management of bleeding
DESCRIPTION
Management of bleeding. Andrew McDonald Alberts Cellular Therapy. “All bleeding eventually stops”. n. Modified Virchow’s triad. Blood flow Size BP. BLEEDING. Coagulation Platelets Clotting factors Fibrinolytic system. Vessel wall Endothelial activation Collagen disorders Age - PowerPoint PPT PresentationTRANSCRIPT
Management of bleeding
Andrew McDonaldAlberts Cellular Therapy
“All bleeding eventually stops”
n Modified Virchow’s triad
BLEEDING
Blood flowSizeBP
Vessel wallEndothelial activation
Collagen disordersAge
Corticosteroids
CoagulationPlatelets
Clotting factorsFibrinolytic system
n• n
n
n Thrombin generation
LOW [Thrombin]
• VIII activation and release from vWF
• V activation and release from platelets
• Platelet activation
• XI activation
HIGH [Thrombin]
• Fibrin formation
• TAFI activation
• XIII activation
• Protein C activation (with thrombomodulin)
n• n
Categories of patients
• Known “bleeders”– Anticoagulants or anti-
platelet agents– Other drugs
• Starch vol expanders, cephalosporins
– Inherited– Acquired
• ITP• Inhibitors• Cirrhosis• Uraemia
• Unknown– With bleeding history– Unexpected bleed
• Type of bleed:– ACUTE vs CHRONIC
– Minor– Major
• Admission required• 2 units RBC• Critical organ
– Life threatening• ICH• Massive GIT• Airway
n• n
Nutrition and bleeding risk
nMake a better clot
Drug• DDAVP• Oestrogen• Factor 8 concentrate• Activated rVIIa (Novoseven)• PCC (plasma derived –
Haemosolvex)• Fibrin glueTransfusion• FFP• Platelets• Cryoprecipitate• [RBC]
Hold on to clot• Make a better clot in the
first place• Tranexamic acid
Strategies for stopping bleeding
Clotting factorsFibrinogen (I) Liver Cryoppt
Prothrombin (II)
Liver PCC
Factor V Liver (Cryoppt)
Factor VII Liver PCC
Factor VIII Liver Cryoppt Factor 8
Factor IX Liver PCC
Factor X Liver PCC
Factor XI Liver
(Factor XII) Liver
Factor XIII Liver + Megakaryocytes
Cryoppt
vWF Endothelium + Megakaryocytes
Cryoppt Factor 8
n• n
n• Tranexamic acid –synthetic lysine analogue
– Blocks lysine binding site on plasminogen, preventing activation to plasmin
• Oral / mouthwash / IV• Typical dose 1-1.5G 6-8 hourly (range dose 2.5-100mg/kg)
• Useful in:– Menorrhagia– Dental extractions– Major surgery – orthopaedic, cardiac, urologic– Bleeding associated with
• Mild Haemophilia A and VWD• Platelet disorders
• Risk of thrombosis low
Anti-fibrinolytic agents
n• Modified analogue of ADH (AVP) • IV formulation (dose 0.3ug/kg/day)
– NB tachyphylaxis (25% less effective on day 2)• Oral tabs and low dose nasal spray not effective for
haemorrhage• Increases endogenous factor 8 and VWF levels (via V2
receptor)
• Useful in mild Haemophilia A and Type 1 VWD• Also useful in platelet derived bleeding
– Mild inherited cytopathies– Antiplatelet agents– Mild/mod thrombocytopenia
• Contraindicated in known coronary artery disease• Side effect – headache, flushing, hyponatraemia
DDAVP
rhVIIa (Novoseven)
• Registered for bleeding in haemophilia with inhibitors• Used as a general haemostatic in severe life threatening
bleeding– Massive trauma– Massive APH / PPH– Cardiac surgery– ICH
• Expensive – reimbursement issues• Increased thrombotic events (OR 1.6)• Dose 90ug/kg; not effective in severe acidosis,
