NOT JUST ANEMIA!DR. EMAD MIR ABBAS SAGHEER

SECOND YEAR POST GRADUATE

UNDER THE GUIDANCE OF PROF. VISHNU

HAYGREEV, DR. PARASHURAM, DR. ANOOP

DR. B. R. AMBEDKAR MEDICAL COLLEGE

1

HISTORY

Chief Complaints

A 19 year old unmarried female from Nepal residing in Bangalore since birth, presented in our OPD in first week of July 2018 with 3 months history of

easy fatigability

generalized weakness

chest pain and palpitations on and off.

2

HISTORY

No h/o fever, joint pains, rash

No h/o loose stools, vomiting

No h/o haemetemesis, hemoptysis,

malena, epistaxis, gum bleeding

No h/o weight loss

3

Past History

Not a k/c/o DM, Hypertension, Bronchial Asthma,

Epilepsy

No previous history of TB

No previous history of blood transfusions

Family History

Mother was newly diagnosed Hashimoto’s Thyroiditis

with Hypothyroidism

Second of 3 siblings who do not have any medical

history.

4

Personal History

Diet – Mixed

Appetite – Normal

Sleep – Adequate

Bowel & Bladder – Normal

No substance abuse

Menstrual History

LMP: 13/6/18

S/O Menorrhagia lasting 1 year uptil 6 months back.

Normal and Regular menses since last 6 months

5

GENERAL PHYSICAL EXAMINATION

19 year old female patient, moderately built and

nourished, conscious, oriented and alert

PALLOR +

No Icterus, cyanosis, clubbing,

lymphadenopathy or pedal oedema.

No skin or nail changes

Breast/Spine/Thyroid– Normal

BMI: 20.61 kg/m2

6

Contd.

Vitals

Pulse rate: 106 /min regular

BP: 100/60 mmHg right arm sitting position

Temp: 98.1 F

SpO2: 98% at room air

RR: 16 cycles/min

7

Systemic Examination

CVS: S1 S2 Heard. Tachycardia+ Haemic Murmur+

RS: Bilateral Normal Vesicular Breath Sounds, No

added sounds

PA: Soft, non-tender, No organomegaly with Bowel

sounds heard

CNS: No focal neurological deficit

8

Provisional Diagnosis

Anemia for evaluation

? Secondary to Menorrhagia

9

Investigations

Hemoglobin: 3.2 g/dl

Total WBC count: 8,100 cells/ mm3

RBC count: 1.35 million/cmm

PCV: 9.6%

MCV: 55.5

MCH:14.6

MCHC: 26.4

Differential Count: Normal

Platelet Count: 4,80,000 cells/mm3

ESR: 72 mm/hr

10

Investigations

Peripheral Blood picture:

Microcytic Hypochromic Anemia

with thrombocytosis

Corrected Reticulocyte Count:

0.7%

Blood Urea: 71 mg/dl

S. Creatinine: 3.6 mg/dl

RBS: 106mg/dll

Na/K/Cl – 136/5.6/108 mEq/L

Urine Routine

Protein 3+

Blood +

Pus Cells: 4-6

Epith Cells: 2-4

RBC’s: 8-10/hpf

Granular Casts seen

11

Investigations

USG Abdomen & Pelvis:

Bilateral Increased Cortical Echogenicity consistent

with renal parenchymal disease

Rt Kidney – 106x41x13mm

Lt Kidney – 97x41x15mm

Normal Uterus

Liver Function- Normal

S. TSH: 1.14 microIU/ml

Chest Radiograph - Normal

12

Provisional Diagnosis

Iron Deficiency Anemia secondary to chronic

blood loss

Acute Nephritic Syndrome

?Cause

13

Investigations

Iron Studies

S. Iron: <15 mcg/dl (50-170 mcg/dl)

TIBC: 277 mcg/dl (250-410 mcg/dl)

S. Ferritin: 8 mcg/L (13-150 mcg/L)

Transferrin Saturation: 5% (13-45%)

Stool for occult blood: Negative

S. Calcium: 7.8 mg/dl

S. Phosphorous: 5.5mg/dl

Lipid Profile - Normal

14

Initial treatment

3 Units of cross matched Packed Red Cells were

transfused over 2 days.

