This case involves a male infant with no family history of hemophilia whose parents elected to have him circumcised.
Following the circumcision, the infant continued to bleed from his circumcision and heel stick sites. The infant’s parents brought this to the attention of the hospital staff, but they were reassured this was normal.
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The infant was discharged with no additional care instructions. In the hours following the infant’s discharge, the circumcision site and heel stick continued to bleed. The infant was then taken back to the emergency room. A blood clot test was conducted on the infant. Although the results came back abnormal, the physicians did not attempt to stitch up the circumcision site nor did they provide the child with any fluids or blood products. A pediatric hematologist decided to order factor studies which revealed that the child had a severe Factor VIII deficiency. The child’s bleeding began to improve, and he was discharged. The next day, the child was limp and would not eat. The infant was rushed back to the emergency room and found to be in critical condition. On exam, his skin was pale blue and he was in respiratory distress. A stitch was placed on the child’s circumcision site, and the infant was given blood transfusions. As a result of these complications, the infant developed impaired kidney function and high-tier Factor VIII inhibitor.
Questions For Expert Witness:
- • Are you more likely to develop inhibitors the more inflammatory you are?
- • Could this bleeding have been the cause of the development of an inhibitor?
- • Is it possible that if the bleeding had not occurred the inhibitor could have been avoided?
Expert Witness Response:
Inhibitors are one of the worst outcomes for any hemophilia patient, as these patients have the greatest morbidities of this disease. The difficulty in hemophilia is that it is rare. Despite a very dedicated and motivated network of clinical and research centers, there is little prospective data, and the limited data out there is actively disputed. There are many risk factors related to inhibitor development and they are well known and summarized in every review article on this topic. In this case, intensive treatment, and treatment during a time of inflammation will be contributory. However, the patient was treated before SIPPET results were known so he likely received recombinant FVIII. Even that study, which is a global randomized multicenter study, is not conclusive to many people, but confirmed genetic risk factors (which were known and this patient may have) as an important risk factor. More importantly, it implied that recombinant FVIII was associated with a higher rate of inhibitors. I would say that >95% of new severe hemophilia patients in the USA got recombinant FVIII in 2013-14. In SIPPET, the recombinant group had an incidence of >40%. In general, we think that 30% of all severe hemophilia A patients will develop inhibitors and that 70% of those can be tolerized. In this case, I think that the delay to Dx is a true problem. I suppose that with more details, the care delivered could be questioned. But whether or not this boy would or would not have developed an inhibitor regardless of this history will always be debatable, even in the presence of risk factors.
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