review

Another great board-type review question, this time on von Willebrand disease and hemophilia:

A 34-year-old male presents with excessive bleeding. He has a family history of bleeding, and his laboratory results are as follows:
1. PTT (partial thromboplastin time): increased
2. Bleeding time: increased
3. Platelet aggregation studies: abnormal (no aggregation with ristocetin)
4. Factor VIII level: decreased.

Which of the following is the most likely diagnosis?
A. Hemophilia A
B. Hemophilia B
C. von Willebrand disease
D. Factor V Leiden
E. Antiphospholipid antibody syndrome

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This question is asking you to a) identify which of the distractors is, in fact, a bleeding disorder, and b) decide based on laboratory tests which is the most likely diagnosis. Let’s take the answers one by one.

Answer A (hemophilia A) is wrong. But if you were in a hurry, you might see the “decreased factor VIII level” part of the question and rush right toward A, because in hemophilia A, the whole problem is that you don’t have enough factor VIII around. However, this is the wrong answer for a few reasons. Although the PTT result is consistent with hemophilia A (if you don’t have enough factor VIII, the intrinsic arm of your coagulation pathway will not be working properly, and the PT will be prolonged), the other lab tests are not. The bleeding time is normal in hemophilia, because this test only measures the how the platelets function in vivo – it has nothing to do with coagulation! Kind of counterintuitive, but it’s true. The bleeding time is really measuring how fast you can form your intitial platelet plug; the test ends at that point. Whether you have enough factor VIII to make fibrin or not is immaterial – the test is over and done by that point. See our previous post on what the bleeding time measures for more information on this. Also, platelet aggregation studies are normal in hemophilia (it’s the coagulation cascade that is abnormal, not the platelets).

Answer B (hemophilia B) is incorrect for all the above reasons; plus, hemophilia B involves factor IX, not factor VIII.

Answer C is correct.  The lab test results in this question are all consistent with von Willebrand disease. Patients with von Willebrand disease have decreased amounts of (or functionally abnormal) von Willebrand factor, which is the factor that glues platelets down onto the subendothelium. In addition, factor VIII is decreased (von Willebrand factor is the carrier for factor VIII, so if there’s less vWF around, there will be less factor VIII around). So, in von Willebrand disease, the PTT is increased (less factor VIII leads to a prolonged PTT). The bleeding time is also increased in von Willebrand disease (in vWD, the platelets are less able to stick to the subendothelium, so it takes longer to form the initial platelet plug). Finally, in von Willebrand disease, platelet aggregation studies are abnormal (the platelets don’t aggregate with ristocetin in von Willebrand disease, because ristocetin causes platelets to express their little GP Ib receptors, which are the receptors that bind vWF. If you don’t have enough vWF around, or it’s functionally abnormal, giving ristocetin won’t do squat to the platelets – they will remain unaggregated.

Answer D is wrong on many levels. First, Factor V Leiden is a thrombotic disorder, not a bleeding disorder. Also, coagulation tests are normal in Factor V Leiden! So are the bleeding time and platelet aggregation studies (not that you’d order these tests – you’d be too smart for that). And the factor VIII level is normal, obviously.

Answer E is wrong too. Antiphospholipid antibody syndrome is a disorder that – if anything – causes thrombosis in patients! Many times, these antibodies do nothing at all in the patient; sometimes they can cause thrombosis. But when you run coagulation tests, the antiphospholipid antibodies bind to the reagent (for example, thromboplastin), effectively using it up and removing it from the test tube – so the coagulation test result looks prolonged! Weird. The patient is either normal or is clotting excessively, and the test results say the patient should be bleeding. So in this question, the PTT result fits with antiphospholipid antibody syndrome. However, none of the other test results are consistent with this disease.

Note: the image of a different type of review was taken by Anna Majkowska and can be found at http://www.flickr.com/photos/majkowska/2622920603/.