Hellp syndrome: concept, clinical forms, possible complications, therapeutic and obstetric tactics. Ozhgb

This disease was called the flashy term “HELLP syndrome” for a reason. If such a diagnosis was made during pregnancy, then it’s time to sound the alarm: urgent medical attention is needed. The body seems to refuse to perform the reproductive function, and all systems begin to fail, threatening the life of the expectant mother and her baby. What is the disease, and what actions should be taken to prevent its development?

What is HELLP syndrome

HELLP syndrome is very dangerous. In short, this is gestosis in a complicated form, caused by the autoimmune reaction of the woman’s body to pregnancy. It includes a whole range of health problems - malfunctions of the liver and kidneys, bleeding, poor blood clotting, increased blood pressure, swelling and much more. As a rule, it develops in the third trimester or in the first two days after birth and requires emergency medical attention. Moreover, clinical manifestations occur before childbirth in 31% of cases, and in the postpartum period - in 69%.

Explanation of the abbreviation HELLP:

• H - Hemollysis - hemolysis;
• EL - elevated liver enzymes - excess activity of liver enzymes;
• LP - Low platelet count - thrombocytopenia.

Doctors are afraid of the syndrome because of its rapid progression and frequent deaths. Fortunately, it is rare: approximately 1–2 cases per 1 thousand pregnancies.

This disease was first described at the end of the 19th century. But it wasn't until 1985 that his symptoms were linked together and named under the umbrella term "HELLP." It is interesting that Soviet medical reference books say almost nothing about this syndrome, and only rare Russian resuscitators mentioned the disease in their works, calling it “an obstetrician’s nightmare.”

HELLP syndrome has not yet been fully studied, so it is difficult to name specific reasons for its development. Today, doctors suggest that the likelihood of the disease increases with:

• repeat pregnancy;
• drug and viral hepatitis;
• unstable emotional and mental state;
• genetic abnormalities in liver function;
• pregnancy in adulthood (28 years and above);
• advanced cases of gestosis;
• disorders of the liver and gallbladder;
• gallstone and urolithiasis;
• systemic lupus;
• gastritis;
• blood clotting disorders.

Clinical picture of the disease

Diagnosing HELLP syndrome is quite difficult, since its symptoms do not always manifest themselves in full force. In addition, many signs of the disease are common during pregnancy and have nothing to do with this serious condition. The development of complicated gestosis can be indicated by:

• nausea and vomiting, sometimes with blood (in 86% of cases);
• pain in the upper abdomen and under the ribs (in 86% of cases);
• swelling of the arms and legs (in 67% of cases);
• pain in the head and ears;
• high blood pressure (over 200/120);
• the appearance of protein and traces of blood in the urine;
• changes in blood composition, anemia;
• yellowness of the skin;
• bruises at injection sites, nosebleeds;
• blurred vision;
• convulsions.

It is worth noting that changes in urine and blood parameters usually appear long before the clinical manifestation of the disease, so every pregnant woman needs to visit her gynecologist in a timely manner and take all the tests he prescribes. Many of the described symptoms also occur with gestosis. However, HELLP syndrome is characterized by a rapid increase in symptoms that develop within 4–5 hours. If the expectant mother feels such changes in her body, she should immediately call an ambulance.

According to statistics, 6–8 hours pass from the first manifestations of the syndrome to death in the absence of necessary medical care. Therefore, if you suspect an illness, it is very important to consult a doctor as soon as possible.

Preeclampsia, preeclampsia, eclampsia or HELLP syndrome?

If HELLP syndrome is suspected, the doctor has no more than 2–4 hours to conduct research and decide on further treatment tactics. He makes a diagnosis based on examination, ultrasound results, liver tests and blood tests. Sometimes pregnant women are prescribed a CT scan to rule out hemorrhage in the liver.

The term “preeclampsia” is used in Russian and Ukrainian medical documents and literature. In the international classification of diseases it is called preeclampsia. If it is accompanied by convulsions, it is called eclampsia. HELLP syndrome is the most severe form of gestosis, which differs in severity and number of clinical symptoms.

Distinctive symptoms for similar diseases - table

	Preeclampsia	Preeclampsia	Eclampsia	HELLP syndrome
Average pressure rise	140/90	160/110	160/110	200/120
Edema	+	+	+	+
Convulsions			+	+
Hemorrhages				+
Headache	+	+	+	+
Fatigue		+	+	+
Yellowness of the skin				+
Nausea, vomiting	+	+	+	+
Vomiting blood				+
Liver pain				+

Prognosis for HELLP syndrome

HELLP syndrome is a serious disease. According to various sources, maternal mortality with it ranges from 24 to 75%. The outcome of pregnancy, the health of the woman and the fetus mainly depend on when the disease was detected.

Statistics of complications in HELLP syndrome (per 1 thousand patients) - table

	1993	year 2000	2008	2015
Pulmonary edema	12%	14%	10%	11%
Liver hematomas	23%	18%	15%	10%
Placental abruption	28%	28%	22%	17%
Premature birth	60%	55%	51%	44%
Death of mother	11%	9%	17%	8%
Death of a child	35%	42%	41%	30%

Obstetric tactics

If HELLP syndrome is suspected, hospitalization is indicated for the patient. It is important to quickly conduct an examination and relieve life-threatening symptoms in order to stabilize the condition of the expectant mother. In the case of premature pregnancy, measures are required to prevent possible complications in the fetus.

The only effective treatment for HELLP syndrome is termination of pregnancy. Natural childbirth is indicated provided that the uterus and cervix are ripe. In this case, doctors use drugs that stimulate labor. If a woman’s body is not physiologically ready for childbirth, then an emergency caesarean section is performed.

With HELLP syndrome, pregnancy must be terminated, regardless of its duration, within 24 hours. Natural birth is possible only after 34 weeks. In other cases, surgery is indicated.

Immediately upon admission to the hospital, the patient is prescribed corticosteroids (for example, dexamethasone). They significantly reduce the risk of liver damage. In addition, other drugs are used, including droppers, to restore water-salt metabolism, improve blood flow in the uterus and placenta, and calm the nervous system.

Often women undergo transfusions and undergo plasmapheresis - blood filtration using special devices. It cleanses the blood of toxins and helps avoid further complications. It is prescribed for disorders of fat metabolism, a history of repeated gestosis, hypertension, and pathologies of the kidneys and liver.

The newborn also needs help immediately after birth, since HELLP syndrome causes many diseases in infants.

What complications can occur as a result of HELLP syndrome for a mother and her baby?

The consequences of HELLP syndrome are serious for both the woman and her child. There is a risk for the expectant mother:

• pulmonary edema;
• acute renal failure;
• cerebral hemorrhages;
• hematoma formation in the liver;
• liver rupture;
• premature placental abruption;
• lethal outcome.

High blood pressure disrupts blood circulation in the placenta, as a result of which the fetus does not receive the necessary oxygen. This leads to the following complications for the baby:

• hypoxia, or oxygen starvation;
• cerebral hemorrhage during childbirth;
• developmental delay (50% of newborns);
• damage to the nervous system;
• breathing problems in a newborn;
• suffocation;
• thrombocytopenia - a blood disease in which the number of platelets sharply decreases (25% of newborns);
• of death.

Recovery after surgery

Most complications can be avoided thanks to a timely caesarean section. The operation is performed under endotracheal anesthesia - a combined method of anesthesia, in which painkillers enter both the blood and the woman’s respiratory tract. It protects the patient from pain, shock and respiratory failure.

After the operation, the young mother is carefully monitored. Especially in the first two days. At this time, there is still a high risk of complications. With proper treatment, all symptoms disappear within 3–7 days. If after a week all blood, liver and other organ parameters are restored, the patient can be discharged home.

The timing of discharge depends on the condition of the woman and her child.

To prevent HELLP syndrome or minimize severe consequences, follow these recommendations:

• plan and prepare for conception, get examined in advance, lead a healthy lifestyle;
• register for pregnancy on time, follow the doctor’s instructions;
• eat right;
• try to lead an active lifestyle, spend more time outdoors;
• give up bad habits;
• avoid stress;
• from the 20th week, keep a pregnancy diary, enter into it everything that happens to the body (weight changes, pressure surges, fetal movements, the appearance of edema);
• regularly take tests prescribed by your doctor;
• Pay attention to unusual symptoms - abdominal pain, tinnitus, dizziness and others.

Preeclampsia and its complications during pregnancy - video

HELLP syndrome is a fairly rare complication. To detect the disease in a timely manner, take the necessary tests prescribed by the doctor and listen to your condition. If dangerous symptoms occur, consult a doctor immediately. Modern diagnostics and correct treatment tactics in most cases bring positive results.

Makatsaria A.D., Bitsadze V.O., Khizroeva D.Kh.

Obstetrics, gynecology and reproduction. 2014; N2: p.61-68

Summary:

HELLP syndrome among pregnant women with gestosis occurs, according to generalized data from the world literature, in 20-20% of cases and is characterized by high maternal and perinatal mortality. HELLP syndrome usually develops in the third trimester of pregnancy, usually at 35 weeks, and can also occur after childbirth during the normal course of pregnancy. The pathophysiology of the syndrome remains not fully understood. Today, it is believed that the key stage in the formation of HELLP syndrome is endothelial dysfunction. As a result of endothelial damage and activation of the inflammatory response, blood coagulation processes are activated, which leads to the development of coagulopathy, increased platelet consumption, and the formation of platelet-fibrin microthrombi. Perhaps, deepening knowledge about the pathogenesis of HELLP syndrome, developing ideas about pregnancy complications as an extreme manifestation of a systemic response to inflammation, leading to the development of multi-organ dysfunction, will make it possible to develop effective methods for the prevention and intensive treatment of this threatening condition.

