What is disseminated intravascular coagulation?
DIC represents a life-threatening condition that is the endpoint of uncontrolled systemic activation of the hemostatic system, leading to a simultaneous widespread microvascular thrombosis, that can compromise the blood supply to different organs and may lead to organ failure. This process is associated with increased degradation of coagulation factors as well as anticoagulation proteins and followed by their impaired synthesis, leading to uncontrolled bleeding.
Acute, severe DIC is characterized by diffuse multiorgan bleeding, hemorrhagic necrosis, microthrombi in small blood vessels, and thrombi in medium and large blood vessels. This condition may occur in the setting of sepsis, major trauma, and obstetric calamities. The final scenario is represented by the exhaustion of coagulation/anticoagulation factors and platelets, leading to profuse uncontrollable bleeding and often death.
In contrast to the acutely ill patient with complicated severe DIC, other patients may have mild or protracted clinical manifestations of consumption or even subclinical disease manifested by only laboratory abnormalities. The clinical picture of subacute to chronic DIC is exemplified by the chronic hypercoagulability that may accompany malignancy, in particular with mucin-producing adenocarcinomas and acute promyelocytic leukemia. However, currently there are no reports in the literature regarding the occurrence of mild subacute DIC in pregnant women.
The development of DIC as a result of predisposing conditions can be a life-threatening complication and is considered one of the leading causes for maternal morbidity and mortality worldwide. However, it is important to emphasize that DIC is not a disease by itself; it is always secondary to an underlying disorder that causes the uncontrolled activation of coagulation.
What are the mechanisms leading to DIC during pregnancy?
The development of DIC during pregnancy can be either abrupt as in acute abruption or PPH or continuous as can be observed in a retained dead fetus. Of interest, obstetric complications such as placental abruption, amniotic fluid embolism, and acute fatty liver of pregnancy are associated with severe early-onset DIC that is accompanied by maternal coagulopathy. The DIC in obstetric hemorrhage activates coagulation and triggers fibrinolysis. Activation of fibrinolysis leads to the production of D-dimers and fibrin-degradation products. These will interfere with platelet function and can impair myometrial contractility.
Clinical presentation of DIC may be the results of the following mechanisms.
Endothelial dysfunction and platelet activation
Intact, dysfunctional, or activated cells, as well as remnants of cell surfaces, inflammatory mediators, and coagulation proteins are all part of an interplay in which uncontrolled activation of coagulation cascade leads to DIC.
Endothelial cells, platelets, but in some cases also leucocytes and cancer cells can participate in the genesis of the process leading to DIC by releasing proinflammatory cytokines, propagating the activation of coagulation on their surface or inducing tissue factor (TF) expression on their membrane. A systemic inflammatory response that is associated with markedly increased circulating proinflammatory cytokines such as tumor necrosis factor-α, interleukin-1 (IL-1), and interleukin-6 (IL-6) can lead to exaggerated expression of TF by leukocyte and endothelial cells. This will generate an uncontrolled coagulation response that will eventually deteriorate into DIC. Lastly, the initiation of coagulation leading to thrombin generation in DIC, is mediated by the TF/factor VIIa pathway, also known as the extrinsic coagulation pathway.
The most significant source of TF is not completely clear in all situations. Tissue factor may be expressed not only in mononuclear cells in response to proinflammatory cytokines (mainly IL-6) but also by vascular endothelial or cancer cells. Despite the potent initiation of coagulation by TF, the activation of coagulation cannot be propagated if the physiological anticoagulant pathways function properly. However, in DIC all major natural anticoagulant pathways (ie, antithrombin III, protein C system, and TF pathway inhibitor [TFPI]) appear to be impaired.
Plasma concentrations of antithrombin III, the most important inhibitor of thrombin, are markedly reduced during DIC because of a combination of consumption, degradation by elastase from activated neutrophils, and impaired synthesis.
