C A S E R E P O R T
Combined factor V and VIII deficiency and pregnancy
Bouchra Oukkache
•Omar El Graoui
•Saadia Zafad
Received: 2 May 2012 / Revised: 28 September 2012 / Accepted: 1 October 2012 / Published online: 17 October 2012 ÓThe Japanese Society of Hematology 2012
Introduction
Combined factor V and factor VIII deficiency (CF5F8D) is a rare recessive disorder, which prevalence is 1 per 1000000 in general population. However, this rate is higher in areas where consanguineous marriages are common [1–
4]. Affected individuals have between 5 and 30 % of
normal levels of factor V and VIII, whereas the levels of other plasma protein are not altered [5]. Patients present with a moderate bleeding tendency. The most common symptoms are epistaxis, menorrhagia, and excessive bleeding during or after trauma [1,
2].The aim of this paper is to report a case of pregnancy in a woman with combined deficiency of FV and FVIII. No remarkable hemorrhage occurred during and after the procedure.
Case report
A 30-year-old woman, from Morocco, was sent to our laboratory for assessment of her haemostasis. The patient was at 6-week gestation. Her clinical and obstetrical exams were normal. The patient was monitored for CF5F8D diagnosed at the age of 4, as she had presented continuous bleeding after tooth extraction. Her family history was negative for bleeding disorders and consanguinity of par- ents. At diagnosis the haemostasis levels showed prolonged partial thromboplastin time (aPTT
=59 s) and prothrom- bin time (PT
=59 %) with FV at 19 % and FVIII at 20 %.
In the current pregnancy, factor levels were, respec- tively, at booking, 28- and 34-week gestation, FV: 21, 18, 22 %, factor VIII: 10, 14, 28 % and prolonged aPTT and PT (58–63 s, 42–45 %, respectively). The platelets were normal. The ultrasound examination of the fetus and pla- centa resulted in the physiological range.
The patient had spontaneous labor at 38-week gestation, haemostasis was then checked: aPTT: 45 s, PT: 56 %, FV:
20 % and FVIII: 36 %. A normal vaginal delivery was attempted but there was a dynamic dystocia. A cesarean section was scheduled, under cover infusion of fresh frozen plasma at 10 ml/kg/day for 3 days, and FVIII concentrate infusion at 30 U/kg before surgery and 12 h, and Desmo- pressin (DDAVP) 0.3
lg/day subcutaneous during 2 daysin postpartum, as no hemorrhagic events were reported in the per or postpartum. Table
1resumes the haemostasis levels in the perinatal period. There was no significant increase in FVIII after DDAVP.
The haemostasis levels of the newborn were normal.
Discussion
Coagulation factor V (FV) and factor VIII (FVIII) are essential cofactors for the proteases factor X and factor IX, respectively, in the blood clotting cascade [1]. The combined deficiency of these 2 factors is rare [6], and was first described on 1954 by Oeri as a coagulation disorder distinct from the other single factor deficiencies [7].
Two different genes involved in the simultaneous decrease of FV and FVIII levels have been identified [7]. A first gene localized on chromosome 18(q21) coding for a protein termed endoplasmic reticulum Golgi intermediate compartment (ERGIC)-53 (also known as lectin mannose
B. OukkacheO. El Graoui (&)S. ZafadCasablanca, Morocco
e-mail: le_medmus@hotmail.com
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Int J Hematol (2012) 96:786–788 DOI 10.1007/s12185-012-1201-z
1, LMAN1), responsible for endoplasmic reticulum (ER) to Golgi transport of glycoproteins selectively based on their sugar moieties [1,
8]. Then, another gene have beendescribed, localized on chromosome 2(2p21-2p16.3) cod- ing for a protein bound to LMAN1 called MCFD2 (mul- tiple coagulation factor deficiency 2) [7].
Epistaxis, post-surgical bleeding and menorrhagia are the most common symptoms [1,
8]. Other types of bleedingcan occur, including hemarthrosis and muscular hemato- mas [1,
8].During pregnancy, the physiological changes in the hemostatic system tend to improve the inherited bleeding disorders [5]. Pregnancy is accompanied by increased concentrations of fibrinogen, FVII, FVIII, FX and von Willebrand factor, while FII, FV and FIX are relatively unchanged [5–10]. The active, unbound form of free protein S is decreased during pregnancy [5,
10] andplasminogen activator inhibitor type 1 (PAI-1) levels are increased [5]. All of these changes contribute to the hypercoagulable state of pregnancy, and to improve hae- mostasis in women with rare bleeding disorders. Despite this improvement, women with factor deficiencies do not achieve the same factor levels as those of women without factor deficiencies [5,
11]. The haemostatic abnormalitiesseem to persist throughout pregnancy, especially if the defect is severe. In our patient there was no great change in factor V levels, whereas there was an increase in FVIII level especially at the end of pregnancy. The bleeding risk during pregnancy or delivery is still particularly high in FII, FV and carriers of FIX deficiencies where there is no increase of the correspondent coagulation factor during pregnancy [5].
To our knowledge, there are no published data in rela- tion to pregnancy in women with combined FV and VIII deficiency [5]. For this reason we adopted the obstetric experience of women with factor V deficiency [5] and hemophilia A, guidelines [12,
13]. The hemophilia A car-riers should have their factor level checked at booking and at 28 and 34 weeks’ gestation to allow appropriate man- agement of labor and delivery, and to assess the need for prophylactic treatment [14]. And as suggested, adminis- tration of factor VIII concentrates was possible in our
patient, but factor V concentrates were not available, so we transfused with FFP.
Conclusion
Women with combined FV and FVIII deficiency have to be considered potentially at risk for developing postpartum hemorrhage, therefore they should be monitored carefully during and immediately after pregnancy. They may require prophylaxis and/or close observation for several weeks.
They should be instructed about possible excessive bleed- ing and should be seen in a follow-up visit 2 weeks post- partum [5,
15]. The ideal management should be throughmultidisciplinary clinics, including laboratory hematolo- gist, an obstetrician–gynecologist, an anesthesiologist, a family physician, a social worker, a pharmacist, and lab- oratory technician.
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Table 1 Hemostasis in the perinatal period Before
delivery
Day 1 of postpartum
Day 3 of postpartum
aPTT 45 s 35 s 35 s
PT 56 % 58 % 62 %
FV 20 % 26 % 30 %
FVIII 36 % 42 % 48 %
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