Their knowledge is essential to formulate an appropriate diagnosis and effective treatment especially take (figure).Disseminated intravascular coagulation are characterized by an imbalance between a systemic activation of hemostasis and a defect or overflow inhibitor systems of this system to cause fibrin deposition in the microcirculation leading to a functional deficiency of certain organs. In many diseases, activation of plasma coagulation is indirect.Thus, in sepsis, it is especially endotoxin released by bacteria that activates monocytes and probably, endothelial cells, triggering the production of tissue factor by these cells and activating the extrinsic coagulation pathway.Thrombin (Factor IIa) is formed, it in turn activates the platelets. In the gynecological pathology is sometimes the passage of amniotic fluid in the circulation that can activate coagulation. In acute hemolysis is the presence of erythrocyte membranes associated with the erythrocyte content which is (Table I).
Simultaneously, the physiological inhibitor systems are reduced. Endotoxin, many cytokines produced by the inflammatory reaction inhibit leukocyte endothelial production thrombomodulin preventing activation of the protein C system and S. Antithrombin is “consumed” by its rapid participation in inhibiting various enzymes from the coagulation but also degraded by the enzymes of leukocytes involved in the inflammatory response. The massive production of cytokines in particular leukocyte origin (interleukin 6 [IL-6], tumor necrosis factor [TNF], IL-1) causes a systemic inflammatory reaction. The participation of fibrinolysis is complex experimentally, there is usually an early fibrinolysis then quickly inhibiting the release of endothelial fibrinolysis plasminogen activator inhibitor, PAI-1 inhibiting the activation of plasminogen.Clinically hyperfibrinolysis appears often due either to the phenomenon triggering (amniotic fluid) consequence of the activation of coagulation, or cell involvement in the inflammatory response. The activation of coagulation resulting in fibrin deposits more or less extensive throughout the microcirculation but more likely in target organs such as the kidneys, liver, lungs, brain, whose functioning is severely impaired. This coagulation activation also causes a risk of occurrence associated thrombosis in the large veins (Table II).
Activation of the coagulation and thus transforms consume clotting factors (hence the term sometimes given to these syndromes “consumption coagulopathy”) that is not compensated by deficient hepatic synthesis. The active thrombin formation platelets leading to thrombocytopenia. If hyperfibrinolysis appears, fibrinogen is degraded as indeed labile factors V and VIII. All this explains the appearance of a hemorrhagic syndrome. This pathological activation of hemostasis is always secondary to various diseases. Intervening on hemostasis can be helpful but much less than treating the triggering causes or, in a given pathology, to do prevention. This is what explains the dramatic paintings of the 1960s descriptions have almost completely disappeared.
This progress must not neglect these phenomena because a sudden worsening due to an unsuitable therapeutic procedure can suddenly disrupt a chronic form.
Bacterial infections are most often involved, but viruses and parasites can intervene. Cytokine production plays a pathophysiological role and worsens the clinical prognosis. Trauma act by passing the tissue material in the circulation especially if the cells are rich in tissue factor such as brain.
The participation of solid tumors is incompletely understood but is common during mucosécrétants cancers. Leukemia cells and especially promyelocytic forms act as by their tissue factor by enzymatic content (Table III).
A- Clinical features:
They are highly variable and often dominated by the triggering element. Above all, their severity varies widely. The elements described herein are those of severe but more often not found in a pathological context as organic disturbances. The elements which determine the clinic are: the symptoms related to the etiology, organs deficits, triggering the seriousness of the phenomenon, the efficacy of etiological treatment and resuscitation, explaining the increasing number of chronic forms.
• Haemorrhage, described as very common (64-73% of cases), are only the preserve of severe forms. They are essentially triggered by trauma and simply appear at venipuncture sites.
• The shock is observed only in very severe forms.
• Lung disease is often revealed by dyspnea. Micro-embolism syndrome appears very quickly after the triggering lesion and is partly due to thrombi in microcirculation and the action of products secreted locally by leukocytes and platelets, with vascular and bronchial constriction. Pulmonary hypertension and an increase in air resistance appear.If the inducing phenomenon disappears, the lesion rapidly regresses through a local fibrinolysis. If the disease persists and the clinical picture worsens, microthrombus increase, associated with alveolar edema rich in proteins.Leukocyte enzymes degrade the alveolar-capillary membrane, further aggravating respiratory failure. This pulmonary micro-embolism syndrome is the cause of acute respiratory distress syndrome (ARDS) with radiological images bilateral infiltrates resembling the “cotton wool”. The protein rich edema is very sensitive to diuretics. The oxygen supply often requires a positive end expiratory pressure (PEEP).