HELLP-SYNDROME

Keywords: HELLP syndrome, eclampsia, catastrophic antiphospholipid syndrome, hemolysis.

State Budgetary Educational Institution of Higher Professional Education “First Moscow State Medical University named after I.M. Sechenov" of the Ministry of Health of the Russian Federation, Moscow

Today, thanks to the successes of molecular medicine and detailed studies of the mechanisms of inflammation, the understanding of many diseases, the cause of which has long remained a mystery, has significantly expanded. More and more evidence is emerging that diseases and syndromes such as thrombotic thrombocytopenic purpura (TTP), hemolytic-uremic syndrome, catastrophic antiphospholipid syndrome (CAPS), HELLP syndrome, heparin-induced thrombocytopenia are various manifestations of a universal reaction of the body - a systemic response to inflammation.

Despite the fact that these pathological processes may be based on various genetic and acquired abnormalities (blood clotting factors, complement system, etc.), the development of clinical manifestations is based on a universal reaction of systemic inflammation. The key mechanism of pathogenesis of each of these pathological processes is progressive damage to the endothelium, the development of an inflammatory response and activation of coagulation processes with the development of thrombosis.

Due to the fact that these diseases are relatively rare and, due to the lack of experimental models, remain largely incomprehensible to researchers today, treatment is predominantly imperial, and mortality, despite the successes of theoretical medicine, is high. However, molecular and genetic studies in recent years have made it possible to significantly expand our understanding of the pathogenetic mechanisms of these diseases, without knowledge of which we cannot hope to improve the diagnosis of treatment methods for these pathologies.

In 1954, Pritchard and colleagues first described three cases of preeclampsia, in which intravascular hemolysis, thrombocytopenia, and liver dysfunction were observed. In 1976, the same author described 95 women with preeclampsia, 29% of whom had thrombocytopenia, and 2% had anemia. At the same time, Goodlin described 16 women with severe preeclampsia accompanied by thrombocytopenia and anemia, and called this disease “the great imitator”, since the manifestations of preeclampsia can be unusually varied. The term HELLP syndrome (hemolysis, elevated liver enzymes, low platelets) was first introduced into clinical practice by Weinstein in 1982 as an extremely progressive form of gestosis, accompanied by the development of microangiopathic hemolysis, thrombocytopenia, and increased concentrations of liver enzymes.

HELLP syndrome among pregnant women with gestosis occurs, according to generalized data from the world literature, in 2-20% of cases and is characterized by high maternal (from 3.4 to 24.2%) and perinatal (7.9%) mortality. HELLP syndrome usually develops in the third trimester of pregnancy, usually at 35 weeks, and can also occur after childbirth during the normal course of pregnancy. Thus, according to Sibai et al. (1993), HELLP syndrome can develop both before childbirth (in 30% of cases) and after childbirth (70%). The latter group of women has a higher risk of developing acute renal and respiratory failure. Signs of HELLP syndrome may appear within 7 days. after childbirth and most often appear within the first 48 hours after birth.

HELLP syndrome is more often observed in multiparous women with gestosis, over the age of 25 years, and with a complicated obstetric history. There is evidence of a possible hereditary predisposition to the development of HELLP syndrome. HELLP syndrome is more common among white and Chinese people, much less often (almost 2.2 times) among the East Indian population.

Clinical picture of HELLP syndrome

In addition to the general manifestations of gestosis - edema, proteinuria, hypertension - HELLP syndrome is characterized by hemolysis, thrombocytopenia, and liver damage. These clinical manifestations lead to serious complications, such as the development of eclampsia, renal failure, intracranial hemorrhage, subcapsular hematoma, and the development of disseminated intravascular coagulation syndrome.

The clinical picture of HELLP syndrome is characterized by a rapid increase in symptoms and is often manifested by a sharp deterioration in the condition of the pregnant woman and fetus (see Table 1). Initial manifestations are nonspecific and include headache, fatigue, malaise, nausea, vomiting, abdominal pain and, especially, pain in the right hypochondrium. Early clinical symptoms of HELLP syndrome can be nausea and vomiting (86%), pain in the epigastric region and right hypochondrium (86%), severe swelling (67%). The most characteristic manifestations of the disease are jaundice, vomiting with blood, hemorrhage at injection sites, and increasing liver failure. Neurological symptoms include headache, convulsions, symptoms of damage to cranial nerves, and in severe cases, the development of coma. Visual disturbances, retinal detachment, and vitreous hemorrhages may occur. One of the signs of developing HELLP syndrome may be hepatomegaly and signs of peritoneal irritation. Irritation of the phrenic nerve by the enlarged liver can cause pain to spread to the pericardium, pleura and shoulder, as well as the gallbladder and esophagus.

Table 1. Symptoms of HELLP syndrome.

Often laboratory changes in HELLP syndrome appear long before the described complaints and clinical manifestations. One of the main and first symptoms of HELLP syndrome is hemolysis (microangiopathic hemolytic anemia), which is determined by the presence of wrinkled and deformed red blood cells, fragments of red blood cells (schistocytes), and polychromasia in a peripheral blood smear. The cause of hemolysis is the destruction of red blood cells as they pass through narrowed microvessels with damaged endothelium and fibrin deposits. Fragments of red blood cells accumulate in spasmodic vessels with the release of substances that promote aggregation. The destruction of red blood cells leads to an increase in the content of lactate dehydrogenase and indirect bilirubin in the blood. The accumulation of indirect bilirubin is also promoted by hypoxia, which develops as a result of hemolysis of red blood cells and limits the activity of hepatocyte enzymes. Excess indirect bilirubin causes staining of the skin and mucous membranes.

Impairment of blood flow in the intrahepatic vessels due to the deposition of fibrin in them and the development of hypoxia lead to degeneration of hepatocytes and the appearance of markers of cytolytic syndrome (increased liver enzymes) and hepatocellular failure syndrome (decreased protein synthesizing function, decreased synthesis of blood coagulation factors, leading to the development of bleeding ) . Ischemic liver damage is explained by a decrease in portal blood flow due to fibrin deposition in the hepatic sinuses and spasm of the hepatic artery, which is confirmed by Doppler ultrasound data. In the postpartum period, the tone of the hepatic artery is restored, while the portal blood flow, which normally provides 75% of the hepatic blood flow due to fibrin deposits, is restored much more slowly.

Due to obstruction of blood flow in dystrophically changed hepatocytes, overstretching of the Glissonian capsule occurs, which leads to the appearance of typical complaints of pain in the right hypochondrium, in the epigastrium. An increase in intrahepatic pressure can lead to the formation of a subcapsular hematoma of the liver and its rupture at the slightest mechanical impact (increased intra-abdominal pressure during vaginal delivery - Kristeller’s manual, etc.). Spontaneous liver rupture is a rare but serious complication of HELLP syndrome. According to world literature, liver rupture in HELLP syndrome occurs with a frequency of 1.8%, while the maternal mortality rate is 58-70%.

Thrombocytopenia in HELLP syndrome is caused by platelet depletion due to the formation of microthrombi during endothelial damage and consumption during DIC. A decrease in platelet half-life is characteristic. The detection of an increase in the level of platelet precursors in the peripheral blood indicates overirritation of the platelet germ.

Laboratory changes are most evident in the postpartum period (within 24-48 hours after birth), at the same time the full clinical picture of HELLP syndrome develops. It is interesting that, in contrast to HELLP syndrome, in severe forms of gestosis, regression of laboratory and clinical symptoms occurs during the first day of the postpartum period. In addition, in contrast to the severe form of gestosis, which is most often found in primiparous women, among patients with HELLP syndrome there is a fairly high percentage of multiparous women (42%).

Only one or two typical signs of HELLP syndrome may appear. HELLP syndrome is called “partial” or ELLP syndrome (in the absence of signs of hemolysis). Women with “partial” HELLP syndrome have a more favorable prognosis. Van Pampus et al. (1998) indicate the occurrence of severe complications (eclampsia, placental abruption, cerebral ischemia) in 10% of cases with ELLP syndrome and in 24% of cases with HELLP syndrome. However, other studies do not support differences in outcomes between ELLP and HELLP syndromes.

The classic triad of symptoms of gestosis (edema, proteinuria, hypertension) with HELLP syndrome is detected only in 40-60% of cases. Thus, only 75% of women with HELLP syndrome have blood pressure exceeding 160/110 mmHg. Art., and in 15% diastolic blood pressure is detected
Maternal and perinatal complications of HELLP syndrome are extremely high (see Table 2).

Table 2. Maternal complications in HELLP syndrome, %.

According to generalized data from Egerman et al. (1999), maternal mortality in HELLP syndrome reaches 11%, although according to earlier data Sibai et al. – 37% Perinatal complications are caused by the severity of the mother's condition, premature birth of the fetus (81.6%), and intrauterine growth retardation (31.6%). According to Eeltnic et al. (1993), who studied the level of perinatal mortality in 87 women with HELLP syndrome, perinatal fetal death develops in 10% of cases, and in another 10% of women the child dies in the first week of life. Children born to mothers with HELLP syndrome exhibit characteristic symptoms: thrombocytopenia – in 11-36%, leukopenia – in 12-14%, anemia – in 10%, DIC syndrome – in 11%, somatic pathology – in 58 %, respiratory distress syndrome (36%), instability of the cardiovascular system (51%) is 3-4 times more common. Intensive care of newborns should include the prevention and control of coagulopathy from the very first hours. Thrombocytopenia in newborns with HELLP syndrome occurs in 36% of cases, which can lead to the development of hemorrhages and damage to the nervous system.

According to Abramovici et al. (1999), who analyzed 269 cases of pregnancies complicated by HELLP syndrome, severe gestosis and eclampsia, with timely diagnosis and adequate treatment, the level of perinatal mortality in HELLP syndrome does not exceed the same indicator in severe gestosis and eclampsia.

Pathological picture of HELLP syndrome

Postmortem changes in HELLP syndrome include platelet-fibrin microthrombi and multiple petechial hemorrhages. At autopsy, polyserositis and ascites, bilateral exudative pleurisy, multiple petechial hemorrhages in the peritoneum and pancreatic tissue, subcapsular hematomas and liver ruptures are characteristic.

The classic liver injury associated with HELLP syndrome is periportal or focal parenchymal necrosis. Immunofluorescence studies reveal microthrombi and fibrin deposits in the sinusoids. According to Barton et al. (1992), who studied 11 liver samples obtained by biopsy during cesarean section in women with HELLP syndrome, there was no correlation between the degree of histological changes in the liver and the severity of clinical and laboratory symptoms.

According to Minakami et al. (1988), who examined 41 liver samples from people who died from HELLP syndrome, found it impossible to distinguish histologically between acute fatty liver disease (AFLD) and HELLP syndrome. Both with ACDP and HELLP syndrome, vacuolization and necrosis of hepatocytes are observed. However, if with ARDP these changes are located in the central zone, then with HELLP syndrome, periportal necrosis is present to a greater extent. The authors conclude that the pathogenetic mechanisms of preeclampsia, HELLP syndrome and OBDP are unified. GDRP is a relatively rare pathology that develops in the third trimester of pregnancy. With this pathology, as with HELLP syndrome, emergency delivery is necessary, which can significantly improve the prognosis for the mother and child.

Basics of the pathogenesis of HELLP syndrome

The etiology and pathogenesis of HELLP syndrome remain not fully understood. Currently, endothelial damage and the development of microangiopathy are considered to be a key element in the pathogenesis of HELLP syndrome. Characteristic features of HELLP syndrome are activation of coagulation with fibrin deposition in the lumen of blood vessels, excessive activation of platelets, manifested in their accelerated consumption and the development of thrombocytopenia.

Today, there is more and more evidence about the role of systemic inflammation in the pathogenesis of preeclampsia. Perhaps the basis of HELLP syndrome is excessive progressive activation of inflammatory processes and endothelial dysfunction, which leads to the development of coagulopathy and multiorgan dysfunction. There is also no doubt that the complement system is involved in the pathogenesis of HELLP syndrome. According to Barton et al. (1991), immune complexes in HELLP syndrome are found in the hepatic sinuses and even in endocardial puncture biopsy. Perhaps the autoimmune mechanism of damage involving the complement system is due to an autoimmune reaction to the semi-allograft fetus. Thus, antiplatelet and antiendothelial autoantibodies are detected in the serum of patients with HELLP syndrome. Activation of the complement system has a stimulating effect on leukocytes. In this case, there is an increase in the synthesis of pro-inflammatory cytokines: 11-6, TNF-a, 11-1 (etc.), which contributes to the progression of the inflammatory response. Additional confirmation of the role of inflammation in the pathogenesis of HELLP syndrome is the detection of neutrophilic infiltration of liver tissue during an immunological study.

Thus, today it is believed that the key stage in the formation of HELLP syndrome is endothelial dysfunction. As a result of endothelial damage and activation of the inflammatory response, blood coagulation processes are activated, which leads to the development of coagulopathy, increased platelet consumption, and the formation of platelet-fibrin microthrombi. The destruction of platelets leads to a massive release of vasoconstrictive substances: thromboxane A2, serotonin. Increased platelet activation and endothelial dysfunction lead to imbalance of the thromboxane-prostacyclin system, which is involved in maintaining the balance of the hemostatic system. There is no doubt that intravascular coagulation parallels the development of HELLP syndrome. Thus, DIC syndrome is observed in 38% of women with HELLP syndrome and causes almost all clinical manifestations and severe complications of HELLP syndrome - premature abruption of a normally located placenta, intrauterine fetal death, obstetric hemorrhage, subcansular hematoma of the liver, liver rupture, cerebral hemorrhage . Although changes are most often found in the liver and kidneys in HELLP syndrome, endothelial dysfunction can also develop in other organs, which is accompanied by the development of heart failure, acute respiratory dysgression syndrome, and cerebral ischemia.

Thus, gestosis in itself is a manifestation of multiple organ failure, and the addition of HELLP syndrome indicates an extreme degree of activation of the processes of systemic inflammation and organ damage.

According to Sullivan et al. (1994), who studied 81 women who had suffered HELLP syndrome, subsequent pregnancy in 23% of cases was complicated by the development of gestosis or eclampsia, and in 19% of cases a relapse of HELLP syndrome was observed. However, subsequent studies by Sibai et al. (1995) and Chames et al. (2003) indicate a lower risk of re-development of HELLP syndrome (4-6%). Sibai et al. indicate a higher risk of preterm birth, IUGR, miscarriage, and perinatal mortality in subsequent pregnancies in women who have had HELLP syndrome. A fairly high risk of recurrence of HELLP syndrome and the development of complications in subsequent pregnancies indicates the possible presence of a certain hereditary predisposition in such women. Thus, according to Kraus et al. (1998), women who have had HELLP syndrome exhibit an increased frequency of resistance to activated protein C and a factor V Leiden mutation. Schlembach et al. (2003) found that factor V Leiden mutation is 2 times more common in women with HELLP syndrome compared to healthy pregnant women. In addition, the combination of HELLP syndrome and thrombophilias was associated with a higher risk of developing IUGR. Moessmer et al. (2005) described the development of HELLP syndrome in a woman with a homozygous mutation of the prothrombin gene G20210A. In this case, a heterozygous mutation of the prothrombin gene was discovered in the child. It should be noted that the frequency of prothrombin gene mutations, especially homozygous ones, in the general population is not high. HELLP syndrome is also a fairly rare complication of pregnancy (0.2-0.3%). In addition, the relationship between thrombophilias and an increased risk of HELLP syndrome is not found in all studies. However, the presence of genetic thrombophilias, especially in combination with hemostasis abnormalities in the fetus, can be a serious risk factor for the development of coagulopathy (in particular HELLP syndrome) during pregnancy. Thus, according to Schlembach et al. (2003), thrombophilia in the fetus can contribute to the formation of placental microthrombi, disruption of placental blood flow and the occurrence of IUGR.

Altamura et al. (2005) described a woman with HELLP syndrome, complicated by the development of stroke, in whom a heterozygous mutation of MTHFR and the prothrombin gene was identified. Pregnancy itself is a condition characterized by hypercoagulability and the development of subclinical systemic inflammation. Thus, according to Wiebers et al. (1985), the incidence of stroke in non-pregnant women aged 15 to 44 years is 10.7/1000,000, while during pregnancy the risk of stroke increases 13 times. In the presence of hereditary pre-existing anomalies of hemostasis (genetic thrombophilia, APS), pregnancy can serve as a trigger factor for excessive activation of systemic inflammation processes and the development of coagulopathy, which form the pathogenetic basis of a number of pathologies: HELLP syndrome, preeclampsia, eclampsia, DIC syndrome, IUGR.

On the one hand, HELLP syndrome may be the first manifestation of a hereditarily determined pathology of hemostasis, and on the other hand, genetic analysis for hereditary thrombophilias makes it possible to identify women at risk for the possibility of developing a complicated pregnancy, who require special attention from doctors and specific prevention.

The development of thrombotic microangiopathy, in addition to HELLP syndrome, is also characteristic of TTP, HUS, and is also one of the manifestations of CAPS. This indicates the presence of a single mechanism for the pathogenesis of these diseases. It is known that APS is associated with a high incidence of pregnancy pathologies: IUGR, intrauterine fetal death, premature birth, preeclampsia. In addition, a number of researchers have described cases of the occurrence of HELLP syndrome in women with APS, which once again confirms the importance of hemostasis pathology as a predisposing factor for the occurrence of HELLP syndrome. Koenig et al. (2005) described a woman with APS whose pregnancy was complicated by the development of HELLP syndrome, and after operative delivery the clinical picture of CAPS with infarctions of the liver, gastrointestinal tract and bone marrow due to progressive microangiopathy developed. It should also be taken into account that HELLP syndrome may be the first manifestation of APS. Therefore, in women with HELLP syndrome, a test for antiphospholipid antibodies is necessary.

Diagnosis of HELLP syndrome

Diagnostic criteria for HELLP syndrome are:
1. Severe form of gestosis (preeclampsia, eclampsia).
2. Hemolysis (microangiopathic hemolytic anemia, deformed red blood cells).
3. Increased bilirubin >1.2 mg/dl;
4. Increased lactate dehydrogenase (LDH) >600 U/l.
5. Increase in liver enzymes - aminotransferases - aspartate aminotransferase (ACT) >70 U/l.
6. Thrombocytopenia (platelet count 7. Hemostasiogram:
– prolongation of the g+k indicator of the thromboelastogram;
– prolongation of APTT;
– prolongation of prothrombin time;
– increase in D-dimer content;
– increased content of the thrombin-antithrombin III complex;
– decrease in the concentration of antithrombin III;
– increased level of prothrombin fragments;
– decreased protein C activity (57%);
– circulation of lupus anticoagulant.
8. Determination of the level of daily proteinuria;
9. Ultrasound of the liver.

A characteristic sign of HELLP syndrome is also a decrease in haptoglobin concentration to less than 0.6 g/l.

Martin et al. (1991) analyzed 302 cases of HELLP syndrome and, depending on the severity of thrombocytopenia, identified three degrees of severity of this pregnancy complication: first degree - thrombocytopenia 150-100H109/ml, second degree - 1.00-50H109/ml, third - less than 50H109/ml .

Differential diagnosis HELLP syndrome should be carried out, first of all, with liver diseases - acute fatty liver, intrahepatic cholestatic jaundice; HELLP syndrome should also be differentiated from liver diseases that can worsen during pregnancy, including Budd-Chiari syndrome (hepatic vein thrombosis), viral diseases, cholelithiasis, chronic autoimmune hepatitis, Wilson-Konovalov disease. The combination of hemolysis, increased activity of liver enzymes and thrombocytopenia can also be observed in obstetric sepsis, spontaneous liver ruptures in pregnant women, and systemic lupus erythematosus. In 1991, Goodlin described 11 cases of misdiagnosis of HELLP syndrome in women with acute cardiomyopathy, dissecting aortic aneurysm, cocaine addiction, glomerulonephritis, gangrenous cholecystitis, SLE, and pheochromacytoma. Therefore, when thrombocytopenia, microangiopathic anemia and signs of cytolysis are detected, the diagnosis of HELLP syndrome can only be made after a careful assessment of the clinical picture and exclusion of other causes of these symptoms.

If you suspect HELLP syndrome the pregnant woman must be hospitalized in the intensive care unit (see Table 3).

Table 3. The required amount of research if HELLP syndrome is suspected.

Principles of treatment of HELLP syndrome

The main goal of treating patients with preeclampsia is, first of all, the safety of the mother and the birth of a viable fetus, the condition of which will not require long-term and intensive neonatal care. The initial step in treatment is hospitalization to assess the condition of the mother and fetus. Subsequent therapy should be individualized, depending on the condition and gestational age. The expected result of therapy in most patients with a mild form of the disease should be a successful completion of pregnancy. The results of therapy in patients with severe forms of the disease will depend on both the condition of the mother and fetus at admission, and on the gestational age.

The main problem in the treatment of HELLP syndrome is the fluctuating course of the disease, the unpredictable occurrence of severe maternal complications and high maternal and perinatal mortality. Since there are no reliable clinical and laboratory, clearly defined criteria for the prognosis and course of the disease, the outcome of HELLP syndrome is unpredictable. High maternal morbidity and mortality are mainly due to the development of disseminated intravascular coagulation (DIC); the frequency of development of the acute form of DIC syndrome significantly increases with increasing interval between diagnosis and delivery.

With HELLP syndrome, delivery by cesarean section is carried out regardless of the stage of pregnancy.

Indications for emergency delivery are:
– progressive thrombocytopenia;
– signs of a sharp deterioration in the clinical course of gestosis;
– disturbances of consciousness and severe neurological symptoms;
– progressive deterioration of liver and kidney function;
– pregnancy 34 weeks or more;
– fetal distress.

Conservative management of pregnancy in these cases is associated with an increased risk of eclampsia, placental abruption, respiratory and renal failure, maternal and perinatal mortality. An analysis of recent studies has shown that aggressive tactics lead to a significant reduction in maternal and perinatal mortality rates. Childbirth through the birth canal is possible only with sufficient maturity of the cervix, a thorough assessment of the condition of the fetus and blood flow in the umbilical artery during a Doppler study. Conservative tactics are justified only in cases of fetal immaturity in a situation where there are no signs of disease progression, intrauterine fetal suffering and intensive monitoring is carried out in a specialized obstetric hospital by a qualified obstetrician-gynecologist in close and mandatory collaboration with an anesthesiologist and neonatologist.

The principles of therapy include replenishment of bcc with restoration of microcirculation with plasma substitutes: hydroxyethyl starch, albumin, fresh frozen plasma. Single-group donor red blood cells are used to eliminate anemia with hemoglobin less than 70 g/l. Platelet transfusion is performed when the platelet level decreases to 40 thousand or less. With the progression of multiple organ failure with signs of functional decompensation of the liver and kidneys, an effective treatment method is hemodiafiltration, hormonal therapy with corticosteroids, and antibacterial therapy. Antihypertensive therapy is prescribed individually (see Table 4).

Table 4. Principles of therapy for HELLP syndrome.

Principles of therapy	Specific measures
1. Replenishment of blood volume and restoration of microcirculation	Hydroxyethyl starch 6% and 10%; albumin 5%; fresh frozen donor plasma
2. Elimination of anemia	With Hb
3. Elimination of thrombocytopenia	For thrombocytopenia
4. Prevention and control of internal combustion engine	Fresh frozen plasma transfusion
5. Hormone therapy	Corticosteroids
6. Efferent treatment methods	Plasmapheresis, hemodiafiltration (with progression of multiple organ failure)
7. Antibacterial therapy	Broad-spectrum drugs
8. Antihypertensive therapy	Target blood pressure Dihydralazine, labetalol, nifedipine; sodium nitroprusside (for blood pressure >180/110 mm Hg), magnesium (prevention of seizures)
9. Hemostasis control	Antithrombin 111 (for the purpose of prevention - 1000-1500 IU/day, for treatment the initial dose is 1000-2000 IU/day, then 2000-3000 IU/day), dipyridamole, aspirin
10. Delivery	C-section

The fight against DIC syndrome in combination with detoxification therapy is carried out by conducting therapeutic discrete plasmapheresis with the replacement of 100% of the bcc with donor fresh frozen plasma in an equivalent volume, and in case of hypoproteinemia - with overtransfusion. The use of plasmapheresis in intensive care for HELLP syndrome can reduce maternal mortality in this complication from 75 to 3.4-24.2%.

High-dose intravenous glucocorticoids not only reduce perinatal mortality through the prevention of ARDS, but also reduce maternal mortality, which has been confirmed in five randomized trials. Goodlin et al. (1978) and Clark et al. (1986) describe cases where the use of glucocorticoids (10 mg dexamethasone IV every 12 hours) and the pregnant woman’s observance of complete rest allowed for a transient improvement in the clinical picture (decrease in blood pressure, increase in platelet count, improvement in liver function, increase in diuresis). Data from studies by Magann et al. (1994), Yalcin et al. (1998), Isler et al. (2001) indicate that the use of glucorticoids before and after birth helps reduce the severity of HELLP syndrome, the need for blood transfusion and allows you to prolong pregnancy by 24-48 hours, which is important for the prevention of respiratory distress syndrome of newborns. Isler (2001) showed greater effectiveness of intravenous administration of glucocorticoids compared to intramuscular administration.

It is assumed that the use of glucocorticoids can help restore endothelial function, prevent intravascular destruction of red blood cells and platelets and the progression of SIRS. However, following an improvement in the clinical picture within 24-48 hours of using glucocorticoids, a so-called rebound phenomenon may occur, manifested by a deterioration in the condition of the pregnant woman. Thus, the administration of glucocorticoids does not completely prevent the development of the pathological process, but only briefly improves the clinical picture, creating conditions for more successful delivery.

In most patients with HELLP syndrome, it is recommended to use 10 mg of dexamethasone IV twice with a break of 6 hours, then additionally, twice, 6 mg of dexamethasone IV every 6 hours. In severe HELLP syndrome (thrombocytopenia
In the postpartum period, some clinicians recommend the administration of corticosteroids (4 times intravenous dexamethasone at 12-hour intervals - 10, 10, 5, 5 mg) immediately after birth and transfusion of fresh frozen donor plasma. According to Martin et al. (1994), the use of glucocorticoids in the postpartum period can reduce the risk of complications and maternal mortality.

In the postpartum period, it is necessary to continue monitoring the woman until the clinical and laboratory symptoms completely disappear. This is due to the fact that, unlike gestosis and eclampsia, the symptoms of which usually quickly disappear after delivery, with HELLP syndrome the peak of hemolysis is observed 24-48 hours after birth, which often requires repeated transfusion of red blood cells. In the postpartum period, it is necessary to continue magnesium therapy for 24 hours. The only exceptions are women with renal failure. If hemolysis continues and the platelet count decreases more than 72 hours after delivery, plasmapheresis is indicated.

In conclusion, it should be noted that the success of intensive therapy for HELLP syndrome largely depends on timely diagnosis both before birth and in the postpartum period. Despite close attention to the problem, the etiology and pathogenesis of HELLP syndrome largely remains a mystery. Perhaps, deepening knowledge about the pathogenesis of HELLP syndrome, developing ideas about pregnancy complications as an extreme manifestation of a systemic response to inflammation, leading to the development of multi-organ dysfunction, will make it possible to develop effective methods for the prevention and intensive treatment of this life-threatening condition.

Literature/References:

1. Abramovici D., Friedman S.A., Mercer B.M. et al. Neonatal outcome in severe preeclampsia at 24 to 36 weeks gestation: does the HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome matter? Am. J. Obstet. Gynecol. 1999; 180: 221-225.
2. Altamura C., Vasapollo B., Tibuzzi F. et al. Postpartum cerebellar infarction and haemolysis, elevated liver enzymes, low platelet (HELLP) syndrome. Z. Neurol. Sci. 2005; 26 (1): 40-2.
3. Barton J.R., Riely S.A., Adamec T.A. et al. Hepatic histopathologic condition does not correlate with laboratory abnormalities in HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count. Am. J. Obstet. Gynecol. 1992; 167: 1538-1543.
4. Barton J.R., Sibai B.M. Care of the pregnancy complicated by HELLP syndrome. Obstet. Gynecol. Clin. North. Am. 1991; 18: 165-179.
5. Baxter J.K., Weinstein L. HELLP syndrome: the state of the art. Obstet. Gynecol. Surv. 2004; 59 (12): 838-45.
6. Brandenburg V.M., Frank R.D., Heintz B. et al. HELLP syndrome, multifactorial thrombophilia and postpartum myocardial infarction. J. Perinat. Med., 2004; 32 (2): 181-3.
7. Chames M.C., Haddad B., Barton J.R. et al. Subsequent outcome in women with a history of HELLP syndrome at 28 weeks of gestation. Am. J. Obstet. Gynecol. 2003; 188: 1504-1508.
8. Clark S.L., Phelan J.R., Allen S.H. et al. Ante-partum reversal of hematologic abnormalities associated with the HELLP syndrome: a report of three cases. J. Reprod. Med. 1986; 31: 70-72.
9. Eeltink C.M., van Lingen R.A., Aarnoudse J.G. et al. Maternal haemolysis, elevated liver enzymes and low platelets syndrome: specific problems in the newborn. Eur. J. Pediatr. 1993; 152: 160-163.
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11. Goodlin R.C., Cotton D.B., Haesslein H.C. Seve-re edema-proteinuria-hypertension gestosis. Am. J. Obstet. Gynecol. 1978; 32: 595-598.
12. Goodlin R.C. Preeclampsia as the great impostor. Am. J. Obstet. Gynecol. 1991; 164: 1577-1581.
13. Isler C.M., Barrilleaux P.S., Magann E.F. et al. A prospective, randomized trial comparing the efficacy of dexamethasone and betamethasone for the treatment of antepartum HELLP (hemolysis, elevated liver enzymes, and low platelet count syndrome. Am. J. Obstet. Gynecol. 2001; 184: 1332-1339.
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16. Krauss T., Augustin H.G., Osmers R. et al. Activated protein resistance and factor V Leiden in patients with hemolysis, elevated liver enzymes, low platelets syndrome. Obstet. Gynecol. 1998; 92: 457-460.
17. Le T.T.D., Tieulie N., Costedoat N. et al. The HELLP syndrome in the antiphospholipid syndrome: retrospective study of 16 cases in 15 women. Ann. Rheum. Dis. 2005; 64: 273-278.
18. Magann E.F., Bass D., Chauhan S.P. et al. Antepartum corticosteroids: disease stabilization in patients with the syndrome of hemolysis, elevated liver enzymes, and low platelets (HELLP). Am. J. Obstet. Gynecol. 1994; 71: 1148-1153.
19. Magann E.F., Perry K.G., Meydrech E.F. et al. Postpartum corticosteroids: accelerated recovery from the syndrome of hemolysis, elevated liver enzymes, and low platelets (HELLP). Am. J. Obstet. Gynecol. 1994; 171: 1154-1158.
20. Martin J.N. Jr., Blake P.G., Perry K.G. et al. The natural history of HELLP syndrome: > patterns of disease progression and regression. Am. J. Obstet. Gynecol. 1991; 164: 1500-1513.
21. Minakami H., Oka N., Sato T. et al. Preeclampsia: a microvesicular fat disease of the liver? Am. J. Obstet. Gynecol. 1988; 159: 1043-1047.
22. Moessmer G., Muller B., Kolben M. et al. HELLP syndrome with fetal growth retardation in a woman homozygous for the prothrombin gene variant 20210A. Thromb. Haemost. 2005; 93 (4): 787-8.
23. O Brien J.M., Barton J.R. Controversies with the diagnosis and management of HELLP syndrome. Clin. Obstet. Gynecol. 2005; 48 (2): 460-77.
24. Osmanagaoglu M.A., Osmanagaoglu S., Bozkaya H. Systemic lupus erythematosus complicated by HELLP syndrome. Anaesth. Intensive Care. 2004; 32 (4): 569-74.
25. Schlembach D., Beinder E., Zingsem J. et al. Association of maternal and/or fetal factor V Leiden and G20210A prothrombin mutation with HELLP syndrome and intrauterine growth res--triction. Clin. Sci (Lond). 2003; 105 (3): 279-85.
26. Sibai B.M., Ramadan M.K., Usta I. et al. Maternal morbidity and mortality in 442 pregnancies with hemolysis, elevated liver enzymes, and low platelets (HELLP syndrome). Am. J. Obstet. Gynecol. 1993: 169: 1000-1006.
27. Sibai B.M., Ramadan M.K., Chari R.S. et al. Pregnancies complicated by HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets): subsequent pregnancy outcome and long-term prognosis. Am. J. Obstet. Gynecol. 1995; 172: 125-129.
28. Sullivan S.A., Magann E.F., Perry K.G. et al. The recurrence risk of the syndrome of hemolysis, elevated liver enzymes, and low platelets (HELLP) in subsequent gestations. Am. J. Obstet. Gynecol. 1994; 171: 940-943.
29. Tanner B. Ohler W.G., Hawighorst S., Schaffer U., Knapstein P.G. Complications in HELLP syndrome due to peripartal hemostatic disorder. Centralbl. Gynakol. 1996; 118 (4): 213-20.
30. VanPampus M.G., Wolf H., Westenberg S.M. et al. Maternal and perinatal outcome after expectant management of the HELLP syndrome compared with preeclampsia without HELLP syndrome. Eur. J. Obstet. Gynecol. Reprod. Biol. 1998; 76: 31-36.
31. Wiebers D.O. Ischemic cerebrovascular complications of pregnancy. Arch. Neurol. 1985; 2: 1106-1113.
32. Witsenburg C.P., Rosendaal F.R., Middeldorp J.M. et al. Factor VIII levels and the risk of pre-eclampsia, HELLP syndrome, pregnancy related hypertension and severe intrauterine growth retardation. Thromb. Res. 2005; 115 (5): 387-92.
33. Yalcin O.T., Sener T., Hassa H. et al. Effects of postpartum corticosteroids in patients with HELLP syndrome. Int. J. Gynaecol. Obstet. 1998; 61: 141-148.

HELLP syndrome Makatsariya A.D., Bitsadze V.O., Khizroeva D.Kh. First Moscow State Medical Sechenov University of the Ministry of Health Russian Federation Abstract: the pathophysiology of HELLP syndrome is not well defined. Nowadays endothelial dysfunction if considered the key moment of the development of HELLP-syndrome. Endothelial cell dysfunction results in hypertension, proteinuria, and increased platelet activation and aggregation. Furthermore, activation of the coagulation cascade causes consumption of platelets due to adhesion onto a damaged and activated endothelium, in addition to microangiopathic hemolysis caused by shearing of erythrocytes as they traverse through capillaries laden with platelet-fibrin deposits. Multiorgan microvascular injury and hepatic necrosis causing liver dysfunction contribute to the development of HELLP. Key words: HELLP-syndrome, catastrophic antiphospholipid syndrome, eclampsia, hemolysis.

During pregnancy, a woman's body experiences enormous stress. All systems ensure the health of not only the mother, but also the baby. The development of pathologies during this period of a person’s life occurs in its most severe form. This is due to the limited “safety margin” of the body, as well as the peculiarities of metabolism during gestation. One of the critical conditions in obstetrics is HELP syndrome. Its consonance with the English word “help” is not accidental. Identification of signs of this disorder is most often recorded in the last trimester or in the first week after birth and requires intensive care and hospitalization of the patient. Several serious violations occur at once, which often threaten not only the health of the child, but also the life of the mother.

HELLP syndrome during pregnancy is a rare pathology that manifests itself with serious hemodynamic disturbances and failure of normal liver function. The mortality rate of women in the absence of medical care reaches 100%. If a patient is diagnosed with such a disease, urgent delivery is required, otherwise both mother and child may die. If the syndrome has formed at a late stage of gestosis, they resort to drug stimulation. At earlier stages, a caesarean section is required. Otherwise the consequences are fatal.

