Thrombotic disorders

Question 1

_ are clots that form within blood vessels, usually within the venous system

Answer 1

Thrombi are clots that form within blood vessels, usually within the venous system

Question 2

_ are pieces of clot that travel through the bloodstream to other places in the body where they become lodged in vessels

Answer 2

Emboli are pieces of clot that travel through the bloodstream to other places in the body where they become lodged in vessels

Question 3

A _ is a clot that forms in one of the deep veins of an extremity, such as the femoral or brachial vein

Answer 3

A deep vein thrombosis (DVT) is a clot that forms in one of the deep veins of an extremity, such as the femoral or brachial vein

Question 4

_ is most commonly caused by a piece of clot that breaks off from a DVT and lodges in the pulmonary arterial system

Answer 4

Pulmonary embolism (PE) is most commonly caused by a piece of clot that breaks off from a DVT and lodges in the pulmonary arterial system

Question 5

DVT patients usually present with _

Answer 5

DVT patients usually present with unilateral swelling of the leg often with pain and redness
* A palpable cord may be present

Question 6

What is a positive Homan sign

Answer 6

Positive homan sign: increased pain with passive dorsiflexion of the ankle with a DVT

Question 7

Three components of Virchow Triad

Answer 7

1. Endothelial damage
2. Hypercoagulable state
3. Abnormal blood flow/venous stasis

Question 8

Name some common causes of endothelial damage

Answer 8

• Smoking
• Hypertension
• Surgery
• Trauma

Question 9

Name some common causes of abnormal blood flow

Answer 9

Abnormal blood flow means blood either moves in a disorganized manner (turbulence) or slows down (stasis); this allows platelets and clotting factors to mingle
* Immobility
* Central venous catheters
* Varicose veins
* Atrial fibrillation

Question 10

Name some common causes of hypercoagulability

Answer 10

• Cancer
• Estrogen-containing contraceptives
• Pregnancy
• Obesity
• Hereditary disorders

Question 11

Postthrombotic syndrome is _ that occurs in up to 50% of patients after a DVT

Answer 11

Postthrombotic syndrome is chronic venous insufficiency that occurs in up to 50% of patients after a DVT
* Causes leg pain, edema, skin ulcers, discoloration

Question 12

_ is a massive iliofemoral DVT that completely occludes the venous drainage of the extremity –> edema, cyanosis, gangrene

Answer 12

Phlegmasia cerulea dolens is a massive iliofemoral DVT that completely occludes the venous drainage of the extremity –> edema, cyanosis, gangrene

Question 13

Patients with a low to moderate Wells score will first get _ testing for DVT; Patients with high Wells score will first get _ test

Answer 13

Patients with a low to moderate Wells score will first get D-dimer test for DVT; Patients with high Wells score will first get D-dimer and ultrasonography

Question 14

An elevated D-dimer test indicates _

Answer 14

An elevated D-dimer test indicates thrombus formation and breakdown

Question 15

D-dimer test has high (specificity/sensitivity) but low (specificity/sensitivity)

Answer 15

D-dimer test has high sensitivity but low specificity
* Smoking, infection, surgery, pregnancy can cause D-dimer to be positive

Question 16

_ is the best radiographic modality to diagnose DVT

Answer 16

Compression ultrasonography is the best radiographic modality to diagnose DVT
* If there is a clot present in the vein, the ultrasound transducer will fail to collapse the vein like a normal vein

Question 17

Patients at risk of DVT in the hospital normally get _ and _ as prophylaxis

Answer 17

Patients at risk of DVT in the hospital normally get low-molecular-weight heparin and leg-compression devices

Question 18

The prefered DVT treatment is _

Answer 18

The prefered DVT treatment is direct oral anticoagulants
* Ex: Rivaroxaban (Xarelto)
* Ex: Apixaban (Eliquis)

Question 19

_ is the most common hereditary thrombotic disease

Answer 19

Factor V Leiden is the most common hereditary thrombotic disease

Question 20

Factor V Leiden involves a _ mutation in the _ gene

Answer 20

Factor V Leiden involves a single-point mutation in the factor V gene
* Makes it invinsible to protein C cleavage and inactivation
* Causes fibrin to continuously be made –> clots

Question 21

Factor V Leiden is a _ to _ substitution; specifically at the location where _

Answer 21

Factor V Leiden is a arginine to glutamine substitution; specifically at the location where protein C cleaves factor V to inactivate it

Question 22

When should we be concerned about herditary thrombosis disorders?

Answer 22

• Young age (< 45)
• Family history
• Lack of risk factors

Question 23

How do we test for Factor V Leiden?

