Successful outcome of therapeutic plasma exchange in post-partum haemolytic-uraemic syndrome: a case report

Introduction

Adult, non-infective, post-partum haemolytic-uraemic syndrome (HUS) is a rare problem of pregnancy and puerperium but is an important differential diagnosis in the evaluation of thrombocytopenia. Like other causes of thrombocytopenia in pregnancy -pre-eclampsia and haemolysis, elevated liver enzymes and low platelet count (HELLP) syndrome - this is a multisystem disorder associated with high morbidity and mortality in the absence of appropriate therapy.

Patients with post-partum HUS display a classical triad of microangiopathic haemolytic anaemia, acute nephropathy, and thrombocytopenia. It is associated with a documented maternal mortality rate of 44% and perinatal mortality rate of 80%¹. The treatment of post-partum HUS involves infusion of fresh-frozen plasma and steroids. Emergency therapeutic plasma exchange (TPE), carried out within 24 to 48 hours of diagnosis, may prevent the high mortality.

Case history

A 21-year old, 55-kg female (G₁P₁A₀) underwent an emergency Caesarean section because of foetal distress. She had had an uneventful pregnancy with no history suggestive of pre-eclampsia such as hypertension, oedema or proteinuria. The first day after surgery was uneventful but from the second day her urine output started to decline and she also had thrombocytopenia, anaemia, impaired renal function (Table I) and increased liver enzymes. Her total serum bilirubin was 4.3 mg/dL, direct bilirubin 3.8 mg/dL, total protein level 4.2 g/dL, serum glutamic oxaloacetic transaminase 366 IU/L, serum glutamic pyruvic transaminase 109 IU/L, serum gamma glutamyl transpeptidase 39 IU/L and alkaline phosphatase 165IU/L. On post-operative day 3, her laboratory parameters further deteriorated and her 24-hour urine output was 20 mL (normal range: 720–2,000 mL). Her serum lactate dehydrogenase (LDH) concentration was found to be high (9,660 U/L). Proteinuria (2+) was detected. Her blood pressure was 130/80 mmHg. A provisional diagnosis of post-partum acute renal failure due to HELLP was made. Haemodialysis was initiated and two sessions were carried out on alternate days. Platelet concentrates were infused to correct the thrombocytopenia. Later she also had an episode of epistaxis and haematuria (10–15 red blood cells in urine).

Table I.

Laboratory parameters before therapeutic plasma exchange.

Post-op day	Haemoglobin (g/dL)	Platelet count (×109/L)	Total leucocyte count (×109/L)	Serum urea (mg/dL)	Serum creatinine (mg/dL)	Serum uric acid (mg/dL)	Lactate dehydrogenase (IU/L)
Normal Range	12.3–15.3	150–450	4–11	10–50	0.80–1.50	2.5–6.2	313–618
Day 2	11.6	72	25.0	62	2.3	4.8	ND
Day 3	9.4	35	26.6	64	2.3	6.7	9,660
Day 5	6.8	20	43.0	173	4.4	6.8	7,580
Day 6	8.3	16	38.9	207	5	7	8,679

On day 6, her overall clinical condition deteriorated further. She was tachypnoeic with bilateral crepitations. Despite transfusion, her platelet count was low (16×10⁹/L), the LDH level was rising (8679 U/L) and her liver and renal function remained abnormal. Her urine output was only 120 mL. She was moved to the Intensive Care Unit for endotracheal intubation and assisted ventilation.

The peripheral blood smear was now showing a few schistocytes and two nucleated cells per 100 white blood cells. Hence, in view of the clinical deterioration with decreasing haemoglobin, low platelet count, high LDH and renal dysfunction (Table I), the possibility of post-partum HUS was considered and an emergency TPE (1.5 plasma volume) was carried out.

A total of four sessions of TPE were performed on alternate days. All procedures were carried out with a Com.Tec cell separator (Fresenius Kabi) exchanging 1.5 plasma volumes using fresh-frozen plasma as the replacement fluid. On day 7 (Table II), after the first TPE, the platelet count and total leucocyte count improved (Figure 1) and the LDH concentration declined (Figure 2). Tachypnoea decreased but the haematuria persisted. The patient was administered packed red cells to increase her haemoglobin. After the second TPE, the haematuria also resolved and the 24-hour urine output improved (480 mL). The patient's general condition improved on day 9; she was no longer tachypnoeic (respiratory rate, 24/min) and her chest cleared. She was moved back from the Intensive Care Unit into the ward. On day 11, her 24-hour urine output was 1,030 mL with increasing platelet counts and falling LDH levels. Her urea levels decreased slightly (Figure 3) although there was not much improvement in serum creatinine and serum uric acid levels. On day 14, the patient was discharged from hospital with a haemoglobin of 8.3 g/dL, total leucocyte count of 9.57×10⁹/L, platelet count of 355×10⁹/L and LDH of 1271 U/L. Renal and liver function test values returned to normal after 1 month.

