What’s up fellow AMBOSSians!
I’m Dr. Zeb, here to get the most of this question with you in the next 7 minutes.
So let’s get started!
The first thing we wanna do is determine our task by reading the lead-in.
Ok, I can already see: Diagnosis.
At this point, I’ll usually read the sentence or even 2 or 3 before.
This is the diagnostic info that often gives me confirmatory findings if I’m lucky.
One pro tip is to look for vitals or lab values, since these are always the start of diagnostics.
So I can read: “Laboratory studies show a platelet count
of 151,000/cubic millimeter” which is normal “and a bleeding time of 13 minutes.”
which is prolonged.
Prothrombin time and partial thromboplastin times are within the reference ranges.
Peripheral blood smear shows normal platelet morphology.
With this info alone, we already should have a good idea of what the right answer could
be.
It’s clinical reasoning time!
So break out those illness scripts.
What conditions have prolonged bleeding time, but normal platelet count and morphology,
PT, and PTT?
That’s right, anything that affects platelet function.
This could be acquired such as medication-induced from Aspirin, NSAIDS, or clopidogrel, or uremia
due to kidney disease.
It could also be genetic, such as Glanzmann thrombasthenia or non-severe von WIllebrand
disease.
Now, we could see if one of these differentials already matches, but we should try answering
without looking at the options.
So let’s go ahead and find more information to narrow down the diagnosis.
“A 22-year-old woman comes to the physician for evaluation of heavy menstrual bleeding.
Two years ago, she had prolonged bleeding after wisdom tooth extraction.
She follows a vegan diet and does not eat any animal products.
Physical examination shows no abnormalities.”
OK, so what important findings do we have?
Two findings indicating a bleeding diathesis, specifically more associated with a primary
hemostasis disorder rather than secondary or mixed, in which you would see deep tissue bleeding.
There’s no history that fits acquired platelet dysfunction like medications or associations
with uremia, as in kidney disease.
So this is likely a genetic cause, which matches the patient’s young age as well.
Now that we’ve narrowed down the most likely cause, it’s time to find the option that
matches best.
And sure enough, there’s von Willebrand disease, the most common bleeding disorder.
Since we clinically reasoned to come up with the correct answer, we don’t even need to
rule out the distractors.
So in the exam, we should mark it and move on.
But let’s say you weren’t 100% sure, or you’re reviewing.
When reviewing questions, I highly recommend looking at all the options and elaborate on
why they’re correct or incorrect.
This strategy of active recall will maximize your learning and strengthen memory as you
connect concepts, especially with AMBOSS questions, in which every option has a teaching objective.
Let’s do that now, starting with the correct option:
Von Willebrand disease is generally a genetic condition that is characterized by a deficient
or dysfunctional von Willebrand factor, or vWF.
What’s vWF?
It’s a blood clotting protein that mediates the adhesion of platelets to collagen of damaged
blood vessels, as in a cut, for example, with the world’s smallest butter knife.
It does this by binding the platelet’s glycoprotein Ib surface receptor.
This activates the platelet, leading to the release of important mediators like ADP to
promote further adhesion and thromboxane A2 to activate more platelets and vasoconstriction.
vWF also plays a role in platelet-to-platelet aggre...
platelet-to-platelet...
bah... beep vWF also plays a role in platelet-to-platelet
aggregation by binding GpIIb/IIIa receptors, as does fibrinogen.
This process leads to clot formation.
So if vWF isn’t working, neither is blood clotting.
Since vWF binds factor VIII to stabilize it, severe cases can also decrease PTT.
(If you’ll remember, PTT measures the integrity of the intrinsic pathway, which includes factor
8, as well as 9, 11, and 12 - not 10.)
But that isn’t the case here.
vWF has no effect on PT, platelet count or morphology.
So now we have a good understanding of why only bleeding time is increased, while PT,
PTT, and platelets are all normal.
As for the other options: As a platelet disorder, immune thrombocytopenic purpura
can cause similar prolonged bleeding, but we would expect thrombocytopenia.
Hemophilia A, would be more aligned with secondary hemostasis disorders, so more deep tissue
bleeding such as bruising, hematomas, and hemarthrosis.
Also, as an x-linked recessive disease, it would instead typically be asymptomatic in
a female carrier since the healthy X allele can keep producing normal factor VIII.
For hemophilia A, remember A-eight.
Since factor VIII is defective, we’d expect a prolonged PTT.
Lastly, bleeding time should be normal as platelets are unaffected.
While vitamin K deficiency can cause bleeding, it is an important cofactor in the development
of coagulation factors 2, 7, 9, and 10 in the liver.
So it’s also associated with secondary hemostasis bleeding, and both PT and PTT would be increased
rather than bleeding time.
For Vitamin K deficiency, remember a Killer 1972 disco.
Bernard-Soulier syndrome is trickier since it’s also a disorder of primary hemostasis,
like von Willebrand disease.
It’s autosomal recessive and caused by a deficient GpIb.
Although it usually causes thrombocytopenia, it’s possible that platelet count is normal.
So why is it wrong?
Well, it’s all in the blood smear here.
Bernard-Soulier syndrome causes giant platelets to form, but this patient had normal platelets.
Now, how can we remember that?
Easy, just think of a St. Bernard dog - they’re huge!
Just like Bernard-Soulier syndrome thrombocytes.
They even have bloodshot eyes to help you remember bleeding.
So what about the vegan diet?
Isn’t that important?
Although this could be associated with some nutritional deficiencies, it’s extraneous
information here.
The NBME question writers refer to this as “window dressing,” and include it to reflect
more realistic clinical vignettes.
This forces examinees to clinically reason with the most salient findings.
While more common in Step 2 and 3, it’s still fair game in Step 1.
It’s important to trust your clinical reasoning and not to get too hung up on it, though.
Continuing our reflective practice, let’s preemptively consider what other questions
could appear on Step 1 for a vignette like this.
They could ask about: A high-yield association: Angiodysplasia
OR how do you diagnose?
Ristocetin cofactor assay not activating vWF to bind GpIb.
OR how do you treat?
Desmopressin, an ADH analog that releases vWF from endothelial cells.
Another correct option could have been Glanzmann thrombasthenia.
In fact, we can’t even rule it out here.
Any of these are fair game for testing this topic.
I recommend thinking this way, so it enables you to answer several questions on test day
from just practicing one.
Comment below if you have any other ideas.
So to recap, the key takeaways of this question are:
1.
Formulate differentials for a prolonged bleeding time based on pathophysiology and platelet
count, PT, and PTT values.
2.
Differentiate disorders of primary hemostasis (in other words, platelet conditions) from
secondary (so, coagulation issues).
3.
Know that von Willebrand disease is the most common genetic bleeding disorder that prevents
clot formation due to insufficient platelet adhesion, and that severe cases may elevate
PTT since factor VIII is no longer protected.
Okay, that’s it for this video - a lot of info, but a very high-yield topic - you’ll
definitely get a von Willebrand disease question on your exam, so I hope you’ve found it
helpful for learning or reinforcing.
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Remember, hard work pays off, so whether you have your exam next week or next year, keep
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