Thrombophilia

Question 1

White clots

Answer 1

Arterial clots

More likely to be composed predominantly of platelets and fibrin

Clue to a thrombotic process primarily reflecting platelet activation (i.e. thrombosis w/ heparin-induced thrombocytopenia)

Question 2

Red clots

Answer 2

Venous clots

Composed predominantly of RBCs and fibrin

Question 3

What type of coagulation factors does antithrombin inhibit?

Answer 3

Serine protease coagulation factors (most important being Xa)

Most of the activated versions of the factors in the intrinsic pathway above factor X are also serine proteases and are also inhibited to some degree by
antithrombin

Question 4

Inheritance pattern of antithrombin deficiency

Answer 4

Autosomal dominant disorder

Question 5

Inherited antithrombin deficiency increases risk for?

Answer 5

Venous thromboembolic events (VTEs)

Patients with inherited antithrombin deficiency are relatively resistant to anticoagulation by heparin.

Question 6

Acquired antithrombin deficiency

Answer 6

Can occur in nephrotic syndrome (proteinuria) and in situations of activated coagulation (i.e. DIC, preeclampsia, sometimes liver disease, pregnancy, and oral hormonal contraceptives)

Question 7

Protein C is vit-K-dependent protein that participates in a feedback relationship w/ what complex?

Answer 7

Thrombomodulin complex

Question 8

What activates protein C

Answer 8

When the thrombin-thrombomodulin complex is formed - it activates protein C

Question 9

What factors does protein C inactivate?

Answer 9

Factors Va and VIIIa

Question 10

Inheritance pattern of protein C deficiency

Answer 10

Autosomal recessive

Question 11

First thrombotic event typically occurs before age 40. Protein C deficiency is seen in approximately 3% of patients with their first VTE and in 6-8% of families with thrombophilia

Answer 11

Heterozygous for protein C deficiency

Question 12

These individuals are born with DIC and have extensive venous and or arterial thrombosis with extremely low levels of protein C (less than 5%)

Answer 12

Children homozygous for protein C deficiency

Question 13

What adverse event can occur when Tx’ing a Pt who is heterozygous for protein C deficiency w/ warfarin

Answer 13

Warfarin-induced skin necrosis - tend to be at “end-vessels” like the fingertips and the areolae of the breasts

Question 14

Main cause of protein C resistance

Answer 14

Factor V Leiden mutation

Question 15

Protein S

Answer 15

Vit-k-dependent factor

Cofactor for protein C

Question 16

What can cause acquired protein S deficiency

Answer 16

Warfarin therapy or other vitamin K deficiency

Also protein S decreases during pregnancy and typically do not lead to VTE

Question 17

Inheritance pattern of protein S deficiency

Answer 17

Autosomal dominant

Question 18

Factor V Leiden is a mutation in factor V that affects the site at which ______ bind ______

Answer 18

Factor V Leiden is a mutation in factor V that affects the site at which protein C binds Va

Prevents protein C from inactivating Va

Most common inherited thrombophilic condition

Question 19

When do homozygous factor V Leiden Pt’s typically experience their first VTE event?

Answer 19

Prior to the age of 40 y/o

Question 20

What demographic is factor V Leiden most common?

Answer 20

European ancestry

Least common is persons of Asian/African ancestry

Question 21

Second-most common inherited thrombophilic defect

Answer 21

Prothrombin mutation (aka Factor II mutation)

Question 22

G20210A GOF mutation

Answer 22

Prothrombin mutation - increases prothrombin levels

Question 23

Cerebral venous sinus thrombosis

Answer 23

Particularly associated w/ prothrombin mutation (factor II mutation)

Question 24

Elevated factor VIII is a risk factor for?

Answer 24

Both VTE and arterial thrombosis

Question 25

Two primary mutations in MTHFR that cause hyperhomocysteinemia

Answer 25

C677T and A1298C

Homozygous C677T mutations can cause elevated homocysteine but primarily in Pt’s who are deficient in folate

Heterozygous and homozygous A1298C mutations do not cause elevated homocysteine

Question 26

Antiphospholipid syndrome

Answer 26

Elevated levels of antiphospholipid (APA) antibodies or anticardiolipin antibodies (aCL; an alternate methodology for the same phenomenon) in association with a qualifying clinical event.

Question 27

Catastrophic antiphosphollillpid syndrome

Answer 27

Multisystem small vessel ischemic occlusions that present as multisystem disease - lungs, kidneys, CNS, heart, and or skin

Requires immunosuppression and frequently plasmapheresis, in addition to anticoagulation

Question 28

Tx of APA/aCL levels

Answer 28

Tx w/ hydroxychloroquine may decreases APA/aCL levels

Does not work in patients without SLE or in triple-positive Pt’s

Question 29

Impaired primary fibrinolysis disorders

Answer 29

1. Dysfibrinogenemia: congenital or acquired (liver disease)
2. Increased plasminogen activator inhibitor
3. Plasminogen deficiency
4. Tissue plasminogen activator deficiency
5. Thrombomodulin deficiency (decreases protein C activation)
6. Tissue factor pathway inhibitor deficiency
7. Increased lipoprotein a (Lp(a) stimulates PAI activity)

Question 30

Major predictor of thrombosis in polycythemia vera

Answer 30

Elevated Hg/Hct (contributing to blood viscosity)

Question 31

Thrombotic locations associated w/ myeloproliferative disorders

Answer 31

1. Cerebral vein
2. Intra-abdominal
3. Renal vein
4. Portal vein
5. Mesenteric vein
6. Hepatic vein

Also characteristic thrombotic locations of paroxysmal nocturnal hemoglobinuria

Question 32

Cerebral vein thrombosis is specifically characteristic of what?

