1. Caroline M. Armas, MD Medical Resident Moderator: Dr Benjamin Benitez

2. OBJECTIVES To present a case of a 52 year old male, who came in due to epigastric pain To discuss a complication of Polycythemia Vera

3. Identifying data NDG 52 year old, male Married Catholic From Brgy. Valenzuela, Makati City Admitted: October 16, 2010

5. History of present illness Diagnosed with Polycythemia Vera (2006) Rx: Hydroxyurea (Litalir); phlebotomy as needed 2 weeks Epigastric pain, grade 10/10, nonradiating Rx: Ranitidine, Pantoprazole and Aluminum/Magnesium Persistence of abdominal pain Admission

6. Review of systems No fever, cough, colds No chest pain, no difficulty of breathing No dysuria, frequency, urgency

7. Past medical history Post Cerebrovascular accident (2006) Acid Peptic Disease on AlOH2 + MgOH2 as needed

8. Family history No hypertension, diabetes, thyroid disorders No history of cancer Denies history of blood dyscrasia

9. PERSONAL AND SOCIAL HISTORY Previous smoker – stopped 2006 14 pack-year (10sticks/day for 28years) Occasional alcoholic beverage drinker 1-2 bottles of beer, 1-2x/month

10. PHYSICAL EXAMINATION Conscious, coherent, ambulatory, not in respiratory distress BP 110/70 mmHg HR 72 bpm RR 19cpm T 36C Ht 152cm Wt 81kg BMI 25.6 Supple neck, no neck vein distention, Symmetric chest expansion, clear breath sounds Quiet precordium, normal rate, regular rhythm, apex beat at 5 th ICS MCL, no murmurs

11. Physical examination Flat abdomen, normoactive bowel sounds, soft, (+) direct tenderness on epigastric area No edema; Full and equal pulses Neurologic examination: unremarkable

12. Salient features 52/M Known case of Polycythemia vera Post cerebrovascular accident – no residuals (+) epigastric pain (+) direct tenderness on epigastric area

13. Initial impression Acid Peptic Disease Acute pancreatitis Polycythemia Vera Post Cerebrovascular accident with no residual

14. COURSE IN THE WARD 1 st Hospital Day CBC, Amylase and Lipase Plain film of abdomen CT of whole abdomen (plain) Nothing per orem Pantoprazole 40mg IV once daily Octreotide 250mcg subcutaneous, followed by 750mcg IV drip Referred to Hematology service

15. COURSE IN THE WARD CBC Hemoglobin10.7 Hematocrit33.5 WBC11.67 Segmenters63 Lymphocytes22 Eosinophils2 Basophils2 Monocytes11 Platelet count1267000 MCV84.4 MCH27 MCHC31.9 RDW17 Amylase48 Lipase33.6

16. PFA October 16 2010

17. COURSE IN THE WARD

22. Course in the ward Plain CT scan of whole abdomen: Acute pancreatitis Minimal ascites Atherosclerotic disease of the abdominal aorta

23. Acute Pancreatitis Most Common causes: Gallstones (30-60%) and Alcohol (15 to 30%) Abdominal pain is the major symptom Diagnosis: increased level of serum amylase CT scan may confirm the clinical impression of acute pancreatitis even in the face of normal serum amylase levels

24. Polycythemia Vera Is a stem cell disorder Prominent feature: elevated absolute red blood cell count because of uncontrolled red blood cell production Increased white blood cell and platelet production due to an abnormal clone of hematopoietic stem cells with increased sensitivity to different growth factors of maturation

25. COURSE IN THE WARD 3 rd Hospital day Still with epigastric pain, grade 7/10 Repeat CBCCBC Referred to Infectious Diseases service Blood culture Imipenem 250mg IV every 6 hours

