Thrombophilias Flashcards
Etiology of arterial clotting generally speaking
largely related to arterial platelet activation (rather than activation of clotting system in venous system)
Highest risk thrombophilias
Protein C and S
Antithrombin
Anticoagulant that will decrease antithrombin levels
heparin
1) APLS diagnostic criteria 2) what is high titer
Clinical criteria (vascular thrombosis or pregnancy mobordity)
1 of below lab criteria –
LA present in plasma, on 2 or more occasions at least 12 weeks apart, detected according to the guidelines of the International Society on Thrombosis and Haemostasis (Scientific Subcommittee on LAs/phospholipid-dependent antibodies).
aCL of IgG and/or IgM isotype in serum or plasma, present in medium or high titer (ie, ***>40 GPL or MPL, or >the 99th percentile), on 2 or more occasions, at least 12 weeks apart, measured by a standardized ELISA.
Anti-beta2 glycoprotein I antibody of IgG and/or IgM isotype in serum or plasma (in titer >the 99th percentile), present on 2 or more occasions, at least 12 weeks apart, measured by a standardized ELISA, according to recommended procedures.
Highest risk positive lab for APLS
lupus anticoagulant
Lab to check in APLS if concern that INR is inaccurate
chromogenic factor X
Antithrombin 3 mechanism
Inhibits thrombin from converting fibrinogen to fibrin
Cutoff for protein c deficiency
Less than 20
Protein c deficiency point and warfarin use for protein c deficiency
IF using warfarin, need to bridge with heparin for 5 days since will induce protein c deficiency
Acquired causes of protein c deficiency
Warfarin →
DIC →
Post surgery →
Liver disease (synthesized in the liver – hepatic congestion) →
Oral anticoagulant treatment
Acquired causes of protein s deficiency
Liver disease (synthesized by hepatocytes) →
Acute thrombosis →
Pregnancy or estrogen treatment → nearly all pregnant people have decreased, physiologic protein s
***Any comorbid illness that causes an acute phase response can lower the level of free protein S →
DIC →
Anticoagulants: Warfarin, NOAC treatment →
Nephrotic syndrome →
HIV
Most common factor V leiden mutation
RS6025 or F5 p.R506Q
Name of prothrombin gene mutation?
G20210A
Thromboprophylaxis for pregnant pts with history of obstetric APLS but no history of VTE
Prophylactic LMWH with each pregnancy (ASH)
ASA + prophylactic LMWH also an option
Management of pregnant APLS patient with VTE history
LMWH during pregnancy, transition back to warfarin postpartum
Antithrombin 3 pts heterozygotes or homozygotes?
They are all heterozygotes because homozygosity is incompatible with life
What are the mild thrombophilias?
Heterozygous FVL
Heterozygous prothrombin gene mutation
STrongest thrombophilias
1) APLS
2) Antithrombin
3) Protein C
4) Protein S
5) Homozygous FVL
6) homozygous prothrombin gene mutation
**But remember that there’s phenotypic variability among families
Most common thrombophilias
FVL
Prothrombin 20210
What effect does liver disease have on endogenous anticoagulants?
Lowers protein C, S, and AT
What effect does warfarin have on endogenous anticoagulants?
Lowers protein C and S
What effect does warfarin have on endogenous anticoagulants?
Lowers antihrombin
What effect does acute thrombosis have on endogenous anticoagulants?
Lowers protein S and AT
How do DOACS affect protein C and S?
false elevation
