Microvascular Coagulation Research Articles

Inflammation, coagulopathy, and the pathogenesis of multiple organ dysfunction syndrome.

An improved understanding of the mechanisms through which infecting pathogens harm the host is leading to new formulations of the concept of sepsis. We review the roles of inflammation and coagulation in the pathogenesis of the multiple organ dysfunction syndrome, and explore the potential of new therapies to restore the fine biological balance between procoagulant and anticoagulant mechanisms that are disrupted during the life-threatening processes that lead to organ dysfunction. Narrative review of published primary sources in the basic and clinical literature. Traditional models of host-pathogen interactions ascribe the morbidity of infection to the direct cytotoxic effects of micro-organisms on host tissues. However, abundant experimental and clinical evidence has revealed that it is the response of the host, rather than the trigger that elicited it, that is the more potent determinant of outcome. The elucidation of a complex network of host-derived inflammatory mediators raised the possibility that targeting these individually could improve patient outcomes, and some modest successes with this approach have been achieved. More recently, it is becoming evident that the inflammatory response, in turn, mediates its deleterious effects by inducing tissue hypoxia, and cellular injury, either through tissue necrosis or through the induction of programmed cell death or apoptosis. Thus, treatment strategies that target the downstream consequences of the activation of inflammation, for example, microvascular coagulation or acute adrenal insufficiency, represent the latest, and some of the most promising approaches to attenuation of the septic response to improve survival, and minimize organ dysfunction. The maladaptive sequelae of systemic inflammation, embodied in the concept of the multiple organ dysfunction syndrome, comprise the leading obstacle to survival for patients admitted to a contemporary intensive care unit. Further insights into this intimidatingly complex process will not only provide potent new therapeutic options, but promise to transform critical illness from a biological standoff, during which the clinician merely supports failing organs, to a disease that can be successfully treated.

Sustained hemostatic abnormality in patients with steroid-induced osteonecrosis in the early period after high-dose corticosteroid therapy

To determine whether the development of steroid- induced osteonecrosis in collagen disease patients was related to hemostatic abnormality after corticosteroid administration, we examined levels of thrombin-antithrombin III complex (TAT) and plasmin-a2-plasmin inhibitor complex (PIC) in 32 patients who were treated with high-dose corticosteroid. All were prospectively followed for osteonecrosis, with serial magnetic resonance imaging (MRI), for at least 12 months from the beginning of corticosteroid therapy. MRI was performed on bilateral hips and knees. Of the 32 patients, 17 (53.1%) had osteonecrosis in the hip or knee. Osteonecrosis was detected on MRI at an average 3.1 months after the start of high-dose corticosteroid therapy. PIC levels were significantly higher in the group of 17 patients with osteonecrosis (ON group) than in the group of 15 patients without osteonecrosis (non-ON group) (P < 0.0001). The difference in PIC levels was most prominent 20 days after the start of the high-dose corticosteroid therapy. Moreover, the number of osteonecrotic joints was significantly correlated with PIC levels (P < 0.0001). The sustained hemostatic abnormality after corticosteroid therapy in the ON group suggests that microvascular coagulation participates in the development of osteonecrosis.

Unlike thrombin, protein C and activated protein C do not affect vascular tone

Because plasma levels of protein C (PC) or activated protein C (APC) are altered in certain diseases associated with vascular dysfunction, and APC has therapeutic potential in preventing microvascular coagulation in severe sepsis, potential vascular effects of PC and APC were compared to those of the vasoactive peptide, thrombin. Thrombin was a more potent relaxant agonist than contractile agonist in aorta. Unlike thrombin, cumulatively administered APC (10 −9-10 −7 M) did not exert vascular effects in rat or rabbit aorta. Noncumulative challenge of PC (10 −7 M) and APC (8 × 10 −8 M) also did not contract rat or rabbit aortae, either with or without endothelium. Likewise, the same concentrations of PC and APC also did not relax norepinephrine-induced (10 −7 M) vascular tone in either rat or rabbit aortae. Thus, in contrast to thrombin, PC and APC failed to modulate vascular tone, suggesting that the therapeutic use of APC is unlikely to be accompanied by any direct effects on vascular motility.

Hypoxic respiratory failure after massive extrathoracic trauma with a case report.

A case is described of massive extrathoracic trauma with the early onset of respiratory failure characterized by hypoxia and stiff lungs. The hypoxia was associated with delirium. The immediate priority in management in this case was to maintain adequate alveolar ventilation and oxygenation. The basis of care in these cases is accurate volume replacement including infusion of colloid, with the aid of central venous pressure monitoring together with endotracheal intubation or tracheostomy and intermittent positive pressure ventilation. Great care must be taken to prevent sepsis in these patients, for this worsens respiratory function. It is suggested that disseminated microvascular coagulation is a factor in the massively injured, and heparinization must be considered when adequate oxygenation of the patient is difficult.