Venous Thromboembolisms

Question 1

________ of persons who survive the first occurrence of Venous Thromboembolism (VTE) develop another VTE within _________.

Answer 1

1/3

10 years

Question 2

What is Virchow’s Triad?

Answer 2

An explanation of VTE pathogenesis. Three risk factors overlap to lead to a thrombosis:

1. Stasis (—> alterations in blood flow)
2. Vascular endothelial injury
3. Hypercoagulability (alterations in the constituents of the blood - inherited or acquired)

Question 3

Previous thrombotic event is associated with a major risk for _________

Answer 3

A recurrent VTE

Majority of patients with VTE fulfill most or all of Virchow’s triad

In over 80% of patients with VTE, a risk factor can be identified

Question 4

Chronic conditions —> risk of VTE

Answer 4

Chronic conditions (CHF, IBD, etc)
***Malignancy
Obesity
***Antiphospholipid antibody syndrome
Advanced age
Smoking
***Myeloproliferative disorders

Question 5

Transient States —> risk for VTE

Answer 5

**Recent surgery (esp ortho)
**Trauma
***Immobilization
Presence of a central venous catheter
Hospitalization
Infections
Extended travel

Question 6

Female specific risk factors for VTE

Answer 6

**Pregnancy
Post-partum
**Hormonal contraceptives
Hormone replacement therapy

In other words, ESTROGEN

Question 7

Inherited risk factors for VTE

Answer 7

Inherited Thrombophilia

**Factor V Leiden mutation
**Prothrombin gene mutation
(50-60% of cases are these two)
Protein S deficiency
Protein C deficiency
Antithrombin deficiency

Question 8

Classic symptoms of DVT include:

Answer 8

Swelling, pain, and erythema of the involved extremity

Not necessarily a correlation between the location of the symptoms and the site of the thrombosis (pain can be more distal)

Other symptoms:
Warmth
Increased calf diameter***
Palpable cord

Question 9

Homan’s Sign

Answer 9

A positive sign is present when there is pain in the calf with forceful and abrupt dorsiflexion of the patient’s foot at the ankle while the knee is extended

Fallen out of favor for Dx of DVT b/c low sensitivity/specificity

Question 10

________________ is the most studied and therefore most commonly used pretest probability scoring system for DVT

Answer 10

Wells (and modified Wells) score

Used before diagnostic tests to confirm or help rule out DVT

Score of 3 or greater = high probability

Active cancer = +1
Immobilization = +1
Recent surgery = +1
Localized tenderness = +1
Swelling = +1
Calf swelling > 3 cm = +1
Pitting edema = +1
Collateral superficial veins = +1
*Alternative diagnosis more likely = -2

Question 11

Problems with the Wells criteria

Answer 11

3 points are related to swelling alone (can overlap)

“Alternative diagnosis more like” is subject

Question 12

Serum D- Dimer

Answer 12

1st dx test outside of Hx
Degradation product of cross-linked fibrin (high when there’s a clot)
Detectable at levels > 500 ng/mL in virtually all patients with VTE

**Sensitive but NOT SPECIFIC - useful only when negative
Therefore only order when there’s a low or moderate pretest probability of DVT (skip if high probability)

Question 13

Previous gold standard for Dx DVT

Answer 13

Contrast Venography

No longer recommended as first line b/c pt discomfort and difficulty

Question 14

Test of choice for Dx of DVT

Answer 14

COMPRESSION ULTRASOUND!

