co mep bruising april10f3
TRANSCRIPT
Bruising (and bleeding conditions)
CoMEP
14th & 27th April 2010
Specific Learning Objectives Understand basics of physiological haemostasis
Recognise and differentiate ‘normal’ and pathological bruising patterns and likely underlying aetiologies
Be able to take a bleeding history with the aim of differentiating acquired & congenital and platelet/vascular & coagulation factor disorders
Understand the appropriate investigative strategies [and interpretation of their results] for bruising/bleeding patients
Specific Learning Objectives Understand & recognise the common causes of
acquired bleeding disorders [drugs and co-morbid disease]
Understand the basics of the more common congenital bleeding disorders – prevalence, inheritance pattern, clinical and laboratory diagnostic features and treatment
What physiological mechanisms come into play when a blood vessel is
damaged?
von Willebrand factor in Primary Haemostasis
Defective Primary Haemostasis
Thrombocytopenia Dysfunctional platelets [anti-platelet agents]
Defective platelet - vessel wall interaction Vessel wall disorder severe VWD
Prolonged Bleeding Time
Petechiaeand
Purpura
Vasculitic Purpura
Senile Purpura
Bleeding Disorder Symptoms
Immediate bleeding Delayed bleedingcontrolled by pressure not controlled by pressure
Purpura & petechiae Muscle & joint bleeds
Mucosal bleeding Large ecchymosesEpistaxis, menorrhagia Haematuria
Bleed after venepunctureBleed after im injection
Post-traumatic bleeds Post-traumatic bleeds
GI & CNS bleeds GI & CNS bleeds
Platelet / Vascular Defects Clotting Factor Defects
FibrinFibrinogen
Extrinsic Activation Intrinsic Activation
Xa
IIa
TF/VIIa
X IX
IXaVIIIa
Va
II
XIa
XIIa
XI
XII
Collagen, HMWK, PK
Common Pathway
Coagulation Pathways
FibrinFibrinogen
Extrinsic Activation Intrinsic Activation
Xa
IIa
TF/VIIa
X IX
IXaVIIIa
Va
II
XIa
XIIa
XI
XII
Collagen, HMWK, PK
Common Pathway
Coagulation Pathways
FibrinFibrinogen
Extrinsic Activation Intrinsic Activation
Xa
IIa
TF/VIIa
X IX
IXaVIIIa
Va
II
XIa
XIIa
XI
XII
Collagen, HMWK, PK
Common Pathway
Coagulation Pathways – lab assays
APTT
TCT
PT
Ca2+ and phospholipidalso required
Current & New Anticoagulant Agents
Adapted from Weitz JI et al. J Thromb Haemost. 2005;3:1843-1853.
FibrinFibrinogen
Indirect Xa inhibitors FondaparinuxDanaparoid
LMWH, UFH
Xa Inhibitors:RivaroxabanApixaban
IIa InhibitorsXimelagatranDabigatran
ORAL PARENTERAL
Xa
IIa
TF/VIIa
X IX
IXaVIIIa
Va
II
Antithrombin
Indirect IIa inhibitors
UFH, [LMWH]
Warfarin
FDPs, D-dimer
Antithrombin
Plasmin
Bleeding Disorder Symptoms
Immediate bleeding Delayed bleedingcontrolled by pressure not controlled by pressure
Purpura & petechiae Muscle & joint bleeds
Mucosal bleeding Large ecchymosesEpistaxis, menorrhagia Haematuria
Bleed after venepunctureBleed after im injection
Post-traumatic bleeds Post-traumatic bleeds
GI & CNS bleeds GI & CNS bleeds
Platelet / Vascular Defects Clotting Factor Defects
Key aspects of bleeding history
Type, location & size of bruising
Precipitating factors Length of bleeding
following lacerations & shaving cuts
Post-op bleeding
Epistaxis Gum bleeding Dental
extractions GI bleeding Menorrhagia
Is the bleeding history only recent or is it life long
Coagulation Pathway Disorders
Congenital– Haemophilia A Factor VIII deficiency
– Haemophilia B Factor IX deficiency
– von Willebrands disease Deficient or abnormal vWF
Acquired– Heparins– Warfarin (and new oral anticoagulants)
– Liver disease
FibrinFibrinogen
Extrinsic Activation Intrinsic Activation
Xa
IIa
TF/VIIa
X IXIX
IXaIXaVIIIaVIIIa
Va
II
XIa
XIIa
XI
XII
Collagen, HMWK, PK
Common Pathway
Coagulation Pathways – Haemophilia
APTT
TCT
PT
Isolated deficiency of Factors VIII, IX, XI or XII
[intrinsic pathway]causes prolonged APTT
with normal PT
Case 1 35y male Attends A&E following altercation in pub
– Has received punches to face and kicks to right leg
– O/E no bleeding or bruising– No fractures on X-rays
Informs staff he has haemophilia B
What would you do next?
