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Morbidity and Mortality Conference January 16, 2002 David Legro

Morbidity and Mortality Conference January 16, 2002 David Legro. Eponyms: In thyrotoxicosis, absence of forehead wrinkling is called?. Dalrymple sign Joffroy sign Kehr’s sign Hegar’s sign Chadwick’s sign. CC: 55 yo man with malaise and fevers s/p hemodialysis

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Morbidity and Mortality Conference January 16, 2002 David Legro

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  1. Morbidity and MortalityConferenceJanuary 16, 2002David Legro

  2. Eponyms: In thyrotoxicosis, absence of forehead wrinkling is called? • Dalrymple sign • Joffroy sign • Kehr’s sign • Hegar’s sign • Chadwick’s sign

  3. CC:55 yo man with malaise and fevers s/p hemodialysis • Recently developed dialysis dependent renal failure secondary to crescentric glomerulonephritis • Began dialysis 1 month prior to this presentation

  4. History of Present Illness • Felt well until hemodialysis 1 day PTA • Subjective fever, malaise, lightheadedness, nausea, vomiting, and fatigue • VSS; exam normal • Sent home, felt better • AM: Fever=103 F, fatigue, anorexia, HA, jaw stiffness • Seen in DHMC ER

  5. Past Medical History • Renal failure – RPGN 2 months ago • c-ANCA, p-ANCA, ANA, HBV, HCV: negative • MPO, PR3 negative, complement normal • Anti-GBM antibody elevated/incidental • Antistreptolysin-O elevated • Sinus CT: nodular soft tissue densities • Renal biopsy c/w crescentic glomerulonephritis • Diagnosed asANCA-negative Wegener’s • Began treatment with IV steroids, oral cyclophosphamide

  6. Past Medical History • S/P tunneled catheter placement • Thrombocytopenia • Heparin and Prilosec related antibodies • Anemia/thrombocytopenia • Early MDS by bone marrow biopsy • Chronic Sinusitis

  7. Medications • Prednisone 40 mg qd • Cyclophosphamide 50 mg qd • Famotidine 20 mg qd • Nephrocaps 1 tablet qd • Terazosin 5 mg qd • Calcium Acetate 2 tabs tid • Epogen 40,000 units 3x/week

  8. Adverse Drug Reactions Heparin Prilosec • Social History Former building-supplies executive Separated Former smoker; quit 8 years ago Social alcohol No recreational drugs Travel to South America/Caribbean

  9. PHYSICAL EXAM • General: NAD, non-toxic, well-appearing • T 37.6 BP 132/74 P 108 R 18 Pox 97% RA • HEENT: Anicteric, oropharynx clear • Neck: JVP 6cm, no nuchal ridigity • CV: RRR without m/r/g • Lungs: Bibasilar crackles • Abd: + BS, soft, non-tender, no hepatosplenomegaly • Extr: + 1 pitting edema to knees, no cords/lesions • Neuro: A+O x 3; nonfocal • Skin: No rashes, petechiae, or purpura. Right IJ catheter clean/nontender without erythema or discharge

  10. LABORATORY 9.4 DIFF: 85 N/ 1 L/ 11 Bands 3.9 131 MCV: 98.3 29 RDW: 22.6 134 / 96 / 68 Ca 8.0 Mag 0.65 Phos 4.3 4.3 / 24/ 8.8 PT 15.6 INR 1.4 PTT 51 Iron 18 Ferritin 600 TIBC 139 T.Bil 0.6 AST 51 AlkP 53 T.protein 5.3 D.Bil 0.2 ALT 16 Albumin 2.7 101

  11. LABORATORY • URINALYSIS: • pH 7.0, specific gravity 1.015 • > 300 protein • 150 RBC • 10 WBC 2 RBC casts, no hyaline casts • negative ketones, leuk. esterase, nitrate • EKG: NSR; no acute changes • CXR: Mild pulmonary congestion

