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

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

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.

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).

Plt vs factor

Laboratory Evaluation of Hemostasis

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

Platelets number vs function

PT/PTT:

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

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

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

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

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

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

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.

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

What do we know? Diagnosis? Special investigations?

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.

Mode of inheritance:

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)

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

Both PT and PTT prolonged?? Diagnosis Special Investigations

Results

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

Rash on legs

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

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.

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.

Lab results PT = 11.2 seconds (ref = 10-15) aPTT = 42 seconds (ref = 25-36) FBC - normal Factor VIII (enzymatic) 45% (ref 50-150%)

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

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

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

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)

???

Treatment? Stop heparin! Antidote – protamine sulphate

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

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

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

Normal FBC,PT/PTT vWD Plt dysfunction Vasculitis

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

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

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