HELLP syndrome

Among the complications that arise in the last trimester of pregnancy is the so-called HELLP syndrome, which can be dangerous for both mother and child. [1]

Epidemiology

HELLP syndrome occurs in 0.5-0.9% of pregnancies, and the incidence increases to 15% in pregnant women with preeclampsia and 30-50% in eclampsia. In two thirds of cases, the syndrome occurs in the antenatal period. [2]

Causes HELLP syndrome

In this syndrome in late pregnancy, and rarely within two to three days after delivery, there is destruction of blood red blood cells - hemolysis, increased levels of liver enzymes and significantly reduced number of platelets in the blood (below 100,000/μL).

To date, the exact causes of HELLP syndrome (abbreviation for Hemolysis, Elevated Liver enzymes, Low Platelet) are unknown. - Hemolysis, Elevated Liver enzymes, Low Platelet) is unknown, and according to experts of the professional association ACOG (American College of Obstetricians and Gynecologists), it is a complication or a severe form of pre-eclampsia or nephropathy of pregnancy - with a combination of elevated BP and proteinuria (high levels of protein in the urine) with other manifestations.

Read - Preeclampsia and high blood pressure

Although the etiology of platelet reduction - thrombocytopenia in pregnancy (which occurs in 8-10% of cases) has been attributed to the effects of hormones, autoimmune or allergic reactions, deficiency of folic acid salts (folate) and vitamin B12 deficiency.

And destruction of blood red blood cells may be the result of microangiopathic hemolytic anemia of an autoimmune nature. [3]

Risk factors

When the etiology is not fully elucidated to the risk factors for the development of this syndrome experts include:

• The presence of pre-eclampsia (which occurs in 12-25% of cases) or eclampsia.
• a second pregnancy;
• multiple pregnancies;
• mother's age ˃ 35 years;
• diabetes;
• obesity;
• gestosis and unfavorable pregnancy outcome in the history.

Pathogenesis

There are versions of the pathogenesis of both preeclampsia and HELLP syndrome, including uteroplacental ischemia, defects in placental formation, vascular remodeling, and mechanisms due to immune responses.

The main version is considered to be insufficient penetration (invasion) of uterine arterial vessels into the placenta, impaired perfusion of the placenta and the development of its ischemia with activation of the hypoxia transcription factor HIF-1, which modulates the cellular response to hypoxia.

Also see. - Pathogenesis of placental insufficiency

In addition, impaired angiogenesis and endothelial (inner layer) function of blood vessels during pregnancy may be associated with a deficiency of placental growth factor (PIGF) and vascular endothelial growth factor (VEGF), as well as with the activation of the complement system in the peripheral blood, which provides a link between innate immunity and adaptive immunity. Endothelial dysfunction leads to aggregation (sticking) of platelets and increased levels of thromboxane (which narrows blood vessels) produced by them.

Another version concerns secondary thrombotic microangiopathy: platelet aggregation provokes occlusion (blockage) of capillaries and arterioles of the liver, resulting in microangiopathic hemolytic anemia. Autoimmune reaction - binding to erythrocytes of immunoglobulins IgG, IgM or IgA produced by lymphocytic plasmocytes of the immune system - also plays an important role in its occurrence.

The following gene mutations are considered to be involved in the mechanisms of development of the complication of preeclampsia in the form of this syndrome: TLR4 gene associated with innate immunity reactions; VEGF gene - vascular endothelial growth factor; FAS gene - receptor of programmed cell apoptosis; leukocyte antigen differentiation cluster gene CD95; beta-globulin proaccelerin gene - blood coagulation factor V, etc. [4]

Symptoms HELLP syndrome

The first signs of HELLP syndrome are general malaise and/or increased fatigue.

In most cases, the following symptoms are noted:

• high blood pressure;
• headache;
• swelling, especially of the upper extremities and face;
• weight gain;
• Epigastric pain on the right side (in the right subcostal area);
• nausea and vomiting;
• blurred vision.

In the advanced stage of the syndrome, there may be seizures and confusion.

It should be borne in mind that in some pregnant women in the clinical picture of the syndrome may not have all the signs, and then it is called partial HELLP-syndrome. [5]

Complications and consequences

In the mother, HELLP syndrome can lead to complications such as:

• placental abruption;
• severe postpartum hemorrhaging;
• Disseminated intravascular coagulation syndrome (DIC);
• functional failure of the liver and kidneys;
• pulmonary edema;
• Adult respiratory distress syndrome;
• hypoglycemia;
• Subcapsular hematoma (accumulation of blood between the liver parenchyma and the surrounding capsule) and liver rupture;
• brain hemorrhage.

The consequences for infants are prematurity, intrauterine developmental delay, neonatal respiratory distress syndrome, and neonatal intraventricular cerebral hemorrhage. [6]

Diagnostics HELLP syndrome

The criteria for clinical diagnosis of HELLP-syndrome are pain in the epigastric region, as well as nausea and vomiting, accompanied by microangiopathic hemolytic anemia, thrombocytopenia, the presence of destroyed erythrocytes in the blood and abnormal liver function parameters.

The diagnosis is verified by blood tests for platelet, hemoglobin and red blood cell counts in plasma (hematocrit); peripheral blood smear (to detect destroyed red blood cells); total blood bilirubin; blood tests for liver tests. Urinalysis for proteins and urobilinogen is necessary.

To exclude other pathologic conditions, laboratory tests of croci samples for prothrombin time, the presence of fibrin breakdown fragments (D-dimer), antibodies (immunoglobulins IgG and IgM) to beta-2 glycoprotein, glucose, fibrinogen, urea, ammonia are performed.

Instrumental diagnostics include uterine ultrasound, CT or MRI of the liver, ECG, cardiotocography.

Differential diagnosis

Differential diagnosis is performed with idiopathic thrombocytopenic purpura, hemolytic-uremic and antiphospholipid syndromes, SLE, acute cholecystitis, hepatitis and acute fatty hepatosis of pregnant women (Sheehan's syndrome). [7]

Treatment HELLP syndrome

Once a diagnosis of HELLP syndrome is confirmed, its treatment can vary depending on the severity of symptoms and the length of labor. And the best way to prevent complications is considered to be an accelerated delivery (most often by cesarean section), as most symptoms subside and disappear a few days or weeks after delivery. But in many cases, the baby is born prematurely.

Corticosteroids can be used to treat the syndrome - if the symptoms are mild or the gestational age of the child is less than 34 weeks (w/v injection of Dexamethasone twice a day). And to control blood pressure (if it is stable above 160/110 mmHg) - antihypertensive drugs.

Pregnant women with this syndrome require hospitalization and close observation of their condition and monitoring of red blood cell, platelet, and liver enzyme levels.

Severe cases may require ventilator or plasmapheresis, and in case of intense bleeding - blood transfusion (red blood cells, platelets, plasma), so emergency care for HELLP syndrome is carried out in the intensive care unit. [8]

Prevention

HELLP syndrome cannot be prevented in most pregnant women because of its unknown etiology. But pregravidarial preparation - examination before the planned pregnancy, as well as a healthy lifestyle and proper diet can somewhat reduce the risk of its development.

Forecast

The key to a good prognosis for HELLP syndrome is early detection. If treatment is started at an early stage, most women recover completely. However, maternal mortality remains quite high (up to 25% of cases); and intrauterine fetal death at late term and neonatal mortality in the first seven days after delivery is estimated at 35-40%.

Pregnant women with the full "set" of the syndrome - hemolysis, thrombocytopenia, and elevated liver enzymes - have worse outcomes than those with partial syndrome.

Patients with HELLP syndrome should be warned of the risk of developing it in subsequent pregnancies, which is estimated at 19-27%.