A significant depression of the protein C system may further compromise an adequate regulation of activated coagulation. This impaired function of the protein C system is caused by a combination of impaired protein synthesis, cytokine-mediated down-regulation of endothelial thrombomodulin, and a fall in the concentration of the free fraction of protein S (the essential cofactor of protein C), resulting in reduced activation of protein C.
Lastly, there seems to be a misbalance of TFPI function in relation to the increased TF-dependent activation of coagulation.
All these anticoagulant pathways are linked to the endothelium, and it is likely that endothelial cell activation and dysfunction are an important component of the imbalance between coagulation and anticoagulation systems. Of interest, experimental and clinical studies indicate that during DIC, the fibrinolytic system is largely suppressed at the time of maximal activation of coagulation. This inhibition of fibrinolysis is caused by a sustained rise in the plasma concentrations of plasminogen activator inhibitor (PAI)-1, the principal inhibitor of the fibrinolytic system.
Activation of platelets may also accelerate fibrin formation. The expression of TF in monocytes is markedly stimulated by the presence of platelets and granulocytes in a P-selectin–dependent reaction. This effect may be the result of nuclear factor kappa B activation induced by binding of activated platelets to neutrophils and mononuclear cells.
During pregnancy maternal leukocytes are in a higher state of activation than in nonpregnant women and have characteristics akin to sepsis. However, they are well controlled during pregnancy, and it has been proposed that the trophoblast plays a role in the maintenance of the balanced systemic maternal inflammation during gestation. Nevertheless, in cases of sepsis caused by an infectious agent or septic abortion and at least in some of the cases of amniotic fluid embolism, this equilibrium is disturbed and the mother develops DIC.
Trophoblast properties and activation of the coagulation system
During normal gestation the trophoblast has 2 hemostatic functions: (1) to allow the laminar flow of maternal blood in the intervillous space and prevent it from clotting during that time; and (2) to prevent bleeding at the maternal fetal interface.
To address these contradicting challenges, the syncytiotrophoblast acquires endothelial-cell like properties ( Figure 1 ). As a consequence, first, in human normal placenta, syncytiotrophoblast strongly expresses TF, and its activity is higher if compared with human umbilical vein endothelial cells. On the contrary, the trophoblast is able to synthesize protein C, protein S, and protein Z as well as a specific inhibitor of the tissue factor pathway known as TFPI-2 (placental protein 5) that will prevent unnecessary activation of the coagulation cascade.
Second, the placenta produces PAI-2 in addition to the gradual increase of PAI-1, observed during normal pregnancy and becomes markedly elevated in the third trimester to prevent fibrinolysis. These changes are associated with relatively unchanged tissue plasminogen activator concentrations, contributing to a state of reduced clot lysis and a prothrombotic bias in the pregnant woman. This mechanism is further mediated through thrombin activatable fibrinolysis inhibitor.
The evidence brought herein supports the fact that any condition that disrupts the integrity of the throphoblast ( Figure 2 ) can lead to a release of a large amount of potent TF that will activate the coagulation cascade and propagate an inflammatory response that can easily become systemic, leading to uncontrolled thrombin generation and the subsequent development of DIC.
There are several conditions that are associated with DIC in which the current evidence suggests that the systemic maternal response is the result of endothelial activation. The classical one is abruption, especially that with concealed bleeding and fetal demise. These patients have a combination of consumption coagulopathy and discharge of thromboplastin (tissue factor) into the maternal circulation.
Although the DIC developed in patients with placental abruption is regarded as a problem of consumption coagulopathy, it seems that there is more to it, meaning that often patients with a retroplacental clot have a much lower blood loss than those who developed PPH, yet the DIC of in these patients is much more severe. A probable explanation is that this complication is associated with the release of procoagulating factors, such as thromboplastin, into the maternal circulation.