Table II.

Laboratory parameters after therapeutic plasma exchange.

Post-op day	Haemoglobin (g/dL)	Platelet count (× 109/L)	Total leucocyte count (× 109/L)	Serum urea (mg/dL)	Serum creatinine (mg/dL)	Serum uric acid (mg/dL)	Lactate dehydrogenase (U/L)
Day 7	10.2	23	30.9	255	5.5	7.3	4,369
Day 8	8.9	39	27.8	234	5	8.9	2,294
Day 10	8	113	18.8	207	5.4	12.4	1,378
Day 12	8.3	300	9.6	113	5.3	7.6	1,271

Figure 1.

Rise in platelet count and fall in leucocyte count after plasma exchange.

Figure 2.

Marked fall in Lactate dehydrogenase noted after plasma exchange.

Figure 3.

Improvement in renal parameter - Serum Urea.

Discussion

Egerman et al.³ reported 11 cases of pregnancy-associated HUS emphasising that improved survival could be attributed to aggressive treatment with TPE. In case of post-partum HUS described here, our patient had a remarkable recovery of both clinical and laboratory parameters following TPE. Platelet count and serum LDH levels are two very important biochemical indicators of post-partum HUS³. Following treatment with TPE our patient's LDH decreased from 9,660 U/L to 1271 U/L and her platelet count rose from 11×10⁹/L to 355×10⁹/L (without any platelet transfusions after initiation of the TPE). We, therefore, found that with TPE, a patient with post-partum HUS entered a sustained remission with some improvement in renal function and discontinuation of dialysis, which is similar to the responses in the three cases described by Shemin et al.¹.

In 2007, the American Society for Apheresis (ASFA) graded HUS (other than idiopathic, diarrhoea-associated paediatric or transplant-associated microangiopathy) as a level III disease indication for performing TPE.

Level III diseases are those in which there is a suggestion of benefit but for which existing evidence is insufficient, either to establish the efficacy of TPE or to clarify the risk/benefit (or sometimes the cost/benefit) ratio associated with TPE. Therapeutic apheresis may reasonably be used in such patients when conventional therapies do not produce an adequate response or as part of an approved research protocol.

TPE has been found to be more effective than plasma infusion. Our patient was managed with TPE, with fresh-frozen plasma used as the replacement fluid (fresh-frozen plasma 90%, normal saline 10%).

Initially the patient was treated as if she had HELLP syndrome, but with continuing deterioration of her clinical and biochemical parameters, the diagnosis was reconsidered and she was treated as a case of HUS. It can be difficult to distinguish HUS from HELLP syndrome³. However, the distinction between the two is important because the management is different, as seen in this patient. Even though thrombotic thrombocytopenic purpura/haemolytic-uraemic syndrome (TTP/HUS) is rare in pregnancy, affecting 1 in 100,000 pregnancies⁴ its differential diagnosis should be considered in acute renal failure with thrombocytopenia and haemolytic anaemia. TTP/HUS frequently persists after delivery whereas the HELLP syndrome typically resolves in the post-partum period¹. Moreover, abnormal laboratory values in TTP/HUS are often extreme or profound as they were in this case⁴.

However, it is important to know when to intervene with TPE in a pregnant patient. If signs and symptoms of TTP HUS occurs in the first trimester the differential diagnosis of pre-eclampsia or HELLP syndrome is not considered and TPE is indicated urgently. If signs and symptoms of TTP HUS occur in late pregnancy then severe pre-eclampsia and HELLP syndrome are important diagnostic issues and delivery is the definitive treatment. If signs and symptoms of HUS occurs after delivery, severe pre-eclampsia and HELLP syndrome remain possible differential diagnoses and so plasma exchange should be started immediately.

The two factors that decide management with TPE are: (i) the severity of the thrombocytopenia, haemolytic anaemia, neurological and renal abnormalities and (ii) the course of these abnormalities following delivery⁵.

Conclusion

TPE is a successful treatment modality for adult, non-infective post-partum HUS when instituted promptly. This case represents the ideal scenario in which an early diagnosis could be made and prompt treatment was started. However, despite a level III recommendation from the American Society for Apheresis, therapeutic plasma exchange remains underutilised.