1. SEVERE HYPERHOMOCYSTEINEMIA IN A PATIENT WITH CHRONIC KIDNEY DISEASE, VITAMIN B12 DEFICIENCY AND SPONTANEOUS ERYTHROCYTOSIS 1 E. G AVRIILAKI, 2 E. P ASCHOU, 3 M. G ALANI, 3 A. P AVLIS, 1 A. K ALAITZOGLOU, 4 G. P APAIOANNOU, 5 N. S ABANIS 1 Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece 2 Department of General Practice & Family Medicine, General Hospital of Pella, Edessa, Greece 3 Department of Internal Medicine, General Hospital of Pella, Edessa, Greece 4 Hematology Department and Hematopoietic Cell Transplantation (HCT) Unit, G. Papanikolaou Hospital, Thessaloniki, Greece 5 Department of Nephrology, General Hospital of Pella, Edessa, Greece

2. CASE REPORT 76 years-old, non-smoker male patient right leg : superficial vein thrombosis great saphenous vein (pain, swelling, warmth, and erythema along the course of the great saphenous vein) BP:128/70 mmHg heart rate 72/min temperature 36.8 o CSpO2 98%. Medical History:hypertension (quinalapril 20 mg/d) T2DM (metformin 850/d, vildagliptin 50 mg/d) Laboratory Examinations: U/S: superficial vein thrombosis (great right saphenous vein)

3. Laboratory Examination Hb (g/dl)17.6 Hct (%)52.1 RBC (x10 6 /μL)4.85 MCV (fL)105 PLT (x10 3 /μL)305 ESR (mm/h)24 Creatinine (mg/dl)2.71 SGOT / SGPT (mg/dl)14/16 LDH (U/l)189 Ca +2 (mg/dl)10 Κ + (mmol/L)4.1 Νa + (mmol/L)138 ERYTHROCYTOSIS Macrocytosis  renal failure (GFR 28 ml/min) Renal u/s & abdominal CT: bilateral renal cysts and reduced kidney size Gastrointestinal endoscopy : atrophic gastritis + H.pylori infection, APCA(+) B12 = 107 (nr 200-900pg/mL Brain CT : leukoencephalopathy Thorax CT : calcification of coronary arteries Tumor markers (CEA, aFP, PSA, Ca15.5, Ca 19.9)  normal Thyroid hormones  normal (TSH, T3, T4, FT3, FT4) gas study : normal

4. thrombophilia testing PT (sec)106ANA- APTT (sec)29,6ACA- INR0,87β 2 GPI- Fibrinogen (g/L)3,7MTHFR mutation- PROT C (%)100PROT S (%)92 AT III (%)92V LEIDEN- Homocysteine = 89,6 (nr 3,5-20mmol/L) Bone marrow smear = normal JAK2 gene:V617F mutation (-) Polycythemia Vera excluded DIAGNOSIS: Superficial vein thrombosis due to severe hyperomocysteinemia accordingly to B12 deficiency in a patient with CKD TREATMENT: Symptomatic treatment LWMH injection (therapeutic dosage) for 6 months Alteration of antihypertensive and antidiabetic therapy B12 injection EPO = 13,28 (nr 4-27)

5. hyperhomocysteinemia B12 deficiency CKD metformin Atrophic gastritis TROMBOSIS/ CVD