POST-PARTUM THROMBOTIC MICROANGIOPATHY: IN THE ERA OF COMPLEMENT INHIBITORS, PLASMA EXCHANGE IS STILL WORTH TRYING IN DEVELOPING COUNTRIES

8 Feb 2025 12 a.m. 12 a.m.
WCN25-AB-4201, Poster Board= SAT-369

Introduction:

Post-partum thrombotic microangiopathy (TMA) rapidly progresses to renal cortical necrosis (RCN), allowing only a narrow window for therapeutic interventions.  Studies have shown that complement inhibitor therapy (CIT) leads to better renal outcomes than therapeutic plasma exchange (TPE), but since CIT is not available in India, TPE remains the only option. However, TPE in post-partum TMA presents challenges due to the lack of standardized protocol and associated procedural risks.

Methods:

We diagnosed TMA in all five post-partum patients based on the presence of platelet count <100,000/μL, hemoglobin level <10 g/dL,  lactate dehydrogenase (LDH) serum level > 1.5 upper limit of normal, negative direct erythrocyte antiglobulin test and the presence of schistocytes on blood smear. Three out of four patients, who underwent renal biopsy had TMA features in renal biopsy. In two patients with an uneventful pregnancy aHUS was a clinical diagnosis of exclusion.  In one patient, post-partum hemolysis, elevated liver enzymes, and low platelet (HELLP) syndrome was diagnosed based on a history of preeclampsia, initial liver involvement, and acute tubular necrosis on renal biopsy. Two patients had obstetric complications, one with puerperal sepsis and the other with post-partum hemorrhage (PPH). The ADAMTS 13 activity assay was available for only one patient and was found to be normal. The thrombotic thrombocytopenic purpura (TTP) in other four patients was ruled out based on the PLASMIC score, although this score has not been validated in the context of pregnancy. Autoimmune profile and antiphospholipid antibody (APLA) workup were negative for all patients.  One patient with aHUS underwent genetic analysis of complement genes and anti-factor H auto-antibody and the results were normal. Functional complement assays were not available for all the patients. All five patients required dialysis and had no history of diarrhea at the time of presentation.

Results:

In our initial experience of using TPE with some modifications in post-partum TMA, we found that three out of five patients experienced renal recovery during follow-up. Detailed information on the standard of care, the rationale of TPE and follow-up for each patient, can be found in Table 1.

Table 1: Details of patients with post-partum TMA and acute kidney injury

Parameter

First case

Second case

Third case

Fourth case

Fifth case

Diagnosis

aHUS

Post-partum HELLP

aHUS

TMA associated with puerperal sepsis*

TMA associated with PPH*

Obstetric complication

Uneventful pregnancy

pre-eclampsia

Uneventful pregnancy

Puerperal Sepsis

PPH

Lab features of TMA

Present

Present

Present

Present

Present

Histological features of TMA

Present

Absent**

Present

Present

Biopsy not done

Recommended therapy

CIT

Supportive therapy

No consensus recommendations of CIT

CIT

Supportive therapy

No consensus recommendations of CIT or TPE

CIT***

Treatment given

TPE

TPE

TPE

TPE

TPE

Recommendation as per ASFA

Category 3

Category 3

Category 3

Category 3 ****

 

Category 3*** 

 

Indication

Non availability of CIT,  severe AKI,  

Persistent post-partum HELLP syndrome with severe AKI,

Non availability of CIT,  severe AKI,

Severe AKI and risk of progression to diffuse RCN

Severe AKI and risk of progression to diffuse RCN

Rationale

Replaces  mutated circulating complement proteins

Removes aggregating and pro coagulant factors released from both activated platelets and endothelial cells.

Replace mutated circulating complement proteins

Removes inflammatory markers and cytokines

Replaces abnormal complement proteins with normal one

 

TPE Prescription

         

Initiation time (post-partum day)

14

8

6

7

5

No. of plasma exchanges

2

2

5

3

3

Replacement fluid

FFP (75%) and 5% albumin (25%)

FFP (75%) and 5% albumin (25%)

FFP (50%) and 5% albumin (50%)

FFP (50%) and 5% albumin (50%)

FFP (50%) and 5% albumin (50%)

Volume of replacement (ml/kg)

40

40

40 first thereafter 35 ml/kg

35

35

Lab parameter guiding duration

Hb, platelet count, & LDH

Hb, platelet count, LDH, & PS for schistocyte

Hb, platelet count, LDH, & PS for schistocyte

Hb, platelet count, LDH, & PS for schistocyte

Hb, platelet count, LDH, &  PS for schistocyte

TPE complications

-

Hypotension

Hypotension

  -

-

TPE modifications /Precautions

No modification.

Initiated TPE late

Initiated TPE early & used PS for schistocyte additionally for guiding TPE

Volume of replacement reduced & replacement fluids ratio changed

Additionally given IVIG (100 mg/kg) post procedure

Additionally given 4 platelet concentrates at the end of procedure

Follow up ( ≥ 3 months)

No renal recovery/ Underwent  live- related renal transplant

Complete renal recovery

Partial renal recovery

No renal recovery/ On MHD

Partial renal recovery

aHUS: atypical hemolytic syndrome, HELLP: hemolysis, elevated liver enzymes, and low platelet count, TMA:  thrombotic microangiopathy, AKI: acute kidney injury, CIT: complement inhibitor therapy, FFP: fresh frozen plasma, PPH: post-partum hemorrhage, Hb: hemoglobulin,  LDH: Lactate dehydrogenase, PS: peripheral smear, TPE: therapeutic plasma exchange, IVIG: intravenous immunoglobulin, MHD: Maintenance hemodialysis, ASFA: American society for apheresis

*PPH and puerperal sepsis are now considered complement-activating triggers for aHUS in predisposed individuals.

 **The most common renal biopsy finding in HELLP is acute tubular necrosis with microangiopathy confined to the glomerulus, which may be missed due to sampling error.

***As per recent literature TMA associated with PPH is considered complement-mediated.

**** TMA, infection associated is category 3 recommendation.

Conclusions:

For pregnancy-associated TMA, in settings where complement inhibitor therapy is unavailable, therapeutic plasma exchange, administered early in the course of the disease with appropriate precautions, may be considered.

I have no potential conflict of interest to disclose.

I did not use generative AI and AI-assisted technologies in the writing process