New test may help fine tune care for those with acquired hemophilia A
Case report suggests use of thrombin test to show clotting fluctuations
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- A test of the blood-clotting enzyme thrombin may help fine-tune care for people with acquired hemophilia, per a new report.
- The test, called TGA, monitors clotting balance in patients on both clot-promoting and blood-thinning medications.
- In a case in the Netherlands, the test showed clotting fluctutations in a woman, 58, with acquired hemophilia A.
Testing levels of thrombin — an enzyme that helps blood clot — in people with acquired hemophilia A could help doctors fine-tune care for these patients when both clot-promoting and blood-thinning medications are used.
That’s the conclusion drawn by researchers in the Netherlands, who found that thrombin testing in a woman with the blood disorder, as well as lupus and heart disease, showed that her clotting balance fluctuated dramatically with anticoagulant, or blood-thinning, treatment.
The test was able to measure thrombin generation in the 58-year-old woman, who initially sought treatment for bruising on her arms and legs.
The scientists noted that treating acquired hemophilia — an autoimmune disease in which self-reactive antibodies mistakenly neutralize the body’s healthy clotting proteins — can be challenging because standard clotting tests often do not reflect how much a patient actually bleeds. There are also no reliable tests to measure how well a treatment is working.
According to the team, a thrombin generation assay, or TGA, may offer a better way to monitor clotting.
The woman’s case was described in “Monitoring the Hemostatic Balance: measuring thrombin generation in a patient with acquired hemophilia A on combined pro- and anticoagulant therapy,” a letter to the editor-in-chief of the journal Thrombosis Research.
Many patients with acquired hemophilia have heart disease and are on anticoagulants, known as blood thinners, which can further interfere with clotting tests. The thrombin generation assay, or TGA, measures how much thrombin a blood sample produces over time. This reflects the balance between clot-promoting and blood-thinning effects of different medications, the researchers noted.
Woman sought treatment for large bruises on her arms and legs
Here, the team used a TGA to monitor clotting in a middle-aged woman with acquired hemophilia A. This means neutralizing antibodies against clotting factor VIII (FVIII) caused her hemophilia. The woman also had lupus, another autoimmune disease, as well as heart disease. For her heart problems, she had a mechanical heart valve, which requires lifelong blood-thinning medication.
The woman sought treatment at the emergency department after experiencing large, spontaneous bruises on her arms and legs, as well as smaller ones on her face and mouth. Two months earlier, she had undergone a surgical procedure to repair an abdominal aortic aneurysm, or a bulge in the aorta, a main blood vessel. Alongside blood thinners, she was on corticosteroids and other immunosuppressants.
Blood tests showed low FVIII activity and high anti-FVIII antibody levels, confirming the diagnosis of acquired hemophilia A.
To control bleeding, the woman received recombinant activated FVII, a bypassing agent that helps blood clot without using FVIII. Her usual blood thinners were discontinued, and she was switched to dalteparin, a low-molecular-weight heparin, to protect her mechanical heart valve.
For the TGA, blood samples were collected at different time points, matched to low and high levels of activated FVII and dalteparin. The samples were carefully processed and frozen. The TGA was then performed using two reagents: one designed to detect bleeding tendency and one designed to detect clotting tendency.
The bleeding-focused reagent produced almost no thrombin and could not distinguish between time points. In contrast, the clotting-focused reagent showed clear differences. When both activated FVII and dalteparin were low, thrombin levels were near normal. However, when activated FVII was high and dalteparin low, thrombin was very high. When dalteparin was high, thrombin dropped.
Treatment strategy for woman could have been ‘superior’ with TGA
To confirm these findings, normal plasma — the clear liquid portion of blood — was “spiked” with known amounts of activated FVII and dalteparin to mimic their levels in the patient, according to the researchers.
These experiments showed a dose-dependent effect: Higher dalteparin doses reduced thrombin generation, while higher activated FVII levels increased it. Dalteparin had the strongest overall effect, the results showed.
Even at low levels of both medications, the patient’s overall thrombin generation was similar to that of normal pooled plasma, despite low FVIII activity. This is partly because the high-tissue factor test, which detects clotting tendency, is less sensitive. However, “these treatments led to significant fluctuations in [thrombin generation],” the researchers wrote, adding that “values varied widely.”
In this woman’s case, discontinuing blood thinners based on the results of the TGA “could have been a superior treatment strategy,” the researchers wrote.
Clinicians may be able to use [thrombin generation] parameters to better guide therapeutic decisions [in acquired hemophilia A].
The team called for further investigations into the role of thrombin testing in individuals with acquired hemophilia — especially for patients given both clot-promoting and blood-thinning medications.
With more research, a TGA could help doctors better tailor treatment, the scientists concluded, noting that “clinicians may be able to use [thrombin generation] parameters to better guide therapeutic decisions.”
