Thrombotic Disorders

Question 1

what are thrombi?

Answer 1

clots that form within vessels and stay where they are

Question 2

what are emboli?

Answer 2

little chunks of clot that break off and float downstream to other places

Question 3

what are thrombotic disorders?

Answer 3

diseases that predispose a patient to forming abnormal clots (thrombi)

usually hereditary, and they usually involve an abnormality in the coagulation cascade

Question 4

what are the three general causes of thrombic disorders?

Answer 4

1. making too much of a coagulation factor
2. making a coagulation factor that can’t be turned off
3. making too little of a coagulation cascade inhibitor

Question 5

what’s usually the cause of thrombi?

Answer 5

risk factors like obesity, smoking and oral contraceptives

don’t start by looking for rare thrombotic disorders

Question 6

what is Virchow’s Triad

Answer 6

the causes of thrombosis and embolism

1. endothelial damage
2. abnormal blood flow
3. hypercoagulability

Question 7

what is endothelial damage?

Answer 7

Anything that rips up the endothelium increases the chances of clot formation.

atherosclerosis falls into this category, due to the damage that atherosclerotic plaques do to the endothelium

Question 8

what are the two types of abnormal blood flow?

Answer 8

stasis

turbulence

Question 9

what is abnormal blood flow?

Answer 9

normally, blood should flow in a nice, laminar, smooth fashion

this keeps the clotting factors away from each other and from platelets

Question 10

what is stasis?

Answer 10

abnormal blood flow

the velocity of flow drops to a point where coagulation factors can attach to each other and platelets, initiating the coagulation cascade

Question 11

what is turbulence?

Answer 11

abnormal blood flow

flow is chaotic, and little eddies form

blood is more static in these areas, allowing the factors and platelets to come into contact with each other

Question 12

what are examples of stasis?

Answer 12

1. varicose veins
2. atrial fibrillation = blood collects in the heart because it’s not pumping uniformly
3. prolonged immobilization (like in a plane ride, or after surgery)

Question 13

when does turbulent blood flow happen?

Answer 13

can occur when there’s a congenital heart defect

Question 14

what risk factors can cause hypercoagulablity?

Answer 14

• smoking
• oral contraceptive use
• adenocarcinoma (because the mucin in the tumor cells is a pro-coagulant)
• thrombotic disorders

they all stimulate the coagulation cascade in some way!!

Question 15

what are the risk factors for thrombosis?

Answer 15

1 risk factor is usually fine but if you start getting more than one you’re in trouble

• atherosclerosis
• trauma
• obesity
• prolonged immobilization
• varicose veins
• pregnancy
• oral contraceptive use
• atrial fibrillation
• carcinoma (especially adenocarcinoma)
• smoking

Question 16

what should raise suspicion that someone has a thrombotic disorder?

Answer 16

• the thrombosis in an abnormal place (“normal” places are leg veins and lungs)
• a history of recurrent thromboses
• there family members have had thrombotic episodes
• he patient is young (<50).
• the patient has had one or more miscarriages

Question 17

what are the hereditary thrombotic disorders?

Answer 17

1. factor V leiden
2. antithrombin deficiency
3. protein C and S deficiencies
4. factor II gene mutation

Question 18

what are the acquired thrombotic disorders?

Answer 18

antiphospholipid antibody syndrome

Question 19

what is factor V leiden?

Answer 19

most common of all the thrombotic disorders

caused by a point mutation in the factor V gene which makes the resulting factor V resistant to inactivation

so factor V Leiden participates in the coagulation cascade just fine – but it can’t be turned off, and the cascade continues to make fibrin when it shouldn’t

Question 20

what is antithrombin deficiency?

Answer 20

super rare genetic defect

patients make too little antithrombin

AT is a super-important inhibitor of the coagulation cascade

Question 21

what are protein C and S deficiencies?

Answer 21

super rare genetic defects

they are inhibitors of the coagulation cascade so if they’re missing, it’s going to be pretty hard to turn the cascade off, and the result is too much fibrin formation

Question 22

what is factor II gene mutation?

Answer 22

rare genetic defect

patients make too much prothrombin

too much prothrombin leads to too much thrombin = lots of clotting

Question 23

what is antiphospholipid antibody syndrome?

Answer 23

the main acquired thrombotic disorder

patients for one reason or another make antibodies to phospholipids

these antiphospholipi antibodies wreak havoc on the endothelium and on platelets in complex ways, leading to a syndrome involving abnormal and excessive clotting