1. Case Discussion Huang Honghui Department of Hematology Ren Ji Hospital

2. Case Summary 26 year-old, female patient persistent nasal bleeding for one day, have an upper respi- ratory infection 2 weeks previously. No fever, chills, nausea, vomiting, abdominal pain, or joint pain. PE: multiple l-mm reddish spots on her lower extremities. No lymphadenopathy or hepatosplenomegaly. No excessive bleeding with menses, childbirth, prior epistaxis, easy bruisability, or bleeding into her joints. No family history of abnormal bleeding. Not take any medication.

3. Objects of Analysis Learn the clinical approach to bleeding disorders, specificly platelets disorders versus coagulation disorders. Learn about the differential diagnosis of thrombocytopenia, specifically thrombocytopenic purpura versus other platelet disorders, such as thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS), or disseminated intravascular coagulation (DIC). Learn about the treatment of ITP.

4. Consideration superficial petechiae and mucosal bleeding disordered primarymary hemostasis laboratory testing complete blood count prothrombin time (PT) screening partial thromboplastin time (PTT) Bone marrow smear

5. APPROACH TO SUSPECTED THROMBOCYTOPENIA

6. HISTORY Liver disease, uremia, malignancy, systemic lupus erythematous Medications: over-the-counter products (aspirin) Family history of abnormal bleeding History of epistaxis, menorrhagia, excessive prolonged bleeding from minor cuts, bruising, prolonged or profuse bleeding after dental extraction, excessive bleeding after major surgery or obstetric delivery, trauma followed by bleeding considered excessive relative to the injury

7. Timing of Bleeding If bleeding following dental extraction is immediate and lasts for longer than 24 hours,a problem with primary hemostatic plug formation may be present. Therefore, this may suggest a platelet disorder. If initial hemostasis seemed normal but prolonged bleeding developed 2-3 days later, a problem in the coagulation phase is suspected.

8. Type of Bleeding Spontaneous mucus membrane bleeding, such as gum bleeding, nose bleeding, and petechiae are suggestive of a vascular disorder, thrombocytopenia, or abnormal platelet function. Hemarthrosis, deep hematoma, and retroperitoneal bleeding are more likely to reflect a severe coagulation abnormality, such as hemophilia, if problems have been lifelong spontaneous inhibitor of factor VIII, if problems appear later in iife.

9. Vascular Disorders Vascular purpura present with bleeding from mucus membranes and the appearance of petechiae but usually the platelet count and the coagulation profile (PT and PTT)are normal Hereditary hemorrhagic telangiectasias inherited as an autosomal trait of high penetrance. the most common hereditary vascular disorder The physical exam will show the presence of telangiectasias.

10. Causes of thrombocytopenia decreased platelet production decreased platelet survival sequestration (hypersplenism) dilutional

11. Spurious Thrombocytopenia Automated cell counters reports spurious thrombocytopenia in approximately 0.l% of patients. This is generally a result of platelet dumping after drawing blood into the anticoagulant ethylene diamine tetra acetate (EDTA). Confirmation Identifying platelet aggregates on peripheral blood smear Using citrate or heparin as an anticoagulant

12. Impaired platelet production Infiltration caused by malignancy or myelofibrosis Marrow hypoplasia Chemicals Drugs Radiation Viruses

13. Decrease platelet survival immune thrombocytopenia purpua (caused by IgG antibody against the platelets), drug-induced thrombocytopenic purpura secondary immunologic purpura (as in lymphoma, lupus,infection with human immunodeficiency virus type 1) posttransfusion purpura. Disseminated intravascular coagulation hemolytic uremic syndrome cavernous hemangioma acute infections

14. ITP Acute ITP early childhood antecedent upper respiratory infection self-limiting, usually resolves spontaneously within 3-6 months. Chronic ITP in adults, most likely to occur in women ages 20-40 years an insidious or subacute present. persist for months to Years, with uncommon spontaneous remission.

