Coagulation Cases

Mike WebbDivision 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, VIIIPT = 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. DeficencyCongenital

Factor VIII, IX

Acquired Liver dieaseWarfarin

2. InhibitorLupusHeparinAcquired Ab vs VIII, IX

Defn vs Inhibitor:Mixing studies

Which factor?

PTT = XII, XI, IX, VIII

PT = VII

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 scalpwound.

• Lab results• FBC - normal • PT = 11 sec (ref = 10 - 15sec) • PTT = 54 sec (ref = 25-36sec)

PTT = XII, XI, IX, VIII

PT = VII

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.

• 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 prolongedPTT = 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– 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

PTT = XII, XI, IX, VIII

PT = VII

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