The influence of hydrogen ions on coagulation in traumatic brain injury, explored by molecular dynamics.

Background: Patients in intensive care units with traumatic brain injuries (TBI) frequently present acid-base abnormalities and coagulability disorders, which complicate their condition.Objective: To identify protonation through in silico simulations of molecules involved in the process of coagulation in standard laboratory tests.Materials and methods: Ten patients with TBI were selected from the intensive care unit in addition to ten "healthy control subjects", and another nine patients as "disease control subjects"; the latter being a comparative group, corresponding to subjects with diabetes mellitus 2 (DM2). Fibrinogen, FVII, FVIII, FIX, FX, and D-dimer in the presence of acidification were evaluated in 20 healthy subjects in order to compare clinical results with molecular dynamics (MD), and to explain proton interactions and coagulation molecules.Results: The TBI group presented a slight, non-significant increase in D-dimer; but this was not present in "disease control subjects". Levels of fibrinogen, FVII, FIX, FX, and D-dimer were affected in the presence of acidification. We observed that various specific residues of coagulation factors "trap" ions.Conclusion: Protonation of tissue factor and factor VIIa may favor anticoagulant mechanisms, and protonation does not affect ligand binding sites of GPIIb/IIIa (PAC1) suggesting other causes for the low affinity to PAC1.

A proposal for the management of COVID-19-induced coagulopathy in adults.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is the cause of the coronavirus disease 2019 (COVID-19) pandemic, which has a high case fatality rate. Most severely ill patients develop a special type of coagulopathy that had not been described before and that is now considered the main cause of death. For this reason, anticoagulant treatment has become one of the cornerstones of the treatment of this infection. However, the rate at which the evidence regarding the use of anticoagulants is generated is quite fast, and sometimes it is difficult to interpret and conflicting. After having performed an extensive review of the published literature, this proposal for the use of anticoagulant treatment is made, taking into account available resources in Mexico.

La infección por coronavirus 2 del síndrome respiratorio agudo grave (SARS-CoV-2) es la causante de la pandemia de enfermedad por coronavirus 2019 (COVID-19), con un índice de letalidad alto. La mayoría de los pacientes graves desarrollan un tipo especial de coagulopatía no descrito hasta ahora y la cual se considera ahora la principal causa de muerte. Por esta razón, el tratamiento anticoagulante se ha convertido en una de las piedras angulares del tratamiento de esta infección. Sin embargo, la velocidad con la que se genera la evidencia respecto al uso de anticoagulantes es muy rápida y, en ocasiones difícil de interpretar y contradictoria. Luego de hacer una revisión extensa de la literatura publicada, se hace esta propuesta para el uso del tratamiento anticoagulante tomando en cuenta los recursos disponibles en México.

Analysis of the quality of anticoagulation with vitamin K antagonists in three clinical scenarios in Mexico.

INTRODUCTION: Vitamin K antagonists (VKA) are a therapeutic alternative in patients with venous thromboembolic disease; however, numerous factors affect their pharmacology. OBJECTIVE: To evaluate the quality of VKA anticoagulation at three different time periods in Mexico. METHODS: Prospective study, nested in patient cohorts at three different clinical scenarios between 2013 and 2019. Outpatients with indication for treatment with VKAs for at least 12 months were included. Patients were managed according to the criteria of the treating physician. RESULTS: Patient general characteristics were similar between groups, except for the VKA indication. The results of 4,148 patients and 38,548 INR assessments were analyzed. The times in therapeutic range during the three phases of the study and pooled data were significantly higher for the anticoagulation clinic. Only the number of patient visits was significantly associated with the results, unlike age, gender, and type of VKA. CONCLUSIONS: VKAs are widely used, but it is difficult for therapeutic goals to be achieved, especially in non-specialized clinical services. Creation of anticoagulation clinics is an urgent need for the Mexican health system.

