470-98 Acta Pñdiatr 88: 342±3. 1999 CLINICAL OBSERVATION Intracranial haemorrhage due to factor V deficiency M Totan and D Albayrak Medical Faculty of Ondokuz Mayıs University, Department of Paediatric Haematology, Samsun, Turkey Totan M, Albayrak D. Intracranial haemorrhage due to factor V deficiency. Acta Pædiatr 1999; 88: 342–3. Stockholm. ISSN 0803–5253 Factor V deficiency is a rare coagulation disorder which is inherited autosomal recessively. Factor V deficiency should be considered in infants with bleeding disorders and prolonged prothrombin and activated partial thromboplastin times if bleeding continues in spite of vitamin K injection. In this article, the case of an infant with an intracranial haemorrhage due to congenital factor V deficiency is reported. & Factor V deficiency, intracranial haemorrhage M Totan, Medical Faculty of Ondokuz Mayıs University, Department of Paediatric Haematology, 55139 Samsun, Turkey (Tel. +90 362 4576000-2498, fax. +90 362 4576041) Factor V (labile factor, proaccelerin) deficiency is a hereditary coagulation disorder which is characterized by clinical manifestations of epistaxis, menorrhagia, echymosis and mucosal bleeding. It is thought to be inherited autosomal recessively and frequently seen with congenital anomalies (1, 2). When the factor V level is below 1% severe bleeding is seen and when it is between 2 and 20% mild or moderate bleeding is seen (3). In this study, a case who has an intracranial haemorrhage due to congenital factor V deficiency and congenital heart disease is reported. Case report A 3-month-old boy was referred to the paediatric haematology department with the complaints of vomiting, epistaxis, pallor and epileptic seizure. There was no history of drug ingestion or trauma and the parents were second-degree relatives. On physical examination, his bodyweight was 5600 g (25–50 percentile), height 61 cm (50–75 percentile), head circumference 41 cm (50–75 percentile), blood pressure 70/40 mmHg and pulse rate 168 beats minÿ1. He was hypoactive and seemed pale. There were evident bleeding foci and oedema on the left fundus. On cardiac examination, a grade III/VI° systolic murmur and a fixed split S2 were heard. The liver was palpable 4 cm below the midclavicular line and other physical examination findings were normal. Laboratory studies revealed: haemoglobin 67 g lÿ1, haematocrit 21%, prothrombin time (PT) 40 s (normal range 11–13 s), activated partial thromboplastin time (APTT) 120 s (normal range 27–36 s), factor V 2.1% (normal range 70–120%). Factor V antibodies could not be detected. Platelets, mean corpuscular volume (MCV), leucocytes, factor VIII, protein C, protein S, antithrombin III, bleeding time, thrombin  Scandinavian University Press 1999. ISSN 0803-5253 time, fibrinogen, liver and kidney function tests were within normal limits. Atrial septal defect (ASD) and atrial septal aneurysm were established by echocardiography (ECHO). Electroencephalography showed a generalized epileptiform anomaly in the right frontocentral region. Computed tomography demonstrated a parenchymal haemorrhage and mild oedema in the parietal region (Fig. 1). Abdominal ultrasonography was normal. Erythrocyte transfusion was given to the patient and haemoglobin level rose to 126 g lÿ1. The seizures could not be controlled with diazepam and phenobarbital was started. Prothrombin time and APTT were prolonged. Late haemorrhagic disease of the newborn was suspected and 5 mg vitamin K was administered intramuscularly. The prolonged PT and APTT did not improve. Bleeding time and thrombin time were normal but factor V was 2.1%. Factor V deficiency was diagnosed and fresh frozen plasma (FFP) was given three times a day. The patient recovered with conservative treatment and was discharged on the 16th hospitalization day. The intracranial haemorrhage gradually resolved. Haemoglobin, platelets, PT and APTT values of the parents and siblings were within normal limits. Discussion Factor V deficiency was first described by Owren in 1947 (4). Symptoms were generally seen in homozygous patients. Although it is