In addition, local hypoxia and hypovolemia trigger endothelial response leading to increased expression of vascular endothelial growth factor, which causes an increased endothelial expression of TF. Evidence in support of this view is brought by Erez at al, who demonstrated that in women with fetal death, those who had abruption had a higher amniotic fluid of TAT complexes. These events result in the consumption of coagulating factors, fibrin deposition in microcirculation, and thrombus formation on maternal surface of the placenta at the site of abruption. This is followed by fibrinolysis and the release of fibrin degradation products further contributing to the development of DIC.
Of interest, if the abruption in concealed or it is severe enough to cause fetal demise, it is at much higher risk for the development of DIC because of a continuous release of TF in the maternal circulation. The probable mechanism leading to this observation is similar to that observed in amniotic fluid embolism with systemic release of TF that leads to systemic activation of coagulation and subsequent DIC.
This view is supported by the experiment reported by Schneider, which demonstrated that the intravenous injection of placental extracts into mice leads to the death of the animal through DIC, which can be prevented by the administration of heparin. The author identified thromboplastin as the causative agent through its effect on the clotting time and its chemical properties and measured its activity by the 1-stage prothrombin-time method.
What are the mechanisms leading to DIC during pregnancy?
The development of DIC during pregnancy can be either abrupt as in acute abruption or PPH or continuous as can be observed in a retained dead fetus. Of interest, obstetric complications such as placental abruption, amniotic fluid embolism, and acute fatty liver of pregnancy are associated with severe early-onset DIC that is accompanied by maternal coagulopathy. The DIC in obstetric hemorrhage activates coagulation and triggers fibrinolysis. Activation of fibrinolysis leads to the production of D-dimers and fibrin-degradation products. These will interfere with platelet function and can impair myometrial contractility.
Clinical presentation of DIC may be the results of the following mechanisms.
Endothelial dysfunction and platelet activation
Intact, dysfunctional, or activated cells, as well as remnants of cell surfaces, inflammatory mediators, and coagulation proteins are all part of an interplay in which uncontrolled activation of coagulation cascade leads to DIC.
Endothelial cells, platelets, but in some cases also leucocytes and cancer cells can participate in the genesis of the process leading to DIC by releasing proinflammatory cytokines, propagating the activation of coagulation on their surface or inducing tissue factor (TF) expression on their membrane. A systemic inflammatory response that is associated with markedly increased circulating proinflammatory cytokines such as tumor necrosis factor-α, interleukin-1 (IL-1), and interleukin-6 (IL-6) can lead to exaggerated expression of TF by leukocyte and endothelial cells. This will generate an uncontrolled coagulation response that will eventually deteriorate into DIC. Lastly, the initiation of coagulation leading to thrombin generation in DIC, is mediated by the TF/factor VIIa pathway, also known as the extrinsic coagulation pathway.
The most significant source of TF is not completely clear in all situations. Tissue factor may be expressed not only in mononuclear cells in response to proinflammatory cytokines (mainly IL-6) but also by vascular endothelial or cancer cells. Despite the potent initiation of coagulation by TF, the activation of coagulation cannot be propagated if the physiological anticoagulant pathways function properly. However, in DIC all major natural anticoagulant pathways (ie, antithrombin III, protein C system, and TF pathway inhibitor [TFPI]) appear to be impaired.
Plasma concentrations of antithrombin III, the most important inhibitor of thrombin, are markedly reduced during DIC because of a combination of consumption, degradation by elastase from activated neutrophils, and impaired synthesis.
A significant depression of the protein C system may further compromise an adequate regulation of activated coagulation. This impaired function of the protein C system is caused by a combination of impaired protein synthesis, cytokine-mediated down-regulation of endothelial thrombomodulin, and a fall in the concentration of the free fraction of protein S (the essential cofactor of protein C), resulting in reduced activation of protein C.
Lastly, there seems to be a misbalance of TFPI function in relation to the increased TF-dependent activation of coagulation.
