What thrombotic disorders can be seen in a uremic patient?
KIDNEY PROTECTION
Revise please the abbreviation list on:
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Q.196. What thrombotic disorders can be seen in a uremic patient?
A. Despite effect of uremia on Plt., CKD ptn. have a hypercoagulable state é:
Enhanced thrombin generation due to tissue f. pathway activation.- Reduced antithrombin level.
- Resistance to activated protein C.
- Plt., monocyte & endothelial cell activation or injury.
-Increased hepatic synthesis of f. II, V, VII, VIII, X & XIII augment thrombin formation & fibrinolytic activity reduced.
- Thrombotic comp. occur in [Site of vascular access-DVT- coronary, cerebral, retinal vessels].
Q197. When to refer a hypertensive patient to the Nephrologist?
A. Four situations necessitate Nephrologist Referral:
I. Urgent treatment needed:
1. Accelerated H.T. (severe H.T. é G. III./IV. Retinopathy).
2. Particularly sev. H.T. (> 220/120 mmhg.).
3. Impending complications. (L.V. failure, transient ischemic attacks).
II. Possible underlying cause:
1. Any clue in history or examination of 2ndry causes (🠋 K + 🠉Na.).
2. Incr. S. Cr.
3. Proteinuria /hematuria.
4. Sudden onset or worsening of H.T.
5. Resistance to multidrug regimen (>3 drugs).
6. Young age: (Any H.T.<20 y. & needing ttt. < 30 y.).
III. Therapeutic problems:
1. Multiple drug intolerance.
2. Multiple C.I.
3. Persistence non-adherence or compliance.
IV. Special situations:
1. Unusual B.P. variability.
2. White coat H.T.
3. H.T. with pregnancy.
Q198. How to classify reno-vascular hypertension?
A. Classification of “renovascular hypertension”:
I. “Two ✌ Kidneys H.T. (= Pres. of a contra-lateral non-affected kidney):
1. Unilateral fibromuscular dysplasia.
2. Unilateral atherosclerotic renovascular dis.
3. Renal artery aneurysm.
4. Renal a. embolism.
5. Traumatic arterial occlusion.
6. A./V. fistula.
7. Renal artery dissection or thrombosis.
8. Aortic dissections with compromise to renal ostium.
9. Page kidney (post-traumatic perirenal fibrosis).
10. Metastatic tumor compressing renal parynchyma.
11. Pheochromocytoma compressing R. A.
12. Phakomatosis pigmentovascularis type IIb.
13. Neurofibromatosis.
14. Behcet’s disease.
15. Renal artery stenosis.
16. Aortic stent graft covering of origin of renal artery.
I. “ One👆 kidney H.T. (The entire renal mass is beyond the vascular lesion, either bilateral dis. or a solitary functioning kidney):
1. Stenosis to solitary kidney.
2. Bilateral arterial stenosis.
3. Coartication of the aorta.
4. Vasculitis involving renal arteries.
5. Congenital vascular anomalies.
6. Atheroembolic renal disease.
Q199. What are the clinical manifestations of renovascular hypertension?
A. Clinical manifestations of renovascular hypertension:
Features of renovascular hypertension:
1. Activations of RAAS early.
2. Paroxysmal symptoms: Sympathetic N.S. activation.
3. Abnormal circadian rhythm: Loss of nocturnal pressure fall.
4. Accelerated target organ damage:
➤ LVH.
➤ Microvascular dis..
➤ Renal injury: fibrosi
Clinical Syndromes ass. with atherosclerotic RAS:
1. “Incidental lesion”: No hemodynamic effect.
2. Renovascular H.T., (see above):
New onset H.T.
Acceleration of previous H.T. ptn.
3. Ac. Renal dysfunction:
ACE/ARBs-induced ARF.
Ac. or ch. R.I.
4. Unexplained ch. kid. dis., esp. in elderly.
5. Circulatory congestion:” Flash pulmonary edema”.
Q.200. How to evaluate and manage renovascular disease?
