Venous thrombosis in unusual sites

Transcription

1 Venous thrombosis in unusual sites Walter Ageno Department of Medicine and Surgery University of Insubria Varese Italy

2 Disclosures Employment Research support Scientific advisory board Consultancy Speakers bureau Major stockholder Patents Honoraria Travel support Other No conflict of interest to disclose Bayer Bayer, BMS/Pfizer, Daiichi Sankyo, Boehringer Ingerlheim No conflict of interest to disclose No conflict of interest to disclose No conflict of interest to disclose No conflict of interest to disclose Bayer, Boheringer, BMS/Pfizer, Daiichi Sankyo, Stago, Aspen Bayer, Boheringer, GSK, BMS/Pfizer, Daiichi Sankyo No conflict of interest to disclose

3 Venous thrombosis in unusual sites Cerebral vein thrombosis Retinal vein thrombosis Thyroid vein thrombosis Upper limb vein thrombosis Splanchnic vein thrombosis Renal vein thrombosis Ovarian vein thrombosis

4 Overview of splanchnic and cerebral vein thrombosis Epidemiology: how (un)common are these diseases? Etiology: Which provoking factors should I assess? Management strategies: which therapies for: Acute phase Long-term secondary prevention

5 Splanchnic vein thrombosis Portal vein Splenic vein Mesenteric veins (superior / inferior) Budd-Chiari syndrome De Stefano et al, Intern Emerg Med. 2010

6 Epidemiology of splanchnic vein thrombosis in Northwestern Italy Incidence of portal vein thrombosis Males 3.78/100,000/year Females 1.73/100,000/year Budd-Chiari syndrome Males 2.0/ /year Females 2.2/ /year Ageno W et al Thromb Haemost 2017

7 Incidence of portal vein thrombosis according to age and gender Ageno W et al Thromb Haemost 2017

8 Incidence of BCS according to age and gender Ageno W et al Thromb Haemost 2017

9 Causes of splanchnic vein thrombosis in a, prospective cohort study Number 613 Liver cirrhosis 27.8% Solid cancer 61.6% 22.3% Abdominal infection/inflammation 11.5% Ageno W et al Semin Thromb Haemost 2014

10 Non cirrhotic non-malignant Cirrhotic patients Malignancy

11 BCS PVT Prevalence of MPN 40.9% 31.5% Prevalence of JAK2V617F 41.1% 27.7% JAK2V617F w/out MPN features 17.1% 15.4%

12 Other factors associated with SVT Abdominal surgery Abdominal trauma Pregnancy/puerperium Hormonal therapy Paroxysmal nocturnal hemoglobinuria Antiphospholipid syndrome Behcet disease Hypereosinophilic syndrome Mebranous webs Ageno et al, Blood 2014

13 Treatment strategies for SVT No RCTs available Observational studies Patient population heterogeneous GI bleeding common at presentation Portal hypertension common consequence

14 Symptomatic splanchnic vein thrombosis: anticoagulation over no anticoagulation (Grade 1B) LMWH may be preferred over VKA if there is active malignancy, liver disease, or thrombocytopenia.

15 ISTH International registry on SVT: Therapeutic strategies according to the site of thrombosis Treatment BCS PVT (n: 51) (n:244) (n: 67) (n: 19) LMWH may be preferred over VKA if there is active malignancy, liver disease, or thrombocytopenia. MVT SpVT Multiple site (n:232) No treatment 31.4% 33.2% 9.0% 15.8% 12.9% UFH 15.7% 4.9% 9.0% % LMWH/fonda parinux 49% 58.6% 83.6% 84.2% 71.8% VKA 47.1% 31.6% 61.2% 63.2% 60.8% Thrombolysis 3.9% 0 1.5% 0 2.6% Ageno et al Semin Thromb Haemost 2014

16 ISTH International registry on SVT: results of 2-year follow up 0.25 Major bleeding events Non-malignant non-cirrhotic Liver cirrhosis 0.25 Vascular thrombotic events Non-malignant non-cirrhotic Liver cirrhosis Liver cirrhosis 10.0/100pt-y Cumulative incidence Non-malignant non-cirrhotic 1.8/100pt-y /100pt-y 5.6/100pt-y Follow-up (years) Follow-up (years) Ageno et al JAMA Intern Med 2015

17 ISTH International registry on SVT: results of 2-year follow up Liver cirrhosis Solid cancer MPN Unprovoked Transient risk factors N Major bleeding 10.0% pt-yrs ( ) 4.4% pt-yrs ( ) 3.6% pt-yrs ( ) 1.7% pt-yrs ( ) 0.5% pt-yrs ( ) Thrombosis 11.3% pt-yrs ( ) 7.6% pt-yrs ( ) 5.9% pt-yrs ( ) 6.3% pt-yrs ( ) 3.2% pt-yrs ( ) Ageno et al, JAMA Intern Med 2015

18 Practical issues on the managent of SVT Anticoagulant treatment for a minimum of 3 months in patients with transient risk factors Consider indefinite treatment duration for patients with recurrent SVT or previous VTE and in patients with persistent risk factors Careful periodic reassessment of risk to benefit ratio of extended treatment Ageno et al Blood 2014

