APLA Positive Pregnancy with Peripartum Complications

APLA Positive Pregnancy with Peripartum Complications

Presentor : Dr. Prashanthi Vemulapalli

Designation : Fellow OBSMED

Hospital : Fernandez Hospital, Hyderabad

Date of Presentation : 17.08.2016

Mrs. J.

Age:26 yrs

Resident of Hyderabad

Graduate, home maker. Earlier worked for

multinational Bank

Primi, booked at 8wks gestation

OBH:ML:1yr,NCM

MH: Irregular cycles

Past History

On and off episodes of unilateral Raynauds

phenomenon involving left hand on exposure to cold

weather

Started when she went to USA in 2013, (cold

temperatures), episodic lasting days during the

3months stay.

Excruciating pain in left index and thumb, followed by

bluish discolouration

MRI hand to r/o glomus tumour was normal

Past History

2014 admitted in NIMS when episode recurred due

to AC in office.

No arthralgias/mucosal ulcers/alopecia/sicca

symptoms/skin tightening

No photosensitivity/malar rash

No Red eye/claudication

No trauma/smoking/DM/HN

Evaluation- ?Secondary Raynauds or local causes

Ds DNA:Negative

ACL IgM :positive

LAC:positive

ANA:Speckled

VIT B12/FOLIC ACID :WNL

Arterial and venous DOPPLER HAND:NORMAL

Started on heparin/amlodepin

Maintained on warfarin

symptom free since then; she was off work

Symptoms recurred 1 year later when she rejoined work: exposed to AC

Stepped up warfarinwas Ok

Family H/O: No history of arthritis

Father died of bone malignancy

Personal H/o: gave up her job as symptoms got

aggravated by AC at workplace

Present Pregnancy

Married, conceived spontaneously

Booked in early pregnancy : 8wks

MULTIDISCIPLINARY CARE

Started on enoxaparin 60mg / Ecospirin 150mg

Follow ups regular

Occasional tingling of fingers; advised nifidepine 10mg

bd at 25 wks for an episode of Raynauds which lasted

10days but took irregularly

At 23 weeks had genital herpes treated with acyclovir

SCANS:WNL

Admitted at 32 weeks with swelling and tingling lower limbs

Admission BP 170/120 mm Hg

Urine albumin:4 +/LDH:331/PLT 49K; transaminases normal

Inj MGSO4/steroid 1st dose was given/

In v/o severe Preeclampsia, partial HELLP, she was taken for

LSCS

Received 6 units RDP intraoperatively: plt 49k

1.6KG boy baby.

Intraperitoneal drain :20cc

26 yrs pirmi At 32 wks

APLA: On Heparin/Ecospirin

Secondary Raynauds phenomenon

Sudden onset severe PE(BP>160/110,Urine

albumin:4+,LDH >,plt:49k)

LSCS

Received MGSO4

POD2

(POD 0 AND 1:Uneventful)