frequently inherited autosomal recessively, a few families with an autosomal dominant inheritance have been reported (1). Factor V is deposited in platelet a-granules and released with platelet activation. The remaining 75–80% of factor V is made in hepatocytes and vascular endothelium. While 470-98 Intracranial haemorrhage ACTA PÆDIATR 88 (1999) Fig. 1. Intracranial haemorrhage due to factor V deficiency on a cranial computed tomography slit. the half-life of factor V in the circulation is generally 12–20 h, it can vary between 5 and 36 h (5). An important characteristic of factor V deficiency is its probability of coincidence with congenital anomalies. Mental retardation, cleft lift and palate, dwarfism, microcephaly, hydrocephalus, hydrocele, duplication of renal pelvis, syndactyly, hypogonadism and congenital heart anomalies (ASD, ventricular septal defect, coarctation of the aorta) have been reported (1, 6). In our patient, ASD and atrial septal aneurysm were established by ECHO. Congenital factor V deficiency must be distinguished from combined factor V and factor VIII deficiencies. The levels of these factors in combined factor V and VIII deficiency range from 15 to 20% (7, 8). Transient bleedings can be seen due to specific antibodies to factor V in postoperative patients and patients who take antibiotics. Factor V deficiency is also seen in disseminated intravascular coagulopathy (DIC) and severe liver diseases (1). In the present case, there was no history of any previous operation, drug taking, DIC or liver disease. Factor V antibodies could not be detected. Intracranial haemorrhage due to factor V deficiency is rare and only five cases have been reported to date in the literature (1, 9). Fresh frozen plasma is given as a treatment. When factor V deficiency is complicated by 343 bleeding, large amounts of FFP are needed and infusion must be given within 3–4 h. In acute bleedings it may be necessary to give platelet transfusions. Since alloimmune antibodies to platelets can develop, prophylactic transfusions should not be administered (1). Fresh frozen plasma was given three times a day to this patient while he was in the hospital (16 d). After discharge, 20 doses every day and 10 doses every other day were given, in total 30 doses of FFP. To summarize, in early infancy, if intracranial haemorrhage with congenital anomalies is detected, factor V deficiency should be considered in the differential diagnosis of late haemorrhagic disease of the newborn (vitamin K deficiency). References 1. Roberts HR, Hoffman M. Haemophilia and related conditions inherited deficiencies of factor II, factor V, and factors VII to XII. In: Beutler E, Lichtman MA, Coller BS, Kipps TJ, editors. Williams Hematology. 5th ed. New York: United States, 1995 2. Manotti C, Quintavalla R, Pini M. Thromboembolic manifestations and congenital factor V deficiency: a family study. Haemostasis 1989; 19: 331–9 3. Seeler RA. Parahaemophilia: factor V deficiency. Med Clin North Am 1972; 56: 119–25 4. Owren PA. Parahaemophilia: haemorrhage diathesis due to absence of a previously unknown clotting factor. Lancet 1947; i: 446–8 5. Tracy PB, Mann KG. Abnormal formation of the prothrombinase complex: factor V deficiency and related disorders. Hum Pathol 1987; 18: 162–9 6. Tsuda H, Mizuno Y, Hara T, Ohtsuki T, Ueda K, Matsuzaki K, et al. A case of congenital factor V deficiency combined with multiple congenital anomalies: successful management of palatoplasty. Acta Haemat 1990; 83: 49–52 7. Fischer RR, Giddings JC, Rosenberg I. Hereditary combined deficiency of clotting factors V and VIII with involvement of von Willebrand factor. Clin Lab Haematol 1988; 10: 53–60 8. Marwaha N, Sarode R, Marwaha RK. Combined factors V and VIII deficiency. Indian Pediatr 1990; 27: 630–7 9. Wadia RS, Sangle SA, Kripalaney S, Bafna M, Karva SR. Familial intracranial haemorrhage due to factor V deficiency. J Neurol Neurosurg Psychiatry 1992; 55: 227–8 Received Sept. 8, 1998. Accepted in revised form Nov. 18, 1998 Copyright of Acta Paediatrica is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.