Coagulopatía por SARS-CoV-2 / SARS-COV-2 COAGULOPATHY

En diciembre de 2019 se descubrió un nuevo coronavirus, asociado a pacientes que sufrían un cuadro de neumonía en Hubei provincia de China, desde ese momento se estudia las características del virus, como también de la patología que produce. En los pacientes graves, se observó un estado proinflamatorio y procoagulante que provocó la disfunción multiorgánica, y, en muchos de ellos, la muerte. El objetivo de este trabajo consiste en describir la fisiopatología de la coagulopatía que esta infección, sorprendentemente, provoca. Es importante remarcar la relación que existe entre los estados inflamatorios y la cascada de la coagulación, cuyas disfunciones ocurren en situaciones de gravedad, como es la sepsis. El SARS-CoV-2 entrara a la célula mediante el receptor de la enzima convertidora de angiotensinógeno. En los estadios avanzados o críticos de la enfermedad, el estímulo hiperinflamatorio y el ambiente protrombótico provocarán un daño multiorgánico. El enfoque de los pacientes en estadios avanzados o críticos debe ser de soporte vital, junto a una terapia anticoagulante completa

In December 2019, a new coronavirus, SARS-CoV-2, was discovered in patients suffering from pneumonia. In critically ill patients, a proinflammatory and procoagulant state was observed: this led to multiorgan dysfunction, and, in many patients, to death. The objective of this work is to describe the pathophysiology of coagulopathy that this infection, surprisingly, causes. It is important to highlight the cross-talk between inflammation and coagulation in serious situations, such as sepsis. SARS-CoV-2 will enter the cell via the angiotensinogen converting enzyme receptor. In the advanced or critical stages of the disease, the hyperinflammatory stimulus and the prothrombotic environment will cause multi-organ damage. The approach of patients in advanced or critical stages should be life support, together with full anticoagulant therapy.

Small intestinal bacterial overgrowth (SIBO) and vitamin K-responsive coagulopathy: a previously unrecorded association.

A 17-year-old woman, with a history of three operations on the upper gut in early life and intermittent diarrhoea, presented with a history of epistaxis and leg ecchymosis for the previous 3 months. Initial investigation revealed mild anaemia, low serum albumin, moderately elevated aminotransferases and an exceedingly prolonged prothrombin time (PT) which was promptly shortened to normal by intravenous vitamin K. Additional investigations revealed a grossly abnormal glucose hydrogen breath test, a dilated duodenum and deficiencies of vitamins A, D and E. Repeated courses of antimicrobial agents caused prompt but transient shortening of PT and eventually a duodenal-jejunal anastomosis was performed. Since then, up to 36 months later, the patient has been in good general health and PT has been consistently normal with no vitamin K supplementation. Small intestinal bacterial overgrowth has previously been associated with several conditions but this is the first description of its association with vitamin K-responsive coagulopathy.

Unilateral livedoid vasculopathy associated with involutional phase of cutaneous infantile hemangioma: the connection to coagulation disorders.

Livedoid vasculopathy is a bilateral painful and recurrent cutaneous ulcerative disorder of the legs that leads to atrophie blanche, atrophic white-porcelain scars, and is associated with disorders of fibrinolysis and/or coagulation. We present a young boy with an association between livedoid vasculopathy in the area of a previous involuted cutaneous hemangioma. We found 4 uncommon abnormalities associated with thrombo-occlusive events: heterozygous 20210 A→G genotype of prothrombin, reduced activity of anticoagulation proteins C and S, and elevated lipoprotein (a).

Reanimación y manejo de la coagulopatía en el trauma / Resuscitation and management of coagulopathy in trauma

La coagulopatía inducida por el shock hemorrágico se encuentra presente en casi un 25 por ciento de los pacientes ingresados por esta causa. Una vez que la coagulopatía se ha instalado aumenta drásticamente la morbimortalidad. Los paradigmas en la reanimación en el paciente traumatizado han variado dramáticamente en los últimos años, cambiando el uso de grandes volúmenes de cristaloides con el uso precoz de los hemoderivados y otros productos para tratar de revertir la coagulopatía y la "triada de la muerte". El objetivo de este trabajo es revisar la fisiopatologia de la coagulopatía en el trauma y las tendencias terapéuticas para revertiría.

Coagulopathy induced by hemorrhagic shock is present in almost 25 percent of patients admitted for this reason. Once the coagulopathy develops patients morbidity and mortality dramatically increases. The paradigms in trauma patients resuscitation have changed considerably in the last years by changing the use of large volumes of crystalloid with the early use of blood products and other products to try to reverse the coagulopathy and the "triad of death." The aim of this paper is to review the pathophysiology of coagulopathy in trauma and therapy trends to reverse it.

