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(C) CM 1A: Heme/Onc/Endo > Lecture 8: Thrombophilias > Flashcards

Lecture 8: Thrombophilias Flashcards

1
Q

What is Virchow’s Triad?

A

Stasis
Vessel Wall Injury
Hypercoagulability

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2
Q

What is the primary cause of arterial thrombosis?

A

Platelet and vessel wall injury

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3
Q

What are the primary etiologies of arterial thrombosis?

A

Bacterial and viral infections
Inflammation
Trauma/injury

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4
Q

What is VT most commonly caused by?

A

Stasis or hypercoagulability

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5
Q

What are abnormalities of vessel walls?

A

Vessel wall injury
Atherosclerosis

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6
Q

What are abnormalities of blood flow/stasis?

A

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

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7
Q

What are abnormalities of coagulation?

A

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

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8
Q

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

A

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

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9
Q

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

A

Factor V leiden

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10
Q

What is the most common cause of inherited thrombophilia?

A

Factor V leiden

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11
Q

What demographic is most susceptible to factor V leiden?

A

White people

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12
Q

How is factor V Leiden inherited?

A

Autosomal dominant

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13
Q

What is factor 5?

A

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

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14
Q

What is the mechanism of factor V leiden?

A

Increased coag because its inactivated slower.

Decreased AC because Protein C needs it to function properly.

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15
Q

What is the gold standard for FV leiden diagnoses?

A

DNA testing.

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16
Q

What is the concern with a prothrombin gene mutation?

A

High plasma levels of prothrombin (G20210A)

Vit-K dependent.

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17
Q

What is the mnemonic for proteins C & S?

A

Clot Stoppers

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18
Q

How is protein C def inherited?

A

Autosomal dominant

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19
Q

What does a homozygous Protein C def cause?

A

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

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20
Q

How common is Protein C def?

A

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

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21
Q

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

A

Warfarin-induced skin necrosis.

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22
Q

How do I treat warfarin-induced skin necrosis?

A

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

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23
Q

How does Protein C exert an AC effect?

A

Regulates F8a and F5a

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24
Q

How do heterozygous Protein C def present on labs?

A

Normal PT/PTT

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25
Q

How do homozygous Protein C def present on labs?

A

Looks like DIC

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26
Q

What is Protein C dependent on?

A

Vit K

27
Q

How is Protein S def inherited?

A

Autosomal Dominant

28
Q

What is protein S?

A

A cofactor for activated Protein C

29
Q

When does Protein S def commonly appear?

A

Pregnancy
OCP
SCD
Inflammation
Nephrotic syndrome
Coumadin therapy

30
Q

Who has low protein S levels?

A

Women, esp when pregnant or on OCPs.

Also liver disease, IBD, and nephrotic syndrome.

31
Q

How is AT3 def inherited?

A

Autosomal dominant

32
Q

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

A

80-90%

33
Q

What does AT do?

A

Inactivates thrombin, F9a, 10a, 11a, 12a

34
Q

What are half of all AT3 cases occurring in?

A

Pregnancy
Parturition (giving birth)
OCP
Surgery
Trauma

Other half is spontaneous

35
Q

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

A

Deep veins of the legs and mesenteric veins

36
Q

Which def is not due to pregnancy?

A

Protein C

37
Q

What def are not due to surgery?

A

Protein C & S

38
Q

What is puerpium?

A

6 week period post birth

Highest risk for thrombosis

39
Q

What are the risk factors for thrombosis in pregnancy?

A

Age
C-section
Prolong immobilization
Obesity
Previous Hx
Thromphilia

40
Q

Why is pregnancy a risk for thrombosis?

A

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.

41
Q

What is APS?

A

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

42
Q

How does APS work?

A

Autoantibody called an aPL does weird stuff

43
Q

When does APS commonly occur?

A

Primary condition or due to underlying autoimmune like SLE.

44
Q

What is APS a common DDx in?

A

Someone who is having multiple miscarriages

45
Q

How does APS present?

A

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

46
Q

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

A

PFO or ASD

47
Q

How does a DVT present?

A

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

48
Q

How does a DVT present on PE?

A

Palpable cord
Edema
Asymmetry
Positive Homans

49
Q

What is the most specific clinical indication of a DVT?

A

Unilateral leg edema.

50
Q

How is a DVT pretested?

A

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

51
Q

How is a PE pretested?

A

Well’s score
4 or greater is high prob

52
Q

What are the diagnostic tests for a DVT?

A

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

53
Q

What does a D-Dimer measure?

A

Degradation products of fibrin

54
Q

What can falsely elevate a D-Dimer?

A

Pregnancy
Infection
Cancer
Recent Surgery
Inflammation

55
Q

What does a doppler US do?

A

Measures speed of blood flow.

56
Q

How is a PE worked up?

A

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

57
Q

What is the treatment for a DVT or acute PE?

A

Heparin (either) + AC (warfarin)

OR

DOAC alone.

58
Q

How long is heparin for a DVT?

A

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

59
Q

What is the emergency option for DVT/PE?

A

Thrombolytics

60
Q

What is the treatment option for someone with recurrent DVTs?

A

IVC filter

61
Q

When is an IVC filter recommended?

A
  1. CI to AC or high risk for proximal VT or PE
  2. Recurrent thromboembolism despite AC
62
Q

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

A

AT
Protein C
Protein S
Protein V leiden

Additional:
Prothombin gene mutations
aPL antibodies

Repeat tests 2-3 months later.

63
Q

What drugs reduce certain factor/protein levels?

A

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

64
Q

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

A

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.

(C) CM 1A: Heme/Onc/Endo (28 decks)

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