Interactive case report

A patient with suspected miscarriage is found to have hypertension, renal failure, and thrombocytopenia: case presentation

BMJ 2007; 334 doi: (Published 28 June 2007)
Cite this as: BMJ 2007;334:1372

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Some other responses have suggested HELLP syndrome, but patient had normal liver enzymes. I do not think that Eclampsia as a possible diagnosis as patient is not pregnant (negative HCG).

1)I would not investigate miscarriage at this point. 2)She has microangiopathic haemolytic anaemia and causes include HUS, TTP, Malignant hypertension and Vasculitis. Neurological involvement points towards TTP as well as Malignant Hypertension. In view of recurrent miscarriages and Raynauds I would consider underlying connective tissue disorder/Vasculitis on top of my differential diagnosis thus causing high blood pressure. Malignant hypertension can result in microangiopathic haemolytic anaemia, pulmonary oedema and renal failure. The underlying diagnosis could be SLE, Anti phospholipids syndrome or possible scleroderma with scleroderma crisis.

3)CXR showing pulmonary oedema is likely secondary to malignant hypertension. I would consider a fluid overload state in background of acute renal failure but there was no mention of ankle oedema or generalized swelling in the case report.

4)HDU / ITU admission

BP needs to be controlled as it is the likely causes of seizures and requires gradual titration.

Involve Haematology and Nephrology teams

Autoantibody screen for above disorders and would consider plasmapharesis.

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Faisal Mohammad, SHO - Medical Rotation

Arrowe Park Hospital Wirral NHS Trust,Arrowe Park Road,Wirral,CH49 5PE

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1. I would not normally investigate the cause of 2 miscarriages in a woman in her 40's as the results would be unlikely to be helpful. 3 consecutive unexplained miscarriages, however, are more likely to have a common aetiology.

2. SLE is the most likely diagnosis as it fits the clinical picture and the blood results are all explainable by this disease. The CXR findings would be consistent with pulmonary oedema. This would be secondary to left ventricular failure secondary to hypertension secondary to chronic renal failure secondary to SLE. The convulsions were either caused by pre-eclampsia(a known complication of SLE in pregnancy) or hypocalcaemia, this in turn due to chronic renal disease. Thrombocytopaenia is a recognised feature of SLE, as is a haemolytic anaemia, as evidenced by the low Hb, high reticulocyte count, red cell fragmentation and very high LDH.

3. As already mentioned the CXR is consistent with pulmonary oedema. There is also probably left ventricular hypertrophy, accounted for by hypertension.

4. I would admit the patient to an ICU. Pre-eclampsia is likely to be the cause of the convulsions and these are likely to continue until the BP is brought down and for some time afterwards and so I would ventilate the patient. Having protected the airway my next priority is to get the BP down, using agents such as labetolol.Dexamethasone can be given for cerebral oedema (another reason for ventilation). The pulmonary oedema should respond to the hypotensive drugs but diuretics can also be administered. The hypocalcaemia should also be corrected. Blood should be taken for an auto immune profile with particular reference to anti ANA and anti DNA antibodies.

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fergus j dignan, civilian medical practitioner

RAF Lyneham SN15 4PZ

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1. Investigation re: miscarriage - the patient is 46 yrs old and has had two previous successful pregnancies and two recent miscarriages from a new partner. Due to her age - the risk of miscarriage is much higher and given that she has had two previous pregnancies (albeit complicated by PET) whether to intensively investigate is difficult. Investigation would include screening for chromosomal (both her and partner) and autoimmune conditions such as SLE and antiphospholipid syndrome. Often screening is unproductive.

2. Diagnosis: TTP secondary to antiphospholipid syndrome. Patient has thrombocytopenia, renal failure, microcytic angiopathic haemolytic anaemia and neuro symptoms. Did she have fever?

Malignant hypertension is a possibility (Raynaulds/hypertension - consider CREST as underlying cause for this).

HELLP unlikely - as only early pregnant.

Patient possibly has underlying vasculitis (note the raised BP a year earlier)

3. Pulmonary vascular leakage/ARDS.

Differential would include causes of pulmonary-renal syndromes eg: Goodpastures, Wegner's Granulomatosis, Microscopic polyangiitis, Henoch- Schönlein purpura, IgA nephropathy, cryoglobulinemia, or pneumonia-related immune complex glomerulonephritis.

4. I would screen for vasculitis:

ANA, RF, cANCA, pANCA, dsDNA, anti Rho, anti La, ENA lupus anticoagulant/anticardiolipin antibodies scl 70 and anticentromere antibodies (to exclude CREST) Cryoglobulins

consider renal biopsy

Needs supportive care: ITU, intubation/ventilation, dialysis if TTP - plasma exchange consider steroids/immunosuppression depending on results of vasculitis screen/exclusion of CREST.

