Hereditary and Acquired Thrombotic Disorders

Question 1

Identify the components of Virchow’s triad and their pathophysiologic contribution to thrombosis

Answer 1

1. Decreased blood flow (venous stasis)
2. Inflammation of or near the blood vessels (altered vessels)
3. Intrinsic alterations in the nature of the blood itself (altered coagulability)

Question 2

Describe at least three major clinical symptoms that occur when a patient suffers from an acute iliofemoral thrombosis of the leg, and indicate the pathophysiologic reason for each one

Answer 2

• obstruction of venous outflow from an extremity -> phlegmasia cerulean dolens (an extremely swollen, blue, painful leg)
• enhanced superficial venous blood flow -> pain, pitting edema of the distal extremity, and a warm, dusky, reddish-blue discoloration of the skin

Question 3

cause, composition and mechanism of a thrombus occurring in the arterial circulation

Answer 3

• conditions of high shear stress
• composition: primarily aggregated platelets with small amts of fibrin and a few RBCs
• “white thrombi” -> ischemia and infarction
• causes: Virchow’s triad

Question 4

cause, composition and mechanism of a thrombus occurring in the venous circulation

Answer 4

• conditions of low shear stress
• composition: large amts of fibrin containing numerous RBCs
• “red thrombi”
• causes: R sided heart failure, pre-existing venous thrombosis, extrinsic vascular compression by tumor, immobility, obesity and chronic venous insufficiency
• altered vascular factors and altered coagulability
• age

Question 5

clinical clues suggesting an inherited hypercoagulable disorder

Answer 5

• First thrombosis age <50
• Recurrent episodes of thrombosis
• Family history of thrombosis
• Thrombosis at unusual sites
• Neonatal thrombosis
• Thrombosis without apparent antecedent thrombogenic event (idiopathic)

Question 6

why patients with antithrombin deficiency are likely to have thrombosis

Answer 6

-inactivates thrombin as well as factors Xa, IXa, XIa and XIIa

Question 7

why patients with protein C deficiency are likely to have thrombosis

Answer 7

-(Vit K dependent) inactivates factors Va and VIIIa to inhibit coagulation

Question 8

why patients with protein S deficiency are likely to have thrombosis

Answer 8

-(Vit K dependent) facilitates the anticoagulant activity of activated protein C

Question 9

why patients with Factor V Leiden are likely to have thrombosis

Answer 9

• mutation of the factor V gene -> partial resistance to inactivation through proteolytic cleavage by protein C
• Factor V Leiden is inactivated 10 times more slowly than normal factor Va
• Resistance to inactivation leads to increased risk for thrombosis

Question 10

why patients with a prothrombin mutation are likely to have thrombosis

Answer 10

-elevated [plasma prothrombin]

Question 11

List and describe four acquired disorders that are associated with recurrent venous or arterial thromboembolism

Answer 11

• Antiphospholipid Antibody syndrome (APL, APLS) - thrombotic or obstetric complications caused by antibodies
• oral contraceptives - alteration in levels of coagulation factors leading to a net increased risk for thrombosis.
• Lupus anticoagulants, anticardiolipin antibodies, and beta-2 glycoprotein 1 antibodies - risk factors for thrombosis as well as increased risk for obstetric complications and fetal death; in the laboratory they lead to prolongation of the APTT.
• Hyperhomocyteinemia can be inherited or acquired. The mechanism underlying increased risk for thrombosis may be enhanced platelet activation and adhesiveness due to endothelial cell injury.

Question 12

Describe the clinical features of antiphospholipid antibody syndrome

Answer 12

• Vascular thrombosis

- Pregnancy complications

Question 13

Describe the criteria for diagnosis of antiphospholipid antibody syndrome

Answer 13

• Anticardiolipin Antibodies
• Lupus anticoagulant
• Beta2-glycoprotein-I antibodies

Question 14

Explain the key factor in determining how long someone should be anticoagulated for a venous thrombosis

Answer 14

Key in the decision-making process is determining if the DVT occurred due to transient risk factors (such as surgery, temporary immobilization, trauma, or pregnancy) or if the patient has an underlying hypercoagulable disorder or ongoing risk factors that require longer treatment. The location and severity of the clot also influences clinical decision making