HELLP syndrome is a severe complication of pregnancy, which is characterized by a triad of signs: hemolysis, damage to the hepatic parenchyma and thrombocytopenia. Clinically manifested by rapidly increasing symptoms — pain in the liver and abdomen, nausea, vomiting, swelling, jaundice of the skin, increased bleeding, impaired consciousness up to coma. It is diagnosed on the basis of a blood test, a study of enzyme activity and the state of hemostasis. Treatment involves emergency delivery, the appointment of active plasma replacement, hepatostabilizing and hepatoprotective therapy, drugs that normalize hemostasis.
ICD 10
14.2 HELLP syndrome
General information
Although HELLP syndrome has been observed infrequently in recent years, it complicates the course of severe gestosis in 4-12% of cases and, in the absence of adequate treatment, has high rates of maternal and child mortality. The syndrome as a separate pathological form was first described in 1954. The name of the disorder is formed by the first letters of the terms defining the key manifestations of the disease: H – hemolysis, EL – elevated liver enzymes, LP – low level platelet.
HELLP syndrome usually occurs in the 3rd trimester of pregnancy at 33-35 weeks. In 30% of cases, it develops 1-3 days after delivery. According to the results of observations, the risk group consists of light-skinned pregnant women over 25 years old with severe somatic disorders. With each subsequent pregnancy, the likelihood of developing the disease increases, especially if we are talking about carrying two or more fetuses.
Causes
To date, the etiology of the disorder has not been definitively determined. Specialists in the field of obstetrics and gynecology have proposed more than 30 theories of the occurrence of this acute obstetric pathology. Most likely, it develops with a combination of a number of factors aggravated by the course of gestosis. Some authors consider pregnancy as one of the variants of allotransplantation, and HELLP syndrome as an autoimmune process. Among the most common causes of the disease are:
- Immune and autoimmune disorders. Depression of B- and T-lymphocytes is noted in the blood of patients, antibodies to platelets and vascular endothelium are determined. The ratio in the prostacyclin/thromboxane pair has been reduced. Sometimes the disease complicates the course of another autoimmune pathology – antiphospholipid syndrome.
- Genetic anomalies. The basis for the development of the syndrome may be the congenital failure of the enzyme systems of the liver, which increases the sensitivity of hepatocytes to the action of damaging factors arising from an autoimmune response. A number of pregnant women also have congenital disorders of the coagulation system.
- Uncontrolled intake of certain medications. The probability of developing pathology increases with the use of pharmacological drugs that have a hepatotoxic effect. First of all, we are talking about tetracycline and chloramphenicol, the damaging effect of which increases with the immaturity of enzyme systems.
Pathogenesis
The starting point in the development of HELLP syndrome is a decrease in the production of prostacyclin against the background of an autoimmune reaction resulting from the action of antibodies on the cellular elements of the blood and endothelium. This leads to microangiopathic changes in the inner lining of the vessels and the release of placental thromboplastin, which enters the mother’s bloodstream. In parallel with damage to the endothelium, vascular spasm occurs, provoking placental ischemia. The next stage in the pathogenesis of HELLP syndrome is the mechanical and hypoxic destruction of erythrocytes, which pass through the spasmodic vascular bed and are actively attacked by antibodies.
Against the background of hemolysis, platelet adhesion and aggregation increases, their overall level decreases, blood thickens, multiple microthrombosis occurs, followed by fibrinolysis, DIC syndrome develops. Violation of perfusion in the liver leads to the formation of hepatosis with necrosis of the parenchyma, the formation of subcapsular hematomas and an increase in the level of enzymes in the blood. Blood pressure increases due to vascular spasm. As other systems are involved in the pathological process, signs of multiple organ failure increase.
Classification
There is no unified systematization of the forms of HELLP syndrome yet. Some foreign authors suggest taking into account laboratory research data when determining the variant of a pathological condition. In one of the existing classifications, there are three categories of laboratory parameters that correspond to hidden, suspected and obvious signs of intravascular coagulation. A more accurate option is based on determining the concentration of platelets. According to this criterion , there are three classes of syndrome:
- 1st grade. The level of thrombocytopenia is less than 50×109/l. The clinic is characterized by a severe course and a serious prognosis.
- 2nd grade. The content of blood platelets ranges from 50 to 100 ×109/l. The course of the syndrome and the prognosis are more favorable.
