Acquired factor X deficiency is an extremely rare situation. It has shown to be associated with systemic amyloidosis, respiratory mycoplasma infection, factor X inhibitors, antiphospholipid antibodies, vitamin K defi ciency/liver disease as well as the use of certain medications
(meropenem, valproic acid). The pathogenesis and transient nature of this deficit remain poorly understood. The authors describe the case of a teenager hospitalised for extensive burns that developed active bleeding after removal of central venous catheter. He was diagnosed with transient factor X deficiency. Normalisation of coagulation status and factor X levels occurred spontaneously 10 days after the bleeding episode

Almeida, T

Eusébio, M

Freitas, O

Mascarenhas, A

PubMed

Repositório do Centro Hospitalar de Lisboa Central, EPE

BMJ Case Reports 2011; doi:10.1136/bcr.12.2010.3618 1 of 3 BACKGROUND  Congenital deﬁ ciency of factor X is a rare autosomal reces-sive bleeding disorder with an incidence of 1:1 000 000 in the general population. 1  2 An acquired factor X deﬁ cit in children with a normal homeostasis is an even rarer situ-ation, and most cases are associated with systemic amy-loidosis. 3 The acquired form also appears sporadically in patients with respiratory mycoplasma infection, vitamin K deﬁ ciency/liver disease and during the use of certain medi-cations (valproic acid, topical thrombin). 4 – 6 In paediatric burn victims, three cases of transient factor X deﬁ ciency are described: one due to the presence of an inhibitor, 7 another associated with anti-cardiolipin antibody 8 and the third apparently related to meropenem use. 9 The patho-genesis and transient nature of this deﬁ ciency remain poorly understood. The authors present a case of a teen-ager with extensive burns who later developed bleeding due to lack of factor X.  CASE PRESENTATION  We report the case of a 16-year-old adolescent, admitted to the Pediatric Intensive Care Unit (PICU) due to a high-volt-age electrical burn (railroad tracks), with 80% of total body surface area (TBSA) (head, face, feet and the distal left leg spared). His family and personal history were negative, especially with regards to a history of bleeding disorder. After initial stabilisation with intravenous ﬂ uids, topical therapy with silver sulfadiazine was initiated. Given the extent of burns, deep sedation and mechanical ventila-tion were initiated and maintained for 6 days without complications. On the second day of hospitalisation (D2) he underwent surgical debridement without the need of transfusion therapy, and alternate-day silver sulfadiazine dressings were maintained. Due to maintenance of hypo-tension after expansion with saline, inotropic support was started (dopamine and epinephrine). On D3, due to devel-opment of high fever and elevation of C reactive protein (370 mg/l), antibiotic therapy with ﬂ ucloxacillin (2 g, 6/6 h, for 21 days) and gentamicin (14 days) was instituted. Blood cultures were negative. The coagulation results at this stage showed no alterations – thrombin time (PT) 12.1 s, interna-tional normalised ratio (INR) 1.1 and partial thromboplastin time (APTT) 33 s. Haemodynamic stability was achieved progressively, and inotropes were suspended on D8. On D9, venous thromboembolism prophylaxis with enoxa-parin and acetylsalicylic acid was initiated. His remaining stay in the PICU progressed favourably and uneventfully from a clinical standpoint. In terms of laboratory results, on D18, a good outcome was conﬁ rmed, with haemoglobin 9.3 mg/dl, leucocytes 18 470/μl with 76.9% neutrophils, C reactive protein of 4.4 mg/dl, PT 13.1 s, APTT 30.5 s, INR 1.1, ﬁ brinogen 227.2 mg/dl (154–488),  D -dimer 178 (<250) and absence of ﬁ brin degradation products.  After 22 days of hospitalisation in the PICU, given the good clinical outcome and after stopping antibiot-ics, he was transferred to the Pediatric Surgery ward. On D23, after removal of a central venous catheter, abundant bleeding was noted, controlled by local compression. Thromboembolism prophylaxis was immediately discon-tinued. Concomitantly, a transient (48-h duration) macu-lopapular, non-pruriginous rash was noted, which after Immunoallergology consult was interpreted as an irritant dermatitis and treated with hydroxyzine.  