CLINICAL CASE 61: Answers and Summary

PREGNANCY STATE CAN LEAD TO THROMBOTIC MICROANGIOPATHY. WHICH OF THE FOLLOWING ARE MECHANISMS VIA WHICH TMA HAPPENS DURING PREGNANCY?( MULTIPLE ANSWERS POSSIBLE)

HELLP syndrome associated 35%

ADAMTS 13 deficiency associated 10%

Complement alternative pathway associated 13%

VEGF deficiency associated 35%

Unknown mechanism associated 5%

Obstetric nephrology is a field with significantly complex patients who have high risk of maternal and fetal complications. Thrombotic microangiopathy(TMA) during pregnancy can have a vast differential. There is a new way of thinking of TMA after the advent of the atypical HUS diseases. Pregnancy associated TMA accounts for 8-18% of all cases of TMA. Its a secondary form of TMA.

Acquired causes of TMA from ADAMTS13 is a cause that is definitely one form that can be see in pregnancy and non pregnancy states that clinically would present as TTP more than HUS.

Dysregulation of the complement cascade especially the alternative pathway would lead to the newly discovered forms of atypical HUS and this can also be noted in pregnancy. Unknown mechanisms would be the other big category in the this as well.

HELLP syndrome: is this really a TMA or not a TMA? AKI is associated with fair amount of cases of HELLP syndrome. The pathology in the liver suggestive of TMA and some forms of HELLP syndrome share same genetic features as some atypical HUS syndromes. Kidney biopsies have rarely been done and those have shown TMA.

VEGF deficiency: Pre eclampsia has now been associated with antiangiogenic factors that might lead to anti VEGF state just like what we might see in cases of avastin toxicity. The biopsy in such cases might be also suggestive of  TMA. 

A recent review in CJASN reviews this nicely. Figure 1 has a nice timeline of when these syndromes might best fit during the three trimesters.