Is Isolated Diastolic Hypertension an Important Phenotype?

PURPOSE OF REVIEW: Isolated diastolic hypertension (IDH) is a frequent hypertension phenotype. We review IDH pathophysiology, risk stratification, and therapeutic decisions. RECENT FINDINGS: Recent guidelines lowering blood pressure cutoff levels have increased IDH prevalence and likely decreased associated cardiovascular risk. Long-term cardiovascular risk and pharmacological intervention in IDH are controversial. Narrow pulse pressure and other physiological and epidemiological characteristics are shared with a systodiastolic hypertension (SDH) subgroup. We propose that IDH be incorporated into a broader category, predominantly diastolic hypertension (PDH), defined by pulse pressure ≤ 45 mmHg and includes IDH and SDH with a narrow pulse pressure. IDH-PDH is associated with cardiovascular risk in the long term, especially in young patients. Standardization of the IDH definition and population may contribute to future research to understand genetics, pathophysiology, and eventually therapy in this important subgroup of hypertensive patients.

Rendimiento de ecuaciones para predecir riesgo cardiovascular en una población de Argentina / Performance of equations to predict cardiovascular risk in an Argentine population

Resumen El rendimiento de las ecuaciones existentes de predicción de riesgo cardiovascular (RCV) en población argentina es desconocido. Se comparó RCV estimado por dichas ecuaciones, con la ocurrencia de eventos cardiovasculares (ECV) en una población de pacientes sin enfermedad cardiovascular de un hospital argentino. Se incluyeron aleatoriamente adultos entre 40 y 70 años, excluyéndose quienes al momento del enrolamiento presentaban historia de ECV mayor, cáncer activo, o tratamiento hipolipemiante. Se calculó RCV a 10 años al momento de inclusión, utilizando ecuaciones de Framingham 2008, SCORE (para poblaciones de bajo y alto riesgo), ATP III, Organización mundial de la saludregión América B (OMS-B) y Ecuación de Cohorte Agrupada (ECA). El fin de seguimiento fue 10 años ± 6 meses, ocurrencia de infarto de miocardio fatal o muerte por cualquier causa. Se utilizaron curvas ROC para evaluar discriminación (ABC > 0.75 buena discriminación). La calibración se evaluó mediante chi-cuadrado de Hosmer Lemeshow (Chi > 20 o p < 0.05 pobre calibración). Incluimos 606 pacientes, 366 mujeres, edad promedio 56.7 ± 8.4 años. Se observaron 10 (1.7%) muertes de causa no cardiovascular, 5 (0.8%) causa cardiovascular. Se registraron 58 (9.8%) ECV no fatales. Hubo aceptable discriminación para ecuaciones de Framingham, ATP-III y ECA. La calibración global solo fue buena con las ecuaciones de ATP-III y ECA. La frecuencia observada de ECV fue baja, y hubo sobreestimación de RCV con todas las ecuaciones. Sin embargo, se podría sugerir la aplicación de las ecuaciones de ATP-III o ECA en esta población.

Abstract The performance of available risk scores to predict cardiovascular risk (CVR) in the Argentinian population is unknown. Our aim was to compare the CVR predicted by several equations with the occurrence of cardiovascular events (CVE) in patients without known cardiovascular disease in an Argentinian hospital. Adults between 40 and 70 years were randomly selected, excluding those with prior history of major CVE, active cancer, lipid lowering treatment and absence of follow-up data. Framingham 2008, SCORE (low and high-risk populations), ATP III, World Health OrganizationAmerican B region (WHO-B) and Pooled Cohort equations (PC) risk scores were used to calculate 10-y CVR at time of enrollment. End of follow-up was 10 years ± 6 months, occurrence of fatal myocardial infarction or death from any cause. We used ROC curves to assess discrimination (AUC > 0.75 good discrimination), and Hosmer Lemeshow chi-square to evaluate calibration (Chi > 20 or p value < 0.05 poor calibration). We included 606 patients in our study, 336 women, average age 56.7 ± 8.4 year. Of those, 10 (1.7%) non-cardiovascular deaths, and 5 (0.8%) cardiovascular deaths were observed. 58 (9.8%) a non-fatal CVE were recorded. There was acceptable discrimination for Framingham, ATP-III, and both PC equations. The global calibration was only good with the ATP-III and PC equations. The observed frequency of CVE was low, and the CVR was overestimated by all equations. However, applying ATP-III or PC equations to assess CVR could be considered in our population.

[Performance of equations to predict cardiovascular risk in an Argentine population]. / Rendimiento de ecuaciones para predecir riesgo cardiovascular en una población argentina.

The performance of available risk scores to predict cardiovascular risk (CVR) in the Argentinian population is unknown. Our aim was to compare the CVR predicted by several equations with the occurrence of cardiovascular events (CVE) in patients without known cardiovascular disease in an Argentinian hospital. Adults between 40 and 70 years were randomly selected, excluding those with prior history of major CVE, active cancer, lipid lowering treatment and absence of follow-up data. Framingham 2008, SCORE (low and high-risk populations), ATP III, World Health Organization- American B region (WHO-B) and Pooled Cohort equations (PC) risk scores were used to calculate 10-y CVR at time of enrollment. End of follow-up was 10 years ± 6 months, occurrence of fatal myocardial infarction or death from any cause. We used ROC curves to assess discrimination (AUC > 0.75 good discrimination), and Hosmer Lemeshow chi-square to evaluate calibration (Chi > 20 or p value < 0.05 poor calibration). We included 606 patients in our study, 336 women, average age 56.7 ± 8.4 year. Of those, 10 (1.7%) non-cardiovascular deaths, and 5 (0.8%) cardiovascular deaths were observed. 58 (9.8%) a non-fatal CVE were recorded. There was acceptable discrimination for Framingham, ATP-III, and both PC equations. The global calibration was only good with the ATP-III and PC equations. The observed frequency of CVE was low, and the CVR was overestimated by all equations. However, applying ATP-III or PC equations to assess CVR could be considered in our population.

El rendimiento de las ecuaciones existentes de predicción de riesgo cardiovascular (RCV) en población argentina es desconocido. Se comparó RCV estimado por dichas ecuaciones, con la ocurrencia de eventos cardiovasculares (ECV) en una población de pacientes sin enfermedad cardiovascular de un hospital argentino. Se incluyeron aleatoriamente adultos entre 40 y 70 años, excluyéndose quienes al momento del enrolamiento presentaban historia de ECV mayor, cáncer activo, o tratamiento hipolipemiante. Se calculó RCV a 10 años al momento de inclusión, utilizando ecuaciones de Framingham 2008, SCORE (para poblaciones de bajo y alto riesgo), ATP III, Organización mundial de la salud- región América B (OMS-B) y Ecuación de Cohorte Agrupada (ECA). El fin de seguimiento fue 10 años ± 6 meses, ocurrencia de infarto de miocardio fatal o muerte por cualquier causa. Se utilizaron curvas ROC para evaluar discriminación (ABC > 0.75 buena discriminación). La calibración se evaluó mediante chi-cuadrado de Hosmer Lemeshow (Chi > 20 o p < 0.05 pobre calibración). Incluimos 606 pacientes, 366 mujeres, edad promedio 56.7 ± 8.4 años. Se observaron 10 (1.7%) muertes de causa no cardiovascular, 5 (0.8%) causa cardiovascular. Se registraron 58 (9.8%) ECV no fatales. Hubo aceptable discriminación para ecuaciones de Framingham, ATP-III y ECA. La calibración global solo fue buena con las ecuaciones de ATP-III y ECA. La frecuencia observada de ECV fue baja, y hubo sobreestimación de RCV con todas las ecuaciones. Sin embargo, se podría sugerir la aplicación de las ecuaciones de ATP-III o ECA en esta población.

Decreased Rivaroxaban Levels in a Patient with Cerebral Vein Thrombosis Receiving Phenytoin.

Combined use of antiepileptic drugs and anticoagulants is common. We describe the first case documenting laboratory interaction between rivaroxaban and phenytoin. A 48-year-old woman was admitted to our hospital due to cerebral venous thrombosis, bilateral pulmonary embolism, and deep vein thrombosis. She came from a small town with difficult access to warfarin monitoring. She was receiving phenytoin 100 mg three times daily (t.i.d.) and started enoxaparin 60 mg twice daily (b.i.d.). An abdominal mass was diagnosed and removed by laparoscopy (gastrointestinal stromal tumor). On day 5, she was switched to rivaroxaban 15 mg b.i.d. First peak anti-Factor Xa was 70 ng/ml (reference value: 100-300 ng/ml). She was discharged on rivaroxaban 15 mg b.i.d. and phenytoin 100 mg t.i.d. A week later, anti-Xa levels were 90 ng/ml. Due to concerns about thrombosis progression, she was switched to dabigatran. During follow-up, she remained asymptomatic and thrombin time >180 s was measured several times along 3 months as surrogate for dabigatran activity. Phenytoin is a combined CYP3A4 and P-glycoprotein inducer, which might reduce rivaroxaban levels. Dabigatran is substrate of P-glycoprotein, meaning potential malabsorption. Despite unavailability of plasmatic dabigatran essays, our patient improved her symptoms without further symptomatic thromboembolism. Facing these interactions, either monitoring serum levels of anticoagulants or other therapeutic options should be considered.

[Gastrointestinal stromal tumor and renal transplant]. / Tumor del estroma gastrointestinal y trasplante renal.

Gastrointestinal stromal tumor (GIST) accounts for nearly 1% of all gastrointestinal tumors. Its association with renal transplantation is not frequent. Approximately 95% of GIST show staining for CD177. DOG1 is a recently described monoclonal antibody that shows positivity even in the absence of CD177 staining. The diagnosis of GIST should be pursued because of the availability of very effective treatments with tyrosine-kinase inhibitors. Herein, we describe the case of a woman with renal transplant who presented a small bowel GIST and weak positivity for CD177, treated initially with surgery. Tumor recurrence was documented 3 years later and histopatology showed loss of CD177 staining and positivity for DOG1. She was treated with imatimib without further recurrence after five years of follow up.

Tumor del estroma gastrointestinal y trasplante renal / Gastrointestinal stromal tumor and renal transplant

El tumor estromal gastrointestinal (GIST) representa alrededor del 1% de todos los tumores digestivos y su aparición en pacientes trasplantados renales es infrecuente. Aproximadamente el 95% muestra tinción positiva para c-kit/CD117. DOG1 es un anticuerpo recientemente descrito que se sobre-expresa en los GIST, incluso en c-kit/ CD117 negativos. El diagnóstico preciso de GIST resulta imperativo, debido a la disponibilidad y la creciente eficacia de los inhibidores de la tirosina quinasa en estos tumores, incluso en el subgrupo c-kit/ CD117 negativo. Se presenta el caso de una mujer trasplantada renal inicialmente con GIST en intestino delgado y débil positividad para CD117 tratada con cirugía y recidiva tumoral a los tres años, pérdida de la expresión CD117 y tinción positiva para DOG1. Recibió tratamiento exitoso con imatimib sin presentar recaída tumoral durante un seguimiento de cinco años.

Gastrointestinal stromal tumor (GIST) accounts for nearly 1% of all gastrointestinal tumors. Its association with renal transplantation is not frequent. Approximately 95% of GIST show staining for CD177. DOG1 is a recently described monoclonal antibody that shows positivity even in the absence of CD177 staining. The diagnosis of GIST should be pursued because of the availability of very effective treatments with tyrosine-kinase inhibitors. Herein, we describe the case of a woman with renal transplant who presented a small bowel GIST and weak positivity for CD177, treated initially with surgery. Tumor recurrence was documented 3 years later and histopatology showed loss of CD177 staining and positivity for DOG1. She was treated with imatimib without further recurrence after five years of follow up.

[Heparin-induced thrombocytopenia. New therapeutical options]. / Trombocitopenia inducida por heparina. Nuevas opciones terapéuticas.

Heparin-induced thrombocytopenia (HIT) is an immune-mediated adverse reaction due to antibodies to a multimolecular complex of heparin and platelet factor 4 (PF4) characterized by moderate thrombocytopenia and paradoxical arterial or venous thrombosis. It is a relatively infrequent complication related to the administration of any type of heparin. In patients undergoing percutaneous coronary revascularization or coronary artery by-pass graft the prevalence of HIT is higher than in other clinical settings. Recognizing clinical and laboratory features of HIT allow immediate discontinuation of heparin and the use of alternative anticoagulants to avoid serious thrombotic complications. In this review, we summarize different therapeutic options for the treatment of HIT with special emphasis on direct oral anticoagulants (DOACS) such as dabigatran, rivaroxaban and apixaban. DOACS might represent a therapeutic alternative for HIT treatment.

Trombocitopenia inducida por heparina: Nuevas opciones terapéuticas / Heparin-induced thrombocytopenia. New therapeutical options

La trombocitopenia inducida por heparina (TIH) es una reacción adversa inmunológica mediada por la formación de anticuerpos contra el complejo heparina-factor plaquetario 4 (FP4), caracterizada por la presencia de trombocitopenia y la asociación paradojal de trombosis arterial o venosa. Es una complicación poco frecuente pero grave del uso de cualquier tipo de heparina. En tratados con procedimientos cardiovasculares como intervención coronaria percutánea y cirugía de revascularización cardiaca, la prevalencia de anticuerpos es significativamente mayor que en otros escenarios clínicos. El reconocimiento de las características clínicas y de laboratorio permite la suspensión inmediata de la heparina y la instauración de tratamiento anticoagulante alternativo, para evitar la progresión y formación de nuevos trombos y sus complicaciones. En la presente revisión se resumen las diferentes alternativas terapéuticas para la TIH, en particular los anticoagulantes orales directos (DOACS) como el dabigatran, rivaroxaban y apixaban que pueden proporcionar una nueva opción para el tratamiento de TIH.

Heparin-induced thrombocytopenia (HIT) is an immune-mediated adverse reaction due to antibodies to a multimolecular complex of heparin and platelet factor 4 (PF4) characterized by moderate thrombocytopenia and paradoxical arterial or venous thrombosis. It is a relatively infrequent complication related to the administration of any type of heparin. In patients undergoing percutaneous coronary revascularization or coronary artery by-pass graft the prevalence of HIT is higher than in other clinical settings. Recognizing clinical and laboratory features of HIT allow immediate discontinuation of heparin and the use of alternative anticoagulants to avoid serious thrombotic complications. In this review, we summarize different therapeutic options for the treatment of HIT with special emphasis on direct oral anticoagulants (DOACS) such as dabigatran, rivaroxaban and apixaban. DOACS might represent a therapeutic alternative for HIT treatment.

[Successful treatment with fondaparinux in heparin-induced thrombocytopenia and thrombosis]. / Tratamiento exitoso con fondaparinux en trombocitopenia inducida por heparina y trombosis.

Heparin induced thrombocytopenia (HIT) is an immune-mediated adverse reaction characterized by thrombocytopenia and paradoxical arterial or venous thrombosis, due to the formation IgG antibodies directed to a multimolecular complex of heparin-platelet factor 4 (PF4). Fondaparinux is a selective factor Xa inhibitor with little affinity for PF4 and thus less likely to induce an immune response, making fondaparinux a potentially useful drug for the treatment of HIT. Herein we report the case of a 73 years old woman with HIT associated with arterial and venous thrombosis that was successfully treated with fondaparinux, with normalization of the platelet countand without progression of thrombosis.

Tratamiento exitoso con fondaparinux en trombocitopenia inducida por heparina y trombosis / Successful treatment with fondaparinux in heparin-induced thrombocytopenia and thrombosis

La trombocitopenia inducida por heparina (TIH) es una reacción adversa inmunológica caracterizada por trombocitopenia y la asociación paradojal de trombosis arterial o venosa. Es causada por la formación de anticuerpos IgG contra el complejo multimolecular de heparina-factor plaquetario 4 (FP4). Fondaparinux es un inhibidor selectivo del factor Xa que tiene escasa afinidad por el FP4 y posee un menor potencial para inducir una respuesta inmunológica, haciendo del mismo un agente potencialmente útil en el tratamiento de la TIH. Se presenta el caso de una mujer de 73 años con TIH asociada a fenómenos trombóticos arteriales y venosos, que recibió exitosamente fondaparinux, con normalización del recuento plaquetario y sin progresión trombótica.

Heparin induced thrombocytopenia (HIT) is an immune-mediated adverse reaction characterized by thrombocytopenia and paradoxical arterial or venous thrombosis, due to the formation IgG antibodies directed to a multimolecular complex of heparin-platelet factor 4 (PF4). Fondaparinux is a selective factor Xa inhibitor with little affinity for PF4 and thus less likely to induce an immune response, making fondaparinux a potentially useful drug for the treatment of HIT. Herein we report the case of a 73 years old woman with HIT associated with arterial and venous thrombosis that was successfully treated with fondaparinux, with normalization of the platelet countand without progression of thrombosis.

[Venous thromboembolic prophylaxis. Guidelines for adults in Argentina]. / Guía de recomendaciones para la profilaxis de la enfermedad tromboembólica venosa en adultos en la Argentina.

The venous thromboembolic disease (VTD) in adults has a high morbidity and mortality. It can be also associated to disabling chronic conditions. In spite of this, prophylaxis in healthcare assistance is still underused. In this article, the available evidence in thromboprophylaxis was analyzed to offer recommendations (1) or suggestions (2) classified according to different levels of evidence (A, B or C). Different medical scenarios and types of thromboprophylaxis were analyzed. In major orthopedic surgeries low molecular weight heparins, LMWH, inhibitors of the Xa and IIa factors are recommended (1B) to be started during hospitalization and continued for 35 days in hip replacement surgery and for 10 days in total knee replacement surgery. Knee arthroscopy and spine surgery do not require pharmacologic treatment (2B) unless the patient has other risks factors for thrombosis. In such cases, LMWH are recommended. Non-surgical patients who have at least one risk factor should receive LMWH, NFH or fondaparinux (1B) if they are to be bedridden or unable to walk for three or more days. Patients undergoing neurosurgery or with intracranial hemorrhage should receive mechanic prophylaxis (2C), and accordingly they should start LMWH or NFH 24 to 72 hours afterwards (2C). The latter two drugs are recommended for critically ill patients. Patients with low risk for VTD undergoing other type of surgeries should be prescribed with mechanical prophylaxis (2C) and encouraged to walk promptly (2C), while those with high risk should be prescribed with LMWH or NFH (1B or 2C according to bleeding risk factors).

Hemodynamic circulatory patterns in young patients with predominantly diastolic hypertension.

To evaluate the spectrum of hemodynamic patterns in patients with isolated diastolic hypertension-predominantly diastolic hypertension, we re-analyzed a previously reported cohort of 189 non-medicated hypertensive individuals that were assessed by impedance cardiography. We selected 46 patients who were less than 50 years old and had pulse pressure less or equal than 45 mm Hg confirmed by ambulatory blood pressure monitoring. The selected cohort had a mean age of 39.7 years and was 47% men. Three distinct groups were identified: a high cardiac index (CI) "hyperdynamic" group, with normal to near normal systemic vascular resistance (SVR); an intermediate CI and SVR group; and a "vasotonic" group, with low CI and high SVR. Heart rate was similar among the three groups. Stroke volume index (SVI) was significantly higher in the hyperdynamic group (61.8, 49.7, and 39.7 mL/m(2) in the high, intermediate, and low CI groups, respectively). The hyperdynamic group had greater total arterial compliance index than the vasotonic group (1.3 ± 0.3 vs 0.92 ± 0.2 mL/m(2) mm Hg for high vs low CI, respectively; P < .001). In conclusion, isolated diastolic hypertension-predominantly diastolic hypertension patients can have diverse hemodynamic patterns that cannot be predicted based on peripherally measured blood pressure and heart rate alone. This hemodynamic complexity must be taken into account when considering the genetic and pathophysiologic mechanisms of hypertension.

Guía de recomendaciones para la profilaxis de la enfermedad tromboembólica venosa en adultos en la Argentina / [Venous thromboembolic prophylaxis. Guidelines for adults in Argentina].

