Journ1al of Neurology, Neurosurgery, and Psychiatry, 1974, 37, 521-525

Pregnancy, subarachnoid haemorrhage, and theintravascular coagulation syndrome

J. R. HERON, E. C. HUTCHINSON, W. N. BOYD, AND G. M. ABER

From the Department of Neurology, North Staffordshire Hospital Centre,Hartshill, Stoke-on-Trent, Staffordshire

SYNOPSIS Two patients are described who developed subarachnoid haemorrhage during pregnancyand the puerperium. In both patients there was clinical, haematological, histological, and renalangiographic evidence of the intravascular coagulation syndrome. No source of intracranial bleedingwas demonstrated by bilateral carotid angiography in either patient. We suggest that the sub-arachnoid haemorrhage was a result of the intravascular coagulation syndrome in both patients.

In the past 10 years, 145 female patients withsubarachnoid haemorrhage have been investi-gated and treated in the Department of Neurol-ogy at the North Staffordshire Hospital Centre.Sixty-eight of these were of child-bearing age.Five were pregnant at the time of the haemor-rhage. Investigations in the group with sub-arachnoid haemorrhage in pregnancy revealedcerebral arteriovenous abnormalities in two ofthe five and an internal carotid aneurysm in athird. The purpose of this communication is todescribe the events in the remaining two patientsin whom the evidence indicates that the sub-arachnoid haemorrhage was caused by the intra-vascular coagulation syndrome.

CASE 1

J.D., aged 36 years, had an uncomplicated pregnancyin 1955. She was admitted to the maternity unit ofthe North Staffordshire Medical Centre on 12December 1970, in the 26th week of pregnancy with atwo-week history of headache, ankle oedema, and atrace of proteinuria. Her blood pressure had beennormal throughout the early pregnancy.

Forty-eight hours before admission she developedincreasingly severe occipitofrontal headache, confu-sion, restlessness, and violent behaviour. Examina-tion on admission to the maternity unit revealed aconfused and irrational patient with severe headacheand vomiting. Her blood pressure was 240/140mmHg and she had generalized oedema and grossproteinuria. A diagnosis of eclampsia was made andshe was treated with morphine, chlorpromazine, and

frusemide. Shortly after admission she was observedto have a classical fit with generalized convulsion,urinary incontinence, and loss of consciousness.Anticonvulsant and hypotensive treatment wasinstituted with diazepam and methyl dopa respec-tively. Labour was induced and a non-viable fetuswas delivered. She continued in an irritable, con-fused, and incoherent state with a blood pressure of180/110 mmHg. Forty-eight hours after admissionshe was transferred to the neurological department.At that time she showed the clinical signs of bilateralpapilloedema and neck rigidity. Cranial nerveexamination was normal and there were no focalneurological signs in the limbs. A clinical diagnosisof subarachnoid haemorrhage was made and con-firmed by lumbar puncture, the cerebrospinal fluid

TABLE 1HAEMATOLOGICAL DATA ON BOTH PATIENTS INDICATINGMAXIMUM ABNORMAL VALUES AND VALUES ON RECOVERY

Case 1 (J.D.) Case 2 (D.T.)

Maxinmumt Value Maximum Valueabnormal after abnormtial af'ter

value recovery value recovery

Haemoglobin(g/100 ml) 11-4 14 6 9 9 15-3

White cell count(/cu. mm) 13,600 6,900 16,200 3,000

Platelet count(/cu. mm) 100,000 504,000 37,000 460,000

Reticulocytes (°/ ) 4 0 5-5 0Abnormal cells* + + + 0 + + + 0

* Burr cells, schistocytes, helmet cells, crenated cells.521

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TABLE 2BIOCHEMICAL DATA ON BOTH PATIENTS INDICATING

MAXIMUM ABNORMAL VALUES AND VALUES ON RECOVERY

Case I (J.D.) Case 2 (D.T.)

