Approach

HELLP syndrome is a serious condition characterized by progressive and sometimes rapid maternal and fetal deterioration. A careful and structured approach by experienced personnel is necessary. A team approach incorporating anesthesiologists, maternal-fetal medicine specialists, intensive care specialists, and neonatologists is key.[71]

The Martin/Mississippi classification is used to facilitate management and estimate risk for major maternal morbidity:[2][3][4]

  • Class 1, severe thrombocytopenia: 0 to ≤50,000/mm³, lactate dehydrogenase (LDH) ≥600 IU/L or twice the upper limit of normal concentration, aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≥70 IU/L or twice the upper limit of normal concentration (major maternal morbidity 40% to 60%)

  • Class 2, moderate thrombocytopenia: >50,000 to ≤100,000/mm³, LDH ≥600 IU/L or twice the upper limit of normal concentration, and AST and/or ALT ≥70 IU/L or twice the upper limit of normal concentration (major maternal morbidity 20% to 40%)

  • Class 3, mild thrombocytopenia: >100,000 to ≤150,000 /mm³, LDH ≥600 IU/L or twice the upper limit of normal concentration, and AST ≥40 IU/L (major maternal morbidity 20%).

Standard management

Recommended management is based upon the series reported in 2012 from Mississippi in which almost 400 patients have been treated with intravenous magnesium sulfate and intravenous dexamethasone since 1994.[30][52][53][72] In recent years, intensive antihypertensive therapy has been used to minimize severe systolic hypertension with its risk of stroke (central nervous system hemorrhage is the most common cause of death in patients with HELLP syndrome).[52][53][73][74] The most recent report of 190 patients demonstrated that early initiation of this combination of interventions inhibits HELLP syndrome disease progression and severity.[53]

Treatment goals are:

  • Arrest, reverse, and shorten the disease process and length of hospitalization

  • Prevent disease progression to class 1 HELLP syndrome

  • Prevent the development of new major maternal morbidity and prevent maternal mortality

  • Minimize perinatal morbidity and mortality

  • Plan timely and appropriately sited delivery to maximize access to intensive maternal and neonatal care.

Seizure prophylaxis and hypertension control should be started immediately in all suspected cases of HELLP syndrome. Laboratory studies (complete blood count, liver transaminases, LDH, prothrombin time/partial thromboplastin time) should be repeated every 6 to 12 hours. Fluid balance should be monitored hourly, with particular attention to decreasing or absent urine output. Continuous fetal monitoring is imperative.

Once laboratory studies are available and the diagnosis is confirmed, the management strategy should be based on a comprehensive review of maternal stability and fetal wellbeing. Cesarean delivery should be performed for the usual obstetric indications, and may be considered for gestational age <30 to 32 weeks in the absence of labor.[30][75][76]

Corticosteroid therapy

Dexamethasone is the mainstay of treatment.[30][77] It is administered intravenously until delivery is employed, initially for:

  • Any patient with class 1 or class 2 HELLP syndrome regardless of gestational age; or

  • Any patient with class 3/partial-incomplete HELLP syndrome regardless of gestational age who also has eclampsia, severe epigastric pain, severe hypertension, or any major organ system morbidity.[53]

This is initiated for antepartum and/or first detected postpartum disease. Following delivery and with evidence of resolving laboratory and clinical parameters of disease, the dose of dexamethasone is reduced for at least 2 doses and then stopped. For patients <34 weeks' gestation and undelivered, it is preferable to delay delivery at least 24 to 48 hours in order to gain maximal fetal benefit; for patients >34 weeks' gestation, delivery is initiated usually 8 to 12 hours after the first dose is given in order to realize maximal maternal benefit and reduce need for transfusion of platelets, increase likelihood of regional anesthesia, and lessen risk of bleeding.

Immediate (first 12 hours) improvement may be seen in laboratory parameters with intravenous dexamethasone treatment. Other expected outcomes are: less progression to class 1 HELLP syndrome, infrequently needed antihypertensive therapy, less transfusion, a lower incidence of new major maternal morbidity after therapy is started, increased latency between diagnosis and delivery to enable vaginal delivery and regional anesthesia, and shortening of postpartum recovery with shorter hospitalization compared with what otherwise would be expected. Another prospective trial is under way to explore the possible value of delaying initiation of dexamethasone therapy until postpartum HELLP syndrome is diagnosed.[78]

Case reports published in 2018-9 showed that failure to initiate potent glucocorticoid therapy for patients diagnosed with HELLP syndrome can lead to major maternal morbidity/mortality. The major benefit shown in some studies for potent glucocorticoids to virtually eliminate maternal stroke or hepatic hemorrhage/infarction/rupture would likely have positively altered the outcome of these patients had high-dose intravenous dexamethasone been initiated early in disease management. Although potent glucocorticoid therapy is intended for utilization early in the course of HELLP syndrome treatment, even utilization initiated late when the patient is already at the class 1 stage can be effective.[79][80][81][82][83][84][85][86]

Seizure prophylaxis

When the diagnosis is suspected, a continuous infusion of magnesium sulfate as prophylaxis should be started, even prior to completion of laboratory studies, owing to the 10% to 33% risk of seizure.[53][87] Following delivery, the infusion should continue for 24 hours. Dose must be reduced in patients with low urine output (<25 mL/hour for 4 hours), and magnesium levels should be checked after 4 hours in these patients. If the magnesium level is >9 mg/dL, the infusion must be stopped and the level rechecked after 2 hours. Infusion can be resumed at a reduced rate when the magnesium level is <8 mg/dL. In patients with renal compromise or acute kidney injury, a single bolus of magnesium sulfate can be given without a continuous infusion. Blood magnesium levels need to be monitored in these patients to determine when pretreatment is safe to undertake.

