Bleeding and Anticoagulation

1. Bleeding and Anticoagulation Dr Oliver Chapman 2011

2. Summary • Objectives: • Understand haemostatic mechanisms • Learn about the commoner haemorrhagic disorders and their treatment • Understand how to initiate and manage anticoagulation • Cases

5. Platelets

6. Platelet adhesion / aggregation

7. Case Scenarios • Abnormal bleeding • “Peri operative screen” / Abnormal coagulation screen • Routine coagulation testing to predict postoperative bleeding risk in unselected patients prior to surgery or other invasive procedures is not recommended • A bleeding history, including family history, evidence of excessive post-traumatic or postsurgical bleeding and use of antithrombotic drugs should be taken in all patients prior to surgery or invasive procedures.

9. Summary of key recommendations 1 Indiscriminate coagulation screening prior to surgery or other invasive procedures to predict postoperative bleeding in unselected patients is not recommended. (Grade B, Level III). 2 A bleeding history including detail of family history, previous excessive post-traumatic or postsurgical bleeding and use of anti-thrombotic drugs should be taken in all patients preoperatively and prior to invasive procedures. (Grade C, Level IV). 3 If the bleeding history is negative, no further coagulation testing is indicated. (Grade C, Level IV). 4 If the bleeding history is positive or there is a clear clinical indication (e.g. liver disease), a comprehensive assessment, guided by the clinical features is required. (Grade C, Level IV).

10. Bleeding History • Include • Previous / current haemostatic challenges • Operation eg appendicectomy / T’s & A’s • Dental extractions • Lacerations / sutures • Menses • Drug History • Including anti platelet Rx / NSAID’s • Family history

11. Laboratory tests Laboratory tests 1 • Platelets • FBC – platelet count and film • Bleeding time * • Platelet function tests (only at centres) * * =in liason with haematology

12. Platelets - Blood film

13. Bleeding Time

14. Platelet function tests • If screening test abnormal and platelet count and VWD screen normal refer for platelet function test: • www.platelet-research.org

15. Platelet disorders • Quantitative • Thrombocytopenia. • Qualitative • Functional disorders – Congenital vs Acquired

16. Congenital platelet function disorders • Bernard Soulier • Rare. AR inheritance. Platelet GP Ib-IX deficiency – adhesion problem. • Glanzmann’s Thrombasthenia • Rare. AR inheritance. Platelet GP IIb-IIIa deficiency – aggregation problem. • Storage Pool Disorders • α-SPD (gray platelet syndrome) / Dense granule storage pool disorders (δ-SPDs) such as Chediak-Higashi, Hermansky-Pudlak syndrome, thrombocytopenia with absent radii (TAR syndrome), or Wiskott-Aldrich syndrome.

17. Acquired platelet dysfunction disorders • Drugs eg aspirin, NSAID’s, clopidogrel, dipyridamole • Uraemia • Myelodysplastic , Myeloproliferative disorders

18. Platelet disorders - treatment • Treatment of aquired platelet disorders • Stop offending drugs (aspirin – 7 days, other NSAID’s generally 1-2 days) • ddAVP in uraemia • Platelet transfusion (if active, significant bleeding aim to maintain platelets >50), otherwise >10. • NB Avoid platelet transfusions in HIT, TTP and PTP (unless life threatening bleeding)

19. Laboratory tests • Laboratory tests 2 • Coagulation • Prothrombin Time (PT) • Activated Partial Thromboplastin Time (APTT) • Fibrinogen • Measurement of clotting factor levels * * =in liason with haematology

20. Clotting factor disorders • Prothrombin Time • Normal 10-14s • Prolonged in deficiency Factor VII (and early warfarin) • APTT ratio • Normal • Prolonged in deficiency Factors VIII, IX, XI, XII • Both PT / APTT-R prolonged • Fibrinogen and other common pathway factors (FII, V, X) • NB International Normalised Ratio should only be used in the context of patients on warfarin

21. Haemorrhagic disorders - coagulation • Prolonged coagulation screening test • Inhibitor (antibody - rare) vs Deficiency (common) • 50:50 mix • Deficiency : prolongation corrects • Inhibitor : no correction of prolongation

22. Clotting factor deficiencies • Congenital • Acquired

23. Congenital deficiencies • Haemophilia A, B • Joint, muscle bleeds • X linked • Other factors (very rare)

28. Haemophilia • DO NOT DELAY TREATMENT • Delays in administration of clotting factor therapy / treatment significantly increase morbidity / costs of therapy and long term disability • Patients at UHCW when bleeding are ALL triaged orange minimum ie assessment in 30 minutes (and treatment within 60 minutes)

29. Von Willebrands Disease • VWF carrier molecule for F VIII • VWF deficiency leads to VIII deficiency • Characterised by mucocutaneous bleeding (bruising, epistaxis, GI bleeds, menorrhagia) • Autosomal inheritance • Common (up to 1:1000)

30. Acquired haemorrhagic coagulation disorders - • Acquired factor deficiencies • Warfarin • Vitamin K deficiency eg sick patients on broad spectrum antibiotics • DIC • Massive transfusion (whole blood volume replaced) • Liver disease

