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Heme/Onc by Minnie (she/her) > 257/258/260 - Too Much Clotting > Flashcards

257/258/260 - Too Much Clotting Flashcards

Thrombophilia, VTE, Anticoagulant therapy for VTE

1
Q

Compare the relative and absolute risk of thrombosis with the inherited thrombophilias

A

Relative risk increases several fold

Absolute risk remains relatively low; can become higher when combined with another risk factor (OCPs, smoking), but still low enough that we don’t need to screen for thrombophilias before prescribing OCPs

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2
Q

What 3 antibodies are associated with antiphospholipid antibody syndrome?

A
  • Lupus anticoagulant
  • Anti-beta 2 glycoprotein antibody
  • Anti-cardiolipin antibody
  • -> Arterial and venous thrombosis, pregnancy complications*
  • Dx requires lab criteria (antibodies) and clinical criteria (thrombosis or obstetric complications)*
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3
Q

What is the inhibitor for dabigatran?

A

Idarucizumab

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4
Q

List the 2 major categories of directa acting oral anticoagulants

A
  • Anti-Xa agents (-xaban)​
    • Rivaroxaban
    • Apixaban
    • Endoxaban
  • Direct thrombin inhibitors (-gat-, -rudin)
    • Argatroban
    • Dabigatran
    • Bivalirudin
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5
Q

Is the following characteristic of arterial or venous thrombus?

Red (rich in RBCs)

A

Venous

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6
Q

What comorbidity increases bleeing risk in patients on LMWH?

A

Renal failure

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7
Q

What enzyme activates clotting factors II, VII, IX, and X?

What is the cofactor?

A

VKOR

Vitamin K

VKOR is the target of Warfarin

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8
Q

What is the most common cause of VTE?

A

Abnormal blood flow

  • Bedrest
  • After surgery
  • Long flights
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9
Q

How long after starting therapy does it take for warfarin to achieve full therapeutic effects?

A

5 days

  • FVII will drop first (shortest half life)
  • Not considered therapeutic until FII drops
    • ​Mus decrease below 20%
  • Use a heparin bridge if immediate anticoagulation is necessary
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10
Q

A clot in which veins are most likely to embolize to the lungs?

A

Deep > superficial

Proximal > distal

Proximal lower extremity clots are most likely to cause PE

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11
Q

List 2 low-molecular weight heparin agents

A

Enoxaparin

Dalteparin

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12
Q

List 4 complications of VTE

A
  • Death
  • Recurrent thrombosis (VTE again)
  • Post-thrombotic syndrome
  • Pulmonary hypertension (CETPH)
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13
Q

What is the goal INR for Warfarin therapy?

A

2-3

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14
Q

Which outpatient anticoagulant is safest to use in renal disease?

A

Warfarin - not excreted renally

  • Of the DOACs, Apixiban relies least on renal excretion*
  • For inpatient/acute setting, unfractionated heparin is safe in renal disease, but NOT LMWH or fondaparinux*
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15
Q

What inherited thrombophilia results in relative heparin resistance?

A

Antithrombin deficiency

Heparin works by potentiating the effects of antithrombin

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16
Q

List 2 demographics for whom direct roal anticoagulants should not be prescribed

A

Pregnant patients

Patients with renal failure

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17
Q

What are the indications for thrombolytic therapy in VTE?

A
  • Systemically if massive PE (hemodynamic instability)
  • Catheter-directed:
    • If DVT is life or limb threatening
    • If PE is submassive but high risk
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18
Q

What imaging method is most commonly used for suspected PE?

What method is gold standard?

A
  • Commonly used = CT pulmonary angiogram
  • Gold standard = Angiography
  • High clinical probability -> CTPA*
  • Low or intermediate with positive D-dimer -> CTPA*
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19
Q

Which clotting factors are inactivated by protein C? (2)

A

Va, VIIIa

Protein C cleaves Va, and then V helps protein C cleave VIIIa

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20
Q

When would an IVC filter be used to treat VTE?

