1. Division of Clinical Hameatology
Coagulation Cases
Mike Webb
Division of Clinical Hameatology
1 March 2010

2. So what does it take to make a healthy blood clot?
Platelets
The blood vessels themselves
Clotting factors

3. Good vs bad Healthy blood clot:
 At the site of a broken blood vessel, the point of injury.
 A healthy clot stays put and does not cause a runaway clotting episode.
A healthy clot knows when it's time to dissolve.
Pathological clot:
It causes vascular narrowing or outright occlusion.
Often inappropriately forms
It may embolize.

4. Evaluation of haemostasis
History:
Site
Recent onset vs. life-long pattern.
Alcohol consumption.
Use of NSAIDs.
Males and females equally affected?
Grandparents?
Does it skip a generation?
Bad arthritis of the ankles or knees in a male grandparent may indicate a clotting factor problem (IX or VIII).

5. Plt vs factor

6. Laboratory Evaluation of Hemostasis

7. Laboratory Evaluation of Hemostasis
FBC and smear
PT/PTT
Plt function
Specialized tests
Quality of the blood specimen
Volume
Clot
Hemolyzed

8. Platelets number vs function

9. PT/PTT:

10. Simple!!
PTT = XII, XI, IX, VIII
PT = VII
Common = I,II,V,X

11. PT = VII
PTT = XII, XI, IX, VIII
Common = I,II,V,X

12. Prolonged PT or PTT Not enough of a single or combination of factors.
Does NOT tell you why.

13. Why? Deficency Inhibitor Congenital Acquired Lupus Heparin
Factor VIII, IX
Acquired
Liver diease
Warfarin
Inhibitor
Lupus
Heparin
Acquired Ab vs VIII, IX

14. Defn vs Inhibitor: Mixing studies
Pt (defn)
Normal Plasma
PT/PTT = normal
Pt (inhibitor)
Normal Plasma
PT/PTT = abnormal

15. Which factor?
PT = VII
PTT = XII, XI, IX, VIII
Common = I,II,V,X

16. Tommy active four-year old
Scalp wound that won't heal.
Bled more than expected from his circumcision.
The mother's father had terrible arthritis of his knees and ankles:
He was wheelchair-bound by the age of 45.
Died of a 'bleeding ulcer' at age 51.
Physical exam – normal except for scalp
wound.

17. Lab results FBC - normal PT = 11 sec (ref = 10 - 15sec)
PTT = 54 sec (ref = 25-36sec)
PT = VII
PTT = XII, XI, IX, VIII
Common = I,II,V,X

18. What do we know?
Diagnosis?
Special investigations?

20. Hemophilia Congenital defn of either A usually more common and severe
VIII = A
IX = B
A usually more common and severe
Both VIII and IX deficiencies are sex-linked recessive traits.

21. Mode of inheritance:

22. Forty-eight year-old man with ease of bruising.
Mr. BA complains of ease of bruising
He was fine until about 8 months ago.
FBC normal with round macrocytes.
PT is 18 sec (N=10-15)
aPTT is 48 sec (N= )

23. PT/PTT prolonged
PTT = XII, XI, IX, VIII
PT = VII
Common = I,II,V,X

24. Both PT and PTT prolonged??
Diagnosis
Special Investigations

25. Results

26. Tiffany is a 15 year-old girl with a rash
  Her mom says she had a cold about 2 weeks ago.
She was fairly sick with upper respiratory symptoms for about 3 days.
She improved quickly, and returned to school.
Now she has a 'rash' from navel down both legs.
Today, she is otherwise healthy and is afebrile.
Tiffany has a little sister who is well.
No one else in the family is sick.
Exam NAD but for rash

27. Rash on legs

28. Lab tests FBC PT = 11 seconds (ref = 11.4 seconds)
aPTT = 29 seconds (ref = seconds)
FBC
WCC – 8
Hgb – 13
Plt – 9 (N = )

29. Viral exanthem vs. petechiae?
Tiffany's spots are regional, not all over her body.
In fact, they seem gravity dependent.
They vary slightly in color from red to blue-brown.

31. Mrs. KL 28 yr old teacher complains of ease of bruising
  Bleeds excessively with dental procedures
She also has menorrhagia
She claims if she takes just one aspirin, she will bruise for a week.
Her family history is significant for bleeding problems.
Some of her relatives, both male and female, have a bleeding tendency.
She's very concerned because an aunt supposedly died in childbirth from a hemorrhage.

32. Lab results PT = 11.2 seconds (ref = 10-15)
aPTT = 42 seconds (ref = 25-36)
FBC - normal
Factor VIII (enzymatic)
45% (ref %)

33. von Willebrand disease
VWD - most common inherited bleeding disorder. (1% of population)
Abnormality in quantity or quality of vWF
Binds platelets to endothelium
Protects Factor VIII from degredation

34. vWD
Symptoms are very mild or lack of recognition (heavy menstrual bleeding)
Bleeding symptoms:
Easy bruising
Skin bleeding
Prolonged bleeding from mucosal surfaces
May mimic hemophilia
Ingestion of aspirin or NSAIDS may precipitate bleeding

35. vWD Lab tests: Normal FBC Normal PT Normal or prolonged PTT
Specialized tests
von Willebrand factor
vWF Antigen: decreased
Ristocetin cofactor activity
Platelet aggregation to Ristocetin

36. 50 yr old man for hip replacement
On heparin pre-op for DVT prophylaxis
Malena stool and epigastic pain
FBC – normal
PT – 18 (N-10-15sec)
PTT >180 (N sec)

37. ???

38. Treatment?
Stop heparin!
Antidote – protamine sulphate

39. Tommy Late bleeder Known with haemophilia A
28 yrs old presents with painful knee
No improvement to factor replacement

40. Mixing studies
PT 14 (10-15sec)
PTT 105 to 104 (25-36sec)
Factor VII = 2%
NOW WHAT???

41. Late bleeder
PT = VII
PTT = XII, XI, IX, VIII
Common = I,II,V,X

42. Normal FBC,PT/PTT
vWD
Plt dysfunction
Vasculitis

43. Prolonged PTT (normal PT)
Intrinsic pathway abn:
Hemophilia
vWD
Heparin
Lupus anticoag
Auired inhibitors

44. Prolonged PT (normal PTT)
Extrinsic pathway:
Vit K defn
Liver disease

45. Prolonged PT and PTT Combined defn Warfarin Heparin DIC Liver disease
Deficency / inhibitor of common pathway