A patient with suspected miscarriage is found to have hypertension, renal failure, and thrombocytopenia: case progression
BMJ 2007; 335 doi: https://doi.org/10.1136/bmj.39239.478495.80 (Published 05 July 2007) Cite this as: BMJ 2007;335:44All rapid responses
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1. Posterior leucoenchalopathy in this lady most likely indicates
hypertensive encephalopathy1,2. Observed MAHA could be due to SLE, HUS,
TTP or scleroderma. An associated immunocompromised state should be
searched for1. Noted hypertension, history suggestive of Raynaud's
syndrome and suspected miscarriage favours diagnosis of SLE, probably with
anticardiolipin or antiphospholipid antibody positivity. One may argue
against it because of successful first three pregnancies. SLE and
"multiparity" are common in "Middle-East", and, we have encountered cases
of SLE diagnosed in third to fifth pregnancies with uneventful or
successful initial pregnancies. One may also speculate development of
scleroderma due to microchimerism after initial three pregnancies3.
2. A 20 to 25% reduction in MAP should be targeted over a few hours.
Many authorities advise it over 2 hrs. Lowe target should be achieved
gradually over days with a watch over target-organ function. Among the
target organs, our priority should be for central nervous system than for
kidneys.
3. Auto-antibody profile targeted for ANAs, dsDNA, ENA, ScL-70,
anticardiolipin antibody titer and dilute Russel's viper venom test
(DRVVT). A kidney biopsy is warranted but contraindicated because of
thrombocytopenia.
References:
1. Judy Hinchey, Claudia Chaves, Barbara Appignani et al. A
Reversible Posterior Leucoenchalopathy Syndrome. N Engl J Med 1996;334:494
-500.
2. Carl J Vaughan, Norman Delanty. Hypertensive emergencies. Lancet
2000; 356: 411–17.
3. J Lee Nelson, Daniel E Furst, Sean Maloney et al. Microchimerism
and HLA-compatible relationships of pregnancy in scleroderma. The Lancet
1998; 351:559-562.
Competing interests:
None declared
Competing interests: No competing interests
1. Posterior leucoencephalopathy on scan indicates oedema casued by
rasied inta-cranial pressure. The probable diagnosis is POSTERIOR
REVERSIBLE CEREBRAL OEDEMA SYNDROME (PREP) which is recognsied to be
caused by raised BP. It is also associated with drug therapies including
Hypertensive drugs, Immunsopression drugs and Chemotherapy. Cocaine has
also been linked to several cases and there are reports in the literature
of cases being linked to meningitis. ECLAMPSIA AND PRE-ECLAMPSIA are
recongnised underlying conditions as is HUS.
Presenting compaints fit with the history and include:
- Headache; altered mental state; Coma and convulsions; Papilloedema;
Elevated BP
2. Lowering blodd pressure: AIM to reduce blood pressure to ~110mmHg
over 4 hrs. Use an intra-arterial line to monitor the pressure changes. A
25% reduction in MAP over 24 hrs is also recognised as appropriate to
limit CVA risks.
The use of i.v Frusemide with either i.v.Sodium Nitroprusside or i.v
Labetalol should be used in the first instance.
GRADUAL decrease is crucial as cerebral autoregulation is lost
3. Diagnostic test carried out should include a sepsis screen to rule
out meningitis. Lumbar puncture would be contra-indicated if sigans of
rasied ICP still present so reducing the BP must be number 1 priority.
An antibody screen including ANA; pANCA would be jusitified as
scleroderma, Glomerulonephritis and SLE have been shown as casues of
malignant hypertensive crises. A renal biopsy would be extremelly helpful
in recognising any glomerulnephritis condition.
Would a screen for a PHAEOCHROMOCYTOMA be warranted in a young
hypertensive??? Cathecholamines could be measured in a 24hr urine
collection and an USS abdomen/ CT scan perfomed.
Competing interests:
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MRI scans shows multiple white matter lesions without any evidence of
surrounding oedema or mass effect i.e. no midline shift. These appearances
are typical of a progressive multifocal leucoencephalopathy (PML),
commonly seen in patients with advanced HIV infection. However PML has
been reported in other non - HIV conditions such as patients with SLE,
lympho- and myeloproliferative diseases, sarcoidosis, chronic
granulomatosis, transplant patients and Whipple’s disease.