A

If a pt has acute PE or proximal DVT and cannot tolerate therapeutic anticoagulation

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21
Q

Is unfractionated heparin safe to use in patients with renal disease?

A

Yes

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22
Q

List 3 loss of function inherited thrombophilias

A
  • Protein C deficiency
  • Protein S deficiency
  • Antithrombin deficiency
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23
Q

What clotting factors are inhibited by antithrombin?

A

IIa, Xa

  • Note: heparin drugs potentiate the effects of antithrombin*
  • Heparin: inactivates IIa, Xa*
  • LMWH: more specific for Xa*
  • Fondaparinux: Most specific for Xa, minimal effects on IIa*
  • IIa = thrombin*
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24
Q

Which inherited thrombophilia mutation is associated with the greatest risk of thrombosis?

A

Factor V Leiden

Venous thrombosis most common

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25
Is the following characteristic of arterial or venous thrombus? ## Footnote **Forms in high shear areas**
Arterial
26
Is Factor V Leiden autosomal recessive or dominant?
Autosomal dominant * Heterozygous: 3-5 fold increased risk of first VTE * Homozygous: 18 fold increased risk of first VTE *FVL has the highest risk of thrombosis of the inherited thrombophilias*
27
Which inherited thrombophilia mutation is associated with the **lowest** risk of thrombosis?
Heterozygous prothrombin gene mutation *Factor V Leiden has the highst risk of thrombosis*
28
What are the differences in **location and pathogenesis** of arterial vs. venous thrombi?
* Arterial * High-shear areas * Driven by platelets (Arterial thrombi will be platelet rich) * Venous * Low-flow areas * Driven by **pro-coagulant factors** *Anti-platelet drugs are better at preventing arterial thrombi than venous thrombi*
29
List 3 gain of function inherited thrombophilias
* Factor V Leiden * Prothrombin gene mutation 20210 * Increased factor VIII
30
What is responsible for the transient pro-thrombotic state after starting warfarin? What is the consequence
* Protein C (endogenous anticoagulant) drops first * -\> Prothrombotic state * -\> **widespread thrombosis of post-capillary venules in skin, muscle** * Results in **warfarin necrosis :(** Prevent by overlapping with Heparin
31
What are the two most common initiating events for arterial thrombus?
* **Injury to vessel wall** (most common overall) * Usually superimposed on an atherosclerotic plaque * **Embolism** (rare)
32
List the 4 most common symptoms of VTE
Pain Unilateral swelling Warmth Redness
33
When is it appropriate to test for an inherited thrombophilia?
Only if the test will influence the management * Don't test if pt has a provoked blood clot * Don't test during an acute event
34
List the 3 items in Virchow's Triad of thrombosis (3 things that lead to a pro-thrombotic state)
Endothelial injury Abnormal blood flow Hypercoagulation
35
What anticoagulant therapy poses particular risk to people with protein C deficiency?
**Warfarin** **-\> Warfarin-induced skin necrosis** Warfarin inhibits II, VII, IX, X, _Protein C_, Protein S Protein C decreases before all of the other factors, resulting in a **transient hypercoagulable state**; **must overalap with heparin in the setting of an acute clot**
36
What is the difference between a massive and a submassive PE?
**Massive** = **hemodynamically unstable**; pt is in shock **Submassive** = RV strain with **no** hemodynamic instability
37
When would it be contraindicated to do a CTPA in a patient with suspected PE? ## Footnote *(Assume the pt has a high enough Wells score to do imaging)*
If the pt has **renal failure;** ## Footnote **Contrast is contraindicated** **Use an echocardiogram instead**
38
List 2 anatomic syndromes that would increase a patient's risk of VTE
* May-Thurner syndrome * Chronic compression of the left common iliac vein between the right common iliac artery and 1st vertebral body * Venous thoracic outlet syndrome
