Thrombosis

Question 1

What is thrombosis

Answer 1

formation of an aggregate of coagulated blood containing platelets, fibrin and entraped cellular elements within the vascular lumen

Question 2

Virchow’s triad of thrombosis

Answer 2

endothelial injury

abnormal blood flow

hypercoagulability

Question 3

how does endothelial injury contribute to thrombosis

Answer 3

• severe injury exposes vWF and tissue factor
• inflammation downregulates protein C and tissue factor protein inhibitor
• when cytokines activate injured cells, they downregulate the expression of thrombomodulin
• injured endothelium secretes plasminogen activator inhibitors, which limits fibrinolysis and downregulates tPA

Question 4

How does abnormal blood flow contribute to thrombosis

Answer 4

disrupted laminar flow brings platelets in contact with the epithelium and prevents the washout/ dilution of activated clotted factors/ inflow of factor inhibitors

Question 5

main cause of arterial and cardiac thrombi

Answer 5

turbulence

endocardial injury

Question 6

main cause of venous thrombi

Answer 6

stasis

Question 7

causes of abnormal blood flow

Answer 7

mitral valve stenosis

hyperviscosity

MI

aortic and arterial dilation

ulcerated athersclerotic plaques

Question 8

contrast the location, growth pattern and factors of formation in venous vs arterial thrombi

Answer 8

Arterial:

Location: coronary> cerebral> femoral arteries

Growth pattern: retrograde

Formation: ruptured atherosclerotic plaques and vascular injury

Venous:

Location: BLE> BUE> periprostatic/ovarian plexus/periuterine veins> dural sinus > hepatic veins

Growth pattern: in te direction of blood flow

Formation: stasis

Question 9

compare and contrast the clinical features of arterial and venous thrombi

Answer 9

Arterial: MI, intestinal infarction, renal infarction, ischemic leg/ gangrene

BOTH: stroke, bowel infarction

Venous:positive homan sign, congestion, edma, cyanosis, induration, budd-chiari syndrome

Question 10

Morphology of a thrombus

Answer 10

lines of zahn

microscopically apparent laminations

pale platelet and fibrin deposits alternating with darker red cell-rich layers

Question 11

compare and contrast antemortem and postmortem thrombi

Answer 11

Question 12

causes of mural thrombi

Answer 12

in heart chambers:

• arrhythmias
• dilated cardiomyopathy
• myocarditis
• catheter trauma
• MI

aortic lumen:

• ulcerated atherosclerotic plaques
• aneurysmal dilation

Question 13

causes of hypercoagulability

Answer 13

Question 14

Factor V Leiden Deficiency

• Pathology
• Consequences
• Clinical features

Answer 14

• Pathology: DNA point mutation where guanine substitutes adenine, leading to glutamine replacing arginine at position 506
• Consequences: Peptide cleavage site is is moved, making it resistant to Protein C
• Clinical features: young caucasian person with no risk factors, but appear with thrombosis

Question 15

Prothrombin mutation

Pathology

Consequences

Answer 15

• Pathology: mutation of G20210A in the promoter region increases the expression of prothrombin by 30%
• Consequences: more prothrombin can be converted to thrombin to form a clot

Question 16

Antithrombin III Deficiency

Pathology

Consequences

Clinical features

Answer 16

• Pathology: liver disease or nephrotic syndrome causes decreased serum concentration
• Consequences: uninhibited thrombin, factors 9a-12a
• Clinical features: heparin resistance

Question 17

Protein C Deficiency

Pathology

Consequences

Clinical features

Answer 17

• Pathology: protein S deficiency, Vitamin deficiency, liver disorders, increased excretion
• Consequences: uninhibited activity of Factor 5a and 8a
• Clinical features: warfarin skin necrosis

Question 18

Explain the pathology of Heparin-induced thrombocytopenia

Answer 18

1. Activated platelets release PF4, which binds to heparin
2. IgG binds to the PF4-heparin complex, destroying them and causing thrombocytopenia
3. compound that were in the platelet are now free to bind to other platelets in circulation
4. cycle repeats with thrombocytopenia and clotting