INTRODUCCIÓN: Los antagonista de la vitamina K (AVK) son una alternativa terapéutica en los pacientes con enfermedad tromboembólica venosa; sin embargo, numerosos factores afectan su farmacología. OBJETIVO: Evaluar la calidad de la anticoagulación AVK durante tres diferentes periodos en México. MÉTODOS: Estudio prospectivo, anidado en cohortes de pacientes en tres escenarios clínicos entre los años 2013-2019. Se incluyeron pacientes no hospitalizados con indicación para recibir AVK por al menos 12 meses, quienes fueron manejados de acuerdo con el criterio del médico tratante. RESULTADOS: Las características generales de los pacientes fueron similares entre los grupos, excepto por la indicación para usar los AVK. Se analizaron los resultados de 4148 pacientes y 38 548 evaluaciones de INR. Los tiempos en rango terapéutico durante las tres fases del estudio y los datos acumulados fueron significativamente mayores en la clínica de anticoagulación. Solo el número de visitas de control de los pacientes se asoció significativamente con los resultados, a diferencia de la edad, el sexo y el tipo de AVK. CONCLUSIONES: Los AVK se utilizan ampliamente, pero es difícil alcanzar la meta terapéutica, sobre todo en servicios clínicos no especializados. La creación de clínicas de anticoagulación es una necesidad urgente en el sistema mexicano de salud.

von Willebrand Disease and other hereditary haemostatic factor deficiencies in women with a history of postpartum haemorrhage.

INTRODUCTION: Postpartum haemorrhage (PPH) is the main cause of maternal morbidity and mortality globally, but it is far more important in non-developed countries. PPH represents 25% of all maternal deaths worldwide. Women with von Willebrand disease (VWD) and other inherited haemorrhagic disorders are at increased risk of PPH. Our aim was to establish a probable association of severe PPH in women with a history of haemostatic abnormalities. METHODS: An observational, controlled study of adult women with a one or more episodes of severe PPH requiring treatment in an intensive care unit or >10 units of blood products during the 24-hour period after diagnosis and their controls. The tests performed were blood cell count, blood group, renal, viral, liver function and haemostatic tests, fibrinogen, activity of the plasma factors and specific test to diagnose and classify VWD. RESULTS: We included 124 women with 133 PPH events and their controls. The median age at the first event was 25.5 years old. Results were significantly different between the groups in terms of fibrinogen concentration, VWF:Ag, VWF:RCo and FVIII. A specific diagnosis was established in 69 (55.6) and 4 (3.2%) patients in the PPH group and controls, respectively. Of 61 patients with VWD, 57 had type 1, two had type 2A, and another two had type 2B. CONCLUSION: Our results show a relationship between PPH and inherited haemostatic disorders. VWD was the most frequent diagnosis. Appropriate and opportune diagnosis before pregnancy of inherited haemostatic disorders may be important to effectively prevent and treat PPH.

Effects of Rivaroxaban on Platelet Aggregation.

Rivaroxaban is a direct oral anti-factor Xa anticoagulant. It has recently been suggested that rivaroxaban may affect platelet function in vitro; however, little is known about the clinical impact of this likely antiplatelet effect and whether this probable phenomenon is dose-dependent. Our aim was to determine whether rivaroxaban at 4 different doses inhibits direct platelet aggregation. We included adult patients of both sexes and who were allocated to one of the following groups depending on the prescribed daily dose of rivaroxaban: 5, 10, 15, and 20 mg. In 80 patients (20 patients/group), the percentage of platelet aggregation was determined by means of platelet aggregometry tests before and after rivaroxaban use. Basal samples were obtained before starting rivaroxaban and 1 month after treatment, both 2 and 24 hours after the last dose of the drug (12 hours after in the case of rivaroxaban 5 mg). We used 5 platelet agonists: adenosine diphosphate, epinephrine, arachidonic acid, collagen, and thrombin. There were no significant changes in the percentage of platelet aggregation before and after rivaroxaban use independently of the dose administered and the agonist used. Our results have clearly shown that rivaroxaban, even at a high dose, does not directly affect platelet aggregation.

Acquired hemophilia.

