Thrombotic Disorders- Lecture

Question 1

Thrombophilias are _ disorders

Answer 1

Thrombophilias are clotting disorders

Question 2

The three common risk factors that make up Virchow’s triad and increase the risk of DVT are _ , _ , and _

Answer 2

The three common risk factors that make up Virchow’s triad and increase the risk of DVT are endothelial damage , abnormal blood flow or venous stasis , and hypercoagulability

Question 3

_ is a cause of endothelial damage (virchow)

Answer 3

Atherosclerosis is a cause of endothelial damage (virchow)

Question 4

Abnormal blood flow or venous stasis (virchow) may be caused by:

Answer 4

• Prolonged immobilization
• Varicose veins
• Atrial fibrillation
• Cardiac valve stenosis

Question 5

Hypercoagulability (virchow) may be caused by:

Answer 5

• Smoking
• Oral contraceptives
• Pregnancy
• Malignancy
• Age
• Trauma/surgery

Question 6

What are some clinical indications that a thrombi is secondary to a thrombotic disorder?

Answer 6

• Thromboses in abnormal places
• History of recurrent thromboses
• Family history
• Less than 50 years old
• One or more miscarriages

Question 7

_ is a particular malignancy that is associated with DVTs due to its production of a mucin that acts as a procoagulant

Answer 7

Adenocarcinoma is a particular malignancy that is associated with DVTs due to its production of a mucin that acts as a procoagulant

Question 8

Name four hereditary thrombotic disorders:

Answer 8

1. Factor V Leiden
2. Factor II gene mutation
3. Protein C and S deficiencies
4. Antithrombin deficiency

Question 9

_ is an autoimmune condition that is most commonly idiopathic or acquired and leads to hypercoagulability and thromboembolitic events

Answer 9

Antiphospholipid antibody syndrome (APS) is an autoimmune condition that is most commonly idiopathic or acquired and leads to hypercoagulability and thromboembolitic events

Question 10

Explain APS and the two-hit hypothesis

Answer 10

• About 5% of the population has antiphospholipid antibodies without having APS
• An additional risk factor is needed to proceed to APS

Question 11

Clinical features of APS

Answer 11

Antiphospholipid antibody syndrome:
* Recurrent venous and arterial thromboses
* Recurrent fetal loss
* Pulmonary emboli
* Heart valve disease
* Nephropathy
* Livedo reticularis

Question 12

PT and PTT values are _ with APS due to _

Answer 12

PT and PTT values are prolonged with APS due to antibodies inhibiting coagultion in vitro (the medium used is a phospholipid)
* Mixing study does not correct PT/ PTT

Question 13

If the PT/ PTT remains prolonged after a mixing study, we can confirm an APS diagnosis by adding _

Answer 13

If the PT/ PTT remains prolonged after a mixing study, we can confirm an APS diagnosis by adding excess phospholipid to soak up the antiphospholipid antibodies

Question 14

False positive syphilis screens may be seen in patients with _

Answer 14

False positive syphilis screens may be seen in patients with anticardiolipin antibodies (APS)

Question 15

We can use _ testing to determine the type of antiphospholipid antibody syndrome

Answer 15

We can use ELISA testing to determine the type of antiphospholipid antibody syndrome
* Lupus anticoagulant
* Anticardiolipin antibodies
* Anti-beta 2 glycoprotein I antibodies

Question 16

_ is associated with an inability of Protein C to cleave the mutated factor V protein

Answer 16

Factor V Leiden is associated with an inability of Protein C to cleave the mutated factor V protein

Question 17

_ is the most common hereditary thrombotic disorder

Answer 17

Factor V Leiden is the most common hereditary thrombotic disorder

Question 18

Atypical clotting locations include:

Answer 18

• Mesenteric veins
• Portal veins
• Hepatic veins (Budd Chiari)
• Ovarian veins
• Renal veins

Question 19

Factor II is activated by factors _ + _

Answer 19

Factor II is activated by factors Va + Xa

Question 20

Factor II gene mutation is a point mutation _ that causes _

Answer 20

Factor II gene mutation is a point mutation G20210A that causes an overproduction of prothrombin
* G –> A

Question 21

Protien C and S work together to stop clotting by inactivating factors _ and _

Answer 21

Protein C and S work together to stop clotting by inactivating factors VIII and V

Question 22

Protein (C/ S) is the sidekick and (C/ S) cleaves

Answer 22

Protein S is the sidekick and Protein C cleaves

Question 23

Protein C and S deficiency can be inherited or acquired from _ , _ , _

Answer 23

Protein C and S deficiency can be inherited or acquired from liver disease , vitamin K deficiency , chemotherapy

Question 24

Warfarin blocks the enzyme _

Answer 24

Warfarin blocks the enzyme vitamin K epoxide reductase

Question 25

The reduced form of vitamin K is needed for _ and activation of _ factors

Answer 25

The reduced form of vitamin K is needed for **gamma-carboxylation of glutamate** and activation of **X, IX, VII, II, protein C and protein S** factors

Question 26

Why should warfarin not be given without a heparin bridge?

Answer 26

* Wafarin inhibits X, IX, VII, II and Protein C and S * Protein C and S have the shortest half life so when they are first to be depleted, the patient ends up in a hypercoagulable state * This increases the risk of thrombosis * Microthrombi in cutaneous and subcutaneous venules can lead to lessions --> bullae --> necrosis

Question 27

Treatment for warfarin skin necrosis includes _ , _ , and _

Answer 27

Treatment for warfarin skin necrosis includes **stop warfarin** , **provide vitamin K** , and **fresh frozen plasma** (replenish C and S), **start heparin product**

Question 28

Purpura fulminans is also known as _

Answer 28

Purpura fulminans is also known as **Waterhouse-Friderichsen syndrome** * It is essentially warfarin skin necrosis but without warfarin

Question 29

Waterhouse-Friderichen syndrome is _

Answer 29

Waterhouse-Friderichen syndrome is **acute, widespread thrombi causing rapid progression of bruising and skin erythema to black-blue bullae and necrotic plaque**

Question 30

Purpura fulminans and TTP and ITP can present very similarly, however, _ has the most rapid progression

Answer 30

Purpura fulminans and TTP and ITP can present very similarly, however, **Waterhouse-Friderichsen** has the most rapid progression

Question 31

Antithrombin deficiency can be acquired or hereditary; it is inherited in _ pattern

Answer 31

Antithrombin deficiency can be acquired or hereditary; it is inherited **autosomal dominant**

Question 32

Antithrombin deficiency can be acquired from decreased production like in _ , increased use like in _ , or loss of antithrombin from _

Answer 32

Antithrombin deficiency can be acquired from decreased production like in **liver disease** , increased use like in **trauma, surgery** , or loss of antithrombin from **nephrotic syndromes**

Question 33

Type I antithrombin deficiency is a _ mutation that results in _

Answer 33

Type I antithrombin deficiency is a **nonsense mutation** that results in **complete loss of antithrombin function**

Question 34

Type II antithrombin deficiency is a _ mutation that results in _

Answer 34

Type II antithrombin deficiency is a **point mutation** that results in **defective antithrombin protein** * End up with normal circulating levels, just not as functional * This is more commont than type I

Question 35

_ is a unique consequence of antithrombin deficiency that can often lead to its diagnosis

Answer 35

**Heparin resistance** is a unique consequence of antithrombin deficiency that can often lead to its diagnosis * Heparin normally induces a conformational change in AT that increases its affinity for X and II * It cannot enhance this anticoagulation in people with AT deficiency