5/5/2010. Goldilocks picture from

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1 Sometimes platelet counts are TOO LOW; Goldilocks and the Three Platelets Robert T. Means, Jr., M.D. Professor & Senior Associate Chair Department of Internal Medicine University of Kentucky Lexington KY Sometimes platelet counts are TOO HIGH; What you want is a platelet count that s JUST RIGHT!! Disclosures: Activities in last 3 years Objectives Honoraria for lectures, consultant Beckman Coulter The attendee will be able to outline the diagnosis and initial management of common syndromes. ITP, DIC,, platelet underproduction, thrombocytosis Goldilocks picture from Case Study 50 yo WM with chronic low back pain. Lab: Hct, Hgb, WBC normal. Platelets 12K PMH: Orthopedic surgery (years ago) without complications; HTN (on beta blocker) Exam No evidence bleeding, bruising, petechiae. Further lab: Normal Panels 1+2, normal PT/PTT, normal blood smear except low platelets Etiologies of Thrombocytopenia Artifacts Underproduction Increased destruction Distribution/Pooling 1

2 Artifacts No in vivo significance Can probably demonstrate by blood smear Can document by using alternate anticoagulant but can be tricky Remember they may be time-dependent: i.e., a count run 5 minutes after being drawn may be normal while one run 30 minutes may be low Photomicrograph original source unknown Underproduction vs. destruction No retic count for platelets Drugs can cause either underproduction or destruction (former more common) Mj Major offenders most antibiotics i (especially beta lactams, sulfa); statins; anticonvulsants; diuretics Rarely a problem: Narcotics; benzodiazepines; beta blockers; erythromycin derivatives Underproduction Drugs clinical decision Primary marrow defects rarely associated with thrombocytopenia only Bone marrow is best way to evaluate, but not ideal Destruction/Sequestration ITP largely diagnosis of exclusion DIC abnormal PT/PTT, Fibrinogen/D-dimer Liver disease may be confused with above Clinical pentad Hypersplenism requires demonstration of portal HTN Drugs Heparin-induced induced thrombocytopenia ITP The most common immune thrombocytopenia Bleeding is less than expected for plt count Splenomegaly unusual Marrow consistent but not diagnostic Mostly idiopathic, but may be secondary Infection Collagen vascular disease Lymphoid malignancy Drugs Solid Tumors 2

3 ITP Antibodies are the pathologic mechanism Most commonly IgG, but may be IgA or IgM Rarely fix complement or form immune complexes Utility of antibody testing depends on assay used PlAIgG 60% sensitive, 77% specific, 81% PPV, 54% NPV (Haematology 2002;87: ) Anti-gpIIb/IIa, Ib/IX 93% specific if clinically appropriate; 84% specific in all comers (J Thromb Haemostasis 2003;1:485-91) Steroids Prednisone 1 mg/kg/d ITP on the way to the OR IVIgG 400 mg/kg Solumedrol 1 gm IV Transfuse 6u platelets on way to OR ITP in Pregnancy Infant usually comes out OK If plts > 70K, no issue In part, reflects comfort level of OB Steroids, IVIgG, Winrho may be used Splenectomy possible, but stressful for all concerned May wish to monitor scalp vein platelet count DIC Thrombocytopenia, evidence of coagulation factor and fibrinogen consumption, evidence of secondary fibrinolysis Prolonged PT/PTT, elevated D-Dimer, Dimer, decreased fibrinogen Schistocytes present but usually not a big deal Factor VIII goes down in DIC, normal or up in liver disease; Factor IX does reverse; V down in both Treat underlying disease; use FFP, platelets, maybe cryo as needed If thrombosis occuring, heparin may be useful, but be careful Clinical diagnosis Pentad rarely present: think with low plts, MAHA, abdominal pain, any urinary abnormalities ADAMTS 13 is pathophysiologically o og y important t but not acutely useful; may predict prognosis. ADAMTS 13 activity and inhibitor should be sent off prior to treatment HUS is part of same spectrum; think HELLP in the pregnant Photomicrograph American Society of Clinical Pathology 3

4 Associations Infection HIV, Shigella, E. coli Pancreatitis Drugs CsA, Ticlid, Plavix, Quinine, mitomycin, m in rapamycin Collagen vascular disease Cancer, especially gastric, breast (? Mitomycin) BMT Treatment Plasmapheresis is mainstay Need transfer to hospital with plasmapheresis. If you can t transfer, give FFP 2-4unitsper24hrs 24 Avoid platelet transfusions unless life-threatening bleeding End point is normal platelets, normal LDH, improving Hct HIT/T Suspect and act on clinical grounds DC heparin Start direct thrombin inhibitor Lepirudin, Argatroban PF4 antibody; serotonin release tests Test interpretation guided by clinical probability All patients with actual HIT need at least 6 mo anticoagulation Distribution/Pooling Hypersplenism Diagnosis of exclusion Presence of portal hypertension supports Hypothermia Cold platelets go off and hide Washout Significance unclear, but avoid if possible Thrombocytopenia Case Study Key Points Lab: Hct, Hgb, WBC normal. PMH: Orthopedic surgery (years ago) (on beta blocker) Exam No evidence bleeding, bruising, petechiae. Further lab: Normal Panels 1+2, normal PT/PTT, normal blood smear except low platelets Probable diagnosis - ITP Reactive Myeloproliferative Thrombocytosis 4

5 Reactive Thrombocytosis Post-operative operative status Inflammation/Infection Iron deficiency Bleeding Mli Malignancy Splenectomy Usually reactive thrombocytosis has a platelet count < 1,000,000/µL, but occasionally can go higher (usually with infection) Myeloproliferative Thrombocytosis Polycythemia vera Essential thrombocytosis Chronic myelogenous leukemia The higher the platelet count, more likely these diagnoses become. Clues are: history of thrombosis, splenomegaly, leukocytosis*, erythrocytosis, basophilia, eosinophilia, myelocytes in the blood Evaluation of Thrombocytosis History/physical CBC/diff, serum ferritin Radiology as indicated by history and physical If suspicious for myeloproliferative thrombocytosis JAK2 Polycythemia vera (>95%+), Essential thrombocytosis (50-60%+) Bcr/abl Chromic myelogenous leukemia Management of Thrombocytosis Reactive Generally does not predispose to thrombosis with possible exception of post-splenectomy splenectomy in liver disease Usually just observe Treat underlying etiology Aspirin 81 mg is not unreasonable Myeloproliferative - refer References Green SL, Means RT. Approach to anemia and thrombocytopenia, in Griffith CH, Hollein A, Feddock C, Harrell H (eds): First Exposure: Hospital Medicine. McGraw Hill, NewYork 2007 pp Buss DH, Cashell AW, O Connor ML, Richards F, Case LD. Occurrence, etiology and clinical significance of extreme thrombocytosis: a study of 280 cases. Am J Med 1994;96: