Hellp syndrome O14.2

Liver rupture in pregnant women was described for the first time in 1844. Around 75 % of those affected had previously suffered from gestational gestosis (Rath 2005).

Detailed records of the triad of haemolysis, thrombocytopenia and elevated liver enzymes in pregnant women and their designation as "HELLP syndrome" can be found for the first time in 1982 by Louis Weinstein (Weinstein 1982 / Lastra 2020).

HELLP syndrome (Hemolysis, Elevated Liver Enzymes, Low Platelets) is a combination of elevated liver enzymes, thrombocytopenia and haemolysis that occurs during pregnancy. This disease is a serious variant in the disease spectrum of pre-eclampsia , not an independent disease (Herold 2023).

However, in around 20% of cases, HELLP syndrome is not preceded by pre-eclampsia (Kasper 2015) or arterial hypertension. For this reason, some authors describe HELLP syndrome as a separate entity (Stepan 2022).

HELLP syndrome is the main cause of morbidity and mortality in pre-eclampsia (Kasper 2015).

HELLP syndrome occurs in around one in 150 - 300 births (Rath 2005). According to the guideline, the incidence is 0.1 - 0.2 % of all pregnant women and 10 - 20 % of women with pre-existing pre-eclampsia (Scharl 2019).

The exact etiology of HELLP syndrome is unclear. Genetic mutations on both the maternal and fetal side as well as inflammatory cytokines from the placenta are thought to be the cause (Pedca 2022)

Risk factors are:

- Family history

- Known anti-phospholipid syndrome

- Abnormal placentation

- Elevated levels of fetal mRNA for FLT 1 and endoglin (Kasper 2015)

- Previous HELLP syndrome in a previous pregnancy (Pedca 2022)

- Vitamin B12 deficiency is discussed as a risk factor (Briese 2015)

The inflammatory reaction in the placenta-liver axis appears to play a decisive role in the pathogenesis. The placental factors and vasoactive substances induce an inflammatory state and thus lead to endothelial damage. This in turn causes sinusoidal obstruction syndrome (SOS).

The endothelial damage to the liver is probably responsible for the blockage of the dissection space by erythrocytes. This in turn leads to increased microthrombus formation, hepatocyte ischemia and ultimately liver failure (Pedca 2022)

HELLP syndrome typically manifests itself in around 75% of pregnant women during the last trimester (Rath 2005).

Only in 20 - 30 % of cases does the disease occur before the 28th week of pregnancy (Pedca 2022).

In pregnant women with gestational hypertensive disease, 7 - 30 % are at risk of developing postpartum HELLP syndrome in the first 7 days after delivery (Scharl 2019).

Even before the typical laboratory changes occur, up to 90% (Pedca 2022) of patients often complain of epigastric or retrosternal pain (Scharl 2019).

The following symptoms are also common:

- Arterial hypertension in approx. 90 % of cases (Herold 2023)

- Arterial hypertension plus proteinuria in 85 % of cases

- Edema (Lastra 2020)

- Icterus (rather rare)

- Typical laboratory changes see below (Herold 2023)

- Visual disturbances in approx. 10 - 20 % (Scharl 2019)

- Circulatory disorders

- Coagulopathy of consumption

- Impairment of numerous organs, e.g. in particular:

- Kidneys with increasing renal insufficiency

- Liver with mild jaundice, pressure pain in the upper abdomen, nausea, vomiting

- Brain with e.g. cerebral hemorrhage, cerebral edema, etc. (Kasper 2015 / Rath 2005)

Diagnosis is based on laboratory chemistry (see above) by detecting the typical triad of haemolysis, thrombocytopenia and elevated liver enzymes (Scharl 2019).

The following two diagnostic classifications are frequently used to classify HELLP syndrome:

1. the Tennessee classification

This 16.5-year study included 777 patients with HELLP syndrome (Martin 1999). This classification is the most commonly used (Lastra 2020).

It includes the following evidence:

- 1. a. Microangiopathic hemolytic anemia with abnormal blood smear and low serum haptoglobin

- 1. b. Elevated LDH levels of > 600 IU / l and elevated ASAT levels of > 70 IU / l or bilirubin elevated to > 1.2 mg / dl

- 1. c. Platelet count < 100 x 109 L-1 (Pedca 2022)

2. mississippi classification

This is divided into 3 classes:

- Class I:

- LDH > 600 Ui / L

- AST / OLD ≥ 70 UI / L

- Thrombocytes ≤ 50 x 10 9 / L

- Class II:

- LDH > 600 Ui / L

- AST / OLD ≥ 70 UI / L

- Platelets ≤ 50 x 10 9 / L

- Class III:

-LDH > 600 Ui / L

- AST / OLD ≥ 40 UI / L

- Platelets > 100 x 10 9 / L

In this classification, the severity of the disease is underlined by the low point of the platelet concentration (Pedca 2022).