In her case, history of suspected miscarriage, renal involvement, seizures
and possible pulmonary haemorrhages are all suggestive of SLE.
Diagnostic tests include HIV test and CSF PCR for JC virus. A negative JC
virus in the CSF will not exclude PML as its sheds intermittently in to
the CSF, another reason for negative JC PCR is deep seated lesions of PML.
So repeated CSF examination is important. A stereotactic brain biopsy will
provide a definitive diagnosis. Histopathological hallmarks of PML are
triad of multifocal demyelination, enlarged oligodendroglial nuclei and
enlarged bizarre astrocytes. However brain biopsy carries a significant
morbidity and mortality. Therefore typical radiological appearances and a
positive JC virus suffice to make a diagnosis of PML in these conditions.
Competing interests:
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1) Posterior leukoencephalopathy syndrome affects the cerebral white
matter. Oedematous lesions particularly involve the posterior parietal and
occipital lobes. This condition is clinically characterised by
headache,vomiting, seizures, visual disturbances and altered sensorium.
Posterior leukoencephalopathy syndrome is often associated with an abrupt
increase in blood pressure and is usually seen in patients with eclampsia,
renal disease, and hypertensive encephalopathy. It is also seen in the
patients treated with cytotoxic and immunosuppressive drugs such as
cyclosporin, tacrolimus, and interferon alfa.
2) In this Hypertensive emergency with a BP of 240/127 and evidence
of end organ damage i.e papilloedema,pulmonary oedema and encephalopathy
immediate reduction of MAP by 20-25% in first 2 hours is necessary to
prevent or minizine end organ damage (i.e hypertensive
encephalopathy,Intracranial Haemorrhage,Unstable angina,Acute MI,Acute
left ventricular failure with pulmonary Odema,Dissection of aorta or renal
failure). Then SBP can be reduced to 160 and diastolic to 100 over next 4-
6 hours.Quick reduction of BP to normal can be catastrophic.
3) Investigate for underlying cause by requesting
Autoantibody screen and especially looking for
ANA,Anti dsDNA and Anti Sm for SLE,
ANCA,
Anti SCL-70 and Anti Centromere,
Anti cardilolipin and Lupus anti coagulant,
Anti GBM,
ADAMST 13 for TTP
Ref:
R K Garg Posterior leukoencephalopathy syndrome ,Postgrad Med J 2001;77:24
( January )
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Competing interests: No competing interests
The MRI reveals the typical pattern of changes seen with posterior
reversible encephalopathy syndrome (PRES). This syndrome is characterised
by visual changes, headache, seizures and altered sensorium. The MRI
changes are thought to represent vasogenic oedema. PRES occurs with a
diverse clinical conditions including preeclampsia, glomerulonephritis,
systemic lupus erythematosus and antiphospholipid syndrome, thrombotic
thrombocytopenic purpura and hemolytic-uremic syndrome, as well as drug
toxicity from agents such as cyclosporine, tacrolimus, cisplatin, and
erythropoietin. Management should be directed towards control of blood
pressure aiming for a mean arterial pressure of 105-125 mm Hg, control of
seizures and discontinuation of provocative drugs. A case report suggested
intravenous nitroglycerin may aggravate PRES, and intravenous nimodipine
may be a useful agent on the basis of its effects in preventing vasospasm
as well as neuroprotection.
The patient's hypertension is chronic, and I suspect her renal
dysfunction is also chronic given her hypocalcemia, hyperphosphatemia,
severe compensated metabolic acidosis and anaemia (the degree of
haemolysis on presentation on presentation seems mild based on the
minimally elevated bilirubin).
The features of microangiopathic haemolytic anaemia,
thrombocytopenia, renal failure, hypertension and pulmonary oedema in this
patient can be seen with any cause of accelerated hypertension. As the
renal failure and thromocytopenia were severe at presentation and rapidly
progressive haemolytic-uraemic syndrome (HUS) seems the most likely
diagnosis, scleroderma renal crisis next most likely in view of the
history of Raynauds and chronic hypertension, although an identical
picture could be seen with catastrophic antiphospholipid syndrome, acute
glomerulonephritis or acute hypertension due to renal artery stenosis,
primary aldosteronism or phaeochromocytoma. The latter needs to be
considered in view of pulmonary oedema which could be due to catecholamine
cardiomyopathy.