Answer 23

Add activated protein C to aPTT assay –> clotting time is prolonged in normal patients but not as prolonged in FVL patients

Question 24

Recurrent thrombosis and history of miscarriages are hallmark signs of _

Answer 24

Recurrent thrombosis and history of miscarriages are hallmark signs of antiphospholipid antibody syndrome

Question 25

Antiphospholipid antibodies can be idiopathic in some patients; more commonly they are caused by systemic disease like _

Answer 25

Antiphospholipid antibodies can be idiopathic in some patients; more commonly they are caused by systemic disease like **lupus (SLE)**

Question 26

Explain the two hit hypothesis of antiphospholipid antibody syndrome

Answer 26

1. Presence of antiphospholipid antibodies 2. Additional risk factor for hypercoagulability

Question 27

What are the common clinical manifestations of antiphospholipid antibody syndrome?

Answer 27

* Venous thrombosis * Arterial thrombosis * Pulmonary embolism * Stroke * Livedo reticularis * Fetal loss * Heart valve disease * Neuropathy *APS can affect any organ in the body because phospholipids are everywhere*

Question 28

_ is discoloration of skin in a reticular pattern due to obstruction of superficial capillaries

Answer 28

**Livedo reticularis** is discoloration of skin in a reticular pattern due to obstruction of superficial capillaries

Question 29

Patients with APS will have a _ PTT and PT

Answer 29

Patients with APS will have a **prolonged** PTT and PT and **thrombocytopenia** * Because antiphospholipid antibodies interfere with the reagents in coagulation studies * The antibodies inhibit coagulation in vitro but act as procoagulants in vivo * Ex: "lupus anticoagulant"

Question 30

How do we test for APS in the lab?

Answer 30

1. Mixing study: we expect PTT to remain prolonged 2. We can then add phospholipids to pick up some of the antibodies --> correction of clotting time confirms ddx 3. ELISA can identify nature of antibody specifically

Question 31

Name 3 ways of acquiring antithrombin deficiency

Answer 31

1. **Liver disease (cirrhosis)**: decreased production of antithrombin 2. **Acute thrombosis, surgery, trauma**: consumption of antithrombin 3. **Nephrotic syndromes**: urinary loss of antithrombin

Question 32

Antithrombin deficiency will cause excessive clotting due to the inability for AT to shut off its normal clotting factors _

Answer 32

Antithrombin deficiency will cause excessive clotting due to the inability for AT to shut off its normal clotting factors **XIa, IXa, Xa, VIIa, IIa**

Question 33

Hereditary antithrombin deficiency is [inheritance pattern]

Answer 33

Hereditary antithrombin deficiency is **autosomal dominant**

Question 34

Type I antithrombin deficiency. is a _ that results from a _

Answer 34

Type I antithrombin deficiency. is a **complete loss of the mutant antithrombin** that results from a **nonsense mutation** at the AT gene

Question 35

Type II antithrombin deficiency is a _ that results from _

Answer 35

Type II antithrombin deficiency is a **functionally defective antithrombin** that results from **missense mutation** at a reactive site; defective antithrombin is still synthesized in normal levels

Question 36

Two key clinical features of antithrombin deficiency:

Answer 36

1. Increased risk of thrombosis 2. Heparin resistance

Question 37

Heparin mechanism of action:

Answer 37

**Heparin** works by *binding antithrombin* and inducing a conformational change that **increases the affinity of AT for thrombin and factor X** * Increases the inactivating ability of antithrombin and promotes anticoagulation

Question 38

We an use a _ assay to test for antithrombin deficiency; this is then followed by a _ test to measure the level of antithrombin antigen in the plasma

Answer 38

We an use a **heparin cofactor assay** to test for antithrombin deficiency; this is then followed by an **ELISA** to measure the level of antithrombin antigen in the plasma (and we can distinguish between type I and type II) * We do not commonly test for AT deficiency because it is very rare

Question 39

Factor _ is very important because it catalyes the conversion of fibrinogen to fibrin; if we have a mutation in this factor that causes its overproduction we tip the balance towards clotting

Answer 39

**Factor II (thrombin)** is very important because it catalyes the conversion of fibrinogen to fibrin; if we have a mutation in this factor that causes its overproduction we tip the balance towards clotting

Question 40

Most patients with an overproduction of factor II have a point mutation known as _

Answer 40

Most patients with an overproduction of factor II have a point mutation known as **G20210A** (guanine --> adenine)

Question 41

How common is factor II genetic mutation?

Answer 41

**Factor II mutation** (G20210A) is the second most common thrombophilia in white people, behind factor V Leiden

Question 42

To test for factor II genetic mutation we can use _

Answer 42

To test for factor II genetic mutation we can use **PCR**

Question 43

Protein S serves as _ while Protein C is able to _

Answer 43

Protein S serves as **sidekick (cofactor)** while Protein C is able to **directly inactivate Va and VIIIa**

Question 44

Thrombophilias cause _

Answer 44

Thrombophilias cause **excessive clotting**