Acquired hemophilia (AH) is an autoimmune hemostatic disorder mediated by autoantibodies directed against factor VIII: C. In 52% of cases, the cause is unknown or is not associated with other pathological entities; in the rest, there are concomitant factors: lupus, rheumatoid arthritis, cancer, pregnancy, and medications. In Mexico, there is not a registry of AH, and awareness of the disease among health personnel is low. The groups with the highest incidence are women of childbearing age and individuals older than 70 years. It is characterized by severe bleeding, especially after trauma and normal childbirth or cesarean delivery, and large ecchymoses in the trunk and extremities. The suspicion is simple, it just takes for sudden, severe hemorrhage and a prolonged activated partial thromboplastin time that is not corrected with plasma to concur in an individual. Treatment involves achieving hemostasis and eradicating the antibody. The former is achieved with recombinant activated factor VII or activated prothrombin complex concentrate. Cyclophosphamide, prednisone or rituximab are used to eradicate the antibody. Most cases of AH are not diagnosed, which translates into a high mortality rate. Given that awareness about the disease among physicians is low, it is not suspected, neither diagnosed, and nor is it treated. This document reviews the most recent data on AH and expands on its diagnosis and treatment.

La hemofilia adquirida (HA) es un trastorno hemostático autoinmune ocasionado por autoanticuerpos dirigidos contra el factor VIII: C. En 52 % de los casos, la causa se desconoce o no se asocia con otra entidad patológica; en el resto, existen factores concomitantes: lupus, artritis reumatoide, cáncer, embarazo y medicamentos. En México no existe registro ni conciencia de la enfermedad entre el personal de salud. Los grupos de mayor incidencia son las mujeres en edad reproductiva y los individuos mayores de 70 años. Se caracteriza por hemorragia grave, sobre todo posterior a traumatismos y parto o cesárea, y equimosis grandes en tronco y extremidades. La sospecha es simple, basta que concurran hemorragia súbita, grave y un TTPa prolongado que no se corrige con plasma. El tratamiento consiste en lograr la hemostasia y erradicar el anticuerpo; lo primero se logra con el factor VII activado recombinante o concentrado del complejo de protrombínico activado. La ciclofosfamida, prednisona o rituximab sirven para erradicar el anticuerpo. La mayoría de los casos no son diagnosticados y la mortalidad es alta. Ya que los médicos desconocen el problema, no se sospecha, no se diagnostica y no se trata. Este documento revisa los datos más recientes de la HA y abunda en el diagnóstico y tratamiento.

Proposal for the management of COVID-19-associated coagulopathy in children.

SARS-CoV-2 infection (COVID-19) has become a pandemic with a high case fatality rate that mainly affects adults. Most severely ill adult patients develop a coagulopathy that was not described until recently, and which is currently considered a main cause of death. Everything indicates that a similar phenomenon also occurs in children with COVID-19. Anticoagulant treatment has become one of the therapeutic foundations for this infection; however, its implementation in children can be difficult since, until recently, it was not considered in the pediatric population. Evidence regarding the use of anticoagulants in COVID-19 is rapidly generated, changes constantly, it is often difficult to interpret, and can be contradictory. After an extensive review of the published literature, a proposal was generated that offers suggestions for anticoagulant treatment, considering available resources in Mexico.

La infección por SARS-CoV-2 (COVID-19) se ha constituido en una pandemia con alto índice de letalidad que afecta principalmente a los adultos. La mayor parte de los pacientes adultos graves desarrolla una coagulopatía que no estaba descrita, la cual actualmente se considera la principal causa de muerte. Todo indica que un fenómeno parecido ocurre también en el niño con COVID-19. El tratamiento anticoagulante se ha convertido en uno de los fundamentos terapéuticos de esta infección; sin embargo, su establecimiento en el niño puede ser difícil ya que, hasta hace poco, no estaba considerado en la población pediátrica. La evidencia respecto al uso de anticoagulantes en COVID-19 se genera con rapidez, cambia constantemente, con frecuencia es difícil de interpretar y puede ser contradictoria. Después de una extensa revisión de la literatura publicada, se generó una propuesta que ofrece sugerencias para el tratamiento anticoagulante en la que se consideran los recursos disponibles en México.