Investigations I would perform would include :
1. Urinalysis on a catheter specimen looking for casts, dysmorhic red
blood cells which might suggest acute glomerulonephritis.
2. I would chase previous results for renal function.
3. Echocardiography to assess cardiac function - globally poor left
ventricular systolic function should raise suspicion of phaeochromocytoma,
left ventricular hypertrophy would confirm longstanding hypertension.
4. Serum haptoglobin should be undetectable in the setting of
haemolysis, a Coombs test should be negative in non-immune mediated
haemolysis.
5. Ultrasound of kidneys (small if chronic disease) with renal artery
dopplers.
6. Autoantibody screen including anti-centromere and SCL-70
antibodies, anticardiolipin antibodies and lupus anticoagulant, and anti-
neutrophil cytoplasmic antibodies.
7. Plasma metanephrines to exclude phaeochromocytoma.
8. ADAMTS13 levels with respect to HUS / TTP.
9. If the above were unhelpful renal biopsy may be illuminating.
With respect to management :
1. This lady would be best managed in intensive care with an arterial
line and Swan-Ganz monitoring.
2. Management of blood pressure must include an angiotensin-
converting enzyme inhibitor given the possibility of scleroderma renal
crisis . In addition I would use intravenous nimodipine, and avoid
nitrates in view of the presence of PRES on MRI. I would lower the
patients blood pressure gradually aiming for a mean arterial pressure of
105-125mm Hg.
3. The possibilities of HUS and catastrophic antiphospholipid
syndrome mandate plasma exchange until these diagnoses are excluded or
other diagnoses are established.
4. If phaeochromocytoma is a possibility I would use intravenous
magnesium because of its specific benefits in phaeochromocytoma crisis /
catecholamine cardiomyopathy. Magnesium levels would need to be monitored
at least every 4 hours because of the potential for toxicity in the
setting of renal failure.
The earliest gestation at which preeclampsia has been reported is at
15 weeks. Significant renal dysfunction is a rare complication of severe
preeclampsia. In 12 years as an obstetric physician at a tertiary referral
obstetric hospital with approximately 3000 deliveries per year, I have
seen only a handful of cases of renal failure with severe preeclampsia. I
doubt that the patient had been pregnant recently. Her alkaline
phosphatase was normal (usually elevated in pregnancy due to placental
isoenzyme), and her serum beta-hCG would have been markedly elevated for a
prolonged period given her renal dysfunction had she been pregnant
recently.
Competing interests:
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This patient has posterior leucoencephalopathy which is related to
malignant hypertension and renal failure. It is reversible if treated
promptly. Blood pressure should be reduced to normal as early as
possible. Such a situation is likely in patient with collagen vascular
disease like SLE. The possibility of lupus with catastrophic
antiphospholipid syndrome or HUS is the likely etiology in this case.
Competing interests:
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We shouldn't forget bacterial endocarditis amongst the causes of
secondary TTP: echocardiogram/TOE, blood cultures --and antibiotics while
we have them.
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Our first impression after reading this fascinating case was
accelerated hypertension leading to acute vascular damage resulting in
end organ dysfuction ( retina, brain, kidney, liver).
The cause of malignant hypertension may be Thrombocytopenic
Thrombocytopenic Purpura (TTP) charachterised by thrombocytopenia,
microangiopathic haemolytic anaemia, acute renal failure and reversible
posterior leukoencephalopathy syndrome (RPLS).
TTP may be accompanying vascular collagen diseases such as Systemic
Lupus Erythematosus (SLE).
Regarding the first question: what does leucoencephalopathy found on
the patient's MRI indicate?
These clear symmetric areas of hyperintensity involving the occipital
lobes may be part of the reversible posterior leucoencephalopathy syndrome
that has been reported in association with malignant hypertension, toxemia
of pregnancy or immunosupresant drugs.
The mechanisms of injury or pathophysiology is not well understood.
There are few theories. One of them postulated that the brain
autoregulation is overcomed by the sudden increased in blood pressure
leading to arteriolar dilatation, capillary leakage and consequently
extracellular oedema secondary to extrasudation of plasma. Another
mechanisms postulated is ischaemia secondary to severe vasoconstriction
that seems to be supported by angiography. Other authors postulate
hypoalbuminemia and steroids as a couse of leucoencephalopathy.
