Thrombophilia in Mexico Benjamín Moncada1, Guillermo Ruiz-Argüelles2 and Olga Johnson-Ponce1 1Universidad Autónoma De San Luis Potosi; Hospital Central Dr

GACETA MÉDICA DE MÉXICO SPECIAL ARTICLE Thrombophilia in Mexico Benjamín Moncada1, Guillermo Ruiz-Argüelles2 and Olga Johnson-Ponce1 1Universidad Autónoma de San Luis Potosi; Hospital Central Dr. Ignacio Morones Prieto; San Luis Potosí, S.L.P., Mexico; 2Centro de Hematologia y Medicina Interna de Puebla, Pue Mexico Primary thrombophilia is among the genetic anom- – Thrombosis at rare sites, not usual for thromboses. alies that translate into important disease. In this pa- – Women that have suffered one or more thology, coagulation takes place when in reality it is miscarriages. not necessary. Thrombophilia is the opposite of he- – Thrombosis in spite of being on anticoagulants. mophilia, where patients suffer excessive bleeding – Family history of thrombosis. even with negligible injuries, which does not occur in – Recurrent thrombosis with no apparent precipi- normal subjects with intact coagulation mechanisms. tating factor. The explanation of hemophilia is reduced to a handful As it can be appreciated in table 2, the explanation of situations, whereas in the case of thrombophilia, of thrombophilia is not a single one, but thrombotic there would be over a dozen explanations. Knowledge phenomena can be of different origins. It is also ap- of these two diseases, both by the public and the preciated that the vast majority of patients have more medical class, is contrastingly in favor of hemophilia. than one alteration on these laboratory tests. The In the case of this disease, there are even therapeutic average age of patients in this group was 30 years. means available to avoid excessive and even mortal Standing out in the lead is the presence of the meth- bleeding when there is the presumption of a problem ylenetetrahydrofolate reductase gene 677C-T muta- such as major surgery would be or one of minor im- tion and platelet adhesiveness alteration, which con- portance such as dental extraction. At the state Min- stitutes the sticky platelet syndrome (SPS). To a lesser istry of Health, there are hemophilia cases registered proportion, there is an increase in the plasmino- which are provided support, while there is not a sec- gen-activator inhibitor, prothrombin gene 20210G-A tion for thrombophilia. mutation, anti-phospholipid antibodies, and activated Dr. J. Guillermo Ruiz Argüelles has been dedicated protein C resistance (Table 3). to the search for alterations that are the cause of Apparently, the thrombotic obstruction site is ran- thrombophilia and thus is the profile of this problem domly established, since there is no preference for in our country known. Since 17 years ago, we have certain place in association with the detected anom- been investigating the class of alteration in a patient aly. It is possible for this concept to be able to be with primary trombophilia has, with the support of Cl- clarified in the future, maybe by the activity of cell inica Ruiz, Laboratorios, in the city of Puebla, in receptors or by a microenvironment of molecules such charge of aforementioned Dr. Ruiz-Argüelles as cytokines and other affine elements that play a role (Table 1). in determining the obstruction site. In thrombophilia, Indication for search occurs in the presence any of all blood vessels can be affected: arteries and veins, the following circumstances: as well as arterioles. – Thrombosis in a young individual, around As it can be observed, there is not a single male in 40 years of age. our series, which surely is due to the fact that, in the Correspondence: Benjamín Moncada Av. Venustiano Carranza, 2395 Date of reception: 23-03-2016 Gac Med Mex. 2017;153:453-458 C.P. 78290 San Luis Potosí, S.L.P., México Date of acceptance: 19-04-2016 Contents available at PubMed E-mail: [email protected] DOI: 10.24875/GMM.M17000029 www.gacetamedicademexico.com 453 Gaceta Médica de México. 2017;153 Table 1. Elements that constitute the thrombophilia profile in this occur anywhere in the body economy. There are no series laboratory marker bases on which the diagnosis of the Lipoprotein syndrome can be established, although attempts have 4 Homocysteine been made to get there . For the moment, it is a “functional” test where platelets are confronted at decreas- Functional fibrinogen ing doses of epinephrine, as well as adenosine di- Fibrin aggregation phosphate, and are compared with normal standards5; Plasminogen since the test has to be performed immediately after the blood sample is obtained, this represents an in- Plasminogen‑activator inhibitor convenience for a seriously ill patient when there is Platelet adhesiveness not an appropriate laboratory at reach. In daily prac- Antithrombin III tice, this test is performed once the patient has recov- ered from the acute problem, as in the case of throm- Circulating anticoagulants boses at critical territories such as the brain or lung. Anti‑phospholipid antibodies Since SPS is common and potentially serious due to Anticardiolipin IgG and IgM the sites that can be affected, it is important to create 6 Anti‑beta‑2 glycoprotein antibodies awareness about it and to