Michael Choo Box Hill Hospital Melbourne

Transcription

1 Michael Choo Box Hill Hospital Melbourne

2 A. Case presentation 20yo, 45kg female Pelvic tumour removal by vascular surgeons Sx of back pain radiated down both legs Takes tramadol PRN, no chemo or radiorx CT scan well-defined hypodense mass Adjacent and anterior to L5 37x45mm, 59mm length Below confluence of iliac veins, displacing CIA and V PET no major uptake or secondary deposits

3 Case continued PMHx: Eosophilic oesophagitis endoscopy (PONV) Depression/Anxiety Vit B deficiency Drugs: Pantoprazole Tramadol, Escitalopram OCP Vit B 12 IM Allergies: Erythromycin, Roxithromycin, Cephelaxin No smoking, alcohol 8 std/weekends

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13 Postoperative Transferred to ICU Intubated, ventilated. Epidural in situ. 950mg Tranexamic acid, 1 PRBC + fluids Extubated next morning and to ward Maintained on 5,000IU Fragmin Epidural removed POD 2 Discharged POD 8

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15 B. Discussion Bleeding risk and LMWH Should LMWH be given intraoperatively? Are all LMWH equal? Dalteparin How to administer Dalteparin Monitoring and treating acute bleeding from LMWH

16 1. Risk of bleeding Is this caused by LMWH? Unlikely for eosinophilic oesophagitis, Schwannoma and Vit K deficiency OCP associated with VTE Parecoxib not related with bleeding Escitalopram SSRI may cause bleeding by downregulating serotonergic receptors

17 SSRIs and platelets Serebruany VL. Selective serotonin reuptake inhibitors and increased bleeding risk: Are we missing something? Am J Med 2006; 119(2):

18 Are colloids safe? In this case not colloids Used to treat hypotension not cause it Mechanisms: vwf, platelets dysfx, fviii, impaired fibrinogen polymerisation Fibrinogen reverses effects

19 LMWH and bleeding Possible initial bleeding compounded by dalteparin Not DIC

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21 Risk of bleeding of LMWH Depends on dose and timing 5000 IU 2 hours pre-op: 11.6% LMWH vs 4.6% UFH 2500 IU 2 hours pre-op: 5.9% Abandoned doses closer to the operation 12 hours pre-op or 4-6 hours post-op: % Rate of major bleeding in patients treated up to 10 days: %

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24 Risk of bleeding.. Compared to placebo: 103% : major haemorrhage (2.8% prevalence) 106% : total haemorrhage 88% : wound haematoma and 53% : no. patients requiring postoperative transfusion Mismetti P, Laporte S, Darmon JY, Buchmuller A, Decousus H. Meta- analysis of low molecular weight heparin in the prevention of venous thromboebolism in general surgery. Br J Surg 2001; 88:

25 Risk of bleeding.. Higher dose of LMWH = More efficacy But = More bleeding Thomas DP. Does low molecular weight heparin cause less bleeding? Thromb Haemost 1997; 78: Gouin-Thibault I, Pautas E, Siguret V. Safety profile of different low-molecular weight heparins used at therapeautic dose. Drug Safety 2005; 28(4): Holzheimer RG. Prophylaxis of thrombosis with low molecular weight heparin (LMWH). Eur J Med Res 2004; 9: Tribout B, Colin-Mercier F. New versus established drugs in venous thromboprophylaxis: efficacy and safety considerations related to timing of administration. Am J Cardiovasc Drugs 2007; 7(1):1-15.

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30 2. Should LMWH be given? Efficacy: From THRift-II and 7th ACCP guidelines VTE risk: Calf DVT: 10-20% Prox DVT: 2-4% Clinical PE: 1-2% Fatal PE: % 8th ACCP: 10-40% Formal risk assessment models

31 But. Risk negligible at 20 yo Assuming no thrombophillic disorders NO published guidelines about lower limit Paed studies <18yo: 5.2/100,000 Cancer Obesity OCP CVL

