AN UNU

            

                       

USUAL CAS

      

SE OF POSSTPARTUM

  

M THROMBBOCYTOPENIA 

Case Report

INTRODUCTION

HELLP syndrome, characterized by hemolysis,elevated liver enzyme levels and a low platelet count, is anobstetric complication, first described by Louis Weinsteinin 1982 [1]. Many investigators consider the syndrome tobe a variant of preeclampsia, but it may be a separate entity.The pathogenesis of HELLP syndrome remains unclear.Early diagnosis is critical because thea morbidity andmortality rates associated with the syndrome have beenreported to be as high as 25%. Platelet count appears to bethe most reliable indicator of the presence of HELLPsyndrome.

CASE REPORT

A twenty-year old previously healthy female withnormal ANC, who had BP = 160/110 mm Hg followed byGTCS, underwent emergency LSCS and delivered healthy2.5 Kg male baby. Postpartum she developed alteredsensorium, low urine output, and hypotension (78/30mmHg) and was managed with inotropes at a hospital inAgra. Her investigations revealed Hb -5.6, Platelet count-51000, TLC-31300, Urea/Creatnine 67.9/1.7, Na/k-134/6.3 SGPT-391, D-dimer-11.5. She was shifted to ApolloHospital Delhi. On admission, she was drowsy, notfollowing verbal commands and had quadriparesis withrecurrent GTCS. Her BP-110/68 mmHg, P-118/min,Anemia (+++), other systemic examinations were normal.Treatment was started with antiepileptics, antibiotics andmechanical ventilation, inotropes were continued withsedation.

Her investigations revealed -Hb 4.6, TLC 33800,Platelet count 1.1 lac (after 2 platelet transfusion) U/C130/4.3, Na/k 145/5.8, PT 13.5/13, INR 1.1, PTT 27.5/33Sr Bil 1.55/0.84, AST/ALT -1927/1200, ALP -112 D-dimer 5.3, FDP > 20, LDH 4434, Lactate 8.2, ECGshowed tall T waves V2-V6, USG abd- uterus bulky,Haemoperitoneum,? Ant uterine wall perforation.2 DEcho revealed mild MR, TR, LVEF 65% CVP 5, LVEDP-N and SVR 900. Provisional Diagnosis: Eclampsia,HELLP syndrome, DIC and Sepsis. Gynecology opiniontaken and advice noted for evacuation ofhaemoperitoneum once coagulopathy settles. Haemodialysis was given for deranged renal functions andmetabolic acidosis. Multiple packed red cells, platelet oncell separators and fresh frozen plasma’s were transfused.In view of worsening sensorium, persistent hemolysis,worsening Platelet count and renal functions-Plasmapheresis was started with - 100% replacement.Antibiotics and antifungal were given according toculture reports.

Repeat investigations after plasmapheresis revealed -Hb 7.0, TLC 23200, Platelet count 58000 (35700), AST/ALT 87/107, Urea/Creat 108/4.7, Na/K 149/3.5, Bil 2.58/0.96. Neurologically patient started spontaneous eyeopening, but no comprehension, no motor response andDTR absent in all limbs. Consultation was taken fromNeurologist and NCCT Brain was done which revealed-non hemorrhagic Infarct in B/L Parasaggital region andcentrum semiovale. Patient was tracheostomised,startedon inj.fraxiparine and shifted out to semi ICU. As patientdeveloped fever, MRI Brain (Fig.1. a & b) was done

AN UNUSUAL CASE OF POSTPARTUM THROMBOCYTOPENIA

J M Dua*, Sudha Kansal*, Nishant Kanodia** and Prashant Nasa***

*Senior Consultant, **Junior Consultant, ***Registrar, Department of Internal Medicine/Critical Care,Indraprastha Apollo Hospitals, Sarita Vihar, New Delhi 110 076, India.

Correspondence to: Dr J M Dua, Senior Consultant, Department of Internal Medicine, Indraprastha Apollo Hospitals,Sarita Vihar, New Delhi 110 076, India.

In a pregnant woman presenting with thrombocytopenia, the possibility of HELLP syndrome should always beconsidered by the treating clinician so as to initiate the therapy at the earliest to prevent the high perinatalmortality and postpartum morbidity. Here we report an unusual case of young Primigravida (postpartum) whopresented at Indraprastha Apollo hospitals, New Delhi with altered sensorium, paraperesis, DIC and septicshock. On evaluation she was found to have HELLP syndrome for which Plasmapheresis was given andpatient showed remarkable improvement.

Key words: HELLP- Hemolysis, Elevated liver enzyme, Low platelet count.