Cirurgia para controle de danos: breve revisão / Damage control surgery: a brief review

A cirurgia de controle de dano é processo de preservação do paciente politraumatizado. É concebida como método cirúrgico que surgiu com a necessidade de restaurar a fisiologia normal do paciente vítima de múltiplos traumas e o objetivo de reduzir a mortalidade relacionada ao tratamento cirúrgico definitivo. A "tríade da morte", caracterizada por hipotermia, acidose metabólica e coagulopatia, é a perturbação fisiológica temida na abordagem cirúrgica de politraumatizados. A melhora nas taxas de sobrevida após o advento da cirurgia de controle de danos, entretanto, ainda convive com taxas de mortalidade, em torno de 50%. É procedimento dispendioso e que exige preparação dos centros e equipes que irão receber esses pacientes. Dessa maneira, muitos estudos têm especulado a possibilidade de predizer a evolução de pacientes candidatos a esse tipo de intervenção, a fim de evitar a aplicação de procedimento tão dispendioso em pacientes sem chances de sobreviver. (AU)

The Damage Control Surgery is a process for the preservation of the polytraumatized patient. It was developed due to the need for restore the physiology of such patients back to their normal condition, in order to reduce the mortality rates related to the definitive surgical approach. The "triad of death" hypothermia, acidosis and coagulopathy is a major threat concerning the surgical approach for the trauma patients. Despite the improvements on the survival rates following the introduction of the Damage Control Surgery, the published data show mortality rates circa 50%. Moreover, it is a costly intervention which demands well-prepared teams and trauma centers. Thus, many studies have sought the capacity of predicting the outcome of patients candidates to this procedure, in order to avoid excessive spending with patients who have no chance of survival. (AU)

Hypercholesterolemia magnitude increases sympathetic modulation and coagulation in LDLr knockout mice.

We investigated the effects of low lipoprotein receptor deficiency in cholesterol blood concentrations, blood pressure, hemostatic factors, and the autonomic nervous system in three groups: control mice fed standard diet (CO, n=9), lipoprotein receptor-deficient mice (LDLr(-/-), n=9) fed standard diet (LDLr-S) or hypercholesterolemic diet (LDLr-H, n=8). Frequency domain analysis of heart rate and blood pressure variability was performed with an autoregressive algorithm. The spectral components were expressed in absolute (s(2) or mmHg(2)) and normalized units. Spontaneous baroreflex sensitivity (BRS) was estimated by alpha index, defined as square root ratio between low frequency power in blood pressure variability and heart rate variability. LDLr/- mice presented a significant increase in the cholesterol blood concentration (mean±SD; mg/dl; LDLr-S=202.01±34.38 and LDLr-H=530.7±75.17) compared to CO (79.2±13.6), p=0.001. The receptor deletion was associated with a heart rate variability reduction (p=0.013). The BRS was reduced (p<0.05) in LDLr-S and LDL-H (mean±SD: 0.96±0.39 and 0.59±0.34, respectively) compared to CO (4.02±1.92). Moreover, hypercholesterolemic diet significantly increased the cardiac sympathetic modulation (0V pattern of symbolic analysis: mean±SD, CO=8.04±4.53; LDLr-S=16.49±4.52 and LDLr-H=21.80±8.24, p=0.006). The 0V pattern was statically correlated to coagulation factor VII (r=0.555, p=0.0208). In LDLr-H, the concentration (interquartile range) of plasmatic fibrinogen and hemostatic factors VII (2.8-3.3) and XII (1.1-1.3) were increased compared to CO (0.9-1.1and 0.9-1.0, respectively) and LDLr-S (0.7-1.0 and 0.8-0.9, respectively) (p<0.004 for FVII and p<0.006 for FXII). Taken together, the results indicate that plasmatic cholesterol magnitude is determinant to increase the coagulation and the sympathetic modulation.

O novo modelo da cascata de coagulação baseado nas superfícies celulares e suas implicações / A cell-based model of coagulation and its implications

O conceito da cascata da coagulação descreve as interações bioquímicas dos fatores da coagulação, entretanto, tem falhado como um modelo do processo hemostático in vivo. A hemostasia requer a formação de um tampão de plaquetas e fibrina no local da lesão vascular, bem como a permanência de substâncias procoagulantes ativadas nesse processo no sítio da lesão. O controle da coagulação sanguínea é realizado por meio de reações procoagulantes em superfícies celulares específicas e localizadas, evitando a propagação da coagulação no sistema vascular. Uma análise crítica do papel das células no processo hemostático permite a construção de um modelo da coagulação que melhor explica hemorragias e tromboses in vivo. O modelo da coagulação baseado em superfícies celulares substitui a tradicional hipótese da "cascata" e propõe a ativação do processo de coagulação sobre diferentes superfícies celulares em quatro fases que se sobrepõem: iniciação, amplificação, propagação e finalização. O modelo baseado em superfícies celulares permite um maior entendimento de como a hemostasia funciona in vivo e esclarece o mecanismo fisiopatológico de certos distúrbios da coagulação.

