Transcript Haema3 - Bleeding disorders case studies

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
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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:
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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
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FBC and smear
PT/PTT
Plt function
Specialized tests
Quality of the blood specimen
• Volume
• Clot
• Hemolyzed
Platelets number vs function
PT/PTT:
PTT = XII, XI, IX, VIII
Simple!!
PT = VII
Common = I,II,V,X
• PTT = XII, XI,
IX, VIII
PT = VII
Common = I,II,V,X
Prolonged PT or PTT
• Not enough of a single or combination of
factors.
• Does NOT tell you why.
Why?
1. Deficency
Congenital
Factor VIII, IX
Acquired
Liver diease
Warfarin
2. 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.
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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
• 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.
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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)
PTT = XII, XI, IX, VIII
PT/PTT prolonged
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.
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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
– 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
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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
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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
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VWD - most common inherited bleeding disorder. (1% of population)
Abnormality in quantity or quality of vWF
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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
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Lab tests:
Normal FBC
Normal PT
Normal or prolonged PTT
Specialized tests
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von Willebrand factor
vWF Antigen: decreased
Ristocetin cofactor activity
Platelet aggregation to Ristocetin
50 yr old man for hip replacement
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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
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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
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Combined defn
Warfarin
Heparin
DIC
Liver disease
Deficency / inhibitor of common pathway