Lecture 8: Thrombophilias

Question 1

What is Virchow’s Triad?

Answer 1

Stasis
Vessel Wall Injury
Hypercoagulability

Question 2

What is the primary cause of arterial thrombosis?

Answer 2

Platelet and vessel wall injury

Question 3

What are the primary etiologies of arterial thrombosis?

Answer 3

Bacterial and viral infections
Inflammation
Trauma/injury

Question 4

What is VT most commonly caused by?

Answer 4

Stasis or hypercoagulability

Question 5

What are abnormalities of vessel walls?

Answer 5

Vessel wall injury
Atherosclerosis

Question 6

What are abnormalities of blood flow/stasis?
ALIVHSHI

Answer 6

AFib
LV Dysfunction
Immobility
Vessel occlusion
Hyperviscosity (polycythemia vera)
SCD
Heart valve disease
Indwelling catheters (PICC or femoral line)

Question 7

What are abnormalities of coagulation?

Answer 7

Protein C or S def
Activated Protein C resistance
AT deficiency
APL antibodies
Malignancy
High dose estrogen/PREGNANCY

Question 8

What are the inherited causes of thrombophilia in causes of VT?

Answer 8

Factor V leiden mutation
Prothrombin gene mutation
Protein S def
Protein C def
AT def
Dysfibrinogenemia

Question 9

In what inherited cause of thrombophilia is DVT/PE most common?

Answer 9

Factor V leiden

Question 10

What is the most common cause of inherited thrombophilia?

Answer 10

Factor V leiden

Question 11

What demographic is most susceptible to factor V leiden?

Answer 11

White people

Question 12

How is factor V Leiden inherited?

Answer 12

Autosomal dominant

Question 13

What is factor 5?

Answer 13

Inactive cofactor activated by thrombin to convert more prothrombin to thrombin.

Question 14

What is the mechanism of factor V leiden?

Answer 14

Increased coag because its inactivated slower.

Decreased AC because Protein C needs it to function properly.

Question 15

What is the gold standard for FV leidin diagnoses?

Answer 15

DNA testing.

Question 16

What is the concern with a prothrombin gene mutation?

Answer 16

High plasma levels of prothrombin (G20210A)

Vit-K dependent.

Question 17

What is the mnemonic for proteins C & S?

Answer 17

Clot Stoppers

Question 18

How is protein C def inherited?

Answer 18

Autosomal dominant

Question 19

What does a homozygous Protein C def cause?

Answer 19

Purpura fulminans neonatalis, which causes widespread VT and skin necrosis.

Question 20

How common is Protein C def?

Answer 20

1-9% of pts with a VT have Protein C def.

Question 21

What are patients specifically at risk for in protein C def?

Answer 21

Warfarin-induced skin necrosis.

Question 22

How do I treat warfarin-induced skin necrosis?

Answer 22

Stop warfarin
Start Vit K, Hep, Protein C concentrate/FFP.

Question 23

How does Protein C exert an AC effect?

Answer 23

Regulates F8a and F5a

Question 24

How do heterocygous Protein C def present on labs?

Answer 24

Normal PT/PTT

Question 25

How do homozygous Protein C def present on labs?

Answer 25

Looks like DIC

Question 26

What is Protein C dependent on?

Answer 26

Vit K

Question 27

How is Protein S def inherited?

Answer 27

Autosomal Dominant

Question 28

What is protein S?

Answer 28

A cofactor for activated Protein C

Question 29

When does Protein S def commonly appear?

Answer 29

Pregnancy OCP SCD Inflammation Nephrotic syndrome Coumadin therapy

Question 30

Who has low protein S levels?

Answer 30

Women, esp when pregnant or on OCPs. Also liver disease, IBD, and nephrotic syndrome.

Question 31

How is AT3 def inherited?

Answer 31

Autosomal dominant

Question 32

What is the lifetime thrombotic risk for a heterozygous AT3 def?

Answer 32

80-90%

Question 33

What does AT do?

Answer 33

Inactivates F9a, 10a, 11a, 12a

Question 34

What are half of all AT3 cases occurring in?

