Hard-to-treat blood clots due to PNH improve with Ultomiris
A woman developed blood clots that resisted anticoagulant treatment
Treatment with Ultomiris (ravulizumab) successfully reduced multiple blood clots that didn’t respond to standard anti-clotting therapy in a woman with paroxysmal nocturnal hemoglobinuria (PNH), a case study shows.
“This report presents a case of myocardial and renal infarction [heart and kidney tissue death due to blood supply obstruction] in which multiple [anticoagulant-resistant blood clots] were observed due to PNH,” and in which Ultomiris treatment “was extremely effective,” the researchers wrote.
The case report, “Recurrent acute myocardial and renal infarction with aplastic anaemia/paroxysmal nocturnal haemoglobinuria syndrome: a case report,” was published in the European Heart Journal Case Reports.
PNH is an acquired disease marked by red blood cell destruction, or hemolysis, that’s driven by the abnormal activation of the complement cascade, a part of the immune system. Hemolysis and the abnormal activation of platelets, the blood fragments involved in blood clotting, are thought to be behind the formation of blood clots within blood vessels, or thrombosis, that marks PNH.
“Moreover, thrombosis itself leads to complement activation, which in turn leads to further thrombosis, a vicious cycle that continues,” wrote the researchers, who noted “a high fatality rate due to thrombosis has been reported” in PNH patients.
Blood clots can travel through the bloodstream to another location in the body, where they can block blood flow and cause potentially fatal clot-related events.
“Thrombosis due to PNH is often resistant to anticoagulation, and anti-C5 … antibodies such as [Soliris (eculizumab) and Ultomiris] have been proven to be effective,” the researchers wrote. Both therapies, which are approved for PNH, are lab-made antibodies that suppress the complement protein C5, preventing the activation of the complement cascade and reducing hemolysis.
Blood clots resistant to treatment
Here, researchers in Japan described the case of a 24-year-old woman who developed multiple blood clots due to PNH that were resistant to standard anticoagulant treatment, but were effectively reduced with subsequent Ultomiris treatment.
The woman had been diagnosed about 1.5 years before with aplastic anemia, where bone marrow fails to produce sufficient red and white blood cells and platelets. She was being treated for the condition with cyclosporine and danazol, both known for controlling immune system activation.
“It is known that PNH can occur during the treatment of [aplastic anemia],” the researchers wrote.
The woman sought emergency care after having chest pain for five days, along with cold sweats. Her vitals were within normal, as was her hemoglobin, the protein in red blood cells that transports oxygen, but she had low platelet counts.
Blood tests showed abnormal heart protein levels, indicating potential heart damage, and a heart test revealed problems with the heart’s electrical activity. The woman underwent an emergency test to see how blood flowed through her heart and it detected infarction of the heart muscle due to a blood clot blockage in its right artery.
Surgery to remove the clots and restore blood flow was performed, and the woman was given anticoagulant medication, but about a week later she developed another blood clot-related blockage in a heart artery. More clot-removal procedures were done, but full blood flow wasn’t recovered.
Starting Ultomiris treatment
The woman developed severe right lower back pain with cold sweats and imaging tests showed a blood vessel blockage in her kidney. Comprehensive analyses found no other clots besides those in the heart and kidney.
She also had high levels of LDH, a marker of hemolysis, along with low hemoglobin levels and high levels of markers of kidney damage, with her platelet counts falling even further.
The woman also had high levels of a thrombosis marker called D-dimer, despite anticoagulant treatment, suggesting a mechanism behind the recurrent blood clots “that would not respond to conventional anticoagulant therapy,” the researchers wrote.
Imaging scans on the 24th day of her clinical course showed her kidney and heart thrombosis had worsened. The woman said her urine was brownish in color in the morning, suggesting hemoglobin in the urine due to excessive hemolysis.
Four days later, the doctors confirmed the diagnosis of PNH by detecting an increase in the percentage of blood cells deficient in two cell surface proteins called CD55 and CD59, a PNH hallmark. Treatment with Ultomiris was started that day and after a few days her chest and back pain eased, while D-dimer and LDH levels fell significantly. She was discharged on day 39 and continued on Ultomiris. After six months, imaging scans showed reduced blood clots and related damage in both the heart and kidneys, “with no observed recurrence of thrombosis,” the researchers wrote.
This case report suggests that “anti-complement component C5 therapy is very effective in improving rapidly progressive multiple … thrombosis resistant to anticoagulants and antiplatelet agents due to PNH,” and that it “should be administered immediately if fatal thrombosis is observed in patients with PNH,” they wrote.