Reasons for the development of the disease in pregnant women

HELLP syndrome in obstetrics has not been fully studied. The exact pathogenesis of its occurrence is unknown. Reasons that can trigger the development of complications include:

1. Autoimmune processes that lead to the destruction of the body's own cells. There is a decrease in the number of platelets and red blood cells, which is accompanied by serious hemodynamic disorders.
2. Congenital abnormalities of the functioning of the liver, consisting of failures in the production of enzymes.
3. Thrombosis of blood vessels of the hepatobiliary system.
4. Antiphospholipid syndrome is classified as a separate nosological entity, although in essence it is an autoimmune process. Excessive destruction of the lipid structures of the cell membranes of the body occurs by antibodies.

The development of HELP syndrome is common due to lack of attention to pregnancy complications, for example, preeclampsia. If a woman is not registered with a gynecologist and does not control her own health and the condition of the baby, such a disorder can progress. A direct connection between the disease and a serious increase in blood pressure has not been established. Moreover, the development of HELLP syndrome is often recorded simultaneously with eclampsia.

Risk factors

Some features of a woman’s body also predispose to the occurrence of pathology, such as:

1. First-time mothers rarely face this problem. But recurrence of gestosis can be complicated by HELP syndrome.
2. Multiple pregnancies more often lead to the formation of such disorders than the development of only one child in the uterus.
3. The patient has a history of severe chronic lesions of the cardiovascular system, liver and kidneys.
4. Age over 25 years is a risk factor for gestosis in relation to the further development of hemodynamic disorders.
5. HELP syndrome is more often recorded in women with fair skin than in dark-skinned patients.

Main symptoms

The clinical picture of the disease is associated with the main pathological processes occurring in the body. Decoding the abbreviation HELLP implies the formation of the following problems:

1. H - hemolysis. Hemolysis is the process of breakdown of red blood cells directly in the bloodstream.
2. EL – elevated liver enzymes. An increase in the level of liver enzymes accompanies serious dysfunction of the organ. An increase in enzyme concentration indicates the death of hepatocytes.
3. LP – low platelet levels. A decrease in the level of platelets - cells that stop bleeding. Such a problem can be either a consequence of the formation of pathological clots and destruction of structures in blood vessels, or it can occur due to insufficient production of platelets by the red bone marrow.

A similar cascade of reactions is accompanied by the following symptoms:

1. Nausea and vomiting normally occur with toxicosis in early pregnancy. However, with HELP syndrome, they can recur in the last trimester.
2. Migraine and dizziness are common symptoms that are often the first signal of the development of preeclampsia and other dangerous hemodynamic disorders.
3. At later stages, icteric staining of the mucous membranes appears. This is due to the active release of the pigment bilirubin, which is found in red blood cells and liver cells, into the blood.
4. The appearance of hematomas and petechiae at the site of minor injuries, such as abrasions or injections. Such a clinical sign indicates disturbances in the coagulation system.
5. The most severe symptom of HELP syndrome is the development of seizures. It is associated with a violation of oxygen transport to brain cells, since there is a decrease in the level of red blood cells that perform this function.

Diagnostics

After the symptoms of the disease appear, doctors have very little time left to save the woman and child. Significant deterioration and death may occur as early as 12 hours after the onset of clinical signs. The diagnosis is made on the basis of anamnesis and hematological tests, which reveal changes characteristic of the problem.

HELP syndrome in pregnant women requires visual diagnosis. Ultrasound allows you to assess the presence of organic damage to the liver and thrombosis of its vessels. Ultrasound examination of the fetus is also recommended.

The difficulty in confirming the occurrence of the disease comes down to the fact that diagnosis is often based on different criteria. Although there are special recommendations both for confirming HELLP syndrome and for its treatment, in many sources the authors refer to various pathological changes. Some argue that the diagnosis is made solely on the basis of characteristic abnormalities in the biochemical blood test, which include increased levels of liver enzymes and bilirubin. Others are inclined to believe that to confirm HELLP syndrome, a combination of pronounced severe preeclampsia with hematological parameters characteristic of this disorder is required. However, in a number of studies describing the problem, there was no indication of suspicion or confirmation of the presence of hemolysis in women with this disease. That is, in some patients, when the disorder develops, the breakdown of red blood cells in the bloodstream is completely absent.

Diagnosis of HELP syndrome requires an integrated approach, although one should focus not only on the clinical manifestations of the disease and the patient’s medical history, but also on the presence of characteristic abnormalities in laboratory tests.

Treatment methods

The problem in gynecology is considered an emergency, so special attention is paid to it in the educational process of doctors. Doctors either stimulate natural labor by administering appropriate medications, or resort to surgery to remove the fetus from the uterus.

Obstetric tactics depend on the time of development of gestosis:

1. If the period exceeds 34 weeks, then prostaglandins and epidural anesthesia are used, since the natural process is preferred. There is no point in waiting: a woman’s condition can worsen at any moment. In severe cases, the patient is placed in the intensive care unit.
2. When HELP syndrome is detected between 27 and 34 weeks, the mother’s condition is stabilized, as well as the fetus is prepared for a cesarean section. Indications for postponing surgery are eclampsia, the formation of disseminated intravascular coagulation, and bleeding.
3. If the pathology develops before 27 weeks, after the use of glucocorticoids, surgery is performed to adapt the baby’s underdeveloped lungs.

HELP syndrome can also occur after childbirth. In such cases, treatment is simplified by the fact that only the mother needs to be saved.

Complications

In the absence of medical care or non-compliance with doctors' recommendations, dysfunction of the mother's liver, kidneys and lungs occurs. The child suffers from developmental delays, respiratory distress syndrome and asphyxia. In 20% of cases, the fetus dies even with timely assistance if there are significant changes in the hemodynamics of the female body.

Recovery process after surgery

After delivery, monitoring of the patient's condition is required, since HELLP syndrome may develop later. Symptomatic treatment is carried out, hormonal drugs are used to normalize blood counts. The timing of a woman’s discharge from the hospital depends on her well-being and the health of the baby.

Prevention and prognosis

Despite the insignificant frequency of detection of HELP syndrome in pregnant women, much attention is paid to it. Preventing the formation of the disease comes down to following the rules of a healthy lifestyle and timely consultation with a doctor. The prognosis depends on the duration of gestosis, as well as on the presence of chronic diseases in the woman.

HELLP syndrome is a rare and very dangerous pathology that occurs during pregnancy. The disease makes itself felt in the third trimester and is characterized by a rapid increase in symptoms. In severe cases, HELLP syndrome can lead to the death of a woman and child.

Causes

At the moment, experts have not been able to find out the exact cause of the development of HELLP syndrome. Among all the possible factors in the formation of this pathology, the following aspects deserve attention:

• immunosuppression (decreased lymphocyte count);
• autoimmune damage (destruction of one’s own cells by aggressive antibodies);
• disturbances in the hemostatic system (pathology of the blood coagulation system and thrombosis in the vessels of the liver);
• antiphospholipid syndrome;
• taking medications (in particular tetracyclines);
• heredity (congenital deficiency of liver enzymes).

There are several risk factors for developing HELLP syndrome:

• woman's age over 25 years;
• bright skin;
• multiple pregnancy;
• multiple births (3 or more);
• severe extragenital diseases (including liver and heart diseases).

HELLP syndrome is considered one of the indicators of a woman’s body’s adaptation to pregnancy. Probably, the conditions for the development of gestosis and HELLP syndrome as its complications are laid in the early stages of gestation. Often, a pregnancy that ends in the formation of such a dangerous pathology proceeds unfavorably from the very beginning. When analyzing the medical history of many women, a previous threat of miscarriage, disturbances in uteroplacental blood flow and other complications of this pregnancy are revealed.

Development mechanisms

There are more than 30 theories trying to explain the occurrence of HELLP syndrome in pregnant women, but none of them has received reliable confirmation. Perhaps one day scientists will be able to solve this mystery, but for now, practicing doctors have to rely on available data. Only one thing is known for sure - HELLP syndrome is one of the most severe complications of preeclampsia. The causes of gestosis during pregnancy are also still not fully understood.

Among all theories, the most popular version is about autoimmune damage to the endothelium (the inner layer of blood vessels). When exposed to some damaging factor, a complex chain of pathological processes is triggered, leading to a narrowing of the blood vessels of the placenta. Ischemia develops, blood clots form, and oxygen supply to all fetal tissues is disrupted. At the same time, liver damage, organ necrosis and the development of toxic hepatosis occur.

What is the risk of endothelial damage? First of all, the formation of microthrombi with a subsequent decrease in the level of platelets (blood platelets responsible for blood clotting). As a result of all processes, a persistent generalized vasospasm is formed. Brain swelling occurs, blood pressure rises sharply, and liver functioning is disrupted. Multiple organ failure develops - a condition in which all important organs stop working normally. The only way to save a woman and her baby is an emergency caesarean section.

Symptoms

HELLP syndrome got its name from the name of the main symptoms of the pathology (translated from English):

• H – hemolysis;
• EL – activation of liver enzymes;
• LP – thrombocytopenia (decreased platelet level).

HELLP syndrome occurs in the third trimester of pregnancy. Most often, the disease is detected after 35 weeks, but earlier manifestation of the disease is also possible. This pathology is characterized by a rapid increase in all symptoms and rapid failure of all internal organs.