INVESTIGATIONS  At this time, the laboratory evaluation revealed no altera-tions signiﬁ cant for bacterial infection (leucocytes 11 000/μl; neutrophils 59.2%; 484 000 platelets/ml; C reactive pro-tein 35.4 mg/l), but signiﬁ cant coagulation changes were demonstrated (PT 28.1 s, INR 2.40, APTT 38.8 s).  Clinically, there were no signs of disseminated intravas-cular coagulation.  A summary examination of the urine showed micro-scopic haematuria (erythrocyturia 3+). The liver function  Rare disease  Acquired-transient factor X defi ciency in a teenager with extensive burns  Andreia  Mascarenhas, 1  Marilene  Eusébio, 2  Orquídea  Freitas, 3  Teresa  Almeida 3  1 Department of General Pediatrics, Hospital Dona Estefânia, Rua Jacinta Marta, Lisboa, Portugal ;  2 Department of General Pediatrics, Centro Hospitalar do Barlavento Algarvio Sítio do Poço Seco, Portimão, Portugal ;  3 Hematology Unit, Hospital Dona Estefânia, Rua Jacinta Marta, Lisboa, Portugal  Correspondence to Dr Andreia Mascarenhas,  amascarenhas22@yahoo.com  Summary  Acquired factor X defi ciency is an extremely rare situation. It has shown to be associated with systemic amyloidosis, respiratory mycoplasma infection, factor X inhibitors, antiphospholipid antibodies, vitamin K defi ciency/liver disease as well as the use of certain medications (meropenem, valproic acid). The pathogenesis and transient nature of this defi cit remain poorly understood. The authors describe the case of a teenager hospitalised for extensive burns that developed active bleeding after removal of central venous catheter. He was diagnosed with transient factor X defi ciency. Normalisation of coagulation status and factor X levels occurred spontaneously 10 days after the bleeding episode. BMJ Case Reports 2011; doi:10.1136/bcr.12.2010.36182 of 3tests were normal. Factor X measurement showed greatly decreased values (10% – normal value between 60% and 150%). A plasma-mixing test was performed with normal-isation of plasma coagulation tests, ruling out the presence of an inhibitor.  OUTCOME AND FOLLOW-UP  By D32, both coagulation studies (PT 11.8 s, INR 1.3, APTT 31.5 s) and the measurement of factor X were normal. The patient suffered no further episodes of bleeding disorder.  DISCUSSION  Patients with major burns develop a tendency towards hypercoagulability, and prophylactic anticoagulant ther-apy was used earlier. In these patients, bleeding disorders may be associated with severe infection or disseminated intravascular coagulation. Acquired factor X deﬁ ciency is extremely rare with few cases reported in the literature. This factor plays a central role in the coagulation cascade, justifying the concomitant changes in APTT and PT (INR). Symptoms related to the factor X deﬁ ciency depend on its serum concentration – values between 1% and 10% are associated with minor bleeding, especially during surgi-cal procedures, or, as was the case with our patient, on removal of a central intravenous catheter. Severe bleeding is described when values fall below 1%. 9 In the present case, despite the absence of fever, signiﬁ cant inﬂ ammatory markers or positive blood cultures, an initial diagnosis of infection, was entertained. After factor X deﬁ ciency was conﬁ rmed, the most frequent causes were systematically excluded. Systemic amyloidosis was highly unlikely given the presence of a previously healthy child. A respiratory mycoplasma infection was rejected given the absence of respiratory symptoms. Vitamin K deﬁ ciency or liver dis-eases, other possible causes, were also rejected because they usually present with associated deﬁ cits of other coagulation factors. In addition, liver function tests were normal. The presence of acquired inhibitors of coagulation factors in children with normal haemostasis is rare. There are two cases reported in paediatric burn victims where the factor X deﬁ ciency results from the presence of inhibi-tors. 7  8 The plasma-mixing test, with resultant normalisa-tion of PT and APTT, contradicted this hypothesis.  In our case, the hypothesis of haemorrhage secondary to anticoagulant therapy was also placed, and this therapy was immediately suspended. However, antithromboem-bolic prophylaxis cannot explain the observed bleeding dis-order because the low molecular weight heparins (HBPM) do not interfere with the PT and APTT. 10  Previous studies report problems in correcting bleeding disorders caused by the factor X deﬁ ciency, requiring fresh frozen plasma and prothrombin complex. In our patient, the minor bleeding and a benign outcome observed were mainly due to the fact that the factor X deﬁ cit was moder-ate (10%), as most cases described in the literature have values less than 1%.  