Coagulation Cases

1. 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. PTT = XII, XI, IX, VIII PT = VII 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 Congenital Factor VIII, IX Acquired Liver diease Warfarin • Inhibitor Lupus Heparin Acquired Ab vs VIII, IX

14. Defn vs Inhibitor:Mixing studies

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 • 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= 25 - 36)

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 • PT = 11 seconds (ref = 11.4 seconds) • aPTT = 29 seconds (ref = 23 - 32 seconds) • FBC • WCC – 8 • Hgb – 13 • Plt – 9 (N = 150-450)

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 50-150%)

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- 25-36sec)

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