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Ken K Hodson, SpR Medicine (interest in Maternal Medicine)

Royal Victoria Infirmary, Newcastle-upon-Tyne

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Dear Dr Anon

Thank you for raising this differential diagnosis. It's difficult to fit in how thrombocytopenia develops in this " scleroderma renal crisis." Unless, TTP develops in association with scleroderma in extremely rare circumstances ! That might have been the case.


1. Yusin J, Lewin K, Clements P. Thrombotic thrombocytopenia purpura in a patient with systemic sclerosis. J Clin Rheumatol. 2001 Apr;7(2):106-11

2. Manadan AM, Harris C, Block JA. Thrombotic thrombocytopenic purpura in the setting of systemic sclerosis. Semin Arthritis Rheum. 2005 Feb;34(4):683-8

3. Kfoury Baz EM, Mahfouz RA, Masri AF et al. Thrombotic thrombocytopenic purpura in a case of scleroderma renal crisis treated with twice-daily therapeutic plasma exchange. Ren Fail. 2001 Sep;23(5):737 -42

4. Towheed TE, Anastassiades TP, Ford SE et al. Thrombotic thrombocytopenic purpura as an initial presentation of limited systemic sclerosis. J Rheumatol. 1999 Jul;26(7):1613-6

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Thein H Oo, MD, FRCP, Attending Hematologist

Caritas St Elizabeth's Medical Center, Tufts University School of Medicine, Boston, USA

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4 July 2007

1 No if the previous pregnancy losses were less than 10 weeks gestation, then two miscarraiges would not be an indication for investigation. Also given her age she is more likely to miscarry anyway. If her pregnancies were complicated by pre-eclampsia (rather than non- proteinuric hypertension) and the babies were small for gestational age, then it may have been worth suggesting an APS screen. 2.TTP/HUS 3.ARDS 4.APS SCreen- acl/LA

Double stranded DNA

Complement levels

vWillibrand cleaving factor

Hourly urine output

MRI Head

Moniter pottasium levels

BD liver/renal profile


Consider dialysis dependin upon urine output

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Seema Chakravarti, Obstetric Consultant

Queen's Hospital, Romford. RM7 0AG

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Just a long shot, but as you say there is one thing not yet mentioned, could it be ???scleroderma renal crisis sine sclerderma. I know it's very rare, but has been reported, and associated with pregnancy/miscarriage - Scand J Rheum 2003;32 (1):55-7.

Should still treat as described in other responses - plasma exchange for ?TTP, dialysis, anticonvulsants, ITU admission etc.... Lower BP with ACE inhibitor ideally.

Other investigations (in addition to those mentioned by others) should include anti-Scl-70 and anti-RNA polymerase III antibodies. Ideally would need renal biopsy, but likely too risky with low platelets and very high BP.

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a anon, .


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4 July 2007

This lady has the HELLP syndrome. The priority would be managing the seizures, pulmonary edema and maintaining the platelet count.

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w afzal, gp reg

de23 6ph

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1. Investigation for recurrent miscarriage might have been appropriate. It'd be more interesting to know the timing of the previous miscarriages (i.e. within the first 8 weeks or early first trimester etc). This information will give us some hints whether miscarriage was due to chromosomal abnormalities versus placental vascular insufficiency .

2. The patient has (a) microangiopathic hemolytic anemia, (b) thrombocytopenia, (c) renal failure, (d) CNS changes such as headaches and convulsions. She also has past history of recurrent miscarriage, history suggestive of Raynaud's syndrome and hypertension. It'd have been worthwhile investigating the cause of hypertension 1 year ago. Could it be hypertension due to nephritis (with renal failure ) related to collagen vascular disease ? Is current renal failure acute-on-chronic renal failure ? Is thrombotic thrombocytopenic purpura primary versus secondary. If secondary, is it related to collagen vascular disease [1-4] ?

3. Chest radiograph also reveals pulmonary edema.

4. Having the above-mentioned thoughts in mind, I believe we should do the following;

(a) admit the patient to intensive care unit.

(b) management of airways, breathing per ICU team.

(c) control of seizures.

(d) control of hypertension.

(e) several tubes and catheters - endotracheal tube and mechanical ventilation if necessary, nasogastric tube, indwelling foley catheters, IV access etc.

(f) consult Hematology and Nephrology teams urgently.

(g) Investigations - Blood - vonWillebrand's factor protease (ADAMTS- 13 enzyme ) activity, type & crossmatch, ANA, RF, ds-DNA, complement and vasculitic panels, etc, plasma protein immunofixation. Urine - urinalysis, urine for microscopy, 24-hour urine for protein, urine for immunofixation.

