- Work-up and evaluate a patient with thrombocytopenia
- Evaluate a patient with suspected immune thrombocytopenia (ITP)
- Manage a patient with ITP and severe bleeding
21 yo F with history of CVID, vasculitis/arthritis, and hypercoagulability with a history of portal vein thrombosis not on any anticoagulation who presents with new petechiae and hemorrhagic blisters on her mucosal membranes that started 12 hours prior to presentation. She additionally reports nausea and 1 episode of emesis.
She has a complicated PMH (full medical history) that includes CVID on weekly IVIg (last received yesterday), unknown arthritis/vasculitis on chronic steroids and methotrexate. She is status post splenectomy for splenomegaly as a result of portal hypertension caused by her portal vein thrombosis and is on chronic Bactrim and penicillin for prophylaxis.
In the ED, she had stable vital signs. She had multiple hemorrhagic blisters over her oral mucosa and lips but no involvement of her conjunctiva or vaginal/rectal mucosa. She has nonpalpable petechiae in her lower extremities without other evidence of bleeding or bruising. She has no palpable spleen or liver edge.
Her initial labs are notable for normal BMP, WBC of 9.5, hct of 30 (baseline from 2 years ago is 42), and plts of 6 (baseline from 2 years ago is normal). Coags are normal.
What is your differential for her thrombocytopenia?
Thrombocytopenia is most concerning when it is new or a change from baseline platelet counts. The differential for thrombocytopenia can be grossly lumped into three broad categories.
Involvement of other cell lines can be helpful in identifying the cause of thrombocytopenia.
What additional work-up and history do you want now?
New anemia and thrombocytopenia should prompt work-up for a thrombotic microangiopathy such as TTP, which is a hematologic emergency!
- Hemolysis labs – LDH, haptoglobin normal
- Peripheral blood smear – few large platelets without platelet clumping, rare schistocytes
- DIC panel – elevated fibrinogen
Additional history to identify medication or infectious etiologies:
- Denies any new medications or recent changes in medication doses
- Denies any recent hospitalizations or heparin administration
- No recent infectious symptoms – fevers, chills, night sweats
- Denies recent blood transfusions or sexual contacts (HIV, HCV)
Even though she had concurrent anemia and thrombocytopenia, a normal peripheral blood smear made a myelodysplastic disorder unlikely and the chronicity of anemia was unclear. Given her history of CVID and autoimmunity, we had high suspicion of either primary or secondary immune thrombocytopenia (ITP) – a disorder of autoantibody mediated platelet destruction. This is a diagnosis of exclusion!Click for laboratory work-up of secondary ITP.
Her Bactrim and penicillin were held given concerns they were causing drug induced ITP. She had ongoing nausea and had an episode of nausea and had 2 large episodes of bloody emesis. She additionally had a large episode of melena. She was started on an IV pantoprazole gtt and octreotide gtt given her history of portal hypertension and variceal bleeding.
What do you want to do now?
Typically, platelet transfusions are not necessary in thrombocytopenic patients (even with severe thrombocytopenia) except in the setting of significant or life threatening bleeding. Platelet transfusion threshold for GI bleeding is >50k. Platelet transfusion was ordered but there was concern that without concurrent treatment of suspected ITP, transfused platelets will be subject to immune mediated destruction.
Hematology was urgently for recommendations on treatment.
Hematology was consulted and recommended IV dexamethasone 40 mg IV daily and IVIg 1 mg/kg to be given concurrently with platelet transfusions. She was transferred to the ICU for closer monitoring.
After her first platelet transfusion (after IV dexamethasone), her platelets improved from 6 → 19. With second transfusion (and after IVIg), her platelets improved to 128. She ultimately underwent endoscopy and was found to have small to medium esophageal varices without stigmata of recent bleeding. Her bleeding was thought to be secondary to diffuse mucosal ulcerations.
ITP is disorder of immune-mediated platelet destruction. It can be either primary or secondary to an underlying disorder, infection, or drug. In children, ITP is typically a self-limited disease (typically < 6 months) with an acute or abrupt onset. In adults, the onset can be more insidious insidious and can result in chronic thrombocytopenia. There is a bimodal distribution of age of onset – peaking between 18 – 40 and again after 60 years of age1.
Secondary ITP is often associated with rheumatologic disorders (SLE), immunodeficiency states (CVID), lymphoma/leukemias, HIV and HCV infection. It can also occur secondary to medications – most notably: quinine, heparin, APAP, NSAIDs, antibiotics (vancomycin, sulfa drugs, pencillins)1-3.
Click for causes of secondary ITP.
American Society of Hematology guidelines from 2011 recommend testing all patients with presumed ITP for HIV and HCV. Bone marrow evaluation is not necessary unless there are concerning features for a myelodysplastic disorder3.
How is it treated?
Treatment of ITP depends on severity of thromcytopenia at presentation1,3.
IVIg should be given concurrently with steroids for significant or life-threatening bleeding because it works fasters than steroids, which typically take several hours to take effect3. Prothrombotic agents such as aminocaproic acid and tranexamic acid can also be considered for significant bleeds but are contraindicated in this patient with history of hypercoagulability3.
Splenectomy can be considered for patients who fail with steroids. Further immunosuppressive agents, such as rituximab, and thrombopoetin receptor agonists can be considered in patients at risk of bleeding who have failed steroids, IVIg or splenectomy.
TAKE HOME POINTS:
- Abnormalities on peripheral blood smear and presence of concurrent anemia or leukopenia can help identify causes of new thrombocytopenia.
- ITP is a disorder of immune mediated platelet destruction and can occur as a primary disorder or secondary to a number of rheumatologic disorders, infections, and medications.
- Patients with ITP and severe bleeding should receive platelet transfusions, IV steroids and IVIg.
- Chines, DB & Blanchette, VS. 2012. “Immuno Thrombocytopenic Purpura.” NEJM. 346(13): 995-1007.
- Neunert, C, et al. 2011. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood.117(16): 4190-4207.
- George, JN & Arnold, DM. Immune thrombocytopenia (ITP) in adults: Clinical manifestations and diagnosis. In: UpToDate, Tinauer, JS (Ed), UpToDate, Waltham, MA. (Accessed on August 05, 2017.)