The term preeclampsia applies to a spectrum of disorders that are pregnancy-dependent, all accompanied (usually) by some degree of hypertension at some point in their evolution. Preeclampsia is subdivided into categories based on the severity of hypertension and accompanying signs, symptoms, and laboratory abnormalities. Although the actual cause of preeclampsia is not known, it is probably the consequence of a placental compensatory mechanism (rather than dysfunction) in response to a suboptimal or even hostile local environment that is the end result of abnormalities of early placental development and growth and/or from conditions that impair placental function later in pregnancy. We will discuss some of the pathologic correlates, clinical characteristics, and risk factors for preeclampsia in a subsequent post, but today let’s focus on defining the various categories of preeclampsia.
Mild preeclampsia is defined as hypertension developing during pregnancy, accompanied by the onset of proteinuria (protein in the urine). Proteinuria is defined as greater than or equal 300 mg/L in a 24 hour urine specimen (or greater than or equal 1+ urine protein by ‘dipstick’ on two random specimens taken 6 or more hours apart). The presence of generalized edema (soft tissue fluid accumulation), or 5 lb or more weight gain (usually mostly fluid retention) within a week, often accompany the hypertension and proteinuria, and may alert us to the onset of the condition, but is not required for the strict diagnosis of preeclampsia. If the criteria for hypertension and proteinuria are met, a pregnant woman remains a ‘mild preeclamptic’ unless she develops evidence of one of the more severe manifestations of preeclampsia.
The diagnosis of severe preeclampsia requires the presence of only one of the following: · BP greater than or equal to 160 mmHg systolic or 110 mmHg diastolic on two occasions 6 or more hours apart at bedrest · Proteinuria greater than or equal to 5 g in 24 hr (or 3-4+ on two dipstick specimens 4 or more hours apart) · Oliguria = urine output less than 500 mL in 24 hr · Abnormal liver function tests · Thrombocytopenia (platelet count less than 100,000/mm3)
Conditions that also help to define severe preeclampsia when present include: · Cerebral or visual disturbances – headache, blurred vision, scotomata, blindness, altered consciousness · Pulmonary edema · Epigastric and right upper quadrant pain · Grand mal seizures · Intrauterine fetal growth restriction – often accompanied by ‘placental insufficiency’, abnormal fetal and maternal Doppler flow patterns (long discussion for another day!), and decreased amniotic fluid (oligohydramnios)
Specific subsets of severe preeclampsia, eclampsia and HELLP syndrome, are major contributors to the fetal and maternal morbidity and mortality that accompany the hypertensive disorders of pregnancy around the world. Eclampsia is defined as the new onset of grand mal seizures in a woman who meets the criteria for preeclampsia in the absence of any other neurologic disorder. This occurs in one of every 2000 pregnancies in the U.S. and in about one-third of cases does not occur until after delivery, usually within the first week postpartum, and sometimes as the first clinical manifestation of preeclampsia. The onset of seizures is often preceded by one or more of the following: severe headache, visual disturbances, irritability, epigastric, nausea, vomiting, and cerebral dysfunction. The cause of the seizures and other neurologic disturbances in eclampsia is at least in part a consequence of soft-tissue edema of the brain. It is prudent, however, if the woman has an atypical course of recovery from seizures, or doesn’t readily respond to therapy, that a more serious central nervous system complication (such as stroke, aneurysm, or tumor) is ruled out.
HELLP syndrome is one of the most interesting, enigmatic, and potentially serious manifestations of preeclampsia. It accounts for 10% or less of all cases of preeeclampsia and ranges in severity in different individuals. HELLP is an abbreviation for the laboratory abnormalities that define the condition: Hemolysis; Elevated Liver enzymes; and Low Platelets. The condition is characterized by intense vasospasm (contraction) of small blood vessels resulting in damage to the internal lining (microvascular endothelial cell damage) of these vessels and activation of the coagulation system(s) along the internal blood vessel walls as the result of the exposure of the thrombogenic (blood clot activating) factors that lie beneath the endothelium.
The hemolysis refers to the breakdown of red blood cells (RBCs) and this occurs in a pattern that is consistent with the RBCs being trapped and fragmented (microangiopathic hemolytic anemia) as they pass through these narrowed and damaged blood vessels in which the clotting system has been activated. The laboratory abnormalities reflect the RBC damage with abnormal appearance of the RBCs on peripheral smear (burr cells, schistocytes, spherocytes, triangular cells), and elevated levels of the RBC enzyme lactate dehydrogenase (LDH greater than 600 U/L) and serum total bilirubin (greater than 1.2 mg/dL) which results from the release and subsequent breakdown of hemoglobin from the RBCs.
The elevated liver enzymes are thought to result from damage to liver cells as the consequence of similar events. Liver transaminase (AST) levels that help to define the condition have to be greater than 70 U/L, but are often many times higher than this (sometimes in the 1000’s U/mL range). It should also be noted that the liver is an extremely vascular organ, and if significant damage occurs, intrahepatic hemorrhage, subcapsular hematoma formation, or even hepatic rupture may occur and can be life-threatening events even if recognized early.
The low platelets, or thrombocytopenia, associated with HELLP has been attributed to increased consumption and destruction of platelets at the sites of vascular endothelial damage where they are also ‘activated’ to clot by the tissues exposed beneath the blood vessel lining. Suspicion of HELLP syndrome is often raised when the platelet count falls below 150,000/mm3, but thrombocytopenia is not used to diagnose HELLP until the count is less than 100,000/mm3. In severe cases, platelet counts can be dangerously low, increasing the risk of hemorrhage during the cesarean sections that are often necessary due to fetal compromise accompanying the more severe forms of preeclampsia. HELLP syndrome, like eclampsia (and often accompanying eclampsia), may worsen or not be evident at all until after delivery in as many as one-third of women.
In our next post on this subject, we will discuss some of the risk factors for developing preeclampsia…