Bleeding and Platelet Disorders

Educational Objectives

The goal of this program is to improve the diagnosis and management of bleeding and platelet disorders. After hearing and assimilating this program, the clinician will be better able to:

1. Diagnose platelet and bleeding disorders using patient history and laboratory test results.

2. Manage common coagulation and platelet disorders.

Summary

History of bleeding: ask patient about bleeding (particularly after surgery, including minor procedures) to determine hemostatic status; includes type of bleeding, age of onset, patient’s sex, family history, drugs taken (eg, antiplatelet drugs), nutritional status (eg, vitamin K), and comorbid conditions that increase risk of bleeding

Laboratory evaluation: begins with general screening (eg, platelet count, peripheral blood smear, coagulation screen); if results abnormal, perform mixing study using 50% plasma from patient and 50% normal plasma (determines presence of inhibitor or deficiency of factor); interpretation of tests of platelet function difficult; results correlate with bleeding history; platelet function screen or test of platelet closure time replaces test of skin bleeding time; platelet aggregation test and flow cytometry used to diagnose qualitative platelet disorder; fibrinolytic tests assess defects that increase risk of bleeding; perform specific factor assays if results of coagulation screen abnormal

Idiopathic thrombocytopenic purpura (ITP): incidence higher in women than men; includes primary ITP (no underlying disease) and secondary ITP (other illness, medication, or infection present); normal or high levels of megakaryocytes found in bone marrow; diagnosis of exclusion; measuring platelet-associated IgG not useful because of passive absorption to platelets; resolves spontaneously in children and rarely without therapy in adults (<20%)

Thrombotic thrombocytopenic purpura (TTP): schistocytes present on peripheral blood smear; immune-mediated process involving ADAMTS13 metalloprotease inhibitor; ADAMTS13 — unable able to cleave von Willebrand factor (VWF) and prevent its overreactivity when antibody directed against it; cleavage sites on VWF present; VWF aggregates into multimers as it circulates; multimers adhere to damaged endothelium and bring in platelets to form initial plug; prevents VWF from exceeding its normal activity and causing increase in platelet activation (leading to thrombotic effects of TTP); management — plasma exchange

Antiphospholipid syndrome (APS): lupus anticoagulant (LAC) — antibodies that produce phospholipid-dependent prolongation of coagulation assays; phospholipids cofactors for binding antibodies to variety of antigens (eg, β2-glycoprotein I); diagnosis — thrombotic event or fetal loss and laboratory evidence of antiphospholipid antibodies or LAC; guidelines recommend testing twice, with 12-wk interval (antibodies transient); catastrophic APS — multiorgan system failure; morbidity and mortality rate high; LAC (continued) — idiopathic or associated with other disorders (eg, connective tissue disorders, lymphoproliferative diseases, drugs, infection); thrombotic condition in majority of cases; may be associated with deficiency in prothrombin or thrombocytopenia; management — study found increasing anticoagulation with warfarin does not increase efficacy and increases risk of bleeding; American College of Chest Physicians recommends 3-mo therapy for first episode of unprovoked thrombosis; role of aspirin unclear; dual therapy indicated (international normalized ratio in normal therapeutic range)

von Willebrand disease (VWD): type 2 defects qualitative (types 1 and 3 quantitative); qualitative differentiated from quantitative defects by levels of VWF antigen, factor VIII (FVII), and ristocetin cofactor; if decrease in all levels similar, diagnosis most likely type I VWD (≈70%); desmopressin (DDAVP) given to patients with type 1 VWD who undergo surgical procedures; DDAVP challenge test — levels of VWF antigen, FVII, and ristocetin cofactor increase after administration of DDAVP (release of VWF and FVIII from storage sites in endothelial cells stimulated)

Heparin-induced thrombocytopenia: typical develops 5 to 10 days after initiation of heparin therapy; decrease in platelet count ≥50%; return to normal platelet count 4 to 5 days after withdrawal of heparin; thrombosis can occur at any platelet count and with administration of any type of heparin (incidence with low-molecular-weight heparin [enoxaparin] lower and with fondaparinux, very low); diagnosis — pretest probability score based on degree of thrombocytopenia, timing, presence of thrombosis, and other causes; presence of antibodies demonstrated by heparin-platelet factor 4 enzyme-linked immunosorbent assay or Serotonin Release Assay; treatment — avoid delay if patient fits clinical criteria (do not rely on laboratory confirmation); discontinue heparin; administer direct thrombin inhibitor (DTI; eg, argatroban, bivalirudin); avoid warfarin until platelet count recovers; then overlap with DTI; avoid enoxaparin or dalteparin (cross-reactivity) and platelet transfusion (increases thrombotic potential)

Readings

Baquero-Salamanca M et al: Variability in the international normalised ratio (INR) in patients with antiphospholipid syndrome and positive lupus anticoagulant: should the INR targets be higher? BMJ Case Rep, 2015 Apr 9;2015. pii: bcr2014209013; Imbach P: Advances in the management of ITP in children and adults. Clin Adv Hematol Oncol, 2014 Jun;12(6):384-7; Knöbl P: Inherited and acquired thrombotic thrombocytopenic purpura (TTP) in adults. Semin Thromb Hemost, 2014 Jun;40(4):493-502; Rodeghiero F, Ruggeri M: Treatment of immune thrombocytopenia in adults: the role of thrombopoietin-receptor agonists. Semin Hematol, 2015 Jan;52(1):16-24; Ruinemans-Koerts J et al: When to screen for lupus anticoagulant? Influence of testing during acute phase and consequences for clinical practise. Lupus, 2015 Oct;24(11):1233-5; Windyga J et al: EHTSB. Practical aspects of DDAVP use in patients with von Willebrand Disease undergoing invasive procedures: a European survey. Haemophilia, 2016 Jan;22(1):110-20.

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose.

Acknowledgements

Dr. Silver was recorded at the 28th Annual Intensive Review of Internal Medicine, held June 5-10, 2016, in Cleveland, OH, and presented by the Cleveland Clinic Foundation Center for Continuing Education. For information about upcoming activities from the Cleveland Clinic Foundation Center for Continuing Education, please visit www.clevelandclinicmeded.com. The Audio Digest Foundation thanks the speakers and the Cleveland Clinic Foundation Center for Continuing Education for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0 CE contact hours.

Lecture ID:

IM640901

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.