Regarding the second question: How quickly should you lower the
patient's blood presure?
This is a difficult one as we have two organs of interest to preserve
function and the mechanism and urgency of control the blood pressure may
differe between them. For instance to avoid further neurological damage
the blood pressure should be controlled in hours, however, this may afect
the perfusion pressure of the kidney aggravating the renal function.
In consequence our goal would be to reduce the mean arterial pressure
by approximately 25-30% over the first 24-48 hours by using Na
Nitroprusiate infusion. The tittration of the infusion per hour will be
according to invasive blood pressure monitoring, clinical signs and
symptoms.
Sodium and volume depletion may be severe, and volume expansion with
isotonic solution may be considered.
Finally, regarding the last question, What diagnostic tests would
you do next?
Laboratory tests:
1- 24-hour urine for proteins and creatinine
2- Eritrosedimentation rate (ESR)
3- CRP
4- Antinuclear antibody
5-Antidouble stranded DNA antibody
6-Anti-Sm (and anti RNP) antibody
7-Anticardiolipine antibody (IgM, IgG, IgA)
8- Antibeta2 glycoprotein 1 antibody
9-Lupus anticoagulant
10-DDimer
11-Dilute Russel Viper Venom Time (or lupus anticoagulant test)
12-C3-4 and CH50
13-Thyroid antibodies
14-Testing lipid basal
15-Hemocysteine
16- Fibrinogen
17- Coombs' test and VDRL
18- Renin level in plasma
19-cathecolamines in urine
20- Serial blood cultures
Others tests:
1- Echocardiogram
2-Renal ultrasound and doppler of renal arteries if caucasian
3-Bone marrow biopsy
4- Renal biopsy (when the patient is stable and depending on the above
results)
Competing interests:
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Competing interests: No competing interests
1. Posterior leucoencephalopathy is an increasingly recognised
complication of hypertensive encephalopathy due to malignant hypertension
and eclampsia.
2. This case presented with a hypertensive emergency, therefore blood
pressure should have been reduced immediately i.e within minutes-hours.
3. Investigation of a case of malignant hypertension,
microangiopathic haemolysis, renal failure and encephalopathy should
include: Autoantibody screen for collagen disease including ANCAs &
anti-GBM antibodies, urinary free catecholamines, plasma
renin/aldosterone, renal arteriography/isotopic renogram and renal biopsy.
With normal prothrombin time and activated partial thromboplastin time,
antiphospholipid syndrome and DIC are less likely. Malignant hypertension
in this case could have been due to eclampsia (HELLP), collagen disease
such as SLE, Goodpasture syndrome, renal artery or renal parenchymal
pathology.
Competing interests:
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Competing interests: No competing interests
Malignant hypertension with underlying disease
1 What does posterior leucoencephalopathy found on the patient's
magnetic resonance imaging scan indicate?
This images can be seen in Malignant Hypertension which was confirmed with
fundoscopy which demonstrated flame haemorrhages and papillo-oedema.
She probably has a chronic hypertension as well as chronic renal failure.
Thrombocytopenia, red cell fragmentation on blood film, raised bilirubin
concentrations, and raised lactate dehydrogenase concentrations were
consistent with a diagnosis of microangiopathic haemolytic anaemia.
2 How quickly should you lower the patient's blood pressure?
First she has to be dialyzed with ultrafiltration which will lower a bit
her blood pressure. After that her blood pressure should be lowered
gradually reaching a median arterial pressure of 100 in the first 24
hours.
3 What diagnostic tests would you do next?
I agree with the author in the diagnosis of microangiopathic haemolytic
anaemia which is secondary to Malignant Hypertension.
She has neither blood cast nor protein in urine which almost exclude
glomerulonephritis.
We should do test to rule out, lupus, antiphospholipidic syndrome,
vascultis.
ANCA, Urine sample for protein/creatinine, CRP, Antinuclear antibody,
Antidouble stranded DNA antibody, Anti-Sm ,anti RNP antibody,
Anticardiolipine antibody,Lupus anticoagulant, C3, C4 and CH50,Coombs'
test.
We should do an echocardiogram to test cardiac function and if there is
repercusion of her chronic hypertension
Renal ultrasonography to evaluate kidney size and renal dupplex to
evaluate renal arteries and intrarrenal perfusion.
Competing interests:
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Competing interests: No competing interests