Haemophilia A
Classical haemophilia Factor VIII deficiency
– severe 1iu/dl– moderate 2 - 5 iu/dl– mild 6 - 40 iu/dl
Incidence 1/20,000 [1/10,000 males]
X-linked inheritance Prolonged APTT
Treatment of coagulation factor deficiency
Education- patients and doctor Desmopressin [DDAVP]
Replacement therapy– FFP / Cryoprecipitate– plasma derived factor concentrate– recombinant produced factor concentrate
Gene therapy
Case 2
Case 2 48y female
– pyrexia + rigors– ? acute abdomen– paracolic abscess at laparotomy
Post-op -> ICU Haematology Results
– Hb 94 g/l PT 21s (NR 11-15)
– WBC 16.0 x109/l APTT 41s (NR 26-37)
– Platelets 78 x109/l D-dimer 4200 (NR <500)
Disseminated Intravascular Coagulation
Systemic activation of coagulation
Intravascular deposition of fibrin
Depletion of platelets and coagulation factors
Thrombosis of small and midsize vessels and
organ failure
Bleeding
DIC - Laboratory Investigations
LOOK FOR UNDERLYING CAUSE– sepsis, trauma, cancer, obstetric disaster
Coagulation PT, APTT, Fibrinogen D-dimers FBC + film platelets, RBC fragments Coag Factors ?
DIC - Treatment TREAT UNDERLYING CAUSE
FFP +/- platelets if bleeding or high risk for bleeding
? Heparin 300-500u/h if thrombotic phenotype ? AT III concentrate (reduces mortality 56% -> 44%)
? Protein C concentrate (meningococcal sepsis)
? Activated Protein C
Case 3 - Confused lady in A&E
80y female found behind door of ground floor sheltered housing
GCS = 9 right sided weakness with dysphasia irregular pulse urinalysis clear
Sent for CT head
Case 3 FBC
– Hb 11.8 g/dl– WBC 12.7 x109/l– Plts 191 x109/l
Coagulation– PT 97s (INR 7.6)
– APTT72s (APTTr 1.9)
– TCT 12s (NR 9-12s)
Bleeding complications with warfarin
fatal haemorrhage 0.25 - 0.64% per year
major haemorrhage 1.1 - 2.7% per yearAchieved INR major bleeds (% per year) minor bleeds
< 2 1.5 112 - 3 2.5 123 - 4 2.5 154 - 5 4 205 - 6 5 34 6 9 96
van der Meer et al., Arch Int Med 1993
What can we do when INR is too high?
Stop warfarin or reduce dose
Give Vitamin K1 (oral or iv)
Give coagulation factors (II, VII, IX, X)
Decline of INRafter warfarin cessation when INR >6
0
10
20
30
40
50
60
70
80
90
100
0 1 2 3 4 5 6 7
Days
% INR> 4
Hylek et al. 2000
Warfarin - Life threatening bleeding
Stop warfarin
5mg intravenous Vit K1
Intravenous factor concentrate– Prothrombin Complex Concentrate
(Beriplex or Octaplex)
Irrespective of INR
Case 4 – 64y male 4 days after commencing warfarin for PE
Case 5
24y female attends GP having noted petechial rash on legs– Suffered a short epistaxis previous week– also gum bleeding after brushing teeth
PMH– ? Recent viral URTI– uncomplicated tonsillectomy age 12y
DH – C-OCP
What lab test would you do next?
Case 5 – blood results
FBC– Hb 98 g/L– WBC 18.7 x109/l– Plts 25 x109/l
Coagulation– PT 14s (INR 1.2)
– APTT 32s (NR 25-35s)
– TCT 12s (NR 9-12s)
What most likely diagnosis? Any other tests?
Case 5 – blood results
FBC– Hb 98 g/L– WBC 18.7 x109/l– Plts 25 x109/l
Coagulation– PT 14s (INR 1.2)
– APTT 32s (NR 25-35s)
– TCT 12s (NR 9-12s)
What most likely diagnosis? Any other tests?
Case 6
44y male brought to A&E confused and tremulous– He is icteric and admits to alcohol intake >60 units/week for
some years– He has many medium sized bruises on limbs and trunk– Abdominal examination reveals hepatosplenomegaly [liver
5cm bcm, spleen 3cm bcm] PMH
– Several previous similar admissions– Stabbing age 21y and # fibula age 24y without excessive
bleeding DH – nil
What lab test would you do next?
Case 6 – blood results FBC
– Hb 110 g/L– WBC 4.0 x109/l– Plts 55 x109/l
Coagulation– PT 23s (=INR 1.2)
– APTT 43s (NR 25-35s)
– TCT 12s (NR 9-12s)
What are the possible mechanisms for this patients coagulopathy?
U&E– Na 127 umol/L– K 4.0 umol/L– Urea 2.7 umol/L– Creat 91 umol/L
LFTs– bili 76 u/L– Alt 143 u/L– Ast 100 u/L
Case 6 – Coagulopathy in liver disease
Poor coagulation factor synthesis in liver If Vit K deficient (poor diet +/- obstructive component to
jaundice)
Poor clearance of activated coagulation factors DIC Hypersplenism ( low WBC and Plts)
Reduced thrombopoietin synthesis ( low Plts)
Summary
Establish type, duration and distribution of bruising & bleeding
Is it platelet/vascular of coagulation factor deficiency pattern?
Determine if acquired or congenital Establish drug history and co-morbid disease What is the pattern of coagulation screen
abnormality?