[Polimorfismos asociados a disfunción endotelial y a un estado protrombótico en jóvenes mexicanos con infarto cerebral].

OBJECTIVE: To examine the contribution the polymorphisms G20210A, G1691A and G10976A in the coagulation factors FII, FV, FVII, respectively; Glu298Asp and C677T in eNOS and 5,10 MTHFR in young Mexican population with cerebral infarction (CI). METHODS: 224 patients ≤ 45 years of age with CI and 224 controls matched by age and gender were recruited from 2006 and 2014. The polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: We identified a significant difference in the genotype distribution of Glu298Asp (p = 0.001) and C677T (p = 0.01) polymorphisms between CI patients and control groups. The genotype distribution in the FII G20210A, FV G1691A and FVII G10976A polymorphisms were similar. There were independent factors for ischemic stroke: Glu298Asp and C677T polymorphisms, smoking; hypertension, and familial history of thrombotic disease. CONCLUSIONS: The Glu298Asp and C677T, but not FII G20210A, FV G1691A and FVII G10976A polymorphisms were associated with CI. Our results suggest that endothelial dysfunction and the synergist interaction with other factors such as smoking and hypertension contribute to CI in young individuals.

OBJETIVO: Examinar la contribución de los polimorfismos G20210A, G1691A y G10976A en los factores de coagulación FII, FV y FVII respectivamente; Glu298Asp y C677T en la óxido nítrico sintasa endotelial y 5,10 metilentetrahidrofolato reductasa, en población joven mexicana con infarto cerebral (IC). MÉTODO: Se incluyeron 224 pacientes ≤ 45 años de edad con diagnóstico de IC y 224 controles pareados por edad y sexo, de 2006 a 2014. Los polimorfismos fueron determinados por la técnica de reacción en cadena de la polimerasa-polimorfismos de longitud de fragmentos de restricción. RESULTADOS: Identificamos una diferencia significativa en la distribución genotípica de los polimorfismos Glu298Asp (p = 0.001) y C677T (p = 0.01) entre el grupo de pacientes con IC y el control. La distribución genotípica de los polimorfismos FII G20210A, FV G1691A y FVII G10976A fue similar entre ambos grupos. Se identificaron como factores independientes de IC los polimorfismos Glu298Asp y C677T, el tabaquismo, la hipertensión y el antecedente de familiar de enfermedad trombótica. CONCLUSIONES: Los polimorfismos Glu298Asp y C677T, pero no FII G20210A, FV G1691A y FVII G10976A, se asociaron con IC. Nuestros resultados sugieren que la disfunción endotelial en interacción sinérgica con otros factores de riesgo, como tabaquismo e hipertensión, contribuye al IC en individuos jóvenes.

Reduced platelet aggregation in women after intercourse: a possible role for the cyclooxygenase pathway.

We hypothesise that molecules in the cyclooxygenase pathway affect platelet activity when seminal fluid (SF) is present. We considered the influence of SF on platelet aggregation in women, and believe that the prostanoids in SF signalling are significant. Thirty-one female subjects were studied, 20 of whom were sexually active. Male partners were given either aspirin or indomethacin to inhibit cyclooxygenase. The 6-keto prostaglandin F1α (6-keto PGF1α) and prostaglandin E metabolite (PGE-M) in SF were measured by competitive assay. Platelets and prostanoids were evaluated in women, periodically, before and after intercourse. The platelets were tested with adenosine diphosphate (ADP) and arachidonic acid (AA). To block the interaction between the uterus and SF, some couples used condoms. We found that the 6-keto prostaglandin F1α in urine at 2 hours post-intercourse (1418.75 pg/mL, Std 688.39) was greater than pre-intercourse (772.68 pg/mL, Std 116.54). Post-intercourse, a transient decrease in platelet aggregation was observed in women whose partners did not use condoms. Averages for platelet aggregation were 20.16% with ADP, and more significantly, 37.79% with AA after 2 hours. In contrast, couples using condoms showed no changes, averaging 64.02% with ADP and 72.06% with AA. Women whose partners were taking aspirin or indomethacin also showed no changes. SF from men taking aspirin or indomethacin led to no reduction in platelet aggregometry in their partners. These results indicate that in cases of exposure to SF, the transient change in women's platelet activity could be related to the cyclooxygenase pathway.