Answer 32

Prothrombin mutation

Antiphospholipid syndrome

Question 34

Recurrent fetal loss is specifically characteristic of?

Answer 34

Antiphospholipid syndrome

Factor V Leiden mutation

Question 36

Migratory superficial thrombophlebitis (Trousseau syndrome) is characteristic of?

Answer 36

Adenocarcinomas, particularly of the G.I. tract and pancreas

Question 37

Neonatal purpura fulminas is specifically characteristic for?

Answer 37

Homozygous protein C or homozygous protein S deficiencies

Question 38

Thrombophilia disorders that have a definite association w/ arterial thrombosis:

Answer 38

1. Antiphospholipid antibody syndrome
2. Hyperhomocysteinemia
3. Myeloproliferative disorders (mostly polycythemia vera, essential thrombocythemia less so)

Question 39

When to order D-dimer

Answer 39

Question 40

Transient risk factors associated w/ venous thrombosis

Answer 40

1. Surgery
2. Trauma
3. Prolonged immobilization

Do not require testing for thrombophilia and should receive a three month course of anticoagulation.

Question 41

Duration of Tx for thrombotic events

Answer 41

Question 42

When to screen asymptomatic relative of Pt’s with VTE

Answer 42

Question 43

What is the predominant cause of activated protein C deficiency?

Answer 43

Factor V Leiden mutation

Question 44

Which of the following is associated w/ resistance to heparin therapy?

A. Factor V Leiden
B. G20210A mutation
C. MTHFR mutation
D. Antithrombin deficiency

Answer 44

D. AT-III deficiency

Question 45

What is the Dx criteria for antiphospholipid Ab syndrome?

Answer 45

Antibody against phospholipid/cardiolipin, β2 glycoprotein 1, or a lupus anticoagulant on two occasions three months apart.

Question 46

Which of the following clinical thrombotic syndromes is most strongly associated with antiphospholipid antibodies?

A. Neonatal purpura fulminans
B. Migratory superficial thrombophlebitis
C. Cerebral venous sinus thrombosis

Answer 46

C. Cerebral venous sinus thrombosis

Question 47

Current guidelines for thrombosis management recommend three months antigocagulation w/ no testing for specific thrombophilic disorders in what DVT occurrences?

Answer 47

Transient causes of DVT:

Surgery
Trauma
Immobility

Question 48

Answer 48

A. Decreased factor Xa

Having a prolonged prothrombin time and INR is same as having decreased factor VII

Question 49

What concludes a Dx of thrombophilia

Answer 49

Pt with two unprovoked DVT on separate instances

Question 50

What is the most common cause of arterial thrombosis?

Answer 50

Athersclerosis

Purely arterial events typically don’t affect PT/PTT and can be managed by platelet inhibition

Question 51

Answer 51

B. Neonatal purpura fulminans

Question 52

When would ATIII be decreased?

Answer 52

ATIII may be excreted curing nephrotic syndrome (associated w/ VTE)

Also may be acutely decreased in VTE, DIC, and sometimes in liver disease

Question 53

Answer 53

D. All of the above

Question 54

Answer 54

C. It is associated w/ phospholipid-dependent prolongation of clotting times

Question 55

Anticoagulant Tx in triple+ antiphospholipid Ab syndrome

Answer 55

Warfarin and DOACs contraindicated

Question 56

Answer 56

Levito reticularis

Question 57

Answer 57

C. Homozygous MTHFR C677T mutation

Question 58

In what disease is CD55/CD59 expression decreased?

Answer 58

Paroxysmal nocturnal hemobloginuria

Tx’d w/ anticomplement therapy (Decay accelerating factor and MAC inhibitor)

Question 59

Answer 59

B. Polycythemia vera

Thrombosis of mesenteric blood vessels is characteristic of myeloproliferative disorders

Question 60

Answer 60

B. DVT w/ not identifiable provoking agent

Rest are transient risk factors

Question 61

Answer 61

C. Normal D dimer after six months of anticoagulant Tx

Question 62

Factor V Leiden inheritance pattern

Answer 62

Factor V Leiden thrombophilia is inherited in an autosomal dominant manner.

Individuals who are heterozygous for the factor V Leiden variant have a slightly increased risk for VTE; individuals who are homozygous for the factor V Leiden variant have a much greater thrombotic risk.