Hematocase Spontaneous intraocular bleeding as an initial presentation of Factor XI deficiency L. Duquenne, MD1, V. Schlesser, PhD2, Z. Jedidi, MD3, L. Plawny, MD4 Haemophilia C, also known as Rosenthal syndrome, is a rare disorder affecting essentially persons of Ashkenazi Jewish ascendancy. We report the case of a 79 year old patient without previous bleeding history, except for slight bruising, who presented with a severe retinal bleeding in the absence of trauma. Biology showed elevated activated partial thromboplastin time (77,7 seconds vs. normal range 30-36 seconds). Factor analysis showed isolated decreased Factor XI of 1%. No Factor XI inhibitor could be found. The patient was subsequently treated with Factor XI infusions which allowed a reduction of the bleeding and normal eyesight within four days. Spontaneous bleeding in old age is a rare inaugural sign of Factor XI deficiency, such episodes mostly occur after haemostatic challenge such as surgery or trauma leading to blood analysis and coagulation tests. Intraocular haemorrhage is an uncommon presentation of mild bleeding disorders.1-5 (Belg J Hematol 2014;5(1):22-24) Introduction most prevalent genetic defects among the Ashkenazy Haemophilia C is defined by a dysfunction of the Factor Jewish population, eight to nine percent of them presents XI activity. It can result from an impairment of secre- a heterozygous mutation while homozygosity varies tion, dimerisation or by a mechanism of heterodimer from 0.22% - 0.53%.1-3 trapping in heterozygous subjects. A bleeding score has been computed by the Interna- Factor XI (FXI) is a plasma glycoprotein that partici- tional Multicentre Study initially described for von pates in the intrinsic phase of blood coagulation.6,7 Un- Willebrand disease, defining grades of bleeding severity like other contact factors, FXI plays an important role in coagulation disorders. It combines symptoms and for the in vivo coagulation. It amplifies the initial coag- their severity. For example a tooth extraction with ulation response by activating Factor IX, thus enhancing bleeding requiring no intervention counts as one point thrombin generation.6,7 whereas cutaneous hematomas denotes two points.9 Approximately 190 FXI mutations have been identified to date. History Rosenthal syndrome is a rare occurrence, affecting A 79 year old man of Ashkenazi Jewish origin, with a one person in a million. Patients are typically of Jewish past medical history of untreated hypertension, reported Ashkenazi origin, but the deficiency has also been a red veil and scotomas for about two weeks prior to described in other ethnic groups such as French Basques consultation. The patient displayed no major bleeding and in the UK.8 Congenital FXI deficiency is one of the history, except prolonged bleeding after tooth extraction. 1Department of Rheumatology, Université de Liège, CHU de Liège, Liège, Belgium 2Laboratory of Haematology and Transfusion, CHL Luxembourg, Luxembourg, Belgium 3Department of Neurology, CHU de Liège, Liège, Belgium 4Department of Haematology, CHL Luxembourg, Luxembourg, Belgium. Please send all correspondence to: L. Duquenne, MD, Université de Liège, CHU de Liège, Department of Rheumatology, Av. de l'hôpital 1, 4000 Liège, Belgium, tel: +32 4 366 78 63, email: [email protected]. Conflict of interest: The authors have nothing to disclose and indicate no potential conflict of interest. Keywords: coagulation Factor XI, Haemophilia C, spontaneous intra-ocular bleeding. Belgian Journal of Hematology Volume 5, Issue 1, March 2014 22 1 Biologic evolution aPTT and FXI Time (hours) Figure 1. Biological evolution of the patient. Hemoleven® injections are indicated by the red arrows. Fresh frozen plasma injections are indicated by the black arrows. The bleeding score was evaluated at three points. The needing treatment with diuretics. We therefore decided patient did not take any anticoagulation medicine. to resort to FXI (Hemoleven®) infusions, to allow the FXI rate to normalise more quickly and to avoid fluid Clinical examination overload. Cutaneous examination revealed no bruises or hemato- The required doses of Hemoleven™ were defined by the mas. Neurological examination was normal, the cranial equation: nerves were spared and there was no sign of oculomotor disturbance. The visual fields were intact and there (Desired FXI(%) –Measured FXI(%)) X weight was no loss of sight of the right eye and no diplopia. 2 Complementary exams Evolution A fundoscopy revealed a severe retinal bleeding. Figure 1 shows the evolution of aPTT and FXI levels Peripheral blood count and liver function tests were during treatment with Hemoleven. A starting dose of normal. Coagulation tests displayed a prothrombin time 3000 units allowed the FXI to rise above 60%. Hemo- of 100%, a normal INR at 1 and a prolonged aPTT of leven dosage was later adjusted to a target FXI level of 77,7 seconds (normal ranges 30-36 seconds). Factor 60%. After three days of treatment, the veil began to VIIIC, IX and XII were normal. FXI was decreased to fade and the patient did not experience scotomas any- 1% (normal range 50-100%). more. Plasmatic FXI levels were maintained during one Factor XI levels were corrected by 50/50 dilution with week until full recovery from the symptoms. During a control plasma sample, indicating the absence of hospitalisation, the patient displayed two episodes of inhibiting antibodies. hypertension requiring treatment with lisinopril. Treatment Conclusion Six units of fresh frozen plasma were transfused in the Intraocular bleeding is a rare condition. It has been first 24 hours, raising the FXI level to 20%. Unfortu- described as a side effect of thrombolysis, use of sero- nately, plasma infusions were complicated by hyper- tonin reuptake medication and warfarin use, especially tension due to fluid overload and pulmonary edema, in combination with anti-platelet treatments. Some Belgian Journal of Hematology Volume 5, Issue 1, March 2014 23 Hematocase Key messages for clinical practice 1. Unusual spontaneous bleeding should lead to a deep coagulation system investigation, especially in disturbed usual coagulation tests. Moreover, tests have to be run in sub-populations, such as the Ashkenazy Jewish population and in other ethnic groups such as the French Basques and in the UK.8 2. Inherited coagulation disorders may be discovered in old age after a haemorrhagic challenge. publications report an intraocular bleeding in associa- In these patients, FFP is still the recommended medi- tion with a subarachnoid haemorrhage, known as the cation. The most worrying side effect is a condition of Terson syndrome. It may occur during a severe throm- increased coagulation, leading to deep vein thrombosis, bocytopenia episode, after eye surgery or after a trauma. pulmonary embolism, the most considerable issue being In our review of the literature, no cases were reported a disseminated intravascular coagulation. of spontaneous ocular bleeding caused by blood hy- pertension, but it may increase the bleeding. Rarely, References spontaneous intraocular bleeding may result from an 1. Peyvandi F, Bolton-Maggs PH, Batorova A, et al. Rare bleeding disorders. underlying coagulation defect.10-12 Haemophilia 2012;18 Suppl 4:148-53. Therefore, each episode of spontaneous bleeding should 2. Bolton-Maggs PH. The rare inherited coagulation disorders. Pediatr Blood be explored with complete coagulation tests. In Jewish Cancer 2013;60 Suppl 1:S37-40. Ashkenazi patients and in other ethnic groups, the 3. Guéguen P, Galinat H, Blouch MT, et al. 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