A new draft guideline for the diagnosis and management of thrombocytopenic purpura (TTP) was recently released by the International Society on Thrombosis and Hemostasis (ISTH).
According to the panel of experts involved, the ISTH guideline takes into account the latest TTP findings, offering a more up-to-date resource for clinicians than the two previously published guidelines in 2012 from the British Committee for Standards in Haematology and in 2017 from the TTP group of Japan’s Blood Coagulation Abnormalities Research Team.
“Since the publication of these guidelines, there have been significant developments in the diagnosis and treatment of TTP, and an increase in published data on how management strategies affect objective health outcomes,” the panel members wrote in the guideline, which is available at.
Despite these advancements, TTP remains a challenging condition for both clinicians and patients for a variety of reasons, the panel noted, which was led by clinical cochair, of the University of Alabama in Birmingham and method cochair , of the University of Oklahoma, Oklahoma City.
The ISTH guideline provides recommendations for adult patients with either immune or hereditary TTP, from acute events through remission, including diagnostic steps to determine if a case of thrombotic microangiopathy is in fact TTP.
Nearly all the recommendations are based on very-low-certainty evidence. Some of the key treatment recommendations include the following:
- For patients with immune TTP experiencing a first acute event, add corticosteroids to therapeutic plasma exchange (TPE), rather than treating with TPE alone. This is a strong recommendation.
- For patients with immune TTP experiencing a first acute event, add rituximab to corticosteroids and TPE, rather than corticosteroids and TPE alone. This is a conditional recommendation.
- For patients with immune TTP experiencing a relapse, add corticosteroids to TPE, rather than TPE alone. This is a strong recommendation.
- For patients with immune TTP experiencing a relapse, add rituximab to corticosteroids and TPE, rather than steroids and TPE alone. This is a conditional recommendation.
- For patients with immune TTP experiencing an acute event – either a first event or a relapse – use caplacizumab. This is a conditional recommendation based on moderate-certainty evidence.
- For patients with immune TTP who are in remission and have low plasma ADAMTS13 activity but no other symptoms of TMA, use rituximab for prophylaxis. This is a conditional recommendation.
- For patients with hereditary TTP who are in remission, plasma infusion or a watch-and-wait strategy is recommended. This is a conditional recommendation.
- For patients with hereditary TTP who are in remission, do not use factor VIII concentrate infusions. A watch-and-wait strategy is advised. This is a conditional recommendation.
- For patients with immune TTP who are pregnant and have decreased plasma ADAMTS13 activity but no symptoms of TMA, use prophylactic treatment. This is a strong recommendation.
- For patients with hereditary TTP who are pregnant, use prophylactic treatment. This is a strong recommendation. The panel further recommended treatment with plasma infusion rather than factor VIII products, which was a conditional recommendation.
The multidisciplinary expert panel included hematologists and pathologists with expertise in TTP, neurologists, nephrologists, intensive care specialists, and patient representatives. The panel followed the GRADE approach and the Population, Intervention, Comparison, Outcome (PICO) framework, and adhered to standards set forth by the Health and Medicine Division (HMD) of the National Academies of Sciences, Engineering, and Medicine and the GIN-McMaster Guideline Development Checklist.
Even with an experienced group of physicians and a structured plan, however, the creation of guidelines for rare diseases like TTP presents a unique set of obstacles, according to the panel members. Challenges include a small body of relevant evidence that is often inconsistent and lacking in high certainty and studies that do not address outcomes important to patients. These shortcomings can make it difficult for guideline developers to issue strong recommendations.
“However, well-developed clinical practice guidelines are vital in rare diseases; these conditions are, by their nature, encountered very infrequently by individual clinicians, who may feel unprepared to address their diagnosis and treatment,” the panelists wrote. “Well-synthesized evidence and clear recommendations play an important role in supporting clinical decision making. Systematically created guidelines can also highlight areas where evidence is uncertain, clinical judgement is required, and future research in the area is warranted.”
The guideline was supported by ISTH. Fifty percent of the panel members had no or minimal conflict of interest; those with conflicts of interest abstained from voting on recommendations relevant to their conflicts.