Redefining I.N.RRedefining I.N.R

An An ‘‘Incidental Incidental NeoplasticNeoplasticRevelationRevelation’’

Dr S DhedaDr S DhedaEdendale hospitalEdendale hospital

PMBPMB

• Our Patient:• 49 year old female patient, • Presented to Edendale hospital • Referred from outlying hospital for

Investigation of epistaxis

• History:• Had a single episode of epistaxis in the

preceding year which abated spontaneously • Subsequently had more persistent epistaxis

of one month duration and visited the local hospital.

• Was started on Anti tuberculous treatment in the month prior to admission, however evidence for this diagnosis is scanty ?ESR

Further enquiry:• Significant weight loss over the last 12

months >10kg in 6/12• Generalised body pain, especially lower back

and hips• No night sweats or fever• No history of flu like symptoms• No herbal/traditional medications• No travel history• No previous medications• No family history of bleeding disorder

On examination:• Significant wasting• Not acutely distressed• Normal Vital signs• No oral thrush, no clubbing• Appeared pale, • axillary alopecia• No generalised lymphadenopathy, No jaundice, • No petechiae, ecchymoses• Sternal and hip bony tenderness

Cardiovascular:• Norma heart sounds • Not in CCF

Respiratory:• Clear

Abdomen:Soft, non tenderNo masses, No hepatosplenomegalyNo palmar erythema, spider naevi. no ascites

CNS:• Higher mental functions intact• No focal signs• Ambulant• Fundi: Normal, no bleeds

Summary:49 year old female patient with• significant weight loss• Epistaxis• pallor• Bone tenderness• Presently on TB Rx with no response

Blood results:Full blood count:Hb - 6.3 Hct - 18(Problematic transfusion)

Wcc - 3.74 Plt - 86

Urea and electrolytes:Na - 126 K – 3.5Cl - 99 Urea – 5.2Cr - 107

Coagulation profile:PI > 120 sec PTT – 36.8Control – 7.9 sec Control – 26.8INR > 11

LFT:TP – 174(60 – 80) Alb – 22 (32-50)Tbil - 12 (N) ALP – 43 (N)GGT - 40 (N) ALT – 21 (N)LDH - 904

Calcium – 2.07Corr Ca - 2.545 (N) Po4 - 0.82 (N)Mg - 0.86 (N)

Differential:• Multiple myeloma• Haematological malignancy• Chronic liver disease with PHT• HIV• Connective tissue disease

CXR:Diffuse infiltratesNo pleural effusionsNo metastases, no fractures

Ultrasound abdomen:- Liver and spleen homogenous, no enlargement- No abdominal LN- Kidneys, pancreas, GB normal

• Insert SXR

SXR:• Multiple lytic lesions

Hep A + B (-)

Coombs (-)

Considering the Elevated INR: 1. Warfarin2. Vit K3. Acquired inhibitor4. Factor deficiency

Mixing test:• INR decreased to 1.81

Serum Protein Electrophoresis:Monoclonal bandM peak - 136↑↑↑IGg – 164.4 (8-17)IgA – 0.13 (0.55 – 4.5)IgM – 0.03 (0.6 – 3.7)

CT Chest: Multiple vertebral lytic lesions, lung infiltrates ? Amyloid

Factor Levels: (50- 150)II - 57.6V - 31.7VII - 47VIII - 740.2IX - 206.2X - 82.6Extremely viscous plasma

• Patient transferred to Tertiary centre for Haematology consult and further investigationUnfortunately she demised the next day

Final Diagnosis:Final Diagnosis:Multiple Myeloma with associated factor V

and VII deficiency

Multiple Myeloma:• Malignant proliferation of plasma cells• Aetiology remains unknown

Clinical Picuture• Hypercalcemia and bone destruction• Susceptibility to infections• Renal failure• Hematological sequelae• Neurological sequelae

• Bone pain and Hypercalcemia– Osteoclast activating factors,– The role of OPL and RANKL– Renal failure– Parathyroid hormone related peptide– Impaired osteoblastic function

Renal Impairment:• Light chain nephropathy• Hypocalcaemia and nephrocalcinosis• Recurrent infections, pylelonephrits• Neurogenic bladder• Amyloidosis• Myelomatous deposits• Renal tubular Acidosis• Interstitial nephritis• Urate nephropathy

Bleeding in Myeloma• Platelet dysfunction • direct inhibition of fibrin monomer aggregation

due to the paraprotein, • Complex with clotting factors• Amyloidosis• thrombocytopenia

Diagnosis:1. Bone marrow involvement – plasmacytosis2. Lytic bone lesions3. Serum or urine M component

IgG > IgA > IgD

Staging:• To predict survival• Based on clinical and laboratory tests• Divided into 3 stages dependant on:

– Hemoglobin– Serum calcium– Presence of bony lesions– M component concentration

• Further sub classification, dependant on– Degree of renal impairment– B2 micoglobulin values

Treatment:• Radiotherapy• Chemotherapy, to suppress myeloma and to

control complications– Melphalan– Cyclophosphamide– Chlorambucil– Prednisone– Bisphosphanates– plasmapheresis

Thank youThank you

References:• NEJM 1993; 328(23): 1724• MYELOMA BONE DISEASE – UPDATE 2003

ByGregory R. Mundy, MD and Babatunde O. Oyajobi, MB, ChB, PhD 7.21.03

• Osteoprotegerin: a novel secreted protein involved in the regulation of bone density: W. S. Simonet, et al.; Cell 89, 309 (1997

• The OPG / RANK-Ligand System – Capotech Assay• Harrisons: Principles of Internal Medicine