The venous thromboembolic disease (VTD) in adults has a high morbidity and mortality. It can be also associated to disabling chronic conditions. In spite of this, prophylaxis in healthcare assistance is still underused. In this article, the available evidence in thromboprophylaxis was analyzed to offer recommendations (1) or suggestions (2) classified according to different levels of evidence (A, B or C). Different medical scenarios and types of thromboprophylaxis were analyzed. In major orthopedic surgeries low molecular weight heparins, LMWH, inhibitors of the Xa and IIa factors are recommended (1B) to be started during hospitalization and continued for 35 days in hip replacement surgery and for 10 days in total knee replacement surgery. Knee arthroscopy and spine surgery do not require pharmacologic treatment (2B) unless the patient has other risks factors for thrombosis. In such cases, LMWH are recommended. Non-surgical patients who have at least one risk factor should receive LMWH, NFH or fondaparinux (1B) if they are to be bedridden or unable to walk for three or more days. Patients undergoing neurosurgery or with intracranial hemorrhage should receive mechanic prophylaxis (2C), and accordingly they should start LMWH or NFH 24 to 72 hours afterwards (2C). The latter two drugs are recommended for critically ill patients. Patients with low risk for VTD undergoing other type of surgeries should be prescribed with mechanical prophylaxis (2C) and encouraged to walk promptly (2C), while those with high risk should be prescribed with LMWH or NFH (1B or 2C according to bleeding risk factors).

Guía de recomendaciones para la profilaxis de la enfermedad tromboembólica venosa en adultos en la Argentina. / [Venous thromboembolic prophylaxis. Guidelines for adults in Argentina].

The venous thromboembolic disease (VTD) in adults has a high morbidity and mortality. It can be also associated to disabling chronic conditions. In spite of this, prophylaxis in healthcare assistance is still underused. In this article, the available evidence in thromboprophylaxis was analyzed to offer recommendations (1) or suggestions (2) classified according to different levels of evidence (A, B or C). Different medical scenarios and types of thromboprophylaxis were analyzed. In major orthopedic surgeries low molecular weight heparins, LMWH, inhibitors of the Xa and IIa factors are recommended (1B) to be started during hospitalization and continued for 35 days in hip replacement surgery and for 10 days in total knee replacement surgery. Knee arthroscopy and spine surgery do not require pharmacologic treatment (2B) unless the patient has other risks factors for thrombosis. In such cases, LMWH are recommended. Non-surgical patients who have at least one risk factor should receive LMWH, NFH or fondaparinux (1B) if they are to be bedridden or unable to walk for three or more days. Patients undergoing neurosurgery or with intracranial hemorrhage should receive mechanic prophylaxis (2C), and accordingly they should start LMWH or NFH 24 to 72 hours afterwards (2C). The latter two drugs are recommended for critically ill patients. Patients with low risk for VTD undergoing other type of surgeries should be prescribed with mechanical prophylaxis (2C) and encouraged to walk promptly (2C), while those with high risk should be prescribed with LMWH or NFH (1B or 2C according to bleeding risk factors).

Prevalence of Janus Kinase 2 mutations in patients with unusual site venous thrombosis.

We aimed to study patients with splanchnic vein thrombosis (SVT) and cerebral vein thrombosis (CVT) searching for JAK2 mutations. We evaluated 14 patients (median age: 41.5 years) with portal vein thrombosis (PVT) = 7; mesenteric vein thrombosis (MVT) = 3; and CVT = 4. JAK2 V617F was assessed by allele specific PCR of peripheral blood DNA. In addition, DNA was sequenced for other JAK2 mutations. Other inherited and acquired thrombophilia risk factors were evaluated. JAK2 V617F was positive in four out of seven patients with PVT and in one CVT patient. These five patients had a diagnosis of myelo-proliferative disorder (MPD) at the moment of the occurrence of thrombosis (n = 2) or later (n = 2). Patients with MVT and CVT were negative for JAK2 V617F, except one patient with CVT and a diagnosis of essential thrombocythemia. No other JAK2 mutations were found in this cohort. Besides MPD, other thrombophilia risk factors were identified in five patients. One patient had MPD as well as thrombophilia risk factor. In this group, 4 out of 7 of the patients with PVT carried the JAK2 V617F mutation with or without overt MPD. However, the investigation of other JAK2 mutations may not be necessary in patients with thrombosis at unusual sites.

