Deep vein thrombosis and pulmonary embolism: Pathology review

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Case Study 0:00–0:42

. Hannah is a 42-year-old woman who came to the emergency department due to pain in her right calf.
She reports flying from Japan to the United States two days ago. She has not had fever, chills, or history of trauma to the leg.
She has a 25 pack year smoking history, and she takes oral contraceptive pills. On physical examination, she is stable, and her BMI is 32.
Her right leg is shown in this image. On laboratory investigation, her D-dimer level is elevated.
Deep vein thrombosis or DVT and pulmonary embolism or PE are the two main clinical manifestations of venous thromboembolism.

Pathophysiology of DVT 0:42–3:01

The pathogenesis and risk factors of both DVT and PE center around virtow triad, that is, stasis of blood flow, hypercoagulability, and endothelial injury.
Important scenarios to remember that promote venous stasis are paralysis after stroke, the postoperative period, as well as long drives or flights.
People with varicose veins are also at increased risk of DVT because incompetent venous valves prevent proper venous outflow, causing stasis.
An interesting risk factor is pregnancy, where the enlarged uterus may compress the iliac veins, causing stasis of venous outflow.
Another similar cause is May Thurner syndrome, where the left iliac vein gets sandwiched between the right iliac artery anteriorly and the lumbar vertebrae posteriorly, which also leads to venous stasis.
Now, the coagulation system is normally balancing clot formation and clot lysis. Hypercoagulability occurs when the scale is tipped toward clot formation.
These may be genetic, such as factor 5 Leiden or antithrombin 3 deficiency, or it may be acquired like when there's high estrogen during pregnancy or when using estrogen containing oral contraceptive pills.
Also, nephrotic syndrome causes loss of antithrombin 3 in the urine, resulting in hypercoagulability. This is especially prominent in membranous glomerulonephropathy.
Other acquired causes of hypercoagulability include malignancies, sepsis, smoking, and autoimmune diseases like lupus or antiphospholipid syndrome.
Last, obesity leads to a hypercoagulable state through mechanisms like chronic inflammation and higher levels of clotting factors.
Finally, endothelial damage, like when there's trauma, can expose the underlying collagen which initiates the coagulation cascade.

Clinical Presentation3:01–4:21

Other important causes of endothelial injury to keep in mind are surgery, chemicals in cigarette smoke, and the pressure and stretching of blood vessels during pregnancy and delivery.
All right, now, DVTs typically affect the deep veins of the lower extremity, such as the posterior tibial vein, perineal vein, and muscular veins in the calf, the popliteal vein in the knee, and the femoral and iliac veins more proximally.
Veins in the calf region are most commonly affected by DVT. However, it's important to remember that the more proximal DVTs, especially those involving the popliteal and femoral veins, are more likely to embolize and cause PE.
DVT usually presents with unilateral painful swelling and redness of the affected extremity. However, up to 50% of DVTs are asymptomatic, so it's important to consider DVT even without the classic signs.
Other common conditions to include in your differential diagnosis for DVT are cellulitis or a ruptured popliteal Baker cyst, which can present similarly.
So when it comes to diagnosis, the best choice for an initial test is a compression ultrasound with Doppler. Normally veins are easily compressible using the ultrasound probe.

Pathophysiology of PE4:21–6:10

But when there's a clot, the affected vein becomes incompressible. Doppler is beneficial because it also shows blood flow within the vein.
In some cases, a test called a D-dimer can be useful. D-dimer is a fibrine degradation product that is usually elevated when a blood clot is present.
A negative test may be helpful to rule out DVT, but a positive test does not necessarily mean there is DVT. So D-dimer has a high sensitivity but a low specificity for DVT.
Now, PE most commonly occurs when a DVT breaks off and travels to the pulmonary artery or one of its branches. When the pulmonary artery is obstructed, perfusion to the supplied segment of the lung is limited.
However, there's nothing wrong with ventilation to that segment, so now we have a ventilation perfusion mismatch or a VQ mismatch where there's plenty of oxygen in the alveoli, but the blood can't reach the area to pick it up.
This is known as dead space and leads to decreased oxygen saturation in the blood or hypoxemia. In response to hypoxemia, the pulmonary blood vessels in the affected area vasoconstrict, attempting to divert blood to better oxygenated lung segments to improve gas exchange.
This process is called hypoxic pulmonary vasoconstriction. While it's generally a protective mechanism, if multiple lung segments are involved, hypoxic pulmonary vasoconstriction can further increase pulmonary pressures and lead to right heart strain.

Clinical Presentation6:10–8:19

Additionally, peripheral chemo receptors pick up on hypoxemia and send signals to the brain to increase ventilation in an attempt to compensate.
This hyperventilation causes the individual to blow off lots of carbon dioxide, resulting in respiratory alkalosis. Now, most of the time when a clot occludes a blood vessel, the distal organ tissue dies, also known as an infarct.
The lung is an exception because it receives a dual blood supply from both the pulmonary artery and bronchial arteries, which are branches of the aorta.
This makes infarction of the lung much less common. OK, so large emboli that occlude the pulmonary trunk place tremendous amounts of sudden pressure on the right heart.
So it's important for you to remember that this can result in acute right heart failure in a form of shock called obstructive shock.
Obstruction of the right ventricular outflow tract means the left heart isn't getting enough blood, which decreases left ventricular filling and ultimately stroke volume.
OK, now let's tie the pathophysiology to the clinical presentation. Hypoxemia and hyperventilation means individuals with PE present with sudden onset shortness of breath and tachypnea.
Additionally, because PE limits left ventricular stroke volume, the heart tries to compensate by increasing the heart rate, so tachycardia.
PE can also present with pleurtic chest pain that is worse on inspiration. Additionally, hemorrhagic infarction may cause the individual to develop hemoptysis.
A combination of hypotension, a distended jugular vein, and clear lung sounds often clue towards obstructive shock. Now, approximately 25% of the population have a patent forum in Ovale.

