Lecture 7: Clotting Disorders

Question 1

Venous thromboembolism (VTE) consists of

Answer 1

(1) Deep vein thrombosis (DVT)

2) Pulmonary embolism (PE

Question 2

Arterial thrombosis consists of

Answer 2

(1) Stroke
(2) Intrabdominal arterial thrombosis
(3) Myocardial infarction

Question 3

What is Virchow’s Triad?

Answer 3

(1) Endothelial injury
(2) Abnormal blood flow
(3) Hypercoagulability

Question 4

Clinical Presentations for Clotting Disorders

Answer 4

(1) Predominantly VTE (PE/upper and lower extremity DVT)
(2) Thrombosis of unusual locations
(3) Recurrent fetal loss, preeclampsia
(4) Stroke, MI
(5) Coumadin skin necrosis
(6) Neonatal purpura fulminans

Question 5

Why is VTE important?

Answer 5

PE is the most common preventable cause of in-hospital deaths
- Associated with long-term risks (post-phlebitic syndrome, chronic pulmonary hypertension, prolonged hospital stay, risk/inconvenience of systemic anticoagulants)

Question 6

Thrombophilia: Definition

Answer 6

Underlying predisposition to thrombosis

• not a disease itself but may be associated with disease, drug exposure, condition
• inherited or acquired

Question 7

Approx how many people with VTE have either an inherited or acquired thrombophilia?

Answer 7

80%

Question 8

What is Antithrombin III

Answer 8

A serine protease inhibitor (SERPIN) that inhibits multiple clotting factors
- t1/2 is 60-70hrs

Question 9

Where is Antithrombin III synthesized?

Answer 9

Liver

Question 10

What does ATIII work well with? Why?

Answer 10

Heparin; inhibitory activity potentiated 1000x

Question 11

What is congenital ATIII deficiency?

Answer 11

Congenital deficiency inherited in autosomal dominant pattern (homozygous fatal in utero)
- Dx: ATIII activity and Ag reference range 80-130%

Question 12

What is Acquired ATIII deficiency?

Answer 12

(1) Impaired synthesis (liver dz, malnutrition, IBD, burns), prematurity
(2) Increased consumption (acute thrombosis, heparin, DIC, sepsis, nephrotic syndrome)

Question 13

ATIII deficiency: Treatment

Answer 13

(1) High doses of heparin
(2) Direct thrombin inhibitors
(3) Recombinant ATIII

Question 14

What does ATIII deficiency predispose you to?

Answer 14

Venous thrombosis, esp. during preganacy

Question 15

What is Protein C?

Answer 15

Vit K dependent protein synthesized in the liver

• t1/2 is 6-7hrs (SHORTEST)
• is a zymogen precursor to activated Prot C (APC)

Question 16

Protein C is a potent anticoagulant through inactivation of what?

Answer 16

FVIIIa and FVa

Question 17

What is congenital Protein C deficiency?

Answer 17

Autosomal dominant
Dx: Protein C activity
Must of be off warfarin for at least 1 week

Question 18

What is acquired Protein C deficiency?

Answer 18

• Decreased synthesis (liver dz, vit K deficiency, warfarin)

- Increased turnover (acute thrombosis, DIC, sepsis, plasma exchange)

Question 19

What does Protein C deficiency predispose you to?

Answer 19

Venous thrombosis

Question 20

What is Protein S?

Answer 20

Vit K dependent protein synthesized in the liver, endothelium, megakaryocytes
- t1/2 is 96hrs

Question 21

What does Protein S inhibit?

Answer 21

Cofactor of APC-mediated inhibition of FVIIIa and FVa

Question 22

What is Protein S deficiency?

Answer 22

• Decreased production (vit K def, warfarin, liver dz)
• Consumption (acute thrombosis, sepsis, DIC)
• Pregnancy, ocps, nephrotic syndrom

Question 23

What does Protein S deficiency predispose you to?

Answer 23

Venous thrombosis and pregnancy complications

Question 24

Prothrombin 20210 Gene Mutation: Dx

Answer 24

Direct DNA based testing