Loss of vein compressibility, using Doppler technique to asses blood flow

Noninvasive, relatively available, inexpensive, and easy to perform/read

May need serial exams to definitely rule out

Question 15

When to treat a DVT

Answer 15

Absolutely treat for proximal DVTs (popliteal, femoral, iliac)

Appropriate to treat many distal DVTs as well especially if symptomatic

Question 16

Purpose of DVT treatment

Answer 16

Prevent further clot propagation
Prevent PD
Reduce risk of recurrent VTE
Reduce complications (ie post-thrombophlebitic syndrome, chronic venous insufficiency)

Question 17

Mainstay Tx for DVT

Answer 17

Anticoagulation

Initial anticoagulation immediately for up to 10 days

Long term but finite anticoagulation for a minimum of 3 months (up to 6-12)

Other important Tx:
Early ambulation for fully anti coagulated, hemodynamically stable pt
Compression stockings (maybe)

Question 18

Upper extremity DVTs

Answer 18

Can be spontaneous (1-4%) but usually secondary to catheter placement (ie - central line or pacemaker) or prothrombotic states

PE occurs in about 4-10% of UE DVTs

Question 19

The most common cause of Pulmonary Embolism is _____

Answer 19

DVT
50-60% of proximal DVT will embolize

Isolated calf DVTs embolize much less frequently

Question 20

Classifications of PE

Answer 20

1. Presence or absence of hemodynamics stability
2. Temporal pattern (acute, subacute, chronic)
3. Anatomic location (saddle*, lobar, segmental, subsegmental)
4. Presence or absence of symptoms

*Saddle = where pulmonary artery first bifurcates

Question 21

Hemodynamic instability is defined as a systolic BP of ________ or a drop in systolic BP of _______________________.

Answer 21

Systolic <90 mmHg or drop of ≥40 mmHg from baseline for >15 min

Hemodynamically unstable patients are more likely to die from obstructive shock in the 1st two hours of presentation

Question 22

SSx for Pulmonary Embolism

Answer 22

Range from asymptomatic to DEATH
*Dyspnea (SOB)
*Pleuritic pain
*DVT Sx
*Cough 
Tachypnea
Tachycardia
Decreased breath sounds
Accentuated pulmonic component of the 2nd heart sound
JVD

Question 23

Evaluating for PE

Answer 23

BE SUSPICIOUS WITH ALL DVTs

ABCs (BP, HR, RR, mental status)

If hemodynamically stable, use combined clinical and pretest probability assessment (Wells for PE), D-dimer, and imaging (CT pulmonary angiogram)

If hemodynamically unstable, beside echo is safest to obtain presumptive Dx

Question 24

Well’s criteria for PE

Answer 24

> 6 is a high probability of PE

\+3 for DVT Sx
\+3 if other dx is less likely
\+1.5 for HR>100
\+1.5 for immobilization ≥3 days
\+1.5 for previous DVT/PE
\+1 for he opts is
\+1 for malignancy

Question 25

Historical “gold standard” for PE

Answer 25

Pulmonary angiography Highly specific and sensitive Not used request Ly due to new generation of CTA scanning Disadvantages: Invasive, high IV contrast load, technically demanding, $$$

Question 26

Test of choice for Dx of PE

Answer 26

CT-Pulmonary Angiography Sensitive and specific Accurate for the detection of large, main, lobar, and segmental PE Less accurate for smaller, peripheral, subsegmental PE Non-invasive Contraindications: IV contrast allergy, renal dysfunction

Question 27

V/Q scanning

Answer 27

Sensitive test for PE but poorly specific due to high number of false positives (creates diagnostic challenge) Most commonly used in patients with IV contrast allergies, renal dysfunction (sometimes pregnancies) Best utilized in those with normal chest X-ray (difficult to differentiate from lung disease like COPD)

Question 28

Classic EKG finding for PE

Answer 28

“S1Q3T3” pattern due to right ventricular strain

Question 29

Chest X-ray findings for PE

Answer 29

Neither sensitive nor specific Hampton’s hump = opacity due to infarct (tissue dying b/c not perfused Western ark sign = oligemia (due to low blood flow)

Question 30

PERC Rule

Answer 30

PE Rule-out Criteria ``` 8 Criteria must ALL be negative to rule out PE: Age < 50 HR < 100 Oxyhemoglobin saturation ≥ 95% No Hemoptysis No estrogen use No prior DVT/PE No unilateral leg swelling No surgery/trauma within the past four weeks ``` If not all are No but probability still low, do a D-dimer