Iron Deficit was corrected with Inj. Ferrous Carboxy

Maltose 1gm followed by initiation of Oral Iron

supplementation.

Supportive treatment for mild hyperkalemia,

hypocalcemia and hyperphosphatemia

Urine output was monitored on a daily basis

15

Investigations

24 Hour Urinary Protein: 2461mg/24hours

24 hour Urine Output: 1.4 Liters/24hours

PT: 14.9 sec INR: 1.12

aPTT: 28.6 sec

HIV 1 & 2, HBsAg, HCV – Negative

HbA1c: 4.7

2D – ECHO - Normal

ASO Titers: Negative

ANA Profile - Negative

16

Day 5 of admission

Patient had 2 episodes of hemoptysis, with no

addition repeated episodes, and no persistent

cough, breathlessness or respiratory distress.

There was also an increase in BP to

160/100mmhg (which persisted through her

course of stay) and a decrease in Urine output

to approx. 750ml

Rise in S. Creatinine and Blood Urea to 5.6mg/dl

and 115mg/dl

17

Day 5 of admission

Fall in Hb level to 6.4g/dl

Repeat Chest

Radiograph did not

show any features s/o

alveolar hemorrhages

HRCT Thorax – Bilateral

Minimal Pleural Effusion

18

Differential Diagnosis

Pulmonary-Renal Syndrome

Goodpasture’s syndrome

ANCA Small Vessel Vasculitis

Granulomatosis with polyangitis (Wegner’s)

Microscopic polyangitis

19

Confirmatory Investigations

Antibody to Glomerular Basement Membrane

(GBM) IgG – 117 units (>20 Positive)

Anti Proteinase 3 (PR3) - Negative

Anti Myeloperoxidase (MPO) – Negative

Complement C3 & C4 Levels – Normal

20

Renal BiopsyPrimary Diagnosis: Anti-GBM

glomerulonephritis

Pattern of Injury: Chronic

Sclerosing glomerulonephritis

with crescents.

Additional Features: Focal

Global Glomerulosclerosis

(83%), Acute Tubular Injury,

severe tubular atrophy and

interstitial atrophy (>50%),

mild arteriosclerosis and

hyaline arteriolosclerosis

21

Immunoflourescence (IF)

2 viable glomeruli seen

These show diffuse and

global strong linear

positivity along capillary

walls with IgG

Diffuse and globar

granular deposits in

mesangial region and

along capillary walls was

noted with C3c

22

Final Diagnosis

Anti-GBM disease with Pulmonary

Involvement

Goodpasture’s Syndrome

23

Treatment

High dose pulse steroid were given

Inj Methylprednisolone 1gm IV once daily for 3 days

Followed by Tab. Prednisolone 40mg Once Daily

Plasmapheresis was initiated

7 cycles of plasmapheresis were done over 10 days

2 more Units of Packed Cells were transfused

Tab Amlodipine 5 mg BD was also started

24

Contd.

After 7 Cycles of plasmapheresis patient was

started on Oral Cyclophosphamide 2mg/kg

daily and it was planned for 8-12 weeks

Tab. Endoxan 50mg 1-1/2-0

Tab. Bactrim DS OD for PCP prophylaxis

25

Response

Patient responded to treatment with

Improvement in Urine Output

Decrease in serial S. Creatinine values over 2 weeks during hospital stay being 2.8mg/dl at the time of discharge

Normalizing of Serum Potassium Levels

Stabilized Hemoglobin levels with no further reduction.

