Hypercoaguable states

Question 1

G to A mutation at base pair 1691 of coagulation factor V which imparts resistance to cleavage by (1)

Answer 1

1. activated protein C

refers to factor V Leiden

Question 2

Heterozygotes have a 5x increased risk of thrombosis and

homozygotes a 50x increased risk

Answer 2

Factor V Leiden

Question 3

Resistance to cleavage by activated protein C leads to?

Answer 3

increased Factor V and increased thrombin

Question 4

hypercoagulability which is also called thrombophilia represents a state of increased risk for ?

Answer 4

thrombosis to occur and in particular for venous thrombosis.

Question 5

3x increased risk of

venous thrombosis

Answer 5

Prothrombin 20210 mutation

Question 6

single G to A mutation at position 20210

Answer 6

Prothrombin 20210 mutation

Question 7

elevation of normal (1) levels occurs in Prothrombin 20210 mutation

Answer 7

1. prothrombin

Question 8

Elevated plasma (1) levels from inherited deficiency of cystathione β‐ synthetase imparts an increased risk for (2)

Answer 8

1. homocysteine

2. both arterial and venous thrombosis, and atherosclerosis

Question 9

It is believed that elevated homocysteine levels cause (1) and convert the normal anticoagulant surface of the (2) to a procoagulant state.

Answer 9

1. endothelial cell dysfunction
2. endothelial cell

refers to cystathione β‐ synthetase deficiency

Question 10

activated protein C (APC) is a (1) dependent enzyme whose function is to inactivate (2) and stimulate (3)

Answer 10

1. vitamin K
2. factor Va and factor VIIIa
3. fibrinolysis

Question 11

There are several clinical syndromes associated with protein C deficiency including ?

Answer 11

Heterozygotes: venous thrombosis; Coumadin skin necrosis.

Homozygotes:
neonatal purpura fulminans.

Question 12

Homozygous deficiency is not compatible with life and heterozygotes are at increased risk for
venous thrombosis and require lifetime anticoagulation therapy

Answer 12

anti-thrombin III deficiency

Question 13

cofactor for activated protein C (APC)

Answer 13

Protein S

Question 14

inhibitor of each of the coagulation factor enzyme

systems

Answer 14

antithrombin

Question 15

The level of protein S is regulated by (1) of the complement system and is reduced in inflammatory
states due to binding to this complement component.

Answer 15

1. C4b

Question 16

Thus when the hereditary deficiency of protein S is combined with these states it poses a very
serious risk for ?

Answer 16

venous thrombosis

Question 17

What other factors reduce the level of protein S?

Answer 17

inflammation due to C4b complement component
pregnancy
estrogens

Question 18

What non-inherited diseases also pose increased risk of venous thrombosis?

Answer 18

Obesity, cardiac, neurologic disease; oral contraceptive use; pregnancy; malignancy; surgery; heparin induced thrombocytopenia

Question 19

Patients with idiopathic DVT or pulmonary embolism have a 3x increased risk of having (1) within 3 years

Answer 19

1. an occult malignancy

Question 20

caused by antibodies against epitopes on proteins which are in some way “unmasked” by phospholipids

Answer 20

Antiphospholipid antibody syndromes

Question 21

Secondary antiphospholipid antibody syndrome is associated with autoimmune disease most notably?

Answer 21

Lupus Erythematosus.

Question 22

Manifestations of APS

Answer 22

recurrent arterial and venous thromboemboli; thrombocytopenia; DVT, PE, cerebrovascular events (stroke, TIA), first trimester fetal loss (recurrent); cerebral vein thrombosis, Budd‐Chiari syndrome, digital infarcts and myocardial infarction

Question 23

Three types of antiphospholipid antibodies are found in APS:

Answer 23

1. Anti‐cardiolipin antibodies
2. Antibodies to beta‐2 glycoprotein
3. “lupus anticoagulant”

Question 24

The lupus anticoagulant is so named because it produces (1) however note that while this in vitro effect is (1) the in vivo effect is (2)

Answer 24

1. prolongation of the PTT assay

2. thrombosis

Question 25

A test called (1) is prolonged in patients with lupus anticoagulant. The test corrects to normal not with addition of normal plasma (as it would in a factor deficiency) but only with addition of (2)

Answer 25

1. Russel Viper venom test

2. excess phospholipid.

Question 26

White thrombi occurs in (1) system and is composed of (2)

Answer 26

1. high flow arterial

2. platelets and WBCs

Question 27

Red thrombi occurs in (1) system and is composed of (2)

Answer 27

1. low flow venous

2. initial platelet plug, RBCs and thrombin

Question 28

Arterial thrombosis is associated with a number of conditions including?

Answer 28

MI, stroke, PVD, ischemic bowel, vascular disease, DM, hyperlipidemia, hypercholesterolemia, vasculitis, heparin induced thrombocytopenia, TTP, HUS, Purpura fulminas, myeloproliferative neoplasms

Question 29

homologous with plasminogen, blocks LDL from its clearance receptor

Answer 29

lipoprotein A

Question 30

inhibits plasminogen activation by preventing it from binding to fibrin and cells

Answer 30

lipoprotein A

Question 31

increases atherogenesis, decreases fibrinolysis; risk factor for arterial thrombosis

Answer 31

lipoprotein A

Question 32

Elevated due to enzyme defects and deficiencies of B12, folate, B6

Answer 32

plasma homocysteine

Question 33

Key risk factors for arterial thrombosis?

Answer 33

lipoprotein A and plasma homocysteine

Question 34

Treatment of arterial thrombosis caused by elevated levels of homocysteine

Answer 34

folic acid

Question 35

Treatment of arterial thrombosis

Answer 35

ASA and anti platelet agents
Glycoprotein IIb/IIIa antagonists
Anti fibrin agents –heparin and low MW heparin

Question 36

Factors which additionally increase risk of thrombosis, particularly venous thrombosis, in patients with inherited thrombotic states?

Answer 36

pregnancy, smoking, immobilization

Question 37

Dysfibrinogenemia

Answer 37

accelerated clotting

Question 38

Dysplasminogenemia

Answer 38

reduced plasmin levels