Doctors find rare clotting disorder combo in man facing amputation
Doctors find acquired hemophilia A, Factor XII deficiency
Doctors discovered a rare combination of blood clotting disorders — acquired hemophilia A alongside an inherited disorder called Factor XII deficiency — in a 70-year-old man set to undergo a leg amputation due to foot gangrene.
“This case highlights the importance of considering acquired hemophilia A in unexplained bleeding with prolonged [blood clotting], especially when coexisting conditions such as FXII deficiency … may obscure diagnosis,” the researchers wrote.
They described the case in a study, “Critical limb ischemia leading to amputation as a presentation of acquired hemophilia A with congenital factor XII deficiency: a case report,” published in the International Journal of Surgery Case Reports.
Acquired hemophilia A is caused by self-reactive antibodies mistakenly targeting factor VIII (FVIII), a protein involved in blood clotting. The resulting drop in FVIII activity leads to unusually easy and prolonged bleeding episodes.
Factor XII (FXII) deficiency is a rare genetic condition marked by prolonged blood clotting in a test tube, without clinical bleeding episodes. While mostly asymptomatic, its co-occurrence with other clotting factor deficiencies may compromise health and complicate lab testing.
Man’s symptoms include leg pain, numbness
The coexistence of acquired hemophilia A and FXII deficiency is exceptionally rare, with only a few case reports published.
In this case, the man reported progressive cramping or aching pain in both legs that had been going on for three months. He also had paresthesia (sensations of numbness, tingling, pricking, or burning) from the toes to the lower legs. He had a history of high blood pressure and smoked about one pack a year, with no history of illicit drug use or prior blood transfusions.
The man was previously diagnosed with severe peripheral arterial disease, characterized by blockages and narrowing of multiple arteries in both legs. He was treated with pain relievers and a cholesterol-lowering medication.
Two days before he was admitted to the hospital, he developed acute worsening in the left leg with pain and cyanosis (bluish-purple skin coloring). After receiving intravenous (IV, or into-the-vein) fluids, he experienced uncontrollable bleeding at the IV site. The excessive blood loss resulted in shock.
He developed low blood pressure (hypotension) and an irregularly fast heartbeat (tachycardia) due to the uncontrolled bleeding. His vitals stabilized after he was resuscitated.
After being transferred to a hospital, the man was alert but pale and fatigued. An examination revealed a hematoma (bleeding outside of blood vessels) on the right forearm IV site and severe blood flow blockages (ischemia) in the left leg with gangrene (death of body tissue due to a lack of blood flow) of the foot. Lab tests showed severe anemia (low red blood cell count), elevated white blood cell and platelet counts, and markedly prolonged blood clotting in a test tube.
Doctors suspected acquired hemophilia A and started the man on corticosteroid therapy to suppress immune responses and the production of anti-FVIII antibodies.
Further blood tests revealed low FVIII activity and high levels of anti-FVIII self-reactive antibodies, confirming the diagnosis of acquired hemophilia A. The man also tested positive for lupus anticoagulant, a self-reactive antibody that — contrary to its name — increases the risk of blood clots by interfering with the body’s clotting process.
A second blood test confirmed prolonged clotting in a test tube, along with low Factor XII activity, suggesting a co-existing congenital FXII deficiency.
The man underwent surgery to amputate his left leg above the knee. To control bleeding, he received a bypassing agent before and during the operation. He was also placed on immunosuppressive therapy — which included corticosteroids started pre-surgery and rituximab (sold as Rituxan and others) started post-surgery — to eliminate the anti-FVIII antibodies. The surgery was successful, though he experienced moderate bleeding during the procedure.
After the operation, he received several red blood cell transfusions, but there were no other complications beyond persistent bleeding.
Two days after surgery, he was started on rituximab and tenofovir (sold as Viread and others) to prevent a hepatitis B virus infection. Bleeding stopped six days after the procedure, and levels of hemoglobin, the protein in red blood cells that carries oxygen, improved. The man was discharged from the hospital with a tapering steroid regimen and was scheduled for outpatient rituximab infusions.
“This case highlights the diagnostic and therapeutic complexities of managing acquired Hemophilia A coexisting with congenital factor XII deficiency and lupus anticoagulant in an elderly patient presenting with acute limb ischemia,” the researchers wrote. “Clinicians should maintain high vigilance for atypical coagulation profiles in vascular emergencies and consider rare hematologic conditions when standard explanations fall short.”
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