All these anticoagulant pathways are linked to the endothelium, and it is likely that endothelial cell activation and dysfunction are an important component of the imbalance between coagulation and anticoagulation systems. Of interest, experimental and clinical studies indicate that during DIC, the fibrinolytic system is largely suppressed at the time of maximal activation of coagulation. This inhibition of fibrinolysis is caused by a sustained rise in the plasma concentrations of plasminogen activator inhibitor (PAI)-1, the principal inhibitor of the fibrinolytic system.
Activation of platelets may also accelerate fibrin formation. The expression of TF in monocytes is markedly stimulated by the presence of platelets and granulocytes in a P-selectin–dependent reaction. This effect may be the result of nuclear factor kappa B activation induced by binding of activated platelets to neutrophils and mononuclear cells.
During pregnancy maternal leukocytes are in a higher state of activation than in nonpregnant women and have characteristics akin to sepsis. However, they are well controlled during pregnancy, and it has been proposed that the trophoblast plays a role in the maintenance of the balanced systemic maternal inflammation during gestation. Nevertheless, in cases of sepsis caused by an infectious agent or septic abortion and at least in some of the cases of amniotic fluid embolism, this equilibrium is disturbed and the mother develops DIC.
Trophoblast properties and activation of the coagulation system
During normal gestation the trophoblast has 2 hemostatic functions: (1) to allow the laminar flow of maternal blood in the intervillous space and prevent it from clotting during that time; and (2) to prevent bleeding at the maternal fetal interface.
To address these contradicting challenges, the syncytiotrophoblast acquires endothelial-cell like properties ( Figure 1 ). As a consequence, first, in human normal placenta, syncytiotrophoblast strongly expresses TF, and its activity is higher if compared with human umbilical vein endothelial cells. On the contrary, the trophoblast is able to synthesize protein C, protein S, and protein Z as well as a specific inhibitor of the tissue factor pathway known as TFPI-2 (placental protein 5) that will prevent unnecessary activation of the coagulation cascade.
Second, the placenta produces PAI-2 in addition to the gradual increase of PAI-1, observed during normal pregnancy and becomes markedly elevated in the third trimester to prevent fibrinolysis. These changes are associated with relatively unchanged tissue plasminogen activator concentrations, contributing to a state of reduced clot lysis and a prothrombotic bias in the pregnant woman. This mechanism is further mediated through thrombin activatable fibrinolysis inhibitor.
The evidence brought herein supports the fact that any condition that disrupts the integrity of the throphoblast ( Figure 2 ) can lead to a release of a large amount of potent TF that will activate the coagulation cascade and propagate an inflammatory response that can easily become systemic, leading to uncontrolled thrombin generation and the subsequent development of DIC.
There are several conditions that are associated with DIC in which the current evidence suggests that the systemic maternal response is the result of endothelial activation. The classical one is abruption, especially that with concealed bleeding and fetal demise. These patients have a combination of consumption coagulopathy and discharge of thromboplastin (tissue factor) into the maternal circulation.
Although the DIC developed in patients with placental abruption is regarded as a problem of consumption coagulopathy, it seems that there is more to it, meaning that often patients with a retroplacental clot have a much lower blood loss than those who developed PPH, yet the DIC of in these patients is much more severe. A probable explanation is that this complication is associated with the release of procoagulating factors, such as thromboplastin, into the maternal circulation.
In addition, local hypoxia and hypovolemia trigger endothelial response leading to increased expression of vascular endothelial growth factor, which causes an increased endothelial expression of TF. Evidence in support of this view is brought by Erez at al, who demonstrated that in women with fetal death, those who had abruption had a higher amniotic fluid of TAT complexes. These events result in the consumption of coagulating factors, fibrin deposition in microcirculation, and thrombus formation on maternal surface of the placenta at the site of abruption. This is followed by fibrinolysis and the release of fibrin degradation products further contributing to the development of DIC.
Of interest, if the abruption in concealed or it is severe enough to cause fetal demise, it is at much higher risk for the development of DIC because of a continuous release of TF in the maternal circulation. The probable mechanism leading to this observation is similar to that observed in amniotic fluid embolism with systemic release of TF that leads to systemic activation of coagulation and subsequent DIC.