  12. ASSESSMENT 55 yo man with dialysis dependent renal failure thought secondary to Wegener’s Granulomatosis • Problem list including: • Fevers, malaise, anorexia • Pancytopenia • Bandemia • Elevated INR/PTT • Mild volume overload • Differential diagnosis: • – Bacteremia/early sepsis, ? line infection • – Vasculitis related • – Opportunistic infxn. • – Cyclophosphamide

  13. Antibiotic choice in potential dialysis catheter line sepsis: • Vancomycin • Cefazolin/Gentamicin • Piperacillin/Gentamicin • Ceftazidime • Linezolid

  14. Plan • Admitted to M2 • Pan-cultured • Cefazolin/gentamycin; await cultures • Cyclophosphamide discontinued • Prednisone reduced to 20 mg • HD to reduce volume overload • Avoid heparin; hirudin-based locks for catheters • Heme consult re: pancytopenia

  15. HOSPITAL DAY # 2 • Afebrile; VS/exam stable; feeling well 8.8 • 3.4 122 • 25.4 • 2/2 blood cx sets: GPC in clusters • Cefazolin/gent changed to vancomycin • HD cath removed  marked oozing • Heme consult: MDS versus cytoxan effect  watchful waiting; clinic f/u in 1 month for repeat marrow biopsy

  16. HOSPITAL DAY #3 • Feeling well but cont’d cath-site bleeding • BP 165/95 P 81 T 37.4 R 20 Pox 92% • 8.8 • 3.0 131 PT 16.7 INR 1.5 PTT 51 • 25.7 • Blood cultures and catheter tip: • coagulase-negative staphylococcus • multiple-resistances but vanco-sensitive • Temporary HD cath placed by IR

  17. HOSPITAL DAY #3 (cont’d) • Continued catheter-site oozing • Treated with pressure dressings • 7.5 • 3.0 127 • 22.9 • Transfused 2 units PRBC’s • Hemodialysis w/o complications • Mild diarrhea w/few blood clots • Another 2 units PRBC’s

  18. Active Problem List • Dialysis dependent renal failure • Elevated INR/PTT • Catheter site bleeding • GI bleeding • Pancytopenia

  19. HOSPITAL DAY # 4 • 1400 cc of melenic stool overnight • Fatigued but o/w asymptomatic • BP 115/80 P 104 R 20 T 37.8 • Exam unchanged; no skin changes • 7.1 PT 19.2 INR 2.0 PTT 56 • 2.3 97 TT > 90 D-dimer 1090 • 20.5 Fibrinogen 424 • LFT’s: WNL Vancomycin: therapeutic

  20. HOSPITAL DAY # 4 continued • GI consult • DDx of uremia-related gastritis versus PUD • EGD: no bleeding or other lesions to last section of duodenum • Heme consult: • Suspected vitamin K deficiency • Recommended treatment with: • dDAVP • Vitamin K 10 mg PO x 1 • 2 units PRBC • 2 units FFP

  21. The mechanism of action of dDAVP when used for uremic platelet dysfunction is? • Increases binding of fibrinogen to glycoprotein IIb/IIIa • Increases the release of factor VIII:von Willebrand factor multimers from endothelial cells • Inhibits the synthesis of nitric oxide • Acts like ADH and stimulates vasoconstriction via smooth muscle V1 receptors • I have no idea

  22. Platelet Dysfunction in Uremia Mechanisms of platelet dysfunction • Uremic toxins • Some factor interferes with binding of fibrinogen to GPIIb-IIIa • Anemia • Platelets dispersed, impaired adherence to the endothelium • Nitric oxide • Increased platelet NO synthesis in uremia • NO is an inhibitor of platelet aggregation Rose, Burton. Platelet dysfunction in uremia. UpToDate 2001.