Fat Emboli8:19–9:19

This means that a clot can travel from the right atrium. To the left atrium.
To the left ventricle. And into the arterial circulation, so a possible presentation to consider is actually an embolic stroke.
The ECG and PE most commonly shows sinus tachycardia, but sometimes a unique pattern called the S1Q3 T3 pattern may appear.
This means an S wave in lead one, a Q wave in lead three, and an inverted T wave also in lead three. This pattern is not sensitive nor specific for PE.
Rather, it's essentially a distress signal from the right heart signifying right heart strain. The best diagnostic test for PE is a CT pulmonary angiogram or CTPA, which shows a filling defect in the pulmonary artery or its branches.

Amniotic Fluid Emb.9:19–10:09

However, some patients can't have a CTPA because of things like severe allergy to contrast dye, severe renal impairment, or pregnancy.
So in those cases, the next best option is a VQ scan, which will show a mismatch between ventilation and perfusion if a PE is present.
It's also important to remember that microscopic examination of the thrombus will show the characteristic lines of zon. These are alternating layers of pink from platelets and fibrin, and red from RBCs.
These lines are only found in thrombi formed before death, so they help distinguish a premortem thrombus from a postmortem clot.

Air Emboli10:09–11:07

OK, when using the term PE, this usually refers to pulmonary thromboembolism. However, there are some rare causes of PE that are also important to know.
Fat emboli can occur when there's long bone fractures, orthopedic procedures, and liposuction. In these scenarios, fat globules are released into the circulation and are exposed to lipoprotein lipase, which degrades them into free fatty acids like oleic acid.
These free fatty acids damage the endothelium of various organs. When the lung endothelium is affected, acute respiratory distress syndrome, a form of non-cardiogenic pulmonary edema, can occur.
When the skin capillaries are involved, a petechial rash appears, and if the brain capillaries are affected, neurological deficits can occur.

Septic emboli11:07–11:28

This culminates into a classic triad of ards, petechia, and diffuse neurological impairment. On microscopy, fat can be seen intravascularly and stains black.

Review11:28–12:35

Then there's amniotic fluid embolism. Risk factors include being in the peripartum period, maternal age above 35, cesarean section or operative delivery, and uterine trauma.
These all increase the risk of amniotic fluid and fetal debris entering the maternal circulation. Amniotic fluid contains substances like fetal cells.
Hair and amino acid metabolites that are considered foreign to the birthing parent's body, so this triggers an immune reaction that looks like anaphylaxis or an anaphylactoid reaction.
This causes vasospasm in the pulmonary arteries, leading to pulmonary hypertension, right heart failure, and potentially left heart failure.
Amniotic fluid also contains tissue factor or thromboplastin, which triggers the coagulation cascade, resulting in disseminated intravascular coagulation or DIC.

Summary12:35–16:23

On microscopy, fetal squamous cells and mucin are seen in the birth parent's pulmonary arteries. Air emboli are up next, and for these to happen, there must be direct communication between the atmosphere and a blood vessel lumen, as well as a pressure gradient favoring air entry.
Risk factors include neurosurgical procedures, laparoscopic surgery, and any blunt or penetrating trauma that exposes blood vessels to air.
Once air enters smaller vessels, it can form bubbles that end up blocking blood flow. A specific form of gas embolism that occurs in divers is decompression sickness, also known as Cason disease or the bends.
To put it simply, when a diver descends into a high pressure environment, nitrogen dissolves in the blood and accumulates in lipid rich tissues.
If they ascend rapidly, the sudden decrease in pressure causes nitrogen to come out of the solution and form gas bubbles which can obstruct blood vessels.
This is why it's advised to ascend slowly to allow nitrogen to slowly get out of the circulation and be exhaled through the lungs.
Finally, septic emboli can occur in people with right-sided or tricuspid infective endocarditis. These septic emboli are little clumps of infected material containing things like pathogens, fibrin, and platelets that detach from the surface of the tricuspid valve and travel through the right heart into the pulmonary arteries, blocking blood flow to the lungs.
Here, it is important to remember that the major risk factor for tricuspid valve endocarditis is intravenous drug use. All right, as a quick recap, the two main forms of venous thromboembolism are DVT and PE.
The pathogenesis and risk factors for both revolve around virtow triad, which includes stasis, hypercoagulability, and endothelial injury.
DVT most commonly affects the calf, but it's the proximal DVTs that usually embolize to cause PE. DVT often presents with unilateral limb swelling, pain, and erythema, and diagnosis is confirmed with a compression ultrasound with Doppler.
PE causes a VQ mismatch resulting in hypoxemia and hyperventilation, which causes respiratory alkalosis. Individuals present with acute sudden onset shortness of breath, pleurtic chest pain, hemoptysis, and sometimes obstructive shock.
Diagnosis is confirmed with a CT, pulmonary angiogram, or VQ scan. It's also important to consider rarer causes of PE such as fat, air, septic, and amniotic fluid emboli.
OK, back to our case. Hannah is presenting with DVT.
Her risk factors include a prolonged period of immobilization from her long flight, obesity, smoking, and use of oral contraceptive pills, which all increase coagulability.
Her D-dimer was elevated, suggesting the possibility of DVT. A compression ultrasound was performed and confirmed DVT.
She is now doing well on anticoagulation therapy. And that's DVT and PE pathology in a