Case report 24 th Summer School of Internal Medicine 2015

Transcription

1 Case report 24 th Summer School of Internal Medicine 2015 Goldmannová D., Horák P., Skácelová M. IIIrd Internal Clinic - endocrinology, diabetology, rheumatology, nephrology University hospital Olomouc, Czech Republic

2 Case report Woman, birth on 1980, send from District Department of internal medicine She was accepted for collapse, serious anemia, thrombocytopenia, progression of renal insufficiency, pleural pain in 12/14 Antiphospholipid syndrome (pos. LAC, ACLA, B2Gl, recurrent deep vein thrombosis, pulmonary embolism) diagnosed 9/14 Focal segmental glomerolosclerosis (with renal insufficiency stable creatinine around 100µmol/l) diagnosed in her 10 years Anamnestically positive ANA, anti-dsdna, ANCA, fleeting pulmonary infiltrates (X-ray and CT) Pharmacology anamnesis: rivaroxaban, methylprednisolon, iron supplementation, PPI

3 Laboratory parameters for acceptance Urea (1,7-8,3 mmol/l) 11,3 Creatinine ( µmol/l) 299 Hemoglobin ( g/l) 78 Thrombocytes ( x10 9 /l) 49 LDH (2,2-3,2 µkat/l) 3,81 Free Hemoglobin (0-50 mg/l) 58 Haptoglobin (0,3-0,8 g/l) 1,3 Schistocytes 5 Proteinuria (g/l) 0,78 Positive LAC (112,8s), ACLA (737U/ml), B2Gl (4263U/ml) Reduction of complement (C3 0,77g/l, C4 pod 0,06g/l) Positive anti-dsdna 64 IU/ml, ANUC 64 IU/ml Negative ANA, ENA, RF, anti-ccp Normal ADAMTS 13

4 Working diagnose?

5 Differential diagnose of trombotic microangiopaties CAPS TTP/HUS HELLP Sepsis DIC HIT Anamnesis APS/SLE Malignancy/diarrhe a/aps/sle Gravidity Infection Infection/ malignity Treatment of heparine Clinical manifestation 3 and more organs in 1 week Hemolysis Thrombocytopenia Renal failure Edema Hypertension Thrombocytopeni a Hepatopathy Infection Bleeding Trombosis Thrombosis Bleeding Trombosis Large/ Small vessels Small vessels Small vessels Large/ Small vessels Small vessels Large/ Small vessels AutoAb apl Anti-ADAMTS-13 (ahus) no no no anti-hp4 Schistocytes yes yes rare rare rare rare Fibrinogen normal/ increased normal/ increased normal/ increased normal/ low normal/ low normal/ increased Cervera R., Autoimmunity Rev, 2014

6 Trombotic trombocytopenic purpura X Hemolyc uremic syndrome?

7 HUS criteria Thrombocytopenia - below 150x10 9 /l or a decrease of 25% compared to a baseline value Microangiopathic hemolytic anemia - Nonimmunologic hemolysis (anemia, bilirubin, LDH, haptoglobin) with fragmentation of erythrocytes (schistocytes) in blood count - 2 and more schistocytes in the microscopic field in 100fold magnification Ryšavá R. Hemolyticko-uremický syndrom a nové možnosti léčby. ZDN 2013 Burns ER1, Lou Y, Pathak A. Am J Hematol Jan;75(1):

8 HUS Organ manifestation - Kidney: acute or chronic x around 17% of patients have normal renal functions with little proteinuria or hematuria - CNS: stroke, cranial nerve palsy, change of psychomotor speed etc. - GIT: diarrhea, abdominal pain, vomitting, pacreatitis, hepatopathy, etc. - KV complications: IM, hypertension, heart failure, cardiomyopathy, etc. - Necrosis and skin purpura, lung bleeding, eye complications

9 What is the first line therapy for HUS?

10 Our therapy Plasmapheresis (5x) Pulses of corticosteroids (1g Methylprednisolon 4x) Substitution of erythrocytes 1st pulse of cyclophosphamide

