An infant presents with blood-streaked stools.
She has been afebrile and breastfeeding well. She has not exhibited any other bleeding. Her perinatal history is unremarkable. Reviewing your conversation with the emergency department personnel, you breathe a sigh of relief, as you have seen this sort of presentation too many times before. However, you realize on your drive over to the hospital that there may be another reason why the emergency department is puzzled.
Physical exam unremarkable
You arrive at the emergency department to see your patient. On physical examination, her temperature is 99.2° F (37.3° C), heart rate is 140 bpm, respirations are 40 bpm, and blood pressure is 73/44 mm Hg. She appears well, and is breastfeeding in her mother's lap. Family history is negative. Her physical exam is unremarkable. There are no petechiae, rectal fissures, organomegaly, or other abnormalities.
The plot thickens
While the emergency physician is concerned your patient has a coagulopathy causing her rectal bleeding, you are sure there must be an error in the PTT measurement due to heparin contamination-or perhaps just a fluke. However, much to your dismay, repeat coagulation studies reveal a persistently elevated aPTT. Her aPTT corrects to normal with 1:1 mixing with normal serum.
Since your infant is a female, you attempt to recall which coagulopathy other than hemophilia could lead to prolongation of the aPTT. Baffled, you reach for a hematology textbook in the emergency department. Because the aPTT normalized following the mixing study, factor deficiency is suspected rather than an inhibitor.
Isolated prolongation of the aPTT can be caused by an inhibitor, heparin, von Willebrand disease (VWD), or deficiency in the intrinsic coagulation pathway, excluding factors in the common pathway (factors V, X, prothrombin, and fibrinogen). VWD is the most common inherited bleeding disorder, and may cause a prolonged aPTT in up to 50% of cases (Table 1).
Factors in the intrinsic pathway include high-molecular-weight kininogen (HMWK), prekallikrein, factors VIII, IX, XI, and XII. Of those in the intrinsic pathway, only deficiencies of factors VIII (hemophilia A), IX (hemophilia B), and XI result in a bleeding tendency. Factors VIII and IX were not tested because the hemophilias are X-linked disorders, and your patient is female-though lyonization or mosaicism may rarely cause such X-linked diseases in females. The only other factor deficiency manifested by an elevated aPTT with bleeding tendency is factor XI, and this infant's level is normal. Further testing revealed an undetectable factor XII level. You start to wonder if you are on a wild goose chase. With that in mind, you decide to give your friendly hematology colleague a call.