(h)Place Vascath catheter.

(i) This patient will need urgent therapeutic plasma exchange performed in tandem with hemodialysis (if feasible)[5]. The replacement fluid for plasmapheresis will be fresh frozen plasma.

(j) systemic corticosteroids such as methylprednisone.

(k) ICU management including strict intake-output data etc.

(l) find out from GP if any investigations were done for miscarriage and hypertension and urgent review of the patient's old hospital chart.


1.Yamada T, Handa Y, Kamikawa T, et al. A case of systemic lupus erythematosus associated with thrombotic thrombocytopenic purpura and hemophagocytic syndrome].Nihon Rinsho Meneki Gakkai Kaishi 2006 Dec;29(6):384-8. Japanese

2.Majithia V, Harisdangkul V : Thrombotic thrombocytopenic purpura in systemic lupus erythematosus: A frequent and severe consequence of active disease. Rheumatology (Oxford). 2006 Sep;45(9):1170-1.

3.Cheung WY: Thrombotic thrombocytopenic purpura and systemic lupus erythematosus - distinct entities or overlapping syndromes? Transfus Apher Sci. 2006 Jun;34(3):263-6

4. Aleem A, Al-Sugair S. Thrombotic thrombocytopenic purpura associated with systemic lupus erythematosus. Acta Haematol. 2006;115(1-2):68-73

5. Mahmood A, Sodano D, Dash A, Weinstein R: Therapeutic plasma exchange performed in tandem with hemodialysis for patients with M-protein disorders. J Clin Apher 2006; 21(2):100-4

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Thein H Oo, MD, FRCP, Attending Hematologist

Caritas St Elizabeth's Medical Center, Tufts University School of Medicine, Boston, USA

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3 July 2007

There have been some very interesting rapid responses here and the range of differential diagnoses suggested reflects the complexity of the case.

Some of the responders have raised a number of very pertinent questions. Please be patient as these will be answered as the case unfolds over the next two parts.

The differences of opinion on likely diagnosis have led to some disagreement on management, for example the appropriateness of the the use of plasma exchange and magnesium sulphate, though there is broad agreement on basic monitoring and stabilisation.

I will not divulge whether the precise diagnosis has been mentioned in the responses, though this will become apparent.

There is one important differential diagnosis that has not been mentioned that we at least considered on the basis of the information already presented. Inclusion of this differential would influence early management.

Many thanks to the responders for their interest in this case.

Competing interests: None declared

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Chris M Laing, SpR nephrology and intensive care medicine

Thames Region

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1. Investigation for recurrent miscarriage would normally begin only after the third miscarriage, so prior to this event would not have necessarily been appropriate.

2. The most likely diagnosis would seem linked to her systemic hypertension. She has had previous pregnancy-induced hypertension, which would increase her risk of developing systemic hypertension later in life, and was noted to be hypertensive in the year preceding these events. Malignant or accelerated hypertension, resulting in malignant arteriolar nephrosclerosis with acute (?on chronic) renal failure and microangiopathic haemolytic anaemia (MAHA) would link all of the presenting features. Did she have papilloedema or hypertensive retinopathy out of interest? Differential diagnosis could include Thrombotic thrombocytopenic purpura (TTP) (but no purpura, and cannot link severe hypertension), systemic lupus erythematosus (SLE) with pre-existing renal involvement (but again I am struggling to link her gross hypertension with this as not classical), Pre-eclampsia/HELLP (but at 10 weeks it is probably too early for this), or sepsis, DIC and ARDS (but would more likely expect hypo- not hypertension).

3. The CXR can be explained by cardiac decompensation and bilateral pleural effusions.

4. She requires intensive monitoring with regular observation, most likely in a HDU/ITU setting, urinary catheterisation and strict fluid balance. A multi-disciplinary approach from cardiologists, nephrologists and intensive care specialists would be optimal. I would request a catheter spcimen urine for urgent microscopy (reducing the contamination from vaginal blood loss), perform an ECG, request a renal ultrasound and organise an autoimmune screen to complete investigations. The most important management step is reduction in blood pressure with careful monitoring as extreme sudden lowering of BP could result in infarction of vital organs. IV furosemide can be used to fluid offload and vasodilate. Hydralazine (iv or orally) and ACE inhibitors (to reduce high circulating renin levels) might be considered, as might a B-blocker such as labetalol, however given her pulmonary oedema, this might be best avoided.

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C M Morgan, SHO O+G (GP VTS)

Chesterfield Royal Hospital, S44 5BL

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