Trombophilia

GACETA MÉDICA DE MÉXICO EDITORIAL © Permanyer 2018 Thrombophilia Abraham Majluf-Cruz Unit of Medical Research on Thrombosis, Hemostasis and Atherogenesis, Hospital General Regional Carlos MacGregor Sánchez Navarro, Instituto Mexicano del Seguro Social, Ciudad de México, Mexico Sin contar con el consentimiento previo por escrito del editor, no podrá reproducirse ni fotocopiarse ninguna parte de esta publicación. The coagulation system maintains blood in a fluid vision. This is one of the fundamental reasons why, state at every moment and, therefore, it is unceasingly rather frequently, we exaggerate blood losses, which active throughout life. However, at the moment a le- drives us to misuse blood and its derivatives, or to sion of the vascular system occurs, the coagulation make absurd or unnecessary decisions, such as call- system immediately turns 180° and transforms blood ing off surgeries or invasive diagnostic procedures. into a perfectly localized solid body, which we call clot. The questions then are: Why does the possibility or This process, by means of which a clot is formed, is the presence of hemorrhage affect us that much? Why known as hemostasis, which is one of the compo- is it that doctors, even after having been trained as nents of the coagulation system1. such, do not escape this connotation imprinted on The workup of a patient with a coagulation system human being’s collective memory? Why, if thrombosis abnormality is really very simple. All the patient’s al- is much more deleterious on human beings, we still terations are classified into two general types: either fail to give it its rightful place? I think the answer is the patient suffers a hemorrhage or has a thrombosis. very simple. Hemorrhage can be seen, and this im- There is nothing else. Thus, every pathological state pacts directly on the psyche, thus being coined and in the human being that predisposes to hemorrhage imprinted throughout the history of man; conversely, is known as hemophilia. Conversely, every patholog- thrombosis is never evident to the eye. However, our ical state that predisposes to thrombosis is called biologic destiny played a dirty trick on us, since when thrombophilia. Hemophilia and thrombophilia can be all our medical knowledge and attitudes were focused hereditary or acquired, temporary or permanent, and on preventing hemorrhage and treating it at any cost, primary or secondary. The “primary” denotation refers thrombosis appeared to us gradually, and in a lethal to a state where the alteration is precisely within the form. In effect, thrombosis is currently recognized as coagulation system, such as hemophilia A or deficien- the leading direct cause of death in the world2. Per- cy of any of the natural anticoagulant proteins. Sec- haps the reader thinks this is an exaggeration, but ondary disorders refer to any morbid state that reflects let’s consider some indisputable and well-documented on the coagulation system and alters its function, such points: In 2010, one out of every four human beings as pregnancy and antiphospholipid antibody syn- were reported to die directly due to thrombosis3, but, drome (APLAS). today, 5-6 out of every 10 possibly die due to this Throughout the entire history of humanity, we have phenomenon; nearly 90% of myocardial infarctions been terrified of hemorrhage, and large part of medi- (until today considered to be the leading cause of cine endeavors has been precisely finding out how to death, at least in the western world) occur as a con- control or prevent it. Even in this day and age, the sequence of the formation of an intracoronary human being holds a deep respect for blood loss thrombus, and nearly 66% of strokes have a throm- (which sometimes verges on terror). Unfortunately, boembolic origin4; pulmonary thromboembolism, doctors themselves quite often do not escape this which maybe in a few years will be recognized as the Correspondence: Abraham Majluf-Cruz Gabriel Mancera, 22 Col. del Valle, Del. Benito Juárez Date of reception: 15-07-2017 Gac Med Mex. 2017;153:392-394 C.P. 03100, Ciudad de México, México Date of acceptance: 30-07-2017 Contents available at PubMed E-mail: [email protected] DOI: 10.24875/GMM.M17000019 www.gacetamedicademexico.com 392  A. Majluf-Cruz: Thrombophilia main cause of mortality worldwide, is another throm- against blood natural antibodies are generated. That boembolic phenomenon that is regarded as the main is, blood is the organ that is essentially affected. The preventable cause of in-hospital death; consumption prothrombotic pathophysiological mechanisms by © Permanyer 2018 coagulopathy (formerly called disseminated intravas- means of which these autoantibodies clinically mani- cular coagulation) is essentially a disseminated throm- fest themselves can be entirely opposed in vitro. This bosis; maybe between 25% and 35% of cancer is true and significant when the APLAS essential di- patients ultimately die due to thrombosis5,6; atrial fibril- agnostic and prognostic test, lupus inhibitor, is evalu- lation, one of the most important threats to health ated. On this test, the activated partial thromboplastin systems, has in thromboembolism the most significant time is prolonged as if there was an anticoagulant in Sin contar con el consentimiento previo por escrito del editor, no podrá reproducirse ni fotocopiarse ninguna parte de esta publicación. associated morbidity and mortality7; and thrombosis the patient’s blood, although, in vivo, it is the factor is increasingly observed as an unrecognized cause of most strongly associated with the appearance of maternal death8. That is, without ceasing to be still thrombosis. When the essential hemostasis tests are important, hemorrhage has