If a grand mal convulsion/eclampsia occurs or is likely in the presence of severe headache and hypertension, intravenous magnesium sulfate is indicated usually for a duration of not less than 24 hours. In addition, treatment of severe systolic and/or diastolic hypertension (>160 mmHg and/or >110 mmHg thresholds, respectively) is urgently needed and important to sustain. If magnesium sulfate use is contraindicated (myasthenia gravis), other medications/anticonvulsants should be considered while blood pressure control is scrupulously pursued. In addition, in the presence of renal compromise, dosing of magnesium sulfate must be reduced and guided by serial blood magnesium levels. There are no clinical trials to indicate which anticonvulsant agent is best in these circumstances and a specialist should be consulted. The UK-based Medicines and Healthcare products Regulatory Agency recommends against using magnesium sulfate for extended periods of time (more than 5-7 days in total) during pregnancy due to concerns for abnormal calcium and magnesium levels and adverse skeletal effects in newborns exposed to such amounts.[88] The Food and Drug Administration issued a similar recommendation in 2013.[89] Maternal and neonatal magnesium concentrations are highly correlated.[90] Several neonatal complications (hypotonia, birth asphyxia, delivery room intubation) are related to increasing maternal and neonatal serum magnesium levels.[91][92]​​ However, there is no convincing evidence that fetal exposure to preeclampsia-spectrum disorders or treatment with magnesium sulfate affects cardiometabolic outcomes in childhood.[93] Despite these concerns for extended fetal exposure to magnesium sulfate, evidence suggests that magnesium sulfate given before anticipated early preterm birth provides neuroprotection for neonates.[94] So, the main target for management with magnesium sulfate is controlling seizures in the mother, but the baby still gets the benefit.​​

Blood pressure control

Blood pressure should be monitored every 15 minutes, and if it is at severe levels (≥160/105 mmHg, mean arterial pressure 120 mmHg), immediate reduction is required.[73]

Reduction to the normal range is not needed; rather, it must be reduced to a level that prevents or limits end-organ damage. A systolic blood pressure of 160-170 mmHg, which may be acceptable in other obstetric settings, is dangerous in the presence of thrombocytopenia. The goal is to reduce systolic pressure to <160 mmHg, but not <130-140 mmHg. A significant, sudden drop in blood pressure may cause fetal distress and hypoperfusion of critical territories, such as the maternal brain and heart. Guidelines such as those provided by the American College of Obstetricians and Gynecologists are recommended.[8]​​

Labetalol is commonly recommended for this indication.[8][10]​​[95][96] It can be administered as a continuous infusion, although bolus intravenous administration is more frequently used. Labetalol is contraindicated in patients with asthma or pre-existing cardiac disease, particularly decreased cardiac function. In these patients, nicardipine can be used.[87] 

Hydralazine is another option, especially if labetalol is contraindicated or ineffective. The most problematic aspect of acute treatment with hydralazine is the hypotensive overshoot episode. This complication is unpredictable and not always dose-related, and it may be prolonged. Although as effective as labetalol, hydralazine is associated with less favorable maternal and perinatal outcomes.[96]

Cesarean delivery

Generalized oozing may be present during surgery, and platelet pack transfusion may be necessary if surgery is required too quickly for the dexamethasone benefits to be realized. Choice of abdominal and uterine incision as well as closure techniques are not altered usually from standard practice in patients treated with the recommended regimen. Patients with a platelet count ≤40,000/mm³ at the time of surgery or delivery are more prone to bleeding during and after delivery.[30]

Management of bleeding problems

Platelet transfusions are necessary for platelet count <25,000/mm³, or <30,000/mm³ in cases of bleeding, massive transfusions (≥10 units of packed red blood cells), or surgical interventions. The effect of the platelet transfusion is only transient as consumption occurs rapidly. One unit of platelets is expected to increase the platelet count by 5000.[97] Rho(D) immune globulin is necessary if type-specific platelets are not available for Rh-negative women.

Fibrinogen replacement is necessary at levels <100 mg/dL. To increase the serum level of fibrinogen by 25 mg, 1g of exogenous fibrinogen has to be administered. This amount is provided by 1 unit of fresh frozen plasma or 6 units of cryoprecipitate. Cryoprecipitate administration is preferable when fluid overload is a concern.

The degree of thrombocytopenia present in patients with HELLP syndrome has important implications with regard to regional anesthesia. Regional anesthesia is contraindicated with platelet counts <80,000/mm³ (especially <50,000/mm³), owing to the risk of epidural hematoma. Intravenous narcotics may be used as alternative analgesia during labor and delivery. Pudendal or paracervical blocks should be avoided because of the risk of hematoma formation. For cesarean delivery, general anesthesia is required in patients who are not candidates for regional anesthesia.

Patients with HELLP syndrome tolerate low hematocrit poorly, and blood transfusions may be required with hematocrit ≤25%. These may be given before delivery.

Use of this content is subject to our disclaimer