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65 Apollo Medicine, Vol. 7, No. 1, March 2010

which revealed-B/L Parasaggital, occipitoparietal andhigh frontal infarcts and MRV (Fig.1c) showed CorticalVenous Thrombosis.

After 25th day of treatment she regainedconsciousness and started responding to verbal commandswith power 1/5 UL with little finger movements and 1/5 inLL and no fever. Ambulation started on wheel chair andshe was put on oral feeds.

By 35th day patient was having full comprehension,started verbalizing but remained quadriparetic and wasdischarged on 45th day. Repeated follow ups in OPDshowed gradual neurological improvement and by 2months she started lifting her hands with power 4/5 in ULand 1/5 left LL and 2/5 right LL and Plantars B/Lextensors. Repeat lab tests were-AST/ALT 56/123, Hb13.5g, Platelet count 2.9 lac and treatment continued withASA, clopidrogel, iron, calcium and multivitaminsupplements. Thereafter further follow up was notundertaken.

DISCUSSION

The acronym HELLP was coined in 1982 to describe asyndrome consisting of hemolysis, elevated liver enzymelevels and low platelet count [1]. The pathogenesis ofHELLP syndrome is not well understood. The findings ofthis multisystem disease are attributed to abnormalvascular tone, vasospasm and coagulation defects [2]. Tilldate, no common precipitating factor has been found. Thesyndrome seems to be the final manifestation of someinsult that leads to microvascular endothelial damage andintravascular platelet activation. Thus begins a cascadethat is only terminated with delivery.

The hemolysis in HELLP syndrome is amicroangiopathic hemolytic anemia.

The elevated liver enzyme levels in the syndrome arethought to be secondary to obstruction of hepatic bloodflow by fibrin deposits in the sinusoids.

The thrombocytopenia has been attributed to increasedconsumption and/or destruction of platelets.

Patients who develop DIC, approximately 0.2 to 0.6%of all pregnancies [3], generally do so in the setting ofwell-developed HELLP syndrome. When preeclampsia isnot present, diagnosis of the syndrome is often delayed[4].The risk factors for HELLP syndrome differ fromthose associated with preeclampsia (Table 1). Thesyndrome presents antepartum in 69% and postpartum in31% of patients [2]. It generally presents in the thirdtrimester of pregnancy, although in 11% it occurs at lessthan 27 weeks of gestation [5]. With postpartumpresentation, the onset is typically within the first 48 hoursafter delivery.

Patients present with generalized malaise, epigastricpain, nausea, vomiting, and with headache [3]. Thedifferential diagnosis of HELLP syndrome includes acute

(a) (b) (c)Fig.1. (a) MRI brain, (b) MRI brain-T2 flair- B/L-Parasaggital, occipitoparietal and high frontal infarcts (c) MRV brain-Cortical

Venous Thrombosis

Table 1. Predisposing factors for HELLP syndrome

and preeclampsia

HELLP syndrome Preeclampsia

Multiparous Nulliparous

Maternal Age>25 years <20 years of >45 years

White race Family history ofpreeclampsia

History of poor pregnancy Minimal prenatal careoutcome Diabetes mellitus

Chronic hypertensionMultiple gestation

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Apollo Medicine, Vol. 7, No. 1, March 2010 66

fatty liver of pregnancy, thrombotic thrombocytopenicpurpura and hemolytic uremic syndrome. Many womanwith this syndrome are initially misdiagnosed with otherdisorders, such as cholecystitis, esophagitis, gastritis,hepatitis or idiopathic thrombocytopenia [3].

The three chief abnormalities found in HELLPsyndrome are hemolysis, elevated liver enzyme levels anda low platelet count. The serum transaminase levels maybe elevated to as high as 4,000 U per L, but milderelevations are typical. Platelet counts can drop to as low as6,000 per mm3, but any platelet count less than 150000 permm3 needs attention. The platelet count is the bestindicator of the HELLP syndrome. A positive D-dimer testin the setting of preeclampsia has recently been reported tobe predictive of patients who will develop HELLPsyndrome [6]. The D-dimer is a more sensitive indicator ofsubclinical coagulopathy and may be positive beforecoagulation studies are abnormal.

The present classification and diagnostic criteria ofHELLP syndrome is shown in Table 2.

Patients with class 1 HELLP syndrome are at higherrisk for maternal morbidity and mortality than patientswith class 2 or 3 HELLP syndrome [5].

MANAGEMENT

Once the diagnosis of HELLP syndrome has beenestablished, the best markers to follow are the maternalLDH and platelet count [7]. The peak lactatedehydrogenase level shows the beginning of recovery andsubsequent normalization of the platelet count [7]. Theincidence of hemorrhagic complications is higher whenplatelet counts are less than 40,000 per mm [8].