Jennes  et al describe a case of transient factor X deﬁ ciency in a 12-month-old child with extensive burns, apparently associated with meropenem use. Other medications have also been implicated, such as valproic acid and topical thrombin. 5  6 In the described case, the antibiotic had been suspended on the eve of the bleeding episode and there-fore could not exclude cause–effect relationship.  In conclusion, our case study is due to a transient deﬁ -ciency of factor X, possibly associated with ﬂ ucloxacillin. In fact, in the previously described three cases, the bleed-ing disorder also did not develop in the time-span imme-diately after burn, in which more complications are to be expected, but between 15 and 19 days of hospitalisation. Further studies of factor X levels in burn patients will have to be conducted to better understand this relationship.  Competing interests  None.  Patient consent  Obtained.  REFERENCES  1.  Uprichard  J,  Perry  DJ .  Factor X defi ciency .  Blood Reviews  2002 ; 16 : 97 – 100 .  2.  Steen  CJ,  Schwartz  RA .  Factor X, Emedicine ,  2008 .  3.  Choufani  EB,  Sanchorawala  V,  Ernst  T,  et al .  Acquired factor X defi ciency in patients with amyloid light-chain amyloidosis: incidence, bleeding manifestations, and response to high-dose chemotherapy .  Blood  2001 ; 97 : 1885 – 87 .  4.  Peuscher  FW,  van Aken  WG,  van Mourik  JA,  et al .  Acquired, transient factor X (Stuart factor) defi ciency in patient with mycoplasma pneumonial infection .  Scand J Haematol  1979 ; 23 : 257 – 64 .  5.  Gallais  V,  Bredoux  H,  le Roux  G,  et al .  Acquired and transient factor X defi ciency associated with sodium valproate treatment .  Eur J Haematol  1996 ; 57 : 330 .  6.  Israels  SJ,  Leaker  MT .  Acquired inhibitors to factor V and X after exposure to topical thrombin: Interference with monitoring of low molecular weight heparin and warfarin .  J Pediatrics  1997 ; 131 : 480 – 83 .  7.  Matsunga  AT,  Shafer  FE .  An acquired inhibitor to factor X in a pediatric patient with extensive burns .  J Pediatr Hematol Oncol  1996 ; 18 : 223 – 26 .  8.  Haberal  M,  Basaran  O,  Sakallioğlu  AE,  et al .  Acquired-transient factor X defi ciency associated with anticardiolipin antibodies in a child with extensive burns .  J Burn Care Res  2006 ; 27 : 113 – 16 .  9.  Jennes  S,  Saidane  G,  Fauville  JP,  et al .  Transient selective factor X defi ciency in a severely burned child .  Burns  2008 ; 34 : 1037 – 40 .  10.  Hirsh  J,  Warkentin  TE,  Shaughnessy  SG,  et al .  Heparin and low-molecular-weight heparin mechanism of action, pharmacokinetics, dosing, monitoring, effi cacy, and safety .  Chest  2001 ; 119 : 64S – 94S . Learning points Acquired factor X defi ciency is extremely rare.  ▶ In paediatric burn victims, three cases of transient  ▶factor X defi ciency are described: one due to the presence of an inhibitor, another associated with anticardiolipin antibody and the third apparently related to meropenem use.  We report a transient defi ciency of factor X in a  ▶teenager with extensive burns possibly associated with fl ucloxacillin.  The pathogenesis and transient nature of this defi ciency  ▶remain poorly understood. BMJ Case Reports 2011; doi:10.1136/bcr.12.2010.3618 3 of 3This pdf has been created automatically from the fi nal edited text and images.Copyright 2011 BMJ Publishing Group. All rights reserved. For permission to reuse any of this content visit http://group.bmj.com/group/rights-licensing/permissions. BMJ Case Report Fellows may re-use this article for personal use and teaching without any further permission.Please cite this article as follows (you will need to access the article online to obtain the date of publication).Mascarenhas A, Eusébio M, Freitas O, Almeida T. Acquired-transient factor X defi ciency in a teenager with extensive burns. 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Acquired-Transient Factor X Deficiency in a Teenager with Extensive Burns

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Acquired-Transient Factor X Deficiency in a Teenager with Extensive Burns

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Repositório do Centro Hospitalar de Lisboa Central, EPE

Repository of the Hospital Center of Central Lisbon