Clotting disorders

Question 1

thrombosis =

Answer 1

an abnormal clot

Question 2

thrombosis risk factors

Answer 2

Endothelial damage
Stasis
Hypercoagulability

Question 3

Endothelial damage is a result of

Answer 3

often atherosclerosis (hypertension, hyperlipidemia, smoking, obesity)

Question 4

Stasis

Answer 4

Immobilization
varicose veins
cardiac dysfunction

Question 5

Hypercoagulability

Answer 5

Trauma/surgery
Carcinoma
Estrogen/postpartum
Thrombotic disorder

Question 6

When should you worry and your patient has a throbmus?

Answer 6

No obvious cause
Family history
weird location
recurrent
young patient 
miscarriages

Question 7

Hereditary thrombotic disorders

Answer 7

Factor V Leiden
ATIII deficiency
Protein C deficiency
Protein S deficiency
Factor II gene mutation
Homocysteinemia

Question 8

Acquired thrombotic disorder

Answer 8

Antiphospholipid Ab

Question 9

About Factor V Leiden

Answer 9

Most common cause of unexplained thromboses
Point mutation in factor V gene
Factor V cannot be turned off
Need GENETIC testing for diagnosis

Question 10

What happens when point mutation occurs in Factor V?

Answer 10

Participation in clotting cascade is not stopped because V cannot be cleaved by protein C

Question 11

How common is factor V leiden?

Answer 11

Half of patients with unexplained thrombosis

5% of caucasians

Question 12

Risk of getting a clot with Factor V Leiden?

Answer 12

Heterozygotes 7x normal

Homozygotes 80x normal

Question 13

How do you diagnose Factor V Leiden?

Answer 13

PTT and INR are not helpful (will be normal, cascade will be fine, test stops when fibrin forming)
GENETIC TESTING

Question 14

How do you treat Factor V Leiden?

Answer 14

Don’t.. unless thrombosis
Then: anticoag for awhile
If multiple episodes (or other risk factors) long term anticoag

Question 15

AT III deficiency - about

Answer 15

At III is a natural coag
Potentiated by heparin
Lots of gene mutations exist
Very rare

Question 16

Antithrombin III

Answer 16

Natural anti coag
Inhibits IIa, VIIa, IXa, Xa, XIa (no PCR assay)
Potentiated by heparin

Question 17

What is wrong with the AT III gene?

Answer 17

Mutated gene produces less ATIII
Rare
No genetic testing

Question 18

Risk of clots in AT III deficiency

Answer 18

Homozygotes - fatal
Heterozygotes - half get clots
Heparin won’t work
Antithrombin concentrates required

Question 19

Protein C and S deficiencies

Answer 19

Natural coagulants
C is also fibrinolytic and anti inflammatory
warfarin induced skin necrosis
C deficiency is rare, S super rare

Question 20

Protein C

Answer 20

anticoagulant - Inactivates Va and VIIIa
Fibrinolytic - promotes t-PA action
anti-inflammatory - keeps cytokine levels low

Question 21

What is wrong with gene in protein C deficiency

Answer 21

Mutated gene produces less protein C (or defective)

Diagnosis via functional testing

Question 22

Risk of clots in protein C deficiency

Answer 22

7x normal (heterozygotes)
Unique risks: warfarin skin necrosis, purpura fulminans

Question 23

Coumadin and Protein C

Answer 23

Coumadin wipes out protein C quickly because short half life

Question 24

Coumadin and protein C deficiency

Answer 24

Be careful - coumadin wipes out protein C and become hypercoagulable

Question 25

Purpura Fulminans

Answer 25

Thrombotic state + vascular injury Net result : skin necrosis Associated with : protein C and S def. and sepsis Treatment: protein C (last resort)

Question 26

Protein S deficiency

Answer 26

So rare, same as C

Question 27

Factor II

Answer 27

prothrombin

Question 28

Factor II gene mutation

Answer 28

makes too much prothrombin

Question 29

Hyperhomocysteinemia

Answer 29

too much cysteine - thromboses MTHFR mutation B12/folate deficiency not so rare

Question 30

Homocysteinuria

Answer 30

Rare metabolic disorder

Question 31

What is so bad about cysteine (in context of hyperhomocysteinemia)

Answer 31

Toxic to endothelium by forming ROS and Interferes with NO (visodilator and antithrombotic)

Question 32

Heterozygous homocysteinemia

Answer 32

Increase thrombosis, premature atherosclerosis (venus 2x risk, arterial 10x normal risk)

Question 33

homocysteinemia in B12 deficiency

Answer 33

less worrisome but still need to watch for other risk factors

Question 34

Antiphospholipid Antibodies

Answer 34

Autoantibodies against phospholipids Falsely prolonged INR May cause thromboses Antiphospholipid syndrome is serious

Question 35

What are antiphospholipid ab?

Answer 35

``` IgG ab against phospholipids 3 variants (anticadiolipin, lupus anticoag, antibodies against other molecules) ```

Question 36

What do antiphospholipid ab do?

Answer 36

Bind to phospholipids Screw up coag tests (bind up PTT, PT reagents so spec. cannot clot, test results appear prolonged) Screw up DAT and syphilis tests

Question 37

Antiphospholipids ______ coagulation in vivo

Answer 37

promote

Question 38

Antiphospholipids ______ coagulation in viro

Answer 38

Inhibit

Question 39

Who develops antiphospholipid ab?

Answer 39

Children (infection - mild risk) Adults (autoimmune disorders - moderate risk) Elderly (drugs - no risk)

Question 40

Antiphospholipid Antibody Syndrome

Answer 40

``` Recurrent thrombosis Recurrent Spontaneous Abortions Increased Risk of Stroke Pulmonary HT Renal failure ```