Maximum Value Maximum Valueabnormal after abnornmal after

value recovery value recovery

Fibrinogen(mg!100 ml) 1,090 350 400 350

Fibrinogen degrada-tion products(jsg/ml) 640 0 160 0

SGOT units (!ml) 100 30 110 15SGPT units (/ml) 45 15 140 15SLD units (/ml) 1,320 730 1,400 500Albumin (g/100 ml) 2 5 3-2 2-8 4-7Urine protein

(g/24 hr) 5 0 0-6 0Blood urea(mg/100 ml) 56 21 250 24

Blood creatinine(mg/100 ml) 1-5 07- 8 5 0-8

Creatinine clearance(ml/min) 40 97 2 109

being uniformly bloodstained with xanthochromiaat an opening pressure of 290mm of water. Haemato-logical, biochemical, and renal investigations carriedout at that time suggested the presence of intra-vascular coagulation (Tables 1 and 2). Bilateral caro-tid angiograms revealed no site of intracranialbleeding. During the next two weeks she made agradual and complete clinical recovery and at dis-charge three weeks after her admission neurologicalexamination was normal and her blood pressure was130/90 mmHg. All treatment was discontinued beforeher discharge. At outpatient follow-up four monthsafter the acute episode the blood pressure was100/80 mmHg and renal function was entirely nor-mal (Table 2). The haematological manifestations ofthe intravascular coagulation syndrome had entirelydisappeared by the fifth day after delivery of thefetus.

CASE 2

D.T., aged 27 years was delivered normally of a

healthy full-term male infant on 21 July 1970. Thiswas her third pregnancy, her second pregnancy threeyears previously having been complicated by a post-partum haemorrhage. She had never been hyper-tensive and her general health was good. Twohours after delivery she became restless and com-plained of headache. Five minutes later she developedextensor spasms of the arms and legs and lostconsciousness. She was transferred to the neuro-logical unit. On examination she was deeply un-

conscious. General system examination was normaland the blood pressure was 140/90 mmHg. Neckrigidity was present, the pupils were pin-point andnon-reacting. The fundi were normal, and the cornealreflexes were absent. In the limbs tone was flaccid,tendon reflexes were normal, and the plantar re-sponses were extensor. A clinical diagnosis of sub-arachnoid haemorrhage was confirmed by lumbarpuncture. The cerebrospinal fluid at an openingpressure of 250 mm of water was uniformly blood-stained with xanthochromia. Bilateral carotidangiograms revealed no source of intracranial bleed-ing. Details of all other investigations are given inTables 1 and 2.

Twenty-four hour urinary output was persistentlybelow 400 ml and there was no response to intra-venous mannitol, confirming the presence of oliguricrenal failure. A diagnosis of subarachnoid haemor-rhage and renal failure associated with the intra-vascular coagulation syndrome was made on thebasis of the clinical, haematological, and bio-chemical findings and treatment was started withheparin and peritoneal dialysis. Within five days ofstarting treatment the patient was responding toquestions but was still drowsy and confused andshowed difficulties in sustained concentration. Overthe subsequent 10 days she became cooperative withinsight and there were no abnormal signs on neuro-logical examination. Clinical improvement wasmaintained and at discharge five weeks after admis-sion she was alert and showed no intellectual deficit.Neurological examination was normal. Peritonealdialysis was discontinued after six days but fullrecovery of renal function was not achieved untilthree months after the acute episode (Tables 1 and 2)at which time the blood pressure was 110/70 mmHg.The haematological features of the intravascularcoagulation syndrome had entirely disappeared 14days after commencing treatment.

CASES 1 AND 2: FURTHER INVESTIGATIONSRADIOLOGY Bilateral carotid angiography Neitherpatient showed any evidence of aneurysm orangioma. In one patient (J.D.) spasm was present inthe terminal portions of the internal carotid arteriesand in the main trunks of the anterior and middlecerebral vessels. In the other patient (D.T.) theanterior cerebral vessels were narrowed andstretched, suggesting a degree of dilatation of thelateral ventricles. Radiographs of the chest werenormal in both patients.

Intravenous pyelography This was performed onD.T. three weeks after the onset of the subarachnoidhaemorrhage. It showed normal renal function withresidual pregnancy dilatation of the upper urinary

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Pregnanicy, subarachnoid haemorrhage, and the intravascular coagulationi syndrome

la)

FIG. 1. (a) Late arterial phase of selective r-enal angiogram (right) showinig focal peripheral arterial diseasecharacterized by beading (white arrow) and cork-screw appearance (black arrow) of peripheral interlobararteries. (b) Nephrogram phase of the same series of renal angiograms showing a small peripheral infarct(arrow) in the lower pole with associated stasis of the contrast medium in this area.

tract on the right side. The pyelogram performed onthe second patient (J.D.) two weeks after the onset ofsubarachnoid haemorrhage was normal.

