Primary Thrombophilia in Mexico: A Single Tertiary Referral Hospital Experience
Authors: Lacayo-Leñero Dennis , Vargas-Ruiz Angel Gabriel , Barrales-Benítez Olga , Hernández-Hernández Darinel , Valencia-Martínez Andrés 
Published: October 2019

Abstract
Background: Thrombophilia is a complex hypercoagulable state that predisposes to thrombosis. Several thrombophilia reports have been conducted in Mexicans with lack of statistical significance. The objective of this study was to describe the prevalence of primary thrombophilia in a tertiary referral hospital in Mexico.
Material and methods: Retrospective study of patients referred for primary thrombophilia between January 2011 and May 2015.. Thrombophilia study included: MTHFR C677T, anti-phopholipid antibodies, protein C, protein S, antithrombin, factor VIII, factor V Leiden, prothrombin mutation G20210A, APCR, JAK2 V617F, homocysteine. We used descriptive statistics according to the distribution of the variables. We used measures of central tendency and dispersion: average, median. All analyses were performed using the SPSS for Windows 20.0®
Results: We identified 224 patients referred for thrombophilia testing in a 4 year period. At the time of statistical analysis 129 patients were excluded for lacking data.Ninety five patients were included.Median age at onset was 36 years. (Table 1) Nine of 60 (15%) female patients reported previous use of contraceptives and 13/60 (21.6%) reported previous obstetric morbidity. (Table 2). We identified at least one anomaly related with thrombophilia in 90/95 patients (94.7%). Eighty patients (84.1%) presented the MTHFR C677T polymorphism; heterozygous 51/95 (53.6%) presenting with hyperhomocysteinemia 18/51 (35.2%) and homozygous 29/95 (30.5%) presenting with hyperhomocysteinemia 10/29 (34.4%).Factor V Leiden was found in 5/95 (5.2%) heterozygous. It co-occurred with APCR in 3/5 cases (60%).In 44 patients we found an isolated anomaly associated with thrombophilia (46.3%). In 51/95 (53.6%) we identified co-occurring anomalies associated with thrombophilia. (Table 3). The median of co-occurring anomalies was 2 (2-4).
Conclusions: The MTHFR C677T polymorphism has a very high prevalence in Mexicans compared to the low prevalence of anticoagulant protein deficiency and factor V Leiden mutation.
Table 1. Demographic characteristics. Demographic characteristics No. Patients (%) -Gender Male Female Total 35 (36.8) 60 (63.1) 95 (100) -Age Median years (range) 36 (17-75) -Family history of thrombosis -Cardiovascular risk factors Arterial Hypertension Diabetes mellitus Dyslipidemia Smoking 15 (15.7) 13 (13.6) 11 (11.5) 13 (13.6) 15 (15.7) -Surgery related thrombosis 3 (3.1) -Cancer related thrombosis 3 (3.1) -Autoimmune disease SLE Other autoimmune disease 11 (11.5) 3 (3.1) 8 (8.4) SLE: Systemic Lupus Erythematosus.
Table 2. Thrombosis characteristics. Thrombosis characteristics No. Patients (%) -Thrombotic events Median (range) 1 (1-4) -Affected territory Venous Arterial Mixed 80 (84.2) 14 (14.7) 1 (1) -Thrombophilia testing indication Age at onset <45 years. Family history of thrombosis Unusual site thrombosis Intra abdominal thrombosis Cerebral vein thrombosis Other unusual site thrombosis Recurrent thrombosis Obstetric morbidity More than one indication for testing 91 (95.7) 77 (81) 15 (15.7) 48 (50.5) 25/48 (52) 11/48 (22.9) 12/48 (25) 26 (27.3) 13/60 (21.6) 62 (65.2) -Treatment VKA LMWH Clopidogrel NOAC's ASA None ND 44 (46.3) 3 (3.1) 1 (1) 8 (8.4) 14 (14.7) 6 (6.3) 19 (20) VKA: Vitamin K Antagonist LMWH: Low Molecular Weight Heparin; NOAC's: New oral anticoagulants; ASA: acetylsalicylic acid. ND: Not described.
Table 3. Results of thrombophilia anomalies. TROMBOPHILIA TOTAL FREQUENCY ISOLATED FREQUENCY CO-OCCURRING WITH ANOTHER THROMBOPHILIA ANOMALY. -MTHFR C677T heterozygous 51/95 (53.6%). 22/51 (43.1%) 29/51 (56.8%) -Hyperhomocysteinemia 36/95 (37.8%). 6/36 (16.6%) 30/36 (83.3%) -MTHFR C677T homoczygous 29/95 (30.5%). 14/29 (48.2%) 15/29 (51.7%) -APCR 13/95 (13.6%). 0 13/13 (100%) -F V Leiden G1691A 5/95 (5.2%) 0 5/5 (100%) -Protein C deficiency 5/95 (5.2%) 0 5/5 (100%) -Elevated FVIII levels (>150%) 4/95 (4.2%) 0 4/4 (100%) -Protein S deficiency 3/95 (3.1%) 1/3 (33.3%) 2/3 (66.6%) -APS 3/95 (3.1%) 0 3/3 (100%) -Prothrombin G20210A 2/95 (2.1%). 0 2/2 (100%) -JAK2V617F 1/95 (1.0%) 1/1 (100%) 0 -Antithrombin deficiency 0 0 0 MTHFR: methylentetrahidrofolate reductase; APCR: Activated protein C resistance; APS: Antiphospholipid syndrome.

Disclosures
No relevant conflicts of interest to declare.