12/13 DVT - Corbett

Question 1

normal venous anatomy

three systems

veins as low pressure system

Answer 1

three systems need to be intact for normal venous flow from lower limb

1. veins superficial to deep muscle fascia (saphenous veins)
2. deep veins (intramuscular, intermuscular vv that run with aa)
3. perforating vv

veins are generally a low pressure system BUT weight of columns of blood can creat pressure due to gravity (up to 90mm in standing adult)

Question 2

how do veins mitigate pressure?

Answer 2

venous valves and venous pump

1. valves: bicuspid valves arranged to ensure blood flow towards heart/prevent backflow (more distal)
   * also prevents blood in deep system from moving over to superficial system
2. venous pump: contraction of LE muscle “pumps” blood

• contingent on competent valves
• reduces walking venous pressure to 20mm!

Question 3

why does standing still for long time lead to edema?

Answer 3

standing still for prolonged periods → incr cap pressure → fluid lead/volume loss

• 10-20% of blood vol can be lost within 15-30min!!!

Question 4

how do thrombi form in venous system?

how do thrombi form in arterial system?

Answer 4

arterial system

• HIGH shear stress
• endothelial cells disrupted
• platelet-rich (therefore…drug tx is anti-platelet)
• “white clots”

venous system

• LOW shear stress
• endothelial cells intact
• fibrin-rich (therefore…drug tx is anti-coagulant)
• “red clots”

Question 5

pathogenesis of DVT

triad and factors that affect them

Answer 5

VIRCHOW’S TRIAD

1. hypercoagulable state

• genetic factors
• acquired risks

2. endothelial injury
   * EC activation somehow (without being stripped or denuded…not clear what is activating them to make them less anti-thrombogenic)
3. stasis

• disruption of flow is worst with immobilization
• valve sinuses are the site of thrombus initiation
  
  • could be that stasis of blood in those pockets causes hypoxia → EC activation!

Question 6

role of TF in DVT

Answer 6

Tissue Factor is a transmembrane protein which is not usually accessible

• synthesized and expressed by endothelial cells and monocytes
• once expressed, triggers first step in extrinsic coag pathway

Question 7

risk for DVT

Answer 7

1. endothelial damage

• endothelial dysfx
  
  • smoking
  • HTN
• endothelial damage
  
  • surgery
  • catheter
  • trauma

2. hypercoagulability

• hereditary
  
  • Factor V Leiden
  • Prothrombin G20210A
  • Protein C and S deficiency
• acquired
  
  • cancer
  • chemotx
  • pregnancy
  • obesity
  • HIT

3. stasis

• immobility
• polycythemia

Question 8

heriditary risk factors for DVT

Answer 8

all autosomal dominant

1. Factor V Leiden mutation
2. Prothrombin gene mutation
3. Protein C deficiency
4. anti-thrombin deficiency
5. Protein S deficiency

Question 9

review of coag cascade @17min-21min

Question 10

Factor V Leiden mutation

Answer 10

most common inherited thrombophilic disorder

• point mutation changing Arg → Gln at position 506

Factor V is resistant to activated Protein C (APC; anticoag!!!)

_end resul_t: Factor V stays around, continues to interact with Factor X and boost coagulation

relative risk_Factor V Leiden = 5

relative risk_OCP = 4

relative risk_both = 30

Question 11

prothrombin mutation

Answer 11

second most common inherited thrombophilic disorder

• mutation in 3’ UTR of prothrombin gene
• glycine → alanine: 20210
• leads to 30% increase in circulating prothrombin via unclear mech

Question 12

protein C deficiency

Answer 12

nonsense mutation → decr quantity of Protein C

clinical conditions:

• VTE at multiple venous sites
• Warfarin-induced skin necrosis
• neonatal purpura fulminans
  
  • homozygous def

Question 13

anti-thrombin deficiency

Answer 13

decr AT3 caused by:

• AT3 deficiency (insertion or deletion)
• functional deficiency

clinical conditions:

• incr thrombotic risk (esp in pregnancy)
• insensitivity to heparin

Question 14

when should a patient with DVT be evaluated for a hypercoagulable disorder?

Answer 14

routine testing for unselected pts NOT recommended

consider if:

• one first deg relative with DVT < 45
• young pt (< 45) with first DVT
• thrombosis in unusual vascular beds
  
  • hepatic, portal, mesenteric, cerebral
• warfarin induced-skin necrosis
• arterial thrombosis

Question 15

acquired risk factors

MOIST

Answer 15

M: malignancy, motherhood, myeloproliferative disorders

O: oral contraceptives, obesity, orthopedics

I: immobilization, infl bowel disease, indwelling central line

S: surgery, syndromes (anti-phospholipid antibody and nephrotic syndrome)

T: trauma, tamoxifen, prior thrombosis

Question 16

anatomic risk factors

Answer 16

1. Paget-Schroetter syndrome

• spontaneous upper extremity thrombosis (#1 cause)
• compression at the thoracic outlet

2. May-Thurner Syndrome
   * compression of left common iliac vein by right common iliac artery

Question 17

superficial venous disease

vs

deep venous thrombosis

Answer 17

superficial venous disease

• thrombophlebitis
• superficial venous thrombosis

deep venous thrombosis

• lower extremity
• upper extremity
  
  • thoracic outlet
  • indwelling central line

Question 18

superficial venous thrombosis

thrombophlebitis

Answer 18

phlebitis: infl of superficial vein
thrombosis: presence of clot

superficial thrombophlebitis

• pain, erythema, induration, tenderness
• low grade fever
• palpable cord
• usually involves tributary varicosity

superficial vein thrombosis

• thrombosis of the axial veins (greater/lesser saphenous veins)
• associated with thromboembolism

risk factors:

• general risk factors
• varicose veins
• vein excision, ablation
• IV catheter use (upper extremity)

Question 19

clinical presentation:

deep venous thrombosis

two types

key symptoms

Answer 19

DVT of lower extremity divided into:

1. proximal vein thrombosis (popliteal v or above)
2. distal vein thrombosis (anterior tibial, posterior tibial, peroneal vv)

distinction is made bc distal involvement means…

• lower risk of PE
• more difficult to detect

^^^ unclear how to go about treating!!!

key symptoms:

• might have NONE
• look for:
  
  • leg pain/heaviness/cramps
  • leg swelling (uni/bilateral)
  • history to ID risk factors
  • family hx

Question 20

phlegmasia cerulea dolens

Answer 20

massive proximal DVT of lower extremities

• sudden severe leg pain with swelling
• cyanosis
• edema
• venous gangrene
• arterial compromise

*

Question 21

chronic venous disease

Answer 21

venous hypertension is the final common pathway for the spectrum of disease

most common cause?

valve incompetence due to DVT → transmits high pressure to superficial caps

long term changes in vasculature and subcutaneous tissue:

• thickened veins; ECM deposition
• leukocyte activation
• abnormal vascular permeability
• erythrocyte extravasation and breakdown
• tissue breakdown/ulcer formation in skin