32 General surgery Different from ortho Mismetti: DVT: 72% Clinical PE: 75% Clinical VTE: 71% Trend to reduce overall mortality Bergqvist D. Low molecular weight heparin for the prevention of venous thromboembolism after abdominal surgery. Br J Surg 2004; 91: Wille-Jørgensen P, Rasmussen MS, Andersen BR, Borly L. Heparins and mechanical methods for thromboprophylaxis in colorectal surgery. Cochrane Database of Systematic Reviews Issue 1. Art. No.: CD DOI: / CD

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43 3. Are all LMWH equal? Dalteparin Short answer = NO LMWH = <8000 Da, anti-xa >70IU/mg, anti-xa:anti-iia ratio >1.5 Other effects: Thrombin activatable fibrinolysis inhibition Tissue factor pathway inhibition Platelet factor 4 inhibition Interactions with cells and proteins Functional modulation of growth factors

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45 Different LMWH Different manufacturing Generic LMWH Similar molecular and structural attributes Different biological and pharmacological behaviour Dalteparin Comparable anti-xa activity with enoxaparin Derived from standard porcine UFH by partial nitrous acid polymerisation 5000Da ( Da), anti-xa:anti-iia ratio 2.7 Multiple uses

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47 4. How to give dalteparin Factors to consider here: a) Dosage b) Timing c) Cessation d) Epidural

48 a) Dosage Old: Dalteparin 2500IU vs UFH 5000IU bd More recent: Dalteparin 5000IU vs UFH 5000IU 2-3xd Even for pre-op 5000IU better than 2500IU In fact <3400IU is as effective, and safer than >3400IU.

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50 45kg? Peads IU/kg = IU Theoretically still need monitoring

51 b) Timing Controversial Orthopaedic data conclusive Raskob GE, Hirsh J. Controversies in timing of the first dose of anticoagulant prophylaxis against venous thromboembolism after major orthopedic surgery. Chest 2003 Dec; 124(6 Suppl):379s-385s. Preop admin is not required for good efficacy Initiation 6-9 hrs postop is effective and not assoc bleeding Initiating <6hrs postop increases major bleeding, without increasing efficacy Initiating hrs postop less effective than at 6 hrs

52 North American Fragmin Trial

53 c) Cessation Controversial Late VTE to 7 weeks Out-of-hospital: Not cost-effective In-hospital: Cost effective

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56 d) Epidural ASRA Recommends 2 hours post epidural removal Consider delaying dalteparin for another hour But SC peak is 3 hours later Compared to vascular surgery Full heparinisation 1 hour after epidural But no reversal No trials Lower VTE risk with epidural

57 5. Monitor and treatment Monitoring argument against APTT insentitive, anti-xa more sensitive but not predictive Expensive, time-consuming?normal therapeutic ranges Once daily dosing: 3-4hr after 3rd or 4th injection Twice daily dosing: 4-6hr after 2nd or 3rd injection Consensus recommendation chromogenic anti-xa activity assay or extrinsic coagulation activity assay 3 different chromogenic methods do not concur

58 Monitoring argument for Routine monitoring recommended for Paediatric patients Patients <50kg Patients >80kg Patients with renal disease Acute bleeding situations

59 Monitoring the ideal world Bedside near-patient test like Factor Xa-activated whole blood clotting time (Xa- ACT) Modified ACT for LMWH bedside monitoring Instead of siliceous earth, use bovine FXa Thromboelastography (TEG)

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62 Reversal Protamine 1mg/100IU LMWH reverses 90% of anti-iia and 60% of anti-xa activity However, both may return after 3 hours Replenish coagulation factors FFP/cryoprecipitate Prothrombinex Activated Factor VIIa (Novoseven) 3 cases -- ~20-30mcg/kg

63 Reversal others Heparinase (ex vivo) Recombinant platelet factor4 Hexadimethrine Engineered peptides

64 Summary A case of LMWH related bleeding Giving dalteparin is not unreasonable in this case The risk of bleeding with intraop administration is approx 11.6% Dalteparin should be given at 2500IU, 6 hours postop with no increase in the risk of bleeding without decreasing efficacy The alternative of heparin 5000IU bd should be considered Near patient testing might benefit To reverse, administer protamine and then replenish coagulation factors, and consider FVIIa if all else fails Good patient care normothermia, normal ph and normovolaemia Better communication

65 Questions Response to surgeons when asked to give intraop Liaison with haematology Monitoring Charting LMWH