Hemophilia Carriers and Bleeding Risk in Anemic Older Adults
Abstract & Commentary
By Andrew S. Artz, MD, Section of Hematology/Oncology, University of Chicago. Dr. Artz reports no financial relationship to this field of study.
Synopsis: Female hemophilia carriers have not usually been considered at increased risk of bleeding unless factor levels are below 40%. In this observational study of comparing female carriers and non-carriers, carriers showed an increased risk of bleeding, particularly after medical interventions. The risk appeared to increase with levels below 60%. Clinicians should be aware that female carriers of hemophilia may be at increased risk of bleeding. Future research is needed to confirm the bleeding risk, identify factor levels predisposing to bleeding, and determine optimal prophylaxis/intervention strategies.
Source: Plug I, et al. Bleeding in Carriers of Hemophilia. Blood. 2006:108:52-56.
Hemophilias refer to bleeding disorders from deficiencies of factor VIII (hemophilia A) or factor IX (hemophilia B). Common bleeding sites include joints, muscles, and the GI tract, although clinical severity varies depending in large part to factor levels. As an X-linked recessive disorder, men are mostly affected and women are heterozygous carriers. The factor levels in female carriers average about 50% of normal although wide variation occurs attributable to random X-chromosome inactivation and potentially other factors as well. In general, carriers have not been considered at increased bleeding risk unless levels were below 40%. Minimal data have actually examined the association of carriers and factor levels with bleeding risk and severity.
In this observational study, all women who were tested for being carriers of hemophilia A or B in the Netherlands were contacted. Factor levels were documented from medical charts. Among the 766 questionnaires on bleeding history, 546 were returned (80%). The final analysis entailed 274 carriers and 245 non-carriers. The mean age was similar at 39 and 40 years, respectively although more carriers had factor levels ascertained. The median factor levels were 0.60 IU/mL for carriers and 1.02 IU/mL for non-carriers. Carriers showed an increased risk of small wound (RR = 2.2) and joint bleeds (RR = 1.9), but no increased risk of epistaxis, bruising, or gum bleeding. Bleeding for greater than 3 hours after a medical intervention was increased in carriers as was the need to receive a medical intervention (intervention not specified). A trend existed for increased bleeding risk for clotting factor levels between 0.60 to 0.41 IU/mL and more severe bleeding for levels 0.40 IU/mL and below.
Commentary
The authors conclude that female hemophilia carriers have an increased risk of bleeding and that levels below 0.60 IU/mL serve as a marker for increased risk. The data are provocative and challenge traditional assumptions that bleeding risk may only be increased at levels of < 40% (40 IU/mL). Limited data have explored at what factor level, particularly for hemophilia carriers, does the risk of bleeding increase.
Important bias may exist in observational studies. Because carriers and non-carriers were ascertained from living in a household with a known case, the impact of environment should have been similar. The authors believe that awareness of carrier status does not necessarily impact report of bleeding tendency1 but one can not exclude this. The important finding that carriers have an increased risk of bleeding after trauma and medical interventions related to factor levels may be biased from health care providers knowledge of carrier status and/or factor levels. Physicians may be more likely to monitor and/or treat bleeding symptoms in a known carrier, particularly if factor levels were low. Another limitation is that factor levels analyzed were the lowest level available in the chart. If factors levels were lower at the time of bleeding, the risk of bleeding from low factors levels would be underestimated.
The authors' work does challenge traditional assumptions and raises awareness of the potential for bleeding in carriers of hemophilia, even at factor levels below between 40 and 60% of normal. The data have enough limitations to definitive recommendations. Prospective data on bleeding risk and severity related to factor levels are needed. Many questions remain unanswered and require more research. Should we routinely check levels in known or suspected carriers before surgery? Should prophylaxis for high-risk surgery be considered when levels are < 0.60 IU/mL? If so, what therapy should be used?
Reference
1. Mauser Bunschoten EP, et al. Bleeding symptoms in carriers of hemophilia A and B. Thromb Haemost. 1988;59:349-352.
Female hemophilia carriers have not usually been considered at increased risk of bleeding unless factor levels are below 40%.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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