thromboembolic complications in ibd
DESCRIPTION
Thromboembolic complications in IBD. Athos Bousvaros MD, MPH Associate Director, IBD Center. With gratitude. Naamah Zitomersky. Cameron Trenor. Menno Verhave. Thrombosis and IBD: A call for improved awareness and prevention. IBD Journal 2011 17:458. Overview. Pathophysiology - PowerPoint PPT PresentationTRANSCRIPT
Thromboembolic complications in IBD
Athos Bousvaros MD, MPHAssociate Director, IBD Center
With gratitude
Naamah Zitomersky Cameron Trenor
Thrombosis and IBD: A call for improved awareness and prevention. IBD Journal 2011 17:458
Menno Verhave
Overview
• Pathophysiology• Risks of venous thromboembolism
– Relative– Absolute
• Risk factors• Workup of thromboembolic event• Prophylaxis• Treatment
Arterial vs. venous thromboembolism
• Arterial– Clot in an artery (carotid, coronary, SMA)– Rare in younger patients (under 40 years)– Preventable with antiplatelet drugs (ASA)
• Venous– Clot in venous system– Deep venous thrombosis (usually in leg or arm)– Preventable with anticoagulation (heparin, coumadin)
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Coagulation cascade
ANTI-THROMBIN
PROTEIN SPROTEIN C
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Risk factors in the general population
• Hereditary thrombophilias– Factor V Leiden mutation
• 5% of Caucasians, 2% Hispanics, 1% African Americans– Prothrombin gene mutation (G20210A)
• 2% of Caucasians– Protein C, Protein S, Antithrombin 3 deficiencies
• Environmental causes– Smoking, oral contraceptives– Surgery, immobility
Why are IBD patients especially at risk?
• Inflammation and disease activity– Increased fibrinogen– Increased D-dimer– Increased factors V, VIII, IX
• Prothrombotic antibodies (antiphospholipid)• Endothelial damage• Increased homocysteine• Prothrombotic medications
– thalidomide
Inflammation is the Most Common Risk Factor; DVT without a Risk Factor is Rare in Children
Lupus anti-coag=40%
Central venous catheter=24%
Acute infec-tion=13%
Chronic in-flamm=10%
Other=8%
Idiopathic=5%
No Risk Factor
Lupus Anticoag
Infl
Infec
NEJM 2004;351:1081-8.
(n=82)
CVL
Venous thromboembolism (VTE) in inflammatory bowel disease
• Relative risk is high– Six fold greater hazard ratio in < 20 years old*– Mainly in patients with flares**
• Absolute risk is low– 2811 IBD patients recruited over 2.5 yrs***– 116 (4%) of patients developed de novo VTE
• Mean age 42 years– Risk of recurrence high if anticoagulation stopped
*Kappelman et al; Gut 2011 Nylund et al; JPGN 2013** Grainge et al, Lancet 2010*** Novacek, Gastro 2010
What complications occur with increased frequency in adults?
• Meta analysis of over 200,000 patients – increased risk of venous, but not arterial events.– Deep venous thrombosis RR 2.4– Pulmonary embolism RR 2.5– Ischemic heart disease RR 1.3– Mesenteric ischemia RR 3.4
Fumery et al, J. Crohn’s Colitis 2013
IBD Clot rates – Boston Children’s
All kids IBD kids
VTE risk 1/10,000/y ~3x higher
VTE in Inpatients
0.58% (58/10,000)
1.5% (8/532)(1.7% incl. arterial)
CVL 4.5% @ CHB* 3.8% (4/104)
*3.82 symptomatic events per 1000 catheter days
Zitomersky et al, JPGN 2013; 57:343-7
A major source of morbidity
IVC clot needing filter in severe UC
Is heparin prophylaxis indicated?
• Not in outpatients, unless another reason– “Prophylaxis would be needed for 312 person-years of IBD flares
to prevent one person developing venous thromboembolism” – G. Nguyen, Lancet
• Yes in inpatients– Included in AGA physician performance measure set, but only
35% of gastroenterologists use it.*– “…heparin has an important role in prophylaxis against
thromboembolism in patients admitted to hospital with severe colitis”
– Kornbluth and Sachar, ACG Guideline 2010
*Tinsley, J. Clin Gastroenterol 2013
Prophylactic Anticoagulation for High Risk Colitis patients
No personal or strong family history of bleeding
Pre-pubertal or < 40kg
Enoxaparin 0.5 mg/kg BID
Post-pubertal or > 40kg
Enoxaparin 40 mg daily
• Continue anticoagulation until either:– Discharge– Resolution of colitis, or– Baseline mobility, if post-op
The “ouch” factor
Colitis: New diagnosis or Admission• Review family history for thrombosis AND
bleeding• Address dehydration• Address immobility (PT consultation, plan for
ambulation)• Alternatives to combined oral contraception• Counsel about smoking, inactivity, long travel• Consider
– factor VIII– D-dimer– lupus anticoagulant– anti-cardiolipin and anti-2 glycoprotein 1 antibodies
Proposed High Risk Definition
*awareness if elevated factor VIII, D-dimer, isolated APLA#Known thrombophilia = factor V Leiden, prothrombin gene mutation, low protein C/S or antithrombin function, persistent APLA >40 for >12 weeks
Inpatient colitisOR
Major surgery
Personal history thrombosis,1st degree family history,
Known thrombophilia,#
OCPs,Smoking > 1ppd,
BMI > 35 OR
PICC/Broviac/Port-a-Cath(especially if ASD)
thalidomide
High Risk
Evaluation of DVT
• High index of suspicion– Headache, vomiting– Extremity swelling
• Labs– D-dimer excellent negative predictive value
• Imaging– Ultrasound of extremity and femoral veins– MR or MR venography preferred for CNS– Spiral CT for pulmonary embolism– Cardiac echocardiogram for patent foramen
Therapy of clots (adult and pediatric)
• Unfractionated heparin– 75 U/kg bolus– 18 U/kg/hour– Goal anti-Xa level, 0.3-0.5 U/ml
• Low molecular weight heparin (enoxaparin)– 1mg/kg sc bid– Goal anti-Xa level 0.5-1 U/ml
• Warfarin for long term management?• Colectomy may be life-saving
– Timing of colectomy is tricky
Additional therapy
• Catheter directed thrombolysis• Inferior vena cava filter
– Protect against pulmonary emboli• Surgical thrombectomy
– When thrombolysis contraindicated• Is a large clot complicating severe colitis an
indication for colectomy? – What is optimal timing for the colectomy?– Control colitis medically, treat clot, then operate
Is heparin safe in IBD?Severe bleeding on anticoagulation is rare
Treatment Prophylaxis
All adults 2% 3%
All kids 2% 4.3% (trauma)
CHB 2.5% (4/162)4.1% HR (2/49)
???
CHB IBD 11.1% (1/9) ???
Conclusions• All patients with IBD are probably at an increased
risk of clots during disease flares– Absolute risk is low
• The highest risk group appears to be inpatients with severe colitis – Inflammation– Immobility
• Prophylaxis with LMWH is indicated in patients hospitalized for severe colitis or post-op – Enoxaparin, 40 mg SQ daily in adults