19 The direct oral anticoagulants for the treatment of splanchnic vein thrombosis Treatment of portal, mesenteric, and splenic vein thrombosis with rivaroxaban. A pilot, prospective cohort study The study is ongoing at Italian, German and Canadian centers

20 Cerebral vein thrombosis Cerebral veins Cortical veins Deep veins Dural venous sinuses Superior sagittal Straight Transverse Sigmoid Cavernous

21 Rate/ inhabitants Epidemiology of cerebral vein thrombosis in Northwestern Italy Standardized rates during years according to gender Female specific incidence: 17.3/10 6 p=0.004 Male specific incidence: 8.3/10 6 p=0.405 Years Dentali et al Blood Transf abstract 2016

22 Rate/ inhabitants Epidemiology of cerebral vein thrombosis in Northwestern Italy Crude incidence rates according to gender and age classes Age Dentali et al Blood Transf abstract 2016

23 Prevalence of risk factors in the International Study on Cerebral Vein Thrombosis (ISCVT) Women (n:465) Men (n:159) Unprovoked 8% 25% Infections (otitis, mastoiditis, sinusitis, meningitis) 10% 21% Cancer 6% 11% Mechanical precipitants 3% 8% Inherited thrombophilia 22% 25% Gender specific risk factors 65% - Oral contraceptives 46% - Pregnancy/puerperium 17% - Hormone replacement therapy 3% - Coutinho JM Stroke 2009

24 Cerebral vein thrombosis in women - ISCVT GSRF GSRF+ no GSRF Men Patients Age Mortality (%) mrs 0-1 (%) Disability (mrs 3-6) GSRF: Gender specific risk factors GSRF +: GSRF and other risk factors Coutinho JM Stroke 2009

25 Other factors associated with CVT Hematologic conditions Polycythemia Thrombocythemia Leukemia Paroxysmal nocturnal hemoglobinuria Asparaginase treatment Lumbar puncture Inflammatory disease Systemic lupus erythematosus Wegener s granulomatosis Sarcoidosis Inflammatory bowel disease Behcet syndrome Stam J, NEJM 2005

26 Safety of thrombolysis in CVT patients 14 studies, 13 retrospective Local thrombolysis for 143 patients Systemic thrombolysis for 5 patients Major bleeding: WM 10.0%, 95% CI Intracranial bleed: WM 7.6%, 95% CI Mortality: WM 7.3%, 95% CI /12 deaths due to ICH Dentali et al Thromb Haemost 2010

27 Evidence supporting acute treatment strategies Two trials involving a total of 79 patients 1. I.v. unfractionated heparin 2. Nadroparin D e a t h o r Coutinho et al Stroke 2012

28 Practical issues on the managent of CVT Use of either LMWH or UFH for the initial treatment Consider delayed introduction of VKAs Concomitant bleeding ( 25% of cases) should not contraindicate anticoagulation Use of thrombolysis to be restricted to selected, high risk patients (e.g. those who deteriorate despite anticoagulant treatment) Adapted from the following guidelines: American Heart Association/American Stroke Association European Federation of Neurological Societies American College of Chest Physicians Italian Society on Thrombosis and Haemostasis Anticoagulation Forum

29 Treatment of CVT in clinical practice Therapy ISCVT 1 USA 2 CEVETIS 3 UFH 64% 54% 21.9% LMWH 34.9% 14% 62.7% Thrombolysis 2.1% 15% 1.5% 1 Ferro et al Stroke Wasay et al J Stroke Cerbrovasc Dis Dentali et al J Thromb Haemost 2012

30 Long-term evaluation of recurrent CVT Patients 145 Women 73.1% Age (median) 33 years Follow up (median) 72 months Recurrent CVT (% pt/yrs) 0.63 ( ) DVT/PE (% pt/yrs) 1.40 ( ) Predictors of recurrent thrombosis Male gender HR 9.66 ( ) Severe thrombophilia* HR 4.71 ( ) *for DVT/PE only Martinelli et al Circulation 2010

31 Long-term evaluation of CVT CEVETIS study Patients 706 Women 73.7% Age (mean) 40 years Follow up (median) 40 months Recurrent thrombosis (% pt/yrs) 2.36 ( ) (N:31 recurrent CVT and 46 VTE in other sites) Recurrent thrombosis after OAT stopped 3.51 ( ) Predictors of recurrent thrombosis Previous VTE HR 2.7 ( ) Dentali et J Thromb Haemost 2012

32 Practical issues on the managent of CVT Anticoagulant treatment for a minimum of 3 months in patients with transient risk factors Consider 6-12 months of anticoagulation in patients without known risk factors Indefinite treatment duration for patients with recurrent CVT/previous VTE and in patients with permanent major risk factors including severe thrombophilia Adapted from the following guidelines: American Heart Association/American Stroke Association European Federation of Neurological Societies American College of Chest Physicians Italian Society on Thrombosis and Haemostasis Anticoagulation Forum

33 Respect-CVT Chair: JM Ferro. Steering Committee: F Dentali, J Coutinho, A Kobayashi, H Diener.