11 TTP/HUS therapy * Specific Anticoagulation Corticosteroids Plasmapheresis IVIG Immunosuppressives Biological therapy * Treatment of trigger factors * Nonspecific Hemodialysis Artificial ventilation Ionotropics Antihypertension therapy PPI * Profylactic Treatment of infection Anticoagulation therapy (APS) surgery gravidity Relapse of SLE Polito M. Jornal Brasileiro dle Nefrologia 2010 Cervera R., Autoimmunity Rev, 2014 Cervera R., Curr Rheumatol Rep, 2010

12 Laboratory parameteres for acceptance Urea (mmol/l) 11,3 Creatinine (µmol/l) 299 Hemoglobin (g/l) 78 Thrombocytes (x10 9 /l) 49 LDH (µkat/l) 3,81 Free Hemoglobin (mg/l) 58 Haptoglobin (g/l) 1,3 Schistocytes 5 Proteinuria (g/l) 0,78 For release 8, ,8 40 0,8 3 Positive LAC (112,8s), ACLA (737U/ml), B2Gl (4263U/ml) Reduction of complement (C3 0,77g/l, C4 pod 0,06g/l) Positive anti-dsdna 64 IU/ml, ANUC 64 IU/ml Negative ANA, ENA, RF, anti-ccp Negative ADAMTS 13

13 Plasmapheresis The first line therapy It should be performed daily untill stabilization of the value of platelets 3 and hemoglobin LDH before 3 rd plasmapheresis/ldh before 1 st plasmapheresis: 0,6 marker (sensitivity 0,96, specificity 0,83) 2 - Ratio of our patient: 0,7 Mortality declined after treatment including plasmapheresis from 50% to 25% 1 There are no randomised controlled trials evaluating interventions for secondary (atypical) HUS 1 Ruggenenti P, Kidney Int 2001; 2 Haas M, Clin Nephrol 2002; 3 Roberts AW,. J Clin Apher 1991;

14 2nd hospitalization On January 2015 she was hospitalized at the Clinic of pneumology Bronchoscopy BAL Conclusion: Suspected pulmonary involvement in systemic disease Then the patient was hospitalized planned to submit a second pulse of cyclophosphamide Clinically asymptomatic, tiredness, state with a history of viral infection

15 Therapy Pulses of corticosteroids (1g Methylprednisolon 5x) Substitution of erythrocytes Intravenous immunoglobulines 0,4g/kg (4 days) Plasmapheresis (5x)

16 Laboratory parameters for acceptance Urea (mmol/l) 21,6 Creatinine (µmol/l) 363 Hemoglobin (g/l) 61 Thrombocytes (x10 9 /l) 74 LDH (µkat/l) 3,9 Free Hemoglobin (mg/l) 40 Haptoglobin (g/l) 1,2 Schistocytes 3 Proteinuria (g/l) 3,2 For release 12, , ,8 2 5/15 7, ,8 40 0,7 2 1,2

17 Diagnostic summary Systemic lupus erythematodes with medium immunological activity Secondary antiphospholipid syndrome Secondary hemolyc-uremic syndrome with renal disease

18 Antiphospholipid syndrome = 3 TROMBOTIC MANIFESTATION +/OR SPECIFIC COMPLICATION OF GRAVIDITY PERSISTENT POZITIVITY apl APS Wilson WA Arthritis Rheum 1999, 42, 1309 Miyakis S J Tromb Haemost 2006, 4, 295

19 Trombotic microangiopathy within APS TTP/HUS 33% Catastrophic APS 23% Acute renal failure 15% Malign hypertension 13% HELLP syndrome 4% Espinosa G, Ann Rheum Dis, 63, 2004 McNeil Adv Immunol 1991, 49, 1993 Diz Kucukkaya R. Blood 2001, 989, 1760

20 Antiphospholipid syndrome, trombotic microangiopathy - TTP/HUS, renal biopsy. You can see two glomeruluses, capillary colaps, endothelial edema, ischemic injury, fibrin trombus. 200fold magnification.

21 Thank you for your attention