thrombotic microangiopathies
- include TTP (thrombotic thrombocytopenic purpura) and HUS (hemolytic uremic syndrome)
- thrombocytopenia secondary to insult causing platelet activation, produces thrombi in microcirculation causing hemolytic anemia (fibrin shears RBC – shistocytes!!)
- causes poor perfusion and organ dysf
pentad a/w thrombotic microangiopathies
- microangiopathic hemolytic anemia
- thrombocytopenia
- fever
- kidney dz (esp hus!!)
- transient neuro dysf (esp TTP!!)
TTP - patho
deficiency in ADAMTS13 which cleaves multimers of vWF normally
w/ deficiency, get large clumps of vWF that deposit and activate platelets
can be acquired or immune (antibodies against ADAMTS13 - GET POSITIVE COOMBS)
TTP - pres
- anemia - pale, fatigue, SOB
- bleeding - purpura, petechiae
- transient neuro def - HA, confusion, lethargy, coma, seizures, paresis, delirium
HUS - patho
- normal ADAMTS13…a/w ECOLI 0157:H7 AND O145 (THINK ABOUT KIDS EATING HAMBURGERS!!!!)
- e.coli relsease shiga toxin causing endo cell dysf and platelet activation
- TOXIN HAS INCREASED AFFINITY FOR RENAL VESSELS!!
HUS - pres
- anemia
- bleding
- KIDNEY FAILURE (esp in kids!)
* rarely have neuro sx!
* **h/o diarrhea!!
TTP and HUS labs / dx
-evidence of hemolytic anemia: normochromic w/ elevated INDIRECT BILIRUBIN, LDH and decreased HAPTOGLOBIN
**check K and EKG!!
-blood smear: reticulocytosis and shistocytosis
-normal coag tests!
TTP: positive coombs and more severe thrombocytopenia!!
HUS: negative coombs! positive stool culture!
treatment TTP
- DAILY IMMEDIATE PLASMA EXCHANGE!!! ASAP and continue until platelets and LDH normal >2 days! then taper slowly and monitor!
- if refractory, do twice daily!
- prednisone for immune mediated TTP
- FFP if plasma exchange not available
- RBC transfusion w/ sig anemi
- w/ refractory: rituximab, corticosteroids, IVIG, vincristine, cyclophosphadmide, splenectomy
treatment HUS
kids: most self-limiting - FLUIDS TO PROTECT KIDNEYS! DONT TREAT W/ ANTIBIOTICS - WILL INCREASE TOXIN RELEASE!
adult: a/w malignancies, SLE, chem, AI
- same as ttp: daily plasma exchange, hemodialysis w/ renal failure
contraindication w/ TTP and HUS
PLATELET TRANSFUSIONS!!!! WORSENS THROMBOSIS!!!!
only give if severe life-threatening bleeding!
pruritis after hot shower / bath w/ hx DVT…
think about POLYCYTHEMIA VERA!
polycythemia vera dx
1st rule out secondary w/ erythropoietin level - should be LOW w/ PV! (will be high w/ secondary!) 3 major or 2 major + 2 minor major: 1. increased red cell mass >32 ml/kg female or >36 ml/kg male 2. normal ox sat >92% 3. splenomegaly minor: 1. throbocytosis >400,000 2. leukocytosis >12,000 3. leukocyte alk phos >4000 4. increased B12 **definitive w/ biopsy!
PV pres
sx d/t:
- increased viscosity: HA, malaise, fatigue, dizzy, PRURITIS!, vision changes, syncope, FACIAL FLUSHING
- increased thrombotic events: MI, CVA, DVT/PE
- bleeding / increased bruising
PV other lab findings….
- hyperuricemia
- high cholesterol
- high histamine..PRURITIS!
- low erythropoietin! w/ high it is secondary i.e. hypoxia
PV treatment
1st line / mainstay: phlebotomy q 2-3 d to reduce hematocrit to about 45%
- ASA 81 mg and adequate hydration
- Hydroxurea - 2nd line if phlebotomy not posible or high risk i.e. >60 / h/x of clot
- allopurinol for increased uric acid
- antihistamines for pruritis
main cause of death in PV
thrombotic events
key sx multiple myeloma
HIGH CALCIUM + HIGH PROTEIN + LOW HGB + RENAL FAILURE!
MM patho…
malignant proliferation of single plasma line - abundant proliferation of abnormal immunoglobulines = M protein!
- proliferates in bone marrow causing PUNCHED OUT LYTIC BONE LESIONS seen on xray and pancytopenia!
- can be entire protein or components (KAPPA / LAMBDA light chains!)
CRAB w/ MM…
key sx:
high calcium, renal failure, anemia (normocytic normochromic) and bone pain / lesions
-more in african americans!
MM sx (most to least common):
- Anemia (n,n): d/t bone marrow infiltration and renal failure
- bone pain - worse w/ movement, NOT worse at night - most in face, back and chest (axial skeleton)
- renal failure / inc crt d/t hypercalcemia and BENCE JONES proteins (myeloma kidney)
- hypercalcemia
- weight loss
- recurrent infections d/t decreased effective immunoglobulins - #1 cause of death! most lung or UTI
- cord compression - MEDICAL EMERGENCY! GET mri AND START STEROIDS!
* Extrameduallary plasmacytomas - purplish mass dx w/ PET
testing if suspect MM…
- SPEP/UPEP (serum / urine protein electrophoresis) - blood or u/a w/ 24 hr urine
+ - immunofixation of serum / urine - done w/ abnormal spep/upep
*KAPPA is predominant light chain seen - serum free light chains (FLC) assay - measures amout of kappa and lambda and gives K:L ratio
- U/A: w/ myeloma cast nephropathy see no / minimal proteinuria b/c U/A detects ALBUMIN! not bence-jones!
-w/ amyloidosis / light chain deposition dz see more significant proteinuria! - peripheral blood smear: pancytopenia w/ ROULEAUX!!!! = coin stacks - hyperglobulinemia makes RBC sticky!
- BM bx: for dx, must have at least 10% abnormal plasma cells!!
- bone survey w/ xray -include humerus and femur for PUNCHED OUT LYTIC BONE LESIONS!! then f/u CT/MRI w/ negative or w/ neuro sx / compression
diagnostic criteria for MM:
- at least 10% abnormal plasma cells plus one of:
A. organ / tissue impairment (CRAB)
B. presence of biomarker near inevitable progression to end organ damage - 60% clonal cells, FLC ratio 100+, MRI w/ 1+ lesion
other similar diseases…
Waldenstrom macroglobulinemia: proliferation of lymphocytes producing Igm paraprotein - leads to viscous blood
- dx: >5g/dl of IgM, bence-jones proteinuria BUT NO LYTIC BONE LESIONS!
2. amyloidosis / light chain deposition disease: see amyloid on biopsy - different b/c deposits cause nephrotic syndrome, heart failure, liver failure - *no bone lesions! w/ modest proteinuria and 20% or less plasma cells on bm bx
tx MM
if young and asx: hematopoietic cell transplant!! DO NOT DO CHEMO PRIOR! CANNOT DO HCT AFTER CHEMO!
if not transplant candidate, do systemic chemo
*prognosis: 2-4 yrs, 5 yr survival = 10%