The concept of a coagulation cascade describes the biochemical interactions of the coagulation factors, but it is flawed as a model of the in vivo hemostatic process. Hemostasis requires both platelet and fibrin plug formation at the site of vessel injury and that the procoagulant substances activated in this process remain at the site of injury. This control of blood coagulation is accomplished as the procoagulant reactions only exist on specific cell surfaces to keep coagulation from spreading throughout the vascular system. A model of coagulation that better explains bleeding and thrombosis in vivo created after considering the critical role of cells. The cellbased model of hemostasis replaces the traditional "cascade" hypothesis, and proposes that coagulation takes place on different cell surfaces in four overlapping steps: initiation, amplification, propagation and termination. The cell-based model allows a more thorough understanding of how hemostasis works in vivo, and sheds light on the pathophysiological mechanism for certain coagulation disorder.

[Coagulation disorders in cirrhosis]. / Trastornos de coagulación en el cirrótico.

The liver plays a central role in the clotting process. In this organ are sintetizated the major part of the coagulation factors. Historically, was considered that alteration in liver function causes important bleeding disorders. However, actual evidence is not in agreement with this asseveration. Decreased synthesis of clotting and inhibitor factors, decrease clearance of activated factors, quantitative and qualitative platelet defects, hyperfibrinolysis and intravascular coagulation are some of the defects observed in liver diseases. Thrombotic events, even if rare in cirrhotic patients, occur manly in the portal and mesenteric veins. The aim of the present work is to review the present evidence in coagulation disorders and liver disease.

Trastornos de coagulación en el cirrótico / Coagulation disorders in cirrhosis

The liver plays a central role in the clotting process. In this organ are sintetizated the major part of the coagulation factors. Historically, was considered that alteration in liver function causes important bleeding disorders. However, actual evidence is not in agreement with this asseveration. Decreased synthesis of clotting and inhibitor factors, decrease clearance of activated factors, quantitative and qualitative platelet defects, hyperfibrinolysis and intravascular coagulation are some of the defects observed in liver diseases. Thrombotic events, even if rare in cirrhotic patients, occur manly in the portal and mesenteric veins. The aim of the present work is to review the present evidence in coagulation disorders and liver disease.

El hígado participa de manera importante en el proceso de la coagulación. En él se sintetizan la mayor parte de los factores pro- y anticoagulantes. De manera histórica se ha considerado que las alteraciones en la función de este órgano provoca trastornos predisponentes para eventos de sangrado. La evidencia actual pone en tela de juicio esta aseveración. En los casos de hepatopatía se hacen evidentes alteraciones en el número y funcionamiento de las plaquetas, disminución de la síntesis de factores de la coagulación, disfibrinogenemia, alteraciones en la fibrinólisis, deficiencia de vitamina K y cambios similares a los ocurridos en la coagulación intravascular diseminada (CID). El presente trabajo está dirigido a revisar los conocimientos actuales respecto a las alteraciones de la coagulación presentes en los pacientes con hepatopatías.

Pediatric reference intervals for uncommon bleeding and thrombotic disorders.

This study provides pediatric reference intervals and median values for factors II, V, VII, X, fibrinogen, alpha-2-antiplasmin (AP), antithrombin (AT), plasminogen, protein C (PC), and protein S (PS) for children 7 to 17 years of age. All analytes exhibited at least some age dependence in late childhood and adolescence either when compared against adult values or when medians for children were regressed against age.

Pathophysiology of posttraumatic temporal lobe lesions.

BACKGROUND: Posttraumatic parenchymal lesions in the temporal lobe may cause neurologic deterioration. An analysis was made of the natural evolution of this type of lesion, with emphasis on its 2 components: hemorrhage (hyperdense on computed tomography [CT]), and edema and necrosis (hypodense on CT). The clinical repercussions were studied, and the factors that might influence such evolution were investigated. METHODS: Forty head-injured patients with temporal lobe lesions admitted within 12 hours after the injury were selected in a prospective manner. Computed tomography scans were systematically repeated within the first 36 hours and at 7 and 30 days postinjury. Factors such as interval between injury and the first CT scan, age, velocity of the injury, alcohol consumption, coagulation abnormalities, and the presence of decompressive measures were compared between the patients that had enlargement of the hemorrhage and those who did not. Increase in hypodensity was compared with that in hyperdensity. RESULTS: Fourteen patients showed enlargement of the hemorrhage. In all cases but one, the interval between injury and admission was 3 hours or less. Other factors had no statistical significance as predisposing causes for such enlargement. In approximately half of the cases, the hypodense component increased in the first 36 hours and continued increasing until the end of the first week. Evolution of the hypodense component was not dependent on behavior of the hemorrhage, surgical drainage, or diameter of the hemorrhagic lesion. CONCLUSIONS: The natural evolution of the hyperdense component of temporal lobe lesions was to enlarge within the first few hours after the injury. Edema and necrosis developed more slowly and with no significant clinical manifestations.