Q. In one of my other courses, the professor was discussing hemophilia. He states that the prothrombin time (PT) is normal, the partial thromboplastin time (PTT) is abnormal, the bleeding time is normal, and patients will not have petechiae. I was wondering how there can be no petechiae and a normal bleeding time in a patient with hemophilia. Is it because they still have an intact extrinsic pathway that can get the job done? How do we ever classify or detect these patients in the first place, if they don’t have the classic signs? Thanks!

A. Great questions! In hemophilia A, the problem is that you don’t have factor VIII. In hemophilia B, you don’t have factor IX. The PT (INR) measures the extrinsic arm of the coagulation cascade (the part of the cascade involving factor VII and tissue factor). Since factors VIII and IX are not involved in that arm of the cascade, the PT is normal in patients with hemophilia.

The PTT measures the intrinsic arm of the coagulation cascade (the part of the cascade involving VIII, IX, and a bunch of other factors). The PTT will be abnormal (prolonged) in patients with hemophilia because they lack factors on this side of the cascade.

The bleeding time is interesting. It measures only the response of platelets to a vascular injury. It has nothing to do with the coagulation cascade! Weird, huh?! If you look here, there is a description of why this is the case. So: in patients with hemophilia, the bleeding time will be normal.

Finally: patients with hemophilia have what is called “factor bleeding” (big, destructive bleeds, usually in joint spaces). Petechiae are more characteristic of “platelet bleeding.” Platelet bleeding occurs in diseases like von Willebrand’s disease and various rare intrinsic platelet abnormalities. It is more of a mucosal type of bleeding (petechiae, nosebleeds, heavy periods).

To diagnose a patient with hemophilia, you’d probably first notice that they have an abnormal pattern of bleeding. Maybe after they fall, they get these huge bleeds (with hemophilia, there is usually a memorable preceding incident). To start the work up, you’d do some common lab tests: the PT (INR) would be normal, the PTT would be prolonged, a PTT mixing study (where you mix in some normal blood and run the PTT again) would show a corrected (normal) PTT, and the bleeding time would be normal. You’d suspect hemophilia at this point, and you’d run further tests, including factor VIII and factor IX levels, and genetic tests looking for the gene mutation in hemophilia A and B.

The image above is of Queen Victoria, who passed hemophilia through her children and into the royal families of Spain, Germany, and Russia.