The use of recombinant factor viia in a jehovah's witness with auto‐immune thrombocytopenia and post‐splenectomy haemorrhage
Year: 2002
Type: article
Abstract: We report a 68-year-old female Jehovah's Witness who presented with a widespread purpuric rash, blood blisters in the mouth and a platelet count of 3 × 109/l. The blood count was otherwise normal and bone marrow examination was consistent with idiopathic auto-immune thrombocytopenia. She was commenced on prednisolone 60 mg/d. On d 11 after presentation, the platelet count was only 10 × 109/l. It was confirmed that immunoglobulins were an acceptable treatment and the patient received a 3 d course of intravenous immunoglobulin (IVIgG) 25 g/d. The maximum platelet count achieved was 31 × 109/l. She therefore received methyl prednisolone 500 mg i.v. for 3 d, but the platelet count remained at 14 × 109/l. On d 40, the patient was again given IVIgG, 30 g (0·4 g/kg) daily for 4 d. On d 44, the platelet count had risen to 52 × 109/l with Hb 14·4 g/dl; this platelet count was considered sufficient to allow splenectomy safely to be performed and surgery was carried out on d 47. The preoperative coagulation screen was prothrombin time (PT) 12 s (normal range, 11–16 s), activated partial thromboplastin time (APTT) 21 s (22–35 s), fibrinogen 3·3 g/l (1·5–4·5 g/l). Several hours after splenectomy, her abdomen was found to be tense and distended; the haemoglobin (Hb) was 8·0 g/dl with platelets 46 × 109/l. Gelatin solution (1500 ml) was given as a non-blood-derived volume expander and packing inserted to try to contain the bleeding; aprotinin and tranexamic acid were commenced. The patient was transferred to the intensive therapy unit (ITU) with Hb 4·5 g/dl, platelet count 17 × 109/l, PT 21 s, APTT 74 s and fibrinogen 1·6 g/l. Cryoprecipitate was acceptable to the patient and she received 8 units on two occasions. Despite continuing life-threatening haemorrhage and in the face of significant thrombocytopenia and coagulopathy, the patient continued to refuse most plasma products. Recombinant factor VIIa (Novosen, Novo Nordisk) was then administered at a dose of 90 µg/kg. Haemostasis was achieved, following a single dose, and after two doses coagulation was normal (PT 11 s, APTT 28 s, fibrinogen 4·4 g/l). A third dose was given after the patient returned to theatre for removal of packs, when the coagulation tests deteriorated (see Fig 1A). Factor VIIa has been reported to promote haemostasis in intractable haemorrhage, e.g. following severe trauma (Kenet et al, 1999; Martinowitz et al, 2001). As it is not derived from blood, the product is acceptable to Jehovah's Witnesses (Majumdar & Savidge, 1993; Papatheodoridis et al, 1999). Her thrombocytopenia was managed by continuing steroid therapy and IVIgG. (A and B) Serial coagulation tests, haemoglobin and platelet counts. Erythropoeitin (10 000 units three times per week) was commenced on the second day in the ITU (Koestner et al, 1990); vitamin B12, folate and intravenous iron sucrose were also administered. Further blood loss was minimized by use of paediatric microsampling. Human or bovine haemoglobin solutions (natural or recombinant) or perfluorocarbons (Marelli, 1994; Doyle, 2001) were found not to be available outside the context of clinical trials in the USA and Canada. Hyperbaric O2 was also considered, but it was thought that the risk of transferring the patient would outweigh the benefit. On d 51, the patient suffered an episode of fast atrial fibrillation and the following day she developed Candida albicans pneumonia. On d 62, there was evidence of auto-immune haemolytic anaemia (Hb 6·4 g/dl, positive direct antiglobulin test, reticulocytes 9·1%, lactate dehydrogenase 1488 iu/l) and further IVIgG was given. By d 72, the Hb had risen to 10·4 g/dl, with a platelet count of 131 × 109/l (Fig 1B). Coagulation was normal as follows: PT 14 s, APTT 25 s, fibrinogen 4·2 g/l. Erythropoeitin was reduced to 3000 units three times per week. Inspired oxygen had been reduced to 40% and it was hoped to wean her off the ventilator. However, on d 73, the patient suffered two rectal bleeds, despite a platelet count of 145 × 109/l and normal coagulation. She continued to bleed and her Hb fell to 6·5 g/dl. It was thought that the patient would not survive total colectomy and she died on d 75. At post mortem, there was evidence of ischaemic colitis, a relatively common complication of long-term treatment on the ITU, as well as adult respiratory distress syndrome and multiorgan failure. The treatment of this patient using non-blood methods resulted in a significantly higher cost. The major drug costs and an estimate of the costs of keeping the patient on ITU totalled almost £44 000. The cost of recombinant FVIIa was £10 250 but, although the final outcome in this patient was unsuccessful, recombinant factor VIIa clearly arrested bleeding in the face of life-threatening haemorrhage and coagulopathy and would be of value again in similar circumstances.
Source: British Journal of Haematology
Authors: Dominic P. Waddington, Frank T. McAuley, John P. Hanley, Geoffrey P. Summerfield
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2006014541