FIGURE 41 -29 Schematic of coagulation pathway. FSP = fibrin split products; PAl = plasminogen activator inhibitor;TFPI = tissue factor pathway inhibitor.
Activation of Pathological Coagulation he initiation of DIC begins with the release of tissue factor by pathological entities. Tissue factor is released by subendothelial tissue and stimulated monocytes, which in turn provoke release of cytokines from the endothelium. With generalized endothelial activation, difuse activation of coagulation follows. his pathological cycle ofcoagulation and ibrinolysis becomes clinically important when coagulation factors and platelets are suiciently depleted to create consumptive coagulopathy.
Several obstetrical syndromes can trigger consumptive coagulopathy. The best known and most common is placental abruption with its significant release of thromboplastin. Another is embolization of amnionic luid and debris into the maternl circulation. This causes activation of factor X by abundant mucin found in fetal squames. Other causes include endotoxins from gram-negative bacteriaand exotoxins from gram-positive bacteria.
Bioassay is an excellent method to detect or suspect clinically signiicant coagulopathy. Excessive bleeding at sites of modest trauma characterizes defective hemostasis. Examples include persistent bleeding from venipuncture sites, nicks from shaving the perineum or abdomen, trauma from bladder catheterization, and spontaneous bleeding from the gums, nose, or gastrointestinal tract. Purpura or petechiae at pressure sites such as sphygmomanometer cufs or tourniquets suggest signiicant thrombocytopenia. Any surgical procedure provides the ultimate bioassay and elicits generalized oozing from abdominal wall layers, the retroperitoneal space, the episiotomy, or incisions and dissections for cesarean delivery or hysterectomy.
Ofaboratory tests, ibrinogen, fibrin, and degradation product leves can be informative. In late pregnancy, plasma fibrinogen levels typicallyhave risen to 300 to 600 mg/dL. Even with severe consumptive coagulopathy, levels may sometimes be suiciently high to protect against clinically signiicant hypofibrinogenemia. For example, deibrination caused by a placental abruption might lower an initial fibrinogen level of 600 mg/dL to 250 mg/dL. Although this would indicate massive ibrinogen consumption, levels are still adequate to promote clinical coagulationusually about 150 mg/dL. If serious hypoibrinogenemia-less than 50 mg/dL-is present, the clot formed from whole blood in a glass tube may initially be sot but not necessarily remarkably reduced in volume. Then, over the next half hour or so, as platelet-induced clot retraction develops, the clot becomes quite small. When many ofthe erythrocytes are extruded, the volume ofliquid in the tube clearlyexceeds that ofclot.
As depicted in Figure 41-29, fibrinolysis cleaves ibrin and ibrinogen into various fibrin degradation products that are detected by several sensitive assays. There are many fragment types, and monoclonal antibodies in assay kits usually measure D-dimers speciic for that assay. These values are always abnormally high with clinically significant consumptive coagulopathy. At least in obstetrical disorders, quantiication has not been correlated with outcomes. Examples of the magnitude of ibrin split product elevations in various obstetrical coagulopathies is shown in Figure 41-30.