Forensic-paternity effectiveness and genetics population analysis of six non-CODIS mini-STR loci (D1S1656, D2S441, D6S1043, D10S1248, D12S391, D22S1045) and SE33 in Mestizo and Amerindian populations from Mexico.

BACKGROUND: STRs are powerful tools intensively used in forensic and kinship studies. AIM: In order to assess the effectiveness of non-CODIS genetic markers in forensic and paternity tests, the genetic composition of six mini short tandem repeats-mini-STRs-(D1S1656, D2S441, D6S1043, D10S1248, D12S391, D22S1045) and the microsatellite SE33 in Mestizo and Amerindian populations from Mexico were studied. SUBJECTS AND METHODS: Using multiplex polymerase chain reactions and capillary electrophoresis, this study genotyped all loci from 870 chromosomes and evaluated the statistical genetic parameters. RESULTS: All mini-STRs studied were in agreement with HW and linkage equilibrium; however, an important HW departure for SE33 was found in the Mestizo population (p ≤ 0.0001). Regarding paternity and forensic statistical parameters, high values of combined power discrimination and mean power of exclusion were found using these seven markers. The principal co-ordinate analysis based on allele frequencies of three mini-STRs showed the complex genetic architecture of the Mestizo population. CONCLUSION: The results indicate that this set of loci is suitable to genetically identify individuals in the Mexican population, supporting its effectiveness in human identification casework. In addition, these findings add new statistical values and emphasise the importance of the use of non-CODIS markers in complex populations in order to avoid erroneous assumptions.

[Economic impact of hemophilia type A and B in Mexico]. / Impacto económico de la hemofilia tipo A y B en México.

BACKGROUND: The treatment of hemophilia generates a disproportionally large economic impact relative to its prevalence. OBJECTIVE: To determine the economic impact of hemophilia A and B in Mexico in 2011 from the perspective of public health institutions. METHODS: Hemophilia was epidemiologically characterized in Mexico during the year of interest, direct costs (diagnosis, monitoring or follow-up, care of bleeding events, and consumption of hemostatic factors), as well as absenteeism associated with illness (indirect costs) were estimated. Records, surveys and official data were supplemented by expert opinion to assess costs. RESULTS: The investment in hemostatic factors is the primary source of cost: 68.6 and 74.3% of total investment in hemophilia A and B, respectively. Sensitivity analysis showed that the most decisive variable is the cost of acquisition of hemostatic factors, including bypass agents. The second most important source of cost is the attention to bleeding events, being significantly higher in patients receiving on-demand treatment compared with those receiving prophylaxis. CONCLUSION: In Mexico, hemophilia is a condition whose treatment requires a large amount of financial resources associated with the cost of hemostatic factors and care of hemorrhage, the latter being lower in patients on prophylaxis relative to on-demand.

[Face-to-face education to optimize knowledge in patients initiating oral anticoagulant treatment (OAT)]. / Intervención educativa individualizada (IEI) cara a cara para optimizar el conocimiento de pacientes que inician tratamiento anticoagulante oral (TAO).

BACKGROUND: Insufficient knowledge of patients about oral anticoagulants that they have been prescribed is recognized as a risk factor for adverse effects. Education of patients under oral anticoagulation may improve quality and control of anticoagulant treatment; limitations of educational interventions include lack of assessment of patients' knowledge. Our goal was to determine the effect of an individualized educational intervention on knowledge of patients who recently started treatment with oral anticoagulants, to assess patients' knowledge, and to analyze factors associated with knowledge acquisition. METHODS: In 49 consecutive patients attending a thrombosis clinic who initiated or re-initiated oral anticoagulant treatment, knowledge about the treatment was assessed by means of a validated questionnaire, before an individualized, face-to-face educational intervention, and at least four weeks after. Educational intervention started after the questionnaire had been answered by patients for the first time. RESULTS: Knowledge level increased by about 50%; the improvement was higher in patients with more years in school. DISCUSSION: Timely acquisition of knowledge about oral anticoagulant drugs is optimized with interventions provided earlier during the patients' treatment. Assessment of knowledge should be performed and instruction should be adapted to patient characteristics such as level of education and availability to receive education.