15. Several immunologic disorders may mimic true ITP drug induced thrombocytopenic purpura Discontinuation of the medication should lead to improvement in the platelet count within a time frame consistent with the drug ’ s metabolism. Many drugs are blown to cause thrombocytopenic purpura, such as quinidine and quinine, Sulfonamide, heparin, and gold compounds. SLE Lymphoma Lymphadenopathy splenomegaly HIV-1 infection Posttransfusion purpura

16. Nonimmunologic disorders may mimic true ITP DIC TTP

17. DIC ETIOLOGY Secondary to some other process: sepsis, trauma, metastatic malignancy, obstetric causes CLINICAL COURSE can be relatively mild indolent course, or severe llfe- threatening process; ongoing coagulation and fibrinolysis; can cause thrombosis or hemorrhage; consumption of coagulation factors is seen as prolonged PT and PTT

18. DIC TREATMENT Treatment aimed at underlying cause. No proven specific treatment for the coagulation problem. If clotting,consider anticoagulate with heparin. If bleeding, replace factors and fibrinogen with fresh frozen plasma or cryoprecipitate.

19. TTP ETIOLOGY Multiple causes, many seemingly trivial drugs/infection lead to endothelial injury and release of von Willebrand factor, triggering formation of mlcrovascular thrombi. CLINICAL COURSE fever altered mental states thrombocytopenia Microangiopathic hemolytic anemia Renal failure

20. TTP TREATMENT Plasmapheresis (removal of the excess/abnormal vWF), most patients recover corticosteroids

21. ITP ETIOLOGY Antiplatelet antibody leading to platelet destruction CLINICAL COURSE Children:following a Viral illness with resolution. Adults:a more indolent course with progression and rarelys spontaneous resolution. Isolated thrombocytopenia, normal PT, PTT. Increased megakaryocytes on bone marrow aspiration.

22. ITP TREATMENT Oral Corticosterolds, Splenectomy if resistant to steroids, Immunosuppressants Intravenous Immmoglobulin

23. Answers Most likely diagnosis: Immune thrombocytopenic purpura Best initial treatment: Oral corticosteroids

24. Comprehension Questions A 50-year-old man has been treated for rheumatoid arthritis for many years. He is currently taking corticosteroids for the disease.On examination, he has stigmata of rheumatoid arthritis and some fullness on his left upper abdomen. His platelet count is slightly low at 56,000/mm3. His WBC count is 3,100/mm3 and Hgb 9.Og/dL. Which of the following is the most likely etiology of the thrombocytopenia? A.Steroid induced B.Sequestration C.Rheumatoid arthritis autoimmune induced D.Prior gold therapy

25. Comprehension Questions A 30-year-old woman with ITP has been taking maximum corticosteroid doses and still has a platelet count of 20,000/mm3 and frequent bleeding episodes. Which of the following should she receive before her splenectomy? A.Washed leukocyte transfusion B.Intravenous interferon therapy C.pneumococcal vaccine D.Bone marrow radiotherapy

26. CLINICAL PEARLS Bleeding abnormalities can be divided into primary hemostatic problems (platelet plug at time of injury)and secondary hemostasis (creation of a stable fibrin clot). Disorders of primary hemostasis (thrombocytopenia or von Willebrand) are characterized by mucosal bleeding and the appearance of petechiae or superficial ecchymoses.

27. CLINICAL PEARLS Disorders of secondary hemostasis (coagulation factor deficiencies such as hemophilia)are usually characterized by the development of superficial ecchymoses,as well as deep hematomas and hemarthroses. ITP is a diagnosis of exclusion.Patients have isolated thrombocytopenia(i.e.,no red or white blood cell abnormalities),no apparent secondary causes such as systemic lupus erythematosus, HIV or medication-induced thrombocytopenia, and normal to increased numbers of megakaryocytes in the bone marrow.

28. CLINICAL PEARLS Treatment of ITP Corticosteroids are the initial treatment of ITP. Patients with more severe disease may be treated with intravenous immunogiobulin (IVIG); chronic refractory cases are treated with splenectomy.

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