Pegylated bovine carboxyhaemoglobin utilisation in a thrombotic thrombocytopenic purpura patient

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Thrombotic thrombocytopenic purpura (TTP) is a condition characterized by thrombotic microangiopathy with anaemia and thrombocytopenia. It is a haematologic emergency, with mortality rates of >90% when left untreated (Amorosi, 1966). The introduction of therapeutic plasma exchange (PLEX) has decreased mortality rates to less than 10%, and it has become the mainstay of the initial management of patients presenting with TTP (Bell et al., 1991; Lara et al., 1999). However, this presents a unique challenge in a Jehovah's Witness patient who is unwilling to accept plasma due to her religious beliefs. Plasma provides ADAMTS13 replacement and reduces risk of bleeding due to depletion of coagulation factors. There are a few reports of various alternative strategies to PLEX, including use of plasma exchange with albumin, chemotherapeutic agents such as vincristine, rituximab and/or steroids (Drummond et al., 2000; Dabak et al., 2007; Walia et al., 2011; Chai et al., 2015). We report the successful management of TTP in a Jehovah's Witness patient using pegylated bovine carboxyhaemoglobin (Sanguinate™, Prolong Pharmaceuticals, Inc., South Plainfield, NJ, USA) as an adjunct medication.
A 22‐year‐old woman presented with 2 months of easy bruising. She had superficial ecchymosis on her upper extremities but no evidence of haemodynamic instability, fevers or neurologic abnormalities. Laboratory studies revealed a white blood cell count of 12·6 (103 per μL) with normal differential, haemoglobin of 10·1 (g dL−1), platelet count of 12 (103 per μL), lactate dehydrogenase increased >4 times the upper limit of normal and low haptoglobin. Coagulation studies, fibrinogen levels and creatinine were within normal limits. Peripheral smear revealed numerous schistocytes, red blood cell fragments and decreased platelets. ADAMTS13 level returned as <5% with an inhibitor level of >8 Bethesda units, confirming the diagnosis of acquired TTP.
PLEX with plasma replacement was recommended; however, she declined plasma infusion due to her religious beliefs as a Jehovah's Witness. She was treated on day 1 with a combination of high dose corticosteroids, folate, erythropoietin and PLEX with albumin replacement. Blood draws were minimised and paediatric tubes to reduce blood loss were utilised. The ability to deliver therapy with PLEX with albumin was limited due to depletion of fibrinogen to levels <100 mg dL−1. She received rituximab on day 3, and vincristine on day 5 (Chai et al., 2015). Platelet count and haemoglobin continued to decline. On day 7, she consented to receive cyroprecipitate, and underwent PLEX with albumin replacement and cryoprecipitate supplementation was given post‐therapy to keep fibrinogen >100 and to reduce bleeding risk. We obtained institutional review board (IRB) approval for enrolment of this patient on a clinical trial investigating the use of Sanguinate in patients with acute severe anaemia (NCT02754999). The patient and family signed the informed consent to enrol into the study. A 40 mg mL−1, 500 mL total volume dose of Sanguinate was infused daily for 4 days based on her symptoms, beginning on the 10th day of hospitalisation. This was given after PLEX with albumin replacement to avoid removal of drug by pheresis. Her platelet count began to trend upwards on day 10, while improvement in haemoglobin began on day 12 (Fig. 1). Treatment was well tolerated, with grade 1 paresthesia of the right face and arm 1 h after the first infusion of Sanguinate that spontaneously resolved and did not recur, and grade 1 cardiac troponin elevation after receiving the medication (with peak at 0·079 ng mL−1), but further workup with electrocardiogram and echocardiogram was unremarkable. By discharge on day 19, her haemoglobin increased to 8·8 g dL−1 and platelet count to 221 000.
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