gradually given up ground prolonged, the possibility to assess Vitamin K antag- to the increasing weight of thrombosis. onists’ anticoagulant effect with certainty becomes On the other hand, the concept that thrombosis af- quite troublesome. This difficulty to know with certain- fects only old patients being taken care of in certain ty the real level of anticoagulation in a patient with areas of medicine is currently obsolete. We know that, APLAS is a very common and important cause of in contrast with what we thought a few years ago, thrombotic events recurrence. thrombosis affects children and adults, pregnant wom- The fact that the problem of thrombosis in Mexico is en, cancer patients, surgical patients, and more com- comprehensively addressed in formal publications is monly non-surgical patients4. Moreover, it occurs to encouraging. However, there is still much to do and patients in whom thrombosis was always assumed to learn. Until now, all the experience on thrombophil- be an impossible complication. In Mexico, an unfortu- ia-associated thrombosis remains sparse and uncer- nate example of this is precisely hematology, since for tain. In fact, all the information we have stems from years it was taught that, in hematological patients, studies of clinical cases in series that are reduced for especially in those with malignant conditions, throm- a country with more than 100 million inhabitants and bosis never occurred. This apparent paradox (the with diverse genetic baggage. Although the information thrombus as an essential disorder of a fluid organ that published so far is of value as a source of alert on the is called blood, which is not recognized or is denied problem of thrombophilia, from the epidemiological and by the very specialists in this organ) has its origin on clinical point of view, it is of no significance. We need the anachronistic concepts that are still being prac- large, controlled, prospective trials that include patients ticed in most hematologist-training schools in Mexico, from all regions of the country, in order for us to have which continue to consider the study of the coagula- a more comprehensive view on how primary thrombo- tion system to be unnecessary and of a lesser impor- philia mechanisms affect our population. tance than malignant conditions. Fortunately, Mexican The economic, social, medical and familiar burden younger hematologists are generating a very healthy imposed by thrombosis is devastating. However, in change of attitude. As an example, this Gaceta Médi- Mexico, we have a poor vision of what this phenom- ca de México issue features an excellent work that enon represents. We have no specific strategies to describes an association that is sparsely addressed fight it, anticoagulation or antithrombotic clinics are in the literature: Thrombosis in patients with primary practically inexistent, research on the field is almost myelofibrosis, a blood disorder with very high throm- absent and, in general, physicians’ knowledge about bogenic potential. the coagulation system and its disorders is rather On the other hand, one of the most common throm- poor. Probably, all this has its origin on the fact that bophilias identified in young patients with thrombosis thrombosis is not known or continues to be regarded is APLAS. This thrombophilia, secondary and ac- as a non-significant area. Maybe it’s time to make a quired, is characterized for affecting both the arterial radical change in public policies, in medical thought and venous system, just as well-described in another and in the collective consciousness as well. In effect, very good case in this Gaceta issue. APLAS is a blood public perception on the problem of thrombosis is disorder essentially defined by the appearance of ar- extremely low and even worse for venous in compar- terial, venous or placental thrombosis in a pathophys- ison with arterial thrombosis. Nevertheless, thrombo- iological scenario where autoantibodies directed sis is there, at every moment, at any age, lurking in 393  Gaceta Médica de México. 2017;153 the darkness of our conscience, feeding on our igno- 3. Raskob GE, Angchaisuksiri P, Blanco AN, et al. Thrombosis. A major contributor to global disease burden. Arterioscler Thromb Vasc Biol. rance and killing more Mexicans than any other patho- 2014;34:2363-71. 4. Wendelboe AM, Raskob GE. Global burden of thrombosis: epidemiolog- physiological phenomenon every day, as in the rest © Permanyer 2018 ic aspects. Circ Res. 2016;118:1340-7. 5. Key NS, Khorana AA, Mackman N, et al. Thrombosis in cancer: research of the world. priorities identified by a National Cancer Institute/National Heart, Lung, and Blood Institute Strategic Working Group. Cancer Res. 2016;76:3671-5. 6. Kourlaba G, Relakis J, Mylonas C, et al. The humanistic and economic References burden of venous thromboembolism in cancer patients: A systematic review. Blood Coagul Fibrinolysis. 2015;26:13-31. 7. Disertori M, Franzosi MG, Barlera S, et al. Thromboembolic event rate 1. Lobato-Mendizábal E, Majluf-Cruz A. Trombofilia, tromboembolia y el uso in paroxysmal and persistent atrial fibrillation: data from the GISSI-AF de las heparinas no fraccionadas y de bajo peso molecular. Rev Invest trial. BMC Cardiovasc Dis. 2013;13:28. Clin. 2000;52:346-65. 8. Kourlaba G, Relakis J, Kontodimas S, et al. A systematic review and Sin contar con el consentimiento previo por escrito del editor, no podrá reproducirse ni fotocopiarse ninguna parte de esta publicación. 2. Majluf-Cruz A, Espinosa-Larrañaga F. Fisiopatología de la trombosis. meta-analysis of the epidemiology and burden of venous thromboembo- Gac Med Mex. 2007;143(Supl 1):11-4. lism among pregnant women. Int J Gynaecol Obstet. 2016;132:4-10. 394