HELLP syndrome

This is a particularly high-risk form of pre-eclampsia. "Haemolysis, LFT derangement, low platelets" is what HELLP stands for.  Basically, it is pre-eclampsia, with all its various haemodynamic and neurological features, but with a vastly more deranged biochemical profile, and with haemolysis. About 20% of pre-eclampsia patients go on to develop this syndrome, and about a third tend to develop it post-partum, when you thought they were safe. The college loves HELLP and the pregnant patient with deranged LFTs keeps coming up in the exam; in fact roughly half of the pregnancy-related SAQs include HELLP as a differential.

Previous SAQs on this topic:

• Question 30.2 from the second paper of 2016
• Question 21.1 from the second paper of 2012
• Question 18.3 from the second paper of 2008
• Question 9.1 from the first paper of 2008

What else would it be? The clever CICM fellowship candidate will be able to regurgitate a stream of differentials:

Differential causes of hemolysis, hepatitis and thrombocytopenia in pregnancy

• benign thrombocytopenia of pregnancy
• Acute fatty liver of pregnancy

Differential causes of hemolysis, hepatitis and thrombocytopenia in general

• Viral hepatitis
• Idiopathic thrombocytopenic pupura (ITP)
• Thrombotic thrombocytopenic purpura (TTP)
• Hemolytic-uremic syndrome (HUS)
• Systemic lupus erythematosus (SLE), antiphospholipid syndrome
• Cholangitis

Diagnosis of HELLP

There are several sets of strict criteria: Sibai's "Tennessee" criteria have been expanded upon and reconfigured as "the Mississippi classification":

Mississippi class 1: platelets less than 50 AST or ALT over 70 LDH over 600

Mississippi class 2: platelets 50-100 AST or ALT over 70 LDH over 600

Mississippi class 3: platelets 100-150 AST or ALT over 70 LDH over 600

These really differ only according to the platelet count (and you should use the platelet nadir). Other feature to be expected is haemolysis due to microangiopathic haemolytic anaemia (MAHA):

• Blood film shows fragmented RBCS - schistocytes
• There is a raised reticulocyte count
• The unconjugated bilirubin fraction increases
• The haptoglobin decreases (as haptoglobin/hemoglobin complexes are removed)

Distinguishing HELLP from the differentials

Benign thrombocytopenia of pregnancy has ...only thrombocytopenia, and none of the other features of HELLP, and perhaps not even pre-eclampsia. Its a completely benign thrombocytopenia, seen in normal pregnant woemn.

Acute fatty liver of pregnancy is very similar to HELLP, but may not have much of a thrombocytopenia, and does not present with proteinuria.

Viral hepatitis should not present with proteinuria either.

In fact, proteinuria (and thus preeclampsia) are pretty specific, and will exclude a lot of these differentials.

TTP can be confirmed with the ADAMTS13 test, and HUS is more likely if renal failure is the dominant presenting feature of the patient.

"How is this not just pre-eclampsia with liver dysfunction?"

Well, reader, that may be exactly what it is.  One classical way of looking at HELLP is as "pre-eclampsia plus",  just the same disease process but farther along on the spectrum of severity. Let us consider that spectrum, order by increasing severity:

1. Gestational hypertension
2. Hypertension with proteinuria, which makes it preeclampsia
3. Pre-eclampsia with deranged LFTs (which makes it "severe")
4. Pre-eclampsia with thrombocytopenia AND deranged LFTs (low platelets are another feature of severe preeclampsia)
5. Pre-eclampsia with thrombocytopenia, deranged LFTs, AND haemolysis (now, you can call it HELLP)

Presumably, you could continue in this way forever (for example, point 6 might be "pre-eclampsia with HELLP as well as DIC"), but none of these are different diseases- they are just increasingly more severe manifestations of the same process; or so the classical teaching goes.

So:  in Question 18.3 from the second paper of 2008, the CICM examiners asked for three differentials for a HELLP-ish set of bloods,  and then listed both HELLP and "pre eclampsia with hepatic involvement". Were they just listing two versions of the same condition as separate differentials?  It would be as if you were asked to give three differentials for the possible causes of headache, and your answers were "Grade I subarachnoid, Grade II subarachnoid and Grade III subarachnoid". 

On the other hand, HELLP may be a distinct entity. This has been considered for some time now (Baha Sibai, writing in 1990, was already looking back on decades of disagreement). It is true that a substantial proportion of HELLP patients do not present with a classical preeclampsia history (i.e. their blood pressure is normal and they might have minimal or absent proteinuria). Some modern authors confidently assert that "it is important to recognise HELLP syndrome as a distinct entity" (Rimaitis et al, 2017), or describe severe preeclampsia with LFT derangement as one of the conditions mimicking HELLP (Azzarolli et al, 2020),  whereas others place it within the preeclampsia-eclampsia continuum (Martin & Morris, 2019). The latter group includes authoritative societies. "For clinicians familiar with the management  of pre-eclampsia, [HELLP] signifies a more serious part of the spectrum of this disorder, and is still considered within the overall context of managing pre-eclampsia, not an isolated and separate disorder", wrote Tranquilli (2014) for the International Society for the Study of Hypertension in Pregnancy (ISSHP), in their statement on the classification, diagnosis and management of the hypertensive
disorders of pregnancy. That this article is hosted by RANZCOG suggests that there is probably some support for this way of thinking in Australia. 

Investigations

In order to discriminate among the differentials, you should launch investigations in addition to the routine FBC/EUC/LFT/Coags that you would normally already have in your pre-eclampsia patient:

• Blood film
• LDH
• Reticulocyte count
• Unconjugated fraction of bilirubin
• Haptoglobin level

Additionally, it would be good to perform a liver ultrasound. It may reveal a subcapsular haematoma, or confirm rupture (which is a surgical emergency).

Management of HELLP

Again, the specific management revolves around getting the baby out. Not much else is of any use. One can press on with the standard suportive care for pre-eclampsia, and replace whatever blood products are being depleted, but none of this is definitive.

Because HELLP is a lifethreatening condition, serious thought must be given to the delivery of a premature foetus. Corticosteroids may not be helpful in preventing maternal mortality and morbidity, but they do play a role in accelerating foetal lung maturation.