Pocket Medicine: The Massachusetts General Hospital Handbook of Internal Medicine (32 page)

•
Malignancy workup
: 12% Pts w/ “idiopathic” DVT/PE will have malignancy; age-appropriate screening adequate; avoid extensive w/u (
NEJM
1998;338:1169)
Risk stratification for Pts with PE

•
Clinical
: hypotension and/or tachycardia (~30% mortality), hypoxemia •
CTA
: RV / LV dimension ratio >0.9 (
Circ
2004;110:3276) •
Biomarkers
: ↑ troponin (
Circ
2002;106:1263), ↑ BNP (
Circ
2003;107:1576) a/w ↑ mortality •
Echocardiogram
: RV dysfxn (controversial in absence of hypotension) • Simplified PE Severity Index: 0 RFs → 1.1% mort.; ≥1 → 8.9% mort (
Archives
2010;170:1383) RFs: age >80 y; h/o cancer; h/o HF or lung disease; HR ≥110; SBP <100; S
_a
O
₂
<90%

Treatment of VTE
(
Lancet
2012;379;1835;
Chest
2012;141:e419S)

• LE DVT: proximal → anticoagulate; distal: anticoagulate if severe sx or risk for extension, o/w may consider serial imaging (although if bleeding risk low, many would anticoagulate) • UE DVT: anticoagulate (same guidelines as LE;
NEJM
2011;364:861). If catheter-associated, need not remove if catheter functional and ongoing need for catheter.

• Superficial venous thrombosis: anticoagulate (esp. if extensive clot) as 10% experience thromboembolic event w/in 3 mo (
Annals
2010;152:218) •
Acute anticoagulation options
(initiate immediately if high clinical suspicion!)

LMWH
(eg, enoxaparin 1 mg/kg SC bid
or
dalteparin 200 IU/kg SC qd)

Preferred over UFH except: renal failure (CrCl <25), ? extreme obesity, hemodynamic instability or bleed risk (
Cochrane
2004;CD001100)

No need to monitor anti-factor Xa unless concern re: dosing (eg, renal insuffic.)

Attractive option as outPt bridge to long-term oral anticoagulation

Fondaparinux
: 5–10 mg SC qd (
NEJM
2003;349:1695); use if HIT
; avoid if renal failure

IV UFH
: 80 U/kg bolus → 18 U/kg/h → titrate to PTT 1.5–2.3 × cntl (eg, 60–85 sec)

Rivaroxaban
: 15 mg bid (for 1st 3 wk)
LMWH followed by warfarin (
NEJM
2010;363:2499 & 2012;366:1287); effect wears off w/in 24 h, but not easily immediately reversed

Direct thrombin inhibitors (eg, argatroban, lepirudin) used in HIT
Pts

• Early ambulation • DVT & low-risk PE can be treated completely as outPt (
Lancet
2011;378:41) •
Thrombolysis
(eg, TPA 100 mg over 2 h or wt-adjusted TNK bolus)

Use if PE a/w hemodynamic compromise (“massive PE”)

Consider if PE w/o hemodynamic compromise, but high-risk (“submassive PE,” eg, marked dyspnea, severe hypoxemia, RV dysfxn on echo, RV enlargement on CTA)
and
low bleed risk. Risk of ICH ~1% and no proven mortality benefit (
NEJM
2002;347:1143;
Cochrane
2006:CD004437).

Consider if extensive (eg, iliofemoral) acute DVT and catheter-directed Rx not available

•
Catheter-directed therapy
(fibrinolytic & thrombus fragmentation/aspiration)

Consider if extensive vs. in all acute DVT as ↓ postthrombotic synd (
Lancet
2012;379:31)

Consider if PE w/ hemodynamic compromise or high risk and not candidate for systemic fibrinolytic therapy or surgical thrombectomy (
Circ
2011;124:2139)

•
Thrombectomy
: if large, proximal PE + hemodynamic compromise + contra. to lysis;

consider in experienced ctr if large prox. PE + RV dysfxn (
  J Thorac CV Surg
2005;129:1018)

•
IVC filter
: if anticoagulation contraindication, failure or bleed, or ? ↓ CP reserve; temp. filter if risk time limited; adding filter to anticoagulation → PE ↓
¹
/
₂
, DVT ↑ 2×, no mort. diff. (
NEJM
1998;338:409;
Circ
2005;112:416) •
Long-term anticoagulation options

Warfarin
(goal INR 2–3): start same day as heparin unless instability and ? need for lytic, catheter-based Rx or surgery; overlap ≥5 d w/ heparin & until INR ≥2 × ≥24 h

Rivaroxaban
(after 15 mg bid for 1st 3 wk, then 20 mg qd)
warfarin (see refs above)

Dabigatran (
NEJM
2009;361:2342) and idrabiotaparinux (weekly SC FXa inhib;
Lancet
2012; 379:123) both appear
warfarin, but neither FDA approved

VTE a/w cancer: LMWH × 3–6 mo, then LMWH/warfarin indefinitely or until cancer cured (
NEJM
2003;349:146); ✓ head CT for brain mets if melanoma, renal cell, thyroid, chorioCA

•
Duration of anticoagulation
:

Superficial venous thrombosis: 4 wk

1st prox DVT
or
PE 2° reversible/time-limited risk factor
or
distal DVT: 3 mo

1st
unprovoked
prox DVT or PE: ≥3 mo, then reassess; if low bleed risk → indefinite Rx w/ warfarin; extended Rx w/ newer agents under study: c/w placebo apixaban (either 2.5 or 5 mg) ↓↓ VTE w/o ↑ major bleeding (
NEJM
2013;368:699); rivaroxaban (20 mg qd) or dabigatran (150 mg bid) also ↓↓ VTE but ↑ major bleeding (
NEJM
2010;363:2499 & 2013;368:709)

2nd VTE event: indefinite warfarin (
NEJM
1997;336:393 & 2003;348:1425)

Can be guided by D-dimer testing at 1 & 3 mo (
NEJM
2006;355:1780;
Blood
2010;115:481)

After
6–18 mo of anticoag for unprovoked VTE, if decide to stop anticoag (eg, b/c of bleeding) ASA ↓ risk of recurrent VTE by 32% (
NEJM
2012;366:1959 & 367:1979)

Complications & prognosis

• Postthrombotic syndrome (25%): pain, swelling; ↓ with compression stockings × 3 mo • Recurrent VTE: 1%/y (after 1st VTE) to 5%/y (after recurrent VTE)

after only 6 mo of Rx: 5%/y & >10%/y, respectively

predictors: abnl D-dimer 1 month after d/c anticoag (
NEJM
2006;355:1780);
U/S after 3 mo of anticoag (
Annals
2002;137:955); thrombin generation >400 nM (
  JAMA
2006;296:397)

• Chronic thromboembolic PHT after acute PE ~3.8% (
NEJM
2004;350:2257), consider thromboendarterectomy • Mortality:
10% for DVT and
10–15% for PE at 3–6 mo (
Circ
2008;117:1711)