26. COURSE IN THE WARD CBC3 rd HD Hemoglobin10.710.9 Hematocrit33.534.6 WBC11.6714.91 Segmenters6352 Lymphocytes2227 Eosinophils23 Basophils22 Monocytes1116 Platelet count12670001342000 MCV84.485.6 MCH27 MCHC31.931.5 RDW1717.1

27. COURSE IN THE WARD 5 th Hospital Day (+) abdominal pain, grade 2/10 CBC, CEA, AFP, CA 19-9 Diet: General liquids Hydroxyurea 500mg 2tabs 2x/day

28. COURSE IN THE WARD CBC3 rd HD5 th HD Hemoglobin10.710.911 Hematocrit33.534.635.4 WBC11.6714.9114.84 Segmenters635255 Lymphocytes222718 Eosinophils2313 Basophils222 Monocytes111612 Platelet count12670001342000978000 MCV84.485.686.1 MCH27 26.8 MCHC31.931.531.1 RDW1717.117 5 th HD AFP (8.6)1.41 CA19-9 (0-39)4.81 CEA (0-5.5)0.92

29. Hydroxyurea Is a nonalkylating agent that inhibits DNA synthesis and cell replication by blocking the enzyme ribonucleotide reductase resulting in a megaloblastic blood picture Onset of action is rapid, usually 3-5 days of initiation of treatment and effect is short-lived once medication is stopped Initial dose is 15mg/kg per day, taken in divided doses

30. COURSE IN THE WARD 7 th hospital day (+) abdominal pain, grade 5/10 CBC CT of whole abdomen with IV contrast

31. COURSE IN THE WARD CBC3 rd HD5 th HD7 th HD Hemoglobin10.710.91111.3 Hematocrit33.534.635.436.4 WBC11.6714.9114.8413.17 Segmenters63525556 Lymphocytes22271827 Eosinophils23138 Basophils222 Monocytes1116129 Platelet count12670001342000978000934000 MCV84.485.686.186.7 MCH27 26.826.9 MCHC31.931.531.131 RDW1717.11717.4

36. COURSE IN THE WARD CT of Whole Abdomen with IV contrast Portal vein thrombosis extending to the SMV. Minimal ascites which has slightly increased since the previous examination. Interval increase in the size of the gallbladder likely reactive in nature. Colonic diverticulosis Atherosclerotic abdominal aorta. Minimal right pleural effusion.

37. Thrombosis in polycythemia vera Thrombosis is a frequent complication in persons with Polycythemia vera Result from the disruption of hemostatic mechanisms because of increased level of red blood cells and an elevation of platelet count. Significant risk factors for thrombosis History of prior thrombosis Age over 60 years old Prolonged exposure to substantial degrees of thrombocytosis

38. Polycythemia Vera:The Natural History of 1213 Patients Followed for 20 Years Retrospective cohort Subjects: 1213 patients with polycythemia vera 14% had thrombotic events before diagnosis of polycythemia vera; and 20% had a thrombotic event as presenting symptom

39. The Natural History of 1213 Patients Followed for 20 Years polycythemia vera Follow-up: Fatal thrombosis – arterial thrombosis (81%) and venous thrombosis (18%); Nonfatal thrombosis: Superficial thrombophlebitis (18.5%) Deep Vein Thrombosis (17.5) Myocardial infarction (14%) Ischemic stroke (9.5%)

40. COURSE IN THE WARD 7 th hospital day Blood C/S: no growth Imipenem was discontinued Referred to TCVS Baseline PT, PTT Heparin drip 10000 units to run for 24 hours

41. Heparin Is an indirect thrombin inhibitor which complexes with antithrombin converting it from a slow to a rapid inactivator of thrombin. Limitation: narrow therapeutic window of adequate anticoagualtion without bleeding. Monitor response using aPTT Therapeutic level for first 24hours: 1.5times the control Maintenance: 1.5-2.5 times