A. Clinical syndrome sugg. of renovascular dis.: {H.T. & renal ischemic disease}:
💢 If Kidney function is stable & B.P. controlled – Optimize medical ttt.:
1. RAAS blockade: ACE/ARB.
2. Statins for lipids.
3. Stop smoking.
4. Aspirin. …. Follow up advised, for a target of stable kidney function & excellent B.P. control.
💢 If there’s progressive dis. with reduced renal mass or co-morbid dis.:– Non-invasive imaging:
1. Captopril renography.
2. Duplex U/S.
3. CTA/ MRA.
…. Either:
🠊 Negative results – Optimize medical therapy. or
🠊 Bilateral dis., high grade stenosis, or progressive lesion– 🠊 PTRA Stent (atherosclerosis), or ….. Surgery é :
· Complex dis.
· Failed stent.
· Aortic disease.
- If B.P./ S. Cr. rises – Re-image & manage é Final goal: Stable kidney function & excellent B.P. control.
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N.B. New European Hypertension Guidelines Released: Goal Is Less Than 140 mm Hg for All, Michael O'Riordan, Jun 15, 2013
MILAN, Italy: The European Society of Hypertension (ESH) & the European Society of Cardiology (ESC) published new guidelines today for management of H.T., simplifying ttt. decisions for physicians e the recommendation: all patients be treated to <140 mm Hg systolic B.P.. The new guidelines do make exceptions for sp. populations, such as those with D.M. & elderly. For diabetics, ESH/ESC writing committee recomm.: physicians treat ptn. to <85 mm Hg diastolic B.P.. In ptns younger thn 80 y.s old, systolic B.P. target shd be 140-150 mm Hg, but physicians cn go lower thn 140 mm Hg if ptn. is fit & healthy. The same advice applies to octogenarians, although physicians shd also factor in patient's mental capacity in addition to physical heath if targeting to < 140 mm Hg. On the whole, Dr. Giuseppe Mancia (Univ. of Milano-Bicocca, Milan, Italy), cochair of ESH/ESC writing committee, said there’s a shift toward "greater conservatism" with regard to drug ttt in the new guidelines. That said, guidelines explicitly state physicians make decisions on ttt strategies based on patient's overall level of CVS risk. Mancia said the guidelines are not prescriptive, or orders, but rather suggestions for practicing physicians. While there’re some aspects of care tht remain the domain of expert opinion, he said there’s "no question that B.P. exceeding 140/90 mm Hg incr. the risk of CVS dis. & stroke," and these are both ass. with massive worldwide socioeconomic cost. Mancia added: 60% of ptns: disabled at one y. foll. a stroke.
Q201. What are the values, advantage & disadvantage of different imaging procedures in evaluating renal vasculature?
A. Imaging procedures & evaluating renal vasculature:
I. Spiral C.T. angiography: Excellent in imaging the vessels, three types of images, it cn examine the venous vessels & useful in Tx. donor exam-ination. Disadv.:🠞 High contrast requirement.
II. Contrast angiography: 👆 Gold Standerd: Excellent in imaging the vessels & tissue perfusion, estimation of viable tissue. Disadv.:🠞 Risk of catheter-induced injury & contrast nephropthy.
III. MRA: No radiation exposure, good in tissue perfusion & imaging vessels. Disadv.:🠞 Gado-linium contrast not used é GFR<30 ml/min., concern of Nephrogenic Systemic Fibrosis.
IV. Captipril renography: Excellent in tissue perfusion. Change in GFR might estimate reversibility of the lesion, widely available, non-invasive, totally normal renogram effectively exclude 🠞 significant vascular dis..
V. Duplex U/S: Adv.: Precise measurement of flow velocity, for serial stud-ies, relatively inexpensive. Disadv.:🠞 Little functional information, not suitable for accessory vessels, operator dependent & time consuming.
Q.202. What is the effect of uremia on homocysteine levels?
A. Hyperhomocystenemia is universal in ESRD. It’s independent risk f. in a. & v. thrombosis & CVS deaths. It cn also cause endothelial dysfunction thr. N.O. inactivation. ttt: No beneficial evidence of vit. B 6,12, folic a.- despite improvement in endothelial function é Folc a. 🠞 thpy, independent effect fr. dcr. in homocysteine level.
