MM & Thrombotic Thrombocytopenic Purpura Flashcards
What is the pathogenesis of multiple myeloma?
1- malignant proliferation of plasma cells
2- myeloma plasma cells produce immunoglobulins of a single heavy & light chain -> PARAPROTEIN
when only light chains are produced they appear in the urine as Bence Jones proteinuria
What are the abnormal immunoglobulins synthesized in MM?
- IgG -> 60%
- IgA -> 20%
- light chains only -> 15% (Bence Jones protein)
What are the clinical manifestations of multiple myeloma?
1- Bone manifestations 2- Renal failure 3- Anemia 4- Recurrent infections 5- Bleeding tendency 6- amyloidosis 7- cryoglobulinaemia 8- hyperviscocity 9- autoimmune disorders
What are the bone manifestations of multiple myeloma?
- bone pain & tenderness
- bone mass (myeloma or plasmacytoma)
- pathological fractures
- hypercalcemia
What are the manifestations of renal failure in multiple myeloma?
- myeloma kidney (due to precipitation of light chains)
- hypercalcemia
- infection
What are the manifestations of anemia in multiple myeloma?
- bone marrow infiltration by plasma cells
- bone marrow aplasia by chemotherapy & radiotherapy
- bleeding (thrombocytopenia)
- renal failure
What investigations are done in case of multiple myeloma?
1- CBC -> normocytic normochromic anemia
- pancytopenia & increased ESR/C reactive protein
- rouleaux formation due to paraprotein
2- BM examination -> plasma cell infiltration
3- Biochemistry -> hypercalcemia & hyperuricemia
- B2 microglobulin & LDH high
- increased total protein with decreased albumin
4- Renal -> Bence Jones proteinuria
5- Plasma protein electrophoresis -> monoclonal hypergammaglobulinaemia
6- Biopsy -> plasmacytoma
7- Radiological
- punched out osteolytic lesions
8- DEXA scan
How is multiple myeloma managed?
SUPPORTIVE
- anemia -> Erythropoietin & blood transfusions
- infection -> antibiotics & flu vaccinations
- bone pain -> NSAIDs & radiotherapy
- hyperuricemia -> allopurinol
- hypercalcaemia -> bisphosphonates & IV fluids
SPECIFIC
- chemo -> MELPHALAN
- radiotherapy -> for localized bone pain
- transplantation -> autologous or allogenic stem cell transplant
What is the classic Pentad of TTP?
1- microangiopathic hemolytic anemia 2- thrombocytopenia 3- fever 4- renal dysfunction 5- neurological dysfunction
Only in 25%
What is the etiology of TTP?
- congenital
- acquired idiopathic
If any other cause it’s not TTP
What is the pathogenesis of TTP?
- thrombotic microangiopathy -> end organ damage
- deficiency in ADAMTS13 (VWF-cleaving protease) -> inherited mutation or acquired antibodies against it
- thrombosis due to ADAMTS13 deficiency increases hemolytic anemia
How is TTP diagnosed?
- thrombocytopenia <20 000
- Hb <10
- negative Coombs test
- schistocytes on peripheral blood smear
- LDH elevation
- reticulocytosis
- increased indirect bilirubin
- decreased haptoglobin
How do we differentiate between hemolytic uremic syndrome & TTP?
HUS TTP
- in 6m-4y olds - 30-40 yo
- more renal failure - less
- less neuro & - more
thrombocytopenia
- due to E. coli infection - ADAMTS13 def
How is TTP & HUS treated?
1- rule out other causes
2- platelets are CONTRAINDICATED except in life-threatening bleeding
3- plasma exchange daily until platelets count & hemolysis is improved (1-1.5 volume replacement)
- gets rid of vWF multimers
- restores ADAMTS13
- removes antibodies
4- increase plasma exchange to twice daily if once is not enough
5- corticosteroids (for antibodies
6- anti platelet in severe cases
7- vincristine
8- immunosuppression
What are the the quickest symptoms to respond to therapy in TTP?
1- rapid response (1-2 days)
-> non focal neurological symptoms
2- moderate response (3-10 days)
- > thrombocytopenia
- > parameters of hemolysis (like LDH)
3- slow response (weeks to months)
- > anemia
- > renal insufficiency