hypothermia, and low platelets
Perc
ent o
f pat
ient
s (%
)
0102030405060708090
100
RBC units within 48 hours 0 5 10 15 20 25 30 35 40 45 50
NovoSeven® (N=52)
Placebo
(N=59)P= 0.019
≥ 8
Boffard KD et al. J Trauma 2005;59(1):8-18
n• All anticoagulants increase bleeding risk• Scoring systems to predict, but bleeding often
unpredictable• HAS-BLED score
– Hypertension,abnormal kidney/liver, Stroke, Bleeding history, labile INR, Elderly (>65), Drugs/alcohol
Reversal of anticoagulation
Risk of bleed
Difficulty in reversal
OLD NEW
nWarfarin:Withhold warfarin only:• 2 older case series total 299 pts, with 352 INR values >6• 2 pts (0.6%) suffered haemorrhage
Glover et al 1995Lousberg et al 1998
• 1104 pts with INR >5• 30 day incidence of major bleeds low at 1.3%• Subanalysis of 42 pts (4.3%) with INR >9
- incidence major bleeds 9.6% (4pts)- more likely to receive Vitamin K (62% vs
7%)Garcia et al 2006
Reversal of anticoagulation
nWarfarin:Withhold wafarin and give Vit K:• IV Vit K - 2 small studies
– 31 pts (10 received 1mg, 21 received 0.5mg IV)– 50% pts with 1mg INR @24h <2, – all pts with 0.5mg between INR 2 - 5.5 @24h Shetty et al 1992
– Anaphylaxis est. 3 / 10 000 administrations
• Oral Vit K 1 – 2.5 mg safe and no risk of warfarin resistance– 7 small studies: less bleeding with Vit K use and more rapid control– 59 pts with mechanical heart valve with INR 6 - 12– 13/29 vs 4/30 with INR in range @24h with Vit K 1mg vs placebo– 3/29 (10%) with INR <1.8 @24h with Vit K Ageno et al 2005
ORAL > IV > Subcut
Reversal of anticoagulation
nWarfarin:Urgent reversal• CNS or vital organ haemorrhage• Major bleed (requiring admission, transfusion
RBC)
• Uncertainty of variable vs fixed dose PCC - Haemosolvex
Reversal of anticoagulation
n• UFH
– Short T1/2 – expectant management possible– Reversal with protamine sulphate 1mg/100IU IV
• Max 50mg in 10 min• LMWH
– Longer T1/2, but more predictable, less bleeding– Prolonged effect in renal dysfunction– Protamine sulphate 50-70% effective– Dose as above or 0.5-1mg/mg enoxaparin
• Fondaparinux– Long T1/2 of 20 hours, longer in renal failure– Protamine not effective– Novoseven ???
Reversal of anticoagulation
n Reversal of anticoagulation
Rivaroxaban Dabigetran• Anti –Xa• Dose 10mg daily• Tmax 2.5-4h• T1/2 5-9h, 9-13h (elderly)• Daily dose• 66% faecal, 33% renal• PCC / VIIA / FEIBA for
bleeding• Assay: anti-Xa• Drug interaction CYP3A4
• Anti-thrombin• Dose 150-200mg• Tmax 2h• T1/2 14-17 h• Daily or BD dose• 80% renal, 20% fecal• No current antidote
• Possible dialysis• Assay: Ecarin clotting time• PPI decrease absorption
nDRUG ACTUAL T1/2
EFFECTIVE THERAPY for
BLEED
Aspirin 15-30min 4-5 days DDAVPPlatelet
transfusionP2Y12 receptor inhibitors: clopidogrel
8h 5-7 days ? DDAVPPlatelet
transfusionP2Y12 receptor inhibitors: prasugrel
7 hours 5-7 days Platelet transfusion
P2Y12 receptor inhibitors: ticagrelor
7 hours < 30% effect after 2 days
Wait
Reversal of anti-platelet agents
n• Chronic bleeding
– Lab tests – make a diagnosis• Acute bleed with anticoagulants
– Reverse as per guidelines• Acute bleed – unexpected
– TEG and lab– Tranexamic acid/DDAVP/FFP
SUMMARY