Prompt recognition of HELLP syndrome and timelyinitiation of therapy are vital to ensure the best outcome

for mother and fetus. The treatment approach should bebased on the estimated gestational age and the condition ofthe mother and fetus (Fig. 2) [9].

Patients with HELLP syndrome should be routinelytreated with corticosteroids. Patients treated withdexamethasone exhibit longer time to delivery andfacilitates postnatal maturity of fetal lungs [10].

Corticosteroid therapy should be instituted in patientswith HELLP syndrome who have a platelet count of lessthan 100,000 per mm3 and should be continued until liverfunction abnormalities are resolved and the platelet countis greater than 100,000 per mm3.

Patient should be treated prophylactically withmagnesium sulfate to prevent seizures.

Antihypertensive therapy should be initiated if bloodpressure is consistently greater than 160/110 mm Hg. Thisreduces the risk of maternal cerebral hemorrhage,placental abruption and seizure. The goal is to maintaindiastolic blood pressure between 90 and 100 mm Hg. Themost common antihypertensive agent’s hydralazine,labetalol and nifedipine have been used with success.

A hypertensive crisis may be treated with a continuousinfusion of nitroglycerin or sodium nitroprusside.

Between 38% and 93% of patients with HELLPsyndrome receive some form of blood product [11].Patients do not require transfusion unless the plateletcount drops to less than 20,000 per mm3. Patients whoundergo cesarean section should be transfused if theirplatelet count is less than 50,000 per mm3.

Patients with DIC should be given fresh frozen plasmaand packed red blood cells. Plasmapheresis has beensuccessful in patients with severe laboratory abnormalities(i.e., a platelet count <30,000 per mm3 and increased liverfunction values). In these patients, plasmapheresis hasresulted in an increase in the platelet count and a decreasein the lactate dehydrogenase level [11,12].

The mortality rate for women with HELLP syndromeis approximately 1.1% [5]. From 1 to 25 % of affectedwomen develop serious complications such as DIC,placental abruption, adult respiratory distress syndrome,hepatorenal failure, pulmonary edema, subcapsularhematoma and hepatic rupture. Infant morbidity andmortality rates range from 10 to 60%; depending on theseverity of maternal disease [3]. Infants affected byHELLP syndrome are more likely to experienceintrauterine growth retardation and respiratory distresssyndrome [13]. Life threatening neurologicalcomplications of the HELLP syndrome are rare. It

Table 2. Diagnostic criteria of HELLP syndrome

HELLP Tennessee Mississippiclass classification classification

1 Platelets 100-109/L Platelets 50.109/LAST 70 IU/L AST or ALT 70 IU/LLDH 600 IU/L LDH 600 IU/L

2. Platelets 100.109/L50.109/L

AST or ALT 70 IU/LLDH 600 IU/L

3. Platelets 150.109/L1000.109/L

AST or ALT 40 IU/LLDH 600 IU/L

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67 Apollo Medicine, Vol. 7, No. 1, March 2010

includes cerebral or brain stem hemorrhage, thrombosisand infarctions or cerebral oedema and had been reportedin post partum period [14].

Patients who have had HELLP syndrome have a 19 to27% risk of developing the syndrome in subsequentpregnancies[15]. Patients with class 1 HELLP syndromehave the highest risk of recurrence [15]. Patients who havehad HELLP syndrome may subsequently use oralcontraceptive pills safely [16]. Patients who developatypical early-onset preeclampsia or HELLP syndromeshould be screened for the presence of antiphospholipidantibodies [17].

To date, neither calcium nor aspirin has been

specifically studied in patients with HELLP syndrome.Although our case showed no deterioration or increaseany complications but has only done benefits till date withthe use of aspirin with clopidrogel and calciumsupplement. One of the studies had suggested that aspirintherapy might be helpful in selected patients with early-onset severe preeclampsia [18]. Similarly several otherstudies had suggested that calcium might be useful inpreventing preeclampsia in high-risk patients of HELLPsyndrome [19, 20].

REFERENCES

1. Weinstein L. Syndrome of hemolysis, elevated liverenzymes and low platelet count: a severe consequenceof hypertension in pregnancy. Am J Obstet Gynecol

Management of HELLP Syndrome

EGA <32 weeks EGA 32 to 34 weeks EGA 34 weeks

Administer a corticosteroid Administer a corticosteroid

Manage the patientbased on the clinical

response during a periodof observation

Patient’sconditionworsens

Patient’scondition is

stable

Deliver Monitor thepatient in atertiary care

facility

Is the patient eligible forconservative

management?