GLU298ASP and 4G/5G Polymorphisms and the Risk of Ischemic Stroke in Young Individuals.

BACKGROUND: Polymorphisms in the endothelial nitric oxide synthase (eNOS) and in the plasminogen activator inhibitor -1 (PAI-1) genes have been implicated in stroke pathogenesis but results are still controversial. The aim of this study was to examine the possible contribution of Glu298Asp in the eNOS and 4G/5G in the PAI-1polymorphisms with ischemic stroke in a young Mexican population. MATERIALS AND METHODS: In a case-control study, conducted between January 2006 and June 2010, 204 patients ≤45 years of age with ischemic stroke and 204 controls matched by age and gender, were recruited. The Glu298Asp and 4G/5G polymorphisms were determined in all participants by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: There was a significant difference in the Glu298Asp genotype distribution (P=0.001) and allele frequency between the two groups (P=0.001). The 4G/5G genotype distribution (P=0.40) and the allele frequency was similar between groups; (P=0.13). There were independent factors for ischemic stroke: Asp carriage (GluAsp+AspAsp) (P=0.02); smoking (P=0.01); hypertension (P=0.03), and familial history of atherothrombotic disease (P=0.04). CONCLUSIONS: The Asp allele from the Gu298Asp gene represents an independent risk factor for ischemic stroke in a young Mexican population. In contrast, the 4G/5G was not associated with an increased risk for this disease in the same group of patients, as previously has been demonstrated in other populations.

Risk Factors for Thrombosis Development in Mexican Patients.

BACKGROUND: To identify inherited factors: Protein C (PC), protein S (PS), antithrombin (AT), plasminogen (Plg), the activated PC resistance (APCR), prothrombin (PT) mutation G20210 A (PTG20210 A) and methylenetetrahydrofolate reductase C677 T polymorphism (MTHFR C677 T), as well as acquired-risk factors such as: diabetes mellitus, surgeries, smoking, obesity, hypertension, trauma, alcoholism, family history; and their association, in Mexican patients with diagnostic of thrombophilia. METHODS: Overall, 200 patients diagnosed with thrombophilia and 100 healthy controls. Commercial kits were used for the coagulometric tests and polymerase chain reaction, restriction fragment length polymorphism for molecular alterations. RESULTS: Alterations were found with an estimated prevalence to PC 0.65%, AT 2.04% and Plg 2.5%, APCR 2%, PT 20210 2%, and MTHFR 65%. The C677 T polymorphism of the MTHFR did not associate with acquired-risk factors so we can suppose that it is an independent risk factor. For the patients that only presented acquired-risk factors (21 of 200), the association smoking-alcoholism showed to be the cause of thrombosis with high risk. The following were also associated: smoking with AT, PC, and alcoholism; obesity with Plg; smoking with alcoholism, and PS deficiency. CONCLUSIONS: Risk factors for both primary and secondary and their association were present as a cause of thrombosis in the patients studied, and the possibility to suffer a recurrent thrombosis.

Metabolic effects of the contraceptive skin patch and subdermal contraceptive implant in Mexican women: a prospective study.