- 3rd grade. There are moderate manifestations of thrombocytopenia (from 100 to 150 × 109 / l). The first clinical signs are observed.
Symptoms
The initial manifestations of the disease are nonspecific. A pregnant woman or a woman in labor complains of soreness in the epigastrium, the right hypochondrium and abdominal cavity, headache, dizziness, a feeling of heaviness in the head, painful sensations in the neck and shoulder girdle muscles. Weakness and fatigue increase, vision deteriorates, nausea and vomiting occur, swelling.
Clinical symptoms progress very quickly. As the condition worsens, areas of hemorrhages form at the injection sites and on the mucous membranes, the skin becomes jaundiced. There is inhibition, confusion of consciousness. With a severe course of the disease, convulsive seizures, the appearance of blood in the vomit are possible. In the terminal stages, a comatose state develops.
Complications
HELLP syndrome is characterized by multiple organ disorders with decompensations of the main vital functions of the body. In almost half of cases, the disease is complicated by DIC syndrome, every third patient has signs of acute kidney injury, every tenth has swelling of the brain or lungs. Some patients develop exudative pleurisy and pulmonary distress syndrome.
In the postpartum period, profuse uterine bleeding with hemorrhagic shock is possible. In rare cases, women with HELLP syndrome exfoliate fiber, hemorrhagic stroke occurs. In 1.8% of patients, subcapsular hematomas of the liver are detected, the rupture of which usually leads to massive intra-abdominal bleeding and the death of a pregnant woman or a woman in labor.
HELLP syndrome is dangerous not only for the mother, but also for the child. If the pathology develops in a pregnant woman, the probability of premature birth or placental abruption with coagulopathic bleeding increases. In 7.4-34.0% of cases, the fetus dies in utero. Almost a third of newborns have thrombocytopenia, which leads to hemorrhages in the brain tissue and subsequent neurological disorders.
Some children are born in a state of asphyxia or with respiratory distress syndrome. A serious, though infrequent complication of the disease is intestinal necrosis, detected in 6.2% of infants.
Diagnostics
Suspicion of the development of HELLP syndrome in the patient is the basis for emergency laboratory tests verifying the defeat of the hemostasis system and hepatic parenchyma. Additionally, the control of the main vital parameters (respiratory rate, pulse temperature, blood pressure, which is elevated in 85% of patients) is provided. The following types of examinations are the most valuable in diagnostic terms:
- Blood test. A decrease in the number of red blood cells and their polychromasia, deformed or destroyed red blood cells are determined. One of the diagnostically reliable criteria is considered to be thrombocytopenia less than 100×109/l. The number of leukocytes and lymphocytes is usually unchanged, there is a slight decrease in ESR. The hemoglobin level drops.
- Liver tests. Violations of enzyme systems typical for liver damage are revealed: aminotransferase activity (AST, AlT) is increased by 12-15 times (up to 500 units / l). The activity of alkaline phosphatase increases by 3 times or more. The level of bilirubin in the blood exceeds 20 mmol/l. The concentrations of proteins and haptoglobin are reduced.
- Assessment of the hemostasis system. Laboratory signs of consumption coagulopathy are characteristic – the content of clotting factors synthesized in the liver with the participation of vitamin K. The level of antithrombin III is reduced. The prolongation of thrombin time, a decrease in APTT and fibrinogen concentration also indicates a violation of blood clotting.
It should be noted that typical laboratory signs of HELLP syndrome may deviate unevenly from the normative indicators, in such cases they speak of variants of the disease — ELLP syndrome (there is no hemolysis of erythrocytes) and HEL syndrome (platelet content is not disturbed). For an express assessment of the condition of the liver, its ultrasound examination is performed.
Since kidney function is impaired in severe forms of the disease, a decrease in the daily amount of urine, the appearance of proteinuria and an increase in the content of nitrogenous substances in the blood (urea, creatinine) is considered a prognostically unfavorable factor. Taking into account the pathogenesis of the disease, ECG, ultrasound of the kidneys, fundus examination are recommended. In the prenatal period, CTG, ultrasound of the uterus, Dopplerometry are performed to monitor the condition of the fetus, hemodynamics of the fetus and the mother.
