Combined treatment successful for woman with TTP and lupus
26-year-old with lupus developed immune-mediated TTP, doctors say
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A 26-year-old woman who arrived at a hospital with lupus and severe thrombocytopenia (very low numbers of blood-clotting platelets) was ultimately diagnosed with immune-mediated thrombotic thrombocytopenic purpura (TTP) and successfully treated with plasma exchange, corticosteroids, rituximab, and Cablivi (caplacizumab), leading to her rapid recovery.
Similar to previous cases, she “had an excellent clinical response,” researchers at Reading Hospital in Pennsylvania wrote in a report, “Immune-Mediated Thrombotic Thrombocytopenic Purpura in a Patient With Systemic Lupus Erythematosus and Recent Epstein-Barr Virus Infection: A Diagnostic Challenge,” published in the Cureus Journal of Medical Science.
In immune-mediated TTP, reduced activity of the ADAMTS13 enzyme causes blood clots to block small blood vessels throughout the body. Normally, ADAMTS13 helps prevent platelets from forming blood clots when they are not needed. Excessive blood clotting can lead to low blood cell counts, among other TTP symptoms.
Having an autoimmune disease, such as lupus, can increase a person’s risk of developing immune-mediated TTP. It can be difficult to distinguish immune-mediated TTP from other conditions resulting in low blood-cell numbers, but “early recognition is critical because delayed treatment is associated with significant morbidity and mortality,” the researchers wrote.
Fever, pain, bleeding
The woman, who had systemic lupus erythematosus, arrived at the hospital with fever, back pain, nosebleeds, and bleeding gums. She also had lupus nephritis, an inflammation of the kidneys that can occur as a complication of lupus, and a previous pulmonary embolism, which occurs when a blood clot blocks blood flow to the lungs.
Blood tests showed the woman had severe thrombocytopenia. Other tests suggested that red blood cells were being destroyed faster than normal (hemolysis). Bilirubin and lactate dehydrogenase, released when red blood cells break down, were elevated. Haptoglobin, which normally binds free hemoglobin released from broken red blood cells, was undetectable.
A blood smear showed schistocytes (fragmented red blood cells), which can form when red blood cells are damaged as they pass through small blood vessels containing clots. This finding raised concern about TTP.
The patient also had a positive direct antiglobulin test, which detects antibodies or complement proteins attached directly to the surface of red blood cells. As a result, doctors initially considered immune thrombocytopenia (ITP), in which the immune system destroys platelets, and Evans syndrome, in which the immune system destroys both red blood cells and platelets.
A CT scan showed enlarged lymph nodes in the armpits and abdomen but no enlargement of the liver or spleen. Since she had a fever, doctors also investigated possible infections. Testing showed evidence of a recent infection with the Epstein-Barr virus (EBV), the virus that causes mononucleosis, commonly called mono.
The woman was first treated for ITP with intravenous immunoglobulin, a treatment that uses antibodies to reduce immune attacks on platelets, and dexamethasone, a corticosteroid that suppresses immune activity. However, her platelet counts did not improve. Red blood cells continued to break down, and schistocytes remained visible on blood smears.
Doctors calculated a PLASMIC score — an algorithm that predicts ADAMTS13 deficiency — of 7, indicating a very high risk. Because untreated TTP can rapidly lead to organ failure and other life-threatening complications, treatment was started before confirmatory test results became available.
On the fourth day of hospitalization, the woman began plasma exchange (plasmapheresis), a procedure that removes disease-causing antibodies from the blood and replaces the plasma with donor plasma containing functional ADAMTS13. The woman also started prednisone, another corticosteroid used to suppress immune activity.
Later that day, testing confirmed that ADAMTS13 activity was undetectable, proving the diagnosis of immune-mediated TTP. Treatment was intensified with rituximab (marketed as Rituximab, with biosimilars available), which destroys the B-cells responsible for producing disease-causing antibodies, and Cablivi, which prevents blood clots from forming. She continued receiving hydroxychloroquine for her lupus.
After TTP-directed treatment began, the woman’s platelet numbers increased rapidly. Plasma exchange was stopped once her platelets remained within the normal range for two consecutive days. Repeat testing showed recovery of ADAMTS13 activity. The woman felt well and was discharged home on prednisone, Cablivi, hydroxychloroquine, and mycophenolate mofetil, another immunosuppressive medication.
“EBV infection may have contributed to the development of immune-mediated TTP in this patient,” the researchers wrote. However, they added, “in patients with [systemic lupus erythematosus] presenting with severe thrombocytopenia, hemolysis, and [schistocytes], immune-mediated TTP should remain a key diagnostic consideration even in the presence of … infection.”