Answer 34

Pregnancy Parturition (giving birth) OCP Surgery Trauma Other half is spontaneous

Question 35

Where is the most common site for AT3 disease to affect?

Answer 35

Deep veins of the legs and mesenteric veins

Question 36

Which def is not due to pregnancy?

Answer 36

Protein C

Question 37

What def are not due to surgery?

Answer 37

Protein C & S

Question 38

What is puerpium?

Answer 38

6 week period post birth Highest risk for thrombosis

Question 39

What are the risk factors for thrombosis in pregnancy?

Answer 39

Age C-section Prolong immobilization Obesity Previous Hx Thromphilia

Question 40

Why is pregnancy a risk for thrombosis?

Answer 40

Alterations in hemostasis in lower ext due to uterus. Trauma to pelvic veins during delivery Alterations in factors Compression of left iliac vein by right iliac artery, causing 3x increase in left leg DVT.

Question 41

What is APS?

Answer 41

Acquired hypercoagulable state causing RECURRENT VT or AT OR pregnancy mortality.

Question 42

How does APS work?

Answer 42

Autoantibody called an aPL does weird stuff

Question 43

When does APS commonly occur?

Answer 43

Primary condition or due to underlying autoimmune like SLE.

Question 44

What is APS a common DDx in?

Answer 44

Someone who is having multiple miscarriages

Question 45

How does APS present?

Answer 45

VT/AT Pregnancy complications such as: Fetal death in 10 weeks Premature birth due to pre-eclampsia or placental insufficiency Embryonic losses Livedo reticularis Libman sacks verrucous endocarditis

Question 46

What two heart defects may lead a DVT to become a PE more easily?

Answer 46

PFO or ASD

Question 47

How does a DVT present?

Answer 47

Swelling, pain and discoloration Tenderness in calf or medial veins of deep thigh. Warmth/erythema

Question 48

How does a PE of a DVT present?

Answer 48

Palpable cord Edema Asymmetry Positive Homans

Question 49

What is the most specific clinical indication of a DVT?

Answer 49

Unilateral leg edema.

Question 50

How is a DVT pretested?

Answer 50

Well's Score. 3 or greater is high prob.

Question 51

How is a PE pretested?

Answer 51

Well's score 4 or greater is high prob

Question 52

What are the diagnostic tests for a DVT?

Answer 52

Venous Doppler US (approach of choice) D-Dimer serum test Impedance plethysmography (IPG) (never used) Contrast Venography (invasive) MRI (costly)

Question 53

What does a D-Dimer measure?

Answer 53

Degradation products of fibrin

Question 54

What can falsely elevate a D-Dimer?

Answer 54

Pregnancy Infection Cancer Recent Surgery Inflammation

Question 55

What does a doppler US do?

Answer 55

Measures speed of blood flow.

Question 56

How is a PE worked up?

Answer 56

Angiography VQ scan CT scan w/ IV contrast D-Dimer

Question 57

What is the treatment for a DVT or acute PE?

Answer 57

Heparin (either) + AC (warfarin) OR DOAC alone.

Question 58

How long is heparin for a DVT?

Answer 58

5 days, then continued on oral AC. INR must be between 2-3

Question 59

What is the emergency option for DVT/PE?

Answer 59

Thrombolytics

Question 60

What is the treatment option for someone with recurrent DVTs?

Answer 60

IVC filter

Question 61

What is an IVC filter recommended?

Answer 61

1. CI to AC or high risk for proximal VT or PE 2. Recurrent thromboembolism despite AC

Question 62

What are the screening tests for someone we suspect has a hypercoagulable state?

Answer 62

AT Protein C Protein S Protein V leiden Additional: Prothombin gene mutations aPL antibodies Repeat tests 2-3 months later.

Question 63

What drugs reduce certain factor/protein levels?

Answer 63

Warfarin reduces protein C & S levels. Heparin reduces AT levels

Question 64

What is considered a high-risk patient for Long-term AC due to VT?

Answer 64

2 or more spontaneous events 1 life-threatening spontaneous event 1 spontaneous unusual thrombosis 1 spontaneous thrombosis in association with APS, cancer, AT3 def, or genetic abnormality.