• Renal disease is characterized by fibrin deposition in the glomerular capillaries that cause oliguria often preceded by polyuria. In typical form, appear multiple bilateral cortical necrosis with micro- or macroscopic hematuria. Diuresis in preserved forms are rarer.Diuretics are little or not effective and hemodialysis may be necessary. Cortical necrosis leave more or less important consequences.
• Liver disease is often discovered biologically barring major malfunction. It aggravates the lesions of hemostasis default synthesis of factors and inhibitors.Appearing usually after damage other organs, it lasts longer.
• thrombosis of the cerebral microvasculature cause confusion and lack of awareness. In fulminant may appear meningeal haemorrhage. Focal neurological signs may evoke intracranial or spinal hematoma.
• The skin is the site of extensive necrotic purpura reddish blackish first then playing in a few days to deep ulcerations and is seen especially in the lower limbs and abdomen. The cyanosis acrocyanosis is sitting with painful swelling in the fingers, toes, ears and nose. It may change either proceed to healing or to a polygangrène. A petechial purpura appears when thrombocytopenia is less than 50 g / L.
• thrombosis and embolism reach the largest trunks are not the preserve of severe forms. The hepatic or renal locations (sometimes described) worsen the prognosis.
B- Biological diagnosis:
No test or tests of association is not sensitive or specific enough for diagnosis. Clinical and biology must be taken into consideration.
1- Screening Tests:
Prothrombin time (PT) and activated partial thromboplastin time (APTT) are easy to obtain quickly and are easily renewable. They are inconstant abnormal except in severe forms. The platelet count is essential and must be able to appreciate not only the absolute level of platelets and therefore the risk of bleeding, but also more or less rapid lowering platelet counts in renewing. Conversely, a stabilization of values reflects the judgment of the thrombin formation. Except in severe forms immediately, the search for a worsening of abnormalities has more interest than the discovery of an anomaly. Screening tests readily available form the basis of diagnosis. Witnesses of activation of hemostasis are useful in chronic forms (sometimes clinically silent).
2- Determination of factors:
Factors V, X and VII are easily measured and their evolution shows that the process but also the risk of bleeding. The dosing of inhibitors (antithrombin, protein C and S) is only of interest in certain forms of chronic diagnosis difficult.The lowering of fibrinogen, which requires a scalable monitoring, can be the witness of consumption as fibrinolysis and lack or excess of its synthesis by the liver.
3- coagulation activation Witnesses:
The increase in fragments 1 + 2 of prothrombin (F1 + 2) of the thrombin-antithrombin complex (TAT) is not specific and can be extravascular origin. Soluble fibrin is formed only in the intravascular and more specific assay.
4- Witnesses fibrinolytic response:
Increased fibrin degradation products (FDP) is less specific than that of D-dimer which however increased in many diseases (venous or arterial thrombosis, hematomas etc.). Accumulation may depend either from the excessive production of either the fault elimination (kidney and liver failure). In chronic forms and difficult diagnosis, monitoring lowering plasminogen or a2-antiplasmin may have an interest but is realized in specialized laboratories.
5- result of intravascular fibrin deposits:
They lead to the formation of erythrocyte fragments or schistocytes, easy to recognize on a slide and even count.
Highlights to include:
• Disseminated intravascular coagulation (DIC) can be defined as an acquired syndrome characterized by intravascular coagulation activation and appearing in many diseases: sepsis, trauma, burns, preeclampsia, cancers.
• This causes a varied symptomatology in a wide range of severity, also accompanied by various biological arrays and thus of important yet difficult diagnoses before initiating appropriate therapy. This should especially try to prevent the extension of the pathophysiological mechanism causing disseminated intravascular coagulation and therefore primarily control the triggering condition.
• The terminology used in this pathology is confused. Disseminated intravascular coagulation, systematic inflammatory response syndrome (SIRS) describe neighboring pathophysiological conditions, while multiple organ deficiency syndrome (MODS) describes the result of this process.
1 / Various biological tables:
Form compensated without clinical signs:
– Prothrombin time and activated partial thromboplastin time: neighbors of normal or normal;
– Normal platelets;
– Normal or increased fibrinogen (excessive synthesis = inflammation);
– Moderate increase in TAT, F1 + 2, inconstant soluble fibrin;
– Schistocytes rare or absent.
Decompensated forms with hemorrhage caused or puncture and decreased function of certain organs (kidneys, lungs):
– Prothrombin time and activated partial thromboplastin time: more or less elongated;
– Continuous lowering of platelets, fibrinogen, coagulation factors and platelets;
– Increase in TAT, F1 + 2, soluble fibrin;
With severe bleeding, organ deficiencies:
– Prothrombin time and activated partial thromboplastin time: elongated or anticoagulated;
– Collapse of platelet factors, fibrinogen;
– Lowering inhibitors;
– Increase in PDF and D-dimer. Lowering plasminogen and a2-antiplasmin;
– Sharp increase in TAT, F1 + 2 and soluble fibrin;
– Many schistocytes.
