Because they have detected sluggishness in hospital diagnoses, researchers have developed an algorithm to help clinicians determine whether patients have acquired hemophilia A (AHA), a rare bleeding disorder that mainly affects elderly men with medical problems.
“A simple algorithm for unexplained bleeding might be helpful to emergency department physicians and other frontline workers to improve recognition of the disease,” said Amar Kelkar, MD, a fellow at the Dana-Farber Cancer Institute, Boston, and corresponding author of “Time is blood: The impact of diagnostic delays on acquired hemophilia A,” a report that appeared in the journal Cureus.
According to Kelkar, AHA is an autoimmune disease caused by the formation of autoantibodies against factor VIII (FVIII). “Classically, patients present with various forms of bleeding symptoms, including extensive bruising, spontaneous prolonged or persistent bleeding, and blood in the urine. These symptoms are usually accompanied by a prolonged activated partial thromboplastin time (aPTT) test,” he said in an interview. “While this is a rare diagnosis to be seen in primary, critical, or emergency care, it’s a disease that most hematologists should have seen and managed before.”
For the new study, researchers retrospectively tracked patients with AHA at the OSF Healthcare System in Illinois from 2010 to 2017. They focused on six patients (mean age, 79.5; male = 5). Cancer was considered a cause in four cases, and autoimmune disease in one. The sixth case was idiopathic. Five of the six patients died, with all but one death related to bleeding.
The researchers note that they saw more cases than expected (6 per 2.1 million vs. an estimated incidence of 1.48 per 1 million per year), although they attributed this high incidence to the population being made up of older hospitalized patients. In fact, Kelkar said, researchers believe this is an undercount reflecting diagnostic misses.
The median time to diagnosis was 14 days, the authors report, reflecting other studies that have also shown delays. Pseudo-thrombosis and preexisting anticoagulant therapy likely contribute to the diagnostic delays, they write.
In their new report, the authors developed an algorithm to speed diagnosis.
“The initial step is the identification of a patient with new, unexplained bleeding,” they write. “In the setting of unexplained bleeding, a detailed clinical history, including medication use, along with a thorough physical examination is critical. Prompt primary laboratory testing should include a complete blood count, a metabolic panel including creatinine and bilirubin, and coagulation testing including aPTT and prothrombin time with international normalized ratio (PT/INR). A resulting isolated aPTT elevation will initiate subsequent steps. Early inpatient hematology consultation is recommended.”
The authors add: “An important point to highlight is that we recommend concurrently ordering an aPTT mixing study and a factor VIII activity (FVIII:C) once a prolonged aPTT is confirmed. This may decrease the time to initiate treatment and improve patient outcomes. If the mixing study result is abnormal with low FVIII:C, hemostatic treatment could be initiated with concurrent confirmatory Bethesda assay or anti-FVIII ELISA, preventing further delay in patient recovery and hopefully reducing potential complications. If there is limited availability of specialty testing or prolonged delays in getting test results, such as for FVIII:C, or an inability to confirm a diagnosis at any stage of the algorithm, transferring the patient to a higher level of care with these laboratory and hematology services should be strongly considered.”
The authors also note that “when the diagnostic delay is greater than 1 month, there will be a significant increase in the days that the patient is required to be on hemostatic therapy, compared to diagnosis before 1 month (23.8 ± 13 vs. 7.6 ± 5.7 days, respectively; P = .003).”
The algorithm is meant to be widely available, Kelkar said. “That is why we targeted an open-source, general medicine journal like Cureus.”
Jerome Teitel, MD, a hematologist with St. Michael’s Hospital in Toronto, said in an interview that the algorithm “might be a useful guide for initial investigation at community hospitals.”
However, he recommended against emphasizing the use of mixing studies. They are “often ambiguous and just delay ordering the definitive tests (FVIII activity and inhibitor assay), which will need to be done regardless,” he said. “The most important message should be that patients with AHA should be referred to, or at least comanaged with, a hematologist who has specific experience and expertise in the field, and who will likely have access to specialized coagulation tests with short turnaround times.”
Another hematologist, George M. Rodgers III, MD, of the University of Utah, Salt Lake City, said in an interview that the algorithm is appropriate for the evaluation of possible AHA. “Patients with the disorder who present with minor bleeding are not evaluated with high priority by physicians,” he said. “Patients with bleeding and a prolonged PTT should be taken very seriously because AHA patients can develop spontaneous fatal bleeding.”
No study funding is reported. The authors, Teitel, and Rodgers report no relevant disclosures.
This story originally appeared on MDedge.com, part of the Medscape Professional Network.
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Cite this: ‘Time Is Blood’: Researchers Devise Shortcut to AHA Diagnosis - Medscape - Apr 20, 2022.