Prevalence of Janus kinase 2 mutations in patients with unusual site venous thrombosis / Prevalencia de las mutaciones del gen quinasa Janus 2 en pacientes con trombosis venosa en sitios poco frecuentes

We aimed to study patients with splanchnic vein thrombosis (SVT) and cerebral vein thrombosis (CVT) searching for JAK2 mutations. We evaluated 14 patients (median age: 41.5 years) with portal vein thrombosis (PVT) = 7; mesenteric vein thrombosis (MVT) = 3; and CVT = 4. JAK2 V617F was assessed by allele specific PCR of peripheral blood DNA. In addition, DNA was sequenced for other JAK2 mutations. Other inherited and acquired thrombophilia risk factors were evaluated. JAK2 V617F was positive in four out of seven patients with PVT and in one CVT patient. These five patients had a diagnosis of myeloproliferative disorder (MPD) at the moment of the occurrence of thrombosis (n = 2) or later (n = 2). Patients with MVT and CVT were negative for JAK2 V617F, except one patient with CVT and a diagnosis of essential thrombocythemia. No other JAK2 mutations were found in this cohort. Besides MPD, other thrombophilia risk factors were identified in five patients. One patient had MPD as well as thrombophilia risk factor. In this group, 4 out of 7 of the patients with PVT carried the JAK2 V617F mutation with or without overt MPD. However, the investigation of other JAK2 mutations may not be necessary in patients with thrombosis at unusual sites.

Nuestro objetivo fue estudiar pacientes con trombosis de las venas esplácnicas (TVE) o trombosis de las venas cerebrales (TVC) en búsqueda de mutaciones del gen quinasa Janus 2 (JAK2). Se estudiaron 14 pacientes (media de edad: 41.5 años) con trombosis de la vena porta (TVP n = 7), trombosis de la vena mesentérica (TVM, n = 3) y TVC (n = 4). La mutación V617F del gen JAK2 fue evaluada por reacción en cadena de la polimerasa (PCR) alelo-específica en muestras de sangre periférica. Además, se realizó secuenciación de ADN en búsqueda de otras mutaciones del gen JAK2 distintas de V617F. También se investigaron factores genéticos y adquiridos para trombofilia. JAK2 V617F fue positiva en 4 de 7 pacientes con TVP y en un paciente con TVC. Estos 5 pacientes con la mutación tuvieron diagnóstico de síndrome mieloproliferativo (SMP) en el momento de la detección de la trombosis (n = 2) o después (n = 3). Un paciente con TVP sufrió el episodio trombótico 18 años después del diagnóstico del SMP y la mutación JAK2 V617F fue negativa. No se encontraron otras mutaciones del gen JAK2 en este grupo d e pacientes. Además del diagnóstico de SMP, se identificaron otros factores de riesgo para trombofilia en 4 pacientes. Un paciente tuvo un factor de riesgo para trombofilia además del diagnóstico de SMP. La mutación JAK2 V617F se presentó en 4/7 de los pacientes con TVP con o sin un diagnóstico obvio de SMP. La investigación de otras mutaciones podría no ser necesaria en pacientes con trombosis en sitios poco frecuentes.

Hypothesis: it is time to reconsider phenotypes in hypertension.

The study of genes and mechanisms associated with hypertension is hampered by the heterogeneity of hypertensive patients. Refining the definition of hypertension is a potential means of improving the clarity of mechanistic studies, but the lack of intermediate phenotypes hinders the assessment of causal relationships. Looking at younger individuals and hemodynamic subsets of hypertension is one such refinement. The authors argue that the separate analysis of patients with isolated diastolic hypertension, predominantly diastolic hypertension, and isolated systolic hypertension in the young in combination with common biomarkers may be an initial step to decrease heterogeneity within patient subsets, thus providing new avenues for genetic and pathophysiological studies.