Antibody Syndrome?
clinical event + persistent presence of an antiphospholipid antibody
elevated coag factor levels: how defined? what is reason for elevation?
defined as >150%
can be either genetic or acquired (medical illness, obesity, APA)
what are the major checkpoints for the clotting cascade?
VIIIa, Va, Xa, thrombin
what does APC/S do?
inhibits Va, VIIIa
what does antithrombin do?
inhibits Xa, thrombin
a deficiency of APC/S or antithrombin will have what effect?
pro-coagulant, thrombin will proceed unchecked.
What is Factor V Leiden mutation?
genetic mutation in Va which prevents the action of APC/S complex. pro-coagulant
what is the prothrombin mutation?
genetic mutation that increases the levels of prothrombin. pro-coagulant
define Activated Protein C Resistance
renders Va resistant to inactivation by activated protein C. Factor V Leiden is most common mutation. Can also be acquired.
factor V Leiden mutation: what is penetrance?
asx in 90% of heterozygotes, even homozygoes may still be asx.
how do we test for Factor V Leiden?
screening test for APC resistance. confirm with PCR, genetic test
Prothrombin 20210A mutation: what is penetrance?
asx in 90% of heterozygotes. homozygotes have a higher risk of thrombus.
what does Protein C do?
VitK-dependent factor, produced by liver. with its cofactor (protein S) inactivates factors V and VIII.
what is an unusual risk associated with protein C and Protein S deficiency?
can have warfarin-induced skin necrosis
Types of protein C deficiency?
Type I: activity low, antigen level low
Type II: activity low, antigen level normal
what does Protein S do?
VitK-dependent factor, produced by liver. cofactor for Protein C; complex of C and S inactivates factors V and VIII
Protein S deficiency: men v women?
women have lower levels than men, esp if preg or on OCPs
Physiology of Protein S: what are the 3 forms in which it is found in the body? what happens in acute inflammatory states?
found bound to C4bBP protein, Free, or bound to Protein C.
in inflammatory states, more is bound to C4bBP protein, less available for Protein C binding. causes pro-coagulant state.
describe the 3 types of Protein S deficiency
Type I: total antigen is low. could be acquired or congenital
Type II: normal level, activity is low
Type III: normal level, activity is low, due to binding to C4bBP, smoking, preg.
what is the most severe/rare deficiency that yields a procoagulant state? by what age does it typically present?
hereditary antithrombin deficiency. typically VTE presents before age 35.
what are the two types of antithrombin deficiency?
Type I: antigen low, activity low
Type II: antigen normal, activity low