Q.203. How to do thromboprophylaxis in a uremic patient?
A. Most hospitalized ptn. hv additional f. for VTE, e.g. [old age, obesity, immo-bility]. One 1/4th dev. deep veins P.E.. So, LMWH Safely 🠞 used in R.I. ptn, but not in ch. base. If heparin C.I. deterrent stocking cn be used unless PVD is present.
Q.204. What are the suggested investigations for a suspected case of VTE?
A. Clinical probability of VTE shd be estimated 1st, then diagnostic tests cn employed safely & cost-effectively. Scoring system (Wells Score) cn be emp-loyed. D Dimers☜ (fibrin breakdown products)highly sensitive to Ac. thrombus formation. So, ptn. é low probability score, a –ve D Dimers cn EXCLUDE Ac. thrombosis. However their accumulation👆 in R.F., make them less helpful tht imaging (Doppler) wd be mandatory.
Q.205. What are the recommendations for anticoagulant use in renal impairment?
A. All ptn commencing anticoagulant thpy shd hv their kid. func. evaluated:
I. Heparin: see HDX.
II. Warfarin: metabolized in the liver & does “not accumulate in renal” disease.. It’s ass. é risk of bleeding in HDX. When monitoring INR, take care of heparin contamination.
Q.206. What are the recommendations for antiplatelet use in renal impairment?
A. (1) Asprin: hs the foll. effects:
i. Anticoagulant.
ii. Aniinflammatory.
iii. Fibrinolysis.
iv. Cyclo-oxygenase–independent plt. Inhibition
v. Cyclo-oxygenase modification irreversible defect in thromboxane synth. plt. dysf..
- As CVS risk is high in ESRD, Aspirin benefit is undoubted, keeping the risk of uremic bleeding under control by suitable measure like keeping Hct to be steady at 👉 30 %.
- Aspirin cn improve graft function & survival, as pathogenesis of allograft Rj 🠞 has common features with atherosclerosis.
(2) Clopidogrel(Plavix): block ADP pathway its amplifying effect on Plt. activ- ation (Permanent). Adding [Aspirin+Clopidogrel], for access patency🠞Risky bleeding.
(3) Glycoprotein IIb/IIIa inhibitors(GPIs): block binding of fibrinogen to activated Plt. GP receptors prevent Plt. thrombi formation. They’re adjunctive thpy for non-ST rise Ac. coronary synd. & essential in PTCA: peri-inerventional thrombotic comp., but é risk of bleeding, wch’s highest in CKD. PT, aPTT, Hct, HB. all shd be monitored. As GPIs cleared by Kid. dose é R.I. Tirofiban shd 50% é GFR <30 ml/min. Avoid👆 eptifibatide é GFR < 30 ml/min. No dose reduction é abciximab, although it is C.I. in DX or sev R.I..
Q.207. What are the common coagulation disorders that occur 2ndry to renal disease?
A. Uremic bleeding: abn. hemostasis (esp. Iry hemostasis, incl. vWF & Plt. adhesion)🠞 clinical bleeding : (bruises, G.I., venipuncture).. due to:
1) Low Hct.: Hct. inversely related to B.T. (B.T. incr. é R. anemia). As Hct rises Plt. adhesion to subendothelium enhanced . As RBCs travel thr. B.V. é fast stream at the centre of lumen, Plt. diffuse radially 🠞 more adhesion to sites of injury, so, dcr. in Hct 🠞 fast Plt. passage in the center of lumen 🠞 less chance for adhesion. Conversely, Hct rise & bld. viscosity(e.g. by diuretics) 🠞 incr. thrombotic risk. Uremic electrolyte procoagulant activity incr. due to phosph-atodylserine exposure. So, maintain Hct at 30 in RF ptn.
