Anticoagulation Forum: Management of Tiny Clots Casey O Connell, MD FACP Associate Professor Jane Anne Nohl Division of Hematology Keck School of Medicine USC
DISCLOSURES None 4/11/2017
Objectives Define and distinguish distal DVT from superficial vein thrombosis (SVT) in the upper and lower extremities Determine whether, how and for what duration to treat distal deep vein and superficial vein thromboses Discuss the prevalence and management of Subsegmental Pulmonary Embolism (SSPE)
Deep Veins of the Leg DISTAL DEEP VEINS: Anterior Tibial Vein Peroneal Vein Posterior Tibial Vein
SUPERFICIAL VEINS of the LEG
Distal DVT: What s the Data? If untreated 15% will progress to involve more proximal vessels Proximal extension occurs within 2 weeks in majority of cases Risk factors for extension: Positive D- Dimer >5cm length of thrombosis Multiple veins involved >7mm max diameter Idiopathic Cancer History of VTE Inpatient
Distal DVT: What s the Data? N=164 noncancer pts vs 860 3 mos AC Ho et al. Thrombosis Res 2016
Distal DVT: What s the Data? Optimev patients with IDDVT & Cancer had significantly poorer outcomes than those without cancer Meta-analysis of IDDVT treatment trials suggests ANTICOAGULATION reduces risk and is NOT associated with more bleeding > 6weeks superior to <6weeks Galanaud et al JTH 2017 epub; Franco et al JTH 2017 epub
2016 ACCP: Management of Distal DVT Anticoagulate if symptoms are present that would significantly improve with therapy Anticoagulate if risk factors for extension present Hold anticoagulation if risk factors and symptoms not present Repeat US in 1-2 weeks Hold anticoagulation if bleeding risk HIGH Repeat US in 1-2 weeks
Case #1 58 yo man with CIDP presents with painful, swollen and erythematous right arm 2 days after his regular IVIG therapy. No chest pain or SOB, VSS PIV for IVIG was placed in the right arm, palpable cord in that region ER US: basilic vein thrombosis
Is This a Distal Deep Vein or a Superficial Vein Thrombosis? A. Distal Deep Vein Thrombosis B. Superficial Vein Thrombosis
Which of the following do you recommend? A. Warm compresses, reimage in 1-2 weeks B. Venography of the right upper extremity C. 6 weeks of anticoagulation with LMWH +/- warfarin D. NSAIDS
Isolated Symptomatic Superficial DVT: What s the Data? A pooled analysis of 2 prospective observational studies, OPTIMEV (n=556) & POST (n=634) Only 4% had active cancer 81% treated with anticoagulation but median duration of tx 15 days Overall incidence of any VTE at 3 months of 3.9%
Symptomatic, Isolated SVT: Risk Factors for VTE at 3 Mos Especially DVT/PE Galanaud et al. JTH 2012;10:1004-11.
AC for SVT: CALISTO TRIAL Decousus et al. 2010;363:13
Management of SVT: What s the Latest? Rivaroxaban 10mg daily noninferior to fondaparinux 2.5mg Jan Beyer-Westendorf et al. Blood 2016;128:85 FULL PUBLICATION PENDING
Incidental Pulmonary Embolism: Defined 1 or more pulmonary arterial filling defects identified on a contrastenhanced CT scan that is ordered for reasons other than rule-out PE INCIDENTAL PE Silent PE IPE Unsuspected PE Asymptomatic PE
Incidental Pulmonary Embolism: Prevalence and Risk Highest mean prevalence = INPATIENTS (4%) Cancer Patients (3.1%) Increased risk with: Age History of PE Smaller slice thickness More proximal location of PE Dentali et al. Thromb Res 2010;125:518-22.