HELLP syndrome does not develop for no apparent reason. It is always preceded by gestosis, a specific complication of pregnancy. Gestosis in expectant mothers makes itself felt with a triad of symptoms:

• peripheral edema;
• arterial hypertension;
• renal dysfunction.

Preeclampsia occurs after 20 weeks of pregnancy. The shorter the gestational age, the more severe the disease and the higher the likelihood of complications. In the initial stages, gestosis is manifested by swelling of the feet and legs, as well as rapid weight gain. Rapid weight gain during pregnancy (more than 500 g per week) indicates the formation of hidden edema and is one of the typical symptoms of gestosis.

An important point: isolated edema cannot be considered a manifestation of gestosis. During pregnancy, edema syndrome develops in many women, but not all lead to the development of a dangerous pathology. Preeclampsia is spoken of when swelling of the feet and legs is accompanied by an increase in blood pressure. In this case, the woman should be under constant medical supervision so as not to miss the development of complications.

Impaired kidney function is a late sign of gestosis. During examination, protein appears in the urine of a pregnant woman, and the higher its concentration, the more severe the condition of the expectant mother. To ensure timely detection of protein, all women are recommended to undergo regular urine testing (every 2 weeks until 30 weeks and every week after 30 weeks).

The primary symptoms of HELLP syndrome are not very specific:

• nausea;
• vomit;
• pain in the epigastric (epigastric) region;
• pain in the right hypochondrium;
• general weakness;
• swelling;
• headache;
• increased excitability.

Few expectant mothers attach importance to such symptoms. Nausea and vomiting are attributed to a general malaise common to all pregnant women. Many women are guilty of overeating or eating stale food. Meanwhile, pathological processes are launched in the body, leading to the appearance of other symptoms:

• jaundice;
• vomiting blood;
• increased blood pressure;
• bruises and bruises at injection sites;
• the appearance of blood in the urine;
• blurred vision;
• confusion, delirium;
• convulsions.

In the absence of adequate help, a pregnant woman loses consciousness. Liver failure develops, leading to the cessation of organ functioning. Damage to the nervous system contributes to the development of coma, from which it will be quite difficult to pull the patient out.

Complications

The progression of HELLP syndrome can lead to the development of serious complications:

• coma;
• pulmonary edema;
• cerebral edema;
• liver failure;
• renal failure;
• liver rupture;
• bleeding;
• hemorrhages in vital organs.

Bleeding is one of the manifestations of DIC syndrome. With the development of this pathology, blood clots form, which damage internal organs and tissues and ultimately lead to increased bleeding. DIC syndrome inevitably affects all systems of the body and provokes massive bleeding of various locations (lungs, liver, stomach, etc.). Particularly dangerous is hemorrhage in the brain with damage to important structures of the central nervous system.

Acute renal failure is a disorder of kidney function, leading to a decrease in the amount of urine and poisoning of the body with dangerous nitrogenous compounds. The condition is extremely dangerous and can cause the death of a woman.

Acute liver failure occurs when the parenchyma (internal tissue) of the liver is damaged. Damage to the organ leads to impaired consciousness, the development of seizures and coma. It is quite rare to save a patient who has fallen into a hepatic coma.

Liver damage can lead not only to disruption of the central nervous system, but also to other dangerous consequences. A change in blood flow in the hepatic vessels leads to stretching of the organ capsule and its further rupture. A liver rupture is accompanied by severe bleeding and is a life-threatening condition. In such a situation, emergency assistance from a surgeon and resuscitator is required.

Complications of pregnancy and consequences for the fetus

It is impossible to maintain pregnancy during the manifestation of HELLP syndrome. If pathology is detected, an emergency caesarean section is performed regardless of the stage of pregnancy. Delay in this situation can lead to the death of the woman and child. The operation is performed against the background of infusion therapy under general anesthesia.

In the case of progressive HELLP syndrome, placental abruption inevitably develops. In this condition, the placenta separates from its attachment in the uterus before the baby is born. Detachment of the fetal place leads to the following symptoms:

• bloody discharge from the genital tract (intensity depends on the size of the detachment);
• abdominal pain;
• increased uterine tone;
• decreased blood pressure;
• increased heart rate;
• dyspnea;
• pronounced weakness.

Massive bleeding due to placental abruption can lead to loss of consciousness and seizures. The baby's condition progressively worsens. Hypoxia develops, leading to damage to important brain structures. If more than 1/3 of the placenta is detached, the fetus dies.

Placental abruption threatens not only the life of the child. Multiple hemorrhages lead to the formation of a special pathology - Kuveler's uterus. The wall of the uterus is saturated with blood from damaged vessels of the placenta. Such a uterus is not capable of contracting. If such a dangerous condition develops, an emergency caesarean section is performed with complete removal of the uterus. It is not always possible to save a child during the development of Kuveler's uterus.

Diagnostics

Laboratory changes in HELLP syndrome occur before the first clinical symptoms appear. General and biochemical blood tests, as well as a coagulogram, help to recognize pathology in the early stages. Blood for analysis is taken from a vein on an empty stomach. The examination reveals characteristic signs of HELLP syndrome:

• hemolysis (the appearance in the blood of deformed erythrocytes - red blood cells that carry oxygen);
• decrease in the number of red blood cells;
• slowing down ESR (erythrocyte sedimentation rate);
• decrease in platelets (cells responsible for blood clotting);
• increased levels of liver enzymes (ALT and AST);
• increased alkaline phosphatase activity;
• increase in bilirubin concentration;
• increased concentration of nitrogenous substances in the blood;
• changes in the concentration of blood clotting factors.

If HELLP syndrome is suspected, all studies are carried out on an emergency basis. Blood is taken from a vein in compliance with all rules, after which it is quickly delivered to the laboratory. Within a short time, the doctor receives the results of the analysis and chooses the optimal tactics for further management of the patient.

Other additional studies:

• Ultrasound of the abdominal cavity (to detect liver hematoma);
• Ultrasound of the kidneys;
• computed tomography (to exclude other dangerous conditions not associated with HELLP syndrome);
• Fetal ultrasound;
• Doppler ultrasound (to assess blood flow in the placenta);
• CTG (to assess fetal heartbeat).

Treatment methods

The goal of treatment for HELLP syndrome is to restore impaired hemostasis (the internal environment of the body) and prevent the development of dangerous complications. All therapy is carried out simultaneously with emergency delivery. With the development of HELLP syndrome, a cesarean section is indicated, regardless of the stage of pregnancy.

Drug therapy takes place in several stages:

1. Infusion therapy (intravenous administration of drugs to restore circulating blood volume and normalize hemostasis).
2. Cell membrane stabilizers (high dose corticosteroids).
3. Hepatoprotectors (drugs that protect liver cells from destruction).
4. Antibacterial drugs (for the prevention and treatment of infectious complications).
5. Drugs affecting the blood coagulation system.
6. Protease inhibitors (drugs that reduce the activity of certain enzymes).

The dosage of drugs is selected individually, taking into account the severity of the pathology. During therapy, constant monitoring of the condition of the woman and fetus is mandatory. Control does not decrease after delivery. After the operation, the woman is transferred to the intensive care ward, where she continues to be monitored by specialists around the clock.

Caesarean section during the development of HELLP syndrome is carried out very carefully. The operation is usually performed under general anesthesia. In special cases, the doctor may use spinal or epidural anesthesia. It should be remembered that in this case the risk of developing hemorrhages under the membranes of the spinal cord increases.

The success of intensive therapy for HELLP syndrome largely depends on the timely diagnosis of this dangerous condition. The sooner the pathology is detected, the greater the chance of a successful outcome. All women at risk of developing HELLP syndrome should visit their doctor regularly and report any changes in their health. If your condition suddenly worsens, you should call an ambulance.

Prevention and prognosis

Specific prevention of HELLP syndrome has not been developed. The only way to prevent the development of this dangerous condition is timely treatment of gestosis. In severe cases, therapy for gestosis is carried out in a hospital.

Timely delivery and competent intensive care can save the life of a woman and child. After childbirth, there is a rapid disappearance of all symptoms of the pathology. 3-7 days after the birth of the child, all laboratory parameters return to normal. The risk of recurrence of HELLP syndrome remains during the second and subsequent pregnancies.

The term HELLP (Hemolysis, Elevated Liver enzymes and Low Platelets) - hemolysis, increased activity of liver enzymes (enzymes) and thrombocytopenia - is associated with an extremely severe form of preeclampsia and eclampsia. Back in 1893, G. Schmorl described the characteristic clinical picture of this syndrome, and the term HELLP (taking into account pathogenesis) was proposed by L. Weinstein (1985).

M.V. Mayorov, antenatal clinic of city clinic No. 5, Kharkov

Domestic literature contains very little information about HELLP syndrome, most often limited to brief mentions. This topic was considered in more detail by the luminaries of Russian anesthesiology and resuscitation A.P. Zilber and E.M. Shifman, as well as the chief obstetrician-gynecologist of the Ministry of Health of Ukraine V.V. Kaminsky.