39
What is the major contraindication to the direct oral anticoagulants?
Renal failure
40
What is the inhibitor for Heparin and LMWH?
Protamine
41
How does the risk of VTE change with... * A major risk factor * A minor risk factor
* A major risk factor: **\>10 fold increased risk** * A minor risk factor: **3-10 fold increased risk**
42
List 2 herbal remedies that increase warfarin levels and 1 that decreases levels
Increase: Ginkgo, Garlik Decrease: St. John's Wort
43
Why is VTE considered a chronic disease?
Large potential for recurrence
44
List 3 direct thrombin inhibitors
Bivalirudin Argatroban Dabigatran *-gat- or -rudin*
45
List 3 indications for tPA
* Acute coronary thrombosis * Massive PE (hemodynamic instability) * Thrombotic stroke
46
Is the following characteristic of arterial or venous thrombus? ## Footnote **Platelet-rich**
Arterial
47
How does the prothrombin gene mutation 20210 lead to increased risk of thrombosis?
Mutation is in the **promoter** region -\> More prothrombin syntheis, inhibition of thrombolysis
48
How does Factor V Leiden increase the risk of venous thrombosis?
Factor V leiden is resistant to cleaveage (and thus, inactivation) by activated protein C
49
What is post-thrombotic syndrome?
* Venous occlusion by thrombi causes increased venous pressure * -\> Venous hypertension * **Valves become incompetent; even when VTE disappears, there is reflux** * **​**Pain, paresthesia, heaviness, swelling * Venous insufficiency; discoloration, ulcers, dilated veins * Can cause permanent disability
50
How can mutations in VKORC1 and CYP2C9 affect warfarin sensitivity?
* VKORC1 = target of warfarin * Mutations can affect dosing * CYP2C9 is involved in warfarin clearance * LOF -\> increased warfarin levels * GOF -\> dcreased warfarin levels
51
Which direct oral anticoagulant is relies least on the kidney for excretion?
Apixaben
52
Describe the appropriate method for diagnosing a suspected PE or DVT
* High clinical suspicion (Wells score \>6 for PE or ≥3 for DVT) * -\> Immediate imaging (CTPA for PE, compression US for DVT) * Low or intermediate clinical suspicion * -\> D-dimer * If low, can rule out PE/DVT * If high, do CTPA for PE, compression US for DVT
53
What is the appropriate management of VTE?
**Anticoagulation** * _3 months_ if provoked by a major transient risk factor * Indefinite if unprovoked, or ongoing risk factor * Balance with bleeding risk Thrombolytic therapy only given... * Systemically if massive PE (hemodynamic instability) * Catheter-directed if DVT is life or limb threatening, or PE is submassive but high risk *IVC filter only if pt cannot tolerate anticoagulation*
54
What is the inhibitor for rivaroxaban and other direct FXa inhibitors?
Andexanet alpha or 4 factor Prothrombin complex concentrate
55
List 3 anti-Xa agents (oral)
Rivaroxaban Apixaban Endoxaban (-xaban)
56
Describe the testing assay for lupus anticoagulant
A patient is positive for lupus anticoagulant if... * Prolonged clot-based assay (ex: PTT) * No correction on mixing study * Corrects with excess phospholipid
57
What constitutes a high Wells score in: * DVT: * PE:
* DVT: ≥ 3 * PE: \>6
58
Which anticoagulant is the only one known to be safe in pregnancy/
Low molecular weight heparin (LMWH) *Warfarin is NOT safe in pregnancy, but is safe in breastfeeding*
59
Is malignancy a risk factor for VTE?
Yes ## Footnote *Up to 20% of VTE in the community is associated with malignancy*
60
Why do patients on heparin need close monitoring?
Risk of heparin-induced thrombodytopenia Heparin undergoes extensive protien binding
61
Which imaging method is most commonly used to assess DVT? What method is gold standard?
* Commonly used = **Compression ultrasound** * **​***Most sensitive for proximal veins* * Gold standard = **Venography** * Do if high clinical suspicion* * OR* * Low suspicion and positive D dimer*

Heme/Onc by Minnie (she/her) (36 decks)

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