26

Follow Up

First Follow up 2 weeks after discharge

Oral Cyclophosphamide was continued

Oral Steroids were also continued

27

DAY 1 DAY 3 DAY 5 DAY 10 DISCHARGE 1ST FOLLOW UP

S. CREATININE

(mg/dl)3.6 3.9 5.6 4.3 2.8 2.9

POTASSIUM (meq/l) 5.6 5.8 5.4 4.9 4.3 4.5

Hb (g/dl) 3.2 8.4 6.4 8.8 8.9 9.2

ANTI-GBM TITRES

(units)117 31 3.57

Urine Output (ml) 1450 1350 750 900 1250 1200

DISCUSSION

Anti-GBM disease accounts for 5-10% of

crescentic glomerulonephritis.

IgG Antibodies to Alpha 3 NC1 domain of type

IV collagen present in lung and kidneys are

produced

Occurs as a renal-limited disease or with

pulmonary involvement (Goodpasture’s

syndrome) or as an ANCA Positivie variant of

Anti-GBM disease.

28

CONTD...

Has two peaks with respect to age

First peak in 2nd and 3rd decade of life, with

male preponderance with higher frequency of

pulmonary hemorrhages

Second peak in 6th and 7th decade, more

common in women, who more often have

renal-limited disease.

29

CONTD...

Rarely the disease has a more insidious onset

and patient remains asymptomatic without

uremic symptoms and fluid retention at

presentation.

Usually associated with arthralgias, fever,

myalgias and abdominal pains. Rarely with

gastrointestinal complaints or neurological

disturbances.

30

CONTD...

The predictors of kidney survival in Anti-GBM GN

are S. Creatinine and the need for dialysis at

presentation and percentage of glomerular

crescents.

In 2 studies, patient with initial S. Creatinine of

>5.7 mg/dl all became dialysis dependent and

all patients who were dialysis dependent at

presentation were never able to come off dialysis

despite aggressive treatment.

31

Levy JB, Turner AN. Ann Intern Med 2001

SURVIVAL STATISTICS

1-yr patient

survival

1-yr kindey

survival

5-yr patient

survival

5-yr kidney

survival

S. Cr <5.7

at presentation100% 95% 94% 94%

S. Cr >5.7

at presentation83% 82% 80% 50%

Dialysis

dependent at

presentation

65% 8% 44% 13%

32

CONTD…

In contrast to most other autoimmune kidney

disease anti-GBM GN is not characterized by a

frequently relapsing course.

The auto-antibodies seem to disappear

spontaneously after 12-18 months.

Relapses are still reported in literature with mean

time to recurrence being 4.3 years.

33

WHY AM I PRESENTING THIS CASE?

Anti-GBM disease has a rare incidence of 0.5 to 1

case per million as per Western Literature of

which only 40-50% have lung involvement.

A. Gupta et al in a 8 year study from 2004 to 2012

published in Indian Journal of Nephrology in 2014

detected only 8 anti-GBM disease cases of the

215 who had Crescentic Glomerulonephritis of

which only 2 were Goodpasture Syndrome.

34

A. Gupta et al. Indian Journal of Nephrology, 2014

CONTD…

A study conducted in a tertiary care center in

Mumbai published in JAPI July 2018

Included 25 patients of Pulmonary-Renal

Syndrome who were enrolled both prospectively

and retrospectively over a 19 year period

Had only 1 case of Goodpasture’s Syndrome who

needed dialysis at presentation, survived and

became dialysis dependent,

35

Yojana Gokhale. Journal of Association of Physicians of India, July 2018

CONTD…Another study in North India found no cases of

anti-GBM nephritis over a 2 year study of 46

patients of Crescentic GN

Our patient being a female despite male

preponderance in that age peak with none of the

usual symptoms at presentation

No radiological evidence of pulmonary

hemorrhages in our case which are usually

present in 80% cases.

Usually100% of the patients are dialysis dependent

on presentation whereas our patient still is not.

36

TAKE HOME MESSAGE

Anti-GBM disease carried more than 90%

mortality in the pre-plasmapheresis era.

Patients may have catastrophic pulmonary

hemorrhage carrying a high mortality rate

More chances of preserving kidney function if

diagnosed early and treatment initiated at the

right time

37

THANK YOU

38

‘TAKE CUES FROM THE SUBTLE CLUES’