In addition to anamnestic information and a physical examination, sonographic fetometry, Doppler sonography of both fetal and maternal vessels and cardiotocography are also indicated (Rath 2005)

The following laboratory changes are typically found in HELLP syndrome:

- (H = Hemolysis): Significant hemolysis with a drop in haptoglobin (haptoglobin is the most sensitive parameter of hemolysis)

- (EL = Elevated liver enzymes): Increase in the transaminases GOT / GPT

- (LP = Low Platelets): Significant thrombocytopenia with platelet counts < 100 G / l (Scharl 2019)

There may also be:

- Proteinuria, this is found in approx. 86 - 100 % (Scharl 2019)

- Signs of renal insufficiency

- Icterus with an increase in bilirubin (Herold 2023) in approx. 5 % (Scharl 2019)

- Disturbance of coagulation values, in particular: fibrinogen, INR = Quick value, thrombin time, antithrombin III, D-dimer thrombin-antithrombin complex (Rath 2005)

- LDH (the LDH value correlates with the severity of the disease)

- Fragmentocytes in the peripheral blood smear are found in approx. 54 - 86 %.

- Increase in the transaminases GOT / GPT or ALT and AST (Lastra 2020)

- C- reactive protein: This is detectable in approx. 62% of cases of HELLP syndrome (Scharl 2019)

- HUS = hemolytic uremic syndrome

- TTP = thrombotic thrombocytopenic purpura (Herold 2023), also known as Moschcowitz syndrome

- aHUS = atypical hemolytic uremic syndrome (Scharl 2019)

- Cholecystitis

- pyelonephritis

- hepatitis

- Idiopathic thrombocytopenic purpura (ITP)

- Wilson's disease and many others (Briese 2015)

- Renal failure in approx. 50 % of those affected (Kasper 2015)

- Hemorrhagic necrosis of the liver

- Liver rupture (Rath 2005)

- DIG = disseminated intravascular coagulation (Scharl 2019)

- Placental abruption

- Death of the fetus

- Permanent loss of vision due to hemorrhagic and vaso-occlusive vasculopathy (Kasper 2015)

- Neurological complications such as

- apoplexy

- cerebral haemorrhage

- Cerebral edema (Kasper 2015)

If there is laboratory or clinical evidence of HELLP syndrome, the patient should be admitted to hospital immediately (Scharl 2019).

The only causal treatment in the event of HELLP syndrome is immediate termination of the pregnancy (Herold 2023), usually by means of a primary caesarean section as the treatment of first choice (Briese 2015).

Corticosteroids

Several authors advise against the use of corticosteroids. Although they can occasionally improve the platelet count, there are otherwise no positive effects with regard to the disease (Kasper 2015).

Fetal lung maturity

In the case of premature delivery, 2 x 12 mg betamethasone should be administered every 24 hours or 2 x 6 mg dexamethasone every 12 hours to induce fetal lung maturity (Briese 2015).

Antihypertensive therapy

The blood pressure of pregnant women should be kept at < 155 / 105 mmHg with medication. Possible medications include:

- Urapidil: 6.25 - 12.5 mg over 2 min i. v.; maintenance dose 6 - 24 mg / h

- Dihydralazine: 5 - 10 mg every 20 min i. v.; maintenance dose 2 - 20 mg / h

- Nifedipine: 10 mg p. o. 10 - 20 mg every 4 - 6 h (Briese 2015)

The risk of maternal morbidity and mortality due to pre-eclampsia increases 10-fold if HELLP syndrome occurs (Stepan 2022).

Approx. 7.4 - 34 % of those affected die perinatally from HELLP syndrome (Briese 2015). After delivery, HELLP syndrome disappears spontaneously (Kasper 2015). Liver function improves within the first 6 weeks after delivery (Pedca 2022).

Newborns are particularly at risk due to leukopenia and thrombocytopenia (Briese 2015).

The risk of recurrence of HELLP syndrome is 12.8% in the event of another pregnancy in Germany (Scharl 2019).

In addition, a repeat pregnancy increases the risk of further hypertensive diseases occurring during pregnancy (Scharl 2019).

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3. Kasper D L, Fauci A S, Hauser S L, Longo D L, Jameson J L, Loscalzo J et al. (2015) Harrison's Principles of Internal Medicine. Mc Graw Hill Education 46, 186
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