Thrombophilias

Question 1

Etiology of arterial clotting generally speaking

Answer 1

largely related to arterial platelet activation (rather than activation of clotting system in venous system)

Question 2

Highest risk thrombophilias

Answer 2

Protein C and S
Antithrombin

Question 3

Anticoagulant that will decrease antithrombin levels

Answer 3

heparin

Question 4

1) APLS diagnostic criteria 2) what is high titer

Answer 4

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.

Question 5

Highest risk positive lab for APLS

Answer 5

lupus anticoagulant

Question 6

Lab to check in APLS if concern that INR is inaccurate

Answer 6

chromogenic factor X

Question 7

Antithrombin 3 mechanism

Answer 7

Inhibits thrombin from converting fibrinogen to fibrin

Question 8

Cutoff for protein c deficiency

Answer 8

Less than 20

Question 9

Protein c deficiency point and warfarin use for protein c deficiency

Answer 9

IF using warfarin, need to bridge with heparin for 5 days since will induce protein c deficiency

Question 10

Acquired causes of protein c deficiency

Answer 10

Warfarin →
DIC →
Post surgery →
Liver disease (synthesized in the liver – hepatic congestion) →
Oral anticoagulant treatment

Question 11

Acquired causes of protein s deficiency

Answer 11

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

Question 12

Most common factor V leiden mutation

Answer 12

RS6025 or F5 p.R506Q

Question 13

Name of prothrombin gene mutation?

Answer 13

G20210A

Question 14

Thromboprophylaxis for pregnant pts with history of obstetric APLS but no history of VTE

Answer 14

Prophylactic LMWH with each pregnancy (ASH)
ASA + prophylactic LMWH also an option

Question 15

Management of pregnant APLS patient with VTE history

Answer 15

LMWH during pregnancy, transition back to warfarin postpartum

Question 16

Antithrombin 3 pts heterozygotes or homozygotes?

Answer 16

They are all heterozygotes because homozygosity is incompatible with life

Question 17

What are the mild thrombophilias?

Answer 17

Heterozygous FVL
Heterozygous prothrombin gene mutation

Question 18

STrongest thrombophilias

Answer 18

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

Question 19

Most common thrombophilias

Answer 19

FVL
Prothrombin 20210

Question 20

What effect does liver disease have on endogenous anticoagulants?

Answer 20

Lowers protein C, S, and AT

Question 21

What effect does warfarin have on endogenous anticoagulants?

Answer 21

Lowers protein C and S

Question 22

What effect does warfarin have on endogenous anticoagulants?

Answer 22

Lowers antihrombin

Question 23

What effect does acute thrombosis have on endogenous anticoagulants?

Answer 23

Lowers protein S and AT

Question 24

How do DOACS affect protein C and S?

Answer 24

false elevation

Question 25

Clinical criteria satisfying sapporo criteria

Answer 25

vascular thrombosis
OR
pregnancy morbidity

Question 26

What does data indicate about warfarin vs. NOACs for APLS?

Answer 26

Higher rate of failure w/ NOACs than warfarin for arterial thrombosis (CVA) in trials, VTE and bleeding rates the same

Question 27

What does evidence indicate about prophylactic lovenox during pregnancy for pts with inherited thrombophilias?

Answer 27

No benefit for birth rates, increased bleeding

Question 28

Should women with recurrent pregnancy loss be tested for thrombophilia?

Answer 28

No, data does not support