2 / Foundations of treatment:
Treatment of the disease in question:
This is obviously the essential basis of treatment. An effective antibiotic treatment and appropriate resuscitation will be more effective than modifiers of hemostasis. It is thanks to the improvement of these treatments and care in intensive care than large dramatic disseminated intravascular coagulation have become more rare and the most common pure organic forms.
Their use in practice not yet been consensual strategy and we lack well conducted clinical trials as it is difficult to establish homogeneous groups of patients. The establishment by the Japanese authors of a clinico-biological score however is a particularly attractive option.
Platelet and plasma substitution:
The indication should not be based solely on biological elements dominated the blood count but on clinical grounds or in patients undergoing surgery or in another situation to severe bleeding risk. This substitution makes sense but did not however subject to confirmation by a controlled clinical trial. A study in newborns comparing the plasma and platelets intake versus exchange transfusion versus no replacement therapy did not show improved survival and evolution of the disease. However, the contribution of platelets is probably effective in disseminated intravascular coagulation in promyelocytic leukemia. Effective plasma volume should be sufficient, taking into account the patient’s plasma volume and its factor levels. The addition of prothrombin, pro-convertine Stuart antihemophilic factor B (PPSB) is cons-indicated because containing activated factors, it may boost the coagulation and contains only a few factors and few inhibitors which desperately needs the patient. The assumption that such substitutions can bring “oil on the fire” and aggravate DIC has never been demonstrated. Based replacement therapy based on biology platelet concentrates, fresh frozen plasma eventually. The addition of inhibitors is likely to be particularly useful (but to confirm by clinical trials): antithrombin protein C anticoagulant treatments If heparin is able to inhibit the activation of coagulation developed experimentally in animals, we lack of clinical demonstrations to argue its systematic prescription. His administration is only justified if the rate of factors or circulating platelets is sufficient or requires prior substitution. The dosages will still be very low, somewhat intravenous administration. The higher dosages have been proposed for purpura fulminans and necrosis tablecloth. After several non-randomized trials, one trial compared a low molecular weight heparin (LMWH) with unfractionated heparin. The results were comparable but with improved bleeding and functional deficits organs. Low doses of heparin and especially low molecular weight heparin may have an interest in preventing thrombosis of large trunks but their actual place remains little discussed and standardized indication. The heparin treatment are never present always, always low dosage and with a strict biological monitoring, usually only after substitution. Heparin is active for only by antithrombin which is low in the case of disseminated intravascular coagulation, some have proposed hirudin (not dependent on antithrombin) with interesting results. However, the lack of antidote, the current difficulties of monitoring this molecule must make prudent face a real risk of bleeding due to this molecule. New modifying molecules of hemostasis are being studied: VIIa inhibitor and factors Xa, tissue factor pathway inhibitor (TFPI) …
Concentrates of inhibitors:
As one of the biggest inhibitors and purified physiologically long, antithrombin has been the subject of several clinical trials with favorable results in septicemia. Although the doses vary greatly, a meta-analysis showed a reduction in mortality with an odds ratio of 0.58. However, it is likely that the need to obtain 100% higher plasma levels and thus to administer large amounts of an expensive product, probably reserved for severe forms with vital risk. Purified more recently, protein C is also active in the experimental disseminated intravascular coagulation.Several clinical trials appear to show efficacy but lack a controlled trial. Many of disseminated intravascular coagulation are clinically silent and well compensated. A therapeutic act can unbalance: cancer surgery, removal of ischemia, providing products activators of hemostasis (type PPSB).
The lysine homologs inhibitors (Exacyl, Spotof: tranexamic acid) are generally against-indicated for preventing the activation of plasminogen on the surface of fibrin, they make insensitive new fibrin deposits to degradation by fibrinolysis. The release of the capillaries of organs becomes difficult, particularly in renal failure. Two long-standing trials, however, were proposed during promyelocytic leukemia or disseminated intravascular coagulation secondary to cancer. By cons, such antiplasmins of aprotinin (Antagosan, Trasylol) cause little long-term risk and can be used in case of dominant fibrinolysis observed for example in the amniotic fluid embolus. The indication is justified only on biological criteria and as the etiological and replacement therapy are ineffective.
Strong Points to remember:
• The disseminated intravascular coagulation are secondary to various causes.
• They cause a wide symptomatology and complex biology (complicated by the consequences of microcirculatory thrombi: functional deficits of organs).
• The diagnosis requires a good understanding pathophysiological.
• The best support for causes reduced severe forms.
• Treatment is mainly with etiology for severe substitution by platelets, plasma charges, inhibitors. Heparin should be considered with great caution.