Differential diagnosis
HELLP syndrome should be differentiated from the severe course of gestosis, fatty hepatosis of pregnant women, viral and medicinal hepatitis, hereditary thrombocytopenic purpura and hemolytic uremic syndrome. Differential diagnosis is also carried out with intrahepatic cholestasis, Dabin-Johnson syndrome and Budd-Chiari syndrome, systemic lupus erythematosus, cytomegalovirus infection, infectious mononucleosis and other pathological conditions.
Taking into account the severity of the prognosis of the disease, its overdiagnosis has recently been noted. In complex clinical cases, a hepatologist, a neurologist, an oculist, an infectious disease specialist and other specialists are involved in the diagnostic search.
Treatment
Medical tactics in detecting the disease in a pregnant woman is aimed at terminating pregnancy within 24 hours from the moment of diagnosis. Patients with a mature cervix are recommended to be delivered through the natural birth canal, but more often an emergency caesarean section is performed under endotrachial anesthesia with the use of non-hepatotoxic anesthetics and prolonged ventilation. At the stage of intensive preoperative preparation, due to the introduction of freshly frozen plasma, crystalloid solutions, glucocorticoids, fibrinolysis inhibitors, the woman’s condition is maximally stabilized, if possible, the disturbed multiple organ disorders are compensated.
Complex drug therapy aimed at the elimination of angiopathies, microthrombosis, hemolysis, effects on various links of pathogenesis, restoration of liver function, other organs and systems, actively continues in the postoperative period. For the treatment of the syndrome, prevention or elimination of its possible consequences, it is recommended:
- Infusion and blood replacement therapy. The introduction of blood plasma and its substitutes, thromboconcentrates, complex salt solutions makes it possible to replenish the destroyed shaped elements and fluid deficiency in the intravascular bed. An additional effect of such therapy is the improvement of rheological parameters and stabilization of hemodynamics.
- Hepatostabilizing and hepatoprotective drugs. To stabilize hepatic cytolysis, parenteral administration of glucocorticoids is prescribed. The use of hepatoprotectors is aimed at improving the work of hepatocytes, protecting them from toxic metabolites, stimulating the restoration of destroyed cellular structures.
- Means for normalization of hemostasis. To improve the parameters of the blood coagulation system, reduce the manifestations of hemolysis and prevent microthrombosis, low-molecular-weight heparins, other disaggregants and anticoagulants, drugs with vasoactive effect are used. The appointment of protease inhibitors is effective.
Taking into account hemodynamic parameters, patients with HELLP syndrome receive individualized hypotensive therapy supplemented with antispasmodics. To prevent possible infectious complications, antibiotics are used with the exception of aminoglycosides, which have hepatotoxic and nephrotoxic effects. According to the indications, nootropic and cerebroprotective drugs, vitamin and mineral complexes are prescribed. When manifestations of acute renal failure occur, plasmapheresis and hemodialysis are performed, depending on the severity of the disorders.
Prognosis and prevention
The prognosis of HELLP syndrome is always serious. In the past, the mortality rate for the disease reached 75%. Currently, thanks to timely diagnosis and pathogenetic methods of therapy, maternal mortality has been reduced to 25%. For preventive purposes, repeat-giving women with chronic somatic diseases are recommended early registration in a women’s consultation and constant supervision by an obstetrician-gynecologist.
If signs of gestosis are detected, it is important to carefully follow the prescriptions of the attending physician, normalize the diet, observe the sleep and rest regime. Rapid deterioration of the pregnant woman’s condition with the onset of symptoms of severe eclampsia and preeclampsia is an indication for emergency hospitalization in an obstetric hospital.
Literature
- Pritchard JA, Weisman R Jr, Ratnoff OD, Vosburgh GJ: Intravascular hemolysis, thrombocytopenia and other hematologic abnormalities associated with severe toxemia of pregnancy. NEngl J Med 1954, 250:89–98.
- Haddad B, Sibai BM. 2005. Expectant management of severe preeclamp- sia: proper candidates and pregnancy outcome. Clinical Obstetrics and Gynecology 48:430–440. Haram K, Svendsen E, Abildgaard U. 2009.
- The HELLP syndrome: clinical issues and management. A review. BMC Pregnancy Childbirth 9:8. Thangaratinam S, Gallos ID, Meah N, Usman S, Ismail KM, Khan KS. 2011. How accurate are maternal symptoms in predicting impending complications in women with preeclampsia? A systematic review and meta-analysis. Acta Obstetricia et Gynecologica Scandinavica 90: 564–573
