USMLE® Step 1 style questions USMLE
A 13-year-old female presents to the emergency room due to persistent bleeding. Earlier in the day, she had a wisdom tooth extracted at the dentist’s office. After the procedure, the patient continued to bleed from the extraction site despite application of manual pressure. She is otherwise healthy and does not take any medications. The patient’s parent reports that she was adopted from Eastern Europe, and her family history is unknown. Laboratory testing is obtained and reveals the following:
Which of the following best describes the inheritance pattern of this patient’s clinical condition?
Content Reviewers:Rishi Desai, MD, MPH
Contributors:Tanner Marshall, MS
The word “hemophilia” is a combination of the Greek words for “blood” and “love”, a way of saying that people with hemophilia “love to bleed”, or rather that it’s hard to stop bleeding. This is because the process called hemostasis, literally meaning to stop the flow of blood, is impaired.
Normally, after a cut and damage to the endothelium, or the inner lining of blood vessel walls, there’s an immediate vasoconstriction or narrowing of the blood vessel which limits the amount of blood flow.
After that, the coagulation cascade is activated.
First off in the blood there’s a set of clotting factors—most of which are proteins synthesized by the liver, and usually these are inactive and just floating around the blood.
The coagulation cascade starts when one of these proteins gets proteolytically cleaved.
This active protein then proteolytically cleaves and activates the next clotting factor, and so on.
The final step is activation of the protein fibrinogen to fibrin, which deposits and polymerizes to form a mesh around the platelets.
Now, that coagulation cascade can get started in two ways.
The first way is called the extrinsic pathway, which starts when tissue factor gets exposed by the injury of the endothelium.
Tissue factor turns inactive factor VII into activated factor VIIa (a for active), and then tissue factor goes on to bind the newly formed factor VIIa to form a complex that turns factor X into active factor Xa.
Factor Xa, with Factor Va as a cofactor, turns factor II (which is also called prothrombin) into factor IIa, also called thrombin.
Thrombin then turns factor I or fibrinogen, which is soluble, into factor Ia or fibrin, which is insoluble and precipitates out of the blood at the site of injury.
Thrombin also turns factor XIII into factor XIIIa which cross links the fibrin to form a stable clot.
The second way is called the intrinsic pathway, and it starts when platelets near the blood vessel injury activate factor XII into factor XIIa, which then activates factor XI to factor XIa, which then activates factor IX to factor IXa.
And factor IXa and factor VIIIa work together to activate factor X to factor Xa, and from that point it follows the same fate as before, so both the extrinsic and intrinsic pathways basically converge on a single final path called the common pathway.
By far the most common of these are deficiencies of factor VIII which gives rise to factor VIIIa and is stabilized by another factor called von Willebrand factor, and this deficiency is called hemophilia A (or classic hemophilia).