42. COURSE IN THE WARD

43. 12 th Hospital day Therapeutic platelet reduction  Repeat CBCCBC

44. COURSE IN THE WARD CBC3 rd HD5 th HD7 th HD13 th HD Hemoglobin10.710.91111.310.7 Hematocrit33.534.635.436.434.4 WBC11.6714.9114.8413.178.54 Segmenters6352555655 Lymphocytes2227182724 Eosinophils231385 Basophils222 Monocytes11161296 Platelet count12670001342000978000934000623000 MCV84.485.686.186.785.4 MCH27 26.826.926.6 MCHC31.931.531.13131.1 RDW1717.11717.417.7

45. Phlebotomy Mainstay of therapy of Polycythemia Vera Objective is to remove excess cellular elements to improve the circulation of blood by lowering blood viscosity.

46. COURSE IN THE WARD 14 th hospital day Minimal abdominal pain Chest heaviness ECG, cardiac enzymes  referred to Cardiology service ECG, cardiac enzymes 2D-Echo Clopidogrel 75mg daily, Nicorandil 5mg 2x/day Trimetazidine 35mg 2x/day, Bisoprolol 2.5mg daily

48. COURSE IN THE WARD ECGProbable old inferior wall MI Nonspecific ST-Twave changes 2D-EchoInterventricular septal hypertrophy with hypokinetic posterior and inferior walls from mid to apex. Mildly depressed left ventricular systolic function with EF of 52%. Mild mitral tricuspid and pumonic regurgitation. Normal pulmonary artery pressure. Doppler evidence of impaired LV diastolic dysfunction. TCPK73 Trop I0.3 CPK-MB1.5

49. COURSE IN THE WARD 16 th hospital day Febrile episodes (Tmax 38C) (+) Rales on left lower base Chest Xray and CBC Chest Xray CBC Digoxin 0.125mg IV daily and Spironolactone 25mg daily

50. CHEST X-ray October 31, 2010

51. COURSE IN THE WARD CBC3 rd HD5 th HD7th HD13th HD 16th HD Hemoglobin10.710.91111.310.710.3 Hematocrit33.534.635.436.434.432.9 WBC11.6714.9114.8413.178.549.16 Segmenters635255565570 Lymphocytes222718272422 Eosinophils2313851 Basophils222 1 Monocytes111612966 Platelet count12670001342000978000934000623000415000 MCV84.485.686.186.785.486.1 MCH27 26.826.926.627 MCHC31.931.531.13131.131.3 RDW1717.11717.417.718

52. COURSE IN THE WARD 20 th Hospital day Still with febrile episode (Tmax 37.9C) (+) cough productive of yellowish phlegm Moxifloxacin 400mg once daily (-) abdominal pain  Octreotide was discontinued

53. COURSE IN THE WARD 22 nd Hospital day Repeat Chest Xray Referred to Pulmonology service Moxifloxacin shifted to Piperacillin Tazobactan 4.5g IV every 8 hours Heparin was titrated and eventually consumed Warfarin initially 5mg/tab daily

54. CHEST X-ray November 4, 2010

55. COURSE IN THE WARD 27 th Hospital day Repeat PT showed INR 4.08 – Warfarin was discontinued Afebrile with decreased episode of coughing Repeat Chest XrayChest Xray

56. CHEST X-ray November 9, 2010

57. COURSE IN THE WARD 29 th hospital day: Afebrile Decrease episodes of coughing No abdominal pain and with good appetite Repeat PT – INR 3.55 Given last dose of antibiotics and was discharged the following day.

58. FINAL DIAGNOSIS Acute Pancreatitis Portal Vein Thrombosis Non ST Elevation MI Hospital Acquired Pneumonia Polycythemia Vera Post Cerebrovascular Accident with no residual

59. FURTHER OUTPATIENT CARE Use of Myelosupressive therapy plus phlebotomies with the intent of normalizing erythrocyte and platelet counts Proven thrombotic complications warrant the use of long term anti-coagulation with warfarin.