2. Bleeding Disorders For Surgeons
J. Bormanis

3. 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

4. Clinical Approach When did it start ? Dental history
Spontanous bruising
Bleeding at surgery
Bleeding into joints
Menstrual bleeding
Epistaxis
One site only? Where ? When ?

5. High yield questions Family history Pattern of bleeding - where
Difficult to stop or
Re-bleeds
Drug history
Alcohol intake
Co Morbid disease

6. 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

7. Laboratory testing
History and physical
Type of tests guided by clinical features
Screening tests
Further tests
Definitive tests

8. Normal Hemostasis

9. Screening Tests INR Extrinsic pathway
PTT (activated partial thromboplastin time)
intrinsic pathway
Thrombin time
final pathway
Platelet count
Bleeding time – PFA (not useful)

10. Laboratory tests further testing
INR
PTT
TT thrombin time
Factor assays
Tests of fibrinolysis
platelet count
Bleeding time
platelet function tests
Special tests

11. 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

12. Clinical Cases

13. Case 1 It is Friday at 4:40pm Lab calls
Your patient is being preped for urgent surgery.
INR 6.5
What to do ?

14. Why INR’s go out of control

15. 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 ?

16. Efficacy of route of administration

17. 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 hours.
1-2 mg will decrease INR to therapeutic
Level within hrs

19. Current practice
Sent as 2 vials in a 50 cc mini bag to infuse at 3c/min

20. 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 ?

21. 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 ?

22. ITP continued If mucosal bleeding platelets are less than 6
Needs action
Steroids
IVIG
Anti D
What about splenectomy
New treatments
Rituximab
TPO agonists

23. 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 Plat 345
INR 2.6 ptt 42
What is likely diagnosis
What to Do ?

24. 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

25. 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 plat 68
INR 1.6 Ptt 41 TT 25
What is likely diagnosis ?

26. 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

27. 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 ?

28. 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

29. Hemophilia types Hemophilia A Hemophilia B
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

30. 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)

31. Hemophilia types Subclassified by level of factors
Levels correspond to clinical symptoms
Mild % factor activity
Moderate 1-5% activity
Severe <1% activity

32. 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

33. 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 ?

34. 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

35. 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

36. 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

37. 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

38. VW -types Type I Type II Type III
most frequent, quantitave defect (decreased VWf )
Type II
qualitative defect (abnormal VWf )
Type III
severe, rare, (absence of VWf )

39. How to diagnose Von Willebrands disease
Clinical history
Factor VIII level
Bleeding time
Measure VWf and perform aggregation tests
Do gel electrophoresis for multimers

40. 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

41. Massive bleeding

42. What are the critical issues ?

43. Questions

44. Massive Transfusion Protocol
The Ottawa Hospital Ottawa, Ontario