31. Haemorrhagic disorders - treatment • Treatment of congenital factor deficiencies • Factor concentrates (except FV deficiency) NOT FFP or cryoprecipitate because of risks of viral transmission • Specialist involvement

32. Haemorrhagic disorders - treatment • Treatment of acquired coagulation disorders if bleeding • PT / APTT prolonged – FFP 10-15mls /kg • Fibrinogen low – Cryoprecipitate (2 pools)

33. Case 1 • 4 year old boy fell over and developed painful swelling of left elbow • What tests?

34. Case 1 • FBC – normal • Coagulation screen • PT 12s (N) • APTR 2.0 (prolonged) • Fibrinogen 2.3 (N) • What are the possible diagnoses? • What tests? – bonus

35. Case 2 • 76 yr old woman admitted with Right sided pneumonia, temp 39.5 C, bruising over arms, legs. • FBC – Hb 12.0, WCC 20.0, Platelets 22 • What test next?

36. Case 2 • Coagulation screen • PT 20s • PTT 48s • Fibrinogen 0.7 • ? Likely diagnosis • What is the treatment? • If she were bleeding actively?

37. Case 3 • 65 year woman with known atrial fibrillation admitted with haematemesis. • FBC – Hb 7.0, WCC 8, Platelets 190 • PT 40, APTT 34, Fibrinogen 2.0 • What is the likely cause? • How would you treat?

38. Warfarin

40. Warfarin in VTE - duration • Calf vein thrombosis - 3 months • Provoked proximal DVT eg post-op - 3 months • Idiopathic proximal DVT - 6 months • Pulmonary Embolism - 6 months • Recurrent DVT / PE - Indefinite • NB If persisting risk factor eg paralysis, immobilised limb / cancer consider extending treatment duration – INDIVIDUALISED THERAPY (the future?)

41. Warfarin and AF • Risk factors for CVA in non-rheumatic AF include: • CCF, previous CVA, age > 75 yrs, hypertension, DM • Patients with no risk factors – stroke risk <1%/yr, treat with aspirin only – low CHAD2 score • Risk of serious bleeding on warfarin 2%, and of fatal bleeding 0.6% • Therefore consider whether warfarin indicated if lone warfarin. Also consider bleeding risk – increased if recurrent falls etc.

42. Starting warfarin • 2 regimes based on degree of urgency for therapeutic anticoagulation • Rapid anticoagulation in patients requiring heparin ie post thrombosis etc • Slow induction of anticoagulation in outpatients not requiring heparin ie prophylaxis eg AF

43. Rapid Warfarinisation • Gedge Nomogram - recommended • Shown to be safer than traditional Fennerty Nomogram in patients >65 years. • Similar time to achievement of therapeutic range (<1/7 difference) • Also concerns with Fennerty Nomogram in other patients with Congestive Cardiac Failure, Hepatic Dysfunction, other bleeding risks etc

44. 1 Modified Fennerty Nomogram : Fennerty A et al (1984) Br Med J; 288: 1268-70 2 Gedge Nomogram : Gedge J et al (2000) Age and Ageing; 29: 31-34

45. Non Urgent Warfarinisation • Liaise with anticoagulation team • Numerous equivalent low dose protocols eg Jane S et al (2004) Clinical Laboratory Pathology; 26: 43-47 • Still beware patients at risk of overanticoagulation eg amiodarone and consider reducing doses

47. Warfarin Maintenance / Dose Modifications • Assuming target INR range 2-3 • INR<1.5 Increase by 1mg • INR 1.6-1.8 Increase by 0.5mg • INR 1.9-3.1 No change • INR 3.2-3.5 Reduce by 0.5 mg • INR 3.6-4.5 Omit dose, reduce by 0.5mg • INR 4.6-5.0 Omit dose, reduce by 1mg • INR 5.1-6.0 Omit 2 doses, reduce by 1mg • INR 6.1-8.0 Omit 3 doses and repeat • NB If interacting medication prescribed more frequent monitoring will be required

48. Warfarin and Surgery • Individualized depending on risk of thrombosis (lone AF low risk vs. mechanical mitral valve high risk) vs. risk of bleeding. • In elective surgery • If low risk of thrombosis may be adequate to simply stop warfarin 4 days pre op and restart post op. Most operations can proceed safely with INR <1.5 (NB not neurosurgery) • If high risk may require bridging therapy with heparin when INR becomes sub therapeutic – discuss with senior colleague • Emergency surgery is likely to require reversal as per bleeding patients in all but minor procedures

49. Warfarin overdose / bleeding • Overdose • INR >8.0 and no bleeding give oral Vitamin K (5mg) and inform anticoagulation team • Reversal agents / bleeding • Vitamin K • Oral – takes 24 hours to reduce INR – little use • IV – takes 6 hours to reduce INR • Fresh frozen plasma • 10-15 mls/kg ie large volume, usually takes 1-2 hours to administer • Prothrombin complex concentrate eg octaplex • Administer over 5-10 minutes slow IV push. Instantaneous reversal but risk of DIC / MI etc

50. Heparin - uses • Prophylaxis vs. Therapeutic • Prophylaxis • No monitoring required (UFH or LMWH) • Generally give clexane 40 mg in most situations • Therapeutic • Monitoring mandatory daily + regular FBC with UFH/ intravenous heparin • Monitoring of LMWH generally not required