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Morbidity and Mortality Conference

Morbidity and Mortality Conference. Brian J. Schwender, M.D. A#50235971-4 May 22,2002. 44 y/o white female presents to another hospital with :. Extreme weakness/fatigue DOE Mild confusion (“feeling foggy”) Jaundice with dark urine Easing bruising Menorrhagia. Past Medical History.

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Morbidity and Mortality Conference

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  1. Morbidity and Mortality Conference Brian J. Schwender, M.D. A#50235971-4 May 22,2002

  2. 44 y/o white female presents to another hospital with : • Extreme weakness/fatigue • DOE • Mild confusion (“feeling foggy”) • Jaundice with dark urine • Easing bruising • Menorrhagia

  3. Past Medical History • Steatohepatitis 7/01 • abnormal LFTs and bruising • Pancreatitis 1996 • alcohol use • Interstitial Lung Disease 5/00 • possibly infectious • Fibromyalgia 1999 • GERD

  4. Medications Amitriptyline 75mg qhs Esomeprazole 20mg qd Quinine 300mg qhs Allergies Penicillin Social History Married without children in Vermont Smoking 30 py history Hx. of heavy alcohol use in past. No IVDA Family History No hematologic or bleeding disorders History Continued

  5. Review of Systems • Bronchitis 3 weeks ago, treated with 10 day course of levofloxacin, since resolved • Stiff hands and feet, mostly in am • GERD without abdominal pain/N/V • No melena/BRBPR • No F/C/S • No CP/palp/ortho/PND • No GU sx

  6. Physical Exam • T 97.2 F HR 100/reg BP 100/60 RR 36  16 with O2 sat 95% 2LNC • Skin- multiple areas of ecchymosis, petechiae, extremities and trunk • HEENT- scleral icterus with some OP petechiae • Lungs- CTAB • CVS- tachy reg, 1/6 systolic murmur LLSB • Abdo- benign, without hepatosplenomegaly • Rectal- guaiac positive • Extremities- no c/c/e b/l • Neuro- AAOX3, non focal, without asterixis

  7. Labs 135 97 15 8.4 12 149 3.1 24 0.7 21.6 Calcium 9.8 77 Seg 18 L 3 M 1 E MCV 97 Smear + schistocytes 124 Haptoglobin < 3 Direct coombs neg LDH 1653 5.6 2.3 LFT’s 128 243 PT/INR 13.9/1.3 Fibrinogen 361 CXR- reported as normal EKG- sinus tachycardia

  8. A&P • TTP- microangiopathic hemolytic anemia and severe thrombocytopenia with mild MS changes • Transfused 3 units PRBCs and 2 units FFP • Solumedrol 40mg IV q8hr • Transfer to DHMC on the hematology service for plasmapheresis and line placement. • Hold quinine as possible cause of thrombocytopenia.

  9. On arrival to DHMC • PE essentially unchanged • T 37.6 HR 88 BP 110/78 RR 16 96% 2LNC • Scleral icterus, multiple ecchymoses and petechiae throughout trunk and limbs with some petechiae on her oropharynx • Neuro.- AAOX3, non focal, no asterixis

  10. DHMC Labs 9.3 139 100 15 13.5 25 2.9 25 0.6 25.8 Diff- unchanged Ca/Mg/PO4- WNL Smear- (show) LDH 1200 RTA 217 RTC 8.3% LFTs PT/INR 14.3/1.2 PTT 26 TT 19 Fibr 397 Dimer 981 140 Alb 3.8 4.9 1.9 146 87

  11. Blood smear- schistocytes

  12. TTP vs. ITP (etiology?) Plasmapheresis Folate, Ca and K Neuro checks QD CBC,LDH,retic counts VWF metalloproteinase PAIG, BMBx ANA, RF and ESR Menorrhagia Severe thrombocytopenia bHCG Elevated LFTs Steatohepatitis with alcohol consumption vs. TTP related Follow with plasmapheresis treatment. A&P

  13. TTP is associated with widespread microthrombi and endothelial damage • Many patients with • TTP have abnormally • reduced vWF protease activity • Abnormalities of the vWF multimer have been reported in TTP autoAb Blood. 2001; 98 (6)

  14. vWF Protease Activity & Thrombocytopenic Disorders Blood. 2001; 98 (6)

  15. Hospital Course • Daily Plasmapheresis • LDH decreasing, Plts increasing, hemoglobin slight rise with rising reticulocyte counts. • Paresthesias of LE responded with Ca supplementation and slower pheresis rates • No new signs of bruising • Vaginal bleeding resolved within 24-36 hrs. bHCG-neg • No renal failure • BMBx- hypercellular marrow with trilineage maturation. Presence of Fe. No left shift of myeloid lineage.