2) Plt. dysfunction: Before DX, Plt. count is N., or slightly reduced, but function is impaired due to uremic toxins (urea, Cr., phenolic a. & methylgua-nidine). Reduced affinity to vWF & expression of Gp1b recep. 🠞 Ineffect-ive adhesion to subendothelium. N.O., PGI2, Ca & cAMP V.D. Plt. aggregation.
3) Thrombocytopenia bleeding, due to :
i. Heparin- induced.
ii. Contact to artificial surface in HDX. 🠞 Thrombosis.
Q.208. How to investigate for uremic bleeding?
A. “Uremic bleeding”:
1) CBC: essential to ensure adequate H.B., Hct. & Plt. count.
2) Coagulation tests: P.T. aPTT.: N. in uremics, abn. in DIC. Fibronigen & D- Dimers Ac. Phase reactant, incr. é inflmm. & accumulate in CKD (cleared by the kidney).
3) B.T.: N.=2-7 min. Largely replaced by PFA 100.
4) PFA 100 system: in vitro system wch attempt to reproduce high shear circulation involving vWF binding & plt. adhesion, activation & aggregation. It’s sensitive to abnormal. in vWF & plt. adhesion. Closures times is shorten in DX & DDAVP.
Q.209. How to manage uremic bleeding?
A. Choice depends on clinical circumstances:
1) DDAVP (Arginine Vsaopressin): acts on endothelial vasopressin V2 receptors & cAMP-mediated signaling of vWF fr. Weibel-balade bodies where it is stored. DDAVP infusion: larger vW f. VIII multimer + B.T. It’s the👉1st choice for uremic bleeding, rapid onset +½ life =10 h. & B.T. returns baseline in 48 h. Single infusion:0.3 ug/kg: suff. to cover R. biopsy & No overload or change in electrolytes, despite osmolality changes, but C.I.: Cardiac insufficiency.
2) Cryoppt.: rich in vWf, f. VIII& fibrinogen, reverse abn. in hemostasis é minutes & given if DDAVP failed or in emergency surgery, if intravasculer vol. tolerated.
3) Platelet Tx.: 4-5 h. hemostatic effect. Pre-storage 👉 leucodepletion & incr. incidence of alloimmunization with subsequent Plt. refractoriness.
4) Red cell Tx.: Allow margination of Plt. & improve markers of Plt. activation.
5) Tranexamic a. 5 mg/24 h.🠞fibrinolysis by forming a reversible complex. é plasminogen & its conversion to plasmin. Single dose used + DDAVP, which release of tPA.
6) Recombinant activated f. VII.: 90 ug/kg., for emergency binds directly to activated Plt. thrombin burst: short ½ life. So, given/2h.
7) Epo: Erythopoiesis, Hct. & facilitating plt. margination & signaling thr. Tyro-sinephospho-relation, metabolically active reticulated plt. & improve HB sca-venging effect for N.O. Effect is delayed several days(not suitable for Ac. cases).
8) Conjugated estrogen:i.v.0.6 mg/kg/30 min/5d., onset: 6 h.7-21 d. It vWF & f.Viii, protein S levels improve clinical bleeding, used é elective surgery & suitable for ♂.
9) DX.: esp. P.D. improves platelet dysfunction & help in uremic bleeding.
Q.210. What precautions should be performed if a uremic patient should be biopsied?
A. 20 % of C.O. reaches the kidney (highly vascular), bleeding risk:2-8 % overt, it reaches 90 % é C.T. (hidden bleeding & peri-R. hematoma). Degree depends é R.I., é highest level é uremics. So, DDAVP 0.3 ug/kg, 30 min before biopsy. Risk of bleeding. Pre-biopsy evaluation incl.:
PT & aPTT.
Hct. & Plt. count.
Asprin & NSAID intake: Stop.
Personal & family bleeding history.
- Stop Asprin 2 w. before biopsy (greater effect on Plt. in uremics thn N.).
- Stop warfarin 5 d. before biopsy, or use Heparin & stop it é day of biopsy.
- Transjuguler biopsy is safer in risky ptn.
-2/3rd of bleeding events occ. é 1st 8 h.s.
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