M&M

1. M&M 7.27.2007 Ji Yeon Lee

2. Case • CC: Rectal bleeding, hematuria • HPI: 77yo Korean female with h/o HTN presented to ER with rectal bleeding and hematuria(+vaginal bleeding). She states that she noticed a little bleeding from her bottom for a week. A couple of days ago, she noticed conjunctival hemorrhage and visited an eye doctor. On the day of admission morning, she went to bathroom and passed out for a short time, and then found heavy bleeding on the floor, and brought to ER by her familly.

3. PMHx • HTN • Lower back pain • Abd pain in 6/06:visited ER.CT abd/pelvis neg • L knee surgery • No prior history of bleeding • No cancer screening • Medication: norvasc. No OTC meds, No herbal meds

4. All: NKDA • FHx: No coagulopathy, No cancer • SHx: no cig/ETOH/drug • Lives with her son and his family at home • Immigrated from Korea 20yrs ago, has 2sons and 3dtrs.

5. ROS • Weakness+, no wt loss, eats small meals, no change in appetite. • No f/c • No sob. Occ chest pain+ • No n/v/c/d, no abd pain • No cough/sputum • No dysuria/frequency

6. Physical Exam • GEN: thin, weak, elderly lady, a/o x3 • VS: 67/51-83-20-98.9 94% RA • HEENT: pale conjunctiva and oral mucosa. No petechiae or ecchymosis • Neck: no mass • Chest: Irregular, nl S1, S2, CTAB • Abd: soft NABS, ND, mild diffuse tenderness • Ext: no edema, R lower leg bruise+

7. 7.1 9.55 167 22.2 139 107 26 231 3.8 21 1 Lab findings MCV 90 Smear normal PT>140 PTT 212.2 D-dimer 0.58 Fibrinogen 315 Thrombin time 15.7 Alb 3.2 Glob 2.4 Alk phos 52 AST 23 ALT 19 Tb 0.8 Ca 8.2

8. Hospital course • IVF for hypovolemia-BP improved. • PRBC transfusion for anemia • FFPs, factor VIIa for coagulopathy-corrected to normal PT/PTT • Cause for coagulopathy-work ups started.

9. Coagulation cascade

11. Mixing study • “weak inhibitor”

12. Further lab findings • Warfarin level <0.1 • SPEP, UPEP nl • Coombs test neg • BCx, Ucx neg • ANA 1:160 speckled • Factor V leiden neg • Beta 2 glycoprotein neg • Lupus anticoagulant neg • cardiolipin Ab IgM 41(mod pos), IgG 7(neg) • Factor II 40%(L, 86-150) • Factor V 117% • Factor VII 676%(H) • Factor VIII 260%(H) • Factor IX 35%(L, 50-150) • Factor X 78%(L, 82-157) • Factor XI 80%

13. Work up • CT abd/pelvis: • small renal cysts • 1.8cm soft tissue density near hepatic flexure • wall thickening in rectosigmoid colon • Colonoscopy: • 4mm sessile polyp in ascending colon • blood clot in area of splenic flexure • -->Bx: ulcer

14. Diagnosis • Suspected prothrombin inhibitor

15. Hospital course • No more bleeding. Stable H/H • No response to PO vitamin K • Continuous needs for FFPs • Treatment started with cyclophosphamide 100mg qd, prednisone 40mg qd, and rituximab qwk. • No improvement over 1 month period

16. Ethical issues • How long should we wait to see the effectiveness of treatment? • Futility? • Withdrawal of care?

17. Prothrombin inhibitors • Most often detected in pts with antiphospholipid antibodies. • Can cause significant clinical bleeding • Bind to a nonactive portion of the molecule, resulting in accelerated clearance of prothrombin • Lab testing is most consistent with a factor deficiency rather than an inhibitor since the functional activity of prothrombin is not impaired • Specific immunochemical measurement of the prothrombin concentration is required to establish the diagnosis.

18. Treatment • Control of active bleeding: • prothrombin complex concentrates • recombinant human factor VIIa • Based upon the severity of bleeding and the titer of the inhibitor • If no response: extracorporeal plasmapheresis with an immunoadsorption column to absorb the autoantibody can be tried. • The suggested dose of FFP is 15 to 20 ml/kg, with a target prothrombin level >30 percent • Eliminating the inhibitor: • Prednisone and cyclophosphomide: • IVIG –not recommended as inintial therapy • Cyclosporine if resistant to all of the above • Rituximab alone or with cyclophosphamide • Cladribine: purine analog