This view is supported by the experiment reported by Schneider, which demonstrated that the intravenous injection of placental extracts into mice leads to the death of the animal through DIC, which can be prevented by the administration of heparin. The author identified thromboplastin as the causative agent through its effect on the clotting time and its chemical properties and measured its activity by the 1-stage prothrombin-time method.
Hemorrhage
Acute obstetrical bleeding is being considered by many as a leading cause for DIC. This form of consumption coagulopathy is classically related to PPH as a result of uterine atony, retained placenta or membranes, uterine rupture, placenta accreta, or severe cervical or vaginal lacerations. In all of these cases, the mother is losing a large volume of blood and coagulation factors in a short time interval, and these patients are usually hemodynamically compromised.
Currently there is a debate whether this form of consumption coagulopathy is truly DIC or just a massive blood loss that depletes the patient’s coagulation factors and can lead to death because of exsanguination. However, massive maternal bleeding may not be that straightforward as a pure loss of coagulation factors. During the time of parturition and postpartum period, there is substantial activation of coagulation cascade and generation of thrombin as a result of the release of TF to the maternal circulation following the separation of the membranes and the placenta. Thus, these women already have increased thrombin generation and indeed are regarded as high-risk patients for the development of deep vein thrombosis during the puerperium.
The evidence brought herein, that parturients with PPH have a higher activation of coagulation cascade even above the physiological threshold, suggests that the clinicians who treat these patients must regard them as a high-risk group for DIC, even though the fundamental pathology is a rapid and massive loss of blood as well as coagulation factors. Therefore, patients with PPH need to be treated promptly, pharmacologically, and/or surgically and by blood products as well as volume expanders to sustain the maternal circulation and perhaps to prevent the subsequent development of DIC.
Disruption of liver function
Acute fatty liver of pregnancy
Acute fatty liver of pregnancy is a rare (an estimated incidence between 6 and 14 per 100,000 pregnancies ) but potentially fatal complication of pregnancy. It is characterized by fatty microvascular infiltration of hepatocytes with progressive loss of liver function, without alteration of the overall structure of the liver. Women who develop this complication have abnormal renal function and DIC. The mechanisms by which DIC develops in this complication is a combination of reduced liver production of fibrinogen as well as coagulation proteins and hemorrhage.
Evidence in support of this view is presented by Nelson et al, who studied 51 women with acute fatty liver of pregnancy. Their hemostatic condition was classified according to the International Society of Thrombosis and Haemostasis DIC score, and 80% of these women had unequivocal DIC defined as composite score of 5 or greater. The authors studied the hepatic and hemostatic function of these patients including fibrinogen, fibrin-fibrinogen split products, coagulation studies, and cholesterol. Those who developed DIC had abnormally low plasma fibrinogen concentrations that persisted for the first several days after delivery along with only mild to moderately elevated fibrin degradation products.
At the same time, there was also evidence for continuing increased procoagulant consumption caused by ongoing DIC provided by the modestly elevated levels of fibrin degradation products in the face of depressed plasma fibrinogen concentrations. This observation was in contrast to that of patients with abruption in whom the fibrinogen concentration recovered into normal range several hours after the acute event. Collectively the continuous low fibrinogen concentration and abnormal function of the coagulation cascade is the result of the liver dysfunction associated with acute fatty liver of pregnancy, leading to a lower production of coagulation factors, anticoagulation proteins, and fibrinogen by the liver.
HELLP syndrome
This condition is an additional cause for DIC in obstetric patients that may involve the liver. The relationship between acute fatty liver of pregnancy and HELLP syndrome has not been clearly established. There are obviously common clinical and biological features between these 2 entities. Indeed, some authors have suggested that acute fatty liver of pregnancy and HELLP syndrome are the 2 faces of the same coin. However, others found that a difference in liver histopathology (fatty microvascular infiltration of hepatocytes vs fibrin deposition or hemorrhage in the periportal areas ) makes an overlap between these 2 entities not possible.