DeliverNo

Yes

Counsel the patient about the potentialbenefit of continuing the pregnancy fortwo more weeks to allow more time for

fetal lungs to mature

Transfer the patient to a tertiarycare facility that has a neonatal

intensive care unit

Patient’s conditionworsens

Patient’s conditionis stable

Deliver Monitor the patientin a tertiary care

facility

Fig 2. Approach to the management of patients with HELLP syndrome.

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Apollo Medicine, Vol. 7, No. 1, March 2010 68

1982;142:159-167.

2. Sibai BM. The HELLP syndrome (hemolysis, elevatedliver enzymes, and low platelets): much ado aboutnothing? Am J Obstet Gynecol 1990;162: 311-316.

3. Wolf JL. Liver disease in pregnancy. Med Clin North Am1996;80:1167-1187.

4. Gleeson R, Farrell J, Doyle M, Walshe JJ. HELLPsyndrome: a condition of varied presentation. Ir J MedSci 1996;165:265-267.

5. Sibai BM, Ramadan MK, Usta I, Salama M, Mercer BM,Friedman SA. Maternal morbidity and mortality in 442pregnancies with hemolysis, elevated liver enzymes, andlow platelets (HELLP syndrome). Am J Obstet Gynecol1993;169:1000-1006.

6. Neiger R, Trofatter MO, Trofatter KF Jr. D-dimer test forearly detection of HELLP syndrome. South Med J1995;88:416-419.

7. Martin JN Jr, Blake PG, Perry KG Jr, McCaul JF, HessLW, Martin RW. The natural history of HELLP syndrome:patterns of disease progression and regression. Am JObstet Gynecol 1991;164:1500-1509.

8. Roberts WE, Perry KG Jr, Woods JB, Files JC, Blake PG,Martin JN Jr. The intrapartum platelet count in patientswith HELLP (hemolysis, elevated liver enzymes, and lowplatelets) syndrome: is it predictive of later hemorrhagiccomplications? Am J Obstet Gynecol 1994;171: 799-804.

9. Sibai BM, Frangieh AY. Management of severepreeclampsia. Curr Opin Obstet Gynecol 1996;8:110-113.

10. Magann EF, Graves GR, Roberts WE, Blake PG,Morrison JC, Martin JN Jr. Corticosteroids for enhancedfetal lung maturation in patients with HELLP syndrome:impact on neonates. Aust N Z J Obstet Gynaecol1993;33:131-135.

11. Martin JN Jr, et al. Plasma exchange for preeclamspia. I.Postpartum use for persistently severe preeclampsia-

eclampsia with HELLP syndrome. Am J Obstet Gynecol1990;162:126-137.

12. Katz VL, Watson WJ, Thorp JM Jr, Hansen W, BowesWA Jr. Treatment of persistent postpartum HELLPsyndrome with plasmapheresis. Am J Perinatol 1992; 9:120-122.

13. Dotsch J, Hohmann M, Kuhl PG. Neonatal morbidity andmortality associated with maternal haemolysis, elevatedliver enzymes and low platelets syndrome. Eur J Pediatr1997;156: 389-391.

14. Altamura C, et al. Postpartum cerebellar infarction andhaemolysis, elevated liver enzymes, low platelet(HELLP) syndrome. Neurol Sci 2005, 26: 40-42.

15. Sullivan CA, Magann EF, Perry KG Jr, Roberts WE,Blake PG, Martin JN Jr. The recurrence risk of thesyndrome of hemolysis, elevated liver enzymes, and lowplatelets (HELLP) in subsequent gestations. Am J ObstetGynecol 1994;171:940-943.

16. Sibai BM, Taslimi MM, el-Nazer A, Amon E, Mabie BC,Ryan GM. Maternal-perinatal outcome associated withthe syndrome of hemolysis, elevated liver enzymes, andlow platelets in severe preeclampsia-eclampsia. Am JObstet Gynecol 1986;155:501-509.

17. Munday DN, Jones WR. Pregnancy complicated by theantiphospholipid syndrome. Aust N Z J Obstet Gynaecol1993;33:255-258.

18. Caritis S, et al. Low-dose aspirin to prevent preeclampsiain women at high risk. National Institute of Child Healthand Human Development Network of Maternal-FetalMedicine Units. N Engl J Med 1998; 338: 701-705.

19. Lopez-Jaramillo P, Delgado F, Jacome P, Teran E, RuanoC, Rivera J. Calcium supplementation and the risk ofpreeclampsia in Ecuadorian pregnant teenagers. ObstetGynecol 1997;90:162-167.

20. Bucher H, et al. Effect of calcium supplementation onpregnancy-induced hypertension and preeclampsia: ameta-analysis of randomized controlled trials. JAMA1996; 275: 1113-1117.

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