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Thin Blood

Thin Blood. Department of Clinical Toxicology and Pharmacology Newcastle Mater Hospital. Case 1. 37 year old male Presented to JHH Emergency Department Drug overdose 120 mg warfarin Activated charcoal Bloods sent Transfer to MMH after d/w Toxicology. Background.

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Thin Blood

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  1. Thin Blood Department of Clinical Toxicology and Pharmacology Newcastle Mater Hospital

  2. Case 1 • 37 year old male • Presented to JHH Emergency Department • Drug overdose • 120 mg warfarin • Activated charcoal • Bloods sent • Transfer to MMH after d/w Toxicology

  3. Background • Precipitating incident : • Brother suicided recently • Planned overdose for 2 days • Psychiatric background : • No previous deliberate self harm • Amphetamine dependence

  4. Medical History • Endocarditis 2º to IVDU • Valve replacement x 2 • mitral and aortic valve replacements • St. Judes : bileaflet • Complicated by AMI and CVA • Lifelong anticoagulation • Nil attendance with cardiology follow up

  5. On arrival • HR 80 BP 144/88 Temp 36.2 • Alert and Cooperative • No bruising or evidence of bleeding • Dysarthric with mild cognitive impairment • HSD, metallic sounds • No signs of cardiac failure

  6. Initial Management • INR 2.0 • Appropriate Management ? • FFP • Vitamin K

  7. Initial Management • Haematology consult • 4 units FFP • 10 mg vitamin K IVI • Neurological observation • 2-3 daily INR

  8. INR Results Vitamin K 10 mg IVI 4 Units FFP

  9. INR Results Heparin 5,000 U Infusion 1000 U/hr

  10. INR Results Heparin ceased Warfarin recommenced, normal dose 5 mg/d

  11. Heparin Ceased Heparin Time course of INR Warfarin Restarted FFP Vit K

  12. Optimal Management - Issues • Perfect dose of vitamin K ! • Normalised INR with FFP; then therapeutic • Required heparinisation for 2 days • No active bleeding

  13. Case 2 • 43 year old male • Drug overdose 1 hour previously • 25 x 5 mg warfarin • 40 x 5 mg oxycodone • Multiple lacerations to left forearm • Vomited in transit to MMH

  14. Background • Precipitating incident : • Argument with wife, asked to leave • Psychiatric background : • Narcotic dependence; 7 year history • No previous deliberate self harm

  15. Medical History • Thromboembolic disease • Pulmonary embolus (definite diagnosis) • Recurrent DVTs, mainly on symptoms • Not thrombophilic ; testing negative • Chronic back pain • Gastro-oesophageal reflux • Hypertension

  16. On arrival • HR 66 BP 155/91 RR 14 • Decreased LOC, just rousable • Small and sluggish pupils • Multiple lacerations on left forearm • Nil else on examination

  17. Initial Management • Response to naloxone; infusion commenced (2mg/50 mL) at 15 mL/hr • Lacerations sutured • Bloods sent including Group + Save

  18. Initial Management 2 • INR 3.7 • Appropriate management ? • FFP • Vitamin K

  19. Initial Management 2 • Haematology consult • 6 units FFP • 10 mg vitamin K IVI • Neurological observation • 2-3 daily INR

  20. Progress - Day 2 • Clinical : no bleeding complications • Naloxone infusion continued • INR Results

  21. Progress - Day 3 • Haematology review : • commenced on daily enoxaparine 1 mg/kg • TED stockings • Daily INR • Naloxone infusion ceased • Psychiatric assessment • Drug and Alcohol review

  22. Progress - Day 2 - 6 • Day 4 : Warfarin recommenced 14 mg daily (normal dose) • Day 5 : Enoxaparin increased to twice daily Warfarin recommenced

  23. Progress - Day 5 - 12 • Transferred to inpatient psychiatric unit • Normal warfarin dose • Continue enoxaparin until therapeutic INR

  24. Time course of INR Vitamin K Warfarin

  25. Comments / Problems • What dose of vitamin K is appropriate ? • Patient still has a non-therapeutic INR two weeks after vitamin K

  26. Case 3 • 44 year old male • Drug overdose 3 hours previously • 150 mg warfarin • 2 g chlorpromazine • Aortic valve replacement 8 years previously • Asthma, OCD, pathological gambling