Question 31

Treatment for PE

Answer 31

Supportive Care: Supplemental O2 Intubation/mechanical ventilation if necessary IV fluids or vasopressors ANTICOAGULATION ``` Other possibilities: Thrombolytics IVC filter Thrombectomy/embolectomy Prophylactic measures ```

Question 32

VTE Anticoagulants

Answer 32

For Acute Tx: IV Unfractionated Heparin (UFH) - preferred for unstable pt or if rapid reversal is needed SQ Low Molecular Weight Heparin (LMWH - Lovenox) - preferred for pregnancy and those with cancer For long term use: Oral Warfarin (Coumadin) Factor Xa Inhibitors • SQ formulation - Arixtra • Oral - Xarelto, Eliquis, Savysa, Lixiana Oral direct thrombin inhibitors (Pradaxa)

Question 33

Transitioning from initial to long-term anticoagulation

Answer 33

Interruptions to tx should be minimized during the first 3 months due to high risk of recurrent thrombosis Traditionally - long term therapy = warfarin • monitor PT and INR (should be between 2-3) • slow onset so must use 2nd agent until in system • takes several days to reverse Can also use oral factor Xa inhibitors or oral direct thrombin inhibitors • depends on many factors • consider if there are reversal agents or not

Question 34

Anticoagulation reversal

Answer 34

UFH = protamine LMW Heparin = protamine (but incomplete) Warfarin = vitamin K (takes time) and fresh frozen plasma Factor Xa inhibitors = Andexanet Alfa (EXPENSIVE) Direct thrombin inhibitors = idarucizumab Can also consider activated prothrombin complex concentrate (aPCC) For all drugs —> discontinue drugs, transfuse blood if necessary, address hemorrhage anatomically.

Question 35

Duration of anticoagulant therapy

Answer 35

Minimum of 3 months for first episode ``` If provoked (ie - identifiable risk factors) —> 3 months If unprovoked —> extended therapy (6-12 months) unless high bleed risk ``` Pt with a first or recurrent episode of unprovoked proximal DVT/unprovoked symptomatic PE can benefit from indefinite anticoagulation but consider underlying conditions

Question 36

Testing for inherited thrombotic disorders and malignancy can ______________________, but does not __________________.

Answer 36

Can lead to the discovery of risk factors Does not improve mortality VTE before 45 years and at least one 1st degree relative with documented VTE should be tested for: • All 5 inherited thrombotic disorders (antithrombin deficiency, protein S and C deficiences, factor V Leiden and prothrombin gene mutation) -AND- • Antiphospholipid syndrome

Question 37

For what patients is a Vena Cava Filter indicated

Answer 37

* Anticoagulation is contraindicated * Risk of bleeding is estimated to outweigh the risk of recurrent thromboembolism * Recurrent PE despite adequate anticoagulation * Complication of anticoagulation (severe bleeding) * Hemodynamic or respiratory compromise IVC filter prevents DVT from propagating to lungs

Question 38

Thrombolytics

Answer 38

Activate plasminogen to form plasmin, resulting in the accelerated lysis of thrombi Given in combo with anticoagulation Used for UNSTABLE patients with PE (ie massive PE and sustained hypotension with cardiogenic shock) Given peripherally (IV) or through catheter directed at the clot Examples: Streptokinase, Urokinase, Recombinant tPA

Question 39

Thrombectomy/Embolectomy

Answer 39

Mechanical device used to remove clots from veins quickly in order to restore normal venous flow, reduce Sx and prevent post-thrombophlebitic syndrome Indicated in hemodynamically unstable PE for whom thrombolytic therapy is contraindicated

Question 40

VTE prophylactic measures

Answer 40

Admitted pt with no risk factors - mechanical prophylaxis (ie TED hose or IPCs) Admitted pt with one risk factor and no increased risk of bleeding —> pharmacological prophylaxis • Low dose SQ LMWH (lovenox) 40 mg SQ daily Admitted pt with multiple risk factors —> both mechanical and pharm prophylaxis