Transcript Bleeding disorders

Bleeding
Disorders
For
Surgeons
J. Bormanis
Bleeding disorders
•
•
•
•
What are the possibilities
What questions have good yield
What are screening tests
What Lab tests are worrisome and what is
the risk
Clinical Approach
•
•
•
•
•
•
•
•
When did it start ?
Dental history
Spontanous bruising
Bleeding at surgery
Bleeding into joints
Menstrual bleeding
Epistaxis
One site only? Where ? When ?
High yield questions
•
•
•
•
•
•
•
Family history
Pattern of bleeding - where
Difficult to stop or
Re-bleeds
Drug history
Alcohol intake
Co Morbid disease
Physical Examination in Bleeding Disorders
• Check sites of bleeding
• Is it local or generalized ?
• what are the manifestations, petichiae,
ecchymoses, hematoma ?
• Are there vessel wall abnormalities, telangectasia,
“palpable purpura, perifollicular hemorrhages” ?
• Are there signs of a connective disease process
• Are There signs of a systemic disease
• The type of bleeding should give a good clue as to
which part of hemostasis is affected as well as
the severity
Laboratory testing
• History and physical
• Type of tests guided by clinical
features
• Screening tests
• Further tests
• Definitive tests
Normal Hemostasis
Screening Tests
• INR
Extrinsic pathway
• PTT (activated partial thromboplastin time)
intrinsic pathway
• Thrombin time
final pathway
• Platelet count
• Bleeding time – PFA (not useful)
Laboratory tests further testing
•
•
•
•
•
•
•
•
•
INR
PTT
TT thrombin time
Factor assays
Tests of fibrinolysis
platelet count
Bleeding time
platelet function tests
Special tests
Inerpretation of tests
•
•
•
•
•
•
•
•
If isolated abnormality likely a single defect
eg PTT - possible hemophilia, vWd
If unexplained do mixing test for inhibitor
IF more than one abnormality then more
complex
eg. INR and PTT - vitamin K- Coumadin
eg. PTT,TT heparin
eg INR , PTT, TT, Platelets
DIC or liver disease
Clinical Cases
Case 1
• It is Friday at 4:40pm
• Lab calls
• Your patient is being preped for urgent
surgery.
• INR 6.5
• What to do ?
Why INR’s go out of control
Vitamin K
•
•
•
•
•
Warfarin affects factors II,VII,IX and X
These are the vitamin K dependent factors
Can reverse warfarin effect
Takes time
Available forms ?
Efficacy of route of administration
Reversing INR wityh vitamin K
•
•
•
•
•
Depends on clinical scenario
Complete reversal
Partial reversal (too high INR)
IV or oral forms prefered
For complete reversal 5-10 mg IV q12h for
2 doses will reverse completely in 36-48
hours.
• 1-2 mg will decrease INR to therapeutic
• Level within 12-24 hrs
Current practice
Sent as 2 vials in a 50 cc mini bag to infuse at 3c/min
Case 2
• You are on call for ENT and are asked to see an
18 year old girl with refractory nosebleed.
• The nose is packed and bleeding does not stop.
• You notice a few bruises
• Blood sent off to lab.
• The lab calls at 6:00 Pm with a “critical” platelet
count of 10
• What is likely diagnosis
• What to do ?
ITP Immune thromboctopenic purpura
•
•
•
•
What is needed for diagnosis
Bone marrow examination
Anti platelet antibodies
When isolated and very low ITP is most
likely diagnosis
• Could be a part of another disease but not
likely (SLE , inf mono)
• Does it require hospitalization ?
ITP continued
•
•
•
•
•
•
•
•
•
If mucosal bleeding platelets are less than 6
Needs action
Steroids
IVIG
Anti D
What about splenectomy
New treatments
Rituximab
TPO agonists
Case3
• A 48 year old woman appears in emerg
with jaundice of 3 weeks duration
• Exam – jaundice - some RUQ pain an
palpation
• Blood tests
• CBC Hgb 125, WBC 7.6 Plat 345
• INR 2.6 ptt 42
• What is likely diagnosis
• What to Do ?
Vitamin K deficiency
•
•
•
•
Obstructive jaundice
Malabsorption of Vit K dependent factors
Older people at risk
Post surgery at risk
• Treatment
• Oral or IV Vitamin K
Case 4
• A 54 year old male comes to emerg feeling
unwell.