Selective renal angiography The main renal vesselsand their segmental branches were normal in bothcases. Bilateral focal peripheral vascular abnormali-ties were present in both cases, characterized bytortuosity and narrowing of the terminal interlobarvessels giving a beaded appearance (Fig. l a). Inaddition, stasis of contrast medium was noted in thelower pole of one kidney (D.T.) (Fig. lb) and an

area of probable cortical ischaemia was observed inthe left kidney of the other patient (J.D.).

RENAL BIOPSY Percutaneous renal biopsies wereperformed at the same time as selective renal angio-graphy. The findings for each patient are detailedbelow.

J.D. Serial sections showed that about one-thirdwas medulla. The remainder was cortex containingan average of 11 assessable glomeruli. There were noabnormalities of the arterioles or of one smallmuscular artery included at the junction of the cor-tex and medulla. There was widespread minimaltubular degeneration, most marked in the convolutedtubules whose cells were about half their normalthickness. In the medulla the tubules appeared nor-

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mal but many contained small cellular 'casts'. Twoglomeruli showed slight pericapsular fibrosis.Adhesions between tuft and capsule were seen in themajority. One showed a small focal area of sclerosisat the site of attachment of the tuft. There were noother abnormalities. The glomerular capillary loopswere all patent and there was no hypercellularity norwere any microthrombi seen. No completelysclerosed glomeruli were included in this biopsy.

D.T. Semi-serial sections at two levels showed thatthe biopsy consisted of one-third medulla and theremainder cortex, which contained an average of 20glomeruli. The interstitial tissues showed focal slightincrease of fibrous tissue, and one area of round cellinfiltration, surrounding glomeruli that showed peri-capsular fibrosis and atrophy of the tuft. Many ofthe remaining glomeruli appeared entirely normal, afew showed pericapsular fibrosis, and some showedsome mesangeal thickening with small foci of hyper-cellularity. No active lesions were present. There wassome tubular damage, possibly associated with themore severely affected glomeruli. The remainingtubules appeared normal. About 50°/ of the glomer-uli seen in this specimen were unaffected. No micro-thrombi were seen.

DISCUSSION

The majority of observers agree with Walton's(1955) conclusion that the occurrence of sub-arachnoid haemorrhage in normal pregnancy is acoincidence. In eclampsia, however, subarach-noid haemorrhage is a recognized complication(Donnelly and Lock, 1954). The figures forincidence vary from 1 in 2,000 (Cannell andBottrell, 1956), to 1 in 11,000 pregnancies(O'Leary et al., 1962); the variation wouldappear to be an expression of the observer'sinterests rather than social or racial factors. Sub-arachnoid haemorrhage may occur at any timein pregnancy and the management and treat-ment is that routinely practised in the non-gravidfemale; the morbidity and the mortality is thesame in both groups (Pool, 1965). Although thecause of subarachnoid haemorrhage may beeither a berry aneurysm or a congenital arterio-venous malformation, negative angiograms arenot uncommon so that the cause of bleeding isfrequently uncertain.

In the two patients described, haematological,biochemical, and histological evidence indicatesthat the intravascular coagulation syndrome was

responsible for both the subarachnoid haemor-rhage and the other clinical features observed inboth patients. In neither patient was a vascularanomaly demonstrated by bilateral carotidangiography and in the clinical circumstancesvertebral angiography was not considered justifi-able. In both patients the haematological criteriaset out by Brain et al. (1962) were satisfied and inboth an elevation in the concentration of theserum fibrin degeneration products was demon-strated.The widespread nature of the disorder was

apparent from the involvement of the lungs,brain, liver, and kidneys. Selective renal angio-graphy showed unequivocal abnormalities of theinterlobar vessels in both patients (Fig. la andb). Minimal abnormalities of the intrarenalvascular pattern were demonstrated on histo-logical examination of the renal biopsies. Theabsence of intravascular microthrombi could beaccounted for by the fact that the renal biopsieswere carried out after recovery from the acuteepisode. The renal histological findings in bothpatients were similar to those noted in otherpatients who have been studied after recoveringfrom the intravascular coagulation syndrome(Shinton et al., 1964; McKay, 1969; Moncrieffand Glasgow, 1970) and we have observedidentical renal angiographic appearance in otherpatients with this syndrome (Boyd, unpublisheddata).Although the 'triggering' factor responsible

for initiating intravascular coagulation in onepatient (J.D.) seems to have been associatedeclampsia, which is the commonest cause of sub-arachnoid haemorrhage during pregnancy (Don-nelly and Lock, 1954), the precipitating cause inthe second patient was by no means clear. In thispatient the onset of acute renal failure in theearly puerperium was similar to that reported byRobson et al. (1968) in four patients in whomthere was histological evidence of partial or com-plete occlusion of interlobular arterioles andglomerular capillaries by fibrin thrombi. Unlikeour patients, congestive cardiac failure associatedwith a 'cardiomyopathy' was a prominentfeature in all four patients of Robson et al. (1968)and indeed it was this rather than renal failurethat was responsible for the death of twopatients. When their data were examined, therewas evidence of thrombocytopenia and haemo-