POD 2:Developed SOB/blurring of vision/

PR:120 /min;BP:150/100;SPO2:77%

RS: Normal

ABG: resp alkalosis

2D Echo: Mild pericardial effusion/no RV strain

ECG: Tachycardia

CXR: Pulmonary edema

Plt:21k.other parameters stable

Received lasix/morphine/ IV labetolol

Pulmonary Embolism

PPCM

Pulmonary edema

Blurring of vision: Retinal detachment/occipital

infarct/

Shifted to century hospital for multidisciplinary care

At Century Hospital

Urinary

metanephrines:wnl

Heparin Ab:negative

CXR:pulmonary edema

Usg abdomen:normlal

Renal Doppler:normal

2D ECHO:normal

MRI:PRES

MRV:normal

Fundoscopy:exudative

RD,Macular

edema,conjunctival edema

LFT: rising LDH:824

Procalcitonin:normal

NASAL SWAB:NO MRSA

RECTAL SWAB:NO VRE

Pulmonary Edema:Hypertensive Crisis

Symptoms improved over 24 hrs

Treated symptomatically

Anti hypertensives:prazosin/amlodepin/ labetolol

Heparin withheld in v/o thrombocytopenia

Diuretics

Topical/systemic steroids for macular edema

Investigations

Platelet:20,000-1 lakh

Hemoglobin:6.0-10gm

Creatinine:1-3

Coagulation profile: WNL

DISCHARGED A WEEK LATER

Nifedepin 5mg od

wysolone 15mg

Topical steroids

Supplements

Opthalmology FU

Treatment

Steroids were being tapered at 5mg/week

Complained of severe pain, photophobia and

redness in both eyes since discharge from century

Referred to LVPEI- diagnosed as anterior uveitis-

local steroids given- improved over 5d-7 days

Retinal angio done at LVPEI. H/o fever one day prior

to the procedure

26th POD

Readmitted on…26th POD with high grade fever of

5days duration with dysuria/cough

Mild anemia 8-9gm/dl Platelet Trend:min-

max10K-1LAKH

Creatinine high 1.9mg/dl

Urine c/s:E coli 10^5 treated with Inj cefaperazone

sulbactum. ( UTI with AKI?)

26th POD

Clexane for 2days later stopped

Labetalol 100mg tid/ nifedepine sr 10mg tid

Fever subsided but mild cough persisted

Creatinine Showed rising trend/ worsening

thrombocytopenia, anemia

Transferred to NIMS for further care

Problems

APLA with secondary Raynauds

POSTPARTUM preeclampsia with ? Partial HELLP

Postpartum pulmonary oedema

PRES

ANTERIOR UVEITIS

Mild anemia, worsening thrombocytopenia

AKI

UTI

At NIMS

Fever, tacycardia, tachypnoea,

sPO2 91%,

BP 140/90

? CAPS triggered by infection

? Sepsis ARDS

TTP/HUS/PTE

At NIMS ANTI GBM Ab:negative:

Anti ccp:negative

IgM RF:negative

ANA by IF:negative

Anti dsDNA:negaive

ACL IgG/IgM:POSITIVE

LFT:WNL

Schistocytes:negative

Procalcitonin:2.6

Usg abdomen:hepatosplenomegalyb/l HUN/ increased cortical

echogenecity in kidneys

CT chest- fibrosing alveolitis with superimposed

infection

BAL cultures sterile

Blood and urine culture: sterile

Nephrologist consult taken

methyl prednisolone for 3 days, therapeutic

anticoagulation, other supportive measures

Creatinine reduced from 3mg to 1.1mg

Renal biopsy planned after correction of

thrombocytopenia ….. ? CAPS vs lupus

Wysolone 60mg od

HCQ 200mg od

Amlodepine 10 mg bd

Metoprolol xl 25mg bd

Prazosin 10mg bd

Warfarin 2mg od

Stabilised over 1week and discharged

Postpartum 5weeks

Readmitted ( 3days after discharge from NIMS)with

hemoptysis ( blood tinged sputum) and cough;

No bleeding from other sites

RS: Basal crepts

Sputum culture: sterile

Plt < 50k

HRCT:PAH/Diffuse alveolar haemorrhage

Bronchoscopy: Normal

– Received 2units SDP, 2 units PRBCs (Hb 6gm/dl)

– Underwent plasmapheresis:6 times

– Inj cyclophosphamide/mesna (1dose)

No clinical or lab improvement(one week……

IV IG over 4days

Multiple platelet transfusion

Inj Rituximab 1 dose given

leukopenia TLC 2000

Was on triple cover ( meropenem+ metrogyl and

antifungal)

Summary

26 yr primary APLA(3YRS)on anticoagulants

Pregnancy :on enoxaparin/Ecospirin

32 wks severe PE/HELLP:LSCS

POD 3:Hypertensive crisis(pul edema)/PRES

Retinal Detachment, uveitis

POD 26: UTI:E Coli

AKI: Creatinine-3; resolved with conservative treatment

Severe thrombocytopenia

Resistant to

wysolone/methylprednisolone/plasmapheresis/IVIG/rituximab

Persistent leukopenia 500 after plasmapheresis

Diffuse alveolar hemorrhage- persistent mild hemoptysis on and

off till 5days ago

Rituximab 2nd dose due next week (15days apart)

Platelets had improved to 1.5lakhs/ again falling trend now at

80k

Bonemarrow biopsy - Myeloid maturation arrest

D/D

CAPS: Trigger infection

???