Case #2 92 year old gentleman with a history of renal cell carcinoma resected 4 years ago is referred by his Urologist who was notified by radiology of pulmonary embolism on a routine surveillance CT scan which is otherwise negative for evidence of recurrent malignancy. According to the Urologist patient was asymptomatic, vitals were stable and he is now at home PMH significant only for hypertension for which he is on amlodipine Laboratories demonstrated NORMAL CBC, CMP, Creatinine 0.6
Which of the following is an appropriate next step? A.Have the patient call 911 and go to the ER B. Start the patient on low dose warfarin C.Schedule an ultrasound of the lower extremities D.Start low molecular weight heparin therapy
Answer: C or D, depending A) PE can be safely treated in the outpatient setting B) Starting warfarin without bridging may lead to progression of VTE C) US of the lower extremities is recommended to assess total clot burden and enhance the certainty of need for AC D) Immediate treatment is appropriate..but ASK: where are these PE located? ASK: any h/o VTE? ASK: is he truly asymptomatic
Incidental Pulmonary Embolism: Radiographic Features Smaller slice thickness leads to better visualization of the pulmonary arterial tree MORE IPE 1.5% 64-MDCT 0.5mm 16-MDCT 0.625mm 4-MDCT 2.5mm SDCT 4mm Patel et al. Radiology 2003. Dentali et al. Thromb Res 2010;125:518-22
Where Do Incidental PE Occur In Cancer Patients? 50% Browne et al. J Thoracic Oncol 2010;5:798-803 Main 7 (10%) Lobar 26 (37%) Segmental 20 (29%) 47% Subsegmental 17 (24%) O Connell CL et al. JTH 2011: 9:305-311
IPE: Reliability of Radiologic Diagnosis can be affected by PE location Among community radiologists, 15% false positive diagnosis of SSPE.* 50% of these due to respiratory motion artifact Another 27% were indeterminate Vascular lesions with short axis <6mm more likely to be false positive or indeterminate *Miller et al. Ann Am Thor Soc 2015.
Does the pulmonary arterial segment involved have prognostic significance? Incidentally found subsegmental PE (SSPE) may be associated with less recurrence, death Few, small reports of untreated non-cancer patients with SSPE who have excellent short-term outcomes Even among cancer patients, survival does not appear to be adversely impacted by SSPE Carrier M et al. JTH 2010; 8:1716-22. Donato AA et al. Thromb Res 2010; 26(4):e266-70. Van der Hull et al. JTH 2016; 14: 105-13
CANCER PATIENTS WITH INCIDENTAL SSPE HAVE SIMILAR SURVIVAL AS MATCHED CANCER CONTROLS O Connell CL et al. JTH 2011: 9:305-311
A pooled analysis of 926 international cancer patients with IPE: Recurrence 6 month cumulative VTE recurrence risk 6 month cumulative VTE recurrence risk 6 month cumulative VTE recurrence risk LMWH VKA No Treatment 6.2% (3.7-8.3) 4.7% (3.5-9.6) 12% (4.7-23) Recurrence for total cohort 5.8%. Risk of recurrence was similar among cancer patients with SSPE Van der Hull et al. JTH 2016; 14: 105-113
A pooled analysis of 926 international cancer patients with IPE: Major Bleeding 6 month cumulative VTE recurrence risk LMWH 3.9% (2.3-5.9) 6 month cumulative major bleeding risk VKA 13% (6.4-20) 6 month cumulative major bleeding risk No treatment 6.4% (1.3-15) Risk of major bleeding was similar among cancer patients with SSPE Van der Hull et al. JTH 2016; 14: 105-113
PROPOSED ALGORITHM FOR APPROACHING THE INCIDENTAL SUBSEGMENTAL PUMONARY EMBOLISM Suggestions only, not a validated tool False positive diagnoses of SSPE may be as high as 15-40% Clinician must weigh: risk of clot progression vs risk of bleeding & Note radiation exposure, concurrent therapies
ISSPE NO DVT PRESENT? YES CANCER? NO SYMPTOMS? YES YES TREAT WITH AC
ISSPE: Proposed Algorithm ISSPE: NO DVT NO CANCER NO SYMPTOMS HIGH BLEED RISK LOW BLEED RISK Consider F/UP CTPA, D-Dimer OR POSITIVE NEGTIVE Consider AC TREAT WITH AC NO AC
ACCP Recommendations 2016 DOACs now recommended OVER the VKAs for longterm anticoagulation (Grade 2B) For VTE in Cancer patients LMWH still treatment of choice OVER DOACs or VKAs (Grade 2B) For SSPE US bilateral lower extremities now recommended Close surveillance OVER anticoagulation for patients with LOW recurrence risk Anticoagulation OVER surveillance for patients with HIGH recurrence risk
SUMMARY IDDVT: meta-analysis suggests 3 months of AC effective and very safe Recurrence/progression risk especially high in cancer patients SVT: 2 Sufficiently powered studies suggest that 6 weeks of LOW-dose AC is safe, effective strategy (fondaparinux 2.5 mg or rivaroxaban 10mg) SSPE: perform bilateral US for DVT, treat if risk for recurrrence/progression is high, bleeding risk low; consider holding AC otherwise Incidental PE has the same risk of recurrence and similar impact on cancer prognosis as symptomatic PE. Truly asymptomatic patients, especially with ISSPE, may be a distinct clinical group with a better prognosis