• Exam
• Mild jaundice, some telangectasis on skin
• Mod ascites.
• CBC - Hgb 110 WBC 2.5 plat 68
• INR 1.6 Ptt 41 TT 25
• What is likely diagnosis ?
Hepatic dysfunction - Cirrhosis
• Liver makes and degrades
• Coagulation is affected by decreased
production and impaired degradation of
activated factors
• Chronic DIC
• Splenomegaly
• Trearment only if bleeding
• Liver transplant
Case 5
• 18 year old male scheduled for
tonsillectomy
• History of easy bleeding
• Exam normal no bruises
• CBC normal
• INR 1.1 PTT 45
• What is likely diagnosis ?
• How to diagnose ?
Hemophilia
• X linked bleeding disorders characterized by
spontaneous development of large hematomes in
deep tissues.
• May lead to joint bleeding, or into other closed
structures
• Joint cavity bleeding leads to deformed joints
• bleeding may be spontaneous or asssociated with
mild or moderate injury
Hemophilia types
• Hemophilia A
• absent or decreased factor VIII
• Hemophilia B
• lack of factor IX
• similar in symptoms to Hemophilia A
• Hemophilia A is 10 times more common
than hemophilia B
Genetics of Factor VIII
• Single chain polypeptide
• Produced mainly in Liver
• remember linked to VWf
•
•
•
•
Gene deletion - no factor VIII
Point mutation - abnormal factor VIII
Base deletion - Abnormal Factor VIII
Coded on X chromosome -therefore only males
affected (transmitted by female carriers)
Hemophilia types
• Subclassified by level of factors
• Levels correspond to clinical symptoms
• Mild
• Moderate
• Severe
5-30% factor activity
1-5% activity
<1% activity
Hemophilia - Clinical Picture
• Mild- do not develop spontaneous bleeding, but
do bleed after injury or surgery
• Many patients have sever disease
• Joint Bleeding results in severe disability
• hemarthroses
• chronic arthritis
• muscle bleeds
• Social, economic,psychological problems
Case 6
•
•
•
•
•
17 year old girl with mennorhagia
History of easy bruising
Possible history of easy bruising
CBC normal
INR 1.1 PTT 32 (2 sec prolonged)
• What is diagnosis
• How to diagnose ?
• Treatment ?
Von Willebrand’s Disease
•
•
•
•
Most frequent inherited bleeding disorder
1% - 1/100 of western population
less severe than hemophilia
Disease results from a decrease or absence
of Von Willebrand factor for platelet
adhesion
• Affects primary hemostasis
Von Willebrand’s Disease and Factor VIII
• VW factor produced in megakaryocytes and
endothelial cells
• Coded on chromosome 12
• Autosomal dominant inheritance
• Large molecule, and multimeric
• Monomers undergoglycolisation and
multimerization before secretion
• Different multimer size = disease
Von Willebrand’s Disease and Factor
• VW is carrier for factor VIII
• Factor VIII-VWf complex
• Factor VIII protein carried in circulation as
complex with VWf
• Reacts with platelet via GP Ib
• Therefore can be problems with platelets
and factor VIII
Clinical features of Von Willebrand’s Disease
• Generally mild bleeding - often
unrecognized until surgery or injury
• epistaxis, menorrhagia, easy bruising, dental
and post operative bleeding
• Can be severe in certain types
• Requires accurate diagnosis
• Requires specific treatment
VW -types
• Type I
• most frequent, quantitave defect (decreased
VWf )
• Type II
• qualitative defect (abnormal VWf )
• Type III
• severe, rare, (absence of VWf )
How to diagnose Von Willebrands disease
•
•
•
•
Clinical history
Factor VIII level
Bleeding time
Measure VWf and perform aggregation
tests
• Do gel electrophoresis for multimers
Anti platelet agents
• ASA
• Not likely to create problems
• Safer to give if there for cardiovascular
reasons
•
•
•
•
Clopidogrel
If elective stop before.
Minimum 3 days
More than 5 days likely unnecessary
Massive bleeding
What are the critical issues ?
Questions
Massive
Transfusion
Protocol
The Ottawa Hospital
Ottawa, Ontario