APLA

Multisystem autoimmune condition

Minority develop life threatening multiple organ

thrombosis

Criteria For APLA

Clinical:

- Vascular thrombosis:venous/arterial/small vessel

thrombosis.

- Pregnancy events:fetal death >10wks/one or >PTB

due to severe PE/eclampsia/placental insufficiency

- 3 or> losses <10 wks(unexplained)

Lab Criteria

Presence of APL on two occasions 12 wks apart

Not >5yrs before clinical manifestation

One or > of following

aCL Ig G/M :Positive

B2 glycoprotein G/M

LA :Positive

Correlation….

LA is better predictor for thrombotic events

LA should be done off coagulation

ACL IgG relate to clinical events

Recently even isolated IgA, B2GP also relate

clinical events

Spectrum Of APLA

APL Positive: Only serology

APL positivity with noncriteria manifestations:

– Thrombocytopenia,hemolytic anaemia,cardiac

valve disease, nephropathy

A PL based on thrombosis/ pregnancy losses

CAPS

Diagnostic Challenges

Positive APS: Infections

APS negative: During thrombosis

Overlap:

- Sepsis: Thrombocytopenia

- HIT: Heparin Ab/heparin induced platelet activation

studies

1.CAPS(ASHERSON)

1% of APS

1. Thrombosis in 3 or more organs(in less than a week)

2. Microthrombosis in atleast one organ

3. APL positivity

4. Biopsy

ALL 4:CAPS

Three out of 4:probable CAPS

CAPS- Unique features

Rapid onset thrombosis resulting in MODS

Common association with other

microangiopathies:TMA’s

Evidence of SIRS

High risk of unusual organ involvement

High mortality despite treatment

CAPS Spectrum

CAPS

Probable CAPS

Microangiopathic APS

Thrombotic Storm

CAPS

50% Mortality:( 20%with newer treatments)

Triggering factor(25%):Infection

/viral/URTI/UTI/sepsis/surgery/anticoagulation

withdrawl/neoplasia/immunization

Infection contributes to 40% of CAPS cases; hence

antibiotics indicated

SIRS

APS vs CAPS

Macrothrombus

Large vessels

Thrombosis is sporadic

Confined to single site

%84 microthrombi

Small vessels

Thrombotic events occur simultaneously in many organs

Diffuse ischaemia in parenchyma

CAPS Vs SIRS

MOLECULAR MIMICRY

INFLAMMATION

CAPS VS TMA

ADAMTS 13

2. CAPS like

APS Positive

Criteria not fulfilled

Close monitoring

Medium-large vessel involvement

Pulmonary/adrenal bleed

Thrombocytopenia

HELLP

Single organ thrombosis

3.Microangiopathic APS

Small blood vessel occlusion

TMA+HEMOLYSIS:TMHA

TMA CAN OVERLAP WITH:

– MALIGNANT HTN

– TTP

– HUS

– HIT

4. Thrombotic Storm

Clinical phenotype

Severe thrombotic events

Macrovascular events

Our patient

Preeclampsia and related complications

Hematological

Eye

Renal

Lung

Overlap:

sepsis,

HELLP

Diagnosis

CAPS

CAPS LIKE

CAPS :HELLP/HUS/TMA/SEPSIS

Conclusion

APS is a systemic autoimmune disease

Thrombotic/nonthrombotic

CAPS: Severe form of APS

Urgent treatment

Most of overlap diagnosis: Same treatment

Mortality: High

Clinical suspicion and active treatment reduces

mortality

References

CAPS Registry

Journal of Rheumatology

Case Reports