Sad as it may be, inexorable statistics indicate the annual death of approximately 585 thousand women in the world, in one way or another related to pregnancy and childbirth. The main causes of maternal mortality in our country are: obstetric sepsis, bleeding, gestosis, as well as extragenital diseases. In severe forms of gestosis, HELLP syndrome accounts for 4 to 12% of cases and is characterized by high maternal mortality (according to various authors, from 24 to 75% of cases).

A consequence of the lack of knowledge about the clinical and laboratory manifestations of the described symptom complex in recent years is the overdiagnosis of HELLP syndrome. The clinical course of severe forms of preeclampsia can be very diverse. That is why the diagnosis of severe gestosis with HELLP syndrome is often erroneous. In reality, the described pathology may hide hepatitis, fatty hepatosis of pregnancy, hereditary thrombocytopenic purpura, etc. Often, “under the guise” of HELLP syndrome, obstetric sepsis or other pathology remains unrecognized.

Consequently, the detection of a triad in pregnant women - hemolysis, hepatic hyperenzymemia and thrombocytopenia - should not yet mean the immediate establishment of an unconditional diagnosis of “HELLP syndrome”. Only a careful and thoughtful clinical and physiological interpretation of these symptoms in each specific case allows us to differentiate it as a form of preeclampsia, which in advanced cases is a variant of severe multiple organ failure.

Differential diagnosis of HELLP syndrome, according to V.V. Kaminsky et al. , should be carried out with the following diseases:

• uncontrollable vomiting of pregnant women (in the first trimester);
• intrahepatic cholestasis (in the first trimester of pregnancy);
• cholelithiasis (at any stage of pregnancy);
• Dabin-Johnson syndrome (in the 2nd or 3rd trimester);
• acute fatty liver degeneration of pregnant women;
• viral hepatitis;
• drug-induced hepatitis;
• chronic liver disease (cirrhosis);
• Budd-Chiari syndrome;
• urolithiasis;
• gastritis;
• idiopathic thrombocytopenic purpura;
• hemolytic uremic syndrome;
• systemic lupus erythematosus.

Most researchers consider HELLP syndrome as a complication or as an atypical variant of gestosis, believing that it is based on generalized arteriolospasm, combined with hemoconcentration and hypovolemia, the development of a hypokinetic type of blood circulation, endothelial damage and the occurrence of respiratory failure, including pulmonary edema.

In typical cases, HELLP syndrome develops in multiparous women with preeclampsia, over the age of 25 years, with a burdened obstetric history. Clinical manifestations occur in 31% of cases before delivery; in the postpartum period - in 69% of cases.

Quite convincing is the point of view that pregnancy is a case of allotransplantation, and HELLP syndrome as an autoimmune reaction manifests itself as an exacerbation in the postpartum period. The autoimmune mechanism of endothelial damage, hypovolemia with blood thickening and the formation of microthrombi with subsequent fibrinolysis (disseminated intravascular coagulation (DIC)) are the main stages of the development of HELLP syndrome in severe forms of gestosis.

The destruction of platelets leads to the release of thromboxanes and imbalance of the thromboxane-prostacyclin system, which causes: generalized spasm of arterioles with increased arterial hypertension (AH), cerebral edema and convulsions; deterioration of uteroplacental blood flow; increased platelet aggregation, fibrin and red blood cell deposition, mainly in the placenta, kidneys and liver. These changes cause profound dysfunction of these organs, creating a vicious circle that can only be broken at a certain stage by terminating the pregnancy.

HELLP syndrome is characterized by the presence of multiple organ disorders, in particular from:

• Central nervous system: headache, blurred vision, hyperreflexia, convulsions. The cause of these disorders is vasospasm and hypoxia, and not cerebral edema, as previously thought.
• Respiratory system: the lungs remain intact for a long time. Edema of the upper respiratory tract and pulmonary edema may develop (usually after delivery). The development of respiratory distress syndrome is often observed.
• Of cardio-vascular system: generalized arteriolospasm leads to a decrease in circulating blood volume and tissue edema. The total peripheral vascular resistance and stroke volume increase, as a result of which the load on the left ventricle increases. Against this background, the development of diastolic dysfunction is possible.
• Hemostasis systems: Thrombocytopenia, as well as qualitative disorders of platelet function, are common. In severe cases, the development of disseminated intravascular coagulation syndrome is often observed.
• Liver: there is a decrease in the activity of liver enzymes with an increase in their level in the serum; areas of ischemia and even necrosis may develop. Spontaneous liver rupture is rare, but its outcome is almost always fatal.
• Kidney: Proteinuria indicates vascular damage to the glomerulus. Oliguria is more often associated with hypovolemia and reduced renal blood flow. Preeclampsia often progresses to acute renal failure.

Clinical signs and symptoms include complaints of spontaneous pain and tenderness on palpation in the epigastrium and right hypochondrium, jaundice, hyperbilirubinemia, proteinuria, hematuria, hypertension, anemia, nausea, vomiting; There may be hemorrhages at the injection sites.

For diagnosing HELLP syndrome The following standard laboratory data are required:

• hemolysis (determined by analyzing a peripheral blood smear);
• increased bilirubin content;
• increased levels of lactate dehydrogenase;
• elevated levels of alanine aminotransferase and aspartate aminotransferase;
• low platelet count (<100х10 9 /л).

In some cases, not the entire complex of classical signs of HELLP syndrome appears. Then, in the absence of hemolysis of erythrocytes, the name “ELLP syndrome” is used, in the absence of thrombocytopenia – “HEL syndrome”. It should be remembered that in 15% of patients with HELLP syndrome, hypertension may be absent or insignificant.

When carrying out differential diagnosis, it is necessary to take into account that thrombocytopenia and impaired liver function reach a maximum in HELLP syndrome 24-48 hours after birth, and in typical severe gestosis, on the contrary, there is a positive dynamics of these indicators during the first days of the postpartum period. Timely diagnosis of HELLP syndrome significantly improves the results of its intensive care. At the same time, according to A.P. Zilber (1999), sometimes slight thrombocytopenia or a moderate increase in the activity of liver enzymes in pregnant women “excites medical passions to diagnose HELLP syndrome.”

Early recognition of HELLP syndrome plays a very important role in preventing possible serious consequences for the life of the mother and child in the future. Treatment is carried out by an obstetrician-gynecologist together with an anesthesiologist-resuscitator, and if necessary, related specialists are involved - an ophthalmologist, a neurologist, etc.

V.V. Kaminsky et al. A detailed and clear algorithm of actions has been developed after the diagnosis of “HELLP syndrome” has been established, which allows us to answer the question: what to do? This algorithm includes:

• elimination of decompensation of multiple organ failure;
• it is possible to completely stabilize the patient’s condition;
• prevention of possible complications for the mother and fetus;
• delivery.

It should be remembered that the only pathogenetic treatment method is termination of pregnancy, i.e. delivery. Most authors emphasize that when a diagnosis of HELLP syndrome is made, pregnancy should be terminated within 24 hours, regardless of its duration. All other organizational and therapeutic measures are essentially preparation for delivery, which must be urgent, because during childbirth, as a rule, the severity of gestosis increases.

The method of delivery for a “mature” cervix is ​​through the natural birth canal, otherwise - cesarean section. After the birth of the placenta, curettage of the uterine cavity is mandatory.

It is necessary to constantly remember possible complications of HELLP syndrome, which is fraught with maternal mortality:

• DIC syndrome and uterine bleeding;
• placental abruption;
• acute hepatic-renal failure;
• pulmonary edema;
• pleural effusion (exudative pleurisy);
• respiratory distress syndrome;
• subcapsular hematoma of the liver with its rupture and intra-abdominal bleeding;
• retinal disinsertion;
• cerebral hemorrhage.

On the part of the fetus, intrauterine growth retardation and intrauterine death are observed; newborns often develop bleeding and cerebral hemorrhages.

The main goals of pathogenetic therapy for HELLP syndrome: elimination of hemolysis and thrombotic microangiopathy, prevention of multiple organ multisystem dysfunction syndrome, optimization of neurological status and excretory function of the kidneys, normalization of blood pressure.

Intensive preoperative preparation, as well as intensive therapy after delivery, are aimed at many pathogenetic links and include the following components:

• strictly individualized antihypertensive therapy;
• reduction of hypovolemia, hypoproteinemia, intravascular hemolysis;
• correction of metabolic acidosis;
• appropriate infusion and transfusion therapy;
• antispasmodics, antiplatelet agents;
• stabilization of hemostasis indicators;
• rheocorrection of blood (anticoagulants and antiplatelet agents, in particular low molecular weight heparins [fraxiparin], pentoxifylline [trental], etc.);
• antibiotic therapy to prevent infectious complications (aminoglycosides are excluded, given their nephro- and hepatotoxicity);
• hepatostabilizing therapy, in particular large doses of glucocorticosteroids - until hepatic cytolysis is stabilized and thrombocytopenia is eliminated;
• protease inhibitors (contrical, gordox, trasylol);
• hepatoprotectors, cerebroprotectors and nootropics, vitamin complex (in high doses);
• magnesium therapy - according to the classical obstetric scheme;
• according to appropriate indications - plasmapheresis, hemodialysis.

For delivery, exclusively endotracheal anesthesia with minimal use of hepatotoxic anesthetics is recommended, as well as prolonged artificial ventilation in the postoperative period with intensive differentiated therapy.

The list of references is in the editorial office