delve into its pathogene- sis5, as well as into therapeutic aspects7,8. Coagulation protein S The plasminogen-activator inhibitor defect occupies Coagulation protein C an intermediate place in this series, and it is already Activated protein C resistance recognized to be a cause of thrombophilia in different reports9. One of our cases (case 13) combines this Mutations: 10 Prothrombin 20210 G‑A alteration with SPS . Methylenetetrahydrofolate reductase 677 C‑T In routine clinical practice, a person with thrombo- Factor V Leiden, Liverpool, Hong Kong, Cambridge sis with no apparent explanation is very often regard- Factor V R2 haplotype ed as having antiphospholipid antibodies syndrome without considering other possibilities. Of course, this presence of a background anomaly, there are contrib- does not redound to patient benefit as regard to treat- uting factors, and one of them, the most important, ment and recovery. In our cases, the presence of appears to be estrogenic hormones. antiphospholipid antibodies occupies a very low Publications in different places of the world have place. considered the MTHFR 677 mutation to be the When contemplating the possibility of thrombophilia, cause of thrombotic disease1. Although on top of the it is also usual in our setting to consider a mutation of list of alterations in patients with thrombosis (62% coagulation factor V as a causative factor. Although this is possible, this alteration is rarely seen among in this series and 67% in the one of Dr. Ruiz Ar- us, and the same occurs with other factor V mutations güelles), in our setting, it has been regarded as a (Cambridge, Hong Kong, and Liverpool)11; however, in “weak” factor for that purpose and to almost always other countries, especially in Europe, the presence of be accompanied by other alterations2. In our series, factor V mutations is, indeed, prevalent. only in one of 27 studied patients was the MTHFR In cases of thrombophilia, it is also common in our 667 mutation the only found alteration. Interestingly, setting ordering as a priority or exclusively a determi- in studies with healthy subjects of the mestizo pop- nation of coagulation proteins C and S values, espe- ulation in this country, the percentage of the pres- cially of the former. Again, this alteration is low-profile ence of the 677 mutation reaches the figure of among us. In the rare cases, it occurs, there is usually 2 78% . a large variety of manifestations12. From that point of view, it is then perceived that the All this has great importance from different most common and important alteration would be SPS. angles: The finding of this alteration was made by Mammen – Recognizing that there is the technical possibility in 1988, and one decade later, he wrote down his to characterize the problem originated by a state clinical findings with regard to the laboratory alter- of primary thrombophilia, thanks to Dr. Argüelles ation3, thus being established that thrombosis can working group efforts. 454 B. Moncada, et al.: Thrombophilia in Mexico Table 2. List with obtained results and clinical diagnoses that motivated the investigation No. Gender Age (years) Diagnosis Affected site Findings 1 F 28 Transient cerebral vascular Brain Methylenetetrahydrofolate reductase 677 C‑T mutation insufficiency Skin Prothrombin 20210 G‑A mutation Malignant atrophic papulosis (Degos Activated protein C resistance disease) 2 M NB Healthy Methylenetetrahydrofolate reductase 677 C‑T mutation Patient 1 son Prothrombin 20210 G‑A mutation 3 F 38 Livedo reticularis Skin Methylenetetrahydrofolate reductase 677 C‑T mutation Transient vascular insufficiency Brain SPS 4 F 22 Normal pregnancy SPS Patient 3 niece 5 F 24 Middle cerebral thrombosis Brain Methylenetetrahydrofolate reductase 677 C‑T mutation SPS 6 F 40 Mesenteric thrombosis Intestine and lung SPS PTE Placenta Miscarriages Legs 7 F 31 Deep venous thrombosis Leg SPS 8 F 30 PTE Leg Methylenetetrahydrofolate reductase 677 C‑T mutation Transient cerebral vascular Lung SPS insufficiency Brain Prothrombin 20210 G‑A mutation PAI 9 F 17 Normal delivery Placenta SPS Patient 8 daughter Prothrombin 20210 G‑A mutation 10 F 17 Erythema nodosum Skin and placenta SPS Pre‑term delivery Prothrombin 20210 G‑A mutation PAI 11 F 34 Longitudinal sinus occlusion Brain SPS 12 F 48 White atrophy Skin Methylenetetrahydrofolate reductase 677 C‑T mutation Lung Prothrombin 20210 G‑A mutation 13 F 12 White atrophy Skin SPS Livedoid vasculopathy PAI 14 F 43 Skin Skin SPS White atrophy Leg veins Antiphospholipid antibodies Previous venous thromboses Anti‑beta‑2 glycoprotein 15 F 37 Post‑abortion PTE Leg veins SPS Lung PAI 16 F 40 Sneddon syndrome Skin and brain Antithrombin (1%) Protein C (8) Leiden (6) Homocystein (1%) 17 F 33 Pre‑term delivery Placenta SPS Grandmother and mother with PAI pre‑eclampsia 18 F 13 Thrombophlebitis Leg veins SPS Circulating anticoagulants Anti‑beta‑2 glycoprotein antibodies Anticardiolipin antibodies Methylenetetrahydrofolate reductase 677 C‑T mutation 19 F 40 Cerebelous artery thrombosis Brain PAI Methylenetetrahydrofolate reductase 677 C‑T mutation Elevated fibrinogen (Continue) 455 Gaceta Médica de México.

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