Compound Homozygous Factor V Leiden and Heterozygous Prothrombin Gene Mutation: The First Report in a Pregnant African with Extensive Thrombosis

Background: Factor V Leiden (FVL) mutation and Protein gene G20210A mutation (PGM) are the most common inherited thrombophilias in the world. (Limdi NA et.al, Blood Cells Mol Dis. 2006 Sep-Oct;37(2):100-6) Both are inherited in an autosomal recessive fashion with individuals who are homozygous having higher risk of thrombosis compared to those who are heterozygous.(Rodger MA et.al, PLoS Med. 2010 Jun 15;7(6):e1000292.) The global prevalence of FVL and PGM is variable with Caucasians carrying the highest prevalence and Africans living in Africa, Asians and Native Americans having the lowest rate of these mutations; it is zero in West and Southern African countries, 2.4%-3.9% in North African countries including Morocco, Tunisia, and Algeria. (Limdi NA et.al, Blood Cells Mol Dis. 2006 Sep-Oct;37(2):100-6, Dziadosz M et. al, Blood Coagul Fibrinolysis. 2016 Jul;27(5):481-9)

Pregnancy increases the risk of developing venous thromboembolism (VTE) by 0.05-1.8 %, (Eldor A, Thromb Haemost. 2001 12.12.2017;86(07):104-11) which is 4 to 5 fold greater than in non-pregnant female.(Croles FN et.al, BMJ. 2017;359, Greer IA, N Engl J Med. 2015 Aug 6;373(6):540-7) Inheritance of FVL and PGM increases the risk for development of VTE in pregnancy, the risk is higher with homozygous than heterozygous mutations.(Rodger MA et.al, PLoS Med. 2010 Jun 15;7(6):e1000292.) Concurrent presentation of FVL and PGM in pregnancy presenting as thrombosis is not common.

Aim: The aim of this case report is to present a patient of African descent with concurrent FVL and PGM mutation who had thrombosis during pregnancy.

The Case: A 32-year-old Nigerian female who was 28 weeks pregnant presented to the gynecologist with a swollen left leg. Physical examination and the Wells score were very suggestive of a deep vein thrombosis (DVT). The Duplex Doppler performed confirmed a diagnosis of bilateral lower limb DVT. The patient was referred to a physician, who together with the haematologist performed a thrombophilia screen including FVL, PGM, Protein C, Protein S and Anticardiolipin antibody tests. The D-DIMERS were raised and the viral markers including HIV, HBV, and HCV were negative. The PT, APTT and full blood counts were normal. The thrombophilia tests revealed that the patient was homozygous for FVL and also heterozygous for the PGM mutations. The rest of the thrombophilia screen including Protein C, Protein S and Antithrombin tests were all negative. She has no family history of thrombosis; no past history of hormone based contraceptives. She was counselled on the need for using anticoagulation, low molecular weight heparin (LMWH) during the rest of her pregnancy period, and therapeutic anticoagulation with a LMWH at a dose of 1mg/kg twice a day until onset of labour was started. During labour LMWH was discontinued, delivery was per vaginal and was uncomplicated. Postpartum LMWH was continued at therapeutic doses for six weeks with no bleeding or thrombotic events. After six weeks, the patient was started on lifelong warfarin.

Results (See Table)

Discussion: To our knowledge this is a first case of a patient born and living in Africa presenting with thrombosis and found to have homozygous FVL and heterozygous PGM during pregnancy, the one report that is similar was in a second generation South African woman of German, Dutch and French ancestry. (Wilson J et. al, Medical Technology SA. [Case Report]. December 2011;25(2):4) Most reports have shown ethnic and regional affectation. (Limdi NA et.al, Blood Cells Mol Dis. 2006 Sep-Oct;37(2):100-6, Bavikatty NR, et.al, Am J Clin Pathol. 2000 Aug;114(2):272-5)

There is no single agreed reason as to why the mutation is rare in Africa though founder effect is being studied to define how the mutation came about, it could have taken place before divergence of race. (Jadaon MM. [Thrombosis, Familiar Thrombophilia]. 2011 2011-11-28;3(1)

We could not do family studies to help define the origin of this mutation whether it is denovo for Nigeria; this has to do with sentiments about genetic inheritance in Africa.

Conclusion: Concurrent inheritance of both FVL and PGM is possible in Africa. This rare case has open opportunities to revisit the prevalence of thrombophilia in Nigeria and other African countries.

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