BACKGROUND: The contraceptive skin patch (CSP) accepted by the U.S. FDA in 2001 includes ethinylestradiol and norelgestromine, whereas the subdermal contraceptive implant (SCI) has etonogestrel and is also approved by the FDA. In Mexico, both are now widely used for contraception but their effects on Mexican population are unknown. The objective of the study was to evaluate if these treatments induce metabolic changes in a sample of indigenous and mestizo Mexican women. METHODS: An observational, prospective, longitudinal, non-randomized study of women between 18 and 35 years of age assigned to CSP or SCI. We performed several laboratory tests: clinical chemistry, lipid profile, and liver and thyroid function tests. Also, serum levels of insulin, C-peptide, IGF-1, leptin, adiponectin, and C reactive protein were assayed. RESULTS: Sixty-two women were enrolled, 25 used CSP (0 indigenous; 25 mestizos) and 37 used SCI (18 indigenous; 19 mestizos). Clinical symptoms were relatively more frequent in the SCI group. Thirty-four contraceptive users gained weight without other clinical significant changes. After 4 months of treatment, significant changes were found in some biochemical parameters in both treatment groups. Most were clinically irrelevant. Interestingly, the percentage of users with an abnormal atherogenic index diminished from 75% to 41.6% after follow-up. CONCLUSIONS: The CSP slightly modified the metabolic variables. Most changes were nonsignificant, whereas for SCI users changes were more evident and perhaps beneficial. Results of this attempt to evaluate the effects of contraceptives in mestizo and native-American populations show that clinical symptoms are frequent in Mexican users of CSP and SCI. Although these medications may affect some metabolic variables, these changes seem clinically irrelevant. Induction of abnormalities in other physiological pathways cannot be ruled out.

[Reference values for blood coagulation factor activity in the Mexican population].

INTRODUCTION: During the fluid phase of hemostasis, fibrinogen is converted into fibrin, but other hemostatic factors are required. Reference values of hemostatic factors are established by manufacturers producing reagents using individuals with a specific genetic background. OBJECTIVE: To establish reference values for hemostatic factors in the Mexican indigenous and Mestizo populations. MATERIAL AND METHODS: We carried out a cross-sectional, descriptive study of healthy adult Mexicans. Clotting activity was evaluated using coagulometric assays. Blood donors were informed about the nature of the study and informed consent was obtained prior to blood being drawn. The protocol was approved by the Ethics Committee of our institution. RESULTS: One hundred and twenty samples were assayed (60 females and 60 males). Fibrinogen was higher in mestizos and in females. Reference values for factor XII ranged from 40-170% in indigenous subjects and from 36-159% in mestizos. Factor VIII ranged from 57-160% in indigenous subjects and from 51-209% in mestizo subjects. Reference values for the other hemostatic factors were also clearly different from the commercial reference values. Reference values for hemostatic factors in the Mexican population are different from traditionally used commercial reference values. There were significant differences between indigenous and mestizo Mexicans in the concentration of hemostatic factors with a tendency among mestizos to have higher factor concentrations. Low levels of plasma factor XII are frequent and perhaps may represent a risk factor for thrombotic events. Using these reference values may individualize the reposition of factors in Mexican hemophiliac patients.

Factor XII Deficiency in Mexico: High Prevalence in the General Population and Patients with Venous Thromboembolic Disease.

INTRODUCTION: Thrombosis is one of the leading causes of morbidity and mortality worldwide. Venous thromboembolic disease (VTD) is considered a new epidemic. FXII deficiency is supposed to be a cause of thrombosis. To search for unknown causes of thrombosis in our population, our aim was to determine if FXII deficiency can be considered a risk factor for VTD. METHODS: Young adult Mexican patients with at least one VTD episode and healthy controls were included in this prospective, observational, controlled study. Liver and renal function tests, blood cytometry, and blood coagulation assays were performed. Plasma FXII activity and its concentration were evaluated. RESULTS: Over a two-year period, 250 patients and 250 controls were included. FXII activity was significantly lower in the control group compared to patients with VTD (p = 0.005). However, percentage of patients and controls with FXII deficiency was 8.8 and 9.2%, respectively (p = 1.000). No significant association was found between FXII deficiency and VTD (p = 1.0). FXII plasma concentration was lower in controls vs. patients with VTD: 4.05 vs. 6.19 ng/mL (p <0.001). Percentage of patients with low FXII plasma concentration was 1.6% and 6.0% in patients and controls, respectively (p = 0.010). CONCLUSIONS: FXII deficiency is a frequent finding in patients with VTD and controls in Mexico. Some patients with FXII deficiency had normal APTT result, an effect not described above. FXII plasma concentration was lower in patients with low activity.