Question 19

clinical presentation of HIT

Answer 19

thrombocytopenia following the administration of unfractioned heparin

Trousseau syndrome

THrombosis with chronic DIC

Nonbacterial thrombotic endocarditis

THrombosis with ALL treatment and estrogen-like drugs

Question 20

pathology of antiphospholipid syndrome

Answer 20

patient procoagulation antibodies target phospholipid-binding proteins that activate platelets and vascular endothelium

Question 21

clinical presentation of antiphospholipid syndrome

Answer 21

recurrent thromboses

repeated miscarriages

cardiac valve vegetations

thrombocytopenia

ulceration

pulmonary HTN

infarctions

renovascular HTN

Question 22

Diagnostics of Antiphospholipid Syndrome

Answer 22

Prolonged PTT that is not corrected with a mixing study

anticardiolipin antibodies

anti-Beta2 glycoprotein antibodies

lupus anticoagulants

false-positive RPR/VDRL

Question 23

Fates of a thrombus

Answer 23

Propagation= accumulation with additional platelets and thrombi

Dissolution= total disappearance via fibrinolysis

Organization and recanalization= ingrowth of endothelial cells, smooth muscle cells and fibroblasts to continue with the original lumen

Embolization= travel to other sites

Question 24

Tyes of emboli

Answer 24

systemic thromboemboli

pulmonary embolism

fat/ marrow embolism

air embolism

amniotic fluid emboism

Question 25

what causes systemic thromboemboli and what are the consequences

Answer 25

cause: displaced thrombi intracardiac mural thrombi aortic aneurysms atherosclerotic plaques valve vegetations paradoxical emboli in the case o ASD/ VSD

Question 26

do systemic thromboemboli prefer the brain or lower extremities

Answer 26

lower extremities

Question 27

clinical features of pulmonary emboli

Answer 27

Sudden onset dyspnea Pleuritic chest pain Tachypnea Tachycardia Cough Hemoptysis Decreasing level of consciousness Flank pain Delirium (in elderly patients)

Question 28

cause of pulmonary emboli

Answer 28

DVT travels to right heart and into pulmonary vasculature OR paradoxical emboli travel through cardiac defects into systemic arteria circulation

Question 29

consequences of pulmonary emboli

Answer 29

cardiovascular collapse cor pumonale pulmonary hemorrhage infarction pulmonary HTN sudden hypotension

Question 30

causes of fat/ marrow emboli

Answer 30

fractures of long ones soft tissue trauma burns

Question 31

pathology/consequences of fat/ marrow emboli

Answer 31

1. ruptured vascular sinusoids in the marrow/ small venules 2. marrow/ adipose tissue herniates into vascular space 3. travel to the lunh

Question 32

clinical features of fat/ marrow emboli

Answer 32

sudden onset of tachypnea dyspnea tachycardia irritability, restlessness delirium or coma diffuse petechial rash due to thrombocytopenia anemia **Typically 1-3 days post injury**

Question 33

pathogenesis of a fat embolism

Answer 33

fat globules release free fatty acids inducing local endothelial injury, platelet activation and granulocyte recruitment

Question 34

**Air Embolism** * Pathology * Etiology * Clinical Presentation

Answer 34

* **Pathology**: gas bubbles within the circulation obstruct vascular flow, causing ischemic injury * **Etiology**: surgery, laparoscopic procedures, chest wall injury, decompression sickness * **Clinical Presentation**: the chokes and the bends

Question 35

consequences of chronic decompression sickness

Answer 35

multiple foci of ischemic necrosis in the femoral heads, tibia and humeri

Question 36

clinical features of amniotic fluid embolism

Answer 36

sudden severe dyspnea cyanosis Shock headache to seizures and coma Pulmonary edema DIC

Question 37

pathology of amniotic fluid emboli

Answer 37

tears in the placental membranes or rupture of uterine veins🡪 infusion of amniotic fluid/fetal tissue into the maternal circulation

Question 38

morphology of amniotic fluid emboli

Answer 38

* squamous cells shed from fetal skin * lanugo hair * fat from vernix caseosa * mucin (derived from the fetal respiratory or gastrointestinal tract in the maternal pulmonary micro­vasculature)