How to make a diagnosis of TTP-HUS in adults?
KIDNEY PROTECTION
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Q.211. How to make a diagnosis of
TTP-HUS in adults?
A. Dgx. of TTP/HUS usually made on clinical grounds é ch.ch. clinical + lab. finding:
•
Microangiopathic
hemolytic anemia (MAHA).
• Thrombocytopenia
•
ARF. (varying degrees of severity).
•
Neurologic abnormal, (fluctuating).
• Fever.
Confirming
Dgx: Only👆presence of { MAHA + thrombocytopenia } without other causes
is sufficient to make initial Dgx. & start Pph.
Idiopathic TTP-HUS:🠞markedly ADAMTS 13(<5%) + AutoA.B. agnst ADAMTS 13.
However, results of these tests are not us. available quickly
enough for ttt decisions.
D.D.: Distinction fr. other causes is important as they do not resp. to Pph.:
1) Vasculitis & other connective tissue diso.
2) • Catastrophic
APA syndrome.
3) • Scleroderma renal crisis.
4) • Disseminated malignancy.
5) • Malignant H.T.
6) • D.I.C.
Q.212. What are the secondary causes of TTP-HUS?
•
Following
severe Drr.é enterohemorrhagic E. coli
•
Idiopathic
(rare).
Adult TTP/HUS syndrome :
•
Idiopathic.
•
Drug toxicity.
•
Cancer chemotherapy.
•
Mitomycin C.
•
Bleomycin & cisplatin.
•
Gemcitabine.
•
Cyclosporine & tacrolimus.
•
Immune mediated.
•
Quinine.
•
Ticlopidine & less often, clopidogrel.
Less certain causes :
•
Oral
contraceptives.
•
Valacyclovir.
•
Condition of hematopoietic cell Tx. (Sm caused by
sepsis and/or Ac. GVHD).
•
Pregnancy/postpartum.
(difficult to DD TTP/HUS fr. Pre-eclampsia/eclampsia-HELLP).
Autoimmune dis.:
•
SLE.
•
APA syndrome
•
Scleroderma renal crisis (SRC).
•
AIDS & early
symptomatic HIV infection
•
Following
bloody Drr. Due to enterohemorrhagic E. coli, typically E. coli 0157:H7.
Q.213. What is the treatment
of TTP-HUS in adults?
A. Suspecting Dgx: Idiop. dis. should be suspected: é MAHA & thrombocytopenia without an alternative etiology. Dgx of TTP/HUS is supported if neurologic abn., us. fluctuating (e.g., confusion, headache, seizures, coma) or R.I. also present., although one of TTP/HUS feature é era before effective ttt, is rare.The only request for making initial Dgx of idiop. TTP/HUS & initiating ttt é Pph is: {presence of thrombocytepenia & MAHA without another clinically apparent cause}.
Initial ttt: Idiop. TTP/HUS
is: MEDICAL EMERGENCY that’s almost
always fatal if not well
ttted. So, all ptns diagnosed shd be
admitted without delay to Pph center: All ptns ttted on urgent
basis é Pph, rather thn pl.
infusion or im/m. therapy alone. Pph
should be initially started daily
until platelet count hs normalized & hemolysis largely ceased, as
evidenced by a return of the s. LDH to
normal or near normal. If Pph is
not immediately available, pl. infusion may serve
as TEMPORARY ttt until ptn transfered to Pph medical center.
Adjunctive ttt é “G.corticoids”
in the foll.:
•
If
there’s no evidence for a drug-induced
etiology or a bloody Drr prodrome,
or
•
In ptns
whose platelet counts do’nt incr. within sev. days
of ttt é Pph, or
•
In those
in whm thrombocytopenia recurs when Pph ttts are or stopped.
Refractory/recurrent TTP-HUS : Ptns e sev. course who don’t rapidly
resp. to Pph, worsen é neurologic abn. despite Pph+steroids, or
hv relapsing dis.:
Add. of rituximab or Csp is recommended.
Incr. Pph frequency to twice daily.
Q.214. How does the recurrence of
TTP/HUS occur after transplantation?
TTP/HUS describes Ac. synd. é abn. in multiple systems in adults. Some
evid-ence sugg.: the two entities may be distinguished,
based upon presence and/or activity of von Willebrand f. cleaving protease (ADAMTS13). Recurrennce of HUS after R.Tx.: 25-50 %, wch may be
overestimating, as both Ac. Vsc. Rj. &
CAI Vasc. Rj. & thrombotic microangiopathy indistinguishable fr. Iry dis.. Multiple clinical ch.ch.
may be ass. é recurrent HUS in R. allograft. As examples: Ptns é P.H. of HUS due to non-Drr. causes (non-shiga associated [NStx] HUS) may be at a much higher risk of recurrence after
T.x. thn those é HUS foll. an episode of Drr..