  23. dDAVP for Uremic Platelet Dysfunction • dDAVP (desmopressin) is an analog of antidiuretic hormone with little pressor activity • Increases the release of factor VIII:von Willebrand factor multimers from endothelial cells • Action within 1 hour, lasts 4-24 hours • Tachyphylaxis develops after 2nd dose • Approximately $130/dose Rose, Burton. Platelet dysfunction in uremia. UpToDate 2001. www.drugstore.com

  24. Does dDAVP Work? Zeigler ZR. Megaludis A. Fraley DS. Desmopressin (dDAVP) effects on platelet rheology and von Willebrand factor activities in uremia. American Journal of Hematology 1992; 39:90.

  25. HOSPITAL DAY # 5 • Several melenic stools overnight • Hematemesis x 1 in AM • Fatigued, mild SOB, o/w asymptomatic • BP 152/82 P=120 T 38.2 Pox=94% RA • 6.6 • 2.3 109 138/ 102 / 80 • 18.3 4.7/ 26 / 6.1 • PT=19.2 INR= 2.0 PTT=60 TT>90 • Fibrinogen WNL D-dimer 740 • Haptoglobin=WNL

  26. HOSPITAL DAY # 5 continued • dDAVP, Vit. K, 2 units PRBC’s, 2 units FFP • EGD # 2: active bleeding at second duodenal section, not able to cauterize/inject • Increased pulmonary crackles and BLE edema • 2LNC for Pox>92% • Hemodialysis

  27. Trouble getting control • To date: 20mg Vitamin K, 2 doses DDAVP, 8 U PRBC’s, 4 U FFP • Hemogloblin 9.4  8.8  7.5  7.1  6.6 • INR/PTT 1.4/51  1.5/51  2.0/56 2.0/60 • Thrombin Time > 90  > 90

  28. A mixing study that does NOT correct the PTT to normal could signify? • Antiphospholipid Ab’s are present • Circulating Heparin • Factor Inhibitor is present • All of the above • None of the above

  29. Modified from MKSAP XII, Hematology.

  30. HOSPITAL DAY #5 continued • Mixing studies to evaluate elevated PTT • Surgery consult: rec’ed angiography • ICU agreed to take patient for 1:1 nursing/monitoring • IR procedure: embolization of branch of gastroduodenal artery • Transfer back to M2 (CCU boarder) • 5.6 • 2.5 98 PT 18.6 INR 1.9 PT 53 • 16.1

  31. HOSPITAL DAY # 5 continued • Mixing Studies • Did NOT correct PTT, PT or TT • Lupus anticoagulant NEGATIVE • Heparin assay negative • Hirudin being used in catheter-locks

  32. HOSPITAL DAY #5 continued • Heme recommendations: Supportive therapy PRBC transfusion PRN No further FFP D/C hirudin locks • Saline KVO’s only Argatroban locks in future • Hemoglobin = 6.1 s/p 10 units PRBC total

  33. HOSPITAL DAY # 6 • Fatigued but alert. • BP 152/82 HR 90’s T 37.2 R 18 Pox 98% RA • Melena decreased. • Hemoglobin = 6.1  7.3 (s/p 4 U PRBC’s) • PT 19.2 INR 2.0 PTT 60 TT >90 • EGD # 3: Active hemorrhage in duodenal ulcer • Successful cauterization and injection

  34. HOSPITAL DAY # 7-8 • Melena stopped • VSS; patient comfortable and alert • Hb up to 8.4 s/p 4 more units PRBC’s • PT 17.1 INR 1.6 PTT 46 TT 52 • Volume overloaded tolerated HD • Started clear PO’s  advanced diet • Hemoglobin stable for 48 hours w/o PRBC’s

  35. HOSPITAL DAY # 9-12 • Hb 9.4, INR 1.2 PT 14.7 PTT 36 TT 21 • Total Blood Products • 13 Units PRBC’s • 6 Units FFP • Discharged home with renal/heme appt’s • D/C diagnosis: • Line Infection • GI bleeding • Hirudin induced coagulopathy

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