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Pregnancy, subarachnoid haemorrhage, and the intravascular coagulation syndrome

lytic anaemia associated with many abnormalred cells in the peripheral circulation, supportingthe possibility that intravascular coagulationmay also have played a part in determining theclinical features.On the basis of our two patients it is interesting

to review the early pathological observations ofMcKay et al. (1953) who presented arguments infavour of intravascular fibrin deposits in arteri-oles and capillaries as one mechanism for thedisseminated tissue necrosis and haemorrhageand the bilateral renal and pituitary necrosisobserved in 21 patients who died from toxaemiaof pregnancy. Reviewing their postmortem find-ings, there were two patients with primary sub-arachnoid haemorrhage, two with subarachnoidhaemorrhage and intracerebral haemorrhagecombined, and one patient with primary intra-cerebral haemorrhage alone. It is not unreason-able to suggest that the underlying mechanismfor subarachnoid haemorrhage in these indi-viduals was similar to that observed in ourpatients.Our decision to treat one patient with post-

partum subarachnoid haemorrhage with heparinwas taken after the diagnosis of the intravascularcoagulation syndrome associated with acuterenal failure had been confirmed and aftercerebral angiography had failed to discloseeither a berry aneurysm or other intracranialvascular malformations in the carotid circulation.Until a controlled trial of this form of therapyhas been carried out in a wide range of patientswith the intravascular coagulation syndrome itis clear that a degree of caution is still called forbefore one can justify this potentially hazardousform of treatment.

We are grateful to Dr. B. Ockenden, consultantpathologist, for the histological details and to Dr.Richard Burden, research fellow, for the estimationsof the plasma fibrinogen and fibrin degradationproducts.

REFERENCES

Brain, M. C., Dacie, J. V., and Hourihane, D. O'B. (1962).Microangiopathic haemolytic anaemia: the possible role ofvascular lesions in pathogenesis. British Journal of Haema-tology, 8, 358-374.

Cannell, D. E., and Bottrell, E. H. (1956). Subarachnoidhemorrhage and pregnancy. American Journal of Obstetricsand Gynecology, 72, 844-855.

Donnelly, J. F., and Lock, F. R. (1954). Causes of death in533 fatal cases of toxemia of pregnancy. American Journalof Obstetrics and Gynecology, 68, 184-190.

McKay, D G, Merrill, S. J., Weiner, A. E., Hertig, A. T.,and Reid, D. E. (1953). The pathologic anatomy ofeclampsia, bilateral renal cortical necrosis, pituitarynecrosis, and other acute fatal complications of pregnancy,and its possible relationship to the generalized Shwartzmanphenomenon. American Journal of Obstetrics and GYnecol-ogy, 66, 507-539.

McKay, D. G. (1969). Progress in disseminated intravascularcoagulation. California Medicine, 111, 186-199.

Moncrieff, M. W., and Glasgow, E. F. (1970). Haemolytic-uraemic syndrome treated with heparin. British MedicalJournal, 3, 188-191.

O'Leary, J. A., Sadowski, J., and Bepko, F. J., Jr. (1963).Subarachnoid hemorrhage and pregnancy. GeorgetowvnMedical Bulletin, 17, 28-32.

Pool, J. L. (1965). Treatment of intracranial aneurysms duringpregnancy. Journal of the American Medical Association,192, 209-214.

Robson, J. S., Martin, A. M., Ruckley, V. A., and Mac-Donald, M. K (1968). Irreversible post-partum renalfailure. A new syndrome. Quarterly Journal of Medicine,37,423-435.

Shinton, N. K, Galpine, J. F., Kendall, A. C., and Williams,H. P. (1964). Haemolytic anaemia with acute renal failure.Archives of Diseases of Childhood, 39, 455-464.

Walton, J. N. (1956). Subarachnoid Haemorrhage. Living-stone: Edinburgh.

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