  16. Hospital course continued • PAIg positive • serum sent for quinine specific PAIg • O2 weaned off • Hg stablized • ANA and RF return negative • ESR 43

  17. Hospital Day #6 • Received total of 4 days of plasmapheresis • Ca and K replacement • Plt 176 189 by afternoon, LDH 248 • Plan • Discharge patient with close f/u in 2 days for repeat CBC, LDH and serum electrolytes • Patient not to take quinine or alcohol

  18. 24 hours after discharge • Presents to another hospital with: • - increase in fatigue, HA with mild confusion, • epigastric pain, subjective fevers and jaundice. • LABS: LFTs 102 7.0 138 98 36 8.7 19 3.3 27 1.5 4.9 1.0 195 88 PT/INR 14.4/1.2 PTT 32 TT 17 Fibr 451 Dimer 1950 LDH 3125 Amy/Lip- WNL U/A- lg prot/lg blood/no bact

  19. On arrival to DHMC • Somnolent, jaundiced, NAD, oriented X3. • T 36.2 HR 95reg BP 105/65 RR 22 O2 96% 2L NC • Skin- new areas of ecchymosis on dorsum of hand and limbs • HEENT- Scleral icterus, without OP lesions • Lungs- CTA B/L • CVS- tachy reg, no r/g/m • Abdo- soft, BS+, slight tenderness throughout without rebound or guarding, ND, no hepatosplenomegaly • Ext- no c/c/e b/l • Neuro- CNII-XII intact, motor 5/5 throughout, sensory grossly intact throughout, DTR symmetric and equal throughout

  20. At DHMC • Relapsing TTP • Transfusion 2 units PRBCs for Hgb 7.0 • Pheresis started without complications • VWF Metalloproteinase sent • CT head negative for bleed • Neuro checks

  21. Plasmapheresis D#1 • Acute severe LLQ abd pain following plasmapheresis • Restless and delusional • VSS • Abdominal exam benign • Delirium • supportive care as altered MS thought to be 2nd to her TTP • continued frequent neuro checks • haloperidol PRN • Abdominal pain • serial abdominal exams and guaiac all stools • meperidine for pain

  22. Plasmapheresis D#2 • More agitated • Intermittent apneic/tachypneic episodes with hypotension while on plasmapheresis • Skin was mottled • Plasmapheresis stopped • Patient placed on cardiac monitor, 100% NRB • ICU team to assess patient

  23. Transfer to ICU • On route to the ICU • agonal breathing, cyanotic and less responsive • 100% FM bagged ventilation • Intubated in the ICU • found to be in PEA • severe AG metabolic acidosis • CPR started

  24. After the Code • Attempts at resuscitation unsuccessful • Patient’s husband notified • Autopsy performed

  25. Epicardium - petechiae Myocardium - microthrombi

  26. AV Node Right atrium near medial leaflet of the tricuspid valve Central fibrous body near summit of the ventricular septum

  27. Intracerebral microthrombi (Cerebrum, basal ganglia, mesencephalon)

  28. Ileum microthrombi

  29. Renal capsule petechial hemorrhages

  30. Microthrombi in afferent renal arterioles

  31. Liver capsule petechial hemorrhage

  32. Portal area microthrombi

  33. Final Pathologic Diagnosis I. Thrombotic thrombocytopenic purpura A. Microthrombotic petechial hemorrhages, diffuse 1. Myocardium, epicardium, AV node a. Arrhythmia 2. Brain a. Mental confusion 3. Liver 4. Kidneys 5. Adrenal glands 6. Ileum B. Localized hemorrhages 1. Right renal medulla 2. Ovaries, bilateral 3. Abdominal aorta, adventitia 4. Gastric mucosa II. Chronic obstructive pulmonary disease A. Chronic bronchitis and emphysema B. Pulmonary edema III. Steatohepatitis IV. Chronic pancreatitis V. Uterine leiomyoma, focally calcified

  34. One month later • Two Metalloproteinase samples • Neg. for presence of metalloproteinase • Low titers of metalloproteinase inhibitor. • C/w acquired TTP

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