Venous thrombosis , why should I care ?

Points you might remember by the end 1. Why does venous thrombosis happen ? 2. What are the risk factors ? 3. How do we prevent it ? 4. How do we treat it ? 5. Are there special considerations for cancer patients ? 6. Scattered pointless NZ photos.

What is venous thrombosis ?

Where does it happen ?

What will kill you ? 10% of DVT embolise to lungs PE associated with 5-10% hospital deaths

Why do people get clots ?

Risk Factors Age ( Over 70 -) Sex , M:F 1.2:1 Hospitalization - Medical and surgical Cancer ( x 20) Immobilization Drugs (OCP – 3,HRT-2) Pregnancy (6-8) Travel (2)

Female risk Pregnancy x 6-8 1 postpartum period -20 2 HRT and OCP x 2 ( Depends on oestrogen content <50ug low risk )3 1.T&H 2010 Feb;103(2):306-11. Epub 2009 Nov 2.Obst Gynae . 2011 Mar;117(3):691-703 3. J OBST GYN Can . 2010 Dec;32(12):1192-7

Cancer risks

Inherited risk factors Antithrombin deficiency Protein C Protein S Factor V Leiden / APC resistance Prothrombin 20210A mutation Increased factor II, VIII, IX, XI

Multiple myeloma 9.7 fold Marked in first year MGUS x 3.5 Increased by IMIDs

Who should receive VTE prophylaxis ?

Consider for all hospitalised patients Most hospitalized patients with cancer require thromboprophylaxis throughout hospitalization ● Thromboprophylaxis is not routinely recommended for ambulatory patients with cancer; it may be considered for very select high-risk patients ● Assess using Khorana score but most inpatient cancer patients need VTE prophylaxis.

High risk patients Myeloma , immobilised patients Myeloma on IMIDs Lymphoma , large intra-abdominal mass

What about indwelling vascular lines ? PICC vs. CICCs A meta-analysis of 11 studies found an increased risk of deep vein thrombosis for PICCs (odds ratio [OR] 2.55, 95% CI 1.54-4.23); there were no pulmonary embolism events Risk factors for DVT associated with PICC catheter placement include prior DVT, recent surgery, and cancer The rate of symptomatic venous thrombosis is 2-5%

Can we prevent thrombosis ACCP- Routine prophylactic systemic anticoagulation is not recommended for patients with indwelling central venous catheters It may be reasonable to administer prophylactic anticoagulation in high–risk patients when the perceived risk of thrombosis outweighs the risk of bleeding

Treating PICC line thrombosis Uncomplicated venous thrombosis anticoagulate Line can be kept in Duration depends on line remaining in place Once line removed continue for 2-6 weeks. Treat with LMWH

How do we treat VTE ? Anticoagulate LMWH and warfarin Dabigatran Rivaroxaban Apixiban Edoxaban

LMWH /Warfarin Can initiate warfarin first day with LMWH Adjust starting warfarin to patient Ensure good communication to warfarin team Ensure follow up Target 2.5 INR

Big problems with warfarin Monitor Narrow therapeutic index High bleeding risk Many drugs interact with it Cumbersome to start and stop

Low molecular weight (LMWH) fractionation from UFH MW 4,000-6,500 daltons bioavailability 90% t ½ 4-12 hours function - accelerates inhibition of Xa > lla Simple, safe and effective

How to treat VTE in cancer patients A meta-analyses (seven RCTs; 1908 patients with cancer), reported that compared to VKAs, LMW heparin reduced the rate of recurrent VTE (hazard ratio [HR], 0.47; 95% CI 0.32-0.71), a benefit that occurred without a survival advantage. The CLOT trial was a multicenter, international, randomized trial of 672 cancer patients with acute VTE that compared six months of treatment with warfarin with the LMW heparin, dalteparin. Dalteparin was associated with a significant reduction in the rate of recurrent VTE at six months (9 versus 17 percent; HR, 0.48, 95% CI 0.30-0.77). There were no significant differences in the rates of major bleeding (6 versus 4 percent), any bleeding (14 versus 19 percent), or overall mortality (39 versus 41 percent).

Current recommendation Six months of treatment with LMWH Consider dose reduction to 75% after 4 weeks Extend duration if persistent cancer If recurrence on treatment consider 25% dose increase Avoid IVC filters if possible

And now into the future and beyond

New agents Direct thrombin inhibitor – Dabigatran Direct Xa inhibitors – Rivaroxaban - Apixiban - Edoxaban

Advantages Effective Safe Fast onset and offset of action As effective as enoxaparin for primary prevention of VTE in patients undergoing total hip or knee replacement1 As effective at treating VTE as warfarin As effective at preventing CVA in atrial fibrillation. Dabigatran is better at preventing stroke Safe Reduced Cerebral bleeds by 60% Reduced major bleeds by 30% No liver toxicity observed2 Fast onset and offset of action Cmax achieved in 2 hours3 Half-life: 12–17 hours4 Predictable anticoagulant effect No routine coagulation monitoring required3 No clinically meaningful drug–food effects4 Low potential for cytochrome P450-related drug interactions3 Cmax = maximum concentration; VTE = venous thromboembolism 1. Wolowacz SE et al. Thromb Haemost 2009;101:77–85; 2. Ezekowitz MD et al. Am Heart J 2009:157: 805–10.e2; 3. Stangier J. Clin Pharmacokinet 2008;47:285–95; 4. Pradaxa™ Product Monograph 32

Problems No accurate monitoring test Compliance Expensive No reversing agent Higher GI bleeding risk

DOACs in cancer In one meta-analysis of six studies that included 1132 patients with DVT and cancer, compared with conventional therapy (heparin plus warfarin) similar rates of VTE recurrence (4 versus 6 percent; odds ratio [OR], 0.63; 95% CI, 0.37-1.10) and major bleeding (OR, 0.77; 95% CI, 0.41-1.44) were reported in those taking DOACs [42].

Current recommendation Not enough evidence with DOACs in cancer Be pragmatic

How we treat DVT in Limerick DVT nurse specialist All VTE patients are seen by coagulation team at outset Reviewed at 3 months and decision on duration made in thrombosis clinic Standard of treatment is DOAC

The future New VTE nurse specialist to investigate and treat PE Expand role of warfarin nurses in Nenagh and Ennis to manage DVT to provide a regional standard service

Summary 1. Venous thrombosis is multifactorial 2. Cancer is a major risk factor for VTE 3. Routine prophylaxis is not recommended outside of hospital but required in hospital 4. PICCs are associated with significant thrombosis rates 5. Venous thrombosis in cancer should be treated with LMWH at present but DOACs maybe on the way 6. VTE in non- cancer patients should be treated with DOACs 7. Hopefully the future lies with Nurse specialist management of VTE

Acknowledgements