One of the major differences between acute fatty liver of pregnancy and HELLP syndrome is the prevalence of DIC. In a study by Vigil-De Gracia, DIC was present in more than 70% of patients with acute fatty liver of pregnancy and less than 15% of those with HELLP syndrome. Thus, although women with HELLP syndrome have a reduced production of fibrinogen and other coagulating as well as anticoagulation factors that can lead to the development of DIC, this is not the central feature of this disease. From the evidence brought herein, DIC is a central feature of acute fatty liver and in a way reflects the severity of the hepatic injury, whereas in HELLP syndrome, it is present in only a fraction of the patients, probably those with a more severe form of the microangiopathic hemolytic anemia associated with this syndrome.
How can we diagnose DIC?
Early and accurate recognition of DIC is the hallmark of success in the treatment of this dire complication. Unfortunately, in the majority of the cases, the diagnosis of DIC is based on the clinical assessment of the patient. Indeed, there is no single laboratory or clinical test that is sensitive and specific enough to diagnose DIC. Also, the effect of the pathologies on the coagulation profile of the patients cited previously and the risk to develop DIC is not evident in all cases.
For these reasons, and the need to provide the clinician a tool for early identification of DIC as well as the need for a common language and definition of DIC, efforts have been made to create scoring systems to identify patients at high risk for this dangerous complication. All these scores use simple and readily available coagulation tests including platelet count, prothrombin time (PT) prolongation, fibrinogen, and fibrin split products/D-dimer concentrations.
One key message is that the tests should be repeated to reflect the dynamic changes on the basis of laboratory results and clinical observations. In the order of relative importance in patients with DIC, the tests are platelet count (decreasing), PT (prolongation), fibrin-related marker (increasing), and fibrinogen (decreasing).
Thrombocytopenia is the most common laboratory diagnostic feature for DIC. However, the platelet count may not always be very low and may even be in the normal range in patients who have recently started developing DIC. On the other hand, the gestational thrombocytopenia of the third trimester may confuse the thrombocytopenia of DIC. To determine whether the thrombocytopenia is due to DIC, a downward trend in the platelet count is most important, even if the count remains in the normal range.
It is useful to bear in mind that thrombocytopenia in preeclampsia and hypertensive disorders of pregnancy may also be related to platelet aggregation or increased adhesion to the vascular endothelium. This is consistent with the finding that A disintegrin and metalloproteinase with thrombospondin-like repeats-13, the Von Willebrand cleaving protease enzyme that typically shows reduced concentration in thrombotic thrombocytopenic purpura, is also lower in women with preeclampsia or HELLP syndrome in comparison with normal pregnant women. Stepanian et al suggested that it may even play a role in the pathophysiology of this obstetrical syndrome and, as a consequence, this might worsen the clinical course of patients with DIC.
A diagnosis of DIC is often considered when the PT and activated partial thromboplastin time (APTT) are considerably prolonged. However, in pregnant women, normal ranges for these tests are considerably shorter than that for the general population. For example, even after significant PPH (up to 1500 mL), because of uterine atony, genital tract trauma, and retained placenta, PT and APPT were normal in 98.4% and 98% of cases, respectively, whereas in the case of placental abruption, they were normal in all cases.
Prolongation of PT and APTT may not occur until the underlying condition has progressed considerably. This is especially true in the case of APTT, which can be shortened because of increased concentrations of factor VIII seen in pregnancy. It is important that in the correct clinical context, attention is paid to prolongation of the PT and APTT, even in the normal range, because suggestive of thrombin generation and clinical worsening and treatment commenced when they are even mildly prolonged.
Low fibrinogen concentration is often considered in the diagnostic algorithm for DIC. However, because of the fact that it is an acute-phase reactant, it is very uncommon for the fibrinogen levels to be low in pregnant women unless in the setting of massive PPH. At the same time, in comparison with the other clotting factors, fibrinogen levels fall below the normal pregnancy range sooner, with reports suggesting a decrease in serum fibrinogen is an accurate biomarker for progression from moderate to severe PPH.
The pivotal study in this area came from Charbit et al, who demonstrated that, in women with uterine resistant atony, a fibrinogen less than 2 g/L had a positive predictive value of 100% for progression to severe PPH, whereas a level greater than 4 g/L had a negative predictive value of 79%. For this reason, importance once again should be given to a decreasing fibrinogen level rather than an absolute value with a threshold value of 1.5 g/dL or even higher recommended for replacement.
Fibrin degradation product measurements also have its problems in pregnancy because D-dimers are already raised, even before pathological states set in. Repeated measurements showing increasing values may be helpful.
Point-of-care testing using devices like thromboelastography (Haemonetics, Braintree, MA) or thromboelastometry (TEM GmBH, Munich, Germany) is useful in the obstetrical coagulopathic disorders to achieve rapid results and decide intervention. Normal ranges have been published for women at the time of delivery compared with the standard ranges.
Collins et al reported the thromboelastometry Fibtem A5 assay as a very useful marker for monitoring hemostasis in this setting. In addition, Sharma and Saxena have proposed a thromboelastographic score, studying 21 patients classified following the International Society for Haemostasis and Thrombosis (ISTH) score. They demonstrated that parameters arising from this technique may reach a sensitivity of 95.2% and specificity of 81.0%, with the highest receiver operating characteristic area under the curve of all parameters of 0.957 for identifying overt DIC.
The use of thromboelastometry has been further evaluated in patients with DIC related to severe sepsis, showing it can be a valuable tool in assessing whole blood coagulation capacity in patients with severe sepsis with and without overt DIC.
Data on thromboelastography and thromboelastometry in pregnant women are limited, especially during the peripartum period and in women with PPH, so more research in this field is needed. Moreover, preliminary data are encouraging because these tests may be able to detect early alteration of coagulation pathways and hyperfibrinolysis, allowing, in combination with the other diagnostic and prognostic means, like DIC scores, an adequate surveillance and, eventually, a prompt intervention in obstetric not yet severely affected patients.
The acutely bleeding patient does not need any score evaluation but prompt infusion of blood products according to preexisting protocols. However, in many cases, DIC develops gradually and through different underlying mechanisms that are described in the manuscript. In the latter group, using such a scoring system can alert the clinician that his patient is deteriorating and needs further attention and treatment. In addition, the introduction of such a scoring system into clinical work will help to validate the diagnosis and create a common language between clinician and researchers that will assist in the promotion of the understanding and management of DIC during pregnancy.
To address the task of facilitating the diagnosis of DIC, in those conditions that do not represent emergencies in which only a clinical diagnosis can be achieved, the use of scoring systems has been introduced. The first DIC score has been recommended by the ISTH in 2001 showing a correlation between key clinical observations and outcomes. Using the same parameters, the Japanese Association for Acute Medicine published an additional score in 2005, offering a good predictive value for the diagnosis of DIC and the identification of critically ill nonpregnant patients. These scores can be used not only as a diagnostic but also as a prognostic tool. Thus, in the nonpregnant state, a DIC score is important in the diagnosis of patients with DIC and carries a diagnostic and prognostic value.
Because the physiological hemostatic changes occurring in pregnancy affect the application of these scores to gestation, an adjusted score for the pregnant state was needed. Based on this consideration, Erez et al have recently constructed a pregnancy modified DIC score by using only 3 components of the ISTH DIC score (platelet count, fibrinogen concentrations, and the PT difference) with an area under the curve of 0.975 ( P < .001) and at a cutoff of 26 or more points had a sensitivity of 88% and a specificity of 96% for the diagnosis of DIC. At this cutoff, the pregnancy-modified DIC score showed a positive likelihood ratio of 22 and a negative likelihood ratio of 0.125 ( Table ).
