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Thrombosis Research (2009) 123 Suppl. 2, S63S64

intl.elsevierhealth.com/journals/thre

Disseminated intravascular coagulation (DIC) in pregnancyand the peri-partum period

Marcel Levi*

Department of Internal Medicine, Academic Medical Center, University of Amsterdam, The Netherlands

Disseminated intravascular coagulation (DIC) is acondition characterized by a systemic activationof coagulation that leads to fibrin depositionwithout specific localization and occurring in-travascularly. There is ample experimental andpathological evidence that the fibrin depositionin DIC contributes to multiple organ failure.The massive and ongoing activation of coagula-tion, may result in depletion of platelets andcoagulation factors, which may cause bleeding(consumption coagulopathy).

(Pre-)eclampsia is the most common obstetricalcondition associated with activation of blood

coagulation resulting in macroscopical fibrindeposits in various organs in severe cases.Thrombocytopenia is an early indicator of DICdeveloping in the course of the HELLP syndrome(hemolysis, elevated liver enzymes and lowplatelets), which complicates pregnancy inducedhypertension in 5 10%, and pre-eclampsia in upto 50% of cases. The central pathophysiologicalstimulus of DIC in this syndrome appears tobe microangiopathic hemolytic anemia (MHA)accompanying vascular endothelial damage, andplatelet adhesion and activation, facilitating fibrin

formation.A more classical form of DIC may be causedby various underlying disorders, of which sepsis,trauma and malignancy are prominent, but alsoincluding a number of peri-partum haemostaticemergencies. The frequency by which peri-partum haemostatic emergencies result in DICis dependent on the characteristics of thecenter. In Western hospitals, it is estimated that1 5% of patients with DIC have a peri-partumhaemostatic emergency as underlying cause. Indeveloping countries this frequency is thoughtto be much higher. Peri-partum haemostatic

emergencies known to be associated with DIC arefor example abruptio placenta and retained deadfetus syndrome.

Recent knowledge on important pathogeneticmechanisms that may lead to DIC-associatedcoagulopathy and microvascular dysfunction hasresulted in novel preventive and therapeuticapproaches to patients with DIC. The triggerfor the activation of the coagulation system ismediated by several pro-inflammatory cytokines,expressed and released by mononuclear cells andendothelial cells. Thrombin generation proceedsvia the (extrinsic) tissue factor/factor VIIa

route and simultaneously occurring depression ofinhibitory mechanisms, such as antithrombin IIIand the protein C and S system. Also, impairedfibrin degradation, due to high circulating levelsof PAI-1, contributes to enhanced intravascularfibrin deposition. Interestingly, the placenta is arich source of tissue factor and hypothetically therelease of tissue factor from placental tissue inthe case of abruptio placenta may be a logicalpathogenetic pathway.

The diagnosis of DIC can be made by sensitivelaboratory tests, however, most of these tests are

not readily available in a routine setting. A reliablediagnosis can also be made on the basis of a smallseries of routine lab tests that can be combined ina scoring algorithm (ISTH-DIC score). Prospectivevalidation of this score, also in patients withpregnancy and in the peri-partum period, showspromising results.

Based on the knowledge of the pathogenesis ofmicrovascular failure and coagulation activationin DIC, strategies aimed at the inhibition ofcoagulation activation were developed and havebeen found favorable in experimental and clinicalstudies. In particular, restoring the function of

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S64 M. Levi

dysfunctional anticoagulant systems is interestingin this respect. DIC in pregnancy is charac-terized by a vast depletion of antithrombinand administration of antithrombin concentrateis an interesting though not very well studiedoption. Restoring the function of the protein C

system by administration of activated protein C,was shown to be of benefit in patients withsepsis and organ failure. Patients in the pivotalprowess trial of activated protein C in sepsis wereretrospectively evaluated for the presence of DICaccording to the ISTH-DIC score. At baseline, 29%(454/1568) of patients had overt DIC. Overt DICwas a strong predictor of mortality, independentof APACHE II score and age. Placebo-treatedpatients with overt DIC had higher mortalitythan patients without (43% vs. 27%). Activatedprotein C-treated patients with overt DIC had a

greater relative risk reduction in mortality thanpatients without (29% vs. 18%, P = 0.261). Alsothe administration of activated protein C has notyet been systematically studied in pregnancy andperi-partum DIC.

The cornerstone of the management of DICis the specific and vigorous treatment of theunderlying disorder. Strategies aimed at the inhi-bition of coagulation activation may theoreticallybe justified and have been found beneficial inexperimental and initial clinical studies. Thesestrategies comprise inhibition of tissue factor-mediated activation of coagulation or restora-

tion of physiological anticoagulant pathways, bymeans of the administration of antithrombinconcentrate, (activated) protein C, or strategiesinvolving (recombinant) thrombomodulin.

Conflicts of interest: The author has no conflict

of interest to declare.

References

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[3] Bernard GR, Vincent JL, Laterre PF, LaRosa SP, Dhainaut JF,Lopez-Rodriguez A, et al. Efficacy and safety ofrecombinant human activated protein C for severe sepsis.N Engl J Med 2001 Mar 8;344(10):699 709.

[4] Warren BL, Eid A, Singer P, Pillay SS, Carl P, Novak I, et al.Caring for the critically ill patient. High-dose antithrombinIII in severe sepsis: a randomized controlled trial. J AmMed Assoc 2001;286:1869 78.

[5] Abraham E, Reinhart K, Opal S, Demeyer I, Doig C,Rodriguez AL, et al. Efficacy and safety of tifacogin(recombinant tissue factor pathway inhibitor) in severesepsis: a randomized controlled trial. J Am Med Assoc2003;290:238 47.

[6] Levi M. Disseminated intravascular coagulation. Crit CareMed 2007;35:2191 5.

[7] Taylor FBJ, Toh CH, Hoots WK, Wada H, Levi M. Towardsdefinition, clinical and laboratory criteria, and a scoringsystem for disseminated intravascular coagulation. ThrombHaemost 2001 Nov;86(5):1327 30.