  27. Initial Assessment • Drowsy but easily roused • Normal observations • No active bleeding or bruising • INR 1.9

  28. Plan • No haematology consult • Q3H INR • Research: • Intermittent factor levels • Serial warfarin determination • Vitamin K 1 mg if INR > 5.0

  29. 100%

  30. Excessive Anticoagulation • Situation : • Therapeutic dose : drug interaction, other • Acute Overdose • Thromboembolic Risk • None • Low-medium : previous DVT/PE/thrombophilia • High : mechanical heart valve

  31. Acute Overdose - not own • No thromboembolic risk • Treatment : • vitamin K 5 - 10 mg IVI or oral • FFP if actively bleeding • Monitor INR • Straight-forward • Complicated in cases of long-acting agents

  32. Overdose or TherapeuticLow-Medium Risk of Thromboembolism • Requirements : • decrease INR to prevent bleeding complications • can tolerate normalisation of INR for a period • need to be restarted and reach therapeutic INR • Issues : • Use of FFP • Use of vitamin K and dose • requirement for heparin and hospital stay

  33. Overdose or TherapeuticHigh Risk of Thromboembolism • Requirements : • decrease INR to prevent bleeding complications • risk of thromboembolic complications with normalisation of INR for any period of time • Issues : • Use of FFP • Use of vitamin K and dose • requirement for heparin and hospital stay

  34. Increased INR & Risk of bleeding • INR > 4.5, 5.0 and 6.0 • Exponential increase in bleeding • Br J. Haem 1998 (Guidelines); • Cannegieter NEJM 1995 • Pal

  35. Increased INR and Risk of bleeding • Palareti et al. • Prospective cohort study • 2745 patients on anticoagulants • F/U for a mean of 267 days • temporally related INRs • Multivariate analysis: patients with an INR > 4.5 had an increased risk of bleeding, RR 5.96 (3.68-9.67, p<0.0001), compared to INR < 4.5

  36. Increased INR and Risk of bleeding • INR > 6.0 : Hylek Arch Intern Med 2000 • Abnormal bleeding 8.8% • Major bleeding 4.4% cf. 0% INR < 6.0 (P<0.001) • INR > 7.0 : Panneerselvam Br J Haem 1998 • Total bleeding 12/31 vs. 13/100 O.R. 5.4 • 5 major bleeds vs. none

  37. Increased INR and Risk of bleeding • INR > 8.0 Baglin Blood Rev 1998; • 12.9% major bleeding Murphy Clin Lab Haematol 1998 • Severe anticoagulation : Hung Br J Haematol 2000 • INR > 9.5 • APTT ratio > 2.0 • Required additional vitamin K doses

  38. Low INR and Risk of Embolism for High risk patients • Patients with mechanical heart valves • Risk of embolism rises with INR < 2.5 • Sub-groups with higher risk : • > 70 years age • Both > mitral > aortic • Caged ball/disk > tilting disk > bileaflet

  39. Therapeutic Options • Fresh frozen plasma • Vitamin K • oral • intravenous • Heparinisation • intravenous unfractionated • low molecular weight

  40. Fresh Frozen Plasma • Major bleeding • Minor bleeding; risk groups eg. age • Guidelines Br J Haematol 1998

  41. Vitamin K ? Appropriate dose • Oral vitamin K • RCT : Vit K, 1 mg vs. placebo (INR 4.5 - 10) • more rapid decrease in INR; 56% vs. 20 % with INR between 1.8 - 3.2 after 24 hrs (p< 0.001) • fewer patients had bleeding episodes during follow up 4% vs. 17% p = 0.05 ( 3 months) • Crowther Lancet 2000

  42. Vitamin K ? Appropriate dose • Intravenous vitamin K; RCT : INR > 6.0 • asymptomatic 0.5 mg vs. 1 mg • symptomatic 1 mg vs. 2 mg • INR fallen to 5 - 5.5 in all 3 groups by 6 hrs • Optimal INR (2-4) in 67% receiving 0.5 mg, but only in 33% receiving 1 or 2 mg • Over-correction in 16% (0.5 mg); 50% (1-2 mg) • no adverse effects • Hung. Br J Haematol 2000

  43. Vitamin K - Suggested dosing • INR > 5.0 ; asymptomatic, mild bleeding • 0.5 mg IV • repeat INR 6 - 12 hours • titrate as required • INR > 9.5; APTT ratio > 2.0 • 1 mg IV • repeat 6 hours • more likely to require repeat doses

  44. Vitamin K

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