1. Venous thrombosis , why should I care ?

2. 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.

4. What is venous thrombosis ?

5. Where does it happen ?

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

8. Why do people get clots ?

9. 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)

10. 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): Epub 2009 Nov
2.Obst Gynae Mar;117(3):
3. J OBST GYN Can Dec;32(12):1192-7

11. Cancer risks

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

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

15. Who should receive VTE prophylaxis ?

16. 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.

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

18. 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 ); 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%

19. 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

20. 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

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

23. 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

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

25. 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

26. 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 ), 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 ).
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).

27. 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

29. And now into the future and beyond

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

32. 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

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

34. 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, ) and major bleeding (OR, 0.77; 95% CI, ) were reported in those taking DOACs [42].

35. Current recommendation
Not enough evidence with DOACs in cancer
Be pragmatic

36. 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

37. 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

38. 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

39. Acknowledgements