Successful pregnancy in a patient with factor V deficiency: Case report and review of the literature

Abstract

T he clotting factor nowknown as factor V(FV)was first described in 1908(1), and adeficiencyofthis factor wasfirst described by Owren as parahaemophiliain1947 (2).FVis predominantlyproduced in the liverand to alesserdegree by the megakaryocytes. Circa80% of FV circulates in the plasma while 20% is stored in platelets. Following α -granule releaseupon platelet activation, plateletFVcan presumably bind immediatelyto surface receptorso ptimising prothrombinase complexa ctivity (3). Ther elationship between plasma FV and platelet FV and their relativesignificance is to date not fully understood,but FV expression in either platelets or plasma wasproventobesufficient forbasal haemostasis in mice(4).FV deficiencyisarare diseasewith an incidenceof1.10 -6 (5, 6, 20-24).I ti sa na utosomal recessively inheritedd isorderi n whicht he lacko ff actor Va ctivity impairsc lotting.H eterozygous patients showav ariable expression with am ild bleeding tendencyin10% of the cases (7),whereashomozygous patients usuallyp resentw ith moderate clinical manifestations of epistaxis, menorrhagiaa nd haemorrhages after trauma (8).T here seemst ob eap oor correlation betweenp lasma factor Vl evels and clinical phenotype (8), and differentopinions exist as to the necessary levelofcirculating FV for adequate haemostasis. Target FV activity levels during treatment are mainlybased on clinical experience(9). Relatively fewreportsonthe subjectoffactor Vd eficiencya nd pregnancyc an be foundi nt he medicall iterature, and these are mainlys poradic case reports (10-18) and threereviews (3,20,21).Case report A19-year-old Moroccanw oman, bornofconsanguineous parents, presented with complaintso ff atigue,e xcessive bleeding after dentalprocedures, frequent nose bleeds,severe menorrhagiaand large haematomas of the skin after minor trauma. Laboratorytests showedamicrocytic anaemia throughiron deficiency withhaemoglobin of 8.1 g/dl (nl 12-15g/dl),anMCV of 61.2 fl (nl 76-96fl) and ferritin of 5ng/ml (nl 13.0-150.0 ng/ml). The APTT wasclearlyprolonged at 110.4sec (nl25-39 sec)with a PT of 12%(nl 70-100%).F actor Vantigen levelw as 3% with factor Vactivity at 1%.All otherclotting factorswere present in normalamounts. No inhibitor againstFVcould be found.Molecular analysis showedt he presenceo fah omozygous factor V(Casablanca) nonsensemutation Q773Terminexon 13.The patient wasput on oralcontraceptivestodecreasemenstrualblood loss, tranexaminic acidand iron supplements. Both the patient and her husband expressed as trong wisht oh ave children on cultural and religiousgrounds, and even after full explanation of the possible complications,t he couple decided to accept the potential risks this entailed. Theyw ere advisedt o avoid ap regnancyu ntil ah aemoglobin levelo f1 2g /dl was reached,and this came about after 18 months of treatment during whicht herew ere only af ew minor bleeding episodes. After reaching the target haemoglobin and stopping of the oral contraceptives the patient becamep regnant after only three months. Thepregnancyitself wasuneventful and...

Successful coronary stenting in a patient with factor V deficiency in the absence of fresh frozen plasma transfusion

“…In particular, transfusing FFP is recommended to maintain factor V activity at >25% to 30% in cases of bleeding, invasive testing, or surgery. [ 3 , 6 ] In this case, FFP was not transfused because coronary stenting was performed without knowledge of the degree of factor V activity or the existence of F5D. We recognized F5D due to hemoptysis, epistaxis, and hematochezia after coronary stenting.…”

“…This strategy was based on previous reports in which factor V activity was not related to bleeding severity. [ 2 , 6 ] Moreover, successful childbirth delivery was possible without an FFP transfusion, and the success rate for bleeding control was low with FFP transfusion. [ 3 , 6 ] Fortunately, mucosal bleeding in the present case was controlled by adjusting the antithrombotic drug dose.…”

“…[ 2 , 6 ] Moreover, successful childbirth delivery was possible without an FFP transfusion, and the success rate for bleeding control was low with FFP transfusion. [ 3 , 6 ] Fortunately, mucosal bleeding in the present case was controlled by adjusting the antithrombotic drug dose. Treatments for the inhibitors or antibodies to factor V are another option and include plasmapheresis, immunosuppressants, steroids, intravenous globulins, and a monoclonal antibody.…”

Contraindications - Hemorrhage and Coagulopathy, and Patient Refusal

“…When the plasma FV antigen level becomes <15%, it is classified as a serious Type I deficiency and when it becomes <60-65%, as a moderate Type I deficiency. A moderate to serious level of bleeding occurs in serious Type I deficiency (Asselta et al, 2006;Vellinga et al, 2006).…”

Genetics of Bleeding Disorders in Women

“…62 Homozygous factor V deficiency also carries an increased risk of bleeding during pregnancy and delivery, although there are numerous case reports of pregnancies successfully managed with fresh-frozen plasma. 64,65 Combined deficiency of factor V and VIII is almost exclusively accounted for by mutations in the LMAN1 and MCFD2 genes, 66,67 which code for proteins implicated in the intracellular transport of factor V and VIII. The familial multiple coagulation factor deficiency is a combined deficiency of vitamin K-dependent factors due to mutations affecting vitamin K metabolism and vitamin K-mediated hepatic g-carboxylation of glutamic acid residues on vitamin K-dependent blood coagulation factors.…”