Meta-analysis: recurrence HUS ws
signif. ass. é [older
age at onset, short dur. betw. onset
& ESRD or T.x. , use of living related donors & to
lesser degree, use of CNI.]. Recurrence occ. in most familial
HUS, which’s usually. due to mutations é C. inhibitor genes . Lower recurrence
occ. é nephrectomy (limited evidence). Ptns typically present é: [MAHA,
thrombocytopenia & ARF]. Graft loss rep. in 10-50 % of cases. Prognosis: Overall graft
success may dcr. é recurrent TTP/HUS.
Q.215. How to manage TTP-HUS recurrence after transplantation?
A.: First
Phases: prevention by:[low-dose aspirin + dipyridamole
]. It’s also sugg.: Csp & ALS
should be used é caution.
Second: ttt of recurrence: Csp>50 % é 1st
Sn of recurrence, Pl. infusions & Pph, as in Iry
dis., have been given é some success in selected ptns. Same is applied
to TTP.
DE NOVO HUS: Rare
problem except for: early Csp toxicity
& Ac. vsc. Rj.. Some ptns receiving OKT3 à a. & v. thrombi within allog. graft loss.
This comp. is mostly occ. é high-dose OKT3 (10 mg/d. rather thn recomm. of 5 mg/d.).
De novo HUS occ.:
Tacro. (FK506). However, R.
allog. recip. dev. TTP-HUS while taking Csp may hv high rate
of graft salvage after switching
to tacro. (13 of 16 in one report).
Siro/Csp combination.
Valacyclovir .
HIV, parvovirus B19 (ass. é red cell aplasia) & other infc., incl. CMV .
A.B. agnst v.W. f.-cleaving metalloprotease ADAMTS13: responsible of idiop. TTP.
Mutations in complement receptors.
De novo dis. may be localized to allog., while
others hv other systemic manf., e.g. thrombocytopenia
& hemolytic anemia. De novo localized dis. app. to be
ass. é better R. prognosis, é
allog. loss & need for Pph and/or
DX.
being less likely thn obs. é
systemic dis. Withdawal of suspect drug resolution of de novo dis., use
of tacro. or siro. instead of Csp. Use of [pred .+ MMF] thrombopathy resolve . Success also rep.
é: [Pph., i.v. IgG., rituxi-mab
& belatacept
].
Q.216. IgA Np is the renal
limited form of which systemic disease? Describe the biopsy
features?
A. Henoch-Schönlein purpura (HSP) is the systemic form of IgA
Np.
- HSP nephritis is defined by: { Presence of IgA deposits detected by I.F. & I.P. = Same features of IgA Np.}.
Q.217. What are the dyslipidemic
changes that associate CKD?
A. CKD dyslipidemia:
1) Dcr.
HDL.
2) Incr.
LDL.
3) Incr.
intermediate density lipoproteins.
4) Incr.
proatherogenic lipid particles.
- All of these changes promote atherogenesis.
Q.218. What are the target level for statin therapy for dyslipidemia in CKD?
A. Current UK guidelines suggest: adoption of guidelines
for Iry & IIry
prevention of CVS dis, tht apply to general population: Statin ttt. é 10
y. risk of >30 % (Based on: joint British
Societies’chart or CVS risk calculator). Statin diso. shd be incr. to achieve:
Total cholesterol of < 5 mmol/L.
30 % reduction fr.
baseline; or
Fasting LDL-cholesterol <3 mmol/L.
- The aim to achieve the target wch.
represent the greatest reduction.
Q.219. What is thrombotic microangiopathy (T.M.A.)?
A. T.M.A. = [Alteration in microvasculature é detachment & swelling of endothelium+ deposition of amorphous material é endothelial space + luminal platelet aggregation microthrombosis].
** Lab.
criteria:
I.
Schistocytes.
II.
Thrombocytopenia.
III.
Hemolytic anemia.
Q.220. What is T.T.P. pentad?
A. T.T.P. pentad: ✋
1) Fever.
2) Thrombocytopenia.
3) Renal
